|
1
|
Han EJ, Park EJ, Lee SR, Lee SY, Cho YH, Lee YI, Choi JI, Kwon RJ, Son SM, Kim YJ, Lee JG, Yi YH, Tak YJ, Lee SH, Kim GL, Ra YJ. Association between breakfast consumption frequency and chronic inflammation in Korean adult males: Korea National Health and Nutrition Examination Survey 2016-2018. Korean J Fam Med 2025; 46:92-97. [PMID: 38965838 PMCID: PMC11969176 DOI: 10.4082/kjfm.23.0151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 01/03/2024] [Accepted: 01/16/2024] [Indexed: 07/06/2024] Open
Abstract
BACKGROUND Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker. METHODS A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016-2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely "0-2 breakfasts per week" and "3-7 breakfasts per week"; hs-CRP concentrations were measured through blood tests. RESULTS Comparing between the "infrequent breakfast consumption (0-2 breakfasts per week)" and "frequent breakfast consumption (3-7 breakfasts per week)" groups, the mean hs-CRP was found to be significantly higher in the "infrequent breakfast consumption" group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036). CONCLUSION Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.
Collapse
Affiliation(s)
- Eun Ji Han
- Department of Family Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Eun Ju Park
- Department of Family Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Sae Rom Lee
- Department of Family Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Sang Yeoup Lee
- Department of Family Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
- Department of Medical Education, Pusan National University School of Medicine, Yangsan, Korea
| | - Young Hye Cho
- Department of Family Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
- Department of Medical Education, Pusan National University School of Medicine, Yangsan, Korea
| | - Young In Lee
- Department of Family Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Jung In Choi
- Department of Family Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Ryuk Jun Kwon
- Department of Family Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Soo Min Son
- Department of Family Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Yun Jin Kim
- Department of Family Medicine, Pusan National University Hospital, Busan, Korea
| | - Jeong Gyu Lee
- Department of Family Medicine, Pusan National University Hospital, Busan, Korea
| | - Yu Hyeon Yi
- Department of Family Medicine, Pusan National University Hospital, Busan, Korea
| | - Young Jin Tak
- Department of Family Medicine, Pusan National University Hospital, Busan, Korea
| | - Seung Hun Lee
- Department of Family Medicine, Pusan National University Hospital, Busan, Korea
| | - Gyu Lee Kim
- Department of Family Medicine, Pusan National University Hospital, Busan, Korea
| | - Young Jin Ra
- Department of Family Medicine, Pusan National University Hospital, Busan, Korea
| |
Collapse
|
|
2
|
He Q, Lai Z, Zhai Z, Zou B, Shi Y, Feng C. Advances of research in diabetic cardiomyopathy: diagnosis and the emerging application of sequencing. Front Cardiovasc Med 2025; 11:1501735. [PMID: 39872882 PMCID: PMC11769946 DOI: 10.3389/fcvm.2024.1501735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 12/27/2024] [Indexed: 01/30/2025] Open
Abstract
Diabetic cardiomyopathy (DCM) is one of the most prevalent and severe complications associated with diabetes mellitus (DM). The onset of DCM is insidious, with the symptoms being obvious only in the late stage. Consequently, the early diagnosis of DCM is a formidable challenge which significantly influences the treatment and prognosis of DCM. Thus, it becomes imperative to uncover innovative approaches to facilitate the prompt identification and diagnosis of DCM. On the traditional clinical side, we tend to use serum biomarkers as well as imaging as the most common means of diagnosing diseases because of their convenience as well as affordability. As we delve deeper into the mechanisms of DCM, a wide variety of biomarkers are becoming competitive diagnostic indicators. Meanwhile, the application of multiple imaging techniques has also made efforts to promote the diagnosis of DCM. Besides, the spurt in sequencing technology has made it possible to give hints about disease diagnosis from the genome as well as the transcriptome, making diagnosis less difficult, more sensitive, and more predictive. Overall, sequencing technology is expected to be the superior choice of plasma biomarkers for detecting lesions at an earlier stage than imaging, and its judicious utilization combined with imaging technologies will lead to a more sensitive diagnosis of DCM in the future. Therefore, this review meticulously consolidates the progress and utilization of various biomarkers, imaging methods, and sequencing technologies in the realm of DCM diagnosis, with the aim of furnishing novel theoretical foundation and guide future research endeavors towards enhancing the diagnostic and therapeutic landscape of DCM.
Collapse
Affiliation(s)
- Qianqian He
- Department of Cardiology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China
| | - Ze Lai
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China
| | - Zhengyao Zhai
- Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Beibei Zou
- Department of Cardiology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China
| | - Yangkai Shi
- Department of Cardiology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China
| | - Chao Feng
- Department of Cardiology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China
| |
Collapse
|
|
3
|
Rade JJ, Kronsberg SS, Kickler TS, Vasan RS, Xanthakis V, Nayor MG, Barton BA. Association of Systemic Thromboxane Generation With Risk of Developing Heart Failure. J Am Coll Cardiol 2025; 85:58-70. [PMID: 39779056 DOI: 10.1016/j.jacc.2024.09.010] [Citation(s) in RCA: 1] [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: 06/16/2024] [Revised: 08/29/2024] [Accepted: 09/09/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND Systemic thromboxane A2 generation, which is readily assessed by quantifying thromboxane B2 metabolites (TXB2-M) in the urine, is associated with impaired cardiac performance and mortality in aspirin (ASA) users with heart failure (HF). OBJECTIVES This study sought to determine the association of urinary TXB2-M with the risk of developing HF in individuals without prior history of HF and with normal left ventricular function irrespective of ASA use. METHODS Urine TXB2-M were measured by immunoassay and adjusted to urine concentration and renal function (TXB2-MGFR) in 2,611 Framingham Heart Study participants (54.9% women, mean age 65 ± 9 years, 43.8% ASA users) without prior history of HF and with left ventricular ejection fraction (LVEF) ≥55%. The association of TXB2-MGFR with HF risk over a median observation period of 14.8 years (Q1-Q3: 12.6-15.7 years) was modeled using Cox regression. RESULTS HF occurred in 189 participants (7.2%), with 104 of the first events (55.0%) classified as HF with preserved LVEF, 56 (29.6%) as HF with reduced LVEF, and 29 (15.3%) were unclassifiable. TXB2-MGFR levels, above compared to below, of 16.6 and 62.1 filtered prostanoid units for ASA users and nonusers, respectively, were associated with increased risk of developing HF (HR: 1.81; 95% CI: 1.38-2.64; P < 0.0001, adjusted for age, sex, ASA use, and HF risk factors), including both HF subtypes (HF with preserved LVEF: HR: 1.81; 95% CI: 1.17-2.80; P = 0.0081, and HF with reduced LVEF: HR: 2.63; 95% CI: 1.48-4.68; P = 0.0010, adjusted for age, sex, ASA use, and cardiovascular disease). Neither ASA use nor evidence of platelet activation, as measured by plasma P-selectin, were independently associated with HF risk. CONCLUSIONS Systemic thromboxane A2 generation as measured by urinary TXB2-MGFR was significantly associated with HF risk and remained so after accounting for traditional risk factors. Urinary TXB2-MGFR is therefore a potentially useful novel biomarker to identify at-risk individuals who might benefit from aggressive primary prevention.
Collapse
Affiliation(s)
- Jeffrey J Rade
- Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
| | - Shari S Kronsberg
- Division of Biostatistics and Health Services Research, Department of Population and Quantitative Health Sciences, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA
| | - Thomas S Kickler
- Department of Pathology, the Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Ramachandran S Vasan
- Department of Quantitative and Qualitative Health Sciences, University of Texas School of Public Health in San Antonio, San Antonio, Texas, USA; Section of Preventative Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Vanessa Xanthakis
- Section of Preventative Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Matthew G Nayor
- Section of Preventative Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA; Section of Cardiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Bruce A Barton
- Division of Biostatistics and Health Services Research, Department of Population and Quantitative Health Sciences, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA
| |
Collapse
|
|
4
|
Arvunescu AM, Ionescu RF, Cretoiu SM, Dumitrescu SI, Zaharia O, Nanea IT. Inflammation in Heart Failure-Future Perspectives. J Clin Med 2023; 12:7738. [PMID: 38137807 PMCID: PMC10743797 DOI: 10.3390/jcm12247738] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 12/01/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023] Open
Abstract
Chronic heart failure is a terminal point of a vast majority of cardiac or extracardiac causes affecting around 1-2% of the global population and more than 10% of the people above the age of 65. Inflammation is persistently associated with chronic diseases, contributing in many cases to the progression of disease. Even in a low inflammatory state, past studies raised the question of whether inflammation is a constant condition, or if it is, rather, triggered in different amounts, according to the phenotype of heart failure. By evaluating the results of clinical studies which focused on proinflammatory cytokines, this review aims to identify the ones that are independent risk factors for heart failure decompensation or cardiovascular death. This review assessed the current evidence concerning the inflammatory activation cascade, but also future possible targets for inflammatory response modulation, which can further impact the course of heart failure.
Collapse
Affiliation(s)
- Alexandru Mircea Arvunescu
- Department of Internal Medicine and Cardiology, “Prof. Dr. Th. Burghele” Clinical Hospital, 061344 Bucharest, Romania; (O.Z.); (I.T.N.)
- Department of Cardio-Thoracic Pathology, Cardio-Thoracic Pathology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050471 Bucharest, Romania
| | - Ruxandra Florentina Ionescu
- Department of Cardiology I, Central Military Emergency Hospital “Dr Carol Davila”, 030167 Bucharest, Romania (S.I.D.)
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Sanda Maria Cretoiu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Silviu Ionel Dumitrescu
- Department of Cardiology I, Central Military Emergency Hospital “Dr Carol Davila”, 030167 Bucharest, Romania (S.I.D.)
- Department of Cardiology, Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania
| | - Ondin Zaharia
- Department of Internal Medicine and Cardiology, “Prof. Dr. Th. Burghele” Clinical Hospital, 061344 Bucharest, Romania; (O.Z.); (I.T.N.)
- Department of Cardio-Thoracic Pathology, Cardio-Thoracic Pathology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050471 Bucharest, Romania
| | - Ioan Tiberiu Nanea
- Department of Internal Medicine and Cardiology, “Prof. Dr. Th. Burghele” Clinical Hospital, 061344 Bucharest, Romania; (O.Z.); (I.T.N.)
- Department of Cardio-Thoracic Pathology, Cardio-Thoracic Pathology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050471 Bucharest, Romania
| |
Collapse
|
|
5
|
Wang Y, Chen W, Ding S, Wang W, Wang C. Pentraxins in invertebrates and vertebrates: From structure, function and evolution to clinical applications. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2023; 149:105064. [PMID: 37734429 DOI: 10.1016/j.dci.2023.105064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 09/18/2023] [Accepted: 09/18/2023] [Indexed: 09/23/2023]
Abstract
The immune system is divided into two broad categories, consisting of innate and adaptive immunity. As recognition and effector factors of innate immunity and regulators of adaptive immune responses, lectins are considered to be important defense chemicals against microbial pathogens, cell trafficking, immune regulation, and prevention of autoimmunity. Pentraxins, important members of animal lectins, play a significant role in protecting the body from pathogen infection and regulating inflammatory reactions. They can recognize and bind to a variety of ligands, including carbohydrates, lipids, proteins, nucleic acids and their complexes, and protect the host from pathogen invasion by activating the complement cascade and Fcγ receptor pathways. Based on the primary structure of the subunit, pentraxins are divided into short and long pentraxins. The short pentraxins are comprised of C-reactive protein (CRP) and serum amyloid P (SAP), and the most important member of the long pentraxins is pentraxin 3 (PTX3). The CRP and SAP exist in both vertebrates and invertebrates, while the PTX3 may be present only in vertebrates. The major ligands and functions of CRP, SAP and PTX3 and three activation pathways involved in the complement system are summarized in this review. Their different characteristics in various animals including humans, and their evolutionary trees are analyzed. The clinical applications of CRP, SAP and PTX3 in human are reviewed. Some questions that remain to be understood are also highlighted.
Collapse
Affiliation(s)
- Yuying Wang
- School of Life Sciences, Ludong University, Yantai, 264025, People's Republic of China
| | - Wei Chen
- School of Life Sciences, Ludong University, Yantai, 264025, People's Republic of China; Yantai Productivity Promotion Center, Yantai, 264003, People's Republic of China
| | - Shuo Ding
- School of Life Sciences, Ludong University, Yantai, 264025, People's Republic of China
| | - Wenjun Wang
- School of Life Sciences, Ludong University, Yantai, 264025, People's Republic of China
| | - Changliu Wang
- School of Life Sciences, Ludong University, Yantai, 264025, People's Republic of China.
| |
Collapse
|
|
6
|
Runhaar J, van Berkel AC, Agricola R, van Meurs J, Bierma-Zeinstra SMA. Risk Factors and Population-Attributable Fractions for Incident Hip Osteoarthritis. HSS J 2023; 19:407-412. [PMID: 37937087 PMCID: PMC10626934 DOI: 10.1177/15563316231192461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 06/09/2023] [Indexed: 11/09/2023]
Abstract
Background Despite the huge burden of hip osteoarthritis (OA) and the lack of effective treatment, research into the primary prevention of hip OA is in its infancy. Purpose We sought to evaluate risk factors for incident clinical and incident radiographic hip OA among middle-aged and older adults, to evaluate the importance of risk factors from a preventive perspective, and to estimate the percentage of new cases attributable to these risk factors. Methods We retrospectively reviewed data from the Rotterdam study, an open-population cohort study of individuals aged 55 years or older. Data including baseline age, sex, body mass index, smoking status, education level, diagnosis of diabetes, C-reactive protein (CRP), cam morphology, acetabular dysplasia, radiographic thumb OA, radiographic hip OA, and hip pain were assessed for their association with incident clinical hip OA and incident radiographic hip OA separately, after 11 years of follow-up. The population-attributable fractions (PAFs) of statistically significant modifiable risk factors were calculated, as well. Results New onset of clinical hip OA was seen in 19.9% (544 of 2729) and incident radiographic hip OA in 9.9% (329 of 3309). Female sex, education level below average (PAF 21.4%), and radiographic hip OA (PAF 3.4%) were statistically significantly associated with incident clinical hip OA. Female sex, age, overweight (PAF 20.0%), cam morphology (PAF 7.9%), acetabular dysplasia (PAF 3.6%), and radiographic thumb OA (PAF 4.7%) were statistically significantly associated with radiographic hip OA. Conclusions Our retrospective analysis suggests that, from a primary prevention perspective, the most important modifiable risk factors among middle-aged and older individuals may be low educational level for incident clinical hip OA and overweight for incident radiographic hip OA. Further study is warranted.
