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.

When a Friend Becomes Your Enemy: Natural Killer Cells in Atherosclerosis and Atherosclerosis-Associated Risk Factors

“…Palmitate, in HFD fed mice, can activate NLRP3 inflammasome in adipose tissue macrophages, increasing IL-1β and IL-18 secretion ( 148 ). Also, adipose tissue macrophages are polarized toward M1 phenotype and secrete inflammatory cytokines, such as IL-1β, IL-6, and TNF-α that, in turn, can recruit and stimulate NK cells ( 148 ).…”

The Beneficial Changes on Inflammatory and Endothelial Biomarkers Induced by Metabolic Surgery Decreases the Carotid Intima-Media Thickness in Men

“…Endothelium expresses adhesion molecules, such as ICAM and VCAM, which recruit inflammatory cells, including monocytes and lymphocytes, and can further propagate inflammation in the vessel wall. This eventually promotes the development of the atherosclerotic lesion by inducing a proliferation of vascular smooth muscle cells and the secretion of pro-coagulant factors such as PAI-1 [ 13 ]. Therefore, we hypothesized that the observed decrease in cIMT after metabolic surgery in men could be mainly associated with an improvement of inflammation and endothelial biomarkers.…”

“…Different mechanisms have been proposed to explain the link between obesity and atherogenesis, and both inflammation and insulin resistance play a well-recognized role in this process [ 11 , 12 ]. The endothelial surface expresses adhesion molecules, which recruit inflammatory cells propagating inflammation in the vessel wall and promoting the development of atherosclerotic plaque [ 13 ]. In patient candidates for metabolic surgery, pro-inflammatory and adiposity biomarkers have been shown to be associated with progressive subclinical atherogenesis measured by cIMT [ 14 ].…”

Approach to Patients with Obesity and Other Cardiovascular Risk Factors in Primary Care Using the Delphi Methodology

“…Obesity is associated with an increased risk of cardiovascular disease (CVD), particularly ischemic heart disease and heart failure, including atrial fibrillation, ventricular arrhythmias, and sudden death [ 10 ]. The increased risk of CVD, particularly atherosclerotic CVD, among people with obesity is largely mediated by established traditional risk factors, such as insulin resistance, type 2 diabetes mellitus, dyslipidemia, hypertension, and obstructive sleep apnea [ 11 ].…”