Ellie J. Coromilas M.D. Columbia University, New York
Natalie A. Bello M.D. Columbia University Medical Center, New York
The Rising Burden of Obesity Has Important Implications for Cardiovascular Morbidity and Mortality
The prevalence of obesity has been increasing globally over the past several decades; in the United States more than one-third of adults are considered obese, and an additional one-third are overweight.1,2 This rising burden of obesity has important implications for cardiovascular morbidity and mortality, as obesity has been identified as a major risk factor for hypertension and coronary heart disease.3,4 Obesity has also been linked with changes in cardiac morphology that collectively play a critical role in the development of heart failure in this population.5-8 In 2005 the American Heart Association and American College of Cardiology issued updated guidelines for the diagnosis and treatment of heart failure, and for the first time described heart failure as a continuum.9 In this new framework, individuals with obesity are classified as Stage A “at high risk for HF [heart failure] but without structural heart disease or symptoms.” Stage B occurs when individuals develop structural heart disease but are not yet symptomatic, a recognition that changes in cardiac morphology collectively play a critical role in the development of heart failure.3,5-8 Understanding how obesity leads to alterations in cardiac structure and function en route to symptomatic heart failure, Stages C and D, is important for the development of lifestyle and pharmacologic interventions targeting this modifiable risk factor.
There is also a growing awareness of the importance of understanding gender differences in the development of cardiovascular disease, as men and women often manifest different signs and symptoms of cardiovascular illness. The role of the hormonal environment and how body composition mediates the mechanism, timing, and prominence of physiologic adaptations to obesity must be considered to understand the implications of the obese state fully, and to develop and apply preventative and therapeutic measures effectively. This review discusses the impact of obesity on cardiac structure and function as well as the different patterns of cardiac remodeling that occur in men and women.
The prevalence of obesity has been increasing globally, with important implications for cardiovascular morbidity and mortality. Obesity is linked to changes in cardiac morphology that collectively play a role in the development of heart failure in this population, as hemodynamic and metabolic alterations lead to cardiac hypertrophy and chamber enlargement. Over time subclinical abnormalities in contractile function occur and could progress to overt clinical heart failure. Understanding the relationship between obesity and alterations in cardiac structure and function has important implications for the development of lifestyle and pharmacologic interventions targeting this modifiable risk factor. There is also a growing awareness of the importance of understanding gender differences in obesity. Gender-specific patterns of adiposity and fat distribution in addition to the distinctive hormonal environments of men and women may lead to sex-specific differences in the degree of cardiometabolic risk associated with obesity. Imaging studies have shown that ventricular remodeling in response to obesity differs among the sexes, and these differences may play a role in the female predominance of heart failure with a preserved ejection fraction.
Association Between Obesity and Maladaptive Cardiac Remodeling
Cardiac remodeling is the process by which alterations in ventricular architecture, including changes in cavity size and wall thickness, occur. Classically described following a myocardial infarction, remodeling has subsequently been described in response to a variety of forms of myocardial injury and increased wall stress.10,11 As it shifts from normal geometry, the left ventricular (LV) adaptive response can be classified in 1 of 3 patterns: (1) concentric remodeling (increased relative wall thickness with normal LV mass index); (2) eccentric hypertrophy (normal relative wall thickness with an increased LV mass index); or (3) concentric hypertrophy (increased relative wall thickness and LV mass index).12,13
Many studies have shown that obesity is independently associated with the development of LV remodeling and hypertrophy, and abnormal LV geometry is associated with increased morbidity and mortality.12-14 This pathologic thickening of cardiac muscle is likely multifactorial in the setting of direct fatty infiltration of the myocardium, hemodynamic alterations associated with obesity, and the metabolic effects of elevated leptin and insulin.15-17
Regarding hemodynamic alterations, eccentric hypertrophy has classically been described in individuals with obesity; adiposity leads to increased circulating blood volume due to alterations in salt retention and activation of the renin–angiotensin–aldosterone system, ultimately resulting in increased cardiac output, wall stress, and dilatation.17-19 However, recent large studies have demonstrated that obesity is associated with a predominance of concentric hypertrophy with increased wall thickness relative to the chamber size.8,14,20-22 Although some studies have suggested that the development of concentric hypertrophy is related to coexisting hypertension, others have suggested that an independent portion of this geometric change is likely attributable to body composition rather than to blood pressure.8,13 In an attempt to harmonize the different patterns of remodeling that have been described, it seems likely that the LV remodeling that occurs as a result of obesity is initially concentric in nature. As the obese state becomes chronic, persistent volume and pressure overload lead to further chamber enlargement and LV hypertrophy, with both eccentric and concentric hypertrophy occurring.
In addition to the hemodynamic changes seen in obesity, metabolic stimuli also affect cardiac remodeling and function. Increased levels of leptin, an adipokine secreted by adipose tissue, can both induce hypertrophy and attenuate systolic contraction, and have also been implicated in cardiac interstitial fibrosis and early diastolic dysfunction.15,17,23 Leptin has also been associated with upregulation of the renin–angiotensin–aldosterone system that might contribute to the sodium retention and blood volume expansion seen in obesity.24 Because many obese individuals have comorbid metabolic syndrome, hyperinsulinemia can contribute to cardiomyocyte hypertrophy through the growth factor effect of insulin.25 Additionally insulin may increase sodium retention through direct interactions with renal tubules and with arteriolar vasoconstriction, contributing to volume expansion and comorbid hypertension.17
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Gender and the Genome, published by Mary Ann Liebert, Inc., a peer-reviewed journal, explores how the new science of the 21st century is profoundly influenced by biological sex. The above article was first published in the June 1, 2017 issue of Gender and the Genome with the title “Gender Differences in Obesity-Associated Cardiac Remodeling”. The views expressed here are those of the authors and are not necessarily those of Gender and the Genome, Mary Ann Liebert, Inc., publishers, or their affiliates. No endorsement of any entity or technology is implied.