Epidemiology of palsma lipids and the metabolic syndrome in multi-ethnic population

Abstract

Cardiovascular disease (CVD) imposes a significant burden in terms of morbidity and mortality in developed countries. Asia is likely to see an increase in the burden of these diseases in the next several decades. In developed countries, most CVD relate to atherosclerosis. Atheroscleorsis is a complex, multifactorial disorder. As such, multiple risk factors contribute to the pathogenesis of CVD. It has been observed that some cardiovascular risk factors, particularly obesity, glucose intolerance, hypertension and dyslipidemia, occur in the same individual more often than can be expected by chance. This cluster of abnormalities has become known as the metabolic syndrome. While the pathogenesis of the metabolic syndrome, and its link to obesity, insulin resistance is an important part of it.

Through the studies described in this thesis, we have shown that the metabolic syndrome is common, and is associated with a 2-3 fold increase in the risk of CVD in the Singapore population. Over half of the CVD events occurring in our population are attributable to the metabolic syndrome. We further show that the metabolic syndrome is not always associated with the presence of central obesity, even when defined using lower cut-points designed for use in Asian populations. Nevertheless, even in the absence of central obesity, individuals with multiple metabolic risk factors are insulin resistant, and experience a greater risk of CVD. To better understand the pathogenesis of the metabolic syndrome, we carried out a study to determine whether a biochemical signature of disordered protein metabolism, first identified in obese individuals, was independently associated with insulin resistance. We found that this signature of increased branch chain amino acid catabolism was indeed associated with insulin resistance independent of obesity. Through a genetic association study, we also found that polymorphisms at the APOA1/C3/A4/A5 locus were important risk factors for dyslipidemia (of the sort associated with the metabolic syndrome). We describe a novel interaction between a polymorphism at the APOA5 locus and plasma triglycerides, which may contribute to the development of hypertriglyceridemia at relatively low levels of obesity.