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Karakasis P, Patoulias D, Rizzo M, Fragakis N, Mantzoros CS. Association between remnant cholesterol and chronic kidney disease: Systematic review and meta-analysis. Diabetes Obes Metab 2025; 27:2573-2583. [PMID: 39950216 PMCID: PMC11964997 DOI: 10.1111/dom.16258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 01/16/2025] [Accepted: 01/28/2025] [Indexed: 04/04/2025]
Abstract
BACKGROUND AND AIMS Adequate lipid control has emerged as a key factor in the prevention and management of chronic kidney disease (CKD). Remnant cholesterol (RC), a lipoprotein with an established association with cardiovascular risk, has been investigated in the context of CKD. Given the conflicting results from recent studies, we performed this meta-analysis to summarize the existing evidence on the association between RC and CKD. METHODS Medline, Cochrane Library and Scopus were searched until 16 September 2024. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using random-effects meta-analyses. We set as primary end-point of interest the association between RC and CKD. RESULTS Twelve studies (4 139 674 participants) were included. Participants with RC values in the highest quantile had significantly greater odds of CKD compared to those in the lowest quantile (Odds Ratio [OR] = 1.46, 95% confidence interval [CI] = 1.26-1.68). In a sensitivity analysis confined to subjects with type 2 diabetes (T2D), those in the higher RC quantile also exhibited significantly increased odds of CKD compared to those in the lowest quantile (OR = 1.46, 95% CI = 1.20-1.78). A significant inverse association was observed between RC and estimated glomerular filtration rate (Mean Difference [MD] = -1.43 mL/min/1.73 m2 for each 1 mmol/L increase in RC, 95% CI = [-2.67, -0.19]). Additionally, individuals with T2D-related CKD had a 24% increased risk of progression to end-stage renal disease for each 1 standard deviation increase in RC (Hazard Ratio [HR] = 1.24, 95% CI = 1.04-1.47). CONCLUSIONS RC is directly associated with higher risk for CKD. Beyond traditional lipid markers, greater emphasis should be placed on RC levels in individuals with or at risk for CKD.
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Affiliation(s)
- Paschalis Karakasis
- Second Department of Cardiology, Hippokration General HospitalAristotle University of ThessalonikiThessalonikiGreece
| | - Dimitrios Patoulias
- Second Propedeutic Department of Internal Medicine, Faculty of Medicine, School of Health Sciences AristotleUniversity of ThessalonikiThessalonikiGreece
| | - Manfredi Rizzo
- Ras Al Khaimah Medical and Health Sciences UniversityRas Al KhaimahUnited Arab Emirates
- School of Medicine, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise)University of PalermoPalermoItaly
| | - Nikolaos Fragakis
- Second Department of Cardiology, Hippokration General HospitalAristotle University of ThessalonikiThessalonikiGreece
| | - Christos S. Mantzoros
- Beth Israel Deaconess Medical Center and Boston VA Healthcare SystemHarvard Medical SchoolBostonMassachusettsUSA
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Balling M, Afzal S, Varbo A, Nordestgaard BG, Langsted A. Remnant Cholesterol: Quantification, Concentrations by Sex and Age, and Risk of Ischemic Heart Disease. Clin Chem 2025; 71:451-462. [PMID: 39723642 DOI: 10.1093/clinchem/hvae217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 10/22/2024] [Indexed: 12/28/2024]
Abstract
BACKGROUND Observational and genetic causal studies have shown an association between high concentrations of remnant cholesterol and increased risk of ischemic heart disease. However, findings from randomized intervention trials that reduced plasma triglycerides, a surrogate marker of remnant cholesterol, have been conflicting. The exact mechanisms by which remnant cholesterol contributes to atherosclerosis and, ultimately, ischemic heart disease remain incompletely understood. Additionally, insight on sex and age differences and the importance of measurement differences of remnant cholesterol in plasma concentrations and risk of ischemic heart disease are sparse. CONTENT This review covers current knowledge regarding remnant cholesterol and its role in ischemic heart disease, with particular attention to measurement and sex- and age-specific differences. SUMMARY Findings from observational, genetic, and mechanistic studies support the notion that higher remnant cholesterol may be an important cause of ischemic heart disease in both women and men. Concentrations of remnant cholesterol vary by age, with a sharp increase at early adulthood for men and around menopause for women. Remnant cholesterol can be calculated from a standard lipid profile and in addition measured directly using manual ultracentrifugation, automated assays, and nuclear magnetic resonance spectroscopy. Irrespective of the method used to assess plasma concentrations, high concentrations of remnant cholesterol are consistently associated with increased risk of myocardial infarction and ischemic heart disease in observational and genetic causal studies; cholesterol rather than triglycerides in remnants drive this risk. Importantly, results from ongoing randomized clinical trials aiming specifically at lowering remnant cholesterol and ischemic heart disease are eagerly awaited.
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Affiliation(s)
- Mie Balling
- Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark
- The Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark
- Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Shoaib Afzal
- Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark
- The Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Anette Varbo
- Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark
- The Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark
| | - Børge G Nordestgaard
- Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark
- The Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Anne Langsted
- The Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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Masuda D, Okada T, Sairyou M, Takafuji K, Ohama T, Koseki M, Nishida M, Sakata Y, Yamashita S. Proteomic Analysis of Human Chylomicron Remnants Isolated by Apolipoprotein B-48 Immunoprecipitation. J Atheroscler Thromb 2025; 32:226-238. [PMID: 39085140 PMCID: PMC11802255 DOI: 10.5551/jat.64920] [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: 02/21/2024] [Accepted: 07/10/2024] [Indexed: 08/02/2024] Open
Abstract
AIM Postprandial hypertriglyceridemia (PHTG) is an independent risk factor for coronary heart diseases. PHTG exhibits accumulation of apoB-48 containing chylomicron remnants (CM-Rs) and apoB-100 containing VLDL remnants (VLDL-Rs), which are both known to be atherogenic. However, unlike VLDL-Rs, structural and functional characterization of CM-Rs remains to be elucidated due to challenges in separating CM-Rs from VLDL-Rs. Recently, we successfully isolated CM-Rs and VLDL-Rs utilizing anti-apoB-48 or apoB-100 specific antibodies. This study aimed to characterize the proteome of CM-Rs along with that of VLDL-Rs. METHODS Eight healthy subjects were enrolled. Venous blood was drawn 3 hours after high-fat-containing meals. We isolated CM-Rs and VLDL-Rs from sera through combination of ultracentrifugation and immunoprecipitation using apoB-48 or apoB-100 specific antibodies, followed by shotgun proteomic analysis. RESULTS We identified 42 CM-Rs or VLDL-Rs-associated proteins, including 11 potential newly identified proteins such as platelet basic protein (PPBP) and platelet factor 4, which are chemokines secreted from platelets. ApoA-I, apoA-IV, and clusterin, which are also known as HDL-associated proteins, were significantly more abundant in CM-Rs. Interestingly, apoC-I, which reduces the activity of lipoprotein lipase and eventually inhibits catabolism of remnant proteins, was also more abundant in CM-Rs. Moreover, we identified proteins involved in complement regulation such as complement C3 and vitronectin, and those involved in acute-phase response such as PPBP, serum amyloid A protein 2, and protein S100-A8, in both CM-Rs and VLDL-Rs. CONCLUSIONS We have firstly characterized the proteome of CM-Rs. These findings may provide an explanation for the atherogenic properties of CM-Rs.
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Affiliation(s)
- Daisaku Masuda
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
- Department of Cardiology, Rinku General Medical Center, Izumisano, Osaka, Japan
| | - Takeshi Okada
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
- Department of Community Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Masami Sairyou
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kazuaki Takafuji
- Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Tohru Ohama
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
- Department of Dental Anesthesiology, Osaka University Graduate School of Dentistry, Osaka, Japan
| | - Masahiro Koseki
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Makoto Nishida
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
- Health Care Division, Health and Counseling Center, Osaka University, Osaka, Japan
| | - Yasushi Sakata
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Shizuya Yamashita
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
- Department of Community Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
- Department of Cardiology, Rinku General Medical Center, Izumisano, Osaka, Japan
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Shang R, Rodrigues B. Lipoprotein lipase as a target for obesity/diabetes related cardiovascular disease. JOURNAL OF PHARMACY & PHARMACEUTICAL SCIENCES : A PUBLICATION OF THE CANADIAN SOCIETY FOR PHARMACEUTICAL SCIENCES, SOCIETE CANADIENNE DES SCIENCES PHARMACEUTIQUES 2024; 27:13199. [PMID: 39081272 PMCID: PMC11286490 DOI: 10.3389/jpps.2024.13199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Accepted: 07/02/2024] [Indexed: 08/02/2024]
Abstract
Worldwide, the prevalence of obesity and diabetes have increased, with heart disease being their leading cause of death. Traditionally, the management of obesity and diabetes has focused mainly on weight reduction and controlling high blood glucose. Unfortunately, despite these efforts, poor medication management predisposes these patients to heart failure. One instigator for the development of heart failure is how cardiac tissue utilizes different sources of fuel for energy. In this regard, the heart switches from using various substrates, to predominantly using fatty acids (FA). This transformation to using FA as an exclusive source of energy is helpful in the initial stages of the disease. However, over the progression of diabetes this has grave end results. This is because toxic by-products are produced by overuse of FA, which weaken heart function (heart disease). Lipoprotein lipase (LPL) is responsible for regulating FA delivery to the heart, and its function during diabetes has not been completely revealed. In this review, the mechanisms by which LPL regulates fuel utilization by the heart in control conditions and following diabetes will be discussed in an attempt to identify new targets for therapeutic intervention. Currently, as treatment options to directly target diabetic heart disease are scarce, research on LPL may assist in drug development that exclusively targets fuel utilization by the heart and lipid accumulation in macrophages to help delay, prevent, or treat cardiac failure, and provide long-term management of this condition during diabetes.
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Affiliation(s)
- Rui Shang
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
| | - Brian Rodrigues
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada
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Jung HN, Huh JH, Roh E, Han KD, Kang JG, Lee SJ, Ihm SH. High remnant-cholesterol levels increase the risk for end-stage renal disease: a nationwide, population-based, cohort study. Lipids Health Dis 2024; 23:165. [PMID: 38835081 DOI: 10.1186/s12944-024-02050-y] [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: 11/30/2023] [Accepted: 02/19/2024] [Indexed: 06/06/2024] Open
Abstract
BACKGROUND The effect of remnant-cholesterol (remnant-C) on incident end-stage renal disease (ESRD) has not been studied longitudinally. This retrospective cohort study evaluated the association between remnant-C and the development of ESRD in a nationwide Korean cohort. METHODS Participants in a National Health Insurance Service health examination (n = 3,856,985) were followed up until the onset of ESRD. The median duration of follow-up was 10.3 years. The Martin-Hopkins equation was used to determine low-density lipoprotein cholesterol (LDL-C) levels from directly measured triglyceride, high-density lipoprotein cholesterol (HDL-C), and total cholesterol levels. Remnant-C levels were determined by subtracting HDL-C and LDL-C from total cholesterol. The risk for incident ESRD was calculated for each quartile of remnant-C, adjusting for conventional risk factors such as baseline renal function, comorbidities, and total cholesterol levels. RESULTS ESRD developed in 11,073 (0.29%) participants. The risk for ESRD exhibited a gradual increase according to higher levels of remnant-C, with a 61% increased risk in the highest quartile than in the lowest (hazard ratio [HR] 1.61 [95% confidence interval (CI) 1.50-1.72]). The elevated risk for ESRD in the highest quartile versus the lowest quartile was more prominent in younger than in older subjects (20-29 years, HR 4.07 [95% CI 2.85-5.83]; 30-39 years, HR 2.39 [95% CI 1.83-3.13]; ≥ 70 years, HR 1.32 [95% CI 1.16-1.51]). In addition, the increased risk for ESRD related to higher remnant-C levels was greater in females than in males. CONCLUSIONS Independent of conventional risk factors, remnant-C levels were positively associated with incident ESRD, particularly in younger populations and adult females. Reducing remnant-C levels may be a novel preventive strategy against ESRD.
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Affiliation(s)
- Han Na Jung
- Department of Internal Medicine, Hallym University College of Medicine, 1, Hallymdaehak-Gil, Chuncheon-Si, Gangwon-Do, 24252, Republic of Korea
| | - Ji Hye Huh
- Department of Internal Medicine, Hallym University College of Medicine, 1, Hallymdaehak-Gil, Chuncheon-Si, Gangwon-Do, 24252, Republic of Korea
| | - Eun Roh
- Department of Internal Medicine, Hallym University College of Medicine, 1, Hallymdaehak-Gil, Chuncheon-Si, Gangwon-Do, 24252, Republic of Korea
| | - Kyung-Do Han
- Department of Statistics and Actuarial Science, College of Natural Sciences, Soongsil University, 369, Sangdo-Ro, Dongjak-Gu, Seoul, 06978, Republic of Korea.
| | - Jun Goo Kang
- Department of Internal Medicine, Hallym University College of Medicine, 1, Hallymdaehak-Gil, Chuncheon-Si, Gangwon-Do, 24252, Republic of Korea.
| | - Seong Jin Lee
- Department of Internal Medicine, Hallym University College of Medicine, 1, Hallymdaehak-Gil, Chuncheon-Si, Gangwon-Do, 24252, Republic of Korea
| | - Sung-Hee Ihm
- Department of Internal Medicine, Hallym University College of Medicine, 1, Hallymdaehak-Gil, Chuncheon-Si, Gangwon-Do, 24252, Republic of Korea
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Goldberg IJ, Cabodevilla AG, Younis W. In the Beginning, Lipoproteins Cross the Endothelial Barrier. J Atheroscler Thromb 2024; 31:854-860. [PMID: 38616110 PMCID: PMC11150724 DOI: 10.5551/jat.rv22017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 03/13/2024] [Indexed: 04/16/2024] Open
Abstract
Atherosclerosis begins with the infiltration of cholesterol-containing lipoproteins into the arterial wall. White blood cell (WBC)-associated inflammation follows. Despite decades of research using genetic and pharmacologic methods to alter WBC function, in humans, the most effective method to prevent the initiation and progression of disease remains low-density lipoprotein (LDL) reduction. However, additional approaches to reducing cardiovascular disease would be useful as residual risk of events continues even with currently effective LDL-reducing treatments. Some of this residual risk may be due to vascular toxicity of triglyceride-rich lipoproteins (TRLs). Another option is that LDL transcytosis continues, albeit at reduced rates due to lower circulating levels of this lipoprotein. This review will address these two topics. The evidence that TRLs promote atherosclerosis and the processes that allow LDL and TRLs to be taken up by endothelial cells leading to their accumulation with the subendothelial space.
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Affiliation(s)
- Ira J Goldberg
- Division of Endocrinology, New York University Grossman School of Medicine
| | | | - Waqas Younis
- Division of Endocrinology, New York University Grossman School of Medicine
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Park HB, Arsanjani R, Hong SJ, Yi JJ, Yi SW. Impact of hypertriglyceridaemia on cardiovascular mortality according to low-density lipoprotein cholesterol in a 15.6-million population. Eur J Prev Cardiol 2024; 31:280-290. [PMID: 37850354 DOI: 10.1093/eurjpc/zwad330] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 10/08/2023] [Accepted: 10/16/2023] [Indexed: 10/19/2023]
Abstract
AIMS The aim of this study was to assess the association between triglyceride (TG) levels and cardiovascular disease (CVD) mortality concerning low-density lipoprotein cholesterol (LDL-C) and age in the general population. METHODS AND RESULTS From the Korean National Health Insurance Service database, 15 672 028 participants aged 18-99 who underwent routine health examinations were followed up for CVD mortality. Hazard ratios for CVD mortality were calculated using Cox models after adjusting for various confounders. During a mean of 8.8 years of follow-up, 105 174 individuals died of CVD. There was a clear log-linear association between TG and overall CVD mortality down to 50 mg/dL. Each two-fold increase in TG was associated with 1.10-fold (overall CVD), 1.22-fold [ischaemic heart disease (IHD)], 1.24-fold [acute myocardial infarction (AMI)], and 1.10-fold (ischaemic stroke) higher CVD mortality. Haemorrhagic stroke and heart failure were not associated with TG levels. The impact of hypertriglyceridaemia (HTG) on CVD weakened but remained present in persons with LDL-C < 100 mg/dL, in whom each two-fold higher TG was associated with 1.05-fold (overall CVD), 1.12-fold (IHD), 1.15-fold (AMI), and 1.05-fold (ischaemic stroke) higher CVD mortality. The younger population (18-44 years) had stronger associations between TG levels and mortality from overall CVD, IHD, and AMI than the older population. CONCLUSION Hypertriglyceridaemia independently raises CVD mortality with lingering risks in young and older individuals with low LDL-C levels, suggesting the importance of management of HTG even with controlled LDL-C.
