Cardiovascular and Metabolic Heterogeneity of Obesity: Clinical Challenges and Implications for Management

Abstract

The prevalence of obesity has increased globally over the last 2 decades. Although the body mass index has been a convenient and simple index of obesity at the population level, studies have shown that obesity defined by body mass index alone is a remarkably heterogeneous condition with varying cardiovascular and metabolic manifestations across individuals. Adipose tissue is an exquisitely active metabolic organ engaged in cross-talk between various systems; perturbation of adipose tissue results in a pathological response to positive caloric balance in susceptible individuals that directly and indirectly contributes to cardiovascular and metabolic disease. Inadequate subcutaneous adipose tissue expansion in the face of dietary triglycerides leads to visceral and ectopic fat deposition, inflammatory/adipokine dysregulation, and insulin resistance. Conversely, preferential fat storage in the lower body depot may act as a metabolic buffer and protect other tissues from lipotoxicity caused by lipid overflow and ectopic fat. Translational, epidemiological, and clinical studies over the past 30 years have clearly demonstrated a strong link between visceral and ectopic fat and the development of a clinical syndrome characterized by atherogenic dyslipidemia, hyperinsulinemia/glucose intolerance, hypertension, atherosclerosis, and adverse cardiac remodeling/heart failure. This relationship is even more nuanced when clinical entities such as metabolically healthy obesity phenotype and the obesity paradox are considered. Although it is clear that the accumulation of visceral/ectopic fat is a major contributor to cardiovascular and metabolic risk above and beyond the body mass index, implementation of fat distribution assessment into clinical practice remains a challenge. Anthropometric indexes of obesity are easily implemented, but newer imaging-based methods offer improved sensitivity and specificity for measuring specific depots. Lifestyle, pharmacological, and surgical interventions allow a multidisciplinary approach to overweight/obesity that may improve outcomes and align with a public health message to combat the growing epidemic of obesity worldwide and to build healthier lives free of cardiovascular diseases.

Keywords: adiposity; cardiac imaging techniques; cardiovascular diseases; obesity; risk factors; waist circumference.

Figure 1. Extreme Variation in Abdominal Fat Distribution

T1-weighted coronal neck-to-knee magnetic resonance images demonstrating variation in visceral fat (shaded red) and abdominal subcutaneous fat (shaded blue) between two individuals with normal weight (left) and obesity (right). Images courtesy of Advanced MR Analytics (Linköping, Sweden)

Figure 2. Factors Associated with Increased Visceral Adiposity

Both modifiable and non-modifiable factors both contribute to and result from excess visceral adiposity and ectopic fat deposition

Figure 3. Mechanistic Model for Effects of Obesity on Cardiac Dysfunction and Heart Failure

Model for adiposity-related cardiac dysfunction integrates our understanding of body fat distribution into a potential etiologic pathway leading from obesity to heart failure. Excessive fat accumulation in visceral and ectopic sites result in increasing circulating blood volume and local and systemic pro-atherogenic inflammatory factors which act to increased stroke volume, cardiac wall stress, and myocardial injury leading to concentric left ventricular hypertrophy, left ventricular remodeling, and ultimately diastolic and systolic cardiac failure. Natriuretic peptides released by cardiomyocytes may exert differential effects on fat metabolism in a positive feedback loop modified by factors such as exercise, sex hormones, and insulin resistance. LBAT=lower body subcutaneous adipose tissue; VAT=visceral adipose tissue