Collapse
Affiliation(s)
- Jos Runhaar
- Department of General Practice, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Annemaria C van Berkel
- Department of General Practice, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Rintje Agricola
- Department of Orthopedics & Sports Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
- Department of Orthopedic Surgery, St Anna Hospital, Geldrop, the Netherlands
| | - Joyce van Meurs
- Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Sita M A Bierma-Zeinstra
- Department of General Practice, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
- Department of Orthopedics & Sports Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| |
Collapse
|
|
7
|
Burger PM, Koudstaal S, Mosterd A, Fiolet ATL, Teraa M, van der Meer MG, Cramer MJ, Visseren FLJ, Ridker PM, Dorresteijn JAN. C-Reactive Protein and Risk of Incident Heart Failure in Patients With Cardiovascular Disease. J Am Coll Cardiol 2023; 82:414-426. [PMID: 37495278 DOI: 10.1016/j.jacc.2023.05.035] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 04/06/2023] [Accepted: 05/10/2023] [Indexed: 07/28/2023]
Abstract
BACKGROUND Patients with established cardiovascular disease (CVD) are at high risk of incident heart failure (HF), which may in part reflect the impact of systemic inflammation. OBJECTIVES The goal of this study was to determine the association between C-reactive protein (CRP) and incident HF in patients with established CVD. METHODS Patients from the prospective UCC-SMART (Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease) cohort with established CVD, but without prevalent HF were included (n = 8,089). Incident HF was defined as a first hospitalization for HF. The association between baseline CRP and incident HF was assessed using Cox proportional hazards models adjusted for established risk factors (ie, age, sex, myocardial infarction, smoking, diabetes mellitus, body mass index, blood pressure, cholesterol, and kidney function). RESULTS During a median follow-up of 9.7 years (IQR 5.4-14.1 years), 810 incident HF cases were observed (incidence rate 1.01/100 person-years). Higher CRP was independently associated with an increased risk of incident HF: HR per 1 mg/L: 1.10 (95% CI: 1.07-1.13), and for last vs first CRP quartile: 2.22 (95% CI: 1.76-2.79). The association was significant for both HF with reduced (HR: 1.09; 95% CI: 1.04-1.14) and preserved ejection fraction (HR: 1.12; 95% CI: 1.07-1.18) (P for difference = 0.137). Additional adjustment for medication use and interim myocardial infarction did not attenuate the association, and the association remained consistent beyond 15 years after the CRP measurement. CONCLUSIONS In patients with established CVD, CRP is an independent risk marker of incident HF. These data support ongoing trial efforts to assess whether anti-inflammatory agents can reduce the burden of HF.
Collapse
Affiliation(s)
- Pascal M Burger
- Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Stefan Koudstaal
- Department of Cardiology, Green Heart Hospital, Gouda, the Netherlands
| | - Arend Mosterd
- Department of Cardiology, Meander Medical Center, Amersfoort, the Netherlands
| | - Aernoud T L Fiolet
- Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Martin Teraa
- Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Manon G van der Meer
- Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Maarten J Cramer
- Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Frank L J Visseren
- Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Paul M Ridker
- Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jannick A N Dorresteijn
- Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
| |
Collapse
|
|
8
|
Habibi D, Daneshpour MS, Asgarian S, Kohansal K, Hadaegh F, Mansourian M, Akbarzadeh M. Effect of C-reactive protein on the risk of Heart failure: a mendelian randomization study. BMC Cardiovasc Disord 2023; 23:112. [PMID: 36882679 PMCID: PMC9993577 DOI: 10.1186/s12872-023-03149-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Accepted: 02/24/2023] [Indexed: 03/09/2023] Open
Abstract
BACKGROUND Traditional observational studies have shown positive associations between c-reactive protein (CRP) and heart failure (HF) risk. However, this association has not been fully elucidated. Therefore, Mendelian randomization was used to examine CRP's possible etiological roles with HF. METHODS We implemented a two-sample Mendelian randomization framework to examine the causality of the association between CRP and HF based on summary statistics by large-scale genome-wide association studies (GWAS) datasets of European ancestry through inverse-variance weighted, weighted median, MREgger regression, and MR-PRESSO methods. The summary statistics dataset on the association of genetic variants with CRP was used from the published GWAS of European descent in UK Biobank participants (N = 427,367) and the CHARGE consortium (N = 575,531). The GWAS dataset used to identify genetic variants underlying HF from the HERMES consortium includes 977,323 participants (47,309 cases and 930,014 controls). The odds ratio (OR) with 95% confidence intervals (CIs) was employed to examine this association. RESULTS The results of our IVW indicated that CRP was strongly associated with HF (OR = 4.18, 95% CI = 3.40-5.13, p < 0.001). The Cochran heterogeneity test showed significant heterogeneity among SNPs of CRP (Q = 317.55, p < 0.001; I2 = 37.6%), and no considerable pleiotropy was detected for the association of CRP with HF [intercept = 0.003; p = 0.234]. This finding remained consistent using different Mendelian randomization methods and sensitivity analyses. CONCLUSION Our MR study did identify convincing evidence to support CRP associated with HF risk. Human genetic data suggest that CRP is a causative factor in HF. Hence, CRP assessment may offer additional prognostic information as an adjuvant to overall risk assessment in HF patients. These findings prompt significant questions about the function of inflammation in the progression of HF. More research into the role of inflammation in HF is needed to guide trials of anti-inflammation management.
Collapse
Affiliation(s)
- Danial Habibi
- Department of Biostatistics and Epidemiology, School of Health, and Student Research Committee, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Maryam S Daneshpour
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Asgarian
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Karim Kohansal
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farzad Hadaegh
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Marjan Mansourian
- Epidemiology and Biostatistics Department, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Mahdi Akbarzadeh
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. .,Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Science, Shahid Beheshti University of Medical Science, P.O. Box: 19395-4763, 1985717413, Tehran, Iran.
| |
Collapse
|
|
9
|
Sanghavi R, Pana TA, Mamayusupova H, Maidment I, Fox C, Boekholdt SM, Mamas MA, Wareham NJ, Khaw K, Myint PK. Higher anticholinergic burden from medications is associated with significant increase in markers of inflammation in the EPIC-Norfolk prospective population-based cohort study. Br J Clin Pharmacol 2022; 88:3297-3306. [PMID: 35118716 PMCID: PMC9373850 DOI: 10.1111/bcp.15261] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 01/30/2022] [Accepted: 01/31/2022] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Higher medication anticholinergic burden is associated with increased risk of cardiovascular disease and cognitive decline. A mechanistic pathway has not been established. We aimed to determine whether inflammation may mediate these associations. METHODS Participants were drawn from the European Prospective Investigation into Cancer, Norfolk cohort (40-79 years at baseline). Anticholinergic burden score (ACB) was calculated at first (1HC) (1993/97) and second (2HC) (1998/2000) health checks. Fibrinogen and C-reactive protein (CRP) were measured during 1HC and tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) during 2HC. Cross-sectional associations between ACB and inflammatory markers were examined for both health checks. Prospective associations were also examined between 1HC ACB and 2HC inflammatory markers. Models were adjusted for age, sex, lifestyle factors, comorbidities and medications. RESULTS In total, 17 678 and 22 051 participants were included in cross-sectional analyses for CRP, and fibrinogen, respectively. Furthermore, 5101 participants with data on TNF-α and IL-6 were included in the prospective analyses. Cross-sectionally, compared to ACB = 0, ACB ≥ 4 was associated with higher fibrinogen, beta (95% confidence interval) = 0.134 g/L (0.070, 0.199), CRP 1.175 mg/L (0.715, 1.634), IL-6 0.593 pg/mL (0.254, 0.932) and TNF-α 0.137 pg/mL (0.033, 0.241). In addition, a point increase in ACB was associated with higher levels of all markers. Prospectively, compared to ACB = 0, ACB ≥ 4 was associated with higher IL-6(pg/mL) of 0.019 (-0.323, 0.361) and TNF-α (pg/mL) of 0.202% (0.81, 0.323). A unit increase in ACB was associated with a significantly higher TNF-α and IL-6. CONCLUSION Higher ACB was associated with higher inflammatory markers. Inflammation may mediate the relationship between anticholinergic medications and adverse outcomes.
Collapse
Affiliation(s)
- Ria Sanghavi
- College of Life SciencesUniversity of LeicesterUK
| | - Tiberiu A. Pana
- Aberdeen Diabetes and Cardiovascular Centre, School of Medicine, Medical Sciences & NutritionUniversity of AberdeenAberdeenScotlandUK
- Ageing Clinical and Experimental Research TeamUniversity of AberdeenUK
| | | | - Ian Maidment
- Pharmaceutical & Clinical Pharmacy Research GroupAston UniversityBirminghamUK
| | - Chris Fox
- Norwich Medical SchoolUniversity of East AngliaNorwichUK
| | - S. Matthijs Boekholdt
- Department of CardiologyAmsterdam University Medical Centre, location AMCAmsterdamThe Netherlands
| | - Mamas A. Mamas
- Keele Cardiovascular Research GroupKeele UniversityStoke‐on‐TrentUK
| | | | - Kay‐Tee Khaw
- Clinical Gerontology Unit, Department of Public Health & Primary CareUniversity of CambridgeCambridgeUK
| | - Phyo K. Myint
- Aberdeen Diabetes and Cardiovascular Centre, School of Medicine, Medical Sciences & NutritionUniversity of AberdeenAberdeenScotlandUK
- Ageing Clinical and Experimental Research TeamUniversity of AberdeenUK
| |
Collapse
|
|
10
|
Guardino CE, Pan S, Vasan RS, Xanthakis V. Multi-system trajectories and the incidence of heart failure in the Framingham Offspring Study. PLoS One 2022; 17:e0268576. [PMID: 35617332 PMCID: PMC9135195 DOI: 10.1371/journal.pone.0268576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 05/02/2022] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Heart failure is a multi-system disease, with non-cardiac systems playing a key role in disease pathogenesis. OBJECTIVE Investigate whether longitudinal multi-system trajectories incrementally predict heart failure risk compared to single-occasion traits. METHODS We evaluated 3,412 participants from the Framingham Heart Study Offspring cohort, free of heart failure, who attended examination cycle 5 and at least one examination between 1995-2008 (mean age 67 years, 54% women). We related trajectories for the following organ systems and metabolic functions to heart failure risk using Cox regression: kidney (estimated glomerular filtration rate), lung (forced vital capacity and the ratio of forced expiratory volume in one second/forced vital capacity), neuromotor (gait time), muscular (grip strength), cardiac (left ventricular mass index and heart rate), vascular function (pulse pressure), cholesterol (ratio of total/high-density lipoprotein), adiposity (body mass index), inflammation (C-reactive protein) and glucose homeostasis (hemoglobin A1c). Using traits selected via forward selection, we derived a trajectory risk score and related it to heart failure risk. RESULTS We observed 276 heart failure events during a median follow up of 10 years. Participants with the 'worst' multi-system trajectory profile had the highest heart failure risk. A one-unit increase in the trajectory risk score was associated with a 2.72-fold increase in heart failure risk (95% CI 2.21-3.34; p<0.001). The mean c-statistics for models including the trajectory risk score and single-occasion traits were 0.87 (95% CI 0.83-0.91) and 0.83 (95% CI 0.80-0.86), respectively. CONCLUSION Incorporating multi-system trajectories reflective of the aging process may add incremental information to heart failure risk assessment when compared to using single-occasion traits.
Collapse
Affiliation(s)
- Cara E. Guardino
- Division of Cardiology, Warren Alpert Medical School of Brown University and Lifespan Cardiovascular Institute, Providence, Rhode Island, United States of America
- Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, United States of America
| | - Stephanie Pan
- Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America
| | - Ramachandran S. Vasan
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, Massachusetts, United States of America
- Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, United States of America
- Section of Cardiology, Boston University School of Medicine, Boston, Massachusetts, United States of America
- Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States of America
| | - Vanessa Xanthakis
- Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America
- National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, Massachusetts, United States of America
- Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, United States of America
| |
Collapse
|
|
11
|
Chavkin NW, Sano S, Wang Y, Oshima K, Ogawa H, Horitani K, Sano M, MacLauchlan S, Nelson A, Setia K, Vippa T, Watanabe Y, Saucerman JJ, Hirschi KK, Gokce N, Walsh K. The Cell Surface Receptors Ror1/2 Control Cardiac Myofibroblast Differentiation. J Am Heart Assoc 2021; 10:e019904. [PMID: 34155901 PMCID: PMC8403294 DOI: 10.1161/jaha.120.019904] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 03/22/2021] [Indexed: 12/25/2022]
Abstract
Background A hallmark of heart failure is cardiac fibrosis, which results from the injury-induced differentiation response of resident fibroblasts to myofibroblasts that deposit extracellular matrix. During myofibroblast differentiation, fibroblasts progress through polarization stages of early proinflammation, intermediate proliferation, and late maturation, but the regulators of this progression are poorly understood. Planar cell polarity receptors, receptor tyrosine kinase-like orphan receptor 1 and 2 (Ror1/2), can function to promote cell differentiation and transformation. In this study, we investigated the role of the Ror1/2 in a model of heart failure with emphasis on myofibroblast differentiation. Methods and Results The role of Ror1/2 during cardiac myofibroblast differentiation was studied in cell culture models of primary murine cardiac fibroblast activation and in knockout mouse models that underwent transverse aortic constriction surgery to induce cardiac injury by pressure overload. Expression of Ror1 and Ror2 were robustly and exclusively induced in fibroblasts in hearts after transverse aortic constriction surgery, and both were rapidly upregulated after early activation of primary murine cardiac fibroblasts in culture. Cultured fibroblasts isolated from Ror1/2 knockout mice displayed a proinflammatory phenotype indicative of impaired myofibroblast differentiation. Although the combined ablation of Ror1/2 in mice did not result in a detectable baseline phenotype, transverse aortic constriction surgery led to the death of all mice by day 6 that was associated with myocardial hyperinflammation and vascular leakage. Conclusions Together, these results show that Ror1/2 are essential for the progression of myofibroblast differentiation and for the adaptive remodeling of the heart in response to pressure overload.