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Affiliation(s)
- Hyung-Bok Park
- Department of Cardiology, Catholic Kwandong University International St. Mary's Hospital, Incheon, South Korea
- CONNECT-AI Research Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea
| | - Reza Arsanjani
- Department of Cardiovascular Diseases, Mayo Clinic Arizona, Phoenix, AZ, USA
| | - Sung-Jin Hong
- Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jee-Jeon Yi
- Institute for Occupational and Environmental Health, Catholic Kwandong University, Gangneung, South Korea
| | - Sang-Wook Yi
- Department of Preventive Medicine and Public Health, Catholic Kwandong University College of Medicine, Bumil-ro 579, Gangwon-do, Gangneung 25601, South Korea
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Jia W, He W, Cui Q, Ye X, Qian H. The effect of sedentary time on cardiovascular disease risk in middle-aged and elderly patients with type 2 diabetes mellitus. Medicine (Baltimore) 2023; 102:e35901. [PMID: 37960772 PMCID: PMC10637485 DOI: 10.1097/md.0000000000035901] [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: 04/02/2023] [Accepted: 10/11/2023] [Indexed: 11/15/2023] Open
Abstract
Sedentary lifestyle has become quite prevalent lately, and it has been associated with cardiovascular diseases (CVDs). CVD is a primary cause of premature death in patients with type 2 diabetes mellitus (T2DM). Some studies have focused on the association between sedentary behavior and blood glucose among T2DM patients. However, the occurrence and development of CVD involves many factors, such as blood glucose, blood lipid and so on. Therefore, we comprehensively examined the association of sedentary time with overall CVD risk and various metabolic risk factors in T2DM patients. A total of 775 middle-aged and elderly patients with T2DM were assessed. Framingham risk equation was employed to assess their overall CVD risk, while the sedentary time was self-reported. Demographic data and anthropometric and cardiac metabolic indicators were separately analyzed for both genders. The median age of the respondents was 55 (range: 45-75) years, and 39.23% were women. The overall risk of CVD in women was lower than that in men. Linear regression analysis revealed that sedentary time was significantly positively correlated with overall CVD risk and triglyceride level, but not with diastolic blood pressure and glycosylated hemoglobin and high-density lipoprotein cholesterol (HDL-C) levels. However, the correlation of sedentary time with fasting blood glucose level, body mass index, total cholesterol, and low-density lipoprotein cholesterol was only detected in women. In middle-aged and elderly patients with T2DM, prolonged sedentary time may increase the triglyceride levels and the overall risk of CVD. The adverse effects of sedentary time on fasting blood glucose, body mass index, total cholesterol, and low-density lipoprotein cholesterol may exhibit sex-based differences, as they were detected only in women.
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Affiliation(s)
- Wei Jia
- Department of Endocrinology and Metabolism, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
| | - Wenxia He
- Department of Endocrinology and Metabolism, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
| | - Qian Cui
- Department of Endocrinology and Metabolism, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
| | - Xinhua Ye
- Department of Endocrinology and Metabolism, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
| | - Hui Qian
- Department of Endocrinology and Metabolism, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
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Liu T, Zhao D, Wang M, Sun J, Liu J, Li J, Duan Y, Sun Z, Hu P, Liu J, Qi Y. Association between Intermediate-Density Lipoprotein Particles and the Progression of Carotid Atherosclerosis: A Community-Based Cohort Study. J Atheroscler Thromb 2023; 30:1644-1660. [PMID: 37045783 PMCID: PMC10627743 DOI: 10.5551/jat.63937] [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: 09/12/2022] [Accepted: 02/27/2023] [Indexed: 04/14/2023] Open
Abstract
AIM Experimental studies report that intermediate-density lipoprotein (IDL), the precursor of low-density lipoprotein, promotes atherosclerotic plaque formation. However, whether IDL is involved in the development of atherosclerosis in humans is still unclear. The aim of this community-based study is to examine the association between IDL particle (IDL-P) concentrations and the 5-year progression of carotid atherosclerosis. METHODS Baseline IDL-P concentrations were measured using nuclear magnetic resonance spectroscopy in 927 participants aged 45-74 years with no history of cardiovascular disease (CVD) at baseline. To estimate the association between baseline IDL-P concentrations and 5-year progression of carotid atherosclerosis, indicated by atherosclerotic plaque progression and changes in total plaque area (TPA), multivariable-adjusted regression was employed. RESULTS During the 5-year follow-up period, 45.8% of participants developed new plaques. Baseline IDL-P concentrations were significantly associated with the progression of carotid atherosclerosis. Participants in the highest quartile of IDL-P concentrations exhibited 1.36-fold (95% confidence interval [CI]: 1.09-1.68) increased progression of carotid plaque and 1.67-fold (95% CI: 1.04-2.69) higher TPA than those in the lowest quartile. These relationships were independent of baseline concentrations of low-density lipoprotein particles and very-low-density lipoprotein particles and their subclasses. CONCLUSIONS Elevated IDL-P concentrations were independently associated with the progression of carotid atherosclerosis, suggesting that IDL-P is a novel risk factor for the development of atherosclerosis.
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Affiliation(s)
- Tianxiao Liu
- Center for Clinical and Epidemiological Research, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart,
Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education,
Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Dong Zhao
- Center for Clinical and Epidemiological Research, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart,
Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education,
Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Miao Wang
- Center for Clinical and Epidemiological Research, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart,
Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education,
Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Jiayi Sun
- Center for Clinical and Epidemiological Research, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart,
Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education,
Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Jun Liu
- Center for Clinical and Epidemiological Research, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart,
Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education,
Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Jiangtao Li
- Center for Clinical and Epidemiological Research, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart,
Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education,
Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Youling Duan
- Center for Clinical and Epidemiological Research, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart,
Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education,
Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Zhaoqing Sun
- Center for Clinical and Epidemiological Research, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart,
Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education,
Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Piaopiao Hu
- Center for Clinical and Epidemiological Research, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart,
Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education,
Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Jing Liu
- Center for Clinical and Epidemiological Research, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart,
Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education,
Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Yue Qi
- Center for Clinical and Epidemiological Research, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart,
Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education,
Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
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10
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Tang J, Wei Y, Pi C, Zheng W, Zuo Y, Shi P, Chen J, Xiong L, Chen T, Liu H, Zhao Q, Yin S, Ren W, Cao P, Zeng N, Zhao L. The therapeutic value of bifidobacteria in cardiovascular disease. NPJ Biofilms Microbiomes 2023; 9:82. [PMID: 37903770 PMCID: PMC10616273 DOI: 10.1038/s41522-023-00448-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 10/03/2023] [Indexed: 11/01/2023] Open
Abstract
There has been an increase in cardiovascular morbidity and mortality over the past few decades, making cardiovascular disease (CVD) the leading cause of death worldwide. However, the pathogenesis of CVD is multi-factorial, complex, and not fully understood. The gut microbiome has long been recognized to play a critical role in maintaining the physiological and metabolic health of the host. Recent scientific advances have provided evidence that alterations in the gut microbiome and its metabolites have a profound influence on the development and progression of CVD. Among the trillions of microorganisms in the gut, bifidobacteria, which, interestingly, were found through the literature to play a key role not only in regulating gut microbiota function and metabolism, but also in reducing classical risk factors for CVD (e.g., obesity, hyperlipidemia, diabetes) by suppressing oxidative stress, improving immunomodulation, and correcting lipid, glucose, and cholesterol metabolism. This review explores the direct and indirect effects of bifidobacteria on the development of CVD and highlights its potential therapeutic value in hypertension, atherosclerosis, myocardial infarction, and heart failure. By describing the key role of Bifidobacterium in the link between gut microbiology and CVD, we aim to provide a theoretical basis for improving the subsequent clinical applications of Bifidobacterium and for the development of Bifidobacterium nutritional products.
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Affiliation(s)
- Jia Tang
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Yumeng Wei
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Chao Pi
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Wenwu Zheng
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Ying Zuo
- Department of Comprehensive Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Peng Shi
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Jinglin Chen
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Linjin Xiong
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Tao Chen
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Huiyang Liu
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Qianjiao Zhao
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Suyu Yin
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Wei Ren
- National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Peng Cao
- The Affiliated Hospital of Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210028, P.R. China.
| | - Nan Zeng
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China.
| | - Ling Zhao
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China.
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China.
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China.
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11
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Johansen MØ, Afzal S, Vedel-Krogh S, Nielsen SF, Smith GD, Nordestgaard BG. From plasma triglycerides to triglyceride metabolism: effects on mortality in the Copenhagen General Population Study. Eur Heart J 2023; 44:4174-4182. [PMID: 37575001 DOI: 10.1093/eurheartj/ehad330] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 03/06/2023] [Accepted: 05/15/2023] [Indexed: 08/15/2023] Open
Abstract
AIMS It is unclear whether higher triglyceride metabolism per se contributes to mortality separate from elevated triglyceride-rich lipoproteins and body mass index. This study tested the hypotheses that higher triglyceride metabolism, measured as higher plasma glycerol and β-hydroxybutyrate, is associated with increased all-cause, cardiovascular, cancer, and other mortality. METHODS AND RESULTS This study included 30 000 individuals nested within 109 751 individuals from the Copenhagen General Population Study. During a median follow-up of 10.7 years, 9897 individuals died (2204 from cardiovascular, 3366 from cancer, and 2745 from other causes), while none were lost to follow-up. In individuals with glycerol >80 µmol/L (highest fourth) vs. individuals with glycerol <52 µmol/L (lowest fourth), the multivariable adjusted hazard ratio for all-cause mortality was 1.31 (95% confidence interval 1.22-1.40). In individuals with β-hydroxybutyrate >154 µmol/L (highest fourth) vs. individuals with β-hydroxybutyrate <91 µmol/L (lowest fourth), the multivariable adjusted hazard ratio for all-cause mortality was 1.18 (1.11-1.26). Corresponding values for higher plasma glycerol and β-hydroxybutyrate were 1.37 (1.18-1.59) and 1.18 (1.03-1.35) for cardiovascular mortality, 1.24 (1.11-1.39) and 1.16 (1.05-1.29) for cancer mortality, and 1.45 (1.28-1.66) and 1.23 (1.09-1.39) for other mortality, respectively. Results were robust to exclusion of first years of follow-up, to stratification for covariates including plasma triglycerides and body mass index, and to further adjustments. CONCLUSION This study observed an increased risk of all-cause, cardiovascular, cancer, and other mortality with higher triglyceride metabolism. This was not explained by higher plasma triglycerides and body mass index. The hypothesis studied in the present paper should be further validated by isotope flux studies.
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Affiliation(s)
- Mia Ø Johansen
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Elevator 7, 4th Floor, N5, Herlev DK-2730, Denmark
- The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Herlev DK-2730, Denmark
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N DK-2200, Denmark
| | - Shoaib Afzal
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Elevator 7, 4th Floor, N5, Herlev DK-2730, Denmark
- The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Herlev DK-2730, Denmark
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N DK-2200, Denmark
| | - Signe Vedel-Krogh
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Elevator 7, 4th Floor, N5, Herlev DK-2730, Denmark
- The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Herlev DK-2730, Denmark
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N DK-2200, Denmark
| | - Sune F Nielsen
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Elevator 7, 4th Floor, N5, Herlev DK-2730, Denmark
- The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Herlev DK-2730, Denmark
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N DK-2200, Denmark
| | - George Davey Smith
- MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Børge G Nordestgaard
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Elevator 7, 4th Floor, N5, Herlev DK-2730, Denmark
- The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Herlev DK-2730, Denmark
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen N DK-2200, Denmark
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12
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Katakura Y, Shimoda M, Ohnishi M, Kusano T, Dan K, Isobe H, Wamata R, Iwamoto Y, Fushimi Y, Sanada J, Obata A, Kimura T, Tatsumi F, Nakanishi S, Mune T, Kaku K, Kaneto H. Efficacy and safety of pemafibrate in patients with hypertriglyceridemia in clinical settings: A retrospective study. Nutr Metab Cardiovasc Dis 2023; 33:1444-1452. [PMID: 37246074 DOI: 10.1016/j.numecd.2023.02.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 02/03/2023] [Accepted: 02/14/2023] [Indexed: 02/23/2023]
Abstract
BACKGROUND AND AIMS Recently, pemafibrate, a selective PPARα modulator, has been developed as a treatment for hypertriglyceridemia and has attracted much attention. The aims of this study were to evaluate the efficacy and safety of pemafibrate in hypertriglyceridemia patients under clinical settings. METHODS AND RESULTS We evaluated changes in lipid profiles and various parameters before and after 24-week pemafibrate administration in patients with hypertriglyceridemia who had not previously taken fibrate medications. There were 79 cases included in the analysis. 24 weeks after the treatment with pemafibrate, TG was significantly reduced from 312 ± 226 to 167 ± 94 mg/dL. In addition, lipoprotein fractionation tests using PAGE method showed a significant decrease in the ratio of VLDL and remnant fractionations, which are TG-rich lipoproteins. After pemafibrate administration, body weight, HbA1c, eGFR, and CK levels were not changed, but liver injury indices such as ALT, AST, and γ-GTP were significantly improved. CONCLUSION In this study, pemafibrate improved the metabolism of atherosclerosis-induced lipoproteins in hypertriglyceridemia patients. In addition, it showed no off-target effects such as hepatic and renal damage or rhabdomyolysis.
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Affiliation(s)
- Yukino Katakura
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Masashi Shimoda
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan.
| | - Mana Ohnishi
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Takashi Kusano
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Kazunori Dan
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Hayato Isobe
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Ryo Wamata
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Yuichiro Iwamoto
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Yoshiro Fushimi
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Junpei Sanada
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Atsushi Obata
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Tomohiko Kimura
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Fuminori Tatsumi
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Shuhei Nakanishi
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Tomoatsu Mune
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Kohei Kaku
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
| | - Hideaki Kaneto
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan
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Samouillan V, Garcia E, Benitez-Amaro A, La Chica Lhoëst MT, Dandurand J, Actis Dato V, Guerra JM, Escolà-Gil JC, Chiabrando G, Enrich C, Llorente-Cortes V. Inhibitory Effects of LRP1-Based Immunotherapy on Cardiac Extracellular Matrix Biophysical Alterations Induced by Hypercholesterolemia. J Med Chem 2023; 66:6251-6262. [PMID: 37116069 PMCID: PMC10184115 DOI: 10.1021/acs.jmedchem.2c02103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
Abstract
The accumulation of lipids in cardiomyocytes contributes to cardiac dysfunction. The specific blockage of cardiomyocyte cholesteryl ester (CE) loading by antibodies (Abs) against the P3 sequence (Gly1127-Cys1140) of the LRP1 receptor improves cardiac insulin sensitivity. The impact of anti-P3 Abs on high-fat diet (HFD)-induced cardiac extracellular matrix (ECM) biophysical alterations was analyzed. Both IrP (without Abs) and P3-immunized rabbits (with Abs) were randomized into groups fed either HFD or a standard chow diet. Cardiac lipids, proteins, and carbohydrates were characterized by Fourier transform infrared spectroscopy in the attenuated total reflectance mode. The hydric organization and physical structure were determined by differential scanning calorimetry. HFD increased the levels of esterified lipids, collagen, and α-helical structures and upregulated fibrosis, bound water, and ECM plasticization in the heart. The inhibitory effect of anti-P3 Abs on cardiac CE accumulation was sufficient to reduce the collagen-filled extracellular space, the level of fibrosis, and the amount of bound water but did not counteract ECM plasticization in the heart of hypercholesterolemic rabbits.
