Research Project
10247453
ABSTRACT Cardiovascular disease is the leading cause of mortality among women. Among symptomatic women presenting to coronary angiography, 40-65% have no obstructive coronary artery disease (CAD). Considered low risk, they often receive no specific therapy. Yet, evidence now documents that such women have higher than expected risk for major adverse cardiac events. The WARRIOR trial is a multicenter, prospective, randomized, blinded outcome evaluation evaluating intensive medical therapy (IMT) with aspirin, statin, angiotensin converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) vs. usual care (UC) in 4,422 women with ischemic symptoms and non- obstructive CAD. The hypothesis of WARRIOR is that IMT will reduce major adverse cardiac events including angina and hospitalization. We hypothesize that the beneficial effects of IMT may be due to changes in plaque composition and flow reserve related to endothelial and microvascular dysfunction rather than from reduction in stenosis severity. Coronary computed tomographic (CT) angiography (CTA) can identify high-risk plaque features associated with endothelial dysfunction and myocardial ischemia. Recent studies have shown that plaque inflammation inhibits adipocyte maturation in pericoronary artery adipose tissue (PCAT) and in turn increases the density of PCAT. Thus, quantitative CTA can potentially allow a comprehensive noninvasive evaluation of changes in plaque burden, coronary flow and plaque inflammation. We have developed validated software for quantitative characterization of plaque and PCAT density using CTA. In this ancillary substudy, we will recruit 400 patients from the WARRIOR trial with 200 patients from each of the treatment groups (IMT vs UC). From this cohort, 150 patients per treatment group, most compliant with WARRIOR protocol will undergo a CTA at the end of 3 years; with changes in plaque and PCAT characteristics quantified. We propose 3 aims: (1) To compare changes in coronary plaque characteristics and their hemodynamic significance using CTA in WARRIOR women treated with IMT vs UC; (2) To compare changes in plaque inflammation-related characteristics in PCAT in WARRIOR women treated with IMT with statin in combination with angiotensin converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) medications vs UC; (3) To relate plaque burden and plaque composition, CT flow reserve, and PCAT density changes to angina score (Seattle Angina Questionnaire [SAQ]) changes in IMT and UC-randomized WARRIOR women. Our study will be the first to quantify the impact of IMT on plaque composition and inflammation and its relation to clinical improvement in women with ischemic symptoms and nonobstructive CAD.
