European Heart Journal Advance Access originally published online on October 3, 2007
European Heart Journal 2007 28(20):2432-2437; doi:10.1093/eurheartj/ehm377
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Familial aggregation of left main coronary artery disease and future risk of coronary events in asymptomatic siblings of affected patients
1 Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg, Regensburg, Germany
2 Klinik für Innere Medizin II, Universität zu Lübeck, Lüebeck, Germany
Received 26 February 2007; revised 6 August 2007; accepted 10 August 2007; online publish-ahead-of-print 4 October 2007.
* Corresponding author. Medizinische Klinik II, Universität zu Lübeck, Lübeck, Germany. Tel: +49 451 5002501; fax: +49 451 5006437. E-mail address: heribert.schunkert{at}innere2.uni-luebeck.de
Aims: Recently, we observed in a hypothesis-generating exploratory search on the heritability of coronary morphology that left main coronary disease (LMD) was frequently shared by siblings with coronary artery disease (CAD). Thus, our aims were, first, to test specifically the familial aggregation of LMD and second, to investigate whether LMD is a stronger predictor for future incident events than other manifestations of CAD in seemingly healthy siblings of CAD patients.
Methods and results: Coronary angiograms of 1801 patients (n = 882 from the initial exploratory study and 919 additional angiograms) were analysed from families with 
2 affected CAD siblings. We estimated the heritability using the variance-component methodology and sibling recurrent risks by logistic regression analysis. Moreover, we studied 1369 healthy siblings of CAD patients with known coronary morphology who had a subsequent coronary event by conducting a prospective, nested case–control study. LMD-frequency was comparable in our initial exploratory study (11%) and the new sample (12%). The heritability of LMD was significant in the exploratory 48%, P = 0.010, in the subsequent 45%, P = 0.045, and in the total study sample 49%, P = 0.002. The sibling recurrent risk ratio to present with LMD was 3.6 [CI 1.7–7.1] when another sibling was affected by LMD. In the prospective study on initially healthy family members of CAD patients, 79 siblings experienced an event during follow-up. LMD was more frequently found in families with an event than in families without (13.9 vs. 6.4%, P = 0.036). The relative risk for initially asymptomatic siblings of patients with LMD to suffer from a coronary event was 2.5 [CI 1.1–5.8] compared with siblings of patients with other manifestations of CAD.
Conclusion: These data confirm our initial observation of familial aggregation of LMD. Moreover, in apparently healthy siblings of patients with LMD, this heritable component results in a risk increase for future events that is greater than that of a strong positive family history by itself.
Key Words: Left main coronary disease • Familial risk • Heritability • Angiography • Prevention
Both authors contributed equally to this work.
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