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Affiliation(s)
- Valerie Samouillan
- CIRIMAT, Université de Toulouse, Université Paul Sabatier, Equipe PHYPOL, 31062 Toulouse, France
| | - Eduardo Garcia
- Biomedical Research Institute Sant Pau (IIB SANTPAU), Universitat Autonoma de Barcelona, 08041 Barcelona, Spain
- Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), 08036 Barcelona, Spain
| | - Aleyda Benitez-Amaro
- Biomedical Research Institute Sant Pau (IIB SANTPAU), Universitat Autonoma de Barcelona, 08041 Barcelona, Spain
- Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), 08036 Barcelona, Spain
| | - Maria Teresa La Chica Lhoëst
- Biomedical Research Institute Sant Pau (IIB SANTPAU), Universitat Autonoma de Barcelona, 08041 Barcelona, Spain
- Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), 08036 Barcelona, Spain
| | - Jany Dandurand
- CIRIMAT, Université de Toulouse, Université Paul Sabatier, Equipe PHYPOL, 31062 Toulouse, France
| | - Virginia Actis Dato
- Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, X5000HUA Córdoba, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Godoy Cruz, 2290 Buenos Aires, Argentina
| | - Jose Maria Guerra
- Department of Cardiology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB-SANTPAU), Universitat Autonoma de Barcelona, 08025 Barcelona, Spain
- CIBERCV, Institute of Health Carlos III, 28029 Madrid, Spain
| | - Joan Carles Escolà-Gil
- Metabolic Basis of Cardiovascular Risk, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain
- CIBER de Diabetes y enfermedades Metabólicas Asociadas (CIBERDEM), 28029 Madrid, Spain
| | - Gustavo Chiabrando
- Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Centro de Investigación en Medicina Translacional Severo R. Amuchástegui (CIMETSA), G. V. al Instituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC-CONICET-UNC), X5016KEJ Córdoba, Argentina
| | - Carlos Enrich
- Unitat de Biologia Cellular, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, 08036 Barcelona, Spain
- Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
| | - Vicenta Llorente-Cortes
- Biomedical Research Institute Sant Pau (IIB SANTPAU), Universitat Autonoma de Barcelona, 08041 Barcelona, Spain
- Institute of Biomedical Research of Barcelona (IIBB)-Spanish National Research Council (CSIC), 08036 Barcelona, Spain
- CIBERCV, Institute of Health Carlos III, 28029 Madrid, Spain
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14
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Park JK, Bafna S, Forrest IS, Duffy Á, Marquez-Luna C, Petrazzini BO, Vy HM, Jordan DM, Verbanck M, Narula J, Rosenson RS, Rocheleau G, Do R. Phenome-wide Mendelian randomization study of plasma triglyceride levels and 2600 disease traits. eLife 2023; 12:e80560. [PMID: 36988189 PMCID: PMC10079290 DOI: 10.7554/elife.80560] [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: 05/25/2022] [Accepted: 03/28/2023] [Indexed: 03/30/2023] Open
Abstract
Background Causality between plasma triglyceride (TG) levels and atherosclerotic cardiovascular disease (ASCVD) risk remains controversial despite more than four decades of study and two recent landmark trials, STRENGTH, and REDUCE-IT. Further unclear is the association between TG levels and non-atherosclerotic diseases across organ systems. Methods Here, we conducted a phenome-wide, two-sample Mendelian randomization (MR) analysis using inverse-variance weighted (IVW) regression to systematically infer the causal effects of plasma TG levels on 2600 disease traits in the European ancestry population of UK Biobank. For replication, we externally tested 221 nominally significant associations (p<0.05) in an independent cohort from FinnGen. To account for potential horizontal pleiotropy and the influence of invalid instrumental variables, we performed sensitivity analyses using MR-Egger regression, weighted median estimator, and MR-PRESSO. Finally, we used multivariable MR (MVMR) controlling for correlated lipid fractions to distinguish the independent effect of plasma TG levels. Results Our results identified seven disease traits reaching Bonferroni-corrected significance in both the discovery (p<1.92 × 10-5) and replication analyses (p<2.26 × 10-4), suggesting a causal relationship between plasma TG levels and ASCVDs, including coronary artery disease (OR 1.33, 95% CI 1.24-1.43, p=2.47 × 10-13). We also identified 12 disease traits that were Bonferroni-significant in the discovery or replication analysis and at least nominally significant in the other analysis (p<0.05), identifying plasma TG levels as a novel potential risk factor for nine non-ASCVD diseases, including uterine leiomyoma (OR 1.19, 95% CI 1.10-1.29, p=1.17 × 10-5). Conclusions Taking a phenome-wide, two-sample MR approach, we identified causal associations between plasma TG levels and 19 disease traits across organ systems. Our findings suggest unrealized drug repurposing opportunities or adverse effects related to approved and emerging TG-lowering agents, as well as mechanistic insights for future studies. Funding RD is supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) (R35-GM124836) and the National Heart, Lung, and Blood Institute of the NIH (R01-HL139865 and R01-HL155915).
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Affiliation(s)
- Joshua K Park
- Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiNew YorkUnited States
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiNew YorkUnited States
- Medical Scientist Training Program, Icahn School of Medicine at Mount SinaiNew YorkUnited States
| | - Shantanu Bafna
- Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiNew YorkUnited States
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiNew YorkUnited States
| | - Iain S Forrest
- Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiNew YorkUnited States
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiNew YorkUnited States
- Medical Scientist Training Program, Icahn School of Medicine at Mount SinaiNew YorkUnited States
| | - Áine Duffy
- Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiNew YorkUnited States
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiNew YorkUnited States
| | - Carla Marquez-Luna
- Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiNew YorkUnited States
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiNew YorkUnited States
| | - Ben O Petrazzini
- Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiNew YorkUnited States
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiNew YorkUnited States
| | - Ha My Vy
- Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiNew YorkUnited States
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiNew YorkUnited States
| | - Daniel M Jordan
- Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiNew YorkUnited States
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiNew YorkUnited States
| | | | - Jagat Narula
- Department of Medicine, Icahn School of Medicine at Mount SinaiNew YorkUnited States
- Cardiovascular Imaging Program, Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Heart, Icahn School of Medicine at Mount SinaiNew YorkUnited States
| | - Robert S Rosenson
- Department of Medicine, Icahn School of Medicine at Mount SinaiNew YorkUnited States
- Metabolism and Lipids Unit, Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Heart, Icahn School of Medicine at Mount SinaiNew YorkUnited States
| | - Ghislain Rocheleau
- Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiNew YorkUnited States
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiNew YorkUnited States
| | - Ron Do
- Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount SinaiNew YorkUnited States
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiNew YorkUnited States
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15
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Imano H, Li J, Tanaka M, Yamagishi K, Muraki I, Umesawa M, Kiyama M, Kitamura A, Sato S, Iso H. Optimal Cut-off Points of Nonfasting and Fasting Triglycerides for Prediction of Ischemic Heart Disease in Japanese General Population: The Circulatory Risk in Communities Study (CIRCS). J Atheroscler Thromb 2023; 30:110-130. [PMID: 35444102 PMCID: PMC9925200 DOI: 10.5551/jat.63358] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 02/24/2022] [Indexed: 02/04/2023] Open
Abstract
AIMS We investigated the optimal cut-off points of nonfasting and fasting triglycerides in Japanese individuals with lower average triglyceride levels than westerners. METHODS Residents aged 40-69 years without a history of ischemic heart disease or stroke were enrolled between 1980 and 1994 and followed. Serum triglyceride concentrations were measured from 10851 nonfasting (＜8 h after meal) and 4057 fasting (≥ 8 h) samples. As a prerequisite, we confirmed the shape of a receiver operating characteristic (ROC) curves, the area under ROC curves (AUC), and the integrated time-dependent AUC. We identified optimal cut-off points for incident ischemic heart disease based on C-statistic, Youden index, and Harrell's concordance statistic. We used dichotomized concentrations of triglycerides via the univariate logistic regression and Cox proportional hazards regression models. We also calculated multivariable hazard ratios and population attributable fractions to evaluate the optimal cut-off points. RESULTS Nonfasting and fasting optimal cut-off points were 145 mg/dL and 110 mg/dL, with C-statistic of 0.594 and 0.626, Youden index of 0.187 and 0.252, and Harrell's concordance statistic of 0.590 and 0.630, respectively. The corresponding multivariable hazard ratios of ischemic heart disease were 1.43 (95%CI 1.09-1.88) and 1.69 (1.03-2.77), and the corresponding population attributable fractions were 16.1% (95%CI 3.3-27.2%) and 24.6 (-0.3-43.3). CONCLUSION The optimal cut-off points of nonfasting and fasting triglycerides in the Japanese general population were 145 mg/dL and 110 mg/dL, respectively, lower than the current cut-off points recommended in the US and Europe.
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Affiliation(s)
- Hironori Imano
- Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
- Department of Public Health, Kindai University Faculty of Medicine, Osaka, Japan
- Osaka Center for Cancer and Cardiovascular Disease Prevention, Osaka, Japan
| | - Jiaqi Li
- Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Mari Tanaka
- Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kazumasa Yamagishi
- Department of Public Health Medicine, Faculty of Medicine, and Health Services Research and Development Center, University of Tsukuba
- Ibaraki Western Medical Center, Ibaraki, Japan
| | - Isao Muraki
- Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Mitsumasa Umesawa
- Department of Public Health, Dokkyo Medical University School of Medicine, Tochigi, Japan
| | - Masahiko Kiyama
- Osaka Center for Cancer and Cardiovascular Disease Prevention, Osaka, Japan
| | | | - Shinichi Sato
- Chiba Prefectural Institute of Public Health, Chiba, Japan
| | - Hiroyasu Iso
- Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
- Institute for Global Health Polycy Research (iGHP), National Center for Global Health and Medicine, Tokyo, Japan
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16
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Cheng Y, Wang Q, Niu G, Luo C. Correlation of Atherosclerotic Dyslipidemia with Long-Term Stroke Recurrence in Patients Undergoing Intravenous Thrombolysis for Acute Ischemic Stroke. Int J Gen Med 2023; 16:1621-1629. [PMID: 37159580 PMCID: PMC10163887 DOI: 10.2147/ijgm.s407971] [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: 02/28/2023] [Accepted: 04/21/2023] [Indexed: 05/11/2023] Open
Abstract
Background Atherosclerotic dyslipidemia (AD) is associated with an increased risk of cardiovascular diseases and stroke events, but the effect of AD among acute ischemic stroke (AIS) patients undergoing intravenous thrombolysis is unclear. This study aimed to investigate the relationship between AD and long-term stroke recurrence in AIS patients undergoing intravenous thrombolysis. Methods This prospective cohort study included 499 AIS patients treated with intravenous thrombolysis. Stroke subtype was classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria, patients' clinical characteristics, and results from multiple diagnostic tests. The primary endpoint event was ischemic stroke recurrence; the time to first AIS recurrence was estimated using Kaplan‒Meier analysis and compared using the two-sided Log rank test. Cox univariate and multivariate regression analyses were used to assess the association between AD and long-term stroke recurrence. Results Of the 499 patients with AIS treated with rt-PA intravenous thrombolysis, 80 (16.0%) had AD, and 60 (12.0%) had a stroke recurrence event. Kaplan‒Meier analysis showed that the stroke recurrence rate was significantly higher in patients with AD than in those without AD (p = 0.035, log rank test) and in the large-artery disease (LAD) subtype (p = 0.006, log rank test). Multivariate Cox regression analysis showed that AD (HR = 2.363, 95% CI: 1.294-4.314, P = 0.005) and atrial fibrillation (HR = 2.325, 95% CI: 1.007-5.366, P = 0.048) were associated with an increased risk of long-term stroke recurrence in AIS patients who underwent intravenous thrombolysis. Furthermore, AD was associated with an increased risk of stroke recurrence in patients undergoing intravenous thrombolysis in the LAD subtype (HR = 3.122, 95% CI: 1.304-7.437, P = 0.011). Conclusion We found that AD increases the risk of long-term stroke recurrence in AIS patients undergoing intravenous thrombolysis. This association may be stronger in the LAD subtype.
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Affiliation(s)
- Yuan Cheng
- Medical School, Fuyang Normal University, Fuyang, Anhui, People’s Republic of China
| | - Qingqing Wang
- Department of Neurology, The Affiliated Fuyang People’s Hospital of Anhui Medical University, Fuyang, Anhui, People’s Republic of China
| | - Guihong Niu
- Medical School, Fuyang Normal University, Fuyang, Anhui, People’s Republic of China
- Correspondence: Guihong Niu, Medical School, Fuyang Normal University, Fuyang, Anhui, 236300, People’s Republic of China, Email
| | - Chun Luo
- Department of Pediatric Surgery, Fuyang Women and Children’s Hospital, Fuyang, People’s Republic of China
- Chun Luo, Department of Pediatric Surgery, Fuyang Women and Children’s Hospital, Fuyang, Anhui, 236300, People’s Republic of China, Email
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17
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Gaggini M, Gorini F, Vassalle C. Lipids in Atherosclerosis: Pathophysiology and the Role of Calculated Lipid Indices in Assessing Cardiovascular Risk in Patients with Hyperlipidemia. Int J Mol Sci 2022; 24:ijms24010075. [PMID: 36613514 PMCID: PMC9820080 DOI: 10.3390/ijms24010075] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/15/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
The role of lipids is essential in any phase of the atherosclerotic process, which is considered a chronic lipid-related and inflammatory condition. The traditional lipid profile (including the evaluation of total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein) is a well-established tool to assess the risk of atherosclerosis and as such has been widely used as a pillar of cardiovascular disease prevention and as a target of pharmacological treatments in clinical practice over the last decades. However, other non-traditional lipids have emerged as possible alternative predictors of cardiometabolic risk in addition to traditional single or panel lipids, as they better reflect the overall interaction between lipid/lipoprotein fractions. Therefore, this review deals with the lipid involvement characterizing the pathophysiology of atherosclerosis, discussing some recently proposed non-traditional lipid indices and, in the light of available knowledge, their actual potential as new additive tools to better stratify cardiovascular risk in patients with hyperlipidemia as well as possible therapeutic targets in the clinical practice.
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Affiliation(s)
- Melania Gaggini
- Institute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy
| | - Francesca Gorini
- Institute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy
| | - Cristina Vassalle
- Fondazione CNR—Regione Toscana G Monasterio, Via Moruzzi 1, 56124 Pisa, Italy
- Correspondence:
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18
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Xiao D, Shao H, Huo Y, Agung Nugroho W, Ifeoluwa Ogunniran B, Fan W, Huo M. Reclamation of ginseng residues using two-stage fermentation and evaluation of their beneficial effects as dietary feed supplements for piglets. WASTE MANAGEMENT (NEW YORK, N.Y.) 2022; 154:293-302. [PMID: 36308796 DOI: 10.1016/j.wasman.2022.10.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 09/24/2022] [Accepted: 10/18/2022] [Indexed: 06/16/2023]
Abstract
Environmental pollution caused by herbal residues, such as ginseng residue (GR), and the huge waste of medicinal ingredients in such residues hinder the development of the pharmaceutical industry. Few studies focused on the biotransformation of GRs and the practical utilization of their bioproducts. In this study, we developed a two-stage fermentation method to optimize GR bioconversion and used the fermented products as dietary supplements for piglets. The tested GR contained abundant lignocelluloses, protein, sugar, and amino acids. Approximately 43.10% of the total lignocelluloses were degraded into sugars by Inonotus obliquus in stage 1 of fermentation. Meanwhile, the sugar content increased by 36.20%, which became the feed for Bacillus subtilis and Saccharomyces cerevisiae in stage 2 of fermentation. These two strains boosted the production of bacterial proteins and other metabolites, including peptides, organic acids, and amino acids. At the end of fermentation, the contents of bioactive compounds significantly increased by 3.18%-21.79%. The dietary supplementation of fermented GR significantly improved the growth performance (6.47%-7.98%), intestinal microbiota, immune function, and healthy status and reduced the diarrhea incidence and noxious gas emission of the piglets. This study provides evidence-based results for the development and deployment of a circular economy between ginseng and livestock industries.
