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(Circulation. 2005;111:855-862.)
© 2005 American Heart Association, Inc.

Coronary Heart Disease

Distinct Heritable Patterns of Angiographic Coronary Artery Disease in Families With Myocardial Infarction

Marcus Fischer, MD; Ulrich Broeckel, MD; Stephan Holmer, MD; Andrea Baessler, MD; Christian Hengstenberg, MD; Bjoern Mayer, MD; Jeanette Erdmann, PhD; Gernot Klein, MD; Guenter Riegger, MD; Howard J. Jacob, PhD; Heribert Schunkert, MD

From the Human and Molecular Genetics Center (M.F., U.B., A.B., H.J.J.), Medical College of Wisconsin, Milwaukee, Wis; the Clinic for Internal Medicine II (M.F., S.H., A.B., C.H., G.R.), University of Regensburg, Regensburg, Germany; the Clinic for Internal Medicine II (B.M., J.E., H.S.), University of Luebeck, Luebeck, Germany; and the LVA Cardiac Rehabilitation Clinic Höhenried (G.K.), Bernried, Germany.

Correspondence to Dr Ulrich Broeckel, Human and Molecular Genetics Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226 (e-mail broeckel{at}mcw.edu); or Prof Dr Heribert Schunkert, Clinic for Internal Medicine II, University of Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany (e-mail heribert.schunkert@innere2.uni-luebeck.de).

Received June 18, 2004; revision received November 3, 2004; accepted November 10, 2004.

Background— Coronary artery disease (CAD) and myocardial infarction (MI) are significantly determined by genetic background. Whether distinct angiographic features of CAD are affected by inherited factors has never been investigated. Thus, we analyzed comprehensively the extent to which various aspects of CAD, including disease severity, distribution of lesions, presence of coronary calcification, morphology of stenoses, and anatomic characteristics, are under genetic control.

Methods and Results— We retrospectively studied the coronary angiograms of 882 siblings with CAD from 401 families. These families were ascertained through index patients defined by MI before the age of 60 years and at least 1 sibling with MI or coronary revascularization procedures. Heritability calculations were performed with variance-component analysis. Additionally, recurrence risks to siblings were analyzed. Traditional cardiovascular risk factors and age at the first coronary event displayed significant heritable components. After adjustment for age and sex, significant heritabilities were identified for proximal stenoses, in particular, left main CAD (h²=0.49±0.12; P=0.01), coronary calcification (h²=0.51±0.17; P=0.001), and ectatic coronary lesions (h²=0.52±0.07; P=0.001). In contrast, no heritability was found for distal disease (h²=0.05±0.19; NS), the pattern of coronary arterial blood supply, or the number of diseased vessels. Calculation of recurrence risks in siblings largely confirmed the heritability estimates.

Conclusions— Distinct morphological characteristics associated with CAD show different degrees of heritability. Notably, the most hazardous localizations, like left main or proximal disease, display a high heritability. In contrast, some features of coronary morphology, such as distal disease, do not appear to be markedly influenced by heritable factors.

Key Words: myocardial infarction • coronary disease • angiography • genetics

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