Collapse
Affiliation(s)
- Nicholas W. Chavkin
- Cardiovascular Research CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Department of Cell BiologySchool of MedicineUniversity of VirginiaCharlottesvilleVA
| | - Soichi Sano
- Cardiovascular Research CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Hematovascular Biology CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Molecular Cardiology/Whitaker Cardiovascular InstituteBoston University School of MedicineBostonMA
- Department of CardiologyGraduate School of MedicineOsaka City UniversityOsakaJapan
- Department of CardiologySchool of MedicineUniversity of VirginiaCharlottesvilleVA
| | - Ying Wang
- Cardiovascular Research CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Hematovascular Biology CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Molecular Cardiology/Whitaker Cardiovascular InstituteBoston University School of MedicineBostonMA
- Department of CardiologyXinqiao HospitalArmy Medical UniversityChongqingChina
| | - Kosei Oshima
- Molecular Cardiology/Whitaker Cardiovascular InstituteBoston University School of MedicineBostonMA
| | - Hayato Ogawa
- Cardiovascular Research CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Department of CardiologyGraduate School of MedicineOsaka City UniversityOsakaJapan
| | - Keita Horitani
- Cardiovascular Research CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Department of CardiologyGraduate School of MedicineOsaka City UniversityOsakaJapan
| | - Miho Sano
- Cardiovascular Research CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Molecular Cardiology/Whitaker Cardiovascular InstituteBoston University School of MedicineBostonMA
- Department of CardiologyGraduate School of MedicineOsaka City UniversityOsakaJapan
| | - Susan MacLauchlan
- Molecular Cardiology/Whitaker Cardiovascular InstituteBoston University School of MedicineBostonMA
| | - Anders Nelson
- Cardiovascular Research CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Department of PharmacologyUniversity of VirginiaCharlottesvilleVA
| | - Karishma Setia
- Cardiovascular Research CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
| | - Tanvi Vippa
- Cardiovascular Research CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
| | - Yosuke Watanabe
- Vascular Biology/Whitaker Cardiovascular InstituteBoston University School of MedicineBostonMA
| | - Jeffrey J. Saucerman
- Cardiovascular Research CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Department of Biomedical EngineeringUniversity of VirginiaCharlottesvilleVA
| | - Karen K. Hirschi
- Cardiovascular Research CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Department of Cell BiologySchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Hematovascular Biology CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Cardiovascular Research CenterSchool of MedicineYale UniversityNew HavenCT
| | - Noyan Gokce
- Boston University School of MedicineBostonMA
| | - Kenneth Walsh
- Cardiovascular Research CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Hematovascular Biology CenterSchool of MedicineUniversity of VirginiaCharlottesvilleVA
- Molecular Cardiology/Whitaker Cardiovascular InstituteBoston University School of MedicineBostonMA
- Department of CardiologySchool of MedicineUniversity of VirginiaCharlottesvilleVA
| |
Collapse
|
|
12
|
Yang X, Zhang D, Zhao Y, Liu D, Li Q, Guo C, Tian G, Han M, Qie R, Huang S, Zhou Q, Zhao Y, Feng Y, Wu X, Zhang Y, Li Y, Wu Y, Cheng C, Hu D, Sun L. Association between serum level of C-reactive protein and risk of cardiovascular events based on cohort studies. J Hum Hypertens 2021; 35:1149-1158. [PMID: 33980977 DOI: 10.1038/s41371-021-00546-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 04/06/2021] [Accepted: 04/23/2021] [Indexed: 11/09/2022]
Abstract
Although the association between serum level of C-reactive protein (CRP) and risk of cardiovascular events (CVEs) has been reported, the comprehensive assessment of the quantitative association of CRP level with risk of CVEs has not been reported. Our meta-analysis aims to quantitatively evaluate the association of CRP level and risk of CVEs. We searched PubMed and Embase databases for articles published up to December 6, 2019. Studies with data on men and women, different types of CVEs and multiple cohorts within a study were treated as independent studies. Generalized least-squares regression models were used to assess the quantitative association between CRP level and risk of CVEs. Restricted cubic splines were used to model the possible linear association between CRP and CVEs. We included 36 articles (60 studies; 227,715 participants) in the analysis. The pooled relative risks (RRs) of high versus low CRP level for cardiovascular disease (CVD), stroke and coronary heart disease (CHD) were 1.64 (95% confidence interval [CI], 1.49-1.82), 1.46 (95% CI, 1.35-1.58), and 1.55 (95% CI, 1.47-1.63), respectively. A linear association was found between CRP level and CVD (P = 0.429), stroke (P = 0.940), and CHD (P = 0.931); with each 1-mg/L increase in CRP level, the pooled RRs for CVD, stroke, and CHD were 1.18 (95% CI, 1.12-1.24), 1.07 (95% CI, 1.04-1.09), and 1.12 (95% CI, 1.08-1.16), respectively. This meta-analysis suggests that risk of CVEs increases with increasing serum CRP level.
Collapse
Affiliation(s)
- Xingjin Yang
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Dongdong Zhang
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Yang Zhao
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Dechen Liu
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.,Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Quanman Li
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Chunmei Guo
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Gang Tian
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Minghui Han
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Ranran Qie
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Shengbing Huang
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Qionggui Zhou
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yang Zhao
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Yifei Feng
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Xiaoyan Wu
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yanyan Zhang
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yang Li
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yuying Wu
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Cheng Cheng
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Dongsheng Hu
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
| | - Liang Sun
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
| |
Collapse
|
|
13
|
Chavkin NW, Min KD, Walsh K. Importance of clonal hematopoiesis in heart failure. Trends Cardiovasc Med 2021; 32:198-203. [PMID: 33892102 PMCID: PMC8526615 DOI: 10.1016/j.tcm.2021.04.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 04/09/2021] [Accepted: 04/10/2021] [Indexed: 01/28/2023]
Abstract
Heart failure is prevalent in the elderly population. Inflammatory processes can contribute to the progression of heart failure by altering the balance of tissue healing and pathological remodeling during the injury response. New findings show that aging can alter immune cell phenotypes through the process of clonal hematopoiesis. This condition results from acquired somatic DNA mutations in specific driver genes that give rise to clonal expansions of mutant hematopoietic cells with overactive inflammatory properties. Recent clinical and experimental studies have shown that clonal hematopoiesis is prevalent in heart failure patients and associated with poor prognosis. In this review, we summarize current evidence that associates clonal hematopoiesis with the progression of heart failure. We further describe the mechanistic links between clonal hematopoiesis and the pro-inflammatory responses that can contribute to pathological outcomes in the heart. Finally, we provide perspectives on future research directions in the area of clonal hematopoiesis and heart failure.
Collapse
Affiliation(s)
- Nicholas W Chavkin
- Berne Cardiovascular Research Center USA; Department of Cardiology USA; Hematovascular Biology Center, University of Virginia, School of Medicine, Charlottesville, VA, 22908 USA
| | - Kyung-Duk Min
- Berne Cardiovascular Research Center USA; Department of Cardiology USA; Hematovascular Biology Center, University of Virginia, School of Medicine, Charlottesville, VA, 22908 USA
| | - Kenneth Walsh
- Berne Cardiovascular Research Center USA; Department of Cardiology USA; Hematovascular Biology Center, University of Virginia, School of Medicine, Charlottesville, VA, 22908 USA.
| |
Collapse
|
|
14
|
Ren L, Guan H, Dai G, Gao W, Su J. Efficacy and safety of Shenfuqiangxin pills in complementary treatment of chronic heart failure: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2021; 100:e24531. [PMID: 33847608 PMCID: PMC8052016 DOI: 10.1097/md.0000000000024531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 01/08/2021] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND As the last link in the chain of cardiovascular events, chronic heart failure (CHF) has high morbidity, high mortality, and poor prognosis. It is one of the main causes of death and disability worldwide. Shenfuqiangxin Pills (SFQX) is widely used as a Chinese herbal medicine (CHM) prescription for CHF, but there is still a lack of strict evidence-based medical evidence. Therefore, we make a protocol for evaluating the efficacy and safety of SFQX for CHF. METHODS According to the search strategy, randomized controlled trials (RCTs) of SFQX for CHF will be retrieved from 8 databases without limitation of publication date or language. First of all, the literature was screened according to the eligibility criteria, and use the Cochrane Collaboration's tool to assess the quality of the included literature. Then, using software for traditional meta-analysis. Finally, using GRADE method to assess the strength of recommendations. RESULTS This study will evaluate the efficacy and safety of SFQX for CHF, thereby providing more evidence support for clinical decision-making in CHF. CONCLUSION Our research will provide more references for the clinical medication of patients with CHF. PROTOCOL REGISTRATION NUMBER INPLASY202110019.
Collapse
Affiliation(s)
- Lili Ren
- First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine
| | - Hui Guan
- First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine
| | - Guohua Dai
- Department of Cardiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
| | - Wulin Gao
- Department of Cardiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
| | - Jing Su
- Department of Cardiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
| |
Collapse
|
|
15
|
McKechnie DG, Papacosta AO, Lennon LT, Welsh P, Whincup PH, Wannamethee SG. Inflammatory markers and incident heart failure in older men: the role of NT-proBNP. Biomark Med 2021; 15:413-425. [PMID: 33709785 PMCID: PMC8559131 DOI: 10.2217/bmm-2020-0669] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Aim: To determine the relationship between baseline inflammation (CRP and IL-6) with natriuretic peptide (NP) activity (measured by NT-proBNP) and incident heart failure (HF) in older men. Methods & results: In the British Regional Heart Study, 3569 men without prevalent myocardial infarction or HF were followed for mean 16.3 years; 327 developed HF. Baseline CRP and IL-6 were significantly and positively associated with NT-proBNP. Those in the highest CRP and IL-6 quartiles had an elevated risk of HF after age and BMI adjustment (HR = 1.42 [1.01–1.98] and 1.71 [1.24–2.37], respectively), which markedly attenuated after NT-proBNP adjustment (HR = 1.15 [0.81–1.63] and 1.25 [0.89–1.75], respectively). Conclusion: NP activity is associated with pro-inflammatory biomarkers and may explain the link between inflammation and incident HF. Inflammation describes the body’s natural response to infections, injuries and toxins. Inflammation is a helpful response in the short term, but it is thought that long-lasting inflammation – for example, due to illnesses such as diabetes or obesity – may have harmful effects. Previous studies have found that people with higher levels of inflammatory molecules in the blood seem to be more likely to develop heart failure (HF) later on. The amount of fluid in the body is controlled, in part, by molecules in the blood known as ‘natriuretic peptides' (NPs). People with HF have much higher levels of NPs in their blood, and these are used to help diagnose HF. There are suggestions that inflammation and natriuretic peptides are linked to one another. Using a sample of men aged 60–79 years, who did not have HF, we compared blood markers of inflammation and NPs at a baseline examination. Men with higher blood inflammatory markers tended to have higher blood NP levels. We then followed these men up for an average of 16.3 years. Men with higher blood inflammatory markers at baseline were more likely to develop HF, as expected, even after accounting for differences in age and BMI. However, when we accounted for NP levels at baseline, the increased risk of HF with inflammation disappeared. This suggests that NP activity is important in the relationship between inflammation and the risk of HF. Future studies should account for this when examining the link. It is possible that NPs or, more likely, whatever is driving their release, may explain why people with inflammation are more likely to get HF.
Collapse
Affiliation(s)
- Douglas Gj McKechnie
- Department of Primary Care & Population Health, University College London, London, UK
| | - A Olia Papacosta
- Department of Primary Care & Population Health, University College London, London, UK
| | - Lucy T Lennon
- Department of Primary Care & Population Health, University College London, London, UK
| | - Paul Welsh
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK
| | - Peter H Whincup
- Population Health Research Institute, St George's University of London, London, UK
| | - S Goya Wannamethee
- Department of Primary Care & Population Health, University College London, London, UK
| |
Collapse
|
|
16
|
Mirolyubova OA, Kudryavtsev AV, Semchyugova EO, Malyutina SK, Ryabikov AN. [C-reactive protein and its associations with сardiometabolic risk factors and echocardiographic indicators of heart failure: results of "Know your heart" study in Arkhangelsk]. ACTA ACUST UNITED AC 2020; 60:68-75. [PMID: 33131477 DOI: 10.18087/cardio.2020.9.n975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Revised: 01/28/2020] [Accepted: 02/12/2020] [Indexed: 11/18/2022]
Abstract
Aim To evaluate the relationship between high-sensitivity C-reactive protein (hsCRP) and echocardiographic (EchoCG) indicators of heart failure (HF) among adult population of the North region of Russia.Material and methods The Know Your Heart transversal study was performed in 2015-2017 on a random sample of adult population of Arkhangelsk aged 35-69 years (n=2381). The exclusion criterion for this study was a concentration of hsCRP >10 mg/l. The group of subclinical inflammation included 686 participants with hsCRP ≥2.0 mg/l; the comparison group consisted of 1158 participants with hsCRP <2.0 mg/l. Analysis included cardiometabolic risk factors, EchoCG indexes of left ventricular (LV) systolic and diastolic function and biomarkers (NT-proBNP, hsTroponin Т, cystatin С). Linear and logistic regressions were used.Results The group with hsCRP ≥2.0 mg/l had higher rates of arterial hypertension, diabetes mellitus, HF, and myocardial infarction in history than the comparison group. The hsCRP level was independently associated with waist circumference (β=0.379, p <0.001), male gender (β=-0.135, p<0.001), smoking (β=0.109, p<0.001), triglycerides (β=0.083, p<0.001), diastolic blood pressure (β=0.082, p<0.001), cystatin C (β=0.082, p<0.001), glycated hemoglobin (β=0.064, p=0.003), and low-density lipoproteins (LDL) (β=0.049, p=0.025). Independent predictors of subclinical inflammation included older age, smoking, abdominal obesity, elevated values of LDL (>3.0 mmol/l), triglycerides (>1.7 mmol/l), and cystatin C (>1.2 mg/l). hsCRP was independently negatively associated with LV ejection fraction, left atrial volume index, ratio of early to late LV diastolic filling velocity (p=0.003, p=0.002, p=0.005, respectively), which reflected the relationship of the increased content of hsCRP with impairment of LV systolic and diastolic function. A relationship between heart remodeling indexes and hsCRP concentration was shown.Conclusion In a sample of adult population from the North region of Russia, the hsCRP concentration was independently associated with cardiometabolic risk factors and structural and functional changes in the heart detected by EchoCG, which reflects a potential contribution of inflammation to heart remodeling and development of HF.