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Affiliation(s)
- Dan Xiao
- Jilin Academy of Agricultural Science, Changchun 130033, China
| | - Hongze Shao
- Jilin Academy of Animal Husbandry and Veterinary Medicine, Changchun 130000, China
| | - Yang Huo
- School of Environment, Northeast Normal University, Changchun 130117, China
| | | | | | - Wei Fan
- School of Environment, Northeast Normal University, Changchun 130117, China.
| | - Mingxin Huo
- School of Environment, Northeast Normal University, Changchun 130117, China
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19
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Dedousis N, Teng L, Kanshana JS, Kohan AB. A single-day mouse mesenteric lymph surgery in mice: an updated approach to study dietary lipid absorption, chylomicron secretion, and lymphocyte dynamics. J Lipid Res 2022; 63:100284. [PMID: 36152881 PMCID: PMC9646667 DOI: 10.1016/j.jlr.2022.100284] [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] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 09/15/2022] [Accepted: 09/16/2022] [Indexed: 02/04/2023] Open
Abstract
The intestine plays a crucial role in regulating whole-body lipid metabolism through its unique function of absorbing dietary fat. In the small intestine, absorptive epithelial cells emulsify hydrophobic dietary triglycerides (TAGs) prior to secreting them into mesenteric lymphatic vessels as chylomicrons. Except for short- and medium-chain fatty acids, which are directly absorbed from the intestinal lumen into portal vasculature, the only way for an animal to absorb dietary TAG is through the chylomicron/mesenteric lymphatic pathway. Isolating intestinal lipoproteins, including chylomicrons, is extremely difficult in vivo because of the dilution of postprandial lymph in the peripheral blood. In addition, once postprandial lymph enters the circulation, chylomicron TAGs are rapidly hydrolyzed. To enhance isolation of large quantities of pure postprandial chylomicrons, we have modified the Tso group's highly reproducible gold-standard double-cannulation technique in rats to enable single-day surgery and lymph collection in mice. Our technique has a significantly higher survival rate than the traditional 2-day surgical model and allows for the collection of greater than 400 μl of chylous lymph with high postprandial TAG concentrations. Using this approach, we show that after an intraduodenal lipid bolus, the mesenteric lymph contains naïve CD4+ T-cell populations that can be quantified by flow cytometry. In conclusion, this experimental approach represents a quantitative tool for determining dietary lipid absorption, intestinal lipoprotein dynamics, and mesenteric immunity. Our model may also be a powerful tool for studies of antigens, the microbiome, pharmacokinetics, and dietary compound absorption.
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Affiliation(s)
- Nikolaos Dedousis
- Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA
| | - Lihong Teng
- Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA
| | - Jitendra S Kanshana
- Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA
| | - Alison B Kohan
- Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
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20
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Fu L, Tai S, Sun J, Zhang N, Zhou Y, Xing Z, Wang Y, Zhou S. Remnant Cholesterol and Its Visit-to-Visit Variability Predict Cardiovascular Outcomes in Patients With Type 2 Diabetes: Findings From the ACCORD Cohort. Diabetes Care 2022; 45:2136-2143. [PMID: 35834242 PMCID: PMC9472497 DOI: 10.2337/dc21-2511] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Accepted: 05/31/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Remnant cholesterol (remnant-C) predicts atherosclerotic cardiovascular disease, regardless of LDL-cholesterol (LDL-C) levels. This study assessed the associations between remnant-C and cardiovascular outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS This post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial used patient (type 2 diabetes >3 months) remnant-C and major adverse cardiovascular event (MACE) data from the study database. The associations between remnant-C and MACEs were evaluated using Cox proportional hazards regression analyses. We examined the relative MACE risk in remnant-C versus LDL-C discordant/concordant groups using clinically relevant LDL-C targets by discordance analyses. RESULTS The baseline analysis included 10,196 participants, with further visit-to-visit variability analysis including 9,650 participants. During follow-up (median, 8.8 years), 1,815 patients (17.8%) developed MACEs. After adjusting for traditional cardiovascular risk factors, each 1-SD increase in remnant-C was associated with a 7% higher MACE risk (hazard ratio [HR] 1.07, 95% CI 1.02-1.12, P = 0.004). In the fully adjusted model, the visit-to-visit remnant-C variability calculated using logSD (HR 1.41, 95% CI 1.18-1.69, P < 0.001) and logARV (HR 1.45, 95% CI 1.22-1.73, P < 0.001) was associated with MACEs. Residual lipid risk (remnant-C ≥31 mg/dL) recognized individuals at a higher MACE risk, regardless of LDL-C concentrations. Within each LDL-C subgroup (>100 or ≤100 mg/dL), high baseline remnant-C was associated with a higher MACE risk (HR 1.37, 95% CI 1.09-1.73, P = 0.007; HR 1.22, 95% CI 1.04-1.41, P = 0.015, respectively). CONCLUSIONS Remnant-C levels were associated with MACEs in patients with type 2 diabetes independent of LDL-C, and visit-to-visit remnant-C variability helped identify those with higher cardiovascular risk.
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Affiliation(s)
- Liyao Fu
- Department of Blood Transfusion, The Second Xiangya Hospital of Central South University, Changsha, China.,Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Shi Tai
- Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Jiaxing Sun
- Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Ningjie Zhang
- Department of Blood Transfusion, The Second Xiangya Hospital of Central South University, Changsha, China.,Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Ying Zhou
- Department of Blood Transfusion, The Second Xiangya Hospital of Central South University, Changsha, China.,Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Zhenhua Xing
- Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yongjun Wang
- Department of Blood Transfusion, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Shenghua Zhou
- Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, China
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21
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Abstract
Mild to moderate hypertriglyceridemia usually results from multiple small-effect variants in genes that control triglyceride metabolism. Hypertriglyceridemia is a critical component of the metabolic syndrome but can also occur secondary to several other conditions or drugs. Hypertriglyceridemia frequently is associated with an increased risk of cardiovascular disease (CVD). Statins are the mainstay of CVD prevention in hypertriglyceridemia, but eicosapentaenoic ethyl esters should be added in very-high-risk individuals. Although fibrates lower triglyceride levels, their role in CVD prevention remains unclear. Familial partial lipodystrophy is another relatively rare cause, although its true incidence is unknown.
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Affiliation(s)
- Alan Chait
- Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, 850 Republican, Box 358062, Seattle, WA 98109, USA.
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22
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Integrated Analysis of the microRNA–mRNA Network Predicts Potential Regulators of Atrial Fibrillation in Humans. Cells 2022; 11:cells11172629. [PMID: 36078037 PMCID: PMC9454849 DOI: 10.3390/cells11172629] [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: 07/28/2022] [Revised: 08/15/2022] [Accepted: 08/15/2022] [Indexed: 11/17/2022] Open
Abstract
Atrial fibrillation (AF) is a form of sustained cardiac arrhythmia and microRNAs (miRs) play crucial roles in the pathophysiology of AF. To identify novel miR–mRNA pairs, we performed RNA-seq from atrial biopsies of persistent AF patients and non-AF patients with normal sinus rhythm (SR). Differentially expressed miRs (11 down and 9 up) and mRNAs (95 up and 82 down) were identified and hierarchically clustered in a heat map. Subsequently, GO, KEGG, and GSEA analyses were run to identify deregulated pathways. Then, miR targets were predicted in the miRDB database, and a regulatory network of negatively correlated miR–mRNA pairs was constructed using Cytoscape. To select potential candidate genes from GSEA analysis, the top-50 enriched genes in GSEA were overlaid with predicted targets of differentially deregulated miRs. Further, the protein–protein interaction (PPI) network of enriched genes in GSEA was constructed, and subsequently, GO and canonical pathway analyses were run for genes in the PPI network. Our analyses showed that TNF-α, p53, EMT, and SYDECAN1 signaling were among the highly affected pathways in AF samples. SDC-1 (SYNDECAN-1) was the top-enriched gene in p53, EMT, and SYDECAN1 signaling. Consistently, SDC-1 mRNA and protein levels were significantly higher in atrial samples of AF patients. Among negatively correlated miRs, miR-302b-3p was experimentally validated to suppress SDC-1 transcript levels. Overall, our results suggested that the miR-302b-3p/SDC-1 axis may be involved in the pathogenesis of AF.
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23
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Abstract
Lipid disorders involving derangements in serum cholesterol, triglycerides, or both are commonly encountered in clinical practice and often have implications for cardiovascular risk and overall health. Recent advances in knowledge, recommendations, and treatment options have necessitated an updated approach to these disorders. Older classification schemes have outlived their usefulness, yielding to an approach based on the primary lipid disturbance identified on a routine lipid panel as a practical starting point. Although monogenic dyslipidemias exist and are important to identify, most individuals with lipid disorders have polygenic predisposition, often in the context of secondary factors such as obesity and type 2 diabetes. With regard to cardiovascular disease, elevated low-density lipoprotein cholesterol is essentially causal, and clinical practice guidelines worldwide have recommended treatment thresholds and targets for this variable. Furthermore, recent studies have established elevated triglycerides as a cardiovascular risk factor, whereas depressed high-density lipoprotein cholesterol now appears less contributory than was previously believed. An updated approach to diagnosis and risk assessment may include measurement of secondary lipid variables such as apolipoprotein B and lipoprotein(a), together with selective use of genetic testing to diagnose rare monogenic dyslipidemias such as familial hypercholesterolemia or familial chylomicronemia syndrome. The ongoing development of new agents-especially antisense RNA and monoclonal antibodies-targeting dyslipidemias will provide additional management options, which in turn motivates discussion on how best to incorporate them into current treatment algorithms.
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Affiliation(s)
- Amanda J Berberich
- Department of Medicine; Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, N6A 5C1.,Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, N6A 5B7
| | - Robert A Hegele
- Department of Medicine; Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, N6A 5C1.,Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, N6A 5B7
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24
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Bhargava S, de la Puente-Secades S, Schurgers L, Jankowski J. Lipids and lipoproteins in cardiovascular diseases: a classification. Trends Endocrinol Metab 2022; 33:409-423. [PMID: 35370062 DOI: 10.1016/j.tem.2022.02.001] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 02/04/2022] [Accepted: 02/07/2022] [Indexed: 12/15/2022]
Abstract
Lipids and lipoproteins, their metabolism, and their transport are essential contributing factors of cardiovascular disease (CVD) as they regulate plasma cholesterol concentration, enhancing cholesterol uptake by macrophages, leading to foam cell formation and ultimately resulting in plaque formation and inflammation. However, lipids and lipoproteins have cardioprotective functions as well, such as preventing oxidation of proatherogenic molecules and downregulating inflammatory proteins.
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Affiliation(s)
- Shruti Bhargava
- Institute of Molecular Cardiovascular Research, Medical Faculty, RWTH Aachen University, Aachen, Germany; Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht, The Netherlands
| | - Sofia de la Puente-Secades
- Institute of Molecular Cardiovascular Research, Medical Faculty, RWTH Aachen University, Aachen, Germany; Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht, The Netherlands
| | - Leon Schurgers
- Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht, The Netherlands
| | - Joachim Jankowski
- Institute of Molecular Cardiovascular Research, Medical Faculty, RWTH Aachen University, Aachen, Germany; Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht, The Netherlands.
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25
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Luna-Castillo KP, Olivares-Ochoa XC, Hernández-Ruiz RG, Llamas-Covarrubias IM, Rodríguez-Reyes SC, Betancourt-Núñez A, Vizmanos B, Martínez-López E, Muñoz-Valle JF, Márquez-Sandoval F, López-Quintero A. The Effect of Dietary Interventions on Hypertriglyceridemia: From Public Health to Molecular Nutrition Evidence. Nutrients 2022; 14:nu14051104. [PMID: 35268076 PMCID: PMC8912493 DOI: 10.3390/nu14051104] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 02/26/2022] [Accepted: 03/03/2022] [Indexed: 11/16/2022] Open
Abstract
Approximately 25–50% of the population worldwide exhibits serum triglycerides (TG) (≥150 mg/dL) which are associated with an increased level of highly atherogenic remnant-like particles, non-alcoholic fatty liver disease, and pancreatitis risk. High serum TG levels could be related to cardiovascular disease, which is the most prevalent cause of mortality in Western countries. The etiology of hypertriglyceridemia (HTG) is multifactorial and can be classified as primary and secondary causes. Among the primary causes are genetic disorders. On the other hand, secondary causes of HTG comprise lifestyle factors, medical conditions, and drugs. Among lifestyle changes, adequate diets and nutrition are the initial steps to treat and prevent serum lipid alterations. Dietary intervention for HTG is recommended in order to modify the amount of macronutrients. Macronutrient distribution changes such as fat or protein, low-carbohydrate diets, and caloric restriction seem to be effective strategies in reducing TG levels. Particularly, the Mediterranean diet is the dietary pattern with the most consistent evidence for efficacy in HTG while the use of omega-3 supplements consumption is the dietary component with the highest number of randomized clinical trials (RCT) carried out with effective results on reducing TG. The aim of this review was to provide a better comprehension between human nutrition and lipid metabolism.
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Affiliation(s)
- Karla Paulina Luna-Castillo
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico; (K.P.L.-C.); (X.C.O.-O.); (R.G.H.-R.); (I.M.L.-C.); (S.C.R.-R.); (A.B.-N.); (B.V.); (E.M.-L.); (J.F.M.-V.)
| | - Xochitl Citlalli Olivares-Ochoa
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico; (K.P.L.-C.); (X.C.O.-O.); (R.G.H.-R.); (I.M.L.-C.); (S.C.R.-R.); (A.B.-N.); (B.V.); (E.M.-L.); (J.F.M.-V.)
| | - Rocío Guadalupe Hernández-Ruiz
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico; (K.P.L.-C.); (X.C.O.-O.); (R.G.H.-R.); (I.M.L.-C.); (S.C.R.-R.); (A.B.-N.); (B.V.); (E.M.-L.); (J.F.M.-V.)
| | - Iris Monserrat Llamas-Covarrubias
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico; (K.P.L.-C.); (X.C.O.-O.); (R.G.H.-R.); (I.M.L.-C.); (S.C.R.-R.); (A.B.-N.); (B.V.); (E.M.-L.); (J.F.M.-V.)
- Instituto de Nutrigenética y Nutrigenómica Traslacional, CUCS, UdeG, Guadalajara 44340, Jalisco, Mexico
| | - Saraí Citlalic Rodríguez-Reyes
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico; (K.P.L.-C.); (X.C.O.-O.); (R.G.H.-R.); (I.M.L.-C.); (S.C.R.-R.); (A.B.-N.); (B.V.); (E.M.-L.); (J.F.M.-V.)
- Instituto de Nutrigenética y Nutrigenómica Traslacional, CUCS, UdeG, Guadalajara 44340, Jalisco, Mexico
| | - Alejandra Betancourt-Núñez
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico; (K.P.L.-C.); (X.C.O.-O.); (R.G.H.-R.); (I.M.L.-C.); (S.C.R.-R.); (A.B.-N.); (B.V.); (E.M.-L.); (J.F.M.-V.)
| | - Barbara Vizmanos
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico; (K.P.L.-C.); (X.C.O.-O.); (R.G.H.-R.); (I.M.L.-C.); (S.C.R.-R.); (A.B.-N.); (B.V.); (E.M.-L.); (J.F.M.-V.)
- Instituto de Nutrigenética y Nutrigenómica Traslacional, CUCS, UdeG, Guadalajara 44340, Jalisco, Mexico
| | - Erika Martínez-López
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico; (K.P.L.-C.); (X.C.O.-O.); (R.G.H.-R.); (I.M.L.-C.); (S.C.R.-R.); (A.B.-N.); (B.V.); (E.M.-L.); (J.F.M.-V.)
- Instituto de Nutrigenética y Nutrigenómica Traslacional, CUCS, UdeG, Guadalajara 44340, Jalisco, Mexico
| | - José Francisco Muñoz-Valle
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico; (K.P.L.-C.); (X.C.O.-O.); (R.G.H.-R.); (I.M.L.-C.); (S.C.R.-R.); (A.B.-N.); (B.V.); (E.M.-L.); (J.F.M.-V.)
- Instituto de Investigación en Ciencias Biomédicas, CUCS, UdeG, Guadalajara 44340, Jalisco, Mexico
| | - Fabiola Márquez-Sandoval
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico; (K.P.L.-C.); (X.C.O.-O.); (R.G.H.-R.); (I.M.L.-C.); (S.C.R.-R.); (A.B.-N.); (B.V.); (E.M.-L.); (J.F.M.-V.)
