Obesity and Cardiovascular Disease: The Emerging Role of Inflammation

Abstract

Obesity is a growing public health challenge across the globe. It is associated with increased morbidity and mortality. Cardiovascular disease (CVD) is the leading cause of mortality for people with obesity. Current strategies to reduce CVD are largely focused on addressing traditional risk factors such as dyslipidemia, type 2 diabetes (T2D) and hypertension. Although this approach is proven to reduce CVD, substantial residual risk remains for people with obesity. This necessitates a better understanding of the etiology of CVD in people with obesity and alternate therapeutic approaches. Reducing inflammation may be one such strategy. A wealth of animal and human data indicates that obesity is associated with adipose tissue and systemic inflammation. Inflammation is a known contributor to CVD in humans and can be successfully targeted to reduce CVD. Here we will review the etiology and pathogenesis of inflammation in obesity associated metabolic disease as well as CVD. We will review to what extent these associations are causal based on human genetic studies and pharmacological studies. The available data suggests that anti-inflammatory treatments can be used to reduce CVD, but off-target effects such as increased infection have precluded its broad therapeutic application to date. The role of anti-inflammatory therapies in improving glycaemia and metabolic parameters is less established. A number of clinical trials are currently ongoing which are evaluating anti-inflammatory agents to lower CVD. These studies will further clarify whether anti-inflammatory agents can safely reduce CVD.

Keywords: athersclerosis; cardiovacsular disease(s); genetic pathway; inflammation; obesity.

Figure 1

Proposed mechanisms linking obesity, inflammation and cardiovascular disease. When adipose storage capacity is exceeded, increased lipid flux, and ectopic lipid in liver, skeletal muscle, and pancreas reduce insulin sensitivity and beta cell function. Compromised adipose storage is also associated with adipose and systemic inflammation, which can potentially potentiate atheroma development. Increased TRL and FFA, which are features of insulin resistance, may also increase inflammation and atheroma development. FFA, free fatty acids; IR, insulin resistance; TRL, triglyceride rich lipoproteins.