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Gender-modulated risk of coronary heart disease, diabetes and coronary mortality among Turks for three major risk factors, and residual adiposity risk.

ABSTRACT: We determined the proportion of the effects of body mass index (BMI) or its categories on cardiometabolic outcomes mediated through systolic blood pressure (SBP), total cholesterol and fasting glucose.Cox regression analyses were performed for incident outcomes among Turkish Adult Risk Factor study participants in whom the three mediators had been determined (n?=?2158, age 48.5?±?11 years). Over a mean 10.2-years' follow-up, new coronary heart disease (CHD) developed in 406, diabetes in 284 individuals, and 149 CHD deaths occurred.Hazard ratios (HR) of BMI for incident diabetes were no more than marginally attenuated by the 3 mediators including glucose, irrespective of gender. Compared to "normal-weight", sex- and age-adjusted RRs for incident CHD of overweight and obesity were 1.40 and 2.24 (95 % CI 1.68; 2.99), respectively, in gender combined. Only three-tenths of the excess risk was retained by BMI in men, six-tenths in women. No mediation of glycemia was discerned in males, in contrast to greatest mediation in females. HR of age-adjusted continuous BMI was a significant but modest contributor to CHD mortality in each gender. While the BMI risk of CHD death was abolished by mediation of SBP in men, HR strengthened to over two-fold in women through mediation of fasting glucose.Mediation of adiposity by 3 traditional factors exhibited among Turkish adults strong gender dependence regarding its magnitude for CHD risk and the mediation by individual risk factors. Retention of the large part of risk for diabetes in each sex and for CHD in women likely reflects underlying autoimmune activation.

SUBMITTER: Can G

PROVIDER: S-EPMC5041572 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Gender-modulated risk of coronary heart disease, diabetes and coronary mortality among Turks for three major risk factors, and residual adiposity risk.

Can Günay G Onat Altan A Yurtseven Eray E Karadeniz Yusuf Y Akbaş-Şimşek Tuğba T Kaya Ayşem A Yüksel Hüsniye H

BMC endocrine disorders 20160929 1

<h4>Background</h4>We determined the proportion of the effects of body mass index (BMI) or its categories on cardiometabolic outcomes mediated through systolic blood pressure (SBP), total cholesterol and fasting glucose.<h4>Methods</h4>Cox regression analyses were performed for incident outcomes among Turkish Adult Risk Factor study participants in whom the three mediators had been determined (n = 2158, age 48.5 ± 11 years). Over a mean 10.2-years' follow-up, new coronary heart disease (CHD) dev ...[more]

PMID: 27680100

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Project description:BackgroundWithin-person variability in measured values of a risk factor can bias its association with disease. We investigated the extent of regression dilution bias in calculated variables and its implications for comparing the aetiological associations of risk factors.MethodsUsing a numerical illustration and repeats from 42,300 individuals (12 cohorts), we estimated regression dilution ratios (RDRs) in calculated risk factors [body-mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR)] and in their components (height, weight, waist circumference, and hip circumference), assuming the long-term average exposure to be of interest. Error-corrected hazard ratios (HRs) for risk of coronary heart disease (CHD) were compared across adiposity measures per standard-deviation (SD) change in: (i) baseline and (ii) error-corrected levels.ResultsRDRs in calculated risk factors depend strongly on the RDRs, correlation, and comparative distributions of the components of these risk factors. For measures of adiposity, the RDR was lower for WHR [RDR: 0.72 (95% confidence interval 0.65-0.80)] than for either of its components [waist circumference: 0.87 (0.85-0.90); hip circumference: 0.90 (0.86-0.93) or for BMI: 0.96 (0.93-0.98) and WHtR: 0.87 (0.85-0.90)], predominantly because of the stronger correlation and more similar distributions observed between waist circumference and hip circumference than between height and weight or between waist circumference and height. Error-corrected HRs for BMI, waist circumference, WHR, and WHtR, were respectively 1.24, 1.30, 1.44, and 1.32 per SD change in baseline levels of these variables, and 1.24, 1.27, 1.35, and 1.30 per SD change in error-corrected levels.ConclusionsThe extent of within-person variability relative to between-person variability in calculated risk factors can be considerably larger (or smaller) than in its components. Aetiological associations of risk factors should be compared through the use of error-corrected HRs per SD change in error-corrected levels of these risk factors.

Project description:Background Identification of patients with stable coronary heart disease who are at significant residual risk could be helpful for targeted prevention. Our aim was to determine the prognostic value of the recently introduced ceramide- and phospholipid-based risk score, the Cardiovascular Event Risk Test (CERT2), in patients with stable coronary heart disease on optimal medical therapy and to identify biological processes that contribute to the CERT2 score. Methods and Results Plasma samples (n=11 222) obtained from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial were analyzed using a tandem liquid chromatography-mass spectrometry method. STABILITY was a trial in patients with stable coronary heart disease randomized to the lipoprotein-associated phospholipase A2 inhibitor darapladib or placebo on optimized medical therapy at baseline, with a median follow-up of 3.7 years. Hazard ratios per SD for the CERT2 risk score were 1.32 (95% CI, 1.25-1.39) for major adverse cardiovascular event, 1.47 (95% CI, 1.35-1.59) for cardiovascular death, 1.32 (95% CI, 1.16-1.49) for stroke, 1.23 (95% CI, 1.14-1.33) for myocardial infarction, and 1.56 (95% CI, 1.39-1.76) for hospitalization due to heart failure, when adjusted for traditional cardiovascular risk factors. CERT2 showed correlation (P<0.001, r>0.2) with inflammatory markers high-sensitivity C-reactive protein, interleukin 6, the heart failure marker N-terminal pro-B-type natriuretic peptide, and low-density lipoprotein cholesterol. After also adjusting for levels of other prognostic biomarkers, the CERT2 score was still independently related to the risk of cardiovascular death but not to nonfatal events. Conclusions The CERT2 risk score can detect residual risk in patients with stable coronary heart disease and is associated with biomarkers indicating inflammation, myocardial necrosis, myocardial dysfunction, renal dysfunction, and dyslipidemia. REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT00799903.

Dataset Information

Gender-modulated risk of coronary heart disease, diabetes and coronary mortality among Turks for three major risk factors, and residual adiposity risk.

Publications

Gender-modulated risk of coronary heart disease, diabetes and coronary mortality among Turks for three major risk factors, and residual adiposity risk.

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