- Instituto de Nutrigenética y Nutrigenómica Traslacional, CUCS, UdeG, Guadalajara 44340, Jalisco, Mexico
- Correspondence: (F.M.-S.); (A.L.-Q.); Tel.: +52-(33)1058-5200 (ext. 33644 or 33704) (F.M.-S.)
| | - Andres López-Quintero
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico; (K.P.L.-C.); (X.C.O.-O.); (R.G.H.-R.); (I.M.L.-C.); (S.C.R.-R.); (A.B.-N.); (B.V.); (E.M.-L.); (J.F.M.-V.)
- Instituto de Nutrigenética y Nutrigenómica Traslacional, CUCS, UdeG, Guadalajara 44340, Jalisco, Mexico
- Correspondence: (F.M.-S.); (A.L.-Q.); Tel.: +52-(33)1058-5200 (ext. 33644 or 33704) (F.M.-S.)
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Childhood Hypertriglyceridemia: Is It Time for a New Approach? Curr Atheroscler Rep 2022; 24:265-275. [PMID: 35107763 DOI: 10.1007/s11883-022-01000-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/06/2022] [Indexed: 11/03/2022]
Abstract
PURPOSE OF REVIEW Hypertriglyceridemia (HTG) is widely prevalent in youth. There is an unmet need for effective medications in the management of HTG in youth. The purpose of this review is to summarize the approach to HTG in acute and chronic settings, and highlight emerging therapies targeted at specific genes, proteins, and enzymes to selectively alter triglyceride (TG) metabolism. RECENT FINDINGS Genetic and lifestyle factors play a significant role in the pathophysiology of HTG. Severe elevation of TG poses a risk of acute pancreatitis, while mild-to-moderate HTG increases the risk for premature atherosclerotic cardiovascular disease (ASCVD) and, increasingly, has been linked with non-alcoholic fatty liver disease. Although a variety of therapeutic agents are in development, strict adherence to a heart healthy lifestyle, including dietary changes, remain the cornerstone of management for youth with HTG. In addition to lifestyle changes, pharmacological interventions, including fibrates, omega 3 fatty acids, and statins may be considered for management of moderate-to-severe HTG. In view of its association with premature cardiovascular disease (CVD), non-high-density-lipoprotein-C (non-HDL-C) is an important target for therapy in children with moderate HTG. Management of HTG is dependent on its etiology, concomitant symptoms, and degree of TG elevation. The last two decades have seen remarkable changes in drug development, specifically those that act through the lipoprotein lipase complex, including new targeted treatments such as inhibitors of apolipoprotein C3 and angiopoietin-like protein 3.
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Shang R, Lal N, Lee CS, Zhai Y, Puri K, Seira O, Boushel RC, Sultan I, Räsänen M, Alitalo K, Hussein B, Rodrigues B. Cardiac-specific VEGFB overexpression reduces lipoprotein lipase activity and improves insulin action in rat heart. Am J Physiol Endocrinol Metab 2021; 321:E753-E765. [PMID: 34747201 DOI: 10.1152/ajpendo.00219.2021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Cardiac muscle uses multiple sources of energy including glucose and fatty acid (FA). The heart cannot synthesize FA and relies on obtaining it from other sources, with lipoprotein lipase (LPL) breakdown of lipoproteins suggested to be a key source of FA for cardiac use. Recent work has indicated that cardiac vascular endothelial growth factor B (VEGFB) overexpression expands the coronary vasculature and facilitates metabolic reprogramming that favors glucose utilization. We wanted to explore whether this influence of VEGFB on cardiac metabolism involves regulation of LPL activity with consequent effects on lipotoxicity and insulin signaling. The transcriptomes of rats with and without cardiomyocyte-specific overexpression of human VEGFB were compared by using RNA sequencing. Isolated perfused hearts or cardiomyocytes incubated with heparin were used to enable measurement of LPL activity. Untargeted metabolomic analysis was performed for quantification of cardiac lipid metabolites. Cardiac insulin sensitivity was evaluated using fast-acting insulin. Isolated heart and cardiomyocytes were used to determine transgene-encoded VEGFB isoform secretion patterns and mitochondrial oxidative capacity using high-resolution respirometry and extracellular flux analysis. In vitro, transgenic cardiomyocytes incubated overnight and thus exposed to abundantly secreted VEGFB isoforms, in the absence of any in vivo confounding regulators of cardiac metabolism, demonstrated higher basal oxygen consumption. In the whole heart, VEGFB overexpression induced an angiogenic response that was accompanied by limited cardiac LPL activity through multiple mechanisms. This was associated with a lowered accumulation of lipid intermediates, diacylglycerols and lysophosphatidylcholine, that are known to influence insulin action. In response to exogenous insulin, transgenic hearts demonstrated increased insulin sensitivity. In conclusion, the interrogation of VEGFB function on cardiac metabolism uncovered an intriguing and previously unappreciated effect to lower LPL activity and prevent lipid metabolite accumulation to improve insulin action. VEGFB could be a potential cardioprotective therapy to treat metabolic disorders, for example, diabetes.NEW & NOTEWORTHY In hearts overexpressing vascular endothelial growth factor B (VEGFB), besides its known angiogenic response, multiple regulatory mechanisms lowered coronary LPL. This was accompanied by limited cardiac lipid metabolite accumulation with an augmentation of cardiac insulin action. Our data for the first time links VEGFB to coronary LPL in regulation of cardiac metabolism. VEGFB may be cardioprotective in metabolic disorders like diabetes.
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Affiliation(s)
- Rui Shang
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
| | - Nathaniel Lal
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
| | - Chae Syng Lee
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
| | - Yajie Zhai
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
| | - Karanjit Puri
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
| | - Oscar Seira
- International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, British Columbia, Canada
- Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Robert C Boushel
- School of Kinesiology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Ibrahim Sultan
- Wihuri Research Institute and Translational Cancer Medicine Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
| | - Markus Räsänen
- Wihuri Research Institute and Translational Cancer Medicine Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
| | - Kari Alitalo
- Wihuri Research Institute and Translational Cancer Medicine Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
| | - Bahira Hussein
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
| | - Brian Rodrigues
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
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Choe HJ, Park S, Han KD, Moon MK, Koo BK. Contribution of hypertriglyceridemia to ischemic cardiovascular disease in Korean Women: A nationwide population-based study. J Clin Lipidol 2021; 16:83-93. [PMID: 34896034 DOI: 10.1016/j.jacl.2021.11.008] [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: 04/03/2021] [Revised: 11/17/2021] [Accepted: 11/17/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND The independent effect of serum triglyceride levels on the development of ischemic cardiovascular disease (CVD) remains inconclusive, which might be due to heterogeneity among study populations. OBJECTIVE To evaluate the effect of triglyceride levels on ischemic CVD and mortality in Korean women, with stratification according to the menopausal status, diabetes mellitus, or low-density lipoprotein cholesterol levels (LDL-C). METHODS We retrospectively investigated Korean women aged 40-69 years who underwent health examination in 2009 and were followed up until 2018 using nationwide claim data. The subjects were divided according to triglyceride quartiles (Q): Q1 <70 mg/dL, Q2 71-99 mg/dL, Q3 100-142 mg/dL, and Q4 ≥143 mg/dL. The primary outcome was the incidence of CVD defined as a composite of myocardial infarction and ischemic stroke. RESULTS Among 2,208,347 women, primary outcome occurred in 62,255 (2.8%) subjects. As triglyceride levels increased, the event rate of primary outcome increased in both premenopausal and postmenopausal women in the fully adjusted model (hazard ratio [HR] per 1 Q, 1.10 [95% confidence interval (CI), 1.08-1.12] and 1.08 [95% CI, 1.07-1.09], respectively), which was maintained on further stratification according to diabetes or LDL-C (P<0.05 in all). Higher triglyceride levels were more significantly associated with the primary outcome, MI, and stroke risk among women with optimal non-high-density lipoprotein cholesterol levels (non-HDL-C) <130 mg/dL, but only weakly with stroke for women with non-optimal non-HDL-C. CONCLUSION Triglyceride is an independent prognosticator in the development of ischemic CVD in Korean women aged 40-69 years.
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Affiliation(s)
- Hun Jee Choe
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea
| | - SangHyun Park
- Department of Medical Statistics, College of Medicine, Catholic University of Korea, Seoul 06591, Korea
| | - Kyung-Do Han
- Department of Medical Statistics, College of Medicine, Catholic University of Korea, Seoul 06591, Korea
| | - Min Kyong Moon
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea; Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul 07061, Korea
| | - Bo Kyung Koo
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea; Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul 07061, Korea.
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Yu D, Wang Z, Zhang X, Qu B, Cai Y, Ma S, Zhao Z, Simmons D. Remnant Cholesterol and Cardiovascular Mortality in Patients With Type 2 Diabetes and Incident Diabetic Nephropathy. J Clin Endocrinol Metab 2021; 106:3546-3554. [PMID: 34291804 DOI: 10.1210/clinem/dgab533] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT The association between remnant cholesterol (remnant-C) and cardiovascular mortality in patients with type 2 diabetes (T2D) and incident diabetic nephropathy remains unclear. OBJECTIVE To examinie the association between remnant-C and cardiovascular mortality in patients with T2D, chronic kidney disease (CKD) stages 3 to 5, and newly diagnosed DN. METHODS This study determined the baseline lipid profile and searched for deaths with cardiovascular disease (CVD) within 2 years of baseline among 2282 adults enrolled between January 1, 2015 and December 31, 2016, who had T2D, CKD stages 3 to 5, and newly diagnosed DN. Adjusted logistic regression models were used to assess the associations between lipid, especially remnant-C concentration (either as continuous or categorical variables), and risk of cardiovascular mortality. RESULTS In multivariable-adjusted analyses, low-density lipoprotein cholesterol (LDL-C) (odds ratio [OR], 1.022; 95% CI, 1.017-1.026, per 10 mg/dL), high-density lipoprotein cholesterol (HDL-C) (OR, 0.929; 95% CI, 0.922-0.936, per 5 mg/dL), non-HDL-C (OR, 1.024; 95% CI, 1.021-1.028, per 10 mg/dL), and remnant-C (OR, 1.115; 95% CI, 1.103-1.127, per 10 mg/dL), but not triglycerides were associated with cardiovascular mortality. Atherogenic dyslipidemia (triglycerides > 150 mg/dL [1.69 mmol/L] and HDL-C < 40 mg/dL in men or < 50 mg/dL in women) was also associated with cardiovascular mortality (OR, 1.073; 95% CI, 1.031-1.116). Remnant-C greater than or equal to 30 mg/dL differentiated patients at a higher risk of cardiovascular mortality from those with lower concentrations, especially with interaction with LDL-C level greater than 100 mg/dL: The highest risk was found in patients with higher levels both of remnant-C and LDL-C (OR, 1.696; 95% CI, 1.613-1.783). CONCLUSION In patients with T2D, CKD stages 3 to 5, and incident DN, remnant-C was associated with a higher risk of death with CVD. Different from the general population, the interaction of remnant-C and LDL-C was associated with the highest risk of cardiovascular mortality.
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Affiliation(s)
- Dahai Yu
- Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China
- Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele ST5 5BG, UK
| | - Zheng Wang
- Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China
| | - Xiaoxue Zhang
- Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China
| | - Bingjie Qu
- Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China
| | - Yamei Cai
- Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China
| | - Shuang Ma
- Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China
| | - Zhanzheng Zhao
- Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China
| | - David Simmons
- Department of Nephrology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China
- Macarthur Clinical School, Western Sydney University, Campbelltown, Sydney NSW 2751, Australia
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Li Z, Tong X, Ma Y, Bao T, Yue J. Relationship Between Low Skeletal Muscle Mass and Arteriosclerosis in Western China: A Cross-Sectional Study. Front Cardiovasc Med 2021; 8:735262. [PMID: 34746254 PMCID: PMC8563701 DOI: 10.3389/fcvm.2021.735262] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 09/23/2021] [Indexed: 02/05/2023] Open
Abstract
Objectives: This study explored the prevalence and the correlation between low muscle mass and arteriosclerosis in different gender and age groups, to increase the attention paid to the risk factors of arteriosclerosis in the young and middle-aged population. Methods: This was an analytical, cross-sectional study. Data were obtained from healthy individuals recruited from the Health Management Center of W Hospital. The brachial-ankle pulse-wave velocity was used as an indicator of arteriosclerosis, and a bioelectrical impedance analysis was used to assess the body composition. Results: A total of 36,374 subjects (men, 58.4%; women, 41.6%; mean age, 43.74 ± 12.34 years [range, 18-80 years]) participated in this study. The prevalence of low skeletal muscle mass and arteriosclerosis was 17.7 and 53.1%, respectively, in all subjects. Low skeletal muscle mass was significantly associated with arteriosclerosis (OR: 1.435, 95% CI: 1.343-1.533, P < 0.001) in all subjects, and the association remained significant in young age (OR: 1.506, 95% CI: 1.353-1.678, P < 0.001), middle-age (OR: 1.329, 95% CI: 1.195-1.479, P < 0.001), and old age (OR: 1.676, 95% CI: 1.191-2.358, P = 0.003), and also significant in men (OR: 1.559, 95% CI: 1.396-1.740, P < 0.001) and women (OR: 1.266, 95% CI: 1.143-1.401, P < 0.001). Conclusions and Implications: Our results show that the prevalence of low muscle mass and arteriosclerosis is high in the general population, even among middle-aged people and young people, and confirmed that there is a significant independent association between low skeletal muscle mass and arteriosclerosis in all subjects and in different age and gender subgroups.
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Affiliation(s)
- Zhenzhen Li
- Health Management Center, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, China
| | - Xiang Tong
- Department of Respiratory and Critical Care Medicine, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, China
| | - Yao Ma
- Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, China
| | - Ting Bao
- Health Management Center, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, China
| | - Jirong Yue
- Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, China
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Lim S, Kim YJ, Khang AR, Eckel RH. Postprandial dyslipidemia after a standardized high-fat meal in BMI-matched healthy individuals, and in subjects with prediabetes or type 2 diabetes. Clin Nutr 2021; 40:5538-5546. [PMID: 34656950 DOI: 10.1016/j.clnu.2021.09.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 08/18/2021] [Accepted: 09/03/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND & AIMS A relationship between postprandial hyperlipidemia and glucose homeostasis/cardiovascular diseases has been suggested. We investigated postprandial plasma lipid patterns after a standardized high-fat meal and their association with glucose homeostasis and subclinical atherosclerosis. METHODS Using matching by BMI, 32 healthy individuals with normal glucose tolerance (NGT), 21 subjects with impaired glucose tolerance (IGT), and 20 subjects with drug-naïve type 2 diabetes (T2D) were enrolled. Plasma concentrations of triglycerides (TGs), apolipoprotein-B (ApoB), ApoB48, ApoB100, glucose, and insulin at baseline and 1, 2, 3, 4, 5, 6, and 8 h after a standardized meal (1041.03 kcal with 70.99 g of fat) were measured. Body composition, abdominal visceral fat area, and resting energy expenditure (REE) were measured using dual energy X-ray absorptiometry, computed tomography, and indirect calorimetry, respectively. The intima-media thickness (IMT) of the carotid artery and the ankle-brachial index (ABI) were used to detect subclinical atherosclerosis. RESULTS Baseline data and area under the curve (AUC) of plasma concentrations of TGs, ApoB, and ApoB48 in the IGT and T2D groups were higher than in the NGT group. The peak TG concentrations after the meal was observed at 5 h in subjects with IGT and T2D, while healthy subjects showed the highest concentrations at 4 h. In multivariable analysis, high abdominal visceral fat area and low HDL-cholesterol concentrations were independently associated with the AUCTG and AUCApoB after adjusting for confounders including baseline TG and the REE. High LDL-cholesterol and high HbA1c concentrations were also associated with the AUCApoB. Furthermore, high AUCTG and AUCApoB values were independent factors for an increased carotid IMT and a low ABI after adjusting for relevant variables. CONCLUSIONS Abdominal visceral obesity and low HDL-cholesterol concentrations were associated with increased post load excursions of TGs and ApoB in this series. These elevated concentrations of TGs and ApoB were linked with subclinical atherosclerosis.
