Mechanisms of HDL Lowering in South Asians

People of South Asian descent (from India, Pakistan, Bangladesh and Nepal) are at very high risk of developing cardiovascular diseases (CVD), such as heart attacks and stroke, at an early age. This risk becomes worse as South Asians become obese and this trend is expected to increase the economic and social burden of CVD in Canada in the near future. A major reason for the high CVD risk in South Asians is that they have the lowest blood levels of particles carrying the "good cholesterol" of any global population group studied. These particles are known as HDL particles and their HDL-cholesterol levels decrease with increasing body fatness. The cause(s) of the low HDL levels in South Asians have not previously been determined. We have preliminary evidence that South Asians have high activity levels (compared with individuals of European white descent) of an important blood protein involved in changing the chemical properties of HDL particles. This protein is called cholesteryl ester transfer protein (CETP). CETP adds fat to HDL particles in the blood, which makes the HDL particles unstable in blood and cleared away faster from the body, thereby lowering blood HDL levels. The purpose of this application is to test whether increased blood CETP levels in South Asians is the cause of their low HDL levels, because if it is correct, therapies aimed at inhibiting CETP should be particularly effective in raising HDL levels and reducing CVD risk in South Asians. This should then help in reducing the high economic and social burden of treating CVD in the health care system.