Biomarkers of obesity and subsequent cardiovascular events

Abstract

Obesity is a major risk factor for cardiovascular diseases, but the mechanisms for increased cardiovascular risk in obesity are still unclear. Inflammation and increased oxidative stress are two potential mechanisms proposed to play a major role in the morbidity associated with obesity. Studies that investigate these mechanisms rely on biomarkers, but validated biomarkers for obesity-related cardiovascular outcomes are lacking. By finding optimal biomarkers, diagnostic criteria for cardiovascular diseases can be refined in the obese beyond "traditional" risk factors to identify early pathologic processes. The objective of this review is to identify potential early biomarkers resulting from obesity and associated with cardiovascular disease. Studies were initially identified through the search engine PubMed by using the keywords "obesity" and "biomarker." Subsequently, combinations of the keywords "obesity," "biomarker," "cardiovascular risk," "adipose tissue," "adipokine," "adipocytokine," and "oxidative stress" were used. The SOURCE database and Online Mendelian Inheritance in Man (OMIM) were used to obtain more information on the biomarkers. Results of the searches yielded a large number of potential biomarkers that occur in obesity and which either correlate with traditional cardiovascular risk factors or predict subsequent cardiovascular events. Several biomarkers are promising regarding their biologic properties, but they require further validation in humans.

FIGURE 1

A proposed schematic for the development of biomarkers that result early in the course of obesity and that may act as risk factors for cardiovascular outcomes. Genetic and environmental factors may interact to alter expression of biomarkers from adipose tissue. Fat deposition is accompanied by increased biomarkers for inflammation and oxidative stress, which can in turn impact adipose tissue function. The biomarkers interact with traditional risk factors that may develop later, leading to cardiovascular disease manifestations. ACE, angiotensin-converting enzyme; ADRP, adipocyte differentiation-related protein; CRP, C-reactive protein; C3, complement factor 3; F₂ IsoPs, F₂ isoprostanes; GPx, glutathione peroxidase; HDL, high density lipoprotein; IL-6, interleukin 6; IL-18, interleukin 18; LDL, low density lipoprotein; MCP-1, monocyte chemoattractant protein 1; oxLDL, oxidized low density lipoprotein; PAI-1, plasminogen activator inhibitor 1; PPAR-γ, peroxisome proliferator-activated receptor gamma; TNF-α, tumor necrosis factor alpha; VCAM, vascular cell adhesion molecule.