Abstract

Introduction: A family history (FH) of premature coronary artery disease (CAD) is an important prognostic risk factor. Emerging evidence suggests that CAD location as well as severity may be heritable. We sought to investigate the association between a FH of premature CAD with the location and severity of angiographically phenotyped CAD. Methods: 2854 patients undergoing coronary angiography were enrolled from the Emory Cardiovascular Biobank. A FH of CAD was defined as having any male or female relative with history of CAD at age ≤55 or ≤65 year old respectively. Coronary angiograms were phenotyped using a 17 segment AHA model. Proximal disease was defined as having ≥70% lesion in the left main or proximal portion of any of the three major epicardial arteries, while CAD severity was assessed by counting the number of vessels with ≥70% stenosis. Results: Among this population (mean age 63±12, male 67%, diabetes 33%), 21% reported a positive FH of premature CAD. After adjustment for age, gender, and traditional cardiovascular risk factors, those with a positive FH were more likely to have significant CAD than those without a positive FH (OR 1.3 (1.1-1.7)). They were 40% more likely to have single vessel (OR 1.4(1.1-1.7)) and up to 80% more likely to have multi-vessel disease (OR 1.8 (1.4-2.4)). In addition, they were also much more likely to have left main (OR 1.9 (1.3-2.8)) and proximal vessel involvement (OR 1.5 (1.2 - 1.9)), but not distal vessel stenosis (OR 1.1 (0.9-1.4)). Conclusions: A FH of CAD is associated with a greater likelihood of multi-vessel and proximal anatomical disease. Whether site specific disease is genetically mediated remains to be explored.

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