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Huang X, Sun T, Zhang B, Ma M, Chen Z, Zhao Z, Dong S, Zhou Y. Prognostic value of remnant-like particle cholesterol in ischemic heart failure patients following percutaneous coronary intervention. Ann Med 2025; 57:2458200. [PMID: 39898975 PMCID: PMC11792126 DOI: 10.1080/07853890.2025.2458200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/20/2024] [Accepted: 01/20/2025] [Indexed: 02/04/2025] Open
Abstract
BACKGROUND The relationship between remnant-like particle cholesterol (RLP-C) and cardiovascular disease risk and prognosis has been established, but its effect on the prognosis of ischemic heart failure (IHF) patients undergoing percutaneous coronary intervention (PCI) remains uncertain. METHOD In this study, 2036 patients with IHF who underwent PCI were included. Patients were categorized into tertiles based on their RLP-C levels. The primary outcome was major adverse cardiovascular events (MACE). Kaplan-Meier survival analysis was used to assess the incidence of MACE and other outcomes. Multivariate Cox regression models were employed to investigate the correlation between RLP-C and the studied outcomes. The nonlinear relationship between RLP-C and MACE was examined through the restricted cubic spline (RCS). Subgroup analyses were performed and interactions were assessed. RESULT The study results showed a clear association between higher RLP-C levels and an increased incidence of MACE in the participants. This association was validated by Kaplan-Meier analyses. The multivariate Cox regression demonstrated RLP-C was an independent risk factor for MACE, whether assessed as a continuous variable[hazard ratio (HR), 95% confidence interval (CI): 1.50, 1.15-1.98, p = 0.003] or categorized into tertiles[HR, 95% CI: 2.57, 2.03-3.26, p < 0.001, tertile 3 vs tertile 1]. A nonlinear relationship between RLP-C and MACE was observed, indicating that the risk of MACE increased with higher RLP-C levels(Nonlinear p < 0.001). This association remained consistent across various subgroups, as no significant interactions were found. CONCLUSION There was an independent and positive correlation between RLP-C and MACE in patients with IHF who underwent PCI.
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Affiliation(s)
- Xin Huang
- Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital, Beijing, China
| | - Tienan Sun
- Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital, Beijing, China
| | - Biyang Zhang
- Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital, Beijing, China
| | - Meishi Ma
- Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital, Beijing, China
| | - Zheng Chen
- Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital, Beijing, China
| | - Zehao Zhao
- Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital, Beijing, China
| | - Shutong Dong
- Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital, Beijing, China
| | - Yujie Zhou
- Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital, Beijing, China
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Dillinger JG, Pezel T, Batias L, Angoulvant D, Goralski M, Ferrari E, Cayla G, Silvain J, Gilard M, Lemesle G, Souteyrand G, Lim P, Roubille F, Georges JL, Bal Dit Sollier C, Petroni T, Morel O, Delarche N, Elbaz M, Puymirat E, Toupin S, Montalescot G, Drouet L, Vicaut E, Henry P. Twice-a-day administration of aspirin in patients with diabetes mellitus or aspirin resistance after acute coronary syndrome: Rationale and design of the randomized ANDAMAN trial. Am Heart J 2025; 288:101-110. [PMID: 40268181 DOI: 10.1016/j.ahj.2025.04.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Revised: 04/11/2025] [Accepted: 04/14/2025] [Indexed: 04/25/2025]
Abstract
BACKGROUND Patients with diabetes mellitus (DM) or aspirin resistance are exposed to recurrent atherothrombotic events after acute coronary syndrome (ACS). Aspirin once-daily can allow the recovery of platelet cyclooxygenase activity before the next intake in these patients. Twice-daily administration provides more stable inhibition of platelet aggregation and may improve prognosis in these patients. AIM To demonstrate the superiority of twice-daily aspirin compared to once daily in reducing major adverse cardiovascular events (MACE) in patients with DM or aspirin resistance after ACS. METHODS The ANDAMAN trial is a randomized, multicenter study including patients (aged ≥18 years) with DM or with aspirin resistance defined as: (1) index event occurring under aspirin; (2) body mass index ≥27 kg/m2); (3) increased waist circumference (≥88 cm for women or ≥ 102 cm for men). The patients will be recruited in 39 centers after an ACS (with or without ST elevation) with at least one significant coronary stenosis and will be randomized before hospital discharge between twice-daily vs once daily low-dose aspirin (100 mg bid vs od). The primary composite endpoint will be the occurrence of MACE including all-cause death, myocardial infarction, stroke, urgent coronary revascularization or acute arterial thrombotic event during a follow-up of 18 months. To achieve a 20% reduction in the relative risk of MACE in the twice-daily aspirin group, a total of 2,574 patients will be included in the trial. The main secondary endpoint will be major bleeding (type 3-5 following BARC classification). CONCLUSIONS The trial will evaluate the prognostic impact of twice-daily aspirin for ACS patients with DM or aspirin resistance and may change the way aspirin is administered to these patients. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02520921.
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Affiliation(s)
- Jean-Guillaume Dillinger
- Department of Cardiology, Université Paris Cité, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Inserm MASCOT - UMRS, Paris, France; MIRACL.ai Laboratory, Multimodality Imaging for Research and Artificial Intelligence Core Laboratory, University Hospital of Lariboisiere (AP-HP), Paris, France; Centre de Référence et d'Education des antithrombotiques d'Ile de France, CREATIF, Hôpital Lariboisière, Publique-Hôpitaux de Paris, Paris, France.
| | - Théo Pezel
- Department of Cardiology, Université Paris Cité, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Inserm MASCOT - UMRS, Paris, France; MIRACL.ai Laboratory, Multimodality Imaging for Research and Artificial Intelligence Core Laboratory, University Hospital of Lariboisiere (AP-HP), Paris, France
| | - Laure Batias
- Centre Hospitalier Métropole Savoie, Service de Cardiologie, Place Lucien Biset, Chambéry, France
| | - Denis Angoulvant
- Cardiology Department, CHU Tours, INSERM Unité 1327 ISCHEMIA, Université de Tours, Tours, France
| | | | - Emile Ferrari
- Cardiology Department, Pasteur University Hospital, Nice, France
| | - Guillaume Cayla
- Cardiology Department, Nimes University Hospital, Montpellier University, ACTION Group, Nimes, France
| | - Johanne Silvain
- Department of Cardiology, Sorbonne Université, ACTION Group, INSERM UMRS1166, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France
| | - Martine Gilard
- Chest Diseases, CHU_Brest, INSERM U1304, Univ_Brest, Brest, France
| | - Gilles Lemesle
- Heart and Lung Institute, University hospital of Lille, CHU Lille, Institut Pasteur of Lille, Inserm U1011-EGID, FACT (French Alliance for Cardiovascular Trials), Paris, France
| | - Géraud Souteyrand
- Institut Pascal, Thérapies Guidées par l'Image, CNRS SIGMA UCA UMR 6602 University Hospital Gabriel Montpied, Clermont-Ferrand, France
| | - Pascal Lim
- Service de Cardiologie, Univ Paris Est Créteil, INSERM, IMRB, AP-HP, Hôpital Universitaire Henri-Mondor, Créteil, France
| | - François Roubille
- Cardiology Department, PhyMedExp, Université de Montpellier, INSERM, CNRS, INI-CRT, CHU de Montpellier, France
| | - Jean-Louis Georges
- Centre Hospitalier de Versailles, Service de cardiologie, cardiologie interventionnelle, Hôpital André Mignot, Le Chesnay-Rocquencourt, France
| | - Claire Bal Dit Sollier
- Centre de Référence et d'Education des antithrombotiques d'Ile de France, CREATIF, Hôpital Lariboisière, Publique-Hôpitaux de Paris, Paris, France
| | - Thibaut Petroni
- Cardiology Department, Clinique Pont de Chaume, Montauban, France
| | - Olivier Morel
- Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, UR 3074 Translational CardioVascular Medicine CRBS, Strasbourg, France
| | | | - Meier Elbaz
- Center for Clinical Investigation (CIC1436)/CARDIOMET, Rangueil University Hospital, Toulouse, France
| | - Etienne Puymirat
- Department of Cardiology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, Université de Paris Cité, Paris, France
| | - Solenn Toupin
- Department of Cardiology, Université Paris Cité, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Inserm MASCOT - UMRS, Paris, France; MIRACL.ai Laboratory, Multimodality Imaging for Research and Artificial Intelligence Core Laboratory, University Hospital of Lariboisiere (AP-HP), Paris, France
| | - Gilles Montalescot
- Department of Cardiology, Sorbonne Université, ACTION Group, INSERM UMRS1166, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France
| | - Ludovic Drouet
- Centre de Référence et d'Education des antithrombotiques d'Ile de France, CREATIF, Hôpital Lariboisière, Publique-Hôpitaux de Paris, Paris, France
| | - Eric Vicaut
- Unité de Recherche Clinique, ACTION Group, Hôpital Fernand Widal (AP-HP), Paris, France
| | - Patrick Henry
- Department of Cardiology, Université Paris Cité, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Inserm MASCOT - UMRS, Paris, France
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Zhou W, Wang T, Zhu L, Shi Y, Yu C, Bao H, Cheng X. Associations of body mass index and remnant cholesterol with hyperuricemia in patients with hypertension. BMC Endocr Disord 2025; 25:73. [PMID: 40102837 PMCID: PMC11917066 DOI: 10.1186/s12902-025-01902-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Accepted: 03/11/2025] [Indexed: 03/20/2025] Open
Abstract
BACKGROUND There is a paucity of prior research on residual cholesterol (RC) and hyperuricemia, and it remains unclear whether body mass index (BMI) functions as a mediating factor between them or intensifies lipid metabolic dysregulation, thereby elevating the risk of hyperuricemia. This study aims to investigate whether BMI mediates the association between RC and hyperuricemia, as well as the interaction or joint effect of BMI and RC on hyperuricemia. METHODS This is a cross-sectional study, involving a total of 14,218 hypertensive patients. Exposure factors include RC and BMI. The outcome was Hyperuricemia, defined as serum uric acid (SUA) ≥ 420 µmol/L. Multivariable logistic regression models and causal mediation analysis were used to examine the association between RC and BMI and the prevalence of hyperuricemia. RESULTS A total of 14,218 hypertensive patients were enrolled in this cross-sectional study, comprising 6,713 (47.2%) males, with a mean age of 63.8 (9.36) years. The prevalence of diabetes mellitus was found to be 10.4% (1,473), while hyperuricemia accounted for approximately 44.4% (6,319). The results show that there is a linear positive correlation between RC and hyperuricemia (P for trend < 0.01). RC and BMI only had significant additive interaction on hyperuricemia, but there was no multiplicative interaction (Additive: RERI = 0.45, 95%CI: 0.13-0.78; Multiplicative, OR = 1.09, 95% CI 0.92-1.3, P = 0.308). There are direct and indirect effects between RC and hyperuricemia [estimate (95% CI): DE = 0.063 (0.048, 0.070), IE = 0.005 (0.003, 0.001)]. In the aforementioned causal mediation analysis, among the hyperuricemia caused by RC, BMI mediates 7.1%. CONCLUSION The intermediary role of BMI and its interaction with RC play a pivotal role in augmenting the prevalence of hyperuricemia. TRIAL REGISTRATION Registered prospectively in the Chinese Clinical Trial Registry (ChiCTR1800017274) on July 20, 2018. Access at https://www.chictr.org.cn/showproj.html?proj=28262 .
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Affiliation(s)
- Wei Zhou
- Department of Cardiovascular Medicine, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 Minde Road, Nanchang, 330006, China
- Center for Prevention and Treatment of Cardiovascular Diseases, the Second Affiliated Hospital, Jiangxi M edical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, China
- Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang, China
| | - Tao Wang
- Department of Cardiovascular Medicine, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 Minde Road, Nanchang, 330006, China
- Center for Prevention and Treatment of Cardiovascular Diseases, the Second Affiliated Hospital, Jiangxi M edical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, China
- Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang, China
| | - Lingjuan Zhu
- Department of Cardiovascular Medicine, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 Minde Road, Nanchang, 330006, China
- Center for Prevention and Treatment of Cardiovascular Diseases, the Second Affiliated Hospital, Jiangxi M edical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, China
- Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang, China
| | - Yumeng Shi
- Department of Cardiovascular Medicine, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 Minde Road, Nanchang, 330006, China.
| | - Chao Yu
- Department of Cardiovascular Medicine, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 Minde Road, Nanchang, 330006, China.
- Center for Prevention and Treatment of Cardiovascular Diseases, the Second Affiliated Hospital, Jiangxi M edical College, Nanchang University, Nanchang, China.
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, China.
- Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang, China.
| | - Huihui Bao
- Department of Cardiovascular Medicine, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 Minde Road, Nanchang, 330006, China
- Center for Prevention and Treatment of Cardiovascular Diseases, the Second Affiliated Hospital, Jiangxi M edical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, China
- Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang, China
| | - Xiaoshu Cheng
- Department of Cardiovascular Medicine, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 Minde Road, Nanchang, 330006, China
- Center for Prevention and Treatment of Cardiovascular Diseases, the Second Affiliated Hospital, Jiangxi M edical College, Nanchang University, Nanchang, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, China
- Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang, China
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Yazdani A, Hoshi R, Ammar M, Li C, Cummings RD, Akmačić-Trbojević I, Cindrić A, Šimunić-Briški N, Gudelj I, Glynn R, Ridker P, Chasman DI, Lauc G, Demler O, Mora S. Statin effects on immunoglobulin-G glycomic architecture and the link to cardiovascular disease. RESEARCH SQUARE 2025:rs.3.rs-6112380. [PMID: 40092445 PMCID: PMC11908345 DOI: 10.21203/rs.3.rs-6112380/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/19/2025]
Abstract
Background Immunoglobulin G (IgG) plays a critical role in immune defense yet our understanding of its role in cardiovascular disease (CVD) is evolving. Observational studies have correlated statin use with changes in IgG N-glycan structures. However, statin effects on IgG N-glycan changes have not been tested in randomized controlled trials, and their direct association with CVD remains unclear. Methods IgG N-glycans were measured at baseline and after one year of randomized high-intensity statin interventions in 2 sub-studies of randomized trials: JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; NCT00239681; primary prevention; discovery, n = 239 participants); and TNT (Treating to New Targets; NCT00327691; secondary prevention; validation, n = 711). Using linear regression adjusted for baseline levels of IgG N-glycans and clinical risk factors (e.g., age, sex) as well as the occurrence of CVD during the year of follow-up, we investigated the one-year randomized effects of high-intensity rosuvastatin v. placebo on IgG N-glycans in JUPITER. Significant statin-IgG N-glycan associations were then validated in TNT with one-year randomized effects of high- v. low-intensity atorvastatin intervention. We examined the architecture of IgG N-glycan connectivity at baseline using a data-driven Bayesian network and compared it with the architecture after one year of randomized statin intervention. We then investigated whether the changes in IgG N-glycans triggered by statins were associated with incident CVD events. Results We identified 5 IgG N-glycans (corresponding to core fucosylated, monosialylated, and disialylated IgG N-glycans) in JUPITER whose levels decreased significantly with statin versus placebo (false discovery rate < 0.05), with an approximate 11.3-25.9% reduction in the individual IgG N-glycan levels. Four out of the five IgG N-glycans altered by statin were validated in TNT. Furthermore, monosialylation and core fucosylation (glycan peaks, GP 16 and 18) were inversely associated with CVD in JUPITER (OR = 0.87 and 0.73 per standard deviation increase, 95% CI: (0.57, 0.98) and (0.55, 0.96) respectively), and validated in TNT. Despite the effect of statin therapy on certain IgG N-glycans, the overall architecture of the IgG N-glycan network remained unchanged after one year of statin intervention. Conclusion High-intensity statin interventions decreased several specific IgG N-glycan levels without changing the overall architecture of IgG N-glycan connectivity. Two IgG N-glycans that were decreased by statins were inversely associated with CVD outcomes, suggesting that statins have effects on monosialylated and core fucosylated IgG N-glycans, which may affect their cardioprotective properties. These findings highlight a potential immunomodulatory role of statins through IgG N-glycan alterations that should be further investigated in relation to CVD.
