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Metabolic Syndrome and its Impact on Cardiovascular Diseases

Abstract

Nilesh Kumar J Patel, Sushruth Edla, Sohil Golwala, Deepak Asti, Nilay Patel, Achint Patel, Nikhil Nalluri, Shantanu Solanki, Shilp Kumar Arora, Hafiz Khan, Ritesh Kanotra, Pandya Bhavi, Abhishek Deshmukh, Apurva O Badheka, James Lafferty and Jeffrey Rothman

Over the past decade, metabolic syndrome has gained recognition as a significant contributor to cardiovascular mortality. Isolated metabolic syndrome, without diabetes mellitus, plays an increasingly essential role in the pathogenesis of Coronary Artery Disease (CAD). The risk factors for metabolic syndrome act synergistically to promote the development of Cardiovascular Disease (CVD); the more the risk factors, the higher the likelihood of developing CVD. Among these risk factors, obesity is the biggest culprit as it leads to an increase in the levels of free fatty acids (FFAs), thereby resulting in insulin resistance. This, in turn, causes impaired intracellular glucose metabolism and consequent production of free radicals that reduce nitrous oxide levels and cause endothelial dysfunction, leading to atherosclerosis. Also, visceral fat, being a source of C-reactive protein, indirectly promotes inflammation and atherosclerosis. However, in certain races, insulin resistance is fairly common, even in non-obese individuals. This implies the possibilities of multiple complex mechanisms at the microcellular level, causing insulin resistance over and above the aforementioned mechanisms occurring due to obesity. In spite of this fact, control of obesity still remains the first line of defense against metabolic syndrome and resulting cardiovascular mortality. Measures like proper diet and physical exercise, and medications such as statins, fibrates, niacin, and ACE inhibitors are the cornerstones of management of metabolic syndrome. Additionally, clinical trials using medications affecting peroxisome proliferator-activated receptors (PPARs) and intestinal enteropeptidases have shown promising results for treatment of metabolic syndrome. Moreover, current research is also focused on the role of adipokines, semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1), 5-HT2c receptors, and the LKB1/AMPK pathway in influencing the mechanisms of insulin resistance. In the near future, newly discovered mechanisms and highly potent novel drugs may reduce the prevalence of metabolic syndrome and subsequent cardiovascular mortality.

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