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Affiliation(s)
- Soo Lim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
| | - Yoon Ji Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Internal Medicine, Mediplex Sejong Hospital, Incheon, South Korea
| | - Ah Reum Khang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University College of Medicine, Yangsan, South Korea
| | - Robert H Eckel
- Division of Endocrinology, Metabolism and Diabetes, Division of Cardiology, Emeritus University of Colorado Anschutz Medical Campus, Aurora, CO, USA
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Hoshino T, Ishizuka K, Toi S, Mizuno T, Nishimura A, Takahashi S, Wako S, Kitagawa K. Atherogenic Dyslipidemia and Residual Vascular Risk After Stroke or Transient Ischemic Attack. Stroke 2021; 53:79-86. [PMID: 34470483 DOI: 10.1161/strokeaha.121.034593] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND PURPOSE Notwithstanding the current guideline-based management, patients with stroke retain a substantial risk of further vascular events. We aimed to assess the contribution of atherogenic dyslipidemia (AD) to this residual risk. METHODS This was a prospective observational study, in which 792 patients (mean age, 70.1 years; male, 60.2%) with acute ischemic stroke (n=710) or transient ischemic attack (n=82) within 1 week of onset were consecutively enrolled and followed for 1 year. AD was defined as having both elevated levels of triglycerides ≥150 mg/dL and low HDL-C (high-density lipoprotein cholesterol) <40 mg/dL in men or <50 mg/dL in women, under fasting conditions. The primary outcome was a composite of major adverse cardiovascular events, including nonfatal stroke, nonfatal acute coronary syndrome, and vascular death. RESULTS The prevalence of AD was 12.2%. Patients with AD more often had intracranial artery stenosis than those without (42.3% versus 24.1%; P=0.004), whereas no differences were observed in the prevalence of extracranial artery stenosis (17.7% versus 12.9%; P=0.62) or aortic plaques (33.3% versus 27.0%; P=0.87). At 1 year, patients with AD were at a greater risk of major adverse cardiovascular events (annual rate, 24.5% versus 10.6%; hazard ratio [95% CI], 2.33 [1.44-3.80]) and ischemic stroke (annual rate, 16.8% versus 8.6%; hazard ratio [95% CI], 1.84 [1.04-3.26]) than those without AD. When patients were stratified according to baseline LDL-C (low-density lipoprotein cholesterol) level, AD was predictive of major adverse cardiovascular events among those with LDL-C ≥100 mg/dL (n=509; annual rate, 20.5% versus 9.6%; P=0.036) as well as those with LDL-C <100 mg/dL (n=283; annual rate, 38.6% versus 12.4%; P<0.001). CONCLUSIONS AD is associated with intracranial artery atherosclerosis and a high residual vascular risk after a stroke or transient ischemic attack. AD should be a promising modifiable target for secondary stroke prevention. Registration: URL: https://upload.umin.ac.jp; Unique identifier: UMIN000031913.
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Affiliation(s)
- Takao Hoshino
- Department of Neurology, Tokyo Women's Medical University Hospital, Japan
| | - Kentaro Ishizuka
- Department of Neurology, Tokyo Women's Medical University Hospital, Japan
| | - Sono Toi
- Department of Neurology, Tokyo Women's Medical University Hospital, Japan
| | - Takafumi Mizuno
- Department of Neurology, Tokyo Women's Medical University Hospital, Japan
| | - Ayako Nishimura
- Department of Neurology, Tokyo Women's Medical University Hospital, Japan
| | - Shuntaro Takahashi
- Department of Neurology, Tokyo Women's Medical University Hospital, Japan
| | - Sho Wako
- Department of Neurology, Tokyo Women's Medical University Hospital, Japan
| | - Kazuo Kitagawa
- Department of Neurology, Tokyo Women's Medical University Hospital, Japan
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Iqbal MA, Ahmad S, Mumtaz T, Naseem Z, Malik J, Ahmad H, Roohi N. Prospective Analysis of Lipid Variations in Hyperthyroid Subjects from Lahore, Pakistan. BIOMED RESEARCH INTERNATIONAL 2021; 2021:9936782. [PMID: 38523861 PMCID: PMC10960653 DOI: 10.1155/2021/9936782] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 08/11/2021] [Indexed: 03/26/2024]
Abstract
Perturbations in the actions of T3 and T4 influence the normal metabolic pathways. Responsiveness of lipid biomarkers like LDL-C, HDL-C, TC, TG, Apo-A, and Apo-B after rehabilitation of thyroid profile attaining euthyroid state was determined. A total of 179 age-matched subjects of both genders were recruited for this research. Sixty healthy controls, thirty-four subclinical, fifty overt hyperthyroid, and thirty-five follow-up subjects having 3 months of Carbimazole therapy were enrolled. Biochemical analysis was performed by chemistry analyzer, RIA, and ELISA. One-way ANOVA was applied for the statistical analysis, while significance (P < 0.05) of means was compared by the Student-Newman-Keuls (SNK) test. Pronounced reduction (P < 0.001) of cholesterol in overt as compared to control and subclinical was noticed, whereas marked improvement (P < 0.001) was evidenced in follow-up. Prominent elevation (P < 0.05) of TG in follow-up was evidenced as compared to control. Overt presented marked reduction of HDL-C as compared to subclinical and control (P < 0.01 and P < 0.001), respectively. Pronounced elevation (P < 0.001) of HDL-C was evidenced after treatment. Overt presented reduction of LDL-C as compared to subclinical and control (P < 0.01 and P < 0.05, respectively). The follow-up group demonstrated considerable (P < 0.001) improvement of LDL-C after treatment and elevation (P < 0.05) as compared to control. Overt presented reduction of Apo-B as compared to subclinical and control (P < 0.05 and P < 0.001, respectively). Improvement (P < 0.05) of Apo-B was evidenced in follow-up. Reduction (P < 0.05) of Apo-A in overt as compared to control and elevation (P < 0.05) in follow-up as compared to overt was evidenced. Conclusively, improvement after treatment was evidenced in lipid profile.
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Affiliation(s)
- Muhammad Amir Iqbal
- Institute of Zoology, University of the Punjab, Canal Road, Lahore, Punjab 54590, Pakistan
| | - Shaaf Ahmad
- King Edward Medical University/Mayo Hospital, Hospital Road, Lahore, Punjab 54000, Pakistan
| | - Tamseela Mumtaz
- Institute of Zoology, University of the Punjab, Canal Road, Lahore, Punjab 54590, Pakistan
- Department of Zoology, Government College for Women University, Faisalabad, Punjab, Pakistan
| | - Zahra Naseem
- Institute of Zoology, University of the Punjab, Canal Road, Lahore, Punjab 54590, Pakistan
| | - Javeria Malik
- Institute of Zoology, University of the Punjab, Canal Road, Lahore, Punjab 54590, Pakistan
| | - Husna Ahmad
- Institute of Zoology, University of the Punjab, Canal Road, Lahore, Punjab 54590, Pakistan
| | - Nabila Roohi
- Institute of Zoology, University of the Punjab, Canal Road, Lahore, Punjab 54590, Pakistan
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Rojas-Humpire R, Jáuregui-Rodríguez K, Albornoz S, Ruiz Mamani PG, Gutierrez-Ajalcriña R, Huancahuire-Vega S. Association and diagnostic value of a novel uric acid index to cardiovascular risk. Pract Lab Med 2021; 26:e00247. [PMID: 34337127 PMCID: PMC8318914 DOI: 10.1016/j.plabm.2021.e00247] [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: 01/04/2021] [Revised: 05/25/2021] [Accepted: 07/14/2021] [Indexed: 11/26/2022] Open
Abstract
OBJECTIVES Cardiovascular diseases (CVD) are the leading cause of death and disability worldwide. The aim of this study was to assess the association and diagnostic value of a novel uric acid index (UA index) to cardiovascular risk (CVR). DESIGN and Methods: An analytical cross-sectional study was performed. We analyzed data from the Plan for Prevention and Surveillance of Communicable and Non-Communicable Diseases at the Hospital de Huaycan, Peru. The QRISK model was used to measure the CVR. Stepwise regression models were performed to determine significant factors to predict CVR and formulate the UA index, then the association of UA index and high CVR was evaluated by Poisson regression models, and the diagnostic accuracy was verified through ROC curves. RESULTS In total 291 participants (206 women and 85 men) were analyzed. The correlation between UA index to CVR was stronger (R 2 :0.31, p < 0.001) than uric acid (UA) alone (R 2 :0.19, p < 0.001), and the contribution of UA was stronger than triglycerides or glucose in the stepwise regression model. In the Poisson models, the UA index adjusted model (PRa: 1.58, CI95% 1.11-2.24) presented significant independent association to CVR. The diagnostic accuracy was similar in men (cut-off: 10.8, AUC:0.81; 0.75-0.87) and women (cut-off: 10.0; AUC: 0.77, 0.71-0.84). CONCLUSION UA index presented a good diagnostic accuracy and independent significant association to high CVR in adults from Peru. This marker can be used to assess CVR and follow therapeutic progress in primary health care.
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Affiliation(s)
- Ricardo Rojas-Humpire
- Departamento de Ciencias Básicas, Escuela de Medicina Humana, Facultad de Ciencias de La Salud, Universidad Peruana Unión, Lima, Peru
| | - Keila Jáuregui-Rodríguez
- Departamento de Ciencias Básicas, Escuela de Medicina Humana, Facultad de Ciencias de La Salud, Universidad Peruana Unión, Lima, Peru
| | - Silvana Albornoz
- Departamento de Ciencias Básicas, Escuela de Medicina Humana, Facultad de Ciencias de La Salud, Universidad Peruana Unión, Lima, Peru
| | | | | | - Salomón Huancahuire-Vega
- Departamento de Ciencias Básicas, Escuela de Medicina Humana, Facultad de Ciencias de La Salud, Universidad Peruana Unión, Lima, Peru
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Dilworth L, Facey A, Omoruyi F. Diabetes Mellitus and Its Metabolic Complications: The Role of Adipose Tissues. Int J Mol Sci 2021; 22:ijms22147644. [PMID: 34299261 PMCID: PMC8305176 DOI: 10.3390/ijms22147644] [Citation(s) in RCA: 99] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/08/2021] [Accepted: 07/12/2021] [Indexed: 12/14/2022] Open
Abstract
Many approaches have been used in the effective management of type 2 diabetes mellitus. A recent paradigm shift has focused on the role of adipose tissues in the development and treatment of the disease. Brown adipose tissues (BAT) and white adipose tissues (WAT) are the two main types of adipose tissues with beige subsets more recently identified. They play key roles in communication and insulin sensitivity. However, WAT has been shown to contribute significantly to endocrine function. WAT produces hormones and cytokines, collectively called adipocytokines, such as leptin and adiponectin. These adipocytokines have been proven to vary in conditions, such as metabolic dysfunction, type 2 diabetes, or inflammation. The regulation of fat storage, energy metabolism, satiety, and insulin release are all features of adipose tissues. As such, they are indicators that may provide insights on the development of metabolic dysfunction or type 2 diabetes and can be considered routes for therapeutic considerations. The essential roles of adipocytokines vis-a-vis satiety, appetite, regulation of fat storage and energy, glucose tolerance, and insulin release, solidifies adipose tissue role in the development and pathogenesis of diabetes mellitus and the complications associated with the disease.
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Affiliation(s)
- Lowell Dilworth
- Department of Pathology, Mona Campus, University of the West Indies, Kingston 7, Jamaica;
| | - Aldeam Facey
- Mona Academy of Sport, Mona Campus, University of the West Indies, Kingston 7, Jamaica;
| | - Felix Omoruyi
- Department of Life Sciences, Texas A&M University, Corpus Christi, TX 78412, USA
- Correspondence:
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Shang R, Rodrigues B. Lipoprotein Lipase and Its Delivery of Fatty Acids to the Heart. Biomolecules 2021; 11:biom11071016. [PMID: 34356640 PMCID: PMC8301904 DOI: 10.3390/biom11071016] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 07/08/2021] [Accepted: 07/08/2021] [Indexed: 02/05/2023] Open
Abstract
Ninety percent of plasma fatty acids (FAs) are contained within lipoprotein-triglyceride, and lipoprotein lipase (LPL) is robustly expressed in the heart. Hence, LPL-mediated lipolysis of lipoproteins is suggested to be a key source of FAs for cardiac use. Lipoprotein clearance by LPL occurs at the apical surface of the endothelial cell lining of the coronary lumen. In the heart, the majority of LPL is produced in cardiomyocytes and subsequently is translocated to the apical luminal surface. Here, vascular LPL hydrolyzes lipoprotein-triglyceride to provide the heart with FAs for ATP generation. This article presents an overview of cardiac LPL, explains how the enzyme works, describes key molecules that regulate its activity and outlines how changes in LPL are brought about by physiological and pathological states such as fasting and diabetes, respectively.
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Hoshino T, Ishizuka K, Toi S, Seki M, Kitagawa K. Effects of Pemafibrate in Patients with Stroke and Hypertriglyceridemia: Baseline Cerebral Artery Diseases and 3-Month Laboratory Outcomes. J Atheroscler Thromb 2021; 29:1020-1030. [PMID: 34248089 PMCID: PMC9252640 DOI: 10.5551/jat.63036] [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] [Indexed: 11/11/2022] Open
Abstract
AIMS The role of hypertriglyceridemia in stroke is poorly understood. The Pemafibrate for Prevention of Atherosclerotic Diseases in Stroke (PPAR Stroke) study was designed to assess the effects of a novel selective peroxisome proliferator-activated receptor alpha modulator, pemafibrate, on vascular outcomes in stroke patients with hypertriglyceridemia. METHODS This was a prospective single-arm study including 74 patients (mean age, 64.1 years; male 75.7%) with stroke and hypertriglyceridemia (defined as fasting serum triglycerides levels of ≥ 150 mg/dL) who were treated with pemafibrate at 0.2 mg or 0.1 mg/day. The present report assessed the association of hypertriglyceridemia with cerebral large and small vessel diseases at baseline and changes in laboratory parameters after a three-month pemafibrate therapy. RESULTS Patients with triglycerides levels of ≥ 227 mg/dL (higher than the median) more often presented with intracranial artery atherosclerotic stenosis than those with triglycerides levels of 150-227 mg/dL (44.4% vs. 21.6%, p=0.037). On the other hand, no differences were found in the prevalence of extracranial artery atherosclerosis and cerebral small vessel diseases. Mean triglycerides levels were significantly reduced from 285 mg/dL at baseline to 175 mg/dL at 3 months (p＜0.001). High-density lipoprotein cholesterol levels increased from 48 mg/dL to 53 mg/dL (p＜0.001). In addition, significant reductions in alanine aminotransferase, γ-glutamyl transpeptidase, and interleukin-6 levels were observed (p＜0.001, p=0.002, and p=0.044, respectively). CONCLUSIONS Higher triglycerides levels are associated with intracranial artery atherosclerosis. Pemafibrate showed pleiotropic effects not only in ameliorating atherogenic dyslipidemia but also in the reduction of the levels of inflammatory markers and hepatobiliary enzymes.