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Yu P, Yuan Q, Huang L, Tao L, Peng Z, Pu J. The prognostic value of remnant cholesterol to adverse renal outcomes in patients with type 2 diabetes. Diabetol Metab Syndr 2025; 17:52. [PMID: 39940009 PMCID: PMC11823253 DOI: 10.1186/s13098-025-01617-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 01/29/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Type 2 diabetes (T2DM) is known to have detrimental effects on renal health. Our study aimed to investigate the relationship between remnant cholesterol (remnant-C) and adverse renal outcomes in patients with T2DM. METHODS We utilized data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which included 10,196 participants with T2DM to investigate the relationship between remnant-C and adverse renal outcomes by performing Kaplan-Meier survival analysis, Cox proportional regression and Restricted cubic spline (RCS) analysis. Finally, several sensitivity analyses were conducted to assess the robustness of our findings. RESULTS Over a 7-year follow-up period, 2039 patients (23.2%) developed albuminuria, 5824 patients (57.1%) experienced worsening renal function, and 280 patients (2.7%) progressed to renal failure. After adjusting for multiple confounding factors, we found that remnant-C was significantly associated with the development of albuminuria (P = 0.007) and worsening renal function (P = 0.002). However, there was no discernible connection between remnant-C and renal faiure (P = 0.621). In sensitivity analyses, the association between remnant-C and the risk of adverse renal outcomes remained robust. CONCLUSION Our findings highlight the association between remnant-C and the risk of adverse renal outcomes in patients with T2DM. This easily calculable index can provide valuable information to physicians for predicting the risk of adverse renal outcomes in patients with T2DM.
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Affiliation(s)
- Pan Yu
- Department of Nephrology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, Hunan Province, China
| | - Qiongjing Yuan
- Department of Nephrology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, Hunan Province, China
- Hunan Key Lab of Organ Fibrosis, Changsha, China
- Xiangya Hospital, National International Collaborative Research Center for Medical Metabolomics, Central South University, Changsha, China
| | - Ling Huang
- Department of Nephrology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, Hunan Province, China
- Hunan Key Lab of Organ Fibrosis, Changsha, China
- Xiangya Hospital, National International Collaborative Research Center for Medical Metabolomics, Central South University, Changsha, China
| | - Lijian Tao
- Department of Nephrology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, Hunan Province, China
- Hunan Key Lab of Organ Fibrosis, Changsha, China
- Xiangya Hospital, National International Collaborative Research Center for Medical Metabolomics, Central South University, Changsha, China
| | - Zhangzhe Peng
- Department of Nephrology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, Hunan Province, China
- Hunan Key Lab of Organ Fibrosis, Changsha, China
- Xiangya Hospital, National International Collaborative Research Center for Medical Metabolomics, Central South University, Changsha, China
| | - Jiaxi Pu
- Department of Nephrology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, Hunan Province, China.
- Hunan Key Lab of Organ Fibrosis, Changsha, China.
- Xiangya Hospital, National International Collaborative Research Center for Medical Metabolomics, Central South University, Changsha, China.
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Lee JH, Ahn SG, Jeon HS, Lee JW, Youn YJ, Lee YJ, Lee SJ, Hong SJ, Ahn CM, Ko YG, Kim JS, Choi D, Hong MK, Jang Y, Kim BK. Remnant cholesterol as a residual risk in atherosclerotic cardiovascular disease patients under statin-based lipid-lowering therapy: A post hoc analysis of the RACING trial. J Clin Lipidol 2024; 18:e905-e914. [PMID: 39322526 DOI: 10.1016/j.jacl.2024.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 07/09/2024] [Accepted: 07/10/2024] [Indexed: 09/27/2024]
Abstract
BACKGROUND Remnant cholesterol (remnant-C) levels during lipid-lowering therapy (LLT) may indicate residual risk. OBJECTIVE We aimed to investigate the clinical outcomes based on on-treatment remnant-C distribution in patients with atherosclerotic cardiovascular disease (ASCVD) under statin-based LLT. METHODS In this post hoc analysis of the RACING trial, 3,348 patients with ASCVD lipid profiles 1 year after randomization were investigated. Remnant-C was calculated as total cholesterol minus low-density lipoprotein cholesterol (LDL-C) minus high-density lipoprotein cholesterol. The primary endpoint was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. RESULTS The study population was grouped into tertiles according to on-treatment remnant-C: high (> 20.5 mg/dL; n = 1,116), intermediate (14‒20.5 mg/dL; n = 1,031), and low (≤14.0 mg/dL; n = 1,201) remnant-C groups. The high remnant-C group showed the highest incidence of the primary endpoint at 3 years (11.0%, 10.3%, and 7.5% in the high, intermediate, and low remnant-C groups, respectively; p = 0.009). The high remnant-C levels at 1 year were independently associated with an increased risk of the primary outcome, whereas achieving LDL-C < 55 or 70 mg/dL was not associated with the incidence of the primary endpoint. The on-treatment remnant-C cut-off of 17 mg/dL (median) demonstrated the ability to discriminate between patients at higher and lower risks for the primary endpoints (hazard ratio: 1.42; 95% confidence interval: 1.14‒1.78; p = 0.002). CONCLUSIONS In patients with ASCVD undergoing statin-based LLT, high on-treatment remnant-C values were associated with unfavorable clinical outcomes. On-treatment remnant-C levels may serve as an additional means of assessing residual cardiovascular risk. CLINICAL TRIAL REGISTRATION ClinicalTrials. gov ID: NCT03044665.
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Affiliation(s)
- Jung-Hee Lee
- Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea (Drs Lee, Ahn, Jeon, Lee, and Youn)
| | - Sung Gyun Ahn
- Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea (Drs Lee, Ahn, Jeon, Lee, and Youn).
| | - Ho Sung Jeon
- Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea (Drs Lee, Ahn, Jeon, Lee, and Youn)
| | - Jun-Won Lee
- Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea (Drs Lee, Ahn, Jeon, Lee, and Youn)
| | - Young Jin Youn
- Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea (Drs Lee, Ahn, Jeon, Lee, and Youn)
| | - Yong-Joon Lee
- Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (Drs Lee, Lee, Hong, Ahn, Ko, Kim, Choi, Hong and Kim)
| | - Seung-Jun Lee
- Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (Drs Lee, Lee, Hong, Ahn, Ko, Kim, Choi, Hong and Kim)
| | - Sung-Jin Hong
- Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (Drs Lee, Lee, Hong, Ahn, Ko, Kim, Choi, Hong and Kim)
| | - Chul-Min Ahn
- Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (Drs Lee, Lee, Hong, Ahn, Ko, Kim, Choi, Hong and Kim)
| | - Young-Guk Ko
- Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (Drs Lee, Lee, Hong, Ahn, Ko, Kim, Choi, Hong and Kim)
| | - Jung-Sun Kim
- Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (Drs Lee, Lee, Hong, Ahn, Ko, Kim, Choi, Hong and Kim)
| | - Donghoon Choi
- Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (Drs Lee, Lee, Hong, Ahn, Ko, Kim, Choi, Hong and Kim)
| | - Myeong-Ki Hong
- Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (Drs Lee, Lee, Hong, Ahn, Ko, Kim, Choi, Hong and Kim)
| | - Yangsoo Jang
- Department of Cardiology, CHA Bundang Medical Center, CHA University College of Medicine, Seongnam, Republic of Korea (Jang)
| | - Byeong-Keuk Kim
- Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (Drs Lee, Lee, Hong, Ahn, Ko, Kim, Choi, Hong and Kim)
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Zhang L, Zeng H, Sun Y, Xue H, Gao L, Zhu W. Effect of Tai Chi Compared to Running on Drug Cravings, Attention Bias, and Physical Fitness in Men with Methamphetamine Use Disorder. Healthcare (Basel) 2024; 12:1653. [PMID: 39201211 PMCID: PMC11353623 DOI: 10.3390/healthcare12161653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 08/18/2024] [Accepted: 08/19/2024] [Indexed: 09/02/2024] Open
Abstract
BACKGROUND Methamphetamine use disorder (MUD) is a global health problem. Studies have shown Tai Chi is a potential treatment for MUD. We aimed to explore the effectiveness of Tai Chi in improving drug cravings, attention bias, and physical fitness in men with MUD compared with aerobic exercise. METHODS A total of forty-eight participants (mean age 39.1 ± 8.7 years) were randomly assigned to either the Tai Chi group (TC) or the running group (RG). The TC performed 60 min of moderate-intensity (65-75% HRmax) Tai Chi exercise three times a week. The RG performed 60 min of moderate-intensity (65-75% HRmax) running on a treadmill three times a week. Before and after the intervention, drug cravings, attention bias, and physical fitness were evaluated. RESULTS After 12 weeks, we found the TC significantly improved in attention bias (F (1, 43) = 6.023, p = 0.019, d = -0.42) and reaction time (F (1, 43) = 6.181, p = 0.017, d = -0.72). No significant improvement was found in other variables in the TC, compared to the RG (p > 0.05). CONCLUSIONS The 12-week Tai Chi intervention improved attention bias and reaction time, compared to RG. Tai Chi exercise might be a potential auxiliary method for the rehabilitation for men with MUD.
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Affiliation(s)
| | | | | | | | - Liquan Gao
- School of Physical Education, Shaanxi Normal University, Xi’an 710119, China; (L.Z.); (H.Z.); (Y.S.); (H.X.)
| | - Wenfei Zhu
- School of Physical Education, Shaanxi Normal University, Xi’an 710119, China; (L.Z.); (H.Z.); (Y.S.); (H.X.)
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8
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Jiang X, Zhuang J, Juan Y, Zheng X, Zhang H. Association between remnant cholesterol and the risk of cardiovascular disease in Chinese population. J Stroke Cerebrovasc Dis 2024; 33:107825. [PMID: 38914356 DOI: 10.1016/j.jstrokecerebrovasdis.2024.107825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 05/09/2024] [Accepted: 06/15/2024] [Indexed: 06/26/2024] Open
Abstract
OBJECTIVES Previous genetic, observational, and clinical intervention studies reported that circulating levels of remnant cholesterol was associated with cardiovascular disease (CVD). However, whether remnant cholesterol can predict CVD events in Chinese population was not well characterized. STUDY DESIGN This was a prospective cohort study. METHODS We used the data of 9456 Chinese adults aged ≥45 years from the China Health and Retirement Longitudinal Study (CHARLS). Estimated remnant cholesterol was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol. Cox proportional hazard models and restricted cubic spline models were used to assess the relationships between remnant cholesterol levels and CVD, stroke and cardiac events. RESULTS During 7 years of follow-up, a total of 886 (9.37 %) respondents experienced CVD, 392 (4.15 %) experienced stroke and 544 (5.75 %) experienced cardiac events. In multivariable-adjusted analyses, the adjusted hazard ratios (95 % confidence interval) for the highest versus lowest quartile of remnant cholesterol were 1.14 (1.02-1.32) for CVD and 1.43 (1.12-1.82) for stroke, and each 1-SD increase of log-transformed remnant cholesterol (2.93 mg/dl) was associated with 5 % and 11 % increased risk of the CVD and stroke, respectively. Remnant cholesterol was not associated with increased risk of cardiac events. CONCLUSION Elevated remnant cholesterol levels were positively associated with CVD and stroke in Chinese adult population, suggesting that remnant cholesterol could be considered as a preferential predictor and treatment target of CVD in Chinese population.
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Affiliation(s)
- Xinye Jiang
- Department of Child Health Care, Wuxi Maternity and Child Health Care Hospital, Women's Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, 214002, China
| | - Jielian Zhuang
- Department of Child Health Care, Wuxi Maternity and Child Health Care Hospital, Women's Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, 214002, China
| | - Yin Juan
- Department of Child Health Care, Wuxi Maternity and Child Health Care Hospital, Women's Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, 214002, China
| | - Xiaowei Zheng
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214002, China; Public Health Research Center and Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, China
| | - Heng Zhang
- Department of Child Health Care, Wuxi Maternity and Child Health Care Hospital, Women's Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, 214002, China; Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214002, China.
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9
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Li W, Sun L, Yan S. PCSK9 inhibitors and inclisiran with or without statin therapy on incident muscle symptoms and creatine kinase: a systematic review and network meta-analysis. Front Cardiovasc Med 2024; 11:1375040. [PMID: 39040999 PMCID: PMC11260805 DOI: 10.3389/fcvm.2024.1375040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 06/24/2024] [Indexed: 07/24/2024] Open
Abstract
Background Atherosclerotic cardiovascular disease (ASCVD), a leading cause of global fatalities, has inconsistent findings regarding the impact of muscle symptoms despite promising clinical trials involving PCSK9 inhibitors (PCSK9i) and siRNA as potential therapeutic options. Methods The databases EMBASE, PubMed, Web of Science, Cochrane, and ClinicalTrials.gov were thoroughly searched without any restrictions on language. Review Manager 5.3 software was utilized to calculate relative risks with 95% confidence intervals (CIs) for dichotomous data and mean differences or standardized mean differences with 95%CIs for continuous data. To evaluate publication bias, Egger's test was employed using Stata/SE software. Results This analysis included 26 studies comprising 28 randomized controlled trials (RCTs) involving a total of 100,193 patients, and 4 different lipid-lowering therapy combinations. For events with creatine kinase >3ULN, evolocumab and alirocumab demonstrated significant advantages compared to inclisiran. Evolocumab showed the best results in terms of both new muscle symptom events and creatine kinase >3ULN. Conclusions Based on this network meta-analysis (NMA) results, evolocumab has emerged as a promising treatment option for patients with hyperlipidemia and muscle disorders compared to other PCSK9 inhibitors and inclisiran. Systematic Review Registration PROSPERO [CRD42023459558].
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Affiliation(s)
- Wenshu Li
- Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Lichaoyue Sun
- Department of Pharmacy, Aerospace Central Hospital, Beijing, China
| | - Sichao Yan
- Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
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10
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Song Y, Dang Y, Feng J, Ruan LT. Remnant Cholesterol and Carotid Intraplaque Neovascularization Assessed by Contrast-Enhanced Ultrasonography in Patients With Ischemic Stroke. Cardiol Res 2024; 15:144-152. [PMID: 38994226 PMCID: PMC11236345 DOI: 10.14740/cr1634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 04/03/2024] [Indexed: 07/13/2024] Open
Abstract
Background We investigated the relationship between remnant cholesterol and carotid intraplaque neovascularization (IPN) assessed by contrast-enhanced ultrasonography (CEUS) in patients with ischemic stroke. Methods This was a single-center study. Remnant cholesterol is calculated as total cholesterol minus low-density lipoprotein cholesterol (LDL-C) minus high-density lipoprotein cholesterol (HDL-C). All patients underwent CEUS. IPN is graded according to the presence and location of microbubbles within each plaque. Results The cohort included 110 patients with ischemic stroke. Patients with an IPN grading of 2 had higher triglyceride (TG), non-HDL-C, and remnant cholesterol concentrations than those with an IPN grading of < 2 (TG: 1.45 ± 0.69 vs. 0.96 ± 0.24 mmol/L, P < 0.001; non-HDL-C: 2.63 ± 0.85 vs. 2.31 ± 0.64 mmol/L, P = 0.037; remnant cholesterol: 0.57 ± 0.23 vs. 0.44 ± 0.07 mmol/L, P < 0.001). The multivariate-adjusted odds ratio (95% confidence interval) for remnant cholesterol was 27.728 (2.714 - 283.253) for an IPN grading of 2 in the subset of patients with an optimal LDL-C concentration. Conclusions The remnant cholesterol concentration is significantly associated with carotid IPN on CEUS in patients with ischemic stroke with an optimal LDL-C concentration. Remnant cholesterol may be an important indicator of risk stratification in patients with ischemic stroke.
