Lamin A/C mutation is independently associated with an increased risk of arterial and venous thromboembolic complications

Ingrid A. W. van Rijsingen, Annemieke Bakker, Donija Azim, Johanna F. Hermans-van Ast, Anneke J. van der Kooi, J. Peter van Tintelen, Maarten P. van den Berg, Imke Christiaans, Ronald H. Lekanne dit Deprez, Arthur A. M. Wilde, Aeilko H. Zwinderman, Joost C. M. Meijers, Anita E. Grootemaat, Rienk Nieuwland, Yigal M. Pinto, Sara-Joan Pinto-Sietsma

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Abstract

Lamin A/C (LMNA) mutation carriers suffer from a variety of clinical phenotypes, including dilated cardiomyopathy (DCM). Although it has been suggested that carriers are at risk for thromboembolic complications, it is unknown whether this risk is higher than can be expected from the underlying cardiac abnormalities. The purpose of this study was to determine whether a LMNA mutation is associated with an increased risk of thromboembolic complications. We compared a cohort of 76 LMNA mutation carriers with a cohort of 224 idiopathic DCM patients without a LMNA mutation, with respect to the prevalence of arterial and venous thromboembolic complications. Furthermore, we carried out a case-control study to explore whether a prothrombotic phenotype was present in LMNA mutation carriers without DCM or atrial tachyarrhythmias (n=14) and compared this with mutation negative relatives (n=13). The prevalence of thromboembolic complications was higher in the cohort of LMNA mutation carriers than in DCM patients (22 vs 11%; p <0.05), after respectively mean follow-up of 42 ± 12 and 49 ± 12 years. After adjustment for possible confounders, including atrial tachyarrhythmias and left ventricular ejection fraction, LMNA mutation carriership was independently associated with an increased risk of thromboembolic complications (HR 4.8, 95% CI: 2.2-10.6). The results of the case-control study suggested a prothrombotic phenotype in LMNA mutation carriers, as reflected by an altered platelet function and increased thrombin generation. LMNA mutation is independently associated with an increased risk of arterial and venous thromboembolic complications. Laboratory research in LMNA mutation carriers without severe cardiac abnormalities suggests a prothrombotic phenotype
Original languageEnglish
Pages (from-to)472-477
JournalInternational journal of cardiology
Volume168
Issue number1
DOIs
Publication statusPublished - 2013

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