Adiposity, Body Fat Distribution and CHD, Stroke, Diabetes

Study Questions:

What is the relative strength of the associations of central adiposity (waist:hip ratio adjusted for body mass index [WHRadjBMI]) and general adiposity (BMI) with cardiometabolic disease?

Methods:

To avoid error and measurement bias for waist and hip measures and owing to benefits of Mendelian randomization (MR) to minimize residual confounding by common lifestyle factors and underlying ill-health, the authors conducted within-study genetic association analysis with adiposity (standardized BMI and WHRadjBMI) as a continuous trait using an additive model. Available single nucleotide polymorphisms (SNPs) for BMI and WHRadjBMI were used to conduct MR analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (combined total 66,842 cases), stroke from METASTROKE (12,389 ischemic stroke cases), type 2 diabetes (T2D) from DIAGRAM (34,840 cases), and lipids from GLGC (213,500 participants) consortia. Primary outcomes were CHD, T2D, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits.

Results:

Each one standard deviation (SD) higher WHRadjBMI (1 SD ~0.08 units) was associated with a 48% excess risk of CHD (odds ratio [OR] for CHD, 1.48), similar to findings for BMI (1 SD ~4.6 kg/m2; OR for CHD, 1.36). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32). For T2D, both measures had large effects: OR, 1.82 and OR, 1.98 per 1 SD higher WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycemic traits, interleukin-6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95% confidence interval, 9%-77% per 1 SD).

Conclusions:

Both general and central adiposity have causal effects on CHD and T2D. Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity.

Perspective:

Over the past several years, clinicians have been encouraged to use waist and waist:hip as indicators of visceral obesity rather than BMI. This study confirms the import of both. In our center, we stopped measuring waist and waist/hip for routine clinical purposes because of lack of reproducibility when taken by medical assistants. Experienced exercise physiologists measure waist when metabolic syndrome is a consideration.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism

Keywords: Adiposity, Body Mass Index, Coronary Artery Disease, Diabetes Mellitus, Type 2, Hypertrophy, Left Ventricular, Interleukin-6, Life Style, Lipids, Metabolic Syndrome X, Obesity, Primary Prevention, Stroke, Waist-Hip Ratio


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