Pathologically Different than Coronary Artery Disease, Myocardial Infarction has a Minimal Heritable Component. B. Horne1,2, S. Knight1,2 1) Intermountain Heart Institute, Intermountain Medical Center, Salt Lake City, UT; 2) Genetic Epidemiology Division, Department of Medicine, University of Utah, Salt Lake City, UT.

   Background: Coronary artery disease (CAD) and its features, including lesion location and morphology, are heritable and dozens of loci for CAD have been validated. In contrast, only one myocardial infarction (MI) locus has been validated among MI cases and non-MI CAD controls (the ABO gene). MI occurs among patients with mild CAD and severe CAD at a similar rate. No study has tested whether MI is heritable independent of its required atherosclerotic substrate. This study evaluated whether MI is familial among patients with mild CAD and with clinically-significant 3-vessel CAD. Methods: The Intermountain Genealogy Registry includes >23 million individuals within extended family pedigrees, which includes ~700,000 patients seen since 1994 who have linked clinical data in the Intermountain Healthcare data warehouse. A genealogical index of familiality (GIF: 10,000 times the average pairwise kinship coefficient) was calculated for MI and CAD cases who had at least 3 generations and 12 ancestors in their pedigree (and for all patients in the registry as a control GIF). MI subjects were studied if they had only 1-vessel CAD (70% stenosis) or mild CAD (20-60% stenosis) with (I) MI when younger (n=194, females aged70 years, males65 years) or (II) MI at any age (n=489), or if they had 3-vessel CAD (70% stenosis) with (III) MI at any age (n=314) or with (IV) no MI ever (n=317, females aged>70 years, males>65 years). The phenotypic characteristics of high-risk pedigrees (n=10 cases per pedigree) were also examined. Results: The GIF was 0.448 for controls and GIF=0.395 in cases with younger MI and mild CAD (p>0.05), while GIF=0.440 in cases with MI at any age and mild CAD (p>0.05 vs. control). In contrast, among cases with MI at any age and 3-vessel CAD, the GIF was 0.564 (p<0.001 vs. control GIF=0.448) and, for older cases who never had an MI but had 3-vessel CAD, the GIF was similarly elevated at 0.645 (p<0.001 vs. control). Conclusion: While CAD was confirmed to be heritable regardless of MI events, the presence of MI without substantial CAD was not familial. This suggests that MI per se is only weakly heritable and that prior claims that MI aggregates in families were likely measuring the inheritance of atherosclerosis/CAD loci and not loci pre-disposing to MI per se. Further investigation of these findings in other cohorts and identification of all environmental triggers of MI are needed.

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