Obesity and Subtypes of Incident Cardiovascular Disease

Abstract

Background--Obesity is a risk factor for various subtypes of cardiovascular disease (CVD), including coronary heart disease (CHD), heart failure (HF), and stroke. Nevertheless, there are limited comparisons of the associations of obesity with each of these CVD subtypes, particularly regarding the extent to which they are unexplained by traditional CVD mediators.Methods and Results--We followed 13 730 participants in the Atherosclerosis Risk in Communities (ARIC) study who had a body mass index ≥18.5 and no CVD at baseline (visit 1, 1987-1989). We compared the association of higher body mass index with incident HF, CHD, and stroke before and after adjusting for traditional CVD mediators (including systolic blood pressure, diabetes mellitus, and lipid measures). Over a median follow-up of 23 years, there were 2235 HF events, 1653 CHD events, and 986 strokes. After adjustment for demographics, smoking, physical activity, and alcohol intake, higher body mass index had the strongest association with incident HF among CVD subtypes, with hazard ratios for severe obesity (body mass index ≥35 versus normal weight) of 3.74 (95% CI 3.24-4.31) for HF, 2.00 (95% CI 1.67-2.40) for CHD, and 1.75 (95% CI 1.40-2.20) for stroke (P<0.0001 for comparisons of HF versus CHD or stroke). Further adjustment for traditional mediators fully explained the association of higher body mass index with CHD and stroke but not with HF (hazard ratio 2.27, 95% CI 1.94-2.64).Conclusions--The link between obesity and HF was stronger than those for other CVD subtypes and was uniquely unexplained by traditional risk factors. Weight management is likely critical for optimal HF prevention, and nontraditional pathways linking obesity to HF need to be elucidated. ( J Am Heart Assoc. 2016;5:e003921 doi: 10.1161/JAHA.116.003921) Key Words: coronary heart disease • epidemiology • heart failure • obesity • stroke O besity is a common risk factor for several subtypes of cardiovascular disease (CVD), including coronary heart disease (CHD), stroke, and heart failure (HF) [1][2][3][4] ; however, increasing evidence suggests that obesity leads to various subtypes of CVD through multiple distinct pathways. Some traditional risk factors, including hypertension, diabetes mellitus, and dyslipidemia, are established as mediators between obesity and atherosclerotic vascular disease. Although weight management is a fundamental component of CVD prevention, the majority of persons with obesity in the general population do not achieve sufficient and sustained weight loss. [5][6][7][8] Consequently, there is great emphasis on controlling the traditional CVD risk factors resulting from obesity as a strategy for reducing cardiovascular risk. Nevertheless, uniform approaches to the control of cardiovascular risk factors may not have the same impact on the likelihood of developing different subtypes of CVD. In this context, data conflict regarding whether the relationships of obesity with CHD and stroke are independent of established CVD mediators. Several prospective studies [9]...

Associations of Obesity With Incident Hospitalization Related to Peripheral Artery Disease and Critical Limb Ischemia in the ARIC Study

“…Obesity, and specifically BMI, has been associated with increased risk of cardiovascular morbidity and mortality in prior studies 7, 17, 18. The strength of association, however, is not consistent across CVD phenotypes.…”

“…PAD‐related hospitalizations were identified according to the following International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD‐9‐CM ) codes based on the previous literature6, 7: atherosclerosis of native arteries of the extremities, unspecified (440.20); atherosclerosis of native arteries of the extremities with intermittent claudication (440.21); atherosclerosis of native arteries of the extremities with rest pain (440.22); atherosclerosis of native arteries of the extremities with ulceration (440.23); atherosclerosis of native arteries of the extremities with gangrene (440.24); other atherosclerosis of native arteries of the extremities (440.29); atherosclerosis of bypass graft of the extremities (440.3); atherosclerosis of other specified arteries (440.8); and leg artery revascularization (38.18, 39.25, 39.29, 39.50). Of these, 440.22, 440.23, and 440.24 were considered CLI.…”

“…Model 3 included all covariates from model 2 as well as potential mediators, including diabetes mellitus, total and HDL cholesterol, systolic blood pressure, antihypertensive medications, and estimated glomerular filtration rate. The covariates in both models 2 and 3 were chosen based on previously published work describing obesity‐related confounding variables and CVD mediators 7. To evaluate whether obesity measures have uniquely strong associations with PAD with CLI, we then compared the hazard ratios (HRs) for PAD without CLI from each model versus those for PAD with CLI using seemingly unrelated estimation that computes a simultaneous sandwich/robust covariance matrix for the 2 models 15.…”

“…Obesity has been shown to be a predictor of cardiovascular disease (CVD), including CHD, stroke, and heart failure, in a large number of previous cohort studies 6, 7, 8. Ndumele et al have also recently shown that the adjustment for obesity‐related risk factors such as diabetes mellitus, hypertension, and dyslipidemia considerably attenuates the association between obesity and CHD and stroke but not heart failure 7.…”

“…Ndumele et al have also recently shown that the adjustment for obesity‐related risk factors such as diabetes mellitus, hypertension, and dyslipidemia considerably attenuates the association between obesity and CHD and stroke but not heart failure 7. This relationship, however, has not been investigated for PAD.…”