Cardiac remodeling in obesity

Abstract

The dramatic increase in the prevalence of obesity and its strong association with cardiovascular disease have resulted in unprecedented interest in understanding the effects of obesity on the cardiovascular system. A consistent, but puzzling clinical observation is that obesity confers an increased susceptibility to the development of cardiac disease, while at the same time affording protection against subsequent mortality (termed the obesity paradox). In this review we focus on evidence available from human and animal model studies and summarize the ways in which obesity can influence structure and function of the heart. We also review current hypotheses regarding mechanisms linking obesity and various aspects of cardiac remodeling. There is currently great interest in the role of adipokines, factors secreted from adipose tissue, and their role in the numerous cardiovascular complications of obesity. Here we focus on the role of leptin and the emerging promise of adiponectin as a cardioprotective agent. The challenge of understanding the association between obesity and heart failure is complicated by the multifaceted interplay between various hemodynamic, metabolic, and other physiological factors that ultimately impact the myocardium. Furthermore, the end result of obesity-associated changes in the myocardial structure and function may vary at distinct stages in the progression of remodeling, may depend on the individual pathophysiology of heart failure, and may even remain undetected for decades before clinical manifestation. Here we summarize our current knowledge of this complex yet intriguing topic.

Figures

FIG. 1

Cumulative incidence of heart failure according to category of body mass index at the baseline examination. The body mass index was 18.5–24.9 in normal subjects, 25.0–29.9 in overweight subjects, and 30.0 or more in obese subjects. The mean age at enrollment ranged between 53 and 60 years in the various categories. Interestingly, the curves for the three groups remain rather close together for almost 15 years in the men. Thereafter, overweight and obese men have significantly more heart failure. Given that the age when the curves begin to diverge is in the late 60s, this again raises the question of whether coronary disease might be a contributing factor. [From Kenchaiah et al. (174), copyright 2004 Massachusetts Medical Society. All rights reserved.]

FIG. 2

Cardiac magnetic resonance image showing epicardial fat (*) with the largest accumulation being seen anterior (A) to the right ventricle (RV). Fat appears white on this steady-state free precision imaging sequence, while myocardium is gray. Smaller amounts of fat are seen around the left ventricular (LV) free wall and in the atrioventricular groove. RA, right atrium; LA, left atrium; R, right; L, left; P, posterior. This example shows a “typical” amount of fat in an average-weight indivdual; however, the extent of epicardial fat varies widely from person to person and correlates better with the amount of visceral abdominal fat than with body mass index.

FIG. 3

Potential direct and indirect effects of adipokines on cardiac remodeling. Various circulating adipokines, the profile of which alters in obesity, may directly (solid lines) influence remodeling events known to occur in heart failure: hypertrophy, apoptosis, fibrosis, and metabolic alterations. Another potential mechanism whereby adipokines may influence cardiac structure and function is via indirect effects (broken lines) on parameters known to influence cardiac remodeling, such as hypertension, insulin resistance, and renal effects.

FIG. 4

Summary of potential mechanisms via which obesity can influence structure and function of the heart.