Collapse
Affiliation(s)
| | | | | | - S K Malyutina
- Research Institute of Internal and Preventive Medicine, Branch of Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
| | - A N Ryabikov
- Novosibirsk State Medical University, Novosibirsk, Russia
| |
Collapse
|
|
17
|
Sex-Specific Epidemiology of Heart Failure Risk and Mortality in Europe: Results From the BiomarCaRE Consortium. JACC-HEART FAILURE 2020; 7:204-213. [PMID: 30819375 DOI: 10.1016/j.jchf.2018.08.008] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 08/13/2018] [Accepted: 08/28/2018] [Indexed: 11/21/2022]
Abstract
OBJECTIVES This study investigates differences between women and men in heart failure (HF) risk and mortality. BACKGROUND Sex differences in HF epidemiology are insufficiently understood. METHODS In 78,657 individuals (median 49.5 years of age; age range 24.1 to 98.7 years; 51.7% women) from community-based European studies (FINRISK, DanMONICA, Moli-sani, Northern Sweden) of the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium, the association between incident HF and mortality, the relationship of cardiovascular risk factors, prevalent cardiovascular diseases, biomarkers (C-reactive protein [CRP]; N-terminal pro-B-type natriuretic peptide [NT-proBNP]) with incident HF, and their attributable risks were tested in women vs. men. RESULTS Over a median follow-up of 12.7 years, fewer HF cases were observed in women (n = 2,399 [5.9%]) than in men (n = 2,771 [7.3%]). HF incidence increased markedly after 60 years of age, initially with a more rapid increase in men, whereas incidence in women exceeded that of men after 85 years of age. HF onset substantially increased mortality risk in both sexes. Multivariable-adjusted Cox models showed the following sex differences for the association with incident HF: systolic blood pressure hazard ratio (HR) according to SD in women of 1.09 (95% confidence interval [CI]: 1.05 to 1.14) versus HR of 1.19 (95% CI: 1.14 to 1.24) in men; heart rate HR of 0.98 (95% CI: 0.93 to 1.03) in women versus HR of 1.09 (95% CI: 1.04 to 1.13) in men; CRP HR of 1.10 (95% CI: 1.00 to 1.20) in women versus HR of 1.32 (95% CI: 1.24 to 1.41) in men; and NT-proBNP HR of 1.54 (95% CI: 1.37 to 1.74) in women versus HR of 1.89 (95% CI: 1.75 to 2.05) in men. Population-attributable risk of all risk factors combined was 59.0% in women and 62.9% in men. CONCLUSIONS Women had a lower risk for HF than men. Sex differences were seen for systolic blood pressure, heart rate, CRP, and NT-proBNP, with a lower HF risk in women.
Collapse
|
|
18
|
Yousefi F, Movahedpour A, Shabaninejad Z, Ghasemi Y, Rabbani S, Sobnani-Nasab A, Mohammadi S, Hajimoradi B, Rezaei S, Savardashtaki A, Mazoochi M, Mirzaei H. Electrochemical-Based Biosensors: New Diagnosis Platforms for Cardiovascular Disease. Curr Med Chem 2020; 27:2550-2575. [DOI: 10.2174/0929867326666191024114207] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Revised: 09/05/2019] [Accepted: 09/12/2019] [Indexed: 02/05/2023]
Abstract
One of the major reasons for mortality throughout the world is cardiovascular diseases.
Therefore, bio-markers of cardiovascular disease are of high importance to diagnose and manage procedure.
Detecting biomarkers provided a promising procedure in developing bio-sensors. Fast, selective,
portable, accurate, inexpensive, and sensitive biomarker sensing instruments will be necessary for
detecting and predicting diseases. One of the cardiac biomarkers may be ordered as C-reactive proteins,
lipoprotein-linked phospho-lipase, troponin I or T, myoglobin, interleukin-6, interleukin-1, tumor necrosis
factor alpha, LDL and myeloperoxidase. The biomarkers are applied to anticipate cardio-vascular
illnesses. Initial diagnoses of these diseases are possible by several techniques; however, they are laborious
and need costly apparatus. Current researches designed various bio-sensors for resolving the respective
issues. Electrochemical instruments and the proposed bio-sensors are preferred over other
methods due to its inexpensiveness, mobility, reliability, repeatability. The present review comprehensively
dealt with detecting biomarkers of cardiovascular disease through electro-chemical techniques.
Collapse
Affiliation(s)
- Fatemeh Yousefi
- Department of Biological Sciences, Faculty of Genetics, Tarbiat Modares University, Tehran, Iran
| | - Ahmad Movahedpour
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Shabaninejad
- Department of Biological Sciences, Faculty of Nanotechnology, Tarbiat Modares University, Tehran, Iran
| | - Younes Ghasemi
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Shahram Rabbani
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Sobnani-Nasab
- Social Determinants of Health (SDH) Research Center, Kashan University of Medical Sciences, Kashan, Iran
| | - Soheila Mohammadi
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Behzad Hajimoradi
- Cardiology Department of Shohaday-e-Tajrish Hospital Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Samaneh Rezaei
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Savardashtaki
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Majid Mazoochi
- Department of Cardiology, Cardiac Electrophysiology Center, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| |
Collapse
|
|
19
|
Schrage B, Geelhoed B, Niiranen TJ, Gianfagna F, Vishram‐Nielsen JKK, Costanzo S, Söderberg S, Ojeda FM, Vartiainen E, Donati MB, Magnussen C, Di Castelnuovo A, Camen S, Kontto J, Koenig W, Blankenberg S, de Gaetano G, Linneberg A, Jørgensen T, Zeller T, Kuulasmaa K, Tunstall‐Pedoe H, Hughes M, Iacoviello L, Salomaa V, Schnabel RB. Comparison of Cardiovascular Risk Factors in European Population Cohorts for Predicting Atrial Fibrillation and Heart Failure, Their Subsequent Onset, and Death. J Am Heart Assoc 2020; 9:e015218. [PMID: 32351154 PMCID: PMC7428582 DOI: 10.1161/jaha.119.015218] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Background Differences in risk factors for atrial fibrillation (AF) and heart failure (HF) are incompletely understood. Aim of this study was to understand whether risk factors and biomarkers show different associations with incident AF and HF and to investigate predictors of subsequent onset and mortality. Methods and Results In N=58 693 individuals free of AF/HF from 5 population‐based European cohorts, Cox regressions were used to find predictors for AF, HF, subsequent onset, and mortality. Differences between associations were estimated using bootstrapping. Median follow‐up time was 13.8 years, with a mortality of 15.7%. AF and HF occurred in 5.0% and 5.4% of the participants, respectively, with 1.8% showing subsequent onset. Age, male sex, myocardial infarction, body mass index, and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) showed similar associations with both diseases. Antihypertensive medication and smoking were stronger predictors of HF than AF. Cholesterol, diabetes mellitus, and hsCRP (high‐sensitivity C‐reactive protein) were associated with HF, but not with AF. No variable was exclusively associated with AF. Population‐attributable risks were higher for HF (75.6%) than for AF (30.9%). Age, male sex, body mass index, diabetes mellitus, and NT‐proBNP were associated with subsequent onset, which was associated with the highest all‐cause mortality risk. Conclusions Common risk factors and biomarkers showed different associations with AF and HF, and explained a higher proportion of HF than AF risk. As the subsequent onset of both diseases was strongly associated with mortality, prevention needs to be rigorously addressed and remains challenging, as conventional risk factors explained only 31% of AF risk.
Collapse
Affiliation(s)
- Benedikt Schrage
- Department of CardiologyUniversity Heart and Vascular Center HamburgHamburgGermany
- DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/LuebeckGermany
| | - Bastiaan Geelhoed
- Department of CardiologyUniversity Heart and Vascular Center HamburgHamburgGermany
| | - Teemu J. Niiranen
- Division of MedicineTurku University Hospital and University of TurkuTurkuFinland
- National Institute for Health and WelfareHelsinkiFinland
| | - Francesco Gianfagna
- Research Center in Epidemiology and Preventive MedicineDepartment of Medicine and SurgeryUniversity of InsubriaVareseItaly
- Mediterranea CardiocentroNapoliItaly
| | - Julie K. K. Vishram‐Nielsen
- Center for Cardiac, Vascular, Pulmonary and Infectious DiseasesRigshospitaletUniversity Hospital of CopenhagenDenmark
- Center for Clinical Research and PreventionBispebjerg and Frederiksberg HospitalThe Capital Region of DenmarkCopenhagenDenmark
| | - Simona Costanzo
- Department of Epidemiology and PreventionIRCCS NeuromedPozzilli (IS)Italy
| | - Stefan Söderberg
- Department of Public Health and Clinical Medicine, and Heart CentreUmeå UniversityUmeåSweden
| | - Francisco M. Ojeda
- Department of CardiologyUniversity Heart and Vascular Center HamburgHamburgGermany
| | | | | | - Christina Magnussen
- Department of CardiologyUniversity Heart and Vascular Center HamburgHamburgGermany
- DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/LuebeckGermany
| | | | - Stephan Camen
- Department of CardiologyUniversity Heart and Vascular Center HamburgHamburgGermany
- DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/LuebeckGermany
| | - Jukka Kontto
- National Institute for Health and WelfareHelsinkiFinland
| | - Wolfgang Koenig
- Deutsches Herzzentrum MünchenTechnische Universität MünchenGermany
- DZHK (German Centre for Cardiovascular Research), partner site Munich Heart AllianceMunichGermany
- Institute of Epidemiology and Medical BiometryUniversity of UlmGermany
| | - Stefan Blankenberg
- Department of CardiologyUniversity Heart and Vascular Center HamburgHamburgGermany
- DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/LuebeckGermany
| | | | - Allan Linneberg
- Department of Clinical MedicineFaculty of Health and Medical SciencesUniversity of CopenhagenDenmark
- Center for Clinical Research and PreventionBispebjerg and Frederiksberg HospitalThe Capital Region of DenmarkCopenhagenDenmark
| | - Torben Jørgensen
- Center for Clinical Research and PreventionBispebjerg and Frederiksberg HospitalThe Capital Region of DenmarkCopenhagenDenmark
| | - Tanja Zeller
- Department of CardiologyUniversity Heart and Vascular Center HamburgHamburgGermany
- DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/LuebeckGermany
| | - Kari Kuulasmaa
- National Institute for Health and WelfareHelsinkiFinland
| | - Hugh Tunstall‐Pedoe
- Cardiovascular Epidemiology UnitInstitute of Cardiovascular ResearchUniversity of DundeeUnited Kingdom
| | - Maria Hughes
- Centre of Excellence for Public HealthQueen′s University Belfast,BelfastNorthern Ireland
| | - Licia Iacoviello
- Research Center in Epidemiology and Preventive MedicineDepartment of Medicine and SurgeryUniversity of InsubriaVareseItaly
- Department of Epidemiology and PreventionIRCCS NeuromedPozzilli (IS)Italy
| | - Veikko Salomaa
- National Institute for Health and WelfareHelsinkiFinland
| | - Renate B. Schnabel
- Department of CardiologyUniversity Heart and Vascular Center HamburgHamburgGermany
- DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/LuebeckGermany
| |
Collapse
|
|
20
|
Lara KM, Levitan EB, Gutierrez OM, Shikany JM, Safford MM, Judd SE, Rosenson RS. Dietary Patterns and Incident Heart Failure in U.S. Adults Without Known Coronary Disease. J Am Coll Cardiol 2020; 73:2036-2045. [PMID: 31023426 PMCID: PMC6501554 DOI: 10.1016/j.jacc.2019.01.067] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 12/20/2018] [Accepted: 01/22/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Dietary patterns and associations with incident heart failure (HF) are not well established in the United States. OBJECTIVES The purpose of this study was to determine associations of 5 dietary patterns with incident HF hospitalizations among U.S. adults. METHODS The REGARDS (REasons for Geographic and Racial Differences in Stroke) trial is a prospective cohort of black and white adults followed from 2003 to 2007 through 2014. Inclusion criteria included completion of a food frequency questionnaire and no baseline coronary heart disease or HF. Five dietary patterns (convenience, plant-based, sweets, Southern, and alcohol/salads) were derived from principal component analysis. The primary endpoint was incident HF hospitalization. RESULTS This study included 16,068 participants (mean age 64.0 ± 9.1 years, 58.7% women, 33.6% black participants, 34.0% residents of the stroke belt). After a median of 8.7 years of follow-up, 363 participants had incident HF hospitalizations. Compared with the lowest quartile, the highest quartile of adherence to the plant-based dietary pattern was associated with a 41% lower risk of HF in multivariable-adjusted models (hazard ratio: 0.59; 95% confidence interval: 0.41 to 0.86; p = 0.004). Highest adherence to the Southern dietary pattern was associated with a 72% higher risk of HF after adjusting for age, sex, and race and for other potential confounders (education, income, region of residence, total energy intake, smoking, physical activity, and sodium intake; hazard ratio: 1.72; 95% confidence interval: 1.20 to 2.46; p = 0.005). However, the association was attenuated and no longer statistically significant after further adjusting for body mass index in kg/m2, waist circumference, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation, and chronic kidney disease. No statistically significant associations were observed with incident HF with reduced or preserved ejection fraction hospitalizations and the dietary patterns. No associations were observed with the other 3 dietary patterns. CONCLUSIONS Adherence to a plant-based dietary pattern was inversely associated with incident HF risk, whereas the Southern dietary pattern was positively associated with incident HF risk.