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Affiliation(s)
- Takao Hoshino
- Department of Neurology, Tokyo Women's Medical University School of Medicine
| | - Kentaro Ishizuka
- Department of Neurology, Tokyo Women's Medical University School of Medicine
| | - Sono Toi
- Department of Neurology, Tokyo Women's Medical University School of Medicine
| | - Misa Seki
- Department of Neurology, Tokyo Women's Medical University School of Medicine
| | - Kazuo Kitagawa
- Department of Neurology, Tokyo Women's Medical University School of Medicine
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Sciarrillo CM, Koemel NA, Keirns BH, Banks NF, Rogers EM, Rosenkranz SK, Kurti SP, Jenkins NDM, Emerson SR. Who would benefit most from postprandial lipid screening? Clin Nutr 2021; 40:4762-4771. [PMID: 34242916 PMCID: PMC10198766 DOI: 10.1016/j.clnu.2021.04.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 03/22/2021] [Accepted: 04/10/2021] [Indexed: 01/22/2023]
Abstract
BACKGROUND & AIMS Individuals with fasting triglycerides (TG) <150 mg/dL can experience a deleterious postprandial TG response ≥220 mg/dL to a high-fat meal (HFM). The purpose of this study was to identify individuals based on fasting TG that would benefit most from additional postprandial screening. METHODS We conducted a secondary analysis of 7 studies from our laboratories featuring 156 disease-free participants (64 M, 92 F; age 18-70 years; BMI 18.5-30 kg/m2). Participants observed a 10-12 h overnight fast, after which they consumed an HFM (10-13 kcal/kg body mass; 61-64% kcal from fat). Two methods were used to identify lower and upper fasting TG cut points. Method 1 identified the lower limit as the TG concentration at which ≥90% of individuals presented peak postprandial TG (PPTG) <220 mg/dL and the upper limit as the concentration which ≥90% of individuals presented PPTG ≥220 mg/dL. Method 2 utilized receiver operating characteristic (ROC) curves and identified the lower limit as the fasting TG concentration where sensitivity was ≈95% and the upper limit as the concentration at which specificity was ≈95%. RESULTS In Method 1, 90% of individuals with fasting TG >130 mg/dL (>1.50 mmol/L) exhibited PPTG ≥220 mg/dL (≥2.50 mmol/L), while 100% of individuals with fasting TG <66 mg/dL (0.75 mmol/L) had PPTG that did not exceed 220 mg/dL (2.50 mmol/L). In Method 2, when sensitivity was ≈95%, the corresponding fasting TG concentration was 70 mg/dL (0.79 mmol/L). When specificity was ≈95%, the corresponding fasting TG concentration was 114 mg/dL (1.29 mmol/L). Based on methods 1 and 2, there was a moderate positive association (r = 0.37, p < 0.004) between fasting and PPTG for individuals with fasting TG between 70 and 130 mg/dL (0.79-1.50 mmol/L), in which 24% exhibited PPTG ≥220 mg/dL (≥2.50 mmol/L) while 76% did not. CONCLUSIONS Postprandial TG testing is likely most useful for individuals with fasting TG concentrations between 70 and 130 mg/dL (0.79-1.50 mmol/L). Outside of this range, postprandial TG responses are largely predictable. Establishing a specific patient group for which postprandial TG testing is most useful may lead to earlier risk detection in these individuals.
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Affiliation(s)
| | - Nicholas A Koemel
- Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA; Boden Collaboration for Obesity, Nutrition, Exercise, and Eating Disorders, University of Sydney, Sydney, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Bryant H Keirns
- Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA
| | - Nile F Banks
- Department of Health and Human Performance, Oklahoma State University, Stillwater, OK, USA; Department of Health and Human Physiology, University of Iowa, Iowa City, IA, USA
| | - Emily M Rogers
- Department of Health and Human Performance, Oklahoma State University, Stillwater, OK, USA; Department of Health and Human Physiology, University of Iowa, Iowa City, IA, USA
| | - Sara K Rosenkranz
- Department of Food, Nutrition, Dietetics and Health, Kansas State University, Manhattan, KS, USA
| | - Stephanie P Kurti
- Department of Food, Nutrition, Dietetics and Health, Kansas State University, Manhattan, KS, USA; Department of Kinesiology, James Madison University, Harrisonburg, VA, USA
| | - Nathaniel D M Jenkins
- Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA; Department of Health and Human Performance, Oklahoma State University, Stillwater, OK, USA; Department of Health and Human Physiology, University of Iowa, Iowa City, IA, USA
| | - Sam R Emerson
- Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA; Department of Food, Nutrition, Dietetics and Health, Kansas State University, Manhattan, KS, USA
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Babusha Wega A, Kelta Wabalo E, Kenenisa Edae C, Bogale Awgichew G. Cardiac Troponin-I Status of Type-2 Diabetic Patients on Anti-Diabetic Drugs Treatment at Jimma Medical Center, Jimma, Southwest Ethiopia. RESEARCH REPORTS IN CLINICAL CARDIOLOGY 2021. [DOI: 10.2147/rrcc.s313432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Yeung E, Daniels SR, Patel SS. Dyslipidemia in childhood and adolescence: from screening to management. Curr Opin Endocrinol Diabetes Obes 2021; 28:152-158. [PMID: 33394719 DOI: 10.1097/med.0000000000000607] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE OF REVIEW To summarize types of dyslipidemia frequently encountered during childhood and adolescence, with a focus on screening, diagnosis, and management. RECENT FINDINGS It is important that screening for atherosclerotic cardiovascular disease (ASCVD) begin in childhood. Genetic testing allows for increased awareness of dyslipidemia and more targeted intervention. Pharmacologic treatment of pediatric dyslipidemias has a good safety profile and can reduce adult ASCVD risk. SUMMARY Much of what is known about pediatric dyslipidemia has been extrapolated from adult data, but recently, there have been increasing investigations within the pediatric population to better guide diagnosis and management of these disorders.
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Affiliation(s)
- Elizabeth Yeung
- Section of Cardiology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
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VLDL Cholesterol Accounts for One-Half of the Risk of Myocardial Infarction Associated With apoB-Containing Lipoproteins. J Am Coll Cardiol 2021; 76:2725-2735. [PMID: 33272366 DOI: 10.1016/j.jacc.2020.09.610] [Citation(s) in RCA: 117] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 09/10/2020] [Accepted: 09/29/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Plasma apolipoprotein B (apoB) is a composite measure of all apoB-containing lipoproteins causing atherosclerotic cardiovascular disease; however, it is unclear which fraction of risk is explained by cholesterol and triglycerides, respectively, in very low-density lipoproteins (VLDLs). OBJECTIVES The authors tested the hypothesis that VLDL cholesterol and triglycerides each explain part of the myocardial infarction risk from apoB-containing lipoproteins. METHODS Nested within 109,751 individuals from the Copenhagen General Population Study, the authors examined 25,480 subjects free of lipid-lowering therapy and myocardial infarction at study entry. All had measurements of plasma apoB (quantitating number of apoB-containing lipoproteins) and cholesterol and triglyceride content of VLDL, intermediate-density lipoproteins (IDLs), and low-density lipoproteins (LDLs). RESULTS During a median 11 years of follow-up, 1,816 were diagnosed with myocardial infarction. Per 1-mmol/l higher levels, multivariable-adjusted hazard ratios for myocardial infarction were 2.07 (95% confidence interval [CI]: 1.81 to 2.36) for VLDL cholesterol, 1.19 (95% CI: 1.14 to 1.25) for VLDL triglycerides, 5.38 (95% CI: 3.73 to 7.75) for IDL cholesterol, and 1.86 (95% CI: 1.62 to 2.14) for LDL cholesterol. Per 1-g/l higher plasma apoB, the corresponding value was 2.21 (95% CI: 1.90 to 2.58). In a step-up Cox regression, risk factors for myocardial infarction entered by importance as VLDL cholesterol, systolic blood pressure, smoking, and IDL + LDL cholesterol, whereas VLDL triglycerides did not enter the model. VLDL cholesterol explained 50% and IDL + LDL cholesterol 29% of the risk of myocardial infarction from apoB-containing lipoproteins, whereas VLDL triglycerides did not explain risk. CONCLUSIONS VLDL cholesterol explained one-half of the myocardial infarction risk from elevated apoB-containing lipoproteins, whereas VLDL triglycerides did not explain risk.
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Abumrad NA, Cabodevilla AG, Samovski D, Pietka T, Basu D, Goldberg IJ. Endothelial Cell Receptors in Tissue Lipid Uptake and Metabolism. Circ Res 2021; 128:433-450. [PMID: 33539224 DOI: 10.1161/circresaha.120.318003] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Lipid uptake and metabolism are central to the function of organs such as heart, skeletal muscle, and adipose tissue. Although most heart energy derives from fatty acids (FAs), excess lipid accumulation can cause cardiomyopathy. Similarly, high delivery of cholesterol can initiate coronary artery atherosclerosis. Hearts and arteries-unlike liver and adrenals-have nonfenestrated capillaries and lipid accumulation in both health and disease requires lipid movement from the circulation across the endothelial barrier. This review summarizes recent in vitro and in vivo findings on the importance of endothelial cell receptors and uptake pathways in regulating FAs and cholesterol uptake in normal physiology and cardiovascular disease. We highlight clinical and experimental data on the roles of ECs in lipid supply to tissues, heart, and arterial wall in particular, and how this affects organ metabolism and function. Models of FA uptake into ECs suggest that receptor-mediated uptake predominates at low FA concentrations, such as during fasting, whereas FA uptake during lipolysis of chylomicrons may involve paracellular movement. Similarly, in the setting of an intact arterial endothelial layer, recent and historic data support a role for receptor-mediated processes in the movement of lipoproteins into the subarterial space. We conclude with thoughts on the need to better understand endothelial lipid transfer for fuller comprehension of the pathophysiology of hyperlipidemia, and lipotoxic diseases such as some forms of cardiomyopathy and atherosclerosis.
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Affiliation(s)
- Nada A Abumrad
- Division of Nutritional Sciences, Department of Medicine, Washington University School of Medicine, Saint Louis, MO (N.A.A., D.S., T.P.)
| | - Ainara G Cabodevilla
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine (A.G.C., D.B., I.J.G.)
| | - Dmitri Samovski
- Division of Nutritional Sciences, Department of Medicine, Washington University School of Medicine, Saint Louis, MO (N.A.A., D.S., T.P.)
| | - Terri Pietka
- Division of Nutritional Sciences, Department of Medicine, Washington University School of Medicine, Saint Louis, MO (N.A.A., D.S., T.P.)
| | - Debapriya Basu
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine (A.G.C., D.B., I.J.G.)
| | - Ira J Goldberg
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine (A.G.C., D.B., I.J.G.)
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Josefs T, Basu D, Vaisar T, Arets B, Kanter JE, Huggins LA, Hu Y, Liu J, Clouet-Foraison N, Heinecke JW, Bornfeldt KE, Goldberg IJ, Fisher EA. Atherosclerosis Regression and Cholesterol Efflux in Hypertriglyceridemic Mice. Circ Res 2021; 128:690-705. [PMID: 33530703 DOI: 10.1161/circresaha.120.317458] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
[Figure: see text].
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Affiliation(s)
- Tatjana Josefs
- Division of Cardiology (T.J., J.L., E.A.F.), Department of Medicine, New York University School of Medicine.,Department of Internal Medicine, MUMC, Maastricht, the Netherlands (T.J., B.A.).,CARIM, MUMC, Maastricht, the Netherlands (T.J., B.A.)
| | - Debapriya Basu
- Division of Endocrinology, Diabetes and Metabolism (D.B., L.-A.H., Y.H., I.J.G.), Department of Medicine, New York University School of Medicine.,Department of Internal Medicine, MUMC, Maastricht, the Netherlands (T.J., B.A.).,CARIM, MUMC, Maastricht, the Netherlands (T.J., B.A.)
| | - Tomas Vaisar
- Department of Medicine, UW Medicine Diabetes Institute, University of Washington, Seattle (T.V., J.E.K., N.C.-F., J.W.H., K.E.B.)
| | | | - Jenny E Kanter
- Department of Medicine, UW Medicine Diabetes Institute, University of Washington, Seattle (T.V., J.E.K., N.C.-F., J.W.H., K.E.B.)
| | - Lesley-Ann Huggins
- Division of Endocrinology, Diabetes and Metabolism (D.B., L.-A.H., Y.H., I.J.G.), Department of Medicine, New York University School of Medicine
| | - Yunying Hu
- Division of Endocrinology, Diabetes and Metabolism (D.B., L.-A.H., Y.H., I.J.G.), Department of Medicine, New York University School of Medicine
| | - Jianhua Liu
- Division of Cardiology (T.J., J.L., E.A.F.), Department of Medicine, New York University School of Medicine
| | - Noemie Clouet-Foraison
- Department of Medicine, UW Medicine Diabetes Institute, University of Washington, Seattle (T.V., J.E.K., N.C.-F., J.W.H., K.E.B.)
| | - Jay W Heinecke
- Department of Medicine, UW Medicine Diabetes Institute, University of Washington, Seattle (T.V., J.E.K., N.C.-F., J.W.H., K.E.B.)
| | - Karin E Bornfeldt
- Department of Medicine, UW Medicine Diabetes Institute, University of Washington, Seattle (T.V., J.E.K., N.C.-F., J.W.H., K.E.B.)
| | - Ira J Goldberg
- Division of Endocrinology, Diabetes and Metabolism (D.B., L.-A.H., Y.H., I.J.G.), Department of Medicine, New York University School of Medicine
| | - Edward A Fisher
- Division of Cardiology (T.J., J.L., E.A.F.), Department of Medicine, New York University School of Medicine
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Castañer O, Pintó X, Subirana I, Amor AJ, Ros E, Hernáez Á, Martínez-González MÁ, Corella D, Salas-Salvadó J, Estruch R, Lapetra J, Gómez-Gracia E, Alonso-Gomez AM, Fiol M, Serra-Majem L, Corbella E, Benaiges D, Sorli JV, Ruiz-Canela M, Babió N, Sierra LT, Ortega E, Fitó M. Remnant Cholesterol, Not LDL Cholesterol, Is Associated With Incident Cardiovascular Disease. J Am Coll Cardiol 2020; 76:2712-2724. [PMID: 33272365 DOI: 10.1016/j.jacc.2020.10.008] [Citation(s) in RCA: 306] [Impact Index Per Article: 61.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 10/08/2020] [Accepted: 10/09/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Genetic, observational, and clinical intervention studies indicate that circulating levels of triglycerides and cholesterol transported in triglyceride-rich lipoproteins (remnant cholesterol) can predict cardiovascular events. OBJECTIVES This study evaluated the association of triglycerides and remnant cholesterol (remnant-C) with major cardiovascular events in a cohort of older individuals at high cardiovascular risk. METHODS This study determined the baseline lipid profile and searched for major adverse cardiovascular events (MACEs) in the high-risk primary prevention PREDIMED (Prevención con Dieta Mediterránea) trial population (mean age: 67 years; body mass index: 30 kg/m2; 43% men; 48% with diabetes) after a median follow-up of 4.8 years. Unadjusted and adjusted Cox proportional hazard models were used to assess the association between lipid concentrations (either as continuous or categorical variables) and incident MACEs (N = 6,901; n cases = 263). RESULTS In multivariable-adjusted analyses, triglycerides (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02 to 1.06, per 10 mg/dl [0.11 mmol/l]; p < 0.001), non-high-density lipoprotein cholesterol (HDL-C) (HR: 1.05; 95% CI: 1.01 to 1.10, per 10 mg/dl [0.26 mmol/l]; p = 0.026), and remnant-C (HR: 1.21; 95% CI: 1.10 to 1.33, per 10 mg/dl [0.26 mmol/l]; p < 0.001), but not low-density lipoprotein cholesterol (LDL-C) or HDL-C, were associated with MACEs. Atherogenic dyslipidemia (triglycerides >150 mg/dl [1.69 mmol/l] and HDL-C <40 mg/dl [1.03 mmol/l] in men or <50 mg/dl [1.29 mmol/l] in women) was also associated with MACEs (HR: 1.44; 95% CI: 1.04 to 2.00; p = 0.030). Remnant-C ≥30 mg/dl (0.78 mmol/l) differentiated subjects at a higher risk of MACEs compared with those at lower concentrations, regardless of whether LDL-C levels were on target at ≤100 mg/dl (2.59 mmol/l). CONCLUSIONS In overweight or obese subjects at high cardiovascular risk, levels of triglycerides and remnant-C, but not LDL-C, were associated with cardiovascular outcomes independent of other risk factors.