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Affiliation(s)
- Yan Song
- Department of Ultrasound, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Ying Dang
- Department of Ultrasound, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Jun Feng
- Department of Vascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Li Tao Ruan
- Department of Ultrasound, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
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11
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Yu Z, Yang H, Shou B, Cheng Z, Jiang C, Ye Y, Xu J. Remnant cholesterol and the risk of carotid plaque in hypertension: results from a community-based screening among old adults in Hangzhou, China. Sci Rep 2024; 14:8407. [PMID: 38600230 PMCID: PMC11006856 DOI: 10.1038/s41598-024-58484-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 03/29/2024] [Indexed: 04/12/2024] Open
Abstract
Elevated remnant cholesterol (RC) is considered a risk factor for atherosclerotic cardiovascular disease, but the evidence on this association applies to the Chinese population with hypertension is limited. We aimed to explore the association between RC levels and carotid plaque in old adults with hypertension. 8523 hypertensive patients aged ≥ 60 years with serum lipids and carotid ultrasonography data were included in this community-based screening. Fasting RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol (LDLC). The associations of RC levels with carotid plaque risk were evaluated using Logistic regression and restricted cubic spline models. Carotid plaque was screened in 4821 (56.56%) subjects. After multivariable-adjusted, RC was significantly related to carotid plaque [Odd ratio (OR)] = 1.043 per 0.1 mmol/L increase, 95% confidence interval (CI): 1.030-1.056). The highest versus the lowest quartile of RC was 1.928 (1.673-2.223) for carotid plaque. A nonlinear association was found between serum RC levels and the risk of carotid plaque (P for nonlinearity < 0.001). Moreover, an RC > 0.78 mmol/L differentiated patients at a higher risk of carotid plaque compared to those at lower concentrations, regardless of whether LDLC was on target at 2.59 mmol/L. In old adults with hypertension, elevated RC was positively associated with carotid plaque, independent of LDLC and other conventional risk factors.
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Affiliation(s)
- Zhecong Yu
- Institute for Chronic Non-Communicable Disease Control and Prevention, Hangzhou Center for Disease Control and Prevention, Hangzhou, 310000, People's Republic of China
| | - Haifeng Yang
- Fuyang Center for Disease Control and Prevention, Hangzhou, 311400, People's Republic of China
| | - Biqi Shou
- Fuyang Center for Disease Control and Prevention, Hangzhou, 311400, People's Republic of China
| | - Zongxue Cheng
- Institute for Chronic Non-Communicable Disease Control and Prevention, Hangzhou Center for Disease Control and Prevention, Hangzhou, 310000, People's Republic of China
| | - Caixia Jiang
- Institute for Chronic Non-Communicable Disease Control and Prevention, Hangzhou Center for Disease Control and Prevention, Hangzhou, 310000, People's Republic of China
| | - Yang Ye
- Tonglu Center for Disease Control and Prevention, Hangzhou, 311400, People's Republic of China
| | - Jue Xu
- Institute for Chronic Non-Communicable Disease Control and Prevention, Hangzhou Center for Disease Control and Prevention, Hangzhou, 310000, People's Republic of China.
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12
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Dankar R, Wehbi J, Refaat MM. Tailoring Treatment in Cardiovascular Diseases: The Role of Targeted Therapies. Pharmaceutics 2024; 16:461. [PMID: 38675122 PMCID: PMC11054164 DOI: 10.3390/pharmaceutics16040461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 03/19/2024] [Accepted: 03/23/2024] [Indexed: 04/28/2024] Open
Abstract
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality around the globe. To address this public health burden, innovative therapeutic agents are being developed to specifically target molecular and genetic markers. Various therapeutic modalities have been implemented, including vaccines, monoclonal or bispecific antibodies, and gene-based therapies. Such drugs precisely target the underlying disease pathophysiology, aiming at notable molecules such as lipid metabolism regulators, proinflammatory cytokines, and growth factors. This review focuses on the latest advancements in different targeted therapies. It provides an insightful overview of the current landscape of targeted cardiovascular therapies, highlighting promising strategies with potential to transform the treatment of CVDs into an era of precision medicine.
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Affiliation(s)
- Razan Dankar
- Department of Biochemistry and Molecular Genetics, American University of Beirut Faculty of Medicine and Medical Center, Beirut P.O. Box 11-0236, Lebanon; (R.D.); (J.W.)
- Department of Internal Medicine, Division of Cardiology, American University of Beirut Faculty of Medicine and Medical Center, Beirut P.O. Box 11-0236, Lebanon
| | - Jad Wehbi
- Department of Biochemistry and Molecular Genetics, American University of Beirut Faculty of Medicine and Medical Center, Beirut P.O. Box 11-0236, Lebanon; (R.D.); (J.W.)
- Department of Internal Medicine, Division of Cardiology, American University of Beirut Faculty of Medicine and Medical Center, Beirut P.O. Box 11-0236, Lebanon
| | - Marwan M. Refaat
- Department of Biochemistry and Molecular Genetics, American University of Beirut Faculty of Medicine and Medical Center, Beirut P.O. Box 11-0236, Lebanon; (R.D.); (J.W.)
- Department of Internal Medicine, Division of Cardiology, American University of Beirut Faculty of Medicine and Medical Center, Beirut P.O. Box 11-0236, Lebanon
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13
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Hoshi RA, Plavša B, Liu Y, Trbojević-Akmačić I, Glynn RJ, Ridker PM, Cummings RD, Gudelj I, Lauc G, Demler OV, Mora S. N-Glycosylation Profiles of Immunoglobulin G and Future Cardiovascular Events. Circ Res 2024; 134:e3-e14. [PMID: 38348651 PMCID: PMC10923145 DOI: 10.1161/circresaha.123.323623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 01/26/2024] [Indexed: 03/02/2024]
Abstract
BACKGROUND Posttranslational glycosylation of IgG can modulate its inflammatory capacity through structural variations. We examined the association of baseline IgG N-glycans and an IgG glycan score with incident cardiovascular disease (CVD). METHODS IgG N-glycans were measured in 2 nested CVD case-control studies: JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; NCT00239681; primary prevention; discovery; Npairs=162); and TNT trial (Treating to New Targets; NCT00327691; secondary prevention; validation; Npairs=397). Using conditional logistic regression, we investigated the association of future CVD with baseline IgG N-glycans and a glycan score adjusting for clinical risk factors (statin treatment, age, sex, race, lipids, hypertension, and smoking) in JUPITER. Significant associations were validated in TNT, using a similar model further adjusted for diabetes. Using least absolute shrinkage and selection operator regression, an IgG glycan score was derived in JUPITER as a linear combination of selected IgG N-glycans. RESULTS Six IgG N-glycans were associated with CVD in both studies: an agalactosylated glycan (IgG-GP4) was positively associated, while 3 digalactosylated glycans (IgG glycan peaks 12, 13, 14) and 2 monosialylated glycans (IgG glycan peaks 18, 20) were negatively associated with CVD after multiple testing correction (overall false discovery rate <0.05). Four selected IgG N-glycans comprised the IgG glycan score, which was associated with CVD in JUPITER (adjusted hazard ratio per glycan score SD, 2.08 [95% CI, 1.52-2.84]) and validated in TNT (adjusted hazard ratio per SD, 1.20 [95% CI, 1.03-1.39]). The area under the curve changed from 0.693 for the model without the score to 0.728 with the score in JUPITER (PLRT=1.1×10-6) and from 0.635 to 0.637 in TNT (PLRT=0.017). CONCLUSIONS An IgG N-glycan profile was associated with incident CVD in 2 populations (primary and secondary prevention), involving an agalactosylated glycan associated with increased risk of CVD, while several digalactosylated and sialylated IgG glycans associated with decreased risk. An IgG glycan score was positively associated with future CVD.
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Affiliation(s)
- Rosangela A. Hoshi
- Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Branimir Plavša
- University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
| | - Yanyan Liu
- Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | | | - Robert J. Glynn
- Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Paul M Ridker
- Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Richard D. Cummings
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Ivan Gudelj
- Genos Glycoscience Research Laboratory, Zagreb, Croatia
- Department of Biotechnology, University of Rijeka, Rijeka, Croatia
| | - Gordan Lauc
- University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
- Genos Glycoscience Research Laboratory, Zagreb, Croatia
| | - Olga V. Demler
- Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Computer Science Department, ETH Zurich, Zurich, Switzerland
| | - Samia Mora
- Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
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14
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Nakao K, Noguchi T, Miura H, Asaumi Y, Morita Y, Takeuchi S, Matama H, Sawada K, Doi T, Hosoda H, Nakashima T, Honda S, Fujino M, Yoneda S, Kawakami S, Nagai T, Nishihira K, Kanaya T, Otsuka F, Nakanishi M, Kataoka Y, Tahara Y, Goto Y, Kusano K, Yamamoto H, Omae K, Ogawa H, Yasuda S. Effect of Eicosapentaenoic Acid/Docosahexaenoic Acid on Coronary High-Intensity Plaques Detected Using Noncontrast T1-weighted Imaging: The AQUAMARINE EPA/DHA Randomized Study. J Atheroscler Thromb 2024; 31:122-134. [PMID: 37704431 PMCID: PMC10857838 DOI: 10.5551/jat.64063] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 07/09/2023] [Indexed: 09/15/2023] Open
Abstract
AIM Omega-3 fatty acids have emerged as a new option for controlling the residual risk for coronary artery disease (CAD) in the statin era. Eicosapentaenoic acid (EPA) is associated with reduced CAD risk in the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention trial, whereas the Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia trial that used the combination EPA/docosahexaenoic acid (DHA) has failed to derive any clinical benefit. These contradictory results raise important questions about whether investigating the antiatherosclerotic effect of omega-3 fatty acids could help to understand their significance for CAD-risk reduction. METHODS The Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technic EPA/DHA study is a single-center, triple-arm, randomized, controlled, open-label trial used to investigate the effect of EPA/DHA on high-risk coronary plaques after 12 months of treatment, detected using cardiac magnetic resonance (CMR) in patients with CAD receiving statin therapy. Eligible patients were randomly assigned to no-treatment, 2-g/day, and 4-g/day EPA/DHA groups. The primary endpoint was the change in the plaque-to-myocardium signal intensity ratio (PMR) of coronary high-intensity plaques detected by CMR. Coronary plaque assessment using computed tomography angiography (CTA) was also investigated. RESULTS Overall, 84 patients (mean age: 68.2 years, male: 85%) who achieved low-density lipoprotein cholesterol levels of ＜100 mg/dL were enrolled. The PMR was reduced in each group over 12 months. There were no significant differences in PMR changes among the three groups in the primary analysis or analysis including total lesions. The changes in CTA parameters, including indexes for detecting high-risk features, also did not differ. CONCLUSION The EPA/DHA therapy of 2 or 4 g/day did not significantly improve the high-risk features of coronary atherosclerotic plaques evaluated using CMR under statin therapy.
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Affiliation(s)
- Kazuhiro Nakao
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Teruo Noguchi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Hiroyuki Miura
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Yasuhide Asaumi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Yoshiaki Morita
- Department of Radiology, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Satoshi Takeuchi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
- Department of Advanced Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hideo Matama
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Keniciro Sawada
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Takahito Doi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Hayato Hosoda
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Takahiro Nakashima
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Satoshi Honda
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Masashi Fujino
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Shuichi Yoneda
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Shoji Kawakami
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Toshiyuki Nagai
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Kensaku Nishihira
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Tomoaki Kanaya
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Fumiyuki Otsuka
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Michio Nakanishi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Yu Kataoka
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Yoshio Tahara
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Yoichi Goto
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Kengo Kusano
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Haruko Yamamoto
- Centre for Advancing Clinical and Translational Science, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Katsuhiro Omae
- Department of Data Science, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Hisao Ogawa
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
| | - Satoshi Yasuda
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
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Khatiwada N, Hong Z. Potential Benefits and Risks Associated with the Use of Statins. Pharmaceutics 2024; 16:214. [PMID: 38399268 PMCID: PMC10892755 DOI: 10.3390/pharmaceutics16020214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/13/2024] [Accepted: 01/22/2024] [Indexed: 02/25/2024] Open
Abstract
HMG-CoA reductase inhibitors, commonly known as statins, are the primary treatment choice for cardiovascular diseases, which stand as the leading global cause of mortality. Statins also offer various pleiotropic effects, including improved endothelial function, anti-inflammatory properties, reduced oxidative stress, anti-thrombotic effects, and the stabilization of atherosclerotic plaques. However, the usage of statins can be accompanied by a range of adverse effects, such as the development of type 2 diabetes mellitus, muscular symptoms, liver toxicity, kidney diseases, cataracts, hemorrhagic strokes, and psychiatric complications. These issues are referred to as statin-associated symptoms (SAS) and are relatively infrequent in clinical trials, making it challenging to attribute them to statin use definitively. Therefore, these symptoms can lead to significant problems, necessitating dose adjustments or discontinuation of statin therapy. This review aims to provide a comprehensive overview of the mechanism of action, potential advantages, and associated risks of statin utilization in clinical settings.
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Affiliation(s)
| | - Zhongkui Hong
- Department of Mechanical Engineering, Texas Tech University, Lubbock, TX 79409, USA;
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16
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Kamiya K, Takei M, Nagai T, Miyoshi T, Ito H, Fukumoto Y, Obara H, Kakuma T, Sakuma I, Daida H, Iimuro S, Shimokawa H, Kimura T, Nagai R, Anzai T. Association between Non-Lipid Residual Risk Factors and Cardiovascular Events in Patients with Stable Coronary Artery Disease Treated with Pitavastatin: An Observation from the REAL-CAD Study. J Atheroscler Thromb 2024; 31:61-80. [PMID: 37574272 PMCID: PMC10776335 DOI: 10.5551/jat.64304] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 06/25/2023] [Indexed: 08/15/2023] Open
Abstract
AIMS We aimed to investigate the association between non-lipid residual risk factors and cardiovascular events in patients with stable coronary artery disease (CAD) who achieved low-density lipoprotein cholesterol (LDL-C) ＜100 mg/dL from the Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study. METHODS The REAL-CAD study was a prospective, multicenter, open-label trial. As a sub-study, we examined the prognostic impact of non-lipid residual risk factors, including blood pressure, glucose level, and renal function, in patients who achieved LDL-C ＜100 mg/dL at 6 months after pitavastatin therapy. Each risk factor was classified according to severity. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unstable angina requiring emergency hospitalization. RESULTS Among 8,743 patients, the mean age was 68±8.2 years, and the mean LDL-C level was 84.4±18 mg/dL. After adjusting for the effects of confounders, an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 showed the highest risk of the primary outcome (hazard ratio [HR] 1.92; 95% confidence interval [CI] 1.45-2.53). The combination of eGFR ≤ 60 and hemoglobin A1c (HbA1c) ≥ 6.0% also showed the highest risk of all-cause death (HR, 2.42; 95% CI, 1.72-3.41). CONCLUSIONS In patients with stable CAD treated with pitavastatin and who achieved guidelines-directed levels of LDL-C, eGFR and HbA1c were independently associated with adverse events, suggesting that renal function and glycemic control could be residual non-lipid therapeutic targets after statin therapy.