Collapse
Affiliation(s)
- Kyla M Lara
- Icahn School of Medicine at Mount Sinai, New York, New York.
| | - Emily B Levitan
- Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Orlando M Gutierrez
- Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - James M Shikany
- Division of Preventive Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Monika M Safford
- Division of General Internal Medicine, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Suzanne E Judd
- Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama
| | - Robert S Rosenson
- Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, New York
| |
Collapse
|
|
21
|
Kerkütlüoglu M, Yucel O, Günes H, Yılmaz M. C-reactive protein/albumin ratio designates advanced heart failure among outpatients with heart failure. INTERNATIONAL JOURNAL OF THE CARDIOVASCULAR ACADEMY 2020. [DOI: 10.4103/ijca.ijca_49_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
|
|
22
|
Everett BM, Cornel JH, Lainscak M, Anker SD, Abbate A, Thuren T, Libby P, Glynn RJ, Ridker PM. Anti-Inflammatory Therapy With Canakinumab for the Prevention of Hospitalization for Heart Failure. Circulation 2019; 139:1289-1299. [PMID: 30586730 DOI: 10.1161/circulationaha.118.038010] [Citation(s) in RCA: 435] [Impact Index Per Article: 72.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Subclinical inflammation is associated with an increased risk of heart failure and with adverse prognosis in patients with established heart failure. Yet, treatments specifically directed at reducing inflammation in patients with heart failure have not yet shown improved clinical outcomes. We tested the hypothesis that the interleukin-1β inhibitor canakinumab would prevent hospitalization for heart failure (HHF) and the composite of HHF or heart failure-related mortality. METHODS We randomized 10 061 patients with prior myocardial infarction and high-sensitivity C-reactive protein ≥2 mg/L to canakinumab 50, 150, or 300 mg or placebo, given subcutaneously once every 3 months. In total, 2173 (22%) reported a history of heart failure at baseline. We tested the hypothesis that canakinumab prevents prospectively collected HHF events and the composite of HHF or heart failure-related mortality. RESULTS A total of 385 patients had an HHF event during a median follow-up of 3.7 years. Patients who had HHF were older, had higher body mass index, and were more likely to have diabetes mellitus, hypertension, and prior coronary bypass surgery. As anticipated, median (quartile 1, 3) baseline concentrations of high-sensitivity C-reactive protein were higher among those who had HHF during follow-up than those who did not (5.7 [3.5, 9.9] mg/L versus 4.2 [2.8, 6.9] mg/L, respectively; P<0.0001). The unadjusted hazard ratios for HHF with each dose of canakinumab compared with placebo were 1.04 (95% CI, 0.79-1.36) for 50 mg, 0.86 (95% CI, 0.65-1.13) for 150 mg, and 0.76 (95% CI, 0.57-1.01) for 300 mg ( P for trend=0.025). The composite of HHF or heart failure-related mortality was also reduced by canakinumab, with unadjusted hazard ratios of 1.00 (95% CI, 0.78-1.29) for 50 mg, 0.88 (95% CI, 0.68-1.13) for 150 mg, and 0.78 (95% CI, 0.60-1.02) for 300 mg ( P for trend=0.042). CONCLUSIONS These randomized double-blind placebo-controlled data suggest that therapy with canakinumab, an interleukin-1β inhibitor, is related to a dose-dependent reduction in HHF and the composite of HHF or heart failure-related mortality in a population of patients with prior myocardial infarction and elevations in high-sensitivity C-reactive protein. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov . Unique identifier: NCT01327846.
Collapse
Affiliation(s)
- Brendan M Everett
- From the Divisions of Cardiovascular (B.M.E., P.L., P.M.R.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA
- Preventive Medicine (B.M.E., R.J.G., P.M.R.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Jan H Cornel
- Department of Cardiology, Noordwest Ziekenhuisgroep, Alkmaar, the Netherlands (J.H.C.)
| | - Mitja Lainscak
- Division of Cardiology, General Hospital Murska Sobota, and Faculty of Medicine, University of Ljubljana, Slovenia (M.L.)
| | - Stefan D Anker
- Department of Cardiology and Berlin-Brandenburg Center for Regenerative Therapies, German Centre for Cardiovascular Research, partner site Berlin, Charité Universitätsmedizin Berlin, Germany (S.D.A.)
| | - Antonio Abbate
- Pauley Heart Center, Virginia Commonwealth University, Richmond (A.A.)
| | - Tom Thuren
- Novartis, East Hanover, NJ, and Basel, Switzerland (T.T.)
| | - Peter Libby
- From the Divisions of Cardiovascular (B.M.E., P.L., P.M.R.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Robert J Glynn
- Preventive Medicine (B.M.E., R.J.G., P.M.R.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Paul M Ridker
- From the Divisions of Cardiovascular (B.M.E., P.L., P.M.R.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA
- Preventive Medicine (B.M.E., R.J.G., P.M.R.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| |
Collapse
|
|
23
|
Everett BM, Siddiqi HK. Heart Failure, the Inflammasome, and Interleukin-1β: Prognostic and Therapeutic? J Am Coll Cardiol 2019; 73:1026-1028. [PMID: 30846096 DOI: 10.1016/j.jacc.2019.01.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 01/07/2019] [Indexed: 11/17/2022]
Affiliation(s)
- Brendan M Everett
- Divisions of Cardiovascular and Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
| | - Hasan K Siddiqi
- Divisions of Cardiovascular and Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| |
Collapse
|
|
24
|
Avan A, Tavakoly Sany SB, Ghayour‐Mobarhan M, Rahimi HR, Tajfard M, Ferns G. Serum C‐reactive protein in the prediction of cardiovascular diseases: Overview of the latest clinical studies and public health practice. J Cell Physiol 2018; 233:8508-8525. [DOI: 10.1002/jcp.26791] [Citation(s) in RCA: 83] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2018] [Accepted: 04/30/2018] [Indexed: 12/14/2022]
Affiliation(s)
- Amir Avan
- Department of Modern Sciences and Technologies School of Medicine, Mashhad University of Medical Sciences Mashhad Iran
| | - Seyedeh Belin Tavakoly Sany
- Social Determinants of Health Research Center Mashhad University of Medical Sciences Mashhad Iran
- Department of Health Education and Health Promotion Faculty of Health, Mashhad University of Medical Sciences Mashhad Iran
| | - Majid Ghayour‐Mobarhan
- Department of Modern Sciences and Technologies School of Medicine, Mashhad University of Medical Sciences Mashhad Iran
| | - Hamid Reza Rahimi
- Department of Modern Sciences and Technologies School of Medicine, Mashhad University of Medical Sciences Mashhad Iran
| | - Mohammad Tajfard
- Social Determinants of Health Research Center Mashhad University of Medical Sciences Mashhad Iran
- Department of Health Education and Health Promotion Faculty of Health, Mashhad University of Medical Sciences Mashhad Iran
| | - Gordon Ferns
- Medical Education and Metabolic Medicine Head, Department of Medical Education, Brighton and Sussex Medical School University of Brighton Falmer Campus, Brighton UK
| |
Collapse
|
|
25
|
Imbalzano E, Mandraffino G, Casciaro M, Quartuccio S, Saitta A, Gangemi S. Pathophysiological mechanism and therapeutic role of S100 proteins in cardiac failure: a systematic review. Heart Fail Rev 2018; 21:463-73. [PMID: 26833319 DOI: 10.1007/s10741-016-9529-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
S100 proteins are a family of highly acidic calcium-binding proteins involved in calcium handling in many tissues and organs. Some of these proteins are highly expressed in cardiac tissue, and an impairment of some specific S100 proteins has been related to heart failure. To check this hypothesis, we decided to review the literature since 2008 until May 2015. According to the studies collected, recovering S100A1 levels may enhance contractile/relaxing performance in heart failure, reverse negative force-frequency relationship, improve contractile reserve, reverse diastolic dysfunction and protect against pro-arrhythmic reductions of sarcoplasmic reticulum calcium. The safety profile of gene therapy was also confirmed. Increased S100B protein levels were related to a worse outcome in chronic heart failure. S100A8/A9 complex plasma levels, as well as other inflammatory biomarkers, were significantly higher in chronic heart failure patients. S100A2 seems to increase both contractile and relaxation performance in animal cardiomyocytes. Otherwise, S100A6 cardiac expression seems to have no effects on contractility. S100A4 KO mice showed reduced cardiac interstitial fibrosis. Data collected encourage a potential prospective application in human. These proteins could be exploited as biomarkers in stadiation and prognosis of chronic heart failure, as well as therapeutic target to rescue failing heart. Registration details The study protocol has been registered in PROSPERO ( http://www.crd.york.ac.uk/PROSPERO/ ) under registration number CRD42015027932.
Collapse
Affiliation(s)
- Egidio Imbalzano
- Department of Clinical and Experimental Medicine, Policlinic University of Messina, Via Consolare Valeria n.1, 98125, Messina, Italy.
| | - Giuseppe Mandraffino
- Department of Clinical and Experimental Medicine, Policlinic University of Messina, Via Consolare Valeria n.1, 98125, Messina, Italy
| | - Marco Casciaro
- School and Division of Allergy and Clinical Immunology, University of Messina, Messina, Italy
| | - Sebastiano Quartuccio
- Department of Clinical and Experimental Medicine, Policlinic University of Messina, Via Consolare Valeria n.1, 98125, Messina, Italy
| | - Antonino Saitta
- Department of Clinical and Experimental Medicine, Policlinic University of Messina, Via Consolare Valeria n.1, 98125, Messina, Italy
| | - Sebastiano Gangemi
- School and Division of Allergy and Clinical Immunology, University of Messina, Messina, Italy.,Institute of Applied Sciences and Intelligent Systems (ISASI) - Messina Unit, Messina, Italy
| |
Collapse
|
|
26
|
Suthahar N, Meijers WC, Brouwers FP, Heerspink HJL, Gansevoort RT, van der Harst P, Bakker SJL, de Boer RA. Heart failure and inflammation-related biomarkers as predictors of new-onset diabetes in the general population. Int J Cardiol 2017; 250:188-194. [PMID: 29074040 DOI: 10.1016/j.ijcard.2017.10.035] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Revised: 09/15/2017] [Accepted: 10/09/2017] [Indexed: 01/17/2023]
Abstract
BACKGROUND There is a strong reciprocal relationship between heart failure (HF) and diabetes mellitus (DM). Shared pathophysiological mechanisms might be a possible explanation. Therefore, we hypothesised that biomarkers linked to HF would also predict new-onset type 2 DM in the general population. METHODS AND RESULTS We utilized the Prevention of Vascular and Renal End-stage Disease (PREVEND) cohort (mean age 48.9years, 51% female) to study the relationship between HF and DM in 7953 participants free of baseline HF and DM. Multiple HF-related, inflammation-related and renal function-related biomarkers were evaluated regarding their predictive utility in new-onset DM. Incidence of DM in participants who developed HF was 11.8%, versus 5.4% in those who had not developed HF (p<0.001). Incidence of HF in participants who developed DM was 8.5%, versus 3.8% in those who had not developed DM (p<0.001). Classical HF biomarkers, NT-proBNP and hs-TnT were not associated with an increased risk for new-onset DM. However, inflammatory biomarkers hs-CRP [hazard ratio (HR) 1.16, (95% CI 1.05 to 1.29), p=0.005], procalcitonin [HR 1.34, (95% CI 1.07 to 1.69), p=0.012] and PAI-1 [HR 1.55, (95% CI 1.37 to 1.75), p<0.001] remained significantly associated with new-onset DM, even after multivariable adjustment for established predictors of DM. CONCLUSIONS Although HF and DM have a strong correlation with each other, systemic biomarkers that predict HF do not have a predictive value in new-onset DM. This suggests that other, indirect, pathophysiological mechanisms related to inflammation may explain their strong relation.
Collapse
Affiliation(s)
- Navin Suthahar
- Department of Cardiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
| | - Wouter C Meijers
- Department of Cardiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
| | - Frank P Brouwers
- Department of Cardiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
| | - Hiddo J L Heerspink
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
| | - Ron T Gansevoort
- Department of Nephrology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
| | - Pim van der Harst
- Department of Cardiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
| | - Stephan J L Bakker
- Department of Nephrology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
| | - Rudolf A de Boer
- Department of Cardiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
| |
Collapse
|
|
27
|
Kupsky DF, Ahmed AM, Sakr S, Qureshi WT, Brawner CA, Blaha MJ, Ehrman JK, Keteyian SJ, Al-Mallah MH. Cardiorespiratory fitness and incident heart failure: The Henry Ford ExercIse Testing (FIT) Project. Am Heart J 2017; 185:35-42. [PMID: 28267473 DOI: 10.1016/j.ahj.2016.12.006] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Accepted: 12/01/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Prior studies have demonstrated cardiorespiratory fitness (CRF) to be a strong marker of cardiovascular health. However, there are limited data investigating the association between CRF and risk of progression to heart failure (HF). The purpose of this study was to determine the relationship between CRF and incident HF. METHODS We included 66,329 patients (53.8% men, mean age 55 years) free of HF who underwent exercise treadmill stress testing at Henry Ford Health Systems between 1991 and 2009. Incident HF was determined using International Classification of Diseases, Ninth Revision codes from electronic medical records or administrative claim files. Cox proportional hazards models were performed to determine the association between CRF and incident HF. RESULTS A total of 4,652 patients developed HF after a median follow-up duration of 6.8 (±3) years. Patients with incident HF were older (63 vs 54 years, P<.001) and had higher prevalence of known coronary artery disease (42.3% vs 11%, P<.001). Peak metabolic equivalents (METs) of task were 6.3 (±2.9) and 9.1 (±3) in the HF and non-HF groups, respectively. After adjustment for potential confounders, patients able to achieve ≥12 METs had an 81% lower risk of incident HF compared with those achieving <6 METs (hazard ratio 0.19 [95% CI 0.14-0.29], P for trend < .001). Each 1 MET achieved was associated with a 16% lower risk (hazard ratio 0.84 [95% CI 0.82-0.86], P<.001) of incident HF. CONCLUSIONS Our analysis demonstrates that higher level of fitness is associated with a lower incidence of HF independent of HF risk factors.
