• Reyhaneh Rajab Boloukat, Azra Ramezankhani, Mitra Hasheminia, Erfan Tasdighi, Fereidoun Azizi, and Farzad Hadaegh.
• Prevention of Metabolic Disorders Research Center, Research Institute of Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
• Clin Nutr. 2018 Dec 1; 37 (6 Pt A): 2060-2067.

Background & AimsTo determine the association of body mass index (BMI) and central adiposity measures with coronary heart disease (CHD)/stroke, and to quantify the impact of blood pressure, cholesterol and glucose as metabolic mediators on these associations.MethodsThe study population included 4631 Iranian participants (males = 2066) aged ≥40 years. Cox proportional hazard model was used to estimate the hazard ratio (HR) of BMI and central adiposity measures, using continuous and categorical variables, on CHD/stroke, with and without adjustment for three metabolic mediators, to calculate the attenuation of excess risk after adjustment for mediators.ResultsDuring a median follow-up of 12.1 years, 606 and 132 subjects experienced incident CHD and stroke, respectively. In the sex and confounders adjusted model, overweight and obesity were associated with increased risk for CHD (HR: 1.56; 95% CI: 1.26-1.92) and [1.53 (1.21-1.94)], respectively; however, after further adjustment for all the mediators, the result was significant only for overweight status [1.29 (1.05-1.59)]. Considering stroke, a significant risk of 70% (1.05-2.72) was found only among obese population. The percentage of risk mediated by three mediators among obese population was 75.47% and 75.71% for CHD and stroke, respectively. Blood pressure was the most important mediator of obesity, accounting for at least 50% of the excess risk for CHD and 60% for stroke. Considering central obesity measures, in the presences of all mediators, a significant risk for CHD was demonstrated; regarding stroke events, the risk was marginally significant for waist to height [1.02 (0.99-1.05)] and waist to hip ratios [1.02 (1.00-1.05)].ConclusionsOverweight and obesity for CHD and, obesity for stroke were associated with increased risk; the negative effect of obesity was potentially ameloriated about 70% after adjustment for mediators. However, overweight status and central adiposity highlighted significant risk that did not decrease after controlling for traditional risk factors.Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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