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Affiliation(s)
- Olga Castañer
- Cardiovascular Risk and Nutrition Research Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Xavier Pintó
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge-Idibell, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Isaac Subirana
- CIBER of Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain
| | - Antonio J Amor
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Lipid and Vascular Risk Clinic, Endocrinology and Nutrition Department, Hospital Clínic, Barcelona, Spain
| | - Emilio Ros
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Lipid and Vascular Risk Clinic, Endocrinology and Nutrition Department, Hospital Clínic, Barcelona, Spain; Cardiovascular Risk, Nutrition, and Aging Research Group, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
| | - Álvaro Hernáez
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Cardiovascular Risk, Nutrition, and Aging Research Group, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
| | - Miguel Ángel Martínez-González
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Preventive Medicine and Public Health, Universidad de Navarra, Pamplona, Spain; Department of Nutrition, Harvard TH Chan School of Public Health, Boston, Massachusetts
| | - Dolores Corella
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Preventive Medicine, Universidad de Valencia, Valencia, Spain
| | - Jordi Salas-Salvadó
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Hospital Universitari San Joan de Reus, Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
| | - Ramón Estruch
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
| | - José Lapetra
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Internal Medicine Service, Hospital Clínic, Barcelona, Spain
| | - Enrique Gómez-Gracia
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Family Medicine, Research Unit, Distrito Sanitario Atención Primaria Sevilla, Sevilla, Spain
| | - Angel M Alonso-Gomez
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Preventive Medicine and Public Health, Universidad de Málaga, Málaga, Spain
| | - Miquel Fiol
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Bioaraba Health Research Institute, Osakidetza Basque Health Service, Araba University Hospital, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain Health Research Institute of the Balearic Islands (IdISBa), Hospital Son Espases Palma de Mallorca, Mallorca, Spain
| | - Lluís Serra-Majem
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Instituto de Investigaciones Biomédicas y Sanitarias, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain; Centro Hospitalario Universitario Insular Materno Infantil (CHUIMI), Servicio Canario de Salud, Las Palmas, Spain
| | - Emili Corbella
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge-Idibell, L'Hospitalet de Llobregat, Barcelona, Spain
| | - David Benaiges
- Cardiovascular Risk and Nutrition Research Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Endocrinology Service, Parc de Salut Mar, Barcelona, Spain
| | - Jose V Sorli
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Preventive Medicine, Universidad de Valencia, Valencia, Spain
| | - Miguel Ruiz-Canela
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Preventive Medicine and Public Health, Universidad de Navarra, Pamplona, Spain; Department of Nutrition, Harvard TH Chan School of Public Health, Boston, Massachusetts
| | - Nancy Babió
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Hospital Universitari San Joan de Reus, Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
| | - Lucas Tojal Sierra
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Preventive Medicine and Public Health, Universidad de Málaga, Málaga, Spain
| | - Emilio Ortega
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Lipid and Vascular Risk Clinic, Endocrinology and Nutrition Department, Hospital Clínic, Barcelona, Spain.
| | - Montserrat Fitó
- Cardiovascular Risk and Nutrition Research Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
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Tomlinson B, Chan P, Lam CWK. Postprandial hyperlipidemia as a risk factor in patients with type 2 diabetes. Expert Rev Endocrinol Metab 2020; 15:147-157. [PMID: 32292091 DOI: 10.1080/17446651.2020.1750949] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 03/31/2020] [Indexed: 02/07/2023]
Abstract
Introduction: Postprandial hyperlipidemia is a common feature of the atherogenic dyslipidemia in patients with type 2 diabetes. Quantification of this with oral fat tolerance tests is not used routinely in clinical practice and abnormal postprandial lipids are usually inferred from non-fasting plasma triglyceride levels. Identifying excessive postprandial hyperlipidemia may help to refine cardiovascular risk assessment but there are no treatments currently available which selectively target postprandial lipids and no large cardiovascular outcome trials using this as the entry criterion.Areas covered: In this review of relevant published material, we summarize the findings from the most important publications in this area.Expert opinion: Postprandial hyperlipidemia appears to contribute to the cardiovascular risk in patients with diabetes. Non-fasting triglyceride levels provide a surrogate marker of postprandial hyperlipidemia but more specific markers such as apoB48 levels may prove to be more reliable. Omega-3 fatty acids, fibrates and ezetimibe can reduce postprandial lipids but may not correct them completely. Several novel treatments have been developed to target hypertriglyceridemia and some of these may be particularly effective in improving postprandial levels. Further clinical trials are needed to establish the role of postprandial lipids in assessment of cardiovascular risk and to identify the most effective treatments.
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Affiliation(s)
- Brian Tomlinson
- Faculty of Medicine, Macau University of Science and Technology, Macau, China
| | - Paul Chan
- Division of Cardiology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan
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Olabode OP, Akinlade OM, Babatunde AS, Abdulazeez MI, Biliaminu SA, Oyabambi AO, Olatunji VA, Soladoye AO, Olatunji LA. Triglyceride/HDL-cholesterol ratio and plasminogen activator inhibitor-1 independently predict high pulse pressure in sickle cell trait and disease. Arch Physiol Biochem 2020; 126:166-171. [PMID: 30145922 DOI: 10.1080/13813455.2018.1499118] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
We hypothesised that TG/HDL-C ratio and PAI-1 would be associated with high pulse pressure (PP) in young adults with sickle cell trait (SCT) and sickle cell disease (SCD). We compared the clinical, biochemical, and cardiometabolic parameters among individuals with normal genotype (HbAA; n = 60), SCT (HbAS; n = 60), and SCD (HbSS; n = 60), all in steady state. Using multivariate linear regression analysis, high PP was positively related to TG/HDL-C ratio in SCT (β = 0.307; p = .014) and PAI-1 (β = 0.499; p = .001) in SCD. The curve of receiver operating characteristic also showed that TG/HDL-C ratio and PAI-1 are efficient predictors of high PP in SCT carriers and SCD patients, respectively. This study suggests that increased levels of TG/HDL-C ratio and PAI-1 may be salient risk factors that would promote the development of arterial stiffness and other CVD in SCT carriers and SCD patients.
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Affiliation(s)
- Olatunde P Olabode
- HOPE Cardiometabolic Research Team, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
- Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
| | - Olawale M Akinlade
- Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
- Department of Medicine, Ladoke Akintola University of Technology Teaching Hospital, Ogbomoso, Nigeria
| | - Abiola S Babatunde
- Department of Haematology and Blood Transfusion, College of Health Sciences, University of Ilorin, Nigeria
| | - Musbau I Abdulazeez
- Department of Chemical Pathology and Immunology, University of Ilorin Teaching Hospital, Ilorin, Nigeria
| | - Sikiru A Biliaminu
- Department of Chemical Pathology and Immunology, University of Ilorin Teaching Hospital, Ilorin, Nigeria
| | - Adewumi O Oyabambi
- HOPE Cardiometabolic Research Team, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
- Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
| | - Victoria A Olatunji
- HOPE Cardiometabolic Research Team, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
- Department of Ophthalmology, University of Ilorin Teaching Hospital, Ilorin, Nigeria
| | - Ayodele O Soladoye
- Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
| | - Lawrence A Olatunji
- HOPE Cardiometabolic Research Team, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
- Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
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Kaltoft M, Langsted A, Nordestgaard BG. Triglycerides and remnant cholesterol associated with risk of aortic valve stenosis: Mendelian randomization in the Copenhagen General Population Study. Eur Heart J 2020; 41:2288-2299. [DOI: 10.1093/eurheartj/ehaa172] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 12/17/2019] [Accepted: 03/09/2020] [Indexed: 01/12/2023] Open
Abstract
AbstractAimsWe tested the hypothesis that higher levels of plasma triglycerides and remnant cholesterol are observationally and genetically associated with increased risk of aortic valve stenosis.Methods and resultsWe included 108 559 individuals from the Copenhagen General Population Study. Plasma triglycerides, remnant cholesterol (total cholesterol minus low-density lipoprotein and high-density lipoprotein cholesterol), and 16 genetic variants causing such increased or decreased levels were determined. Incident aortic valve stenosis occurred in 1593 individuals. Observationally compared to individuals with triglycerides <1 mmol/L (<89 mg/dL), the multifactorially adjusted hazard ratio for aortic valve stenosis was 1.02 [95% confidence interval (CI) 0.87–1.19] for individuals with triglycerides of 1.0–1.9 mmol/L (89–176 mg/dL), 1.22 (1.02–1.46) for 2.0–2.9 mmol/L (177–265 mg/dL), 1.40 (1.11–1.77) for 3.0–3.9 mmol/L (266–353 mg/dL), 1.29 (0.88–1.90) for 4.0–4.9 mmol/L (354–442 mg/dL), and 1.52 (1.02–2.27) for individuals with triglycerides ≥5 mmol/L (≥443 mg/dL). By age 85, the cumulative incidence of aortic valve stenosis was 5.1% for individuals with plasma triglycerides <2.0 mmol/L (77 mg/dL), 6.5% at 2.0–4.9 mmol/L (177–442 mg/dL), and 8.2% for individuals with plasma triglycerides ≥5.0 mmol/L (443 mg/dL). The corresponding values for remnant cholesterol categories were 4.8% for <0.5 mmol/L (19 mg/dL), 5.6% for 0.5–1.4 mmol/L (19–57 mg/dL), and 7.4% for ≥1.5 mmol/L (58 mg/dL). Genetically, compared to individuals with allele score 13–16, odds ratios for aortic valve stenosis were 1.30 (95% CI 1.20–1.42; Δtriglycerides +12%; Δremnant cholesterol +11%) for allele score 17–18, 1.41 (1.31–1.52; +25%; +22%) for allele score 19–20, and 1.51 (1.22–1.86; +51%; +44%) for individuals with allele score 21–23.ConclusionHigher triglycerides and remnant cholesterol were observationally and genetically associated with increased risk of aortic valve stenosis.
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Affiliation(s)
- Morten Kaltoft
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Elevator 7, DK-2730 Herlev, Denmark
- The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, DK-2730 Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark
| | - Anne Langsted
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Elevator 7, DK-2730 Herlev, Denmark
- The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, DK-2730 Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark
| | - Børge G Nordestgaard
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Elevator 7, DK-2730 Herlev, Denmark
- The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, DK-2730 Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark
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Campbell AW, Sinatra D, Zhang Z, Sinatra ST. Efficacy of Spore Forming Bacilli Supplementation in Patients with Mild to Moderate Elevation of Triglycerides: A 12 week, Randomized, Double-Blind, Placebo Controlled Trial. Integr Med (Encinitas) 2020; 19:22-27. [PMID: 33041703 PMCID: PMC7482325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
OBJECTIVE The purpose of this randomized double-blind placebo controlled clinical trial was to evaluate the effects of a commercial spore-based probiotic supplement consisting of 5 different spore forming bacilli (Bacillus indicus HU36, Bacillus subtilis HU58, Bacillus coagulans SC-208, Bacillus licheniformis, and Bacillus clausii SC-109) on reducing the triglyceride levels (TG) in patients with mild to moderate hypertriglyceridemia (HT). STUDY DESIGN A randomized, double-blind, placebo-controlled study with eighty participants with non-fasting triglyceride levels greater than 150 mg/dL. METHODS Eighty participants with non-fasting triglyceride levels greater than 150 mg/dL were randomized to receive oral probiotic supplement consisting of two capsules containing 5 different spore forming bacilli once daily in the morning or a placebo (rice flour). Their non-fasting triglyceride levels were measured again at six weeks and at twelve weeks. RESULTS Compared to the placebo group, participants in the probiotic supplement group had significant lowering of their triglyceride levels after 90 days. CONCLUSION Mild to moderately elevated triglyceride levels can be lowered in patients with mild to moderate HT by a probiotic supplement consisting of five different spore forming bacilli.
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Affiliation(s)
| | - Drew Sinatra
- naturopathic doctor of integrative medicine at the CLEAR Center for Health in Mill Valley, California
| | - Zhiwei Zhang
- Department of Statistics-University of California Riverside, in Riverside California
| | - Stephen T Sinatra
- assistant clinical professor of medicine at the School of Medicine, University of Connecticut in Farmington, Connecticut
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Alahakoon TI, Medbury HJ, Williams H, Lee VW. Lipid profiling in maternal and fetal circulations in preeclampsia and fetal growth restriction-a prospective case control observational study. BMC Pregnancy Childbirth 2020; 20:61. [PMID: 32000699 PMCID: PMC6993402 DOI: 10.1186/s12884-020-2753-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 01/20/2020] [Indexed: 12/18/2022] Open
Abstract
Background While many risk factors for preeclampsia, such as increased body mass index, advanced maternal age, chronic hypertension, diabetes, are now established in clinical practice, maternal lipid profile has not been included in the risk assessment for preeclampsia. We aim to characterize the serum levels of Total Cholesterol (TC), High density lipoprotein (HDL), Low density lipoprotein (LDL), Triglycerides (TG), Apolipoprotein A1, Apolipoprotein B and their ratios TC/HDL and ApoB/ApoA1 in the maternal and fetal circulations of normal pregnancy, preeclampsia (PE), fetal growth restriction (FGR) and PE + FGR. Methods A prospective cross-sectional case control study was conducted measuring maternal and fetal lipid levels by enzymatic analysis and immune-turbidimetric enzymatic assays. FGR was defined by elevated umbilical artery Doppler resistance in association with estimated fetal weight < 10%. Kruskal Wallis non-parametric analysis of variance was used to test for homogeneity across the clinical groups for each of the variables, Mann-Whitney tests for pairwise comparisons and Spearman rank correlation were used to quantify gestational age-related changes. Results (1) TG levels were elevated in maternal PE and cord blood PE + FGR groups compared to normal pregnancies. (2) A statistically significant elevation of fetal ApoB levels was observed in PE, FGR and PE + FGR compared to normal pregnancies. Apolipoprotein levels A1 and B were not different between maternal groups. (3) TC, HDL, LDL and TC/HDL levels did not show any significant gestational variation or between clinical groups in the maternal or fetal circulation. Conclusions Elevation in maternal TG levels may have a role in the pathogenesis of PE. The implications of elevated maternal and fetal TG levels and elevated fetal Apolipoprotein B levels deserves further exploration of their role in long term cardiovascular risk in the mother as well as the offspring.
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Affiliation(s)
- Thushari I Alahakoon
- University of Sydney, Sydney Medical School, Sydney, NSW, Australia. .,Westmead Institute for Maternal and Fetal Medicine, Westmead Hospital, Westmead, NSW, Australia.
| | - Heather J Medbury
- University of Sydney, Sydney Medical School, Sydney, NSW, Australia.,Department of Surgery, Westmead Hospital, Westmead, NSW, Australia
| | - Helen Williams
- University of Sydney, Sydney Medical School, Sydney, NSW, Australia.,Department of Surgery, Westmead Hospital, Westmead, NSW, Australia
| | - Vincent W Lee
- University of Sydney, Sydney Medical School, Sydney, NSW, Australia.,Department of Renal Medicine, Westmead Hospital and University of Sydney, Westmead, NSW, Australia
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Li Y, Peng M, Zeng T, Zheng J, Liao Y, Zhang H, Yang S, Chen L. Protein Arginine Methyltransferase 4 Regulates Adipose Tissue Lipolysis in Type 1 Diabetic Mice. Diabetes Metab Syndr Obes 2020; 13:535-544. [PMID: 32161480 PMCID: PMC7049750 DOI: 10.2147/dmso.s235869] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Accepted: 02/10/2020] [Indexed: 12/19/2022] Open
Abstract
PURPOSE Hypertriglyceridemia is considered to be driven by increased lipolysis in type 1 diabetes mellitus (T1DM). However, information regarding the transcriptional circuitry that governs lipolysis remains incomplete in T1DM. Protein arginine methyltransferase 4 (PRMT4), a transcriptional coactivation factor, promotes autophagy and may play an important role in lipolysis. We wonder whether activated lipolysis in T1DM is regulated by PRMT4. MATERIALS AND METHODS Recombinant adeno-associated virus was adopted to overexpress PRMT4 in adipose tissue of mice. Streptozotocin (150 mg/kg) was injected intraperitoneally into mice to induce T1DM. Plasma insulin, triglycerides, free fatty acids (FFAs) levels were determined using commercial assay kits. Differentiated adipocytes were applied to verify the regulation of PRMT4 on lipolysis. RESULTS Elevated serum triglycerides and FFAs were observed in PRMT4-overexpressed T1DM mice. We also observed that PRMT4 over-expression induced the decrease of fat pads weights and adipocyte sizes. Moreover, expression levels of lipolysis-related molecules, including ATGL, HSL, and MAGL, and HSL phosphorylation levels were increased in PRMT4-overexpressed mice when compared to those of control mice. In vitro, PRMT4 promoted FFAs release and activated HSL phosphorylation, whereas PRMT4 knockdown inhibited these processes. CONCLUSION PRMT4 promotes lipolysis and increases serum triglyceride in T1DM.
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Affiliation(s)
- Yuanxiang Li
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei430022, People’s Republic of China
| | - Miaomiao Peng
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei430022, People’s Republic of China
| | - Tianshu Zeng
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei430022, People’s Republic of China
| | - Juan Zheng
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei430022, People’s Republic of China
| | - Yunfei Liao
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei430022, People’s Republic of China
| | - Hao Zhang
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei430022, People’s Republic of China
| | - Songtao Yang
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei430022, People’s Republic of China
| | - Lulu Chen
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei430022, People’s Republic of China
- Correspondence: Lulu Chen Email
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