Collapse
Affiliation(s)
- Daniel F Kupsky
- Heart and Vascular Institute, Henry Ford Hospital System, Detroit, MI
| | - Amjad M Ahmed
- King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King AbdulAziz Cardiac Center, Ministry of National Guard, Health Affairs, Riyadh, Kingdom of Saudi Arabia
| | - Sherif Sakr
- King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King AbdulAziz Cardiac Center, Ministry of National Guard, Health Affairs, Riyadh, Kingdom of Saudi Arabia
| | | | - Clinton A Brawner
- Heart and Vascular Institute, Henry Ford Hospital System, Detroit, MI
| | - Michael J Blaha
- Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD
| | - Jonathan K Ehrman
- Heart and Vascular Institute, Henry Ford Hospital System, Detroit, MI
| | - Steven J Keteyian
- Heart and Vascular Institute, Henry Ford Hospital System, Detroit, MI
| | - Mouaz H Al-Mallah
- Heart and Vascular Institute, Henry Ford Hospital System, Detroit, MI; King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King AbdulAziz Cardiac Center, Ministry of National Guard, Health Affairs, Riyadh, Kingdom of Saudi Arabia.
| |
Collapse
|
|
28
|
Zhu L, Zou Y, Wang Y, Luo X, Sun K, Wang H, Jia L, Liu Y, Zou J, Yuan Z, Hui R, Kang L, Song L, Wang J. Prognostic Significance of Plasma High-Sensitivity C-Reactive Protein in Patients With Hypertrophic Cardiomyopathy. J Am Heart Assoc 2017; 6:JAHA.116.004529. [PMID: 28154166 PMCID: PMC5523755 DOI: 10.1161/jaha.116.004529] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Background Elevated high‐sensitivity C‐reactive protein (hsCRP) has been associated with increased risks of adverse outcomes of various cardiovascular diseases. The relationship between hsCRP and the prognosis of hypertrophic cardiomyopathy remains to be evaluated. Methods and Results The study used an observational cohort methodology. A total of 490 patients were enrolled in the Fuwai Hospital from 2001 to 2011 and were followed for 3.7±2.0 years. According to the risk category of hsCRP, subjects in the high hsCRP group (>3.0 mg/L) had a higher risk of developing adverse events than the low hsCRP group (<1.0 mg/L): cardiovascular death (adjusted hazard ratios[HR] 5.41, 95% CI 1.96–14.93, P=0.001), all‐cause mortality (adjusted HR 4.78, 95% CI 1.99–11.47, P<0.001), sudden cardiac death (adjusted HR 11.29, 95% CI 1.38–92.20, P=0.024), and heart failure–related death (adjusted HR 4.38, 95% CI 1.15–16.60, P=0.030). Similarly, the continuous variable of hsCRP was also an independent predictor for adverse outcomes: cardiovascular death (adjusted HR 1.15, 95% CI 1.06–1.25, P=0.001), all‐cause mortality (adjusted HR 1.17, 95% CI 1.09–1.26, P<0.001), sudden cardiac death (adjusted HR 1.20, 95% CI 1.06–1.36, P=0.003), and heart failure–related death (adjusted HR 1.15, 95% CI 1.02–1.30, P=0.020). Conclusions Our results indicate that elevated plasma hsCRP is associated with increased risk for adverse outcomes in patients with hypertrophic cardiomyopathy.
Collapse
Affiliation(s)
- Ling Zhu
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China
| | - Yubao Zou
- Department of Cardiovascular Internal Medicine, Hypertension Center, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, Shaanxi, China
| | - Yilu Wang
- Department of ICU, China Meitan General Hospital, Beijing, China
| | - Xiaoliang Luo
- Department of Cardiovascular Internal Medicine, Hypertension Center, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, Shaanxi, China
| | - Kai Sun
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hu Wang
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lei Jia
- Department of Cardiovascular Internal Medicine, Hypertension Center, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, Shaanxi, China
| | - Yan Liu
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Juan Zou
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Zuyi Yuan
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Rutai Hui
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lianming Kang
- Department of Cardiovascular Internal Medicine, Hypertension Center, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, Shaanxi, China
| | - Lei Song
- Department of Cardiovascular Internal Medicine, Hypertension Center, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, Shaanxi, China
| | - Jizheng Wang
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
29
|
Mirza SS, de Bruijn RFAG, Koudstaal PJ, van den Meiracker AH, Franco OH, Hofman A, Tiemeier H, Ikram MA. The N-terminal pro B-type natriuretic peptide, and risk of dementia and cognitive decline: a 10-year follow-up study in the general population. J Neurol Neurosurg Psychiatry 2016; 87:356-62. [PMID: 25918047 DOI: 10.1136/jnnp-2014-309968] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Accepted: 03/18/2015] [Indexed: 12/31/2022]
Abstract
BACKGROUND The N-terminal pro B-type natriuretic peptide (NT-proBNP) has a well-documented prognostic value for cardiovascular disease (CVD) and higher levels are associated with cognitive-dysfunction in patients with CVD. However, how NT-proBNP relates to incident dementia and cognitive-decline in community-dwelling persons is unknown. METHODS Between 1997 and 2001, serum NT-proBNP was measured in 6040 participants (mean age 69 years, 57% women) free of heart-failure and dementia from the Rotterdam Study. Participants were continuously followed-up for incident dementia until 2012, for 56,616 person-years. Cognition was assessed at baseline and reassessed between 2002 and 2006 by Letter-Digit-Substitution-task, Stroop test and Word-Fluency test. Associations of NT-proBNP with dementia (555 cases), Alzheimer's disease (357 cases) and vascular dementia (32 cases) were assessed linearly, and in quartiles using Cox regression. Associations of NT-proBNP with cognitive-decline were assessed using multiple linear regression. All analyses were repeated after excluding patients with CVD. RESULTS Higher NT-proBNP was associated with a higher risk of dementia, even after excluding patients with CVD and adjusting for cardiovascular risk factors, HR per SD 1.27 (95% CI 1.13 to 1.44). Associations were particularly strong for vascular dementia, HR per SD 2.04 (95% CI 1.18 to 3.55), but also for Alzheimer's disease when comparing the second and third quartile with first. Higher NT-proBNP was cross-sectionally associated with poorer performance in multiple cognitive tests but longitudinally only in Letter-Digit-Substitution-task. CONCLUSIONS NT-proBNP reflecting subclinical CVD is associated with dementia, particularly vascular dementia. NT-proBNP can be a useful marker of imminent cognitive-decline and dementia in absence of clinical CVD.
Collapse
Affiliation(s)
- Saira Saeed Mirza
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Renée F A G de Bruijn
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Peter J Koudstaal
- Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
| | | | - Oscar H Franco
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Albert Hofman
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Henning Tiemeier
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands
| | - M Arfan Ikram
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands
| |
Collapse
|
|
30
|
Lewicka E, Dudzinska-Gehrmann J, Dabrowska-Kugacka A, Zagozdzon P, Lizewska A, Danilowicz-Szymanowicz L, Raczak G. Neopterin and interleukin-6 as predictors of recurrent atrial fibrillation. Anatol J Cardiol 2016; 16:563-571. [PMID: 27004701 PMCID: PMC5368511 DOI: 10.5152/anatoljcardiol.2015.6272] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
OBJECTIVE Available evidence suggests that inflammation may be associated with atrial fibrillation (AF). This prospective and observational study aimed to assess whether plasma neopterin (NPT) and interleukin-6 (IL-6) levels before and after electrical cardioversion (CV) predict AF recurrence. METHODS The study was designed as a prospective observational trial. Blood samples were collected (24 hours before, 24 h after CV, and 7 days after CV) in 60 patients with a dual-chamber pacemakar and preserved left ventricular systolic function who underwent successful CV of persistent AF. All significant parameters associated with AF recurrence lasting ≥30 min and detected by pacemaker data logs were evaluated in multivariate logistic regression analysis. Echocardiography was performed 7 days after CV in patients with sinus rhythm. The control group included 17 subjects without AF. RESULTS The analysis included 51 patients who remained in sinus rhythm 7 days after CV. During 12 months of follow-up, AF recurred in 46 patients. Baseline IL-6 levels did not differ between the two groups, but baseline NPT levels were higher in the study group than in the control group (19±7 vs. 11±5 nmol/mL, p<0.001). NPT levels of ≥14.6 nmol/L at baseline and ≥13.3 nmol/L 7 days after CV separated the patients with AF recurrence from those without arrhythmia after CV. Only left atrial emptying fraction <38% was an independent predictor of AF recurrence (p=0.03), whereas NPT levels of ≥13.3 nmol/L 7 days after CV showed borderline statistical significance (p=0.07). CONCLUSION Increased NPT level was observed in patients with persistent AF. Neither baseline IL-6 and NPT levels nor their changes within 7 days after CV were predictive of AF recurrence. Further studies are needed to establish the prognostic significance of NPT in patients with AF.
Collapse
Affiliation(s)
- Ewa Lewicka
- Department of Cardiology and Electrotherapy Medical University of Gdansk, Gdansk-Poland
| | | | | | - Pawel Zagozdzon
- Department of Hygiene and Epidemiology, Medical University of Gdansk, Gdansk-Poland
| | - Aleksandra Lizewska
- Department of Cardiology and Electrotherapy Medical University of Gdansk, Gdansk-Poland.
| | | | - Grzegorz Raczak
- Department of Cardiology and Electrotherapy Medical University of Gdansk, Gdansk-Poland
| |
Collapse
|
|
31
|
|
|
32
|
Silva N, Bettencourt P, Guimarães JT. The lymphocyte-to-monocyte ratio: an added value for death prediction in heart failure. Nutr Metab Cardiovasc Dis 2015; 25:1033-1040. [PMID: 26482565 DOI: 10.1016/j.numecd.2015.07.004] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2015] [Revised: 06/18/2015] [Accepted: 07/13/2015] [Indexed: 11/22/2022]
Abstract
BACKGROUND AND AIM Leukocytes and their subpopulation have been long implicated in the progression of the syndrome of heart failure (HF), especially heart infiltration cells. Previous reports have suggested that they can predict worse outcome in patients with HF, and can also affect the function of other cells and myocardial extracellular matrix remodeling process. However, the lymphocyte-to-monocyte ratio (LMR) and its possible value as prognostic marker have not been evaluated. METHODS AND RESULTS A total of 390 patients with acute HF were recruited and followed for 6 months. Their total blood count with leukocyte differential was obtained. Two groups were formed according to the endpoints of HF death and optimal cut-off value of LMR, and were compared. A multivariate Cox-regression model was used to establish the prognostic value with the endpoints of HF and all-cause mortality. Median age of the patients was 78 years and 48.5% of them were men. No major difference was observed between the clinical characteristics of the two groups. Patients who died of HF had significantly higher values of B-type natriuretic peptide and lower values of LMR. Leukocyte and monocyte counts revealed a multivariate-adjusted risk for both endpoints, whereas relative lymphocyte counts had only significant value for all-cause mortality. The multivariate-adjusted hazard ratios for the 6-month HF and all-cause mortality in patients with LMR values < 2.0 were, respectively, 2.28 (95% CI: 1.25-4.15) and 2.39 (95% CI: 1.39-4.10). CONCLUSION Our results show that, upon discharge from hospital after an episode of acute HF, a lower value of LMR is independently associated with a higher risk of mortality within 6 months.
Collapse
Affiliation(s)
- N Silva
- Unidade I&D Cardiovascular do Porto, Faculdade de Medicina da Universidade do Porto, 4202-451 Porto, Portugal; Departamento de Bioquímica, Faculdade de Medicina da Universidade do Porto, 4202-451 Porto, Portugal; Serviço de Patologia Clínica, Centro Hospitalar São João, 4202-451 Porto, Portugal.
| | - P Bettencourt
- Unidade I&D Cardiovascular do Porto, Faculdade de Medicina da Universidade do Porto, 4202-451 Porto, Portugal; Serviço de Medicina Interna, Centro Hospitalar São João, 4202-451 Porto, Portugal
| | - J T Guimarães
- Departamento de Bioquímica, Faculdade de Medicina da Universidade do Porto, 4202-451 Porto, Portugal; Serviço de Patologia Clínica, Centro Hospitalar São João, 4202-451 Porto, Portugal; EPIUnit, Instituto de Saúde Pública da Universidade do Porto, 4050-600 Porto, Portugal
| |
Collapse
|
|
33
|
Pentraxin-3 Predicts Long-Term Cardiac Events in Patients with Chronic Heart Failure. BIOMED RESEARCH INTERNATIONAL 2015; 2015:817615. [PMID: 26579541 PMCID: PMC4633533 DOI: 10.1155/2015/817615] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 09/13/2015] [Accepted: 10/05/2015] [Indexed: 12/27/2022]
Abstract
The aim of this study was to investigate the long-term prognostic value of pentraxin-3 (PTX3) in patients with chronic heart failure (CHF). 377 patients were prospectively followed up for 3 years to determine cardiac events including cardiac death or rehospitalization for worsening heart failure. The plasma PTX3 levels were significantly higher in CHF patients than in healthy subjects (p < 0.001), and they increased with advancing New York Heart Association (NYHA) Functional Classification (p < 0.001). Plasma PTX3 levels in CHF patients with cardiac events were significantly higher than in event-free patients (p < 0.001). We determined the normal upper limit of plasma PTX3 levels from the mean + 2 SD value of 64 control subjects (3.64 ng/mL). A Kaplan-Meier analysis revealed that patients with increased PTX3 (≥3.64 ng/mL) were at a higher risk for cardiac events than those without increased PTX3 (p < 0.01). A multifactorial Cox proportional hazards model showed that increased PTX3 (≥3.64 ngImL) was an independent risk factor for cardiac events in CHF patients (hazard ratio (HR) = 4.224, p < 0.01; 95% CI: 1.130–15.783). Plasma PTX3 levels are a long-term independent predictor of prognosis in patients with CHF.
Collapse
|
|
34
|
Borné Y, Persson M, Melander O, Smith JG, Engström G. Increased plasma level of soluble urokinase plasminogen activator receptor is associated with incidence of heart failure but not atrial fibrillation. Eur J Heart Fail 2015; 16:377-83. [PMID: 24464777 DOI: 10.1002/ejhf.49] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2013] [Revised: 11/08/2013] [Accepted: 11/15/2013] [Indexed: 11/10/2022] Open
Abstract
AIMS Soluble urokinase plasminogen activator receptor (suPAR) in plasma is a novel inflammatory marker thought to be released from the cell surface of neutrophils, T cells, and macrophages. Other inflammatory markers, mainly acute phase proteins produced in the liver, have been associated with the incidence of heart failure (HF) and atrial fibrillation (AF). We investigated the association between suPAR and incident HF and AF in a population-based cohort. METHODS AND RESULTS Soluble urokinase plasminogen activator receptor was measured in 4530 subjects (aged 46–68 years, 61% women), who participated in the Malmö Diet and Cancer study during 1991–1996. Incident cases of HF and AF were identified from the Swedish hospital discharge register during a median follow-up of 16.3 years. During follow-up, 109 subjects (55% men) were diagnosed with new-onset HF and 321 individuals (50% men) with AF. suPAR was significantly associated with increased plasma levels of NT-proBNP (P<0.001). suPAR was significantly associated with incidence of HF [hazard ratio (HR) for the third vs. first tertile 3.33, 95% confidence interval (CI) 1.91–5.81 after adjustment for age and sex; and HR 1.82, 95% CI 1.02–3.27, P for trend 0.018 after adjustment for conventional risk factors and biomarkers]. suPAR was significantly associated with incidence of AF, when adjusted for age and sex (HR 1.40, 95% CI 1.06–1.85). However, this relationship was non-significant after adjustment for conventional risk factors and biomarkers. CONCLUSION Soluble urokinase plasminogen activator receptor was associated with increased plasma levels of NT-proBNP and incidence of HF, but not with AF among middle-aged subjects.
