Grant: CIHR Fellowship

Cardiovascular disease (CVD) is a major cause of death and disability in North America and is known to be caused by both genetic and dietary factors. Because low levels of antioxidants in the blood have been shown to increase the risk of CVD, many studies of CVD and dietary antioxidants, such as vitamins A, C and E, have been conducted, but the results have been mixed. Our previous research suggests that this inconsistency may be due to genetic differences in the subjects studied that lead some people to have higher levels of antioxidants in their blood after consuming antioxidants than others. We will expand this research to find out whether these genetic differences in response to dietary antioxidants can predict the risk of CVD events such as heart attacks. Recent technologies have made it possible to examine the whole genome of subjects, and so it is timely to conduct a thorough analysis of genetic predictors of CVD and examine how their combined influence can enhance the prediction of CVD risk by dietary and conventional risk factors. The Nurses' Health Study (NHS) of women and the Health Professionals Follow-up Study (HPFS) of men are among the largest and longest running (>20 years) health investigations, and have produced landmark data on CVD, showing that diet, physical activity and other lifestyle factors can powerfully promote better health. Now that genome-wide data is available for 1000 NHS and HPFS subjects who have had a heart attack and 2000 controls who have not, we plan to combine the genetic, dietary, lifestyle and other risk factors to create a CVD risk predictor score that will be more useful in predicting heart attacks than any single risk factor alone. This research will also help to determine the optimal dietary recommendations of antioxidants for preventing CVD in individuals and populations, enable future studies of antioxidants to be more consistent, and provide a template for creating predictor scores for other complex diseases.