Cardiovascular consequences of obesity and targets for treatment

Abstract

Obesity is a risk factor for cardiovascular disease, including coronary artery disease and heart failure, but the mechanisms by which it may cause them are not completely clear. Currently, therapies aimed at obesity-related cardiovascular disease include weight loss strategies and reduction of the other risk factors that are associated with obesity and cardiovascular disease. Other pathways with for potential drug development for obesity-related CVD are also discussed. Keywordsobesity; myocardium; metabolism; systolic function; diastolic function; coronary artery disease Cardiovascular disease (CVD) is still the leading cause of death in developed countries, despite a recent decline in coronary artery disease-related deaths. In the United States approximately 35% of all deaths are due to CVD [1]. Obesity (defined as a body mass index [BMI] of ≥ 30 kg/m 2 ) is a risk factor for CVD, especially coronary heart disease and heart failure. It is estimated that the relative risk of coronary heart disease in obesity is approximately 1.5 even after adjusting for all other traditional coronary heart disease risk factors that often co-migrate with obesity (e.g. hyperlipidemia, hypertension) [2]. Obesity also is associated with an increased risk of heart failure, with ~11 -14% of all heart failure thought to be attributable to obesity [3]. Given that excess body weight now affects more than 300 million persons worldwide, prevention and treatment of obesity should be considered one of the cornerstones for the prevention of CVD (http://www.who.int/dietphysicalactivity/publications/facts/obesity/en/). This review will focus on the impact of obesity on CVD, particularly atherosclerotic coronary artery disease and heart failure and treatment of obesity-related heart disease.

Treatment with low-dose resveratrol reverses cardiac impairment in obese prone but not in obese resistant rats

“…In fact, heart failure is one of the major causes of death in obese individuals [4]. Obesity induces diastolic heart failure [5], with many cellular and molecular changes triggering the onset of this pathology. Lipotoxicity [6], adipose tissue dysfunction [7] and increased release of adipokines such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) are factors that favor the development of cardiovascular diseases [8].…”

The Risk of Heart Failure and Cardiometabolic Complications in Obesity May Be Masked by an Apparent Healthy Status of Normal Blood Glucose

“…Cardiac complications including heart failure are among the major causes of mortality in obese individuals. Obesity causes lipotoxicity and adipose tissue dysfunction with excessive production of adipokines like tumor necrosis factor- α (TNF- α ) and interleukin 6 (IL-6) IL-1 β , all of which are implicated in heart failure and related cardiometabolic complications [ 4 , 5 ]. However, obesity may not always translate into increased risk for these comorbidities [ 6 ].…”

Trimetazidine Reduces Endogenous Free Fatty Acid Oxidation and Improves Myocardial Efficiency in Obese Humans

“…Obesity is an independent predictor of heart failure [4,5]. There is compelling evidence that myocardial metabolic toxicity due to obesity and insulin resistance is implicated in the pathogenesis of the related cardiac complications [6]. We and others have recently documented the occurrence of cardiac steatosis in obese and type 2 diabetic patients, correlating with cardiac dimensions and function [7,8].…”