Collapse
|
|
35
|
Parrinello CM, Lutsey PL, Ballantyne CM, Folsom AR, Pankow JS, Selvin E. Six-year change in high-sensitivity C-reactive protein and risk of diabetes, cardiovascular disease, and mortality. Am Heart J 2015; 170:380-9. [PMID: 26299237 DOI: 10.1016/j.ahj.2015.04.017] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2015] [Accepted: 04/12/2015] [Indexed: 12/22/2022]
Abstract
BACKGROUND Single measurements of elevated high-sensitivity C-reactive protein (hs-CRP) are associated with increased risk of diabetes, cardiovascular disease, and mortality. Large increases or sustained elevations in hs-CRP may be associated with even greater risk of these outcomes. The objective of this study was to characterize the association of 6-year change in hs-CRP with incident diabetes, incident cardiovascular events (heart disease, stroke, and heart failure), and mortality. METHODS We included 10,160 ARIC participants with hs-CRP measured at visits 2 (1990-1992) and 4 (1996-1998). Change in hs-CRP was categorized as sustained low/moderate (<3 mg/L at both visits), decreased (≥3 mg/L at visit 2 and <3 mg/L at visit 4), increased (<3 mg/L at visit 2 and ≥3 mg/L at visit 4), and sustained elevated (≥3 mg/L at both visits). Cox proportional hazards models were used to assess the association of 6-year change in hs-CRP with incident diabetes, cardiovascular events, and death during ~15 years after visit 4. RESULTS Compared with persons with sustained low/moderate hs-CRP, those with increased or sustained elevated hs-CRP had an increased risk of incident diabetes (hazard ratios [95% CIs] 1.56 [1.38-1.76] and 1.39 [1.25-1.56], respectively), whereas those with deceased hs-CRP did not. Persons with sustained elevated hs-CRP had an increased risk of coronary heart disease, ischemic stroke, heart failure, and mortality (hazard ratios [95% CIs] 1.51 [1.23-1.85], 1.70 [1.32-2.20], 1.60 [1.35-1.89], and 1.52 [1.37-1.69], respectively) compared with those with sustained low/moderate hs-CRP. Associations for sustained elevated hs-CRP were greater than for those with increased hs-CRP over 6 years. CONCLUSIONS Large increases or sustained elevations in hs-CRP over a 6-year period were associated with a subsequent increased risk of diabetes, and persons with sustained elevations in hs-CRP were at the highest risk for cardiovascular disease and mortality. Two measurements of hs-CRP are better than one for characterizing risk, and large increases are particularly prognostic.
Collapse
|
|
36
|
Gupta SK, Dongare S, Mathur R, Mohanty IR, Srivastava S, Mathur S, Nag TC. Genistein ameliorates cardiac inflammation and oxidative stress in streptozotocin-induced diabetic cardiomyopathy in rats. Mol Cell Biochem 2015; 408:63-72. [PMID: 26092427 DOI: 10.1007/s11010-015-2483-2] [Citation(s) in RCA: 72] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Accepted: 06/13/2015] [Indexed: 12/20/2022]
Abstract
The present study was undertaken to evaluate the protective effects of genistein against cardiac inflammation and oxidative stress in streptozotocin (STZ) (45 mg/kg body weight)-induced diabetic rats. genistein (300 mg/kg/day) was administered orally for 24 weeks to STZ-induced diabetic rats. The effects of genistein on blood glucose, % glycosylated hemoglobin (HbA1c), C-reactive protein, tumor necrosis factor (TNF- α), transforming growth factor (TGF-β1), and total antioxidant were studied. Ultrastructural and histopathological assessment of injury were also undertaken using transmission electron microscope. STZ-induced diabetes resulted in significant increase in the levels of blood glucose, HbA1c, C-reactive protein, TNF- α and TGF-β1, and a decline in total antioxidant reserve of the myocardium. Administration of genistein to diabetic rats resulted in a decrease in blood glucose (p < 0.001), % HbA1c (p < 0.0001), C-reactive protein (p < 0.001), and expression of TNF- α (p < 0.001) and TGF-β1 (p < 0.0001) proteins. In addition, genistein treatment results in augmentation of total antioxidant (p < 0.01) reserve of the hearts. The above findings were supported by histological as well as immunohistochemical localization of NF-κB (p65) in the heart. Genistein treatment ameliorated the ultrastructural degenerative changes in the cardiac tissues as compared to the diabetic control. The result demonstrates that genistein restored the integrity of the diabetic myocardium by virtue of its anti-inflammatory and antioxidant effects.
Collapse
Affiliation(s)
- Suresh K Gupta
- Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research, Pushp Vihar, Sec. -3, New Delhi, 110017, India.
| | - Shirish Dongare
- Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research, Pushp Vihar, Sec. -3, New Delhi, 110017, India
| | - Rajani Mathur
- Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research, Pushp Vihar, Sec. -3, New Delhi, 110017, India
| | | | - Sushma Srivastava
- Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research, Pushp Vihar, Sec. -3, New Delhi, 110017, India
| | - Sandeep Mathur
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Tapas C Nag
- Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India
| |
Collapse
|
|
37
|
Bouloukaki I, Mermigkis C, Kallergis EM, Moniaki V, Mauroudi E, Schiza SE. Obstructive sleep apnea syndrome and cardiovascular disease: The influence of C-reactive protein. World J Exp Med 2015; 5:77-83. [PMID: 25992322 PMCID: PMC4436942 DOI: 10.5493/wjem.v5.i2.77] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 12/28/2014] [Accepted: 03/20/2015] [Indexed: 02/06/2023] Open
Abstract
Obstructive sleep apnea syndrome (OSAS) is a common medical condition, associated with atherosclerosis and cardiovascular disease (CVD). The underlying pathophysiologic mechanisms of this association have not been completely understood and may be multifactorial in origin. A number of studies suggest that inflammatory processes have emerged critical in the pathogenesis of CVD in OSAS. A range of circulating inflammatory molecules has been identified and measured, with a view to assess inflammation and predict vascular damage risk, such as plasma cytokines, adhesion molecules, and C-reactive protein (CRP). CRP is a relevant marker worthy of further study, because not only is elevated in patients with OSAS, but also is rapidly becoming a risk factor for cardiac disease. Furthermore, in selected OSAS patients, aggressive treatment of the disorder may lead to retarding or even improvement of CVD progression. However, still there is a debate on the true correlation between CRP and OSAS, as well as the clinical effect of any reduction after OSAS treatment. Further research is required to define those OSAS patients who will have a considerable reduction with treatment, as well as to understand the significance of the interaction between cardiovascular risk factor and CRP reduction in patients with OSAS.
Collapse
|
|
38
|
Huynh K, Van Tassell B, Chow SL. Predicting therapeutic response in patients with heart failure: the story of C-reactive protein. Expert Rev Cardiovasc Ther 2015; 13:153-61. [PMID: 25578159 DOI: 10.1586/14779072.2015.1000307] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Heart failure continues to be a major public health burden in the USA. With markedly high rates of morbidity and mortality upon diagnosis, effective treatment and prognosis are critical in the management of chronic heart failure. Growing evidence now supports the hypothesis that inflammation plays a key role in the progression and worsening of heart failure. Of the various inflammatory mediators identified, C-reactive protein, an acute phase inflammatory marker, has been associated with poor prognosis in patients with heart failure. Several interventional studies have been investigated to explore C-reactive protein modulation and potential treatment options and health outcomes; however, further studies are warranted before C-reactive protein-targeted therapy may be recommended in the management of heart failure.
Collapse
Affiliation(s)
- Kitty Huynh
- Western University of Health Sciences, Pharmacy Practice, 309 E. Second Street, Pomona, 91766, USA
| | | | | |
Collapse
|
|
39
|
Eisen A, Benderly M, Behar S, Goldbourt U, Haim M. Inflammation and future risk of symptomatic heart failure in patients with stable coronary artery disease. Am Heart J 2014; 167:707-14. [PMID: 24766981 DOI: 10.1016/j.ahj.2014.01.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2013] [Accepted: 01/04/2014] [Indexed: 12/01/2022]
Abstract
BACKGROUND Heart failure (HF) carries poor prognosis in coronary artery disease (CAD) patients despite advances in therapy. Inflammation predicts recurrent cardiovascular events in CAD patients. It is unknown whether increased levels of inflammatory markers are associated with incident HF in these patients. AIM The aims of this study were to evaluate the association between inflammatory markers and future HF risk in patients with stable CAD and to explore possible mediation by myocardial infarction (MI). METHODS The study comprised 2,945 patients with stable CAD without HF at baseline during a median follow-up of 7.9 years. Inflammatory baseline markers were the basis of this study. RESULTS Heart failure was diagnosed in 508 patients (17.2%). Patients who developed HF were older and had more often previous MI, diabetes, hypertension, and peripheral vascular disease. Baseline levels of C-reactive protein (CRP), fibrinogen, and white blood cells (WBCs) were significantly higher in patients who developed HF compared with those who did not. Age-adjusted incident HF rates were related to elevated baseline inflammatory markers in a dose-response manner. Adjusting for multiple confounders, the HF hazard ratios were 1.38 (95% CI 1.11-1.72), 1.33 (95% CI 1.07-1.66), and 1.36 (95% CI 1.10-1.68) for the third tertiles of CRP, fibrinogen, and WBC levels, respectively. Hazard ratio for the fifth quintile of a combined "inflammation score" was 1.83 (95% CI 1.40-2.39). Mediation by MI preceding the HF onset during follow-up accounted for 10.4%, 10.8%, and 8.6% of the association of subsequent HF with CRP, fibrinogen, and WBC, respectively. CONCLUSIONS Increased levels of CRP, fibrinogen, and WBC are independently related to the incidence of HF in patients with stable CAD.
Collapse
Affiliation(s)
- Alon Eisen
- Cardiology Department, Rabin Medical Center, Petah-Tikva, Israel.
| | - Michal Benderly
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Gertner Institute for Epidemiology and Health Research Policy, Sheba Medical Center, Tel-Hashomer, Israel
| | - Solomon Behar
- The Israel Society for the Prevention of Heart Attacks, Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer, Israel
| | - Uri Goldbourt
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Israel Society for the Prevention of Heart Attacks, Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer, Israel
| | - Moti Haim
- Cardiology Department, Rabin Medical Center, Petah-Tikva, Israel
| |
Collapse
|
|
40
|
Iqbal N, Alim KS, Aramin H, Iqbal F, Green E, Higginbotham E, Maisel AS. Novel biomarkers for heart failure. Expert Rev Cardiovasc Ther 2014; 11:1155-69. [DOI: 10.1586/14779072.2013.832476] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
|
|
41
|
Lai YH, Liu CC, Kuo JY, Hung TC, Wu YJ, Yeh HI, Bulwer BE, Hung CL. Independent effects of body fat and inflammatory markers on ventricular geometry, midwall function, and atrial remodeling. Clin Cardiol 2014; 37:172-7. [PMID: 24399410 DOI: 10.1002/clc.22242] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2013] [Revised: 12/03/2013] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND The effect of body fat distribution on left ventricular (LV) mass and geometry has been recently recognized. However, data regarding circulating inflammatory markers in relation to regional visceral fat deposits, which are metabolically active tissues that can impact cardiac structural remodeling, remain sparse. HYPOTHESIS We hypothesized that obesity has adverse effects on cardiac function and structure. METHODS We consecutively studied 1071 asymptomatic subjects (age 49.5 ± 10.5 years, 39.4% female) free from significant valvular disorders, chronic lung disease, or renal disease. Echocardiography-defined cardiac structures and LV geometries including LV mass, mass-to-volume ratio, and fractional shortening were all determined. Body fat composition (Tanita-305 Body-Fat Analyzer; Tanita Corp., Tokyo, Japan) was obtained and calculated. Multivariate regression models from various models were used to represent the independent association between body fat and echo-derived ventricular mass and geometries. RESULTS In multivariable analysis, increasing body fat was significantly related to increase in left atrial (LA) and LV diameter, posterior wall thickness, relative wall thickness (RWT), LV mass, mass-to-volume ratio, and decreased midwall fractional shortening with or without stress correction (all P < 0.001). When LV mass and severity of mitral regurgitation was further added, the independent association between increased body fat composition and larger LA diameter remained significant (β coefficient = 0.37, P < 0.001). Elevated high-sensitivity C-reactive protein (Hs-CRP) level was associated with larger LA diameter, increased RWT, and worsened midwall mechanics in the female gender (all interaction P < 0.05). CONCLUSIONS Accumulated body fat seemed to be related to worse ventricular midwall contractility and atrial remodeling, particularly in the female gender, with high systemic inflammation. These gender and Hs-CRP-specific modification effects may potentiate the pathological mechanisms involved in heart failure with preserved ejection fraction.
