Title: Impact of Multiple Risk Factors and Preventive Interventions on Cardiovascular Diseases and Disparities
Description: Major cardiovascular risk factors have changed over the past 3-4 decades throughout the world. While adiposity and diabetes are rising worldwide, blood pressure and cholesterol are declining in high-income and even some middle-income countries, possibly due to improvements in diet or better diagnosis and treatment; the same risk factors have remained unchanged or even increased in low-income countries. To formulate effective prevention and health system policies, there is need to understand the implications of these diverse trends for cardiovascular diseases (CVDs).

This dissertation focuses on quantifying the impact of multiple risk factors and preventive interventions on CVDs and their disparities at the population level. Answering this question requires information on how much of the effects of adiposity on CVDs are mediated through other metabolic risk factors (i.e. high blood pressure, high serum cholesterol and high blood glucose), which themselves have other determinants. The first paper quantifies the direct as well as the mediated effects of excess weight on coronary heart disease (CHD) and stroke through blood pressure, serum cholesterol and blood glucose. The analyses use data of 97 prospective cohorts with more than 1.8 million participants. This allows for assessing whether the extent of mediation is modified by geographical region, study period, and other characteristics of study populations. The second paper revisits the above question using causal inference models and further quantifies the role of inflammatory markers as potential mediators. The analyses use individual-level data from 9 prospective cohort studies that have high-quality measurements of metabolic and inflammatory biomarkers. The third paper uses national data sources in the United States (US) and estimates the distributions of 10-year risk of fatal CHD by race. It also assesses the effects of different population-wide and targeted interventions on CHD risk distributions and their disparities between blacks and whites.

Our findings suggest that nearly half of excess risk for CHD and three-quarters of excess risk for stroke due to excess weight were mediated through three metabolic risk factors: blood pressure, cholesterol, and glucose. Inflammatory biomarkers had much smaller roles than the combination of metabolic risk factors. In the US, the distribution of 10-year CHD risk was shifted to the right among blacks compared to whites and had a heavier tail, leading to a substantially larger proportion of blacks in the high-risk group. A risk-based intervention that identifies and treats these individuals could substantially reduce both the overall risk of CHD and its racial disparities. These results together provide the quantitative evidence on the impact of cardiovascular risk factors and selected interventions on CVDs and their disparities.