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Affiliation(s)
- Kiwamu Kamiya
- Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Makoto Takei
- Department of Cardiology, Saiseikai Central Hospital, Tokyo, Japan
| | - Toshiyuki Nagai
- Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Toru Miyoshi
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroshi Ito
- Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan
| | - Yoshihiro Fukumoto
- Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan
| | - Hitoshi Obara
- Biostatistics Center, Kurume University, Fukuoka, Japan
| | | | - Ichiro Sakuma
- Caress Sapporo Hokko Memorial Clinic, Sapporo, Japan
| | - Hiroyuki Daida
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Satoshi Iimuro
- Innovation and Research Support Center, International University of Health and Welfare, Tokyo, Japan
| | - Hiroaki Shimokawa
- Graduate School, International University of Health and Welfare, Chiba, Japan
- Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takeshi Kimura
- Hirakata Kohsai Hospital, Department of Cardiology, Osaka, Japan
| | - Ryozo Nagai
- Innovation and Research Support Center, International University of Health and Welfare, Tokyo, Japan
| | - Toshihisa Anzai
- Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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LI TY, ZHU P, SONG Y, TANG XF, GAO Z, GAO RL, YUAN JQ. Discordance analysis for apolipoprotein and lipid measures for predicting myocardial infarction in statin-treated patients with coronary artery disease: a cohort study. J Geriatr Cardiol 2023; 20:845-854. [PMID: 38161343 PMCID: PMC10755212 DOI: 10.26599/1671-5411.2023.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2024] Open
Abstract
BACKGROUND The optimal apolipoprotein or lipid measures for identifying statin-treated patients with coronary artery disease (CAD) at residual cardiovascular risk remain controversial. This study aimed to compare the predictive powers of apolipoprotein B (apoB), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), apoB/apolipoprotein A-1 (apoA-1) and non-HDL-C/HDL-C for myocardial infarction (MI) in CAD patients treated with statins in the setting of secondary prevention. METHODS The study included 9191 statin-treated CAD patients with a five-year median follow-up. All measures were analyzed as continuous variables and concordance/discordance groups by medians. The hazard ratio (HR) with 95% CI was estimated by Cox proportional hazards regression. Patients were classified by the clinical presentation of CAD for further analysis. RESULTS The high-apoB-low-LDL-C and the high-non-HDL-C-low-LDL-C categories yielded HR of 1.40 (95% CI: 1.04-1.88) and 1.51 (95% CI: 1.07-2.13) for MI, respectively, whereas discordant high LDL-C with low apoB or non-HDL-C was not associated with the risk of MI. No association of MI with discordant apoB versus non-HDL-C, apoB/apoA-1 versus apoB, non-HDL-C/HDL-C versus non-HDL-C, or apoB/apoA-1 versus non-HDL-C/HDL-C was observed. Similar patterns were found in patients with acute coronary syndrome. In contrast, no association was observed between any concordance/discordance category and the risk of MI in patients with chronic coronary syndrome. CONCLUSIONS ApoB and non-HDL-C better predict MI in statin-treated CAD patients than LDL-C, especially in patients with acute coronary syndrome. ApoB/apoA-1 and non-HDL-C/HDL-C show no superiority to apoB and non-HDL-C for predicting MI.
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Affiliation(s)
- Tian-Yu LI
- National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Pei ZHU
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ying SONG
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiao-Fang TANG
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhan GAO
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Run-Lin GAO
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jin-Qing YUAN
- National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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18
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Wang L, Wang S, Song C, Yu Y, Jiang Y, Wang Y, Li X. Bibliometric analysis of residual cardiovascular risk: trends and frontiers. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2023; 42:132. [PMID: 38017531 PMCID: PMC10683255 DOI: 10.1186/s41043-023-00478-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 11/24/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUND The presence of residual cardiovascular risk is an important cause of cardiovascular events. Despite the significant advances in our understanding of residual cardiovascular risk, a comprehensive analysis through bibliometrics has not been performed to date. Our objective is to conduct bibliometric studies to analyze and visualize the current research hotspots and trends related to residual cardiovascular risk. This will aid in understanding the future directions of both basic and clinical research in this area. METHODS The literature was obtained from the Web of Science Core Collection database. The literature search date was September 28, 2022. Bibliometric indicators were analyzed using CiteSpace, VOSviewer, Bibliometrix (an R package), and Microsoft Excel. RESULT A total of 1167 papers were included, and the number of publications is increasing rapidly in recent years. The United States and Harvard Medical School are the leading country and institution, respectively, in the study of residual cardiovascular risk. Ridker PM and Boden WE are outstanding investigators in this field. According to our research results, the New England Journal of Medicine is the most influential journal in the field of residual cardiovascular risk, whereas Atherosclerosis boasts the highest number of publications on this topic. Analysis of keywords and landmark literature identified current research hotspots including complications of residual cardiovascular risk, risk factors, and pharmacological prevention strategies. CONCLUSION In recent times, global attention toward residual cardiovascular risk has significantly increased. Current research is focused on comprehensive lipid-lowering, residual inflammation risk, and dual-pathway inhibition strategies. Future efforts should emphasize strengthening international communication and cooperation to promote the comprehensive evaluation and management of residual cardiovascular risk.
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Affiliation(s)
- Lin Wang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Sutong Wang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Chaoyuan Song
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
- Department of Neurology, Zibo Central Hospital, Zibo, China
| | - Yiding Yu
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yuehua Jiang
- Central Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yongcheng Wang
- Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xiao Li
- Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
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Li S, Zhang Y, Yang Y, Chen S, Yang Z, Kuang C, Zhong Y, Liu F. The impact of statin use before intensive care unit admission on patients with acute kidney injury after cardiac surgery. Front Pharmacol 2023; 14:1259828. [PMID: 37781714 PMCID: PMC10537929 DOI: 10.3389/fphar.2023.1259828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Accepted: 09/04/2023] [Indexed: 10/03/2023] Open
Abstract
Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious complication after cardiac surgery. The influence of statin use before surgery on the renal outcome of patients undergoing cardiac surgery is controversial. The purpose of this study was to evaluate the effect of statins on postoperative renal outcomes in patients undergoing cardiac surgery. Methods: We included CSA-AKI patients in the Medical Information Mart for Intensive Care (MIMIC)-IV database and were divided into statin group and non-statin group according to whether they used statins before entering intensive care units (ICU). The main outcomes were hospitalization and 30-day mortality, and the secondary outcomes were 60-day mortality and 90-day mortality. We used propensity score matching (PSM) to adjust for confounding factors. The 95% confidence interval (CI) and risk ratio (RO) were calculated by the COX proportional regression model. At the same time, stratified analysis was used to explore whether the relationship between the statins use before intensive care units and mortality was different in each subgroup and whether the relationship between different doses of Atorvastatin and mortality was different. Result: We identified 675 pre-ICU statin users and 2095 non-statin users. In the COX proportional regression model, pre-ICU statin use was associated with decreased in-hospital (HR = 0.407, 95%confidence interval 0.278-0.595, p < 0.001) and 30-day mortality (HR = 0.407, 95%CI 0.279-0.595, p < 0.001). The survival rate of patients who took statins before entering ICU was significantly higher than that of those who did not use statins at 30 days, 60 days and 90 days. There is a significant interaction between patients with aged>65 years (HR = 0.373, 95%CI 0.240-0.581, p < 0.001), Acute kidney injury grade I (HR = 0.244, 95%CI 0.118-0.428, p < 0.001), and without post-myocardial infarction syndrome (HR = 0.344, 95%CI 0.218-0.542, p < 0.001). The mortality in hospital and 60 days of CSA-AKI patients treated with ≥80 mg Atorvastatin before operation was significantly reduced (p < 0.05). Conclusion: The pre-ICU statin use was significantly associated with decreased risk in hospital and 30-day mortality. The preoperative use of ≥80 mg Atorvastatin may improve the prognosis of CSA-AKI.
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Affiliation(s)
- Shishi Li
- Department of Nephrology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Youlin Zhang
- Department of the Second Clinical, Shaanxi Provincial People’s Hospital, Xi’an, China
| | - Yan Yang
- Department of Nephrology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Sining Chen
- Department of Nephrology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Zhiqian Yang
- Department of Nephrology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Chaoying Kuang
- Department of Nephrology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Yuzhen Zhong
- Department of Nephrology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Fanna Liu
- Department of Nephrology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
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20
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Khan MS, Ghumman GM, Baqi A, Shah J, Aziz M, Mir T, Tahir A, Katragadda S, Singh H, Taleb M, Ali SS. Efficacy of Pemafibrate Versus Fenofibrate Administration on Serum Lipid Levels in Patients with Dyslipidemia: Network Meta-Analysis and Systematic Review. Am J Cardiovasc Drugs 2023; 23:547-558. [PMID: 37524955 DOI: 10.1007/s40256-023-00593-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/02/2023] [Indexed: 08/02/2023]
Abstract
BACKGROUND Pemafibrate is a novel fibrate class drug that is a highly potent and selective agonist of peroxisome proliferator-activated receptor α (PPARα). We performed the first ever network meta-analysis containing the largest ever group of patients to test the efficacy of pemafibrate in improving lipid levels compared with fenofibrate and placebo in patients with dyslipidemia. METHODS Potentially relevant clinical trials were identified in Medline, PubMed, Embase, clinicaltrials.gov, and Cochrane Controlled Trials registry. Nine randomized controlled trials met the inclusion criteria out of 40 potentially available articles. The primary effect outcome was a change in the levels of triglycerides (TG), high-density lipoproteins (HDL), or low-density lipoproteins (LDL) before and after the treatment. RESULTS A total of 12,359 subjects were included. The mean patient age was 54.73 (years), the mean ratio for female patients was 18.75%, and the mean examination period was 14.22 weeks. The dose for pemafibrate included in our study was 0.1, 0.2, or 0.4 mg twice daily, whereas the dose for fenofibrate was 100 mg/day. Data showed a significant reduction in TG and a mild increase in HDL levels across the pemafibrate group at different doses and fenofibrate 100 mg group (with greatest effect observed with pemafibrate 0.1 mg twice daily). A mild increase in LDL was also observed in all groups, but the increase in LDL in the 0.1 mg twice daily dose group was statistically insignificant. CONCLUSION Pemafibrate 0.1 mg twice daily dose led to highest reduction in TG levels and the highest increase in HDL levels compared with other doses of pemafibrate, fenofibrate, and placebo.
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Affiliation(s)
| | | | - Abdul Baqi
- Department of Internal Medicine, Mercy Saint Vincent Medical Center, Toledo, OH, USA
| | - Jay Shah
- Department of Cardiology, Mercy Saint Vincent Medical Center, Toledo, OH, USA
| | - Muhammad Aziz
- Department of Gastroenterology, University of Toledo, Toledo, OH, USA
| | - Tanveer Mir
- Department of Internal Medicine, Detroit Medical Center, Wayne State University, Detroit, MI, USA
| | - Ayesha Tahir
- Department of Internal Medicine, Mercy Saint Vincent Medical Center, Toledo, OH, USA
| | - Srinivas Katragadda
- Department of Internal Medicine, Mercy Saint Vincent Medical Center, Toledo, OH, USA
| | - Hemindermeet Singh
- Department of Cardiology, Mercy Saint Vincent Medical Center, Toledo, OH, USA
| | - Mohammed Taleb
- Department of Cardiology, Mercy Saint Vincent Medical Center, Toledo, OH, USA
| | - Syed Sohail Ali
- Department of Cardiology, Mercy Saint Vincent Medical Center, Toledo, OH, USA
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21
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Bao J, Zhang Y, Li Y, Guo J, He L. Low-to-moderate dose statins improve the functional outcome of acute ischemic stroke with conventional medication treatment. Cardiovasc Diagn Ther 2023; 13:686-699. [PMID: 37675093 PMCID: PMC10478016 DOI: 10.21037/cdt-23-77] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Accepted: 06/28/2023] [Indexed: 09/08/2023]
Abstract
Background Low-to-moderate dose statins (LMDSs) are more commonly used among Asian acute ischemic stroke (AIS) patients in clinical practice. However, the correlation between the LMDS use and prognosis has not been evaluated in AIS patients with conventional medication treatment alone. This study aimed to investigate the influence of LMDS on the prognosis of AIS patients and how prognosis and potential prognostic factors interact with different statin doses. Methods This retrospective cohort study included AIS patients who were admitted within 7 days after symptom onset and received conventional medication treatment alone from November 2019 to November 2020 in the Neurology, Department of West China Hospital, Sichuan University. From a total of 782 initial patients, a final cohort of 327 patients was included in the study. These patients were divided into three groups based on statin doses: non-statin (48 patients), LMDS (152 patients), and high-dose statin (HDS) (127 patients). The follow-up period was 3 months after the onset of stroke and the primary outcome was defined as a modified Rankin scale (mRS) score of 0 to 2 at 3 months, secondary outcomes were hemorrhagic transformation (HT) and death within 3 months. Stratified analysis was also conducted to test the robustness of the relationship between the use of different statin doses and functional outcomes in various subgroups. Results Compared with non-statin therapy, both LMDS therapy and HDS therapy were associated with good functional outcomes [odds ratio (OR) =3.68, 95% confidence interval (CI): 1.13-12.01, P=0.0309; OR =3.45, 95% CI: 1.06-11.26, P=0.0402, respectively] and a lower risk of HT (OR =0.30, 95% CI: 0.11-0.86, P=0.0253; OR =0.36, 95% CI: 0.13-0.99, P=0.0488, respectively). However, there was no significant difference in all-cause death within 3 months among the three groups (OR =0.84, 95% CI: 0.29-2.46, P=0.7468; OR =0.76, 95% CI: 0.26-2.22, P=0.6104). Additionally, no significant differences were observed between LMDS therapy and HDS therapy regarding good functional outcomes at 3 months (OR =0.94, 95% CI: 0.50-1.77, P=0.8411) and the occurrence of HT (OR =1.19, 95% CI: 0.47-3.02, P=0.7093). The results of the relationship between different statin doses and 3-month good functional outcome were consistent after interaction tests. Conclusions Our findings provide evidence for the benefit and safety of LMDS therapy in AIS patients with medication treatment alone. LMDS therapy is associated with favorable impacts on 3-month functional outcomes and a reduced risk of HT compared to non-statin therapy. There were no significant differences in achieving 3-month good functional outcome, the risk of HT or death within 3 months were observed between LMDS and HDS therapy in our study. Further studies with prospective design and larger sample sizes are necessary to validate our results.
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22
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Akinosun AS, Kamya S, Watt J, Johnston W, Leslie SJ, Grindle M. Cardiovascular disease behavioural risk factors in rural interventions: cross-sectional study. Sci Rep 2023; 13:13376. [PMID: 37591952 PMCID: PMC10435574 DOI: 10.1038/s41598-023-39451-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 07/25/2023] [Indexed: 08/19/2023] Open
Abstract
This study aims to (1) assess the distribution of variables within the population and the prevalence of cardiovascular disease (CVD) behavioural risk factors in patients, (2) identify target risk factor(s) for behaviour modification intervention, and (3) develop an analytical model to define cluster(s) of risk factors which could help make any generic intervention more targeted to the local patient population. Study patients with at least one CVD behavioural risk factor living in a rural region of the Scottish Highlands. The study used the STROBE methodology for cross-sectional studies. Demographic and clinical data of patients (n = 2025) in NHS Highlands hospital were collected at the point of admission for PCI between 04.01.2016 and 31.12.2019. Collected data distributions were analysed by CVD behavioural risk factors for prevalence, associations, and direction of associations. Cluster definition was measured by assignment of a unit score each for the overall level of prevalence and significance of associations, and general logistics modelling for direction and significance of the risk. The mean (SD) age was 69.47(± 10.93) years [95% CI (68.99-69.94)]. The key risk factors were hyperlipidaemia, hypertension, and elevated body mass index (BMI). Approximately 40% of the population have multiple risk factor counts of two. Analytical measures revealed a population risk factor cluster with elevated BMI [77.5% (1570/2025)] that is mostly either hyperlipidaemic [9.43%, co-eff. (17), P = 0.007] or hypertensive [22.72%, co-eff. (17), P = 0.99] as key risk factor clusters. Carefully modelled analyses revealed clustered risk associated with elevated BMI. This information would support a strategy for targeting risk factor clusters in novel interventions to improve implementation efficiency. Exposure to and outcome of an elevated BMI is linked more to the population's socio-economic outcomes rather than to regional rurality or urbanity.
