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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:ImportanceObesity is associated with a higher risk of cardiovascular disease (CVD), but little is known about the role that circulating protein biomarkers play in this association.ObjectiveTo examine the observational and genetic associations of adiposity with circulating protein biomarkers and the observational associations of proteins with incident CVD.Design, setting, and participantsThis subcohort study included 628 participants from the prospective China Kadoorie Biobank who did not have a history of cancer at baseline. The Olink platform measured 92 protein markers in baseline plasma samples. Data were collected from June 2004 to January 2016 and analyzed from January 2019 to June 2020.ExposuresMeasured body mass index (BMI) obtained during the baseline survey and genetically instrumented BMI derived using 571 externally weighted single-nucleotide variants.Main outcomes and measuresCross-sectional associations of adiposity with biomarkers were examined using linear regression. Associations of biomarkers with CVD risk were assessed using Cox regression among those without prior cancer or CVD at baseline. Mendelian randomization was conducted to derive genetically estimated associations of BMI with biomarkers.FindingsIn observational analyses of 628 individuals (mean [SD] age, 52.2 [10.5] years; 385 women [61.3%]), BMI (mean [SD], 23.9 [3.6]) was positively associated with 27 proteins (per 1-SD higher BMI; eg, interleukin-6: 0.21 [95% CI, 0.12-0.29] SD; interleukin-18: 0.13 [95% CI, 0.05-0.21] SD; monocyte chemoattractant protein-1: 0.12 [95% CI, 0.04-0.20] SD; hepatocyte growth factor: 0.31 [95% CI, 0.24-0.39] SD), and inversely with 3 proteins (Fas ligand: -0.11 [95% CI, -0.19 to -0.03] SD; TNF-related weak inducer of apoptosis, -0.14 [95% CI, -0.23 to -0.06] SD; and carbonic anhydrase 9: (-0.14 [95% CI, -0.22 to -0.05] SD), with similar associations identified for other adiposity traits (eg, waist circumference [r = 0.96]). In mendelian randomization, the associations of genetically elevated BMI with specific proteins were directionally consistent with the observational associations. In meta-analyses of genetically elevated BMI with 8 proteins, combining present estimates with previous studies, the most robust associations were shown for interleukin-6 (per 1-SD higher BMI; 0.21 [95% CI, 0.13-0.29] SD), interleukin-18 (0.16 [95% CI, 0.06-0.26] SD), monocyte chemoattractant protein-1 (0.21 [95% CI, 0.11-0.30] SD), monocyte chemotactic protein-3 (0.12 [95% CI, 0.03-0.21] SD), TNF-related apoptosis-inducing ligand (0.23 [95% CI, 0.13-0.32] SD), and hepatocyte growth factor (0.14 [95% CI, 0.06-0.22] SD). Of the 30 BMI-associated biomarkers, 10 (including interleukin-6, interleukin-18, and hepatocyte growth factor) were nominally associated with incident CVD.Conclusions and relevanceMendelian randomization shows adiposity to be associated with a range of protein biomarkers, with some biomarkers also showing association with CVD risk. Future studies are warranted to validate these findings and assess whether proteins may be mediators between adiposity and CVD.

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.

Similar Datasets

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