Coronary artery disease (CAD) is the principal basis of morbidity and mortality worldwide, and more than half of individuals experiencing acute myocardial infarction (AMI) have no premonitory symptoms. The prognosis for women with AMI is worse than for men, with higher case fatality rates and greater morbidity and mortality in the post-AMI period. Limited invasive and autopsy studies have identified gender-specific differences in coronary atherosclerotic plaque features at the time of presentation of AMI. To date, no study has examined (a) gender differences in atherosclerotic plaque characteristics (APCs) for individuals before AMI occurrence and (b) whether APC assessment can improve stratification of women and men who present with stable CAD but are at risk for future unheralded AMI. Coronary CT angiography (CT) is a non-invasive test that permits diagnosis of coronary stenosis with high diagnostic accuracy in women and men, as well as evaluation of atherosclerotic plaque and coronary arterial wall features. We have recently developed the prospective multicenter international CONFIRM observational cohort study of 32,308 carefully followed patients undergoing CT with comprehensive CAD risk factor, image finding, and CAD event ascertainment. We propose to use this rich resource to elucidate the gender-specific prognostic significance of coronary artery plaque characteristics beyond angiographic coronary stenosis for the non-invasive identification of coronary lesions that will be implicated in future AMI. The OVERALL HYPOTHESIS of the present proposal is that APCs quantified by CT will enhance gender- specific identification of coronary plaques that will cause future AMI. To examine this, we have assembled an unparalleled team of leading researchers in CAD, CT, women's health, outcomes research, and epidemiology. We describe a study protocol that is a logical and natural extension of our prior work with 3 specific aims:
AIM 1 : To identify the atherosclerotic features of coronary plaques that will be subsequently implicated in future AMI.
AIM 2 : To compare gender-specific differences in coronary plaques for women versus men who will subsequently experience future AMI.
AIM 3 : To determine the gender-specific risk of coronary atherosclerotic plaque characteristics that prognosticates AMI. If successful, the work in this proposal will provide the rationale for a novel diagnostic and potentially therapeutic paradigm that not only precisely identifies women and men who are at risk for future AMI, but also the gender-specific coronary lesions implicated as the cause.

Public Health Relevance

For women and men who are at risk of developing heart attacks, the study of patients with coronary artery disease (CAD) has traditionally been focused on severity of blockages, rather than coronary plaque characteristics, or the makeup of blockages in heart arteries. Computed tomography (CT) scans of the heart now allow for non-invasive evaluation of coronary plaque characteristics. This study will evaluate the specific makeup of coronary plaque by gender and determine its relationship to risk of future heart attacks, which may redefine the diagnostic approach to women and men with suspected CAD.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Fleg, Jerome
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Weill Medical College of Cornell University
Schools of Medicine
New York
United States
Zip Code
Baskaran, Lohendran; Ó Hartaigh, Bríain; Schulman-Marcus, Joshua et al. (2017) Dense calcium and lesion-specific ischemia: A comparison of CCTA with fractional flow reserve. Atherosclerosis 260:163-168
Han, Donghee; Hartaigh, Bríain Ó; Gransar, Heidi et al. (2017) Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals. Eur Heart J Cardiovasc Imaging :
Cho, Iksung; Ó Hartaigh, Bríain; Gransar, Heidi et al. (2017) Prognostic implications of coronary artery calcium in the absence of coronary artery luminal narrowing. Atherosclerosis 262:185-190
Ó Hartaigh, Bríain; Gransar, Heidi; Callister, Tracy et al. (2017) Development and Validation of a Simple-to-Use Nomogram for Predicting 5-, 10-, and 15-Year Survival in Asymptomatic Adults Undergoing Coronary Artery Calcium Scoring. JACC Cardiovasc Imaging :
Rizvi, Asim; Hartaigh, Bríain Ó; Danad, Ibrahim et al. (2017) Diffuse coronary artery disease among other atherosclerotic plaque characteristics by coronary computed tomography angiography for predicting coronary vessel-specific ischemia by fractional flow reserve. Atherosclerosis 258:145-151
Lee, Ji Hyun; Han, Donghee; Danad, Ibrahim et al. (2016) Multimodality Imaging in Coronary Artery Disease: Focus on Computed Tomography. J Cardiovasc Ultrasound 24:7-17
Shalev, Aryeh; Nakazato, Ryo; Arsanjani, Reza et al. (2016) SYNTAX Score Derived From Coronary CT Angiography for Prediction of Complex Percutaneous Coronary Interventions. Acad Radiol 23:1384-1392
Han, Donghee; Lee, Ji Hyun; Hartaigh, Bríain Ó et al. (2016) Role of computed tomography screening for detection of coronary artery disease. Clin Imaging 40:307-10
Baldassarre, Lauren A; Raman, Subha V; Min, James K et al. (2016) Noninvasive Imaging to Evaluate Women With Stable Ischemic Heart Disease. JACC Cardiovasc Imaging 9:421-35
Valenti, Valentina; Hartaigh, Bríain Ó; Cho, Iksung et al. (2016) Absence of Coronary Artery Calcium Identifies Asymptomatic Diabetic Individuals at Low Near-Term But Not Long-Term Risk of Mortality: A 15-Year Follow-Up Study of 9715 Patients. Circ Cardiovasc Imaging 9:e003528

Showing the most recent 10 out of 46 publications