“Metabolic Syndrome” (MetS), refers to the clustering of abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, diminished high density lipoprotein (HDL) cholesterol, and/or hypertension in an individual. MetS is consistently associated with high Cardio-Vascular event risk and high incidence of Type 2 Diabetes mellitus. Each component of the MetS is an independent risk factor for cardiovascular disease and together enhances and compounds the atherosclerotic risk in the individual. However, this complex disorder is not well understood and it is important to explain the increased CV risk.
It is now known that Central/Visceral Obesity with its Insulin Resistance and or Hyperinsulinemia is central in the pathogenesis of MetS. However, insulin resistance is not considered to be part of the definition in MetS. It is the pathophysiologic aspects of obesity coupled with MetS that leads to changes in hemodynamics, atherosclerosis and calcification, myocardial metabolism, microvascular dysfunction that culminates in myocardial infarction and heart failure. The rising body weight from increasing adipose tissue mass results in significant neuro-hormonal changes and maladaptations in the cardiovascular system. This includes the activation of the renin-angiotensin-aldosterone system, abnormal elevations in adipocytokines, and the pro-inflammatory cytokines, that causes the sympathetic nervous system to activate. A persistent sympathetic nervous system activation typically leads to an increase in the resting heart rate, circulating blood volume, cardiac output, renal sodium retention, ventricular end-diastolic volume (pre-load), and/or blood pressure. The metabolic counterpart is excess lipolysis driving fatty acid levels, cathecholamine-induced peripheral, hepatic insulin resistance and fatty liver disease.
Obesity-related changes in cardiac structure and function have been referred to as the ‘cardiomyopathy of obesity. The molecular mechanisms underlying this obesity-induced cardiac phenotype disorder are not well understood. Abnormalities in intracellular Ca2+ handling due to sub-cellular/receptor level dysfunction are implicated. Also, the microvascular tone and microvascular density are significantly impacted by obesity. The alterations in micro-vasculature perpetuates chronic myocardial ischemia and progressive myocyte loss and contractile dysfunction leading to heart failure. Micro-vascular dysfunction in obese subjects has been noticed in other vascular territories as well.
The myocardium is capable of sustained function using fuels not limited to acetate, glucose or long-chain fatty acids – it is indeed a metabolic omnivore. In health the heart preferentially consumes fatty acids generating the most energy per unit of fuel consumed. Abnormalities in myocardial fuel substrate selection in obesity have been noted. In obesity, the myocardium abnormally utilises fatty acids and shows an impaired ability to shift away from this increased fatty acid utilization. This preferential lipid fuel usage and associated hyperglycemia with insulin resistance lead to a combined Gluco-lipotoxicity and higher free radical generation mediated cardiac injury leading to heart failure as a final sequel in obesity. Even a modest increase in body weight may lead to a rather significant increase in the prevalence of cardiovascular morbidity and mortality. These pathogenetic models are depicted in Fig:1
Fig:1 Schematic diagram of the pathologic features, adverse molecular and systemic changes, and cardiovascular consequences of the metabolic syndrome1
Unhealthy diets leading to an excessive calorie intake coupled with sedentary lifestyles are the most common causes of obesity and excess weight. It must be noted that even a modest rise in body weight can cause a significant rise in the rate of cardiovascular morbidity and mortality. A metanalysis review of MetS indicated an increased risk of cardiovascular-related adverse events among patients with CVD, especially among those with low HDL-C and FPG>100 mg/dl2.
This understanding of the enhanced high risk of CVD morbidity and mortality among subjects with MetS strongly underlines the need for implementation of positive measures to strengthen the prevention and treatment of hyperglycemia and hyperlipidemia through consistent therapeutic lifestyle measures and other cardiac friendly therapies aiming to address the dysglycemia and dyslipidemia.
References:
Dr. Manoj Sivaramakrishnan Senior Consultant & Interventional Cardiologist Kauvery Hospital Chennai