Collapse
Affiliation(s)
- Yau-Huei Lai
- Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medicine, Mackay Medical College and Mackay Medicine Nursing and Management College, Taipei, Taiwan
| | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Khan H, Kunutsor S, Rauramaa R, Savonen K, Kalogeropoulos AP, Georgiopoulou VV, Butler J, Laukkanen JA. Cardiorespiratory fitness and risk of heart failure: a population-based follow-up study. Eur J Heart Fail 2013; 16:180-8. [PMID: 24464981 DOI: 10.1111/ejhf.37] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2013] [Revised: 07/31/2013] [Accepted: 08/02/2013] [Indexed: 12/22/2022] Open
Abstract
AIM To examine the relationship between cardiorespiratory fitness (CRF) and risk of incident heart failure (HF). METHODS AND RESULTS Cardiorespiratory fitness, as measured by maximal oxygen uptake (VO2 max), was assessed at baseline in a prospective cohort of 1873 men aged 42-61 years without HF or chronic respiratory disease. During a mean follow-up of 20.4 years, 152 incident HF events were recorded. Within-person variability was calculated using data from repeat measurements taken 11 years apart. The age-adjusted hazard ratio (HR) per unit increase (1 mL/kg/min of VO2 max) in CRF was 0.89 [95% confidence interval (CI) 0.86-0.93], which was minimally attenuated to 0.94 (95% CI 0.90-0.98) after further adjustment for established HF risk factors (body mass index, systolic blood pressure, history of cardiovascular disease, diabetes, heart rate, and LV hypertrophy) and incident coronary events as a time-varying covariate. In a comparison of extreme quartiles of CRF levels (VO2 max ≥35.4 vs. ≤25.7 mL/kg/min), the corresponding HRs were 0.27 (0.15-0.50) and 0.48 (0.25-0.92), respectively. Each 1 MET (metabolic equivalent of oxygen consumption) increment in CRF was associated with a 21% (7-33%) reduction in multivariable adjusted risk of HF. Addition of CRF to a HF risk prediction model containing established risk factors did not significantly improve risk discrimination (C-index change = 0.0164, P = 0.07). CONCLUSIONS In this Finnish population, there is a strong, inverse, and independent association between long-term CRF and HF risk, consistent with a dose-response relationship. The protective effect of CRF on HF risk warrants further evaluation.
Collapse
Affiliation(s)
- Hassan Khan
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | | | | | | | | | | | | | | |
Collapse
|
|
43
|
Fernandez ML, Webb D. The LDL to HDL Cholesterol Ratio as a Valuable Tool to Evaluate Coronary Heart Disease Risk. J Am Coll Nutr 2013; 27:1-5. [DOI: 10.1080/07315724.2008.10719668] [Citation(s) in RCA: 124] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
|
|
44
|
Inflammatory cytokines, apoptotic, tissue injury and remodeling biomarkers in children with congenital heart disease. Indian J Clin Biochem 2013; 29:145-9. [PMID: 24757294 DOI: 10.1007/s12291-013-0341-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2013] [Accepted: 05/13/2013] [Indexed: 12/16/2022]
Abstract
The present study aims to evaluate specific biomarkers involved in congenital heart disease (CHD), and whether there is a significant differences between the levels of these biomarkers in the cyanotic CHD (CCHD) and acyanotic CHD (ACHD). We prospectively measured tumor necrosis factor (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), vasoendothelial growth factor (VEGF), troponin T, creatin kinase MB (CKMB), and Caspase 3 levels in 120 consecutive children with CHD (60 cyanotic and 60 a cyanotic with age 1:4 years), and 30 healthy control children. Significant elevated levels of inflammatory markers; TNF-α, IL-6 and CRP was detected in CHD, with percentage increase in cyanotic than a cyanotic subjects as compared to the normal one. Apoptotic biomarker; caspase 3 showed also significant increases in CCHD than ACHD. In addition, tissue injury mechanisms included troponin T and CKMB, exhibited significant increase in cyanotic than a cyanotic CHD. The present results demonstrate also, significant enhancement in remodeling process (VEGF), in cyanotic than a cyanotic patients. Thus, it could be concluded that, the children with CCHD were shown to have elevated levels of inflammatory cytokines, caspase 3, troponin T, and CKMB as these biomarkers may implicated in cardiac functional status.
Collapse
|
|
45
|
Rosell J, Nordenskjöld B, Bengtsson NO, Fornander T, Hatschek T, Lindman H, Malmström PO, Wallgren A, Stål O, Carstensen J. Effects of adjuvant tamoxifen therapy on cardiac disease: results from a randomized trial with long-term follow-up. Breast Cancer Res Treat 2013; 138:467-73. [PMID: 23456195 DOI: 10.1007/s10549-013-2457-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2013] [Accepted: 02/18/2013] [Indexed: 12/01/2022]
Abstract
Tamoxifen is associated with a reduced risk of coronary heart disease (CHD). However, there are few reports on long-term effects. Using data from a large Swedish randomized trial of 5 and 2 years of adjuvant tamoxifen in women with early breast cancer, we here present results on morbidity and mortality from cardiac diseases during treatment and long-term after treatment. A total of 4,150 patients were breast cancer recurrence-free after 2 years. Data from the Swedish National Hospital Discharge Registry combined with information from the Swedish Cause of Death Registry were used to define events of disease. Hazard ratios were estimated using Cox regression. Patients assigned to 5 years in comparison with 2 years of postoperative tamoxifen experienced a reduced incidence of CHD [hazard ratio (HR), 0.83; 95 % CI 0.70-1.00], especially apparent during the active treatment period (HR 0.65; 95 % CI 0.43-1.00). The mortality from CHD was significantly reduced (HR 0.72; 95 % CI 0.53-0.97). During the active treatment, the morbidity of other heart diseases was also significantly reduced (HR 0.40; 95 % CI 0.25-0.64) but not after treatment stopped (HR 1.06; 95 % CI 0.87-1.30). Similar results were seen for both heart failure and atrial fibrillation/flutter. As compared to 2 years of therapy, 5 years of postoperative tamoxifen therapy prevents CHD as well as other heart diseases. The risk reduction is most apparent during the active treatment period, and later tends to diminish.
Collapse
Affiliation(s)
- Johan Rosell
- Regional Cancer Centre, County Council of Östergötland, University Hospital, 581 85, Linköping, Sweden.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
46
|
Nagai T, Anzai T, Mano Y, Kaneko H, Anzai A, Sugano Y, Maekawa Y, Takahashi T, Yoshikawa T, Fukuda K. Eicosapentaenoic acid suppresses adverse effects of C-reactive protein overexpression on pressure overload-induced cardiac remodeling. Heart Vessels 2012; 28:404-11. [PMID: 22875408 DOI: 10.1007/s00380-012-0270-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2012] [Accepted: 06/22/2012] [Indexed: 10/28/2022]
Abstract
Serum C-reactive protein (CRP) elevation is associated with poor clinical outcome in patients with heart failure (HF). We previously reported that CRP exacerbates the development of pressure overload-induced cardiac remodeling through an enhanced inflammatory response and oxidative stress. In the present study, we examined the effect of eicosapentaenoic acid (EPA), a suppressor of inflammatory response and oxidative stress, on pressure overload-induced cardiac remodeling. Transverse aortic constriction (TAC) was performed on transgenic mice overexpressing CRP (CRPtg) and nontransgenic littermates (TAC/CON). CRPtg with TAC operation were randomly assigned to be fed a standard diet (TAC/CRPtg) or an EPA-enriched diet (7 % of total energy) (TAC/CRPtg/EPA). Myocardial mRNA level of transforming growth factor-β1, proinflammatory cytokines, and oxidative stress markers were increased in TAC/CRPtg in comparison with TAC/CON 1 and 4 weeks after the operation. These parameters were significantly suppressed in TAC/CRPtg/EPA compared with TAC/CRPtg. In addition, after 4 weeks of EPA treatment, as compared with TAC/CRPtg, TAC/CRPtg/EPA mice demonstrated reduced heart and lung weights, increased left ventricular fractional shortening, and decreased left ventricular end-diastolic pressure, together with decreased cardiac hypertrophy, fibrosis, and improved cardiac function. In conclusion, the anti-inflammatory and antioxidative properties of EPA may make it an effective therapeutic strategy for adverse cardiac remodeling associated with CRP overexpression.
Collapse
Affiliation(s)
- Toshiyuki Nagai
- Division of Cardiology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Anaemia is a predictor of early death or cardiac transplantation in children with idiopathic dilated cardiomyopathy. Cardiol Young 2012; 22:293-300. [PMID: 22008642 DOI: 10.1017/s1047951111001442] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
INTRODUCTION The aim of our study was to establish the prevalence and the prognostic value of haematological abnormalities in children with cardiac failure. PATIENTS AND METHODS A series of 218 consecutive children with a first diagnosis of idiopathic dilated cardiomyopathy were retrospectively examined. Haematological evaluation was performed at first diagnosis. Death or cardiac transplantation was the main outcome measure. RESULTS The median age was 0.6 years, ranging from 1 day to 15.8 years and median follow-up was 2.65 years, ranging from 0 to 17.2 years. After a median interval of 0.2 years, ranging from 0 to 8.7 years, 56 patients died and 25 were transplanted. Event-free survival at 1 and 5 years was 68% (95% confidence interval, 63-75%) and 62% (95% confidence interval, 56-69%). Blood levels of haemoglobin less than 10 grams per decilitre, urea over 8 millimoles per litre, and C-reactive protein over 10 milligrams per litre were found in 24%, 20%, and 24% of patients, respectively. The log-rank test showed that haemoglobin (p = 0.000) and C-reactive protein (p = 0.021) were predictors of death or transplantation. In the multivariate Cox model, haemoglobin (hazard ratio = 0.735; confidence interval = 0.636-0.849; p = 0.000) and urea (hazard ratio = 1.083; confidence interval = 1:002-1:171; p = 0.045) were predictive of poor outcome. Cubic spline functions showed that the positive role of haemoglobin on survival was linear for values less than 12 grams per decilitre and null for values more than 12 grams per decilitre. Adaptive index models for risk stratification and Classification and Regression Tree analysis allowed to identify the cut-off values for haemoglobin (less than 10.2 grams per decilitre) and urea (more than 8.8 millimoles per litre), as well as to derive a predictor model. CONCLUSIONS In children with idiopathic dilated cardiomyopathy, anaemia is the strongest independent prognostic factor of early death or transplantation.
Collapse
|
|
48
|
Pfister R, Sharp SJ, Luben R, Wareham NJ, Khaw KT. Differential white blood cell count and incident heart failure in men and women in the EPIC-Norfolk study. Eur Heart J 2012; 33:523-530. [PMID: 22173908 DOI: 10.1093/eurheartj/ehr457] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
AIMS Markers of inflammation are associated with increased risk of heart failure, but data on differential white blood cell (WBC) count are lacking. We examined the prospective association between differential WBC count and incident heart failure events. METHODS AND RESULTS Hazard ratios (HRs) (per increase of 1000 cells/μL, 95% confidence interval) of total WBC count and individual components on heart failure were calculated in apparently healthy 7195 men and 8816 women aged 39-79 participating in the 'European Prospective Investigation into Cancer and Nutrition' (EPIC) study in Norfolk. During a mean follow-up of 12.4 years, 935 incident cases of heart failure occurred. In women, neither total WBC count (1.02, 0.96-1.09) nor individual components were associated with HR of heart failure after accounting for known risk factors. In men, HR of heart failure increased with increasing levels of total WBC count (1.09, 1.04-1.15) after accounting for established risk factors; analysis of WBC components showed increased hazard with increasing levels of granulocyte count (1.16, 1.09-1.24) and, independently of this, decreased hazard with increasing levels of monocyte count (0.71, 0.53-0.93); lymphocyte count was not significantly associated with heart failure (0.97, 0.83-1.13). Results did not change materially after excluding smokers, adjusting for intermediate myocardial infarction and coronary heart disease and C-reactive protein. CONCLUSION Inflammation as measured by WBC count was independently associated with incident heart failure in apparently healthy men but not women. The association observed in men was driven by granulocyte count, but there was an independent inverse association between monocyte count and incident heart failure.
Collapse
Affiliation(s)
- Roman Pfister
- Medical Research Council Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
| | | | | | | | | |
Collapse
|
|
49
|
Masugata H, Senda S, Okada H, Murao K, Inukai M, Himoto T, Hosomi N, Murakami K, Noma T, Kohno M, Goda F. Association between Cardiac Function and Pulmonary Function in Hypertensive Patients. J Int Med Res 2012; 40:105-14. [DOI: 10.1177/147323001204000111] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE: This study examined the association between cardiac function and pulmonary function in hypertensive patients. METHODS: Hypertensive patients without overt cardiovascular disease were enrolled ( n = 43; mean ± SD age 71 ± 9 years). Pulmonary function was measured by the percentage of predicted forced vital capacity (%FVC) and the ratio of 1 s forced expiratory volume (FEV1) to FVC (FEV1/FVC ratio). Left ventricular ejection fraction (LVEF) and the ratio of peak early diastolic transmitral flow (E) to peak early diastolic mitral annular velocity (e′) (E/e′ ratio) were assessed using echocardiography. RESULTS: Multiple linear regression analysis revealed that E/e′ was independently associated with %FVC and that LVEF was independently associated with FEV1/FVC ratio. Both LVEF and FEV1/FVC ratio were significantly lower in hypertensive former or current smokers than in hypertensive never smokers. CONCLUSIONS: Subclinical cardiac dysfunction was independently associated with reduced pulmonary function in hypertensive patients. Hypertensive patients with decreased pulmonary function may need preventive care to prevent the progression of heart failure.
Collapse
Affiliation(s)
- H Masugata
- Department of Integrated Medicine, Kagawa University, Kagawa, Japan
| | - S Senda
- Department of Integrated Medicine, Kagawa University, Kagawa, Japan
| | - H Okada
- Department of Medical Education, Kagawa University, Kagawa, Japan
| | - K Murao
- Department of Advanced Medicine and Laboratory Medicine, Kagawa University, Kagawa, Japan
| | - M Inukai
- Department of Integrated Medicine, Kagawa University, Kagawa, Japan
| | - T Himoto
- Department of Integrated Medicine, Kagawa University, Kagawa, Japan
| | - N Hosomi
- Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan
| | - K Murakami
- Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University, Kagawa, Japan
| | - T Noma
- Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University, Kagawa, Japan
| | - M Kohno
- Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University, Kagawa, Japan
| | - F Goda
- Department of Integrated Medicine, Kagawa University, Kagawa, Japan
| |
Collapse
|
|
50
|
Kamioka M, Suzuki H, Yamada S, Kamiyama Y, Saitoh SI, Takeishi Y. High Sensitivity C-Reactive Protein Predicts Nonresponders and Cardiac Deaths in Severe Heart Failure Patients After CRT Implantation. Int Heart J 2012; 53:306-12. [DOI: 10.1536/ihj.53.306] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Masashi Kamioka
- Department of Cardiology and Hematology, Fukushima Medical University
| | - Hitoshi Suzuki
- Department of Cardiology and Hematology, Fukushima Medical University
| | - Shinya Yamada
- Department of Cardiology and Hematology, Fukushima Medical University
| | | | - Shu-ichi Saitoh
- Department of Cardiology and Hematology, Fukushima Medical University
| | | |
Collapse
|