Project Objectives

1) To achieve conceptual and methodological advancements in the examination of gender and sex determinants of the etiology, presentation, processes of care (diagnosis/treatment), and outcomes of CVD through A) creation of a team of basic science, clinical epidemiological and health services researchers, and B) the performance of 5 pilot projects with the following objectives:

Project 1 To identify candidate genes that are determinants of obesity in men and women.
Project 2 To identify behavioral and environmental determinants of obesity in boys and girls.
Project 3 To identify different prodromal symptoms in men and women that may predict outcome post-acute myocardial infarction (AMI).
Project 4 To compare the outcomes of men and women with coronary artery stenosis of <50%.
Project 5 To compare the effectiveness of cardiac drugs post-AMI in men and women.

2) To promote intra- and inter-institutional networking, collaboration and mentoring among Canadian researchers through collaborative work on the 5 proposed projects.

3) To provide full salary support for two PhD and/or Post-Doctoral students, and one young investigator.

4) To build capacity for knowledge translation by integrating routine knowledge translation plans into ICE team activities that are targeted towards key stakeholders (government policy makers, public health officers, clinicians).

5) To better position the team to successfully access CIHR open competition funds through pilot funding that will culminate in the formulation of large scale project (a cohort and a trial) proposals at the end of the 3-year research program.

To explain the differences in CVD between men and women, we propose a new conceptual framework centered around the following equation: "sex" + "gender" -> CVD, where the "sex" determinants are biological and genetic factors, and "gender" determinants are behavioral and environmental factors. Each stage of the disease process may develop, manifest and respond differently in men and women.

We hypothesize that 1) Genes with a different impact on the cardiovascular system in men and women can be identified by total genome scan analysis; 2) there are differences in the behavioral and environmental determinants of excess weight gain in girls and boys; 3) different prodromal symptoms for AMI predict future CVD events in women and men; 4) women presenting for coronary angiography are more likely than men to have less than 50% stenosis in all epicardial vessels and women with this level of stenosis are at increased risk of hospitalization for cardiac causes compared with men; 5) the use of and response to evidence-based cardiac medications is different between men and women with AMI.

The first step of the proposed research program has a 3-year timeline. In year 1, young investigators and students will be recruited. At the end of the first year, investigators and students will present analyses plans and preliminary results. At the end of the second year, they will present their results and propose small operating grants. The third year will focus on knowledge translation and planning the key elements of several large scale projects, including a Canadian cohort study and a randomized controlled trial enrolling only women. The second step of the research program has 2-year timeline. The funding for those additional years will be devoted to enhanced knowledge translation activities, for feasibility studies of two large projects which will be submitted for funding in year 3 and for the recurrent costs mostly related to personnel. The feasibility studies will be useful in that when funding is obtained for the large multicenter studies, the pilot studies will already have been conducted.