0000000000053876

AUTHOR

Mahir Karakas

Cardio‐Renal Biomarker Soluble Urokinase‐Type Plasminogen Activator Receptor Is Associated With Cardiovascular Death and Myocardial Infarction in Patients With Coronary Artery Disease Independent of Troponin, C‐Reactive Protein, and Renal Function

Background Risk stratification among patients with coronary artery disease ( CAD ) is of considerable interest due to the potential to guide secondary preventive therapies. Thus, we evaluated the predictive value of soluble urokinase‐type plasminogen activator receptor (su PAR ) levels for cardiovascular mortality and nonfatal myocardial infarction in patients with CAD . Methods and Results Plasma levels of su PAR were measured in a cohort of 1703 patients with documented CAD as evidenced by coronary angiography—including 626 patients with acute coronary syndrome and 1077 patients with stable angina pectoris. Cardiovascular death and/or nonfatal myocardial infarction were defined as main o…

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Relations of Sex to Diagnosis and Outcomes in Acute Coronary Syndrome

Background The atypical presentation of women with acute coronary syndrome ( ACS ) has been related to delayed diagnosis and treatment, which may explain worse outcome compared with men. Methods and Results We analyzed pooled data of 2520 patients of 2 prospective cohorts in terms of differences in presentation and management of women and men suggestive of ACS . Using logistic regression, we established 2 diagnostic models and tested their diagnostic performance in both sexes separately. Sex‐specific differences in management of patients with ACS were ascertained and a 2‐year follow‐up was performed. Women were older than men (median 67 versus 61 years, P =0.001), had more often dyspnea (2…

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Head-to-Head Comparison of the Incremental Predictive Value of The Three Established Risk Markers, Hs-troponin I, C-Reactive Protein, and NT-proBNP, in Coronary Artery Disease

Risk stratification among patients with coronary artery disease (CAD) is of considerable interest to potentially guide secondary preventive therapies. Cardiac troponins as well as C-reactive protein (hsCRP) and natriuretic peptides have emerged as biomarkers for risk stratification. The question remains if one of these biomarkers is superior in predicting adverse outcomes. Thus, we perform a head-to-head comparison between high-sensitivity troponin I (hsTnI), hsCRP, and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with CAD. Plasma levels were measured in a cohort of 2193 patients with documented CAD. The main outcome measures were cardiovascular (CV) death and/or nonfata…

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Iron Metabolism Contributes to Prognosis in Coronary Artery Disease: Prognostic Value of the Soluble Transferrin Receptor Within the AtheroGene Study

Background Coronary heart disease is a leading cause of mortality worldwide. Iron deficiency, a frequent comorbidity of coronary heart disease, causes an increased expression of transferrin receptor and soluble transferrin receptor levels (sTfR) levels, while iron repletion returns sTfR levels to the normal physiological range. Recently, sTfR levels were proposed as a potential new marker of iron metabolism in cardiovascular diseases. Therefore, we aimed to evaluate the prognostic value of circulating sTfR levels in a large cohort of patients with coronary heart disease. Methods and Results The disease cohort comprised 3423 subjects who had angiographically documented coronary heart diseas…

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Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure.

Hypertension represents a major cardiovascular risk factor. The pathophysiology of increased blood pressure (BP) is not yet completely understood. Transcriptome profiling offers possibilities to uncover genetics effects on BP. Based on 2 populations including 2549 individuals, a meta-analyses of monocytic transcriptome-wide profiles were performed to identify transcripts associated with BP. Replication was performed in 2 independent studies of whole-blood transcriptome data including 1990 individuals. For identified candidate genes, a direct link between long-term changes in BP and gene expression over time and by treatment with BP-lowering therapy was assessed. The predictive value of pro…

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Discovery and Fine Mapping of Serum Protein Loci through Transethnic Meta-analysis

Many disorders are associated with altered serum protein concentrations, including malnutrition, cancer, and cardiovascular, kidney, and inflammatory diseases. Although these protein concentrations are highly heritable, relatively little is known about their underlying genetic determinants. Through transethnic meta-analysis of European-ancestry and Japanese genome-wide association studies, we identified six loci at genome-wide significance (p −8 ) for serum albumin ( HPN-SCN1B , GCKR-FNDC4 , SERPINF2-WDR81 , TNFRSF11A-ZCCHC2 , FRMD5-WDR76 , and RPS11-FCGRT , in up to 53,190 European-ancestry and 9,380 Japanese individuals) and three loci for total protein ( TNFRS13B , 6q21.3, and ELL2 , in …

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Circulating microRNAs strongly predict cardiovascular death in patients with coronary artery disease—results from the large AtheroGene study

Introduction Stratification for subsequent coronary events among patients with coronary artery disease (CAD) is of considerable interest because of the potential to guide secondary preventive therapies. Recently, we identified eight microRNAs (miRNAs), which facilitated acute coronary syndrome (ACS) diagnosis. In this study, we aimed to evaluate their potential role as prognostic biomarkers for cardiovascular disease. Methods The serum concentrations of eight candidate miRNAs -miR-19a, miR-19b, miR-132, miR-140-3p, miR-142-5p, miR-150, miR-186, and miR-210 were measured in a cohort of 1112 patients with documented CAD—including 430 patients with ACS and 682 patients with stable angina pecto…

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Relative Telomere Length and Cardiovascular Risk Factors

(1) Background: Telomeres are repetitive DNA sequences located at the extremities of chromosomes that maintain genetic stability. Telomere biology is relevant to several human disorders and diseases, specifically cardiovascular disease. To better understand the link between cardiovascular disease and telomere length, we studied the effect of relative telomere length (RTL) on cardiovascular risk factors in a large population-based sample. (2) Methods: RTL was measured by a real-time quantitative polymerase chain reaction in subjects of the population-based Gutenberg Health Study (n = 4944). We then performed an association study of RTL with known cardiovascular risk factors of smoking status…

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Novel DNA Methylation Sites Influence GPR15 Expression in Relation to Smoking

Smoking is a major risk factor for cardiovascular diseases and has been implicated in the regulation of the G protein-coupled receptor 15 (GPR15) by affecting CpG methylation. The G protein-coupled receptor 15 is involved in angiogenesis and inflammation. An effect on GPR15 gene regulation has been shown for the CpG site CpG3.98251294. We aimed to analyze the effect of smoking on GPR15 expression and methylation sites spanning the GPR15 locus. DNA methylation of nine GPR15 CpG sites was measured in leukocytes from 1291 population-based individuals using the EpiTYPER. Monocytic GPR15 expression was measured by qPCR at baseline and five-years follow up. GPR15 gene expression was upregulated i…

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