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Affiliation(s)
- Adewale Samuel Akinosun
- Digital Health, Institute of Health Research and Innovation, University of the Highlands and Islands, Inverness, UK.
| | - Sylvia Kamya
- Cardiology Unit, Raigmore Hospital, NHS Highland, Inverness, Scotland, UK
| | - Jonathan Watt
- Cardiology Unit, Raigmore Hospital, NHS Highland, Inverness, Scotland, UK
| | - William Johnston
- Insight Centre for Data Analytics, University College Dublin, Dublin, Ireland
| | - Stephen J Leslie
- Cardiology Unit, Raigmore Hospital, NHS Highland, Inverness, Scotland, UK
| | - Mark Grindle
- Digital Health, Institute of Health Research and Innovation, University of the Highlands and Islands, Inverness, UK
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23
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Yuan T, Ding C, Xie Y, Zhou X, Xie C, Wang T, Yu C, Zhou W, Zhu L, Bao H, Cheng X. Association between remnant cholesterol and chronic kidney disease in Chinese hypertensive patients. Front Endocrinol (Lausanne) 2023; 14:1189574. [PMID: 37415665 PMCID: PMC10321593 DOI: 10.3389/fendo.2023.1189574] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Accepted: 06/02/2023] [Indexed: 07/08/2023] Open
Abstract
Background Remnant cholesterol (RC) and chronic kidney disease (CKD) have not been definitively linked in individuals with different characteristics. This study aims to investigate the relationship between serum RC level and CKD and examine possible effect modifiers in Chinese patients with hypertension. Methods Our study is based on the Chinese H-type Hypertension Project, which is an observational registry study conducted in real-world settings. The outcome was CKD, defined as an estimated glomerular filtration rate of less than 60 ml/min·1.73 m2. Multivariate logistic regression and smooth curve fitting were used to analyze the association between RC and CKD. Subgroup analyses were subsequently conducted to examine the effects of other variables. Results The mean age of the 13,024 patients with hypertension at baseline was 63.8 ± 9.4 years, and 46.8% were male. A conspicuous linear positive association was observed between RC level and CKD (per SD increment; odds ratio [OR], 1.15; 95% confidence interval [CI], 1.08-1.23). Compared with the lowest quartile group of RC, the risk of CKD was 53% higher (OR, 1.53; 95% CI, 1.26-1.86) in the highest quartile group. Furthermore, a stronger positive association between RC level and CKD was found among participants with a higher body mass index (BMI <24 vs. ≥24 kg/m2; P-interaction = 0.034) or current non-smokers (smoker vs. non-smoker; P-interaction = 0.024). Conclusions Among Chinese adults with hypertension, RC level was positively associated with CKD, particularly in those with a BMI of ≥24 kg/m2 and current non-smokers. These findings may help improve lipid management regimens in patients with hypertension.
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Affiliation(s)
- Ting Yuan
- Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, Jiangxi, China
| | - Congcong Ding
- Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, Jiangxi, China
| | - Yanyou Xie
- Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, Jiangxi, China
| | - Xinlei Zhou
- Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, Jiangxi, China
| | - Chong Xie
- Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, Jiangxi, China
| | - Tao Wang
- Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, Jiangxi, China
- Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang, Jiangxi, China
| | - Chao Yu
- Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, Jiangxi, China
- Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang, Jiangxi, China
| | - Wei Zhou
- Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, Jiangxi, China
- Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang, Jiangxi, China
| | - Lingjuan Zhu
- Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, Jiangxi, China
- Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang, Jiangxi, China
| | - Huihui Bao
- Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, Jiangxi, China
- Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang, Jiangxi, China
| | - Xiaoshu Cheng
- Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, Jiangxi, China
- Jiangxi Sub-center of National Clinical Research Center for Cardiovascular Diseases, Nanchang, Jiangxi, China
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Fonseca AF, Byrne H, Laguna A, Itani T, Studer R, Heo J, Dillon A, Ferber P, Costa-Scharplatz M. Burden of lipoprotein(a) for patients with atherosclerotic cardiovascular disease: A retrospective analysis from the United States. J Manag Care Spec Pharm 2023; 29:519-529. [PMID: 37121256 PMCID: PMC10387958 DOI: 10.18553/jmcp.2023.29.5.519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2023]
Abstract
BACKGROUND: Lipoprotein(a) (Lp(a)) is an inherited, independent, and causal risk factor for atherosclerotic cardiovascular disease (ASCVD). OBJECTIVE: To assess the burden of elevated Lp(a) for patients with ASCVD in a real-world setting in the United States. METHODS: This retrospective cohort study assessed US patients with available Lp(a) measurement and established ASCVD using Optum's Clinformatics Data Mart database (2007-2020). Index date was defined as the first diagnosis of an ASCVD event. Patient demographics, medications, health care resource utilization (HCRU), and occurrence of cardiovascular events were assessed for patients with elevated (≥150 nmol/L) vs normal (≥65 nmol/L) Lp(a) levels, within the first year of index date. HCRU was characterized by inpatient hospitalization, inpatient length of stay (LOS), outpatient visits, and emergency department (ED) visits. All comparative analyses of patients with elevated (≥150 nmol/L) vs normal (≥65 nmol/L) Lp(a) levels within the first year of index date were adjusted for age, sex, baseline statin use, and diabetes. RESULTS: 8,372 patients with ASCVD and Lp(a) measurement in nmol/L were included in this study. Patient demographics and baseline clinical characteristics were similar among those with normal and elevated Lp(a). However, the proportion of patients receiving statins and β-blockers at baseline were significantly higher in the elevated vs normal Lp(a) group (54.76% vs 42.91%, P < 0.0001, and 30.92% vs 27.32%, P = 0.0183, respectively). At 1 year of follow-up, the rates per 100 person-years for ASCVD-related inpatient hospitalizations, outpatient hospitalizations, and ED visits were higher among patients with elevated Lp(a) compared with normal Lp(a) (13.33 vs 9.46, 89.08 vs 85.10, and 2.89 vs 2.29, respectively). The mean LOS per ASCVD-related hospitalization was 7.21 days in the elevated and 6.26 days in the normal Lp(a) group (P = 0.3462). During the 1-year post-index follow-up period, 15% of patients in the elevated Lp(a) group required revascularization compared with 10% of patients in the normal Lp(a) group (P = 0.0002). The odds of composite myocardial infarction, ischemic stroke, and revascularization occurrence of events within the first year of index was significantly higher in the elevated Lp(a) group compared with the normal Lp(a) group (1.46; 95% CI = 1.20-1.77; P < 0.05). CONCLUSIONS: HCRU within the first year of ASCVD diagnosis is substantial among patients with ASCVD and elevated Lp(a). Relatively higher rates of inpatient hospitalizations, increased LOS per hospitalization, and requirement of revascularization procedures within the first year of ASCVD index diagnosis were observed in patients with elevated Lp(a) compared with normal Lp(a) levels. Lp(a) testing in routine clinical practice could help in identification of high-risk patients with ASCVD and play an important role in the overall cardiovascular risk management, aiming to reduce the HCRU associated with ASCVD. DISCLOSURES: Ms Fonseca, Dr Laguna, Dr Itani, Dr Rachel Studer, and Dr Ferber are employees of Novartis Pharma AG, Basel, Switzerland. Ms Byrne is an employee of Novartis AG, Dublin, Ireland. Dr Costa-Scharplatz is an employee of Novartis Sweden AB, Stockholm, Sweden. Dr Heo and Ms Dillon are employees of Genesis Research. Genesis Research was commissioned to conduct the study (data extraction and analysis) on behalf of Novartis Pharma AG.
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Malick WA, Waksman O, Do R, Koenig W, Pradhan AD, Stroes ESG, Rosenson RS. Clinical Trial Design for Triglyceride-Rich Lipoprotein-Lowering Therapies: JACC Focus Seminar 3/3. J Am Coll Cardiol 2023; 81:1646-1658. [PMID: 37076219 DOI: 10.1016/j.jacc.2023.02.034] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/14/2023] [Accepted: 02/17/2023] [Indexed: 04/21/2023]
Abstract
Triglyceride-rich lipoproteins (TRLs) are a source of residual risk in patients with atherosclerotic cardiovascular disease, and are indirectly correlated with triglyceride (TG) levels. Previous clinical trials studying TG-lowering therapies have either failed to reduce major adverse cardiovascular events or shown no linkage of TG reduction with event reduction, particularly when these agents were tested on a background of statin therapy. Limitations in trial design may explain this lack of efficacy. With the advent of new RNA-silencing therapies in the TG metabolism pathway, there is renewed focus on reducing TRLs for major adverse cardiovascular event reduction. In this context, the pathophysiology of TRLs, pharmacological effects of TRL-lowering therapies, and optimal design of cardiovascular outcomes trials are major considerations.
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Affiliation(s)
- Waqas A Malick
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Ori Waksman
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Ron Do
- Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Wolfgang Koenig
- Deutsches Herzzentrum Munchen, Technische Universitat Munchen, Munich, DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany; Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
| | - Aruna D Pradhan
- Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Division of Cardiovascular Medicine, VA Boston Medical Center, Boston, Massachusetts, USA
| | - Erik S G Stroes
- Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Robert S Rosenson
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
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Dai R, Zhao X, Zhuo H, Wang W, Xu Y, Hu Z, Zhang T, Zhao J. CYP2C19 metabolizer phenotypes may affect the efficacy of statins on lowering small dense low-density lipoprotein cholesterol of patients with coronary artery disease. Front Cardiovasc Med 2022; 9:1016126. [PMID: 36601065 PMCID: PMC9806256 DOI: 10.3389/fcvm.2022.1016126] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 11/21/2022] [Indexed: 12/23/2022] Open
Abstract
Background Dyslipidemia is a major cause of arteriosclerotic cardiovascular disease (ASCVD), and low-density lipoprotein cholesterol (LDL-C) is the profile to be reduced to prevent disease progression. Small dense low-density lipoprotein cholesterol (sdLDL-C) has been proven to be a more effective biomarker than LDL-C for ASCVD primary and secondary prevention. CYP2C19 is an important drug metabolism gene. This study aimed to investigate the relationship between sdLDL-C and coronary artery disease (CAD) risk factors and explore the influence of CYP2C19 metabolizer phenotypes on the sdLDL-C lowering efficacy of statins. Methods This study recruited 182 patients with CAD and 200 non-CAD controls. Baseline laboratory indices of fasting blood were detected, including blood lipids, glucose, and creatinine. In addition, LDL-C subfractions were separated and quantified. Gene polymorphisms of SLCO1B1 and CYP2C19 were detected in patients with CAD. The LDL-C subfractions levels of patients with CAD were followed up after statin drug treatment. Results Total cholesterol, LDL-C, LDLC-2, LDLC-3, LDLC-4, LDLC-5, LDLC-6, LDLC-7, and sdLDL-C levels of patients with CAD were significantly higher than those in non-CAD controls. Meanwhile, sdLDL-C (AUC = 0.838) and LDLC-4 (AUC = 0.835) performed outstandingly in distinguishing patients with CAD from controls. Based on CYP2C19 metabolizer phenotypes, 113 patients with CAD were divided into the extensive metabolizer (EM, n = 49), intermediate metabolizer (IM, n = 52), and poor metabolizer (PM, n = 12) groups. The patients with IM and PM metabolizer phenotypes had better sdLDL-C lowering efficacy after taking statin drugs than patients with EM phenotype (P = 0.0268, FDR = 0.0536). The SLCO1B1 genotype had no significant impact on the efficacy of statins (P = 0.1611, FDR = 0.1611). Conclusion sdLDL-C and LDLC-4 outperformed other blood lipids such as LDL-C for CAD risk screening. CYP2C19 metabolizer phenotypes had the potential to predict the efficacy of statins in lowering sdLDL-C.
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Affiliation(s)
- Ruozhu Dai
- Department of Cardiology, Quanzhou First Hospital Afliated to Fujian Medical University, Quanzhou, Fujian, China
| | - Xiaoyu Zhao
- Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
| | - Huilin Zhuo
- Department of Cardiology, Quanzhou First Hospital Afliated to Fujian Medical University, Quanzhou, Fujian, China
| | - Wei Wang
- Department of Cardiology, Quanzhou First Hospital Afliated to Fujian Medical University, Quanzhou, Fujian, China
| | - Yue Xu
- Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
| | - Zixin Hu
- Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China,Artificial Intelligence Innovation and Incubation Institute, Fudan University, Shanghai, China,Fudan Zhangjiang Institute, Shanghai, China,*Correspondence: Zixin Hu ✉
| | - Tiexu Zhang
- Department of Cardiovascular Medicine, The First People's Hospital of Pingdingshan, Pingdingshan, Henan, China,Tiexu Zhang ✉
| | - Jiangman Zhao
- Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China,Jiangman Zhao ✉
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Ischemic Risk Prediction Scores. J Am Coll Cardiol 2022; 80:1748-1750. [DOI: 10.1016/j.jacc.2022.08.766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 08/30/2022] [Indexed: 11/19/2022]
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Wang X, Wen D, Chen Y, Ma L, You C. PCSK9 inhibitors for secondary prevention in patients with cardiovascular diseases: a bayesian network meta-analysis. Cardiovasc Diabetol 2022; 21:107. [PMID: 35706032 PMCID: PMC9202167 DOI: 10.1186/s12933-022-01542-4] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 05/27/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The Food and Drug Administration has approved Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors for the treatment of dyslipidemia. However, evidence of the optimal PCSK9 agents targeting PCSK9 for secondary prevention in patients with high-risk of cardiovascular events is lacking. Therefore, this study was conducted to evaluate the benefit and safety of different types of PCSK9 inhibitors. METHODS Several databases including Cochrane Central, Ovid Medline, and Ovid Embase were searched from inception until March 30, 2022 without language restriction. Randomized controlled trials (RCTs) comparing administration of PCSK9 inhibitors with placebo or ezetimibe for secondary prevention of cardiovascular events in patients with statin-background therapy were identified. The primary efficacy outcome was all-cause mortality. The primary safety outcome was serious adverse events. RESULTS Overall, nine trials totaling 54,311 patients were identified. Three types of PCSK9 inhibitors were evaluated. The use of alirocumab was associated with reductions in all-cause mortality compared with control (RR 0.83, 95% CrI 0.72-0.95). Moreover, evolocumab was associated with increased all-cause mortality compared with alirocumab (RR 1.26, 95% CrI 1.04-1.52). We also found alirocumab was associated with decreased risk of serious adverse events (RR 0.94, 95% CrI 0.90-0.99). CONCLUSIONS In consideration of the fact that both PCSK9 monoclonal antibody and inclisiran enable patients to achieve recommended LDL-C target, the findings in this meta-analysis suggest that alirocumab might provide the optimal benefits regarding all-cause mortality with relatively lower SAE risks, and evolocumab might provide the optimal benefits regarding myocardial infarction for secondary prevention in patients with high-risk of cardiovascular events. Further head-to-head trials with longer follow-up and high methodologic quality are warranted to help inform subsequent guidelines for the management of these patients.
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Affiliation(s)
- Xing Wang
- West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, 610041, People's Republic of China
| | - Dingke Wen
- West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, 610041, People's Republic of China
| | - Yuqi Chen
- West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, 610041, People's Republic of China
| | - Lu Ma
- West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, 610041, People's Republic of China.
- West China Brain Research Centre, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.
| | - Chao You
- West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, 610041, People's Republic of China.
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Berzinji B, Dizaye K. Investigating the effect of Fenofibrate on biomarkers of vascular inflammation in L-NAME induced hypertensive rats. PHARMACIA 2022. [DOI: 10.3897/pharmacia.69.e81078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
This study aims to evaluate the impact of fenofibrate on the levels of (IL-6, hsCRP, Lp-PLA2, sCD40L, and cystatin C) in hypertensive rats. Twenty-four rats were divided into two groups each of twelve. The first group served as the normotensive group, while the second group was regarded as the hypertensive group. Each group was further divided into two subgroups (control and treated). The control subgroups only received a placebo and the treated subgroups were given fenofibrate 30 mg/kg daily orally by gastric gavage for 4 weeks. The level of hsCRP, IL6, and Lp-PLA2 significantly increased, but sCD40L and cystatin C levels were not changed in hypertensive rats. Fenofibrate has significantly reduced the levels of hsCRP and Lp-LPA2 in hypertensive rats while IL6 and sCD40s have not been changed in both groups. In conclusion, Fenofibrate has revealed a pleiotropic anti-inflammatory effect by reducing the level of hsCRP and Lp-LPA2 in hypertensive rats.
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Lin Y, Yang Q, Liu Z, Su B, Xu F, Li Y, Kang J, Zhou Z. Relationship between Apolipoprotein E Genotype and Lipoprotein Profile in Patients with Coronary Heart Disease. Molecules 2022; 27:molecules27041377. [PMID: 35209166 PMCID: PMC8879216 DOI: 10.3390/molecules27041377] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/07/2022] [Accepted: 02/12/2022] [Indexed: 02/05/2023] Open
Abstract
(1) Background: Apolipoprotein E(ApoE) plays a critical role in lipid transport. The specific allele of APOE being expressed is associated with the development of coronary heart disease (CHD), however the specific mechanisms by which ApoE drives disease are unclear. In this study, we investigated the relationship between APOE allele, lipoprotein metabolome, and CHD severity to provide evidence for the efficacy of clinical cholesterol-lowering therapy; (2) Methods: Blood samples were collected from 360 patients with CHD that were actively being treated with statins. The lipoprotein profile, including particle numbers, particle size, and lipoprotein composition concentrates, was measured by nuclear magnetic resonance (NMR) spectroscopy. The severity of CHD was determined by quantifying coronary angiography results using the Gensini scoring system; (3) Results: We found there was no significant difference in low-density lipoprotein cholesterol (LDL-C) levels among ε2+ (ε2 allele carriers, consisting of ε2/ε2 and ε2/ε3 genotypes), ε3 (consisting of ε3/ε3 and ε2/ε4 genotypes), and ε4+ (ε4 allele carriers, consisting of ε3/ε4 and ε4/ε4 genotypes) participants receiving statin treatment. Compared with the ε3 group, patients with the ε2+ genotype showed lower concentrations of total low-density lipoprotein (LDL), small-LDL, and middle-LDL particles, as well as a larger LDL size, higher very low-density lipoprotein (VLDL) composition concentrates, and higher intermediate density lipoprotein (IDL) composition concentrates. The ε4+ group showed higher concentrations of total LDL, small LDL particles, and LDL compositions with smaller LDL size. The higher level of small LDL concentration was associated with a high Gensini score (B = 0.058, p = 0.024). Compared with the ε3 group, the risk of increased branch lesions in the ε2+ group was lower (OR = 0.416, p = 0.027); (4) Conclusions: The specific allele of APOE being expressed can affect the severity of CHD by altering components of the lipoprotein profile, such as the concentration of small LDL and LDL size.
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High Frequency of Microvascular Dysfunction in US Outpatient Clinics: A Sign of High Residual Risk? Data from 7,105 Patients. Int J Vasc Med 2022; 2022:4224975. [PMID: 35036009 PMCID: PMC8758294 DOI: 10.1155/2022/4224975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 10/24/2021] [Accepted: 10/26/2021] [Indexed: 11/18/2022] Open
Abstract
Previous studies have linked peripheral microvascular dysfunction measured by arterial tonometry to high residual risk in on-statin patients. Digital thermal monitoring (DTM) of microvascular function is a new and simplified technique based on fingertip temperature measurements that has been correlated with the burden of atherosclerosis and its risk factors. Here, we report analyses of DTM data from two large US registries: Registry-I (6,084 cases) and Registry-II (1,021 cases) across 49 US outpatient clinics. DTM tests were performed using a VENDYS device during a 5-minute arm-cuff reactive hyperemia. Fingertip temperature falls during cuff inflation and rebounds after deflation. Adjusted maximum temperature rebound was reported as vascular reactivity index (VRI). VRI distributions were similar in both registries, with mean ± SD of 1.58 ± 0.53 in Registry-I and 1.52 ± 0.43 in Registry-II. In the combined dataset, only 18% had optimal VRI (≥2.0) and 82% were either poor (<1.0) or intermediate (1.0-2.0). Women had slightly higher VRI than men (1.62 ± 0.56 vs. 1.54 ± 0.47, p < 0.001). VRI was inversely but mildly correlated with age (r = −0.19, p < 0.001). Suboptimal VRI was found in 72% of patients <50 years, 82% of 50-70 years, and 86% of ≥70 years. Blood pressure was not correlated with VRI. In this largest registry of peripheral microvascular function measurements, suboptimal scores were highly frequent among on-treatment patients, possibly suggesting a significant residual risk. Prospective studies are warranted to validate microvascular dysfunction as an indicator of residual risk.
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Sakata K, Kumakura H, Funada R, Matsuo Y, Nakashima K, Iwasaki T, Ichikawa S. Lipoprotein(a) is a Promising Residual Risk Factor for Long-Term Clinical Prognosis in Peripheral Arterial Disease. Ann Vasc Dis 2022; 15:186-192. [PMID: 36310737 PMCID: PMC9558143 DOI: 10.3400/avd.oa.22-00046] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 06/13/2022] [Indexed: 11/17/2022] Open
Abstract
Objectives: We investigated the relationship between plasma lipoprotein(a) [Lp(a)] level and long-term prognosis, cardiovascular events, or pure leg events (LE) in patients with peripheral arterial disease (PAD). Materials and Methods: We prospectively enrolled 1104 PAD patients. The endpoints were LE, cerebrovascular- or cardiovascular-related death (CVRD), all-cause death (ACD), and major adverse cardiovascular events (MACE). Results: The incidences of LE, CVRD, ACD, and MACE were correlated with Lp(a) level (P<0.05). Lp(a) was positively correlated with low-density lipoprotein cholesterol and C-reactive protein (CRP) and negatively correlated with estimated glomerular filtration rate (eGFR). In the Cox multivariate regression analysis, high Lp(a), CRP, age, low ankle-brachial pressure index (ABI), eGFR, albumin, critical limb ischemia (CLI), cerebrovascular disease (CVD), and diabetes were associated with LE; high Lp(a), age, CRP, low ABI, body mass index, eGFR, albumin, CLI, coronary heart disease (CHD), CVD, and diabetes were associated with CVRD; high Lp(a), CRP, age, low ABI, eGFR, albumin, CLI, and CVD were associated with ACD; and high Lp(a), CRP, age, low eGFR, albumin, CLI, CHD, and diabetes were associated with MACE (P<0.05). Statins improved all endpoints (P<0.01). Conclusion: Lp(a) was a significant residual risk factor for LE, CVRD, ACD, and MACE in PAD patients.
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Affiliation(s)
- Kimimasa Sakata
- Department of Cardiovascular Surgery, Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital)
| | - Hisao Kumakura
- Department of Cardiovascular Medicine, Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital)
| | - Ryuichi Funada
- Department of Cardiovascular Medicine, Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital)
| | - Yae Matsuo
- Department of Cardiovascular Medicine, Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital)
| | - Kuniki Nakashima
- Department of Cardiovascular Surgery, Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital)
| | - Toshiya Iwasaki
- Department of Cardiovascular Medicine, Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital)
| | - Shuichi Ichikawa
- Department of Cardiovascular Medicine, Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital)
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OUP accepted manuscript. J Appl Lab Med 2022; 7:1047-1061. [DOI: 10.1093/jalm/jfac039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 04/25/2022] [Indexed: 11/14/2022]
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Wang J, Sun Q, An Y, Liu J, Leng S, Wang G. The association of remnant cholesterol (RC) and interaction between RC and diabetes on the subsequent risk of hypertension. Front Endocrinol (Lausanne) 2022; 13:951635. [PMID: 36093110 PMCID: PMC9452782 DOI: 10.3389/fendo.2022.951635] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 07/29/2022] [Indexed: 11/21/2022] Open
Abstract
PURPOSE Whether elevated remnant cholesterol (RC) is associated with hypertension (HTN) and whether elevated RC interacts with diabetes on the subsequent risk of HTN have not been illustrated. Thus, this study is aimed to investigate the associations and interactions of RC, diabetes, and the management of cardiovascular risk factors with the risk of incident HTN in a Chinese population. PATIENTS AND METHODS This cohort study included 42,994 individuals who participated in the routine health check-up from April 2016 to August 2020 and follow-ups from April 2017 to August 2021 at the Medical Examination Center of Beijing Chao-Yang Hospital. RC was divided into quintiles as follows: the < 20% group, the 20-39% group, the 40-59% group, the 60-79% group, and the ≥ 80% group. This study finally included 17,006 participants who were free from HTN at baseline. RESULTS This study had 1,861 (10.90%) HTN occurred, 205 (5.30%) in the first quintile of RC, 335 (8.98%) in the second quintile of RC, 388 (11.17%) in the third quintile of RC, 420 (13.42%) in the fourth quintile of RC, and 513 (17.91%) in the fifth quintile of RC. Compared with participants in the first quintile of RC, participants in the fifth quintile of RC showed a greater risk of HTN events among participants with diabetes [hazard ratio (HR), 4.95; 95% confidence interval (CI), 1.05-23.39; P = 0.0432) than among participants without diabetes (HR, 1.67; 95% CI, 1.26-2.22, P = 0.0004; P for interaction = 0.0420). Compared with participants without diabetes, participants with diabetes who have the ideal management of RC and other risk factors showed no excess risk of HTN. CONCLUSIONS Elevated RC is significantly predictive of HTN among the diabetic population. RC and diabetes interacted with each other on the subsequent risk of HTN, and the desired management of RC, glucose, and cardiovascular risk factors on HTN risk was quite favorable.
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Affiliation(s)
- Jie Wang
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Qi Sun
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Yu An
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Jia Liu
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Song Leng
- Health Management Center, The Second Hospital of Dalian Medical University, Dalian, China
- *Correspondence: Song Leng, ; Guang Wang,
| | - Guang Wang
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
- *Correspondence: Song Leng, ; Guang Wang,
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Ishii J, Kashiwabara K, Ozaki Y, Takahashi H, Kitagawa F, Nishimura H, Ishii H, Iimuro S, Kawai H, Muramatsu T, Naruse H, Iwata H, Tanizawa-Motoyama S, Ito H, Watanabe E, Matsuyama Y, Fukumoto Y, Sakuma I, Nakagawa Y, Hibi K, Hiro T, Hokimoto S, Miyauchi K, Ohtsu H, Izawa H, Ogawa H, Daida H, Shimokawa H, Saito Y, Kimura T, Matsuzaki M, Nagai R. Small Dense Low-Density Lipoprotein Cholesterol and Cardiovascular Risk in Statin-Treated Patients with Coronary Artery Disease. J Atheroscler Thromb 2021; 29:1458-1474. [PMID: 34880156 PMCID: PMC9529381 DOI: 10.5551/jat.63229] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Aim: We investigated the relationship between small dense low-density cholesterol (sdLDL-C) and risk of major adverse cardiovascular events (MACE) in patients treated with high- or low-dose statin therapy.
Methods: This was a prospective case-cohort study within the Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study, a randomized trial of high- or low-dose (4 or 1 mg/d pitavastatin, respectively) statin therapy, in patients with stable coronary artery disease (CAD). Serum sdLDL-C was determined using an automated homogenous assay at baseline (randomization after a rule-in period, ＞1 month with 1 mg/d pitavastatin) and 6 months after randomization, in 497 MACE cases, and 1543 participants randomly selected from the REAL-CAD study population.
Results: High-dose pitavastatin reduced sdLDL-C by 20% than low-dose pitavastatin (p for interaction ＜0.001). Among patients receiving low-dose pitavastatin, baseline sdLDL-C demonstrated higher MACE risk independent of LDL-C (hazard ratio [95% confidence interval], 4th versus 1st quartile, 1.67 [1.04–2.68];p for trend=0.034). High-dose (versus low-dose) pitavastatin reduced MACE risk by 46% in patients in the highest baseline sdLDL-C quartile (＞34.3 mg/dL; 0.54 [0.36–0.81];p=0.003), but increased relative risk by 40% in patients with 1st quartile (≤ 19.5 mg/dL; 1.40 [0.94–2.09];p=0.099) and did not alter risk in those in 2nd and 3rd quartiles (p for interaction=0.002).
Conclusions: These findings associate sdLDL-C and cardiovascular risk, independent of LDL-C, in statin-treated CAD patients. Notably, high-dose statin therapy reduces this risk in those with the highest baseline sdLDL-C.
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Affiliation(s)
- Junnichi Ishii
- Department of Clinical Laboratory, Bantane Hospital, Fujita Health University School of Medicine
| | - Kosuke Kashiwabara
- Data Science Office, Clinical Research Promotion Center, The University of Tokyo Hospital
| | - Yukio Ozaki
- Department of Cardiology, Fujita Health University School of Medicine
| | | | - Fumihiko Kitagawa
- Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine
| | - Hideto Nishimura
- Department of Cardiology, Fujita Health University School of Medicine
| | - Hideki Ishii
- Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine
| | - Satoshi Iimuro
- Innovation and Research Support Center, International University of Health and Welfare
| | - Hideki Kawai
- Department of Cardiology, Fujita Health University School of Medicine
| | - Takashi Muramatsu
- Department of Cardiology, Fujita Health University School of Medicine
| | - Hiroyuki Naruse
- Faculty of Medical Technology, School of Health Sciences, Fujita Health University
| | - Hiroshi Iwata
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine
| | | | - Hiroyasu Ito
- Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine
| | - Eiichi Watanabe
- Department of Cardiology, Fujita Health University School of Medicine
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health, The University of Tokyo
| | - Yoshihiro Fukumoto
- Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine
| | | | - Yoshihisa Nakagawa
- Department of Cardiovascular Medicine, Shiga University of Medical Science
| | - Kiyoshi Hibi
- Division of Cardiology, Yokohama City University Medical Center
| | - Takafumi Hiro
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine
| | | | - Katsumi Miyauchi
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine
| | - Hiroshi Ohtsu
- Clinical Pharmacology and Regulatory Science, Graduate School of Medicine, Juntendo University
| | - Hideo Izawa
- Department of Cardiology, Fujita Health University School of Medicine
| | | | - Hiroyuki Daida
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine
| | - Hiroaki Shimokawa
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan, and International University of Health and Welfare
| | | | - Takeshi Kimura
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
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Honda S, Puri R, Anderson T, Kastelein JJP, Brennan DM, Kassahun H, Somaratne R, Wasserman SM, Nissen SE, Nicholls SJ. Determinants of Plaque Progression Despite Very Low Low-Density Lipoprotein-Cholesterol Levels With the PCSK9 Inhibitor, Evolocumab. JACC Cardiovasc Imaging 2021; 15:709-711. [PMID: 34922870 DOI: 10.1016/j.jcmg.2021.11.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 10/25/2021] [Accepted: 11/10/2021] [Indexed: 11/29/2022]
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Talasaz AH, Ho ACJ, Bhatty F, Koenig RA, Dixon DL, Baker WL, Van Tassell BW. Meta-analysis of clinical outcomes of PCSK9 modulators in patients with established ASCVD. Pharmacotherapy 2021; 41:1009-1023. [PMID: 34657313 DOI: 10.1002/phar.2635] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 09/09/2021] [Accepted: 09/29/2021] [Indexed: 12/29/2022]
Abstract
The advent of monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) ushered in a new era of dyslipidemia pharmacotherapy. The first two antibodies targeting PCSK9 (evolocumab, alirocumab) approved by the United States Food and Drug Administration (FDA) provided significant and sustained reductions in atherogenic lipids and a reduced risk of atherosclerotic cardiovascular disease (ASCVD) events. More recently, phase 3 trials of inclisiran-a small interfering RNA-based agent targeting PCSK9-reported similar lipid-lowering effects and preliminary evidence of ASCVD risk reduction, although significant questions remain regarding the extent of benefits across cardiovascular outcomes. We conducted a systematic review and meta-analysis (random-effects model) of the available data on lipid lowering, incidence of atherosclerotic cardiovascular disease (ASCVD) events, and safety of pharmacologic agents targeting PCSK9. A significant and consistent reduction in low-density lipoprotein cholesterol (LDL-C) was observed across all agents (-51% [95% confidence interval {CI}: -61%, -41%]). Despite the impressive reduction in LDL-C, the individual effects on mortality, cardiovascular death, myocardial infarction (MI), and stroke remained nonsignificant. However, a consistent reduction was observed in the composite outcomes of MI, stroke, and cardiovascular death [relative risk {RR} (95% CI): 0.80 (0.73-0.87)] and MI, stroke, unstable angina (requiring revascularization), and cardiovascular death [RR (95% CI): 0.85 (0.74-0.97)]. In terms of safety outcomes, there was no significant difference in severe adverse events, new onset diabetes, neurocognitive disorders, or myalgia. Meanwhile, injection site reaction was more frequent in patients receiving these agents compared to placebo [RR 2.11 (95% CI): 1.26-3.54]. These findings suggest a class effect for favorable lipid changes and a low risk of serious adverse events among pharmacologic agents targeting PCSK9. Although there is compelling evidence that PCSK9-targeting agents reduce the risk of some cardiovascular outcomes, adequately powered studies with longer follow-up may be needed to fully characterize the magnitude of benefits across the cardiovascular spectrum.
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Affiliation(s)
- Azita H Talasaz
- Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA
| | - Ai-Chen Jane Ho
- Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA
| | - Fawzia Bhatty
- Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA
| | - Rachel A Koenig
- Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA
| | - Dave L Dixon
- Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA
| | - William L Baker
- Department of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Connecticut, USA
| | - Benjamin W Van Tassell
- Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA
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Yamamoto H, Shinke T, Otake H, Kawamori H, Toba T, Kuroda M, Hirota Y, Sakaguchi K, Ogawa W, Hirata K. Impact of daily glucose fluctuations on cardiovascular outcomes after percutaneous coronary intervention for patients with stable coronary artery disease undergoing lipid-lowering therapy. J Diabetes Investig 2021; 12:1015-1024. [PMID: 33098191 PMCID: PMC8169349 DOI: 10.1111/jdi.13448] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 10/20/2020] [Indexed: 12/20/2022] Open
Abstract
AIMS/INTRODUCTION Glucose fluctuation (GF) is a residual risk factor for coronary artery disease (CAD). We investigated whether GF influenced clinical outcomes and progression of coronary stenosis in stable CAD patients. MATERIALS AND METHODS In this prospective study, 101 consecutive lipid-controlled stable CAD patients underwent percutaneous coronary intervention were enrolled, and GF was expressed as the mean amplitude of glycemic excursion (MAGE) obtained by continuous glucose monitoring before the procedure was evaluated. At 9 months after enrollment, culprit and non-culprit (mild-to-moderate stenosis without ischemia) lesions were serially assessed by angiography. Cardiovascular events (CVE) consisting of cardiovascular death, non-fatal myocardial infarction or ischemia-driven revascularization during 2-year follow up, rapid progression in non-culprit lesions (defined as ≥10% luminal narrowing progression in lesions with stenosis ≥50%, ≥30% luminal narrowing progression in non-culprit lesions with stenosis <50% or normal segment, or progression to total occlusion) were evaluated. RESULTS CVE occurred in 25 patients, and MAGE was significantly higher in the CVE group (76.1 ± 24.8 mg/dL vs 59.3 ± 23.7 mg/dL; P = 0.003). Multivariate analysis showed that MAGE was an independent predictor of CVE (odds ratio 1.027, 95% confidence interval 1.008-1.047; P = 0.005). The optimal MAGE value to predict CVE was 70.7 mg/dL (area under the curve 0.687, 95% confidence interval 0.572-0.802; P = 0.005). Furthermore, MAGE was independently associated with rapid progression, and with the luminal narrowing progression in all non-culprit lesions (r = 0.400, P < 0.05). CONCLUSIONS Daily GF might influence future CVE in lipid-controlled stable CAD patients.
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Affiliation(s)
- Hiroyuki Yamamoto
- Division of Cardiovascular MedicineDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Toshiro Shinke
- Division of Cardiovascular MedicineDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
- Division of CardiologyDepartment of MedicineShowa University School of MedicineTokyoJapan
| | - Hiromasa Otake
- Division of Cardiovascular MedicineDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Hiroyuki Kawamori
- Division of Cardiovascular MedicineDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Takayoshi Toba
- Division of Cardiovascular MedicineDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Masaru Kuroda
- Division of Cardiovascular MedicineDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Yushi Hirota
- Division of Diabetes and EndocrinologyDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Kazuhiko Sakaguchi
- Division of Diabetes and EndocrinologyDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Wataru Ogawa
- Division of Diabetes and EndocrinologyDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Ken‐ichi Hirata
- Division of Cardiovascular MedicineDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
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Padro T, Muñoz-Garcia N, Badimon L. The role of triglycerides in the origin and progression of atherosclerosis. CLINICA E INVESTIGACION EN ARTERIOSCLEROSIS 2021; 33 Suppl 2:20-28. [PMID: 34006350 DOI: 10.1016/j.arteri.2021.02.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 02/13/2021] [Indexed: 01/02/2023]
Abstract
Hypertriglyceridaemia has been associated with cardiovascular disease risk in humans for several decades. However, only recently, data from basic research, as well as from genetic and observational studies, have suggested triglyceride-rich lipoproteins (TRLs) as causal factors for atherosclerotic cardiovascular disease. Novel findings highlighting the relevance of TRL-derived lipolytic products (remnant lipoprotein particles "RLPs"), rather than plasma triglycerides or TRL themselves, as the true mediators in atherosclerosis, have contributed to explain a causal relationship through a number of direct and indirect mechanisms. Thus, experimental studies in animal models and in vitro cell culture methods reveal that RLPs, having sizes below 70-80nm, enter the arterial wall and accumulate within the sub-endothelial space. They then become involved in the cholesterol deposition of cholesterol in the intima in addition to several pro-inflammatory and pro-apoptotic pathways. In this review, a summary is presented of current understanding of the pathophysiological mechanisms by which TRLs and their lipolytic derived RLP induce the formation and progression of atherosclerotic lesions, and actively contribute to cardiovascular disease.
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Affiliation(s)
- Teresa Padro
- Cardiovascular-Program ICCC, Research Institute Hospital Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain; CIBERCV Instituto de Salud Carlos III, Barcelona, Spain.
| | - Natalia Muñoz-Garcia
- Cardiovascular-Program ICCC, Research Institute Hospital Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain
| | - Lina Badimon
- Cardiovascular-Program ICCC, Research Institute Hospital Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain; CIBERCV Instituto de Salud Carlos III, Barcelona, Spain; Cardiovascular Research Chair, UAB, Barcelona, Spain
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40
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Johansen MØ, Vedel-Krogh S, Nielsen SF, Afzal S, Davey Smith G, Nordestgaard BG. Per-Particle Triglyceride-Rich Lipoproteins Imply Higher Myocardial Infarction Risk Than Low-Density Lipoproteins: Copenhagen General Population Study. Arterioscler Thromb Vasc Biol 2021; 41:2063-2075. [PMID: 33827253 DOI: 10.1161/atvbaha.120.315639] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
[Figure: see text].
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Affiliation(s)
- Mia Ø Johansen
- Department of Clinical Biochemistry (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.), Herlev and Gentofte Hospital, CopenhagenUniversity Hospital, Denmark.,The Copenhagen General Population Study (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark.,Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.)
| | - Signe Vedel-Krogh
- Department of Clinical Biochemistry (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.), Herlev and Gentofte Hospital, CopenhagenUniversity Hospital, Denmark.,The Copenhagen General Population Study (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark.,Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.)
| | - Sune F Nielsen
- Department of Clinical Biochemistry (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.), Herlev and Gentofte Hospital, CopenhagenUniversity Hospital, Denmark.,The Copenhagen General Population Study (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark.,Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.)
| | - Shoaib Afzal
- Department of Clinical Biochemistry (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.), Herlev and Gentofte Hospital, CopenhagenUniversity Hospital, Denmark.,The Copenhagen General Population Study (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark.,Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.)
| | - George Davey Smith
- MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, United Kingdom (G.D.S.).,Population Health Sciences, Bristol Medical School, University of Bristol, United Kingdom (G.D.S.)
| | - Børge G Nordestgaard
- Department of Clinical Biochemistry (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.), Herlev and Gentofte Hospital, CopenhagenUniversity Hospital, Denmark.,The Copenhagen General Population Study (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark.,Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (M.O.J., S.V.-K., S.F.N., S.A., B.G.N.)
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Kawahira Y, Shiga Y, Inoue H, Suematsu Y, Tashiro K, Kato Y, Fujimi K, Takamiya Y, Kuwano T, Sugihara M, Miura SI. Association between high-density lipoprotein cholesterol levels and major adverse cardiovascular events in patients who underwent coronary computed tomography angiography: FU-CCTA registry. Heart Vessels 2021; 36:1457-1465. [PMID: 33744994 DOI: 10.1007/s00380-021-01831-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Accepted: 03/05/2021] [Indexed: 11/29/2022]
Abstract
It is unclear whether higher levels of serum high-density lipoprotein cholesterol (HDL-C) prevent major adverse cardiovascular events (MACE). We prospectively evaluated 501 patients who had undergone coronary computed tomography angiography at Fukuoka University Hospital and either were clinically suspected of having coronary artery disease (CAD) or had at least one cardiovascular risk factor with a follow-up of up to 5 years. The primary endpoint was MACE (cardiovascular death, ischemic stroke, acute myocardial infarction and coronary revascularization). The patients were divided into tertiles according to the HDL-C level: 47 mg/dl ≥ HDL-C level [n = 167, lower HDL-C level (L-HDL)], 58 mg/dl ≥ HDL-C level ≥ 48 mg/dl [n = 167, middle HDL-C level (M-HDL)] and HDL-C level ≥ 59 mg/dl [n = 167, higher HDL-C level (H-HDL)] groups. There were significant differences in %CAD among the L-HDL, M-HDL and H-HDL groups. Unexpectedly, there was no difference in %MACE between M-HDL and H-HDL, although %MACE in M-HDL was significantly lower than that in L-HDL (p < 0.05). By a multivariate logistic regression analysis, MACE in H-HDL-C was independently associated with diabetes mellitus (DM) (p = 0.03). A Kaplan-Meier curve according to the HDL subgroup indicated that M-HDL, not H-HDL, enjoyed the greatest freedom from MACE among the 3 groups (log-rank test p = 0.047). Finally, the results of a Cox regression model indicated that L-HDL and H-HDL had significantly higher risk of MACE than M-HDL. In conclusions, patients with middle HDL-C levels, not higher HDL-C levels, showed the greatest freedom from MACE. Patients with higher HDL-C levels need to be strictly managed for DM to prevent MACE.
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Affiliation(s)
- Yuto Kawahira
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.,Department of Cardiology, Fukuoka University Nishijin Hospital, Fukuoka, Japan
| | - Yuhei Shiga
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Hiroko Inoue
- Department of Cardiology, Fukuoka University Nishijin Hospital, Fukuoka, Japan
| | - Yasunori Suematsu
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Kohei Tashiro
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Yuta Kato
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Kanta Fujimi
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.,Cardiac Rehabilitation Center, Fukuoka University Hospital, Fukuoka, Japan
| | - Yosuke Takamiya
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Takashi Kuwano
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Makoto Sugihara
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Shin-Ichiro Miura
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. .,Department of Cardiology, Fukuoka University Nishijin Hospital, Fukuoka, Japan. .,Cardiac Rehabilitation Center, Fukuoka University Hospital, Fukuoka, Japan.
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Liu H, Cao Y, Jin J, Hua Q, Li Y, Guo Y, Zhu C, Wu N, Gao R, Li J. Liver Fibrosis Scoring Systems as Novel Tools for Predicting Cardiovascular Outcomes in Patients Following Elective Percutaneous Coronary Intervention. J Am Heart Assoc 2021; 10:e018869. [PMID: 33506689 PMCID: PMC7955446 DOI: 10.1161/jaha.120.018869] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 12/16/2020] [Indexed: 12/25/2022]
Abstract
Background Previous studies have suggested a strong association of liver fibrosis scores (LFSs) with cardiovascular outcomes in patients with different cardiovascular diseases. Nonetheless, it is basically blank regarding the prognostic significance of LFSs in patients following percutaneous coronary intervention (PCI). This study sought to examine the potential role of LFSs in predicting long-term outcomes in a large cohort of patients with stable coronary artery disease after elective PCI. Methods and Results In this multicenter, prospective study, we consecutively enrolled 4003 patients with stable coronary artery disease undergoing PCI. Eight currently available noninvasive LFSs were assessed for each subject. All patients were followed up for the occurrence of cardiovascular events including cardiovascular death, nonfatal myocardial infarction, and stroke. During an average follow-up of 5.0±1.6 years, 315 (7.87%) major cardiovascular events were recorded. Subjects who developed cardiovascular events were more likely to have intermediate or high LFSs, including nonalcoholic fatty liver disease fibrosis score; fibrosis-4 score; body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes mellitus score (BARD); and aspartate aminotransferase/alanine aminotransferase ratio. Furthermore, compared with subjects with low scores, those with intermediate plus high score levels had significantly increased risk of cardiovascular events (adjusted hazard ratios ranging 1.57-1.92). Moreover, the addition of non-alcoholic fatty liver disease fibrosis score; fibrosis-4 score; or body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes mellitus score into a model with established cardiovascular risk factors significantly improved the prediction ability. Conclusions High LFSs levels might be useful for predicting adverse prognosis in patients with stable coronary artery disease following PCI, suggesting the possibility of the application of LFSs in the risk stratification before elective PCI.
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Affiliation(s)
- Hui‐Hui Liu
- State Key Laboratory of Cardiovascular DiseaseFuWai HospitalNational Center for Cardiovascular DiseasesNational Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Ye‐Xuan Cao
- State Key Laboratory of Cardiovascular DiseaseFuWai HospitalNational Center for Cardiovascular DiseasesNational Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jing‐Lu Jin
- State Key Laboratory of Cardiovascular DiseaseFuWai HospitalNational Center for Cardiovascular DiseasesNational Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Qi Hua
- Department of CardiologyXuanWu HospitalCapital Medical UniversityBeijingChina
| | - Yan‐Fang Li
- Department of CardiologyBeijing AnZhen HospitalCapital Medical UniversityBeijingChina
| | - Yuan‐Lin Guo
- State Key Laboratory of Cardiovascular DiseaseFuWai HospitalNational Center for Cardiovascular DiseasesNational Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Cheng‐Gang Zhu
- State Key Laboratory of Cardiovascular DiseaseFuWai HospitalNational Center for Cardiovascular DiseasesNational Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Na‐Qiong Wu
- State Key Laboratory of Cardiovascular DiseaseFuWai HospitalNational Center for Cardiovascular DiseasesNational Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Run‐Lin Gao
- State Key Laboratory of Cardiovascular DiseaseFuWai HospitalNational Center for Cardiovascular DiseasesNational Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jian‐Jun Li
- State Key Laboratory of Cardiovascular DiseaseFuWai HospitalNational Center for Cardiovascular DiseasesNational Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
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43
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Watts GF, Chan DC. Atherogenic Dyslipoproteinemia and Management of ASCVD: Will New Indices Untie the Gordian Knot? J Am Coll Cardiol 2020; 75:2136-2139. [PMID: 32354381 DOI: 10.1016/j.jacc.2020.03.032] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 03/10/2020] [Indexed: 01/22/2023]
Affiliation(s)
- Gerald F Watts
- Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia; School of Medicine, Faculty of Medicine and Health Sciences, University of Western Australia, Perth, Western Australia, Australia; Metabolic Research Centre, School of Medicine, Faculty of Medicine and Health Sciences, University of Western Australia, Perth, Western Australia, Australia.
| | - Dick C Chan
- School of Medicine, Faculty of Medicine and Health Sciences, University of Western Australia, Perth, Western Australia, Australia; Metabolic Research Centre, School of Medicine, Faculty of Medicine and Health Sciences, University of Western Australia, Perth, Western Australia, Australia
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Clouet-Foraison N, Marcovina SM, Guerra E, Aarsand AK, Coşkun A, Díaz-Garzón J, Fernandez-Calle P, Sandberg S, Ceriotti F, Carobene A. Analytical Performance Specifications for Lipoprotein(a), Apolipoprotein B-100, and Apolipoprotein A-I Using the Biological Variation Model in the EuBIVAS Population. Clin Chem 2020; 66:727-736. [PMID: 32353129 DOI: 10.1093/clinchem/hvaa054] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 01/27/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND With increased interest in lipoprotein(a) (Lp[a]) concentration as a target for risk reduction and growing clinical evidence of its impact on cardiovascular disease (CVD) risk, rigorous analytical performance specifications (APS) and accuracy targets for Lp(a) are required. We investigated the biological variation (BV) of Lp(a), and 2 other major biomarkers of CVD, apolipoprotein A-I (apoA-I) and apolipoprotein B-100 (apoB), in the European Biological Variation Study population. METHOD Serum samples were drawn from 91 healthy individuals for 10 consecutive weeks at 6 European laboratories and analyzed in duplicate on a Roche Cobas 8000 c702. Outlier, homogeneity, and trend analysis were performed, followed by CV-ANOVA to determine BV estimates and their 95% CIs. These estimates were used to calculate APS and reference change values. For Lp(a), BV estimates were determined on normalized concentration quintiles. RESULTS Within-subject BV estimates were significantly different between sexes for Lp(a) and between women aged <50 and >50 years for apoA-I and apoB. Lp(a) APS was constant across concentration quintiles and, overall, lower than APS based on currently published data, whereas results were similar for apoA-I and apoB. CONCLUSION Using a fully Biological Variation Data Critical Appraisal Checklist (BIVAC)-compliant protocol, our study data confirm BV estimates of Lp(a) listed in the European Federation of Clinical Chemistry and Laboratory Medicine database and reinforce concerns expressed in recent articles regarding the suitability of older APS recommendations for Lp(a) measurements. Given the heterogeneity of Lp(a), more BIVAC-compliant studies on large numbers of individuals of different ethnic groups would be desirable.
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Affiliation(s)
- Noemie Clouet-Foraison
- Northwest Lipid Metabolism and Diabetes Research Laboratories, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA
| | - Santica M Marcovina
- Northwest Lipid Metabolism and Diabetes Research Laboratories, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA
| | - Elena Guerra
- Laboratory Medicine, Ospedale San Raffaele, Milan, Italy
| | - Aasne K Aarsand
- Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.,Norwegian Organization for Quality Improvement of Laboratory Examinations (Noklus), Haraldsplass Deaconess Hospital, Bergen, Norway
| | - Abdurrahman Coşkun
- Acibadem Mehmet Ali Aydınlar University, School of Medicine, Atasehir, Istanbul, Turkey
| | - Jorge Díaz-Garzón
- Department of Laboratory Medicine, Hospital Universitario La Paz, Madrid, Spain.,Quality Analytical Commission of Spanish Society of Laboratory Medicine (SEQCML), Madrid, Spain
| | - Pilar Fernandez-Calle
- Department of Laboratory Medicine, Hospital Universitario La Paz, Madrid, Spain.,Quality Analytical Commission of Spanish Society of Laboratory Medicine (SEQCML), Madrid, Spain
| | - Sverre Sandberg
- Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.,Norwegian Organization for Quality Improvement of Laboratory Examinations (Noklus), Haraldsplass Deaconess Hospital, Bergen, Norway.,Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
| | - Ferruccio Ceriotti
- Central Laboratory, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Anna Carobene
- Laboratory Medicine, Ospedale San Raffaele, Milan, Italy
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45
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Cao YX, Zhang HW, Jin JL, Liu HH, Zhang Y, Xu RX, Gao Y, Guo YL, Zhu CG, Hua Q, Li YF, Santos RD, Wu NQ, Li JJ. Prognostic utility of triglyceride-rich lipoprotein-related markers in patients with coronary artery disease. J Lipid Res 2020; 61:1254-1262. [PMID: 32641433 PMCID: PMC7469882 DOI: 10.1194/jlr.ra120000746] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 06/17/2020] [Indexed: 01/22/2023] Open
Abstract
TG-rich lipoprotein (TRL)-related biomarkers, including TRL-cholesterol (TRL-C), remnant-like lipoprotein particle-cholesterol (RLP-C), and apoC-III have been associated with atherosclerosis. However, their prognostic values have not been fully determined, especially in patients with previous CAD. This study aimed to examine the associations of TRL-C, RLP-C, and apoC-III with incident cardiovascular events (CVEs) in the setting of secondary prevention of CAD. Plasma TRL-C, RLP-C, and total apoC-III were directly measured. A total of 4,355 participants with angiographically confirmed CAD were followed up for the occurrence of CVEs. During a median follow-up period of 5.1 years (interquartile range: 3.9-6.4 years), 543 (12.5%) events occurred. Patients with incident CVEs had significantly higher levels of TRL-C, RLP-C, and apoC-III than those without events. Multivariable Cox analysis indicated that a log unit increase in TRL-C, RLP-C, and apoC-III increased the risk of CVEs by 49% (95% CI: 1.16-1.93), 21% (95% CI: 1.09-1.35), and 40% (95% CI: 1.11-1.77), respectively. High TRL-C, RLP-C, and apoC-III were also independent predictors of CVEs in individuals with LDL-C levels ≤1.8 mmol/l (n = 1,068). The addition of RLP-C level to a prediction model resulted in a significant increase in discrimination, and all three TRL biomarkers improved risk reclassification. Thus, TRL-C, RLP-C, and apoC-III levels were independently associated with incident CVEs in Chinese CAD patients undergoing statin therapy.
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Affiliation(s)
- Ye-Xuan Cao
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Hui-Wen Zhang
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Jing-Lu Jin
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Hui-Hui Liu
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yan Zhang
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Rui-Xia Xu
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Ying Gao
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yuan-Lin Guo
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Cheng-Gang Zhu
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Qi Hua
- Department of Cardiology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yan-Fang Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Raul D Santos
- Heart Institute (InCor), University of Sao Paulo Medical School Hospital and Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | - Na-Qiong Wu
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Jian-Jun Li
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
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46
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Zhao Q, Zhang TY, Cheng YJ, Ma Y, Xu YK, Yang JQ, Zhou YJ. Prognostic impact of estimated remnant-like particle cholesterol in patients with differing glycometabolic status: an observational cohort study from China. Lipids Health Dis 2020; 19:179. [PMID: 32736631 PMCID: PMC7393817 DOI: 10.1186/s12944-020-01355-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 07/27/2020] [Indexed: 12/02/2022] Open
Abstract
Background It is uncertain whether estimated remnant-like particle cholesterol (RLP-C) could predict residual risk in patients with different glycometabolic status. This study aimed to evaluate the relationship between estimated RLP-C and adverse prognosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) treated with percutaneous coronary intervention (PCI) and to identify the potential impact of glycometabolism on the predictive value of estimated RLP-C. Methods The study assessed 2419 participants with NSTE-ACS undergoing PCI at Beijing Anzhen Hospital from January to December 2015. Estimated RLP-C was calculated as follows: total cholesterol (TC) minus low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The adverse events included all-cause death, non-fatal myocardial infarction (MI), and ischemia-driven revascularization. Results Estimated RLP-C was prominently associated with adverse prognosis in the total population [hazard ratio (HR) 1.291 per 1-SD increase, 95% confidence interval (CI) 1.119–1.490, P < 0.001], independent of confounding risk factors. However, subgroup analysis showed that increasing estimated RLP-C was related to a higher risk of adverse events in the diabetic population only [HR 1.385 per 1-SD increase, 95% CI 1.183–1.620, P < 0.001]. Estimated RLP-C failed to be a significant determinant of adverse prognosis in non-diabetic and pre-diabetic subgroups. The addition of estimated RLP-C to a baseline model including traditional risk factors enhanced the predictive performance both in total and diabetic populations. Conclusions High estimated RLP-C level is a significant predictor for recurrent adverse events in patients with diabetes and NSTE-ACS treated with PCI.
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Affiliation(s)
- Qi Zhao
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.,Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical center for coronary heart disease, Capital Medical University, Beijing, 100029, China
| | - Ting-Yu Zhang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.,Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical center for coronary heart disease, Capital Medical University, Beijing, 100029, China
| | - Yu-Jing Cheng
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.,Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical center for coronary heart disease, Capital Medical University, Beijing, 100029, China
| | - Yue Ma
- Research Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Ying-Kai Xu
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.,Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical center for coronary heart disease, Capital Medical University, Beijing, 100029, China
| | - Jia-Qi Yang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.,Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical center for coronary heart disease, Capital Medical University, Beijing, 100029, China
| | - Yu-Jie Zhou
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China. .,Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical center for coronary heart disease, Capital Medical University, Beijing, 100029, China.
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47
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Mora S. Lp(a)'s Odyssey: Should We Measure Lp(a) Post-ACS and What Should We Do With the Results? J Am Coll Cardiol 2020; 75:145-147. [PMID: 31948642 DOI: 10.1016/j.jacc.2019.11.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 11/06/2019] [Accepted: 11/08/2019] [Indexed: 10/25/2022]
Affiliation(s)
- Samia Mora
- Center for Lipid Metabolomics, Brigham and Women's Hospital, Boston, Massachusetts.
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48
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Suwa S, Ogita M, Takahashi N, Wada H, Dohi T, Kasai T, Okazaki S, Shimada K, Miyauchi K, Bujo H, Daida H. Impact of LR11 as Residual Risk on Long-Term Clinical Outcomes in Patients with Coronary Artery Disease Treated with Statins after First Percutaneous Coronary Intervention. Int Heart J 2020; 61:470-475. [PMID: 32350212 DOI: 10.1536/ihj.19-686] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Cardiovascular events still occur despite statin-based lipid-lowering therapy in patients with coronary artery disease (CAD). LR11, a member of the low-density lipoprotein receptor family, is a novel marker for the proliferation of intimal smooth muscle cells, which are critical to atherosclerotic plaque formation. We evaluated the impact of LR11 on long-term clinical outcomes in CAD patients treated with statins after percutaneous coronary intervention (PCI).This study included 223 consecutive CAD patients (age, 64.5 ± 9.6 years; male, 81.2%) treated with statin after first PCI between March 2003 and December 2004 at our institution. Patients were stratified to two groups according to LR11 levels (median). Composite cardiovascular disease (CVD) endpoints that included cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke were compared between groups.The rate of CVD endpoints was significantly higher in the high LR11 group (log-rank, P = 0.0029) during the median follow-up period of 2844 days. Multivariate Cox regression analysis showed that a higher LR11 level was significantly associated with adverse clinical outcomes (adjusted hazard ratio for composite CVD endpoints, 2.47; 95% confidence interval, 1.29-4.92; P = 0.006).Elevated levels of LR11 were significantly associated with long-term clinical outcomes among CAD patients treated with statins after first PCI.
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Affiliation(s)
- Satoru Suwa
- Department of Cardiology, Juntendo University Shizuoka Hospital
| | - Manabu Ogita
- Department of Cardiology, Juntendo University Shizuoka Hospital
| | | | - Hideki Wada
- Department of Cardiology, Juntendo University Shizuoka Hospital
| | - Tomotaka Dohi
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine
| | - Takatoshi Kasai
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine
| | - Shinya Okazaki
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine
| | - Kazunori Shimada
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine
| | - Katsumi Miyauchi
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine
| | - Hideaki Bujo
- Department of Clinical Laboratory and Experimental Research Medicine, Toho University Sakura Medical Center
| | - Hiroyuki Daida
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine
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49
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Kolovou GD, Watts GF, Mikhailidis DP, Pérez-Martínez P, Mora S, Bilianou H, Panotopoulos G, Katsiki N, Ooi TC, Lopez-Miranda J, Tybjærg-Hansen A, Tentolouris N, Nordestgaard BG. Postprandial Hypertriglyceridaemia Revisited in the Era of Non-Fasting Lipid Profile Testing: A 2019 Expert Panel Statement, Main Text. Curr Vasc Pharmacol 2020; 17:498-514. [PMID: 31060488 DOI: 10.2174/1570161117666190507110519] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 04/01/2019] [Accepted: 04/21/2019] [Indexed: 12/12/2022]
Abstract
Residual vascular risk exists despite the aggressive lowering of Low-Density Lipoprotein Cholesterol (LDL-C). A contributor to this residual risk may be elevated fasting, or non-fasting, levels of Triglyceride (TG)-rich lipoproteins. Therefore, there is a need to establish whethe a standardised Oral Fat Tolerance Test (OFTT) can improve atherosclerotic Cardiovascular (CV) Disease (ASCVD) risk prediction in addition to a fasting or non-fasting lipid profile. An expert panel considered the role of postprandial hypertriglyceridaemia (as represented by an OFTT) in predicting ASCVD. The panel updated its 2011 statement by considering new studies and various patient categories. The recommendations are based on expert opinion since no strict endpoint trials have been performed. Individuals with fasting TG concentration <1 mmol/L (89 mg/dL) commonly do not have an abnormal response to an OFTT. In contrast, those with fasting TG concentration ≥2 mmol/L (175 mg/dL) or nonfasting ≥2.3 mmol/L (200 mg/dL) will usually have an abnormal response. We recommend considering postprandial hypertriglyceridaemia testing when fasting TG concentrations and non-fasting TG concentrations are 1-2 mmol/L (89-175 mg/dL) and 1.3-2.3 mmol/L (115-200 mg/dL), respectively as an additional investigation for metabolic risk prediction along with other risk factors (obesity, current tobacco abuse, metabolic syndrome, hypertension, and diabetes mellitus). The panel proposes that an abnormal TG response to an OFTT (consisting of 75 g fat, 25 g carbohydrate and 10 g proteins) is >2.5 mmol/L (220 mg/dL). Postprandial hypertriglyceridaemia is an emerging factor that may contribute to residual CV risk. This possibility requires further research. A standardised OFTT will allow comparisons between investigational studies. We acknowledge that the OFTT will be mainly used for research to further clarify the role of TG in relation to CV risk. For routine practice, there is a considerable support for the use of a single non-fasting sample.
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Affiliation(s)
- Genovefa D Kolovou
- Cardiology Department and LDL-Apheresis Unit, Onassis Cardiac Surgery Center, Athens, Greece
| | - Gerald F Watts
- Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Crawley, Australia
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), London, United Kingdom
| | - Pablo Pérez-Martínez
- Lipid and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Cordoba, and CIBER Fisiopatologia Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Samia Mora
- Center for Lipid Metabolomics, Divisions of Preventive and Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Helen Bilianou
- Department of Cardiology, Tzanio Hospital, Piraeus, Greece
| | | | - Niki Katsiki
- First Department of Internal Medicine, Division of Endocrinology-Metabolism, Diabetes Center, AHEPA University Hospital, Thessaloniki, Greece
| | - Teik C Ooi
- Department of Medicine, Division of Endocrinology and Metabolism, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - José Lopez-Miranda
- Lipid and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Cordoba, and CIBER Fisiopatologia Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Anne Tybjærg-Hansen
- Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Nicholas Tentolouris
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Børge G Nordestgaard
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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50
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Jin JL, Zhang HW, Cao YX, Liu HH, Hua Q, Li YF, Zhang Y, Wu NQ, Zhu CG, Xu RX, Gao Y, Li XL, Cui CJ, Liu G, Sun J, Dong Q, Guo YL, Li JJ. Association of small dense low-density lipoprotein with cardiovascular outcome in patients with coronary artery disease and diabetes: a prospective, observational cohort study. Cardiovasc Diabetol 2020; 19:45. [PMID: 32245386 PMCID: PMC7118853 DOI: 10.1186/s12933-020-01015-6] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Accepted: 03/16/2020] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Elevation in small dense low-density lipoprotein (sdLDL) is common in patients with diabetes mellitus (DM), which has already been reported to be associated with incidence of coronary artery disease (CAD). The aim of the present study was to investigate the prognostic value of plasma sdLDL level in patients with stable CAD and DM. METHODS A total of 4148 consecutive patients with stable CAD were prospectively enrolled into the study and followed up for major cardiovascular events (MACEs) up to 8.5 years. Plasma sdLDL level was measured in each patient by a direct method using automated chemistry analyzer. The patients were subsequently divided into four groups by the quartiles of sdLDL and the association of sdLDL level with MACEs in different status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] was evaluated. RESULTS A total of 464 MACEs were documented. Both Kaplan-Meier analysis and Cox regression analysis indicated that the patients in quartile 4 but not quartile 2 or 3 of sdLDL level had significantly higher rate of MACEs than that in lowest quartile. When the prognostic value of high sdLDL was assessed in different glucose metabolism status, the results showed that the high sdLDL plus DM was associated with worse outcome after adjustment of confounding risk factors (hazard ratio: 1.83, 95% confident interval: 1.24-2.70, p < 0.05). However, no significant association was observed for high sdLDL plus Pre-DM or NGR. CONCLUSIONS The present study firstly indicated that elevated levels of plasma sdLDL were associated with increased risk of MACEs among DM patients with proven CAD, suggesting that sdLDL may be useful for CAD risk stratification in DM.
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Affiliation(s)
- Jing-Lu Jin
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Hui-Wen Zhang
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Ye-Xuan Cao
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Hui-Hui Liu
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Qi Hua
- Department of Cardiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
| | - Yan-Fang Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Yan Zhang
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Na-Qiong Wu
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Cheng-Gang Zhu
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Rui-Xia Xu
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Ying Gao
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Xiao-Lin Li
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Chuan-Jue Cui
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Geng Liu
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Jing Sun
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Qian Dong
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
| | - Yuan-Lin Guo
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China.
| | - Jian-Jun Li
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China.
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