Overlapping Genetic Background of Coronary Artery and Carotid/Femoral Atherosclerotic Calcification

Abstract

Background and objectives: Multivessel atherosclerosis and its genetic background are under-investigated, although atherosclerosis is seldom local and still causes high mortality. Alternative methods to assess coronary calcification (CAC) might incorporate genetic links between different arteries’ atherosclerotic involvement, however, co-occurrences of coronary calcification have not been investigated in twins yet. Materials and Methods: We assessed the heritability of radio morphologically distinct atherosclerotic plaque types in coronary (non-enhanced CT, Agatston score), carotid, and femoral arteries (B-mode ultrasound) in 190 twin subjects (60 monozygotic, 35 dizygotic pairs). Four-segment scores were derived in order to assess the dissemination of the distinct plaque types in the carotid and femoral arteries taking bilaterality into account. We calculated the genetic correlation between phenotypically correlating plaque types in these arteries. Results: CAC and dissemination of calcified plaques in the carotid and femoral arteries (4S_hyper) were moderately heritable (0.67 [95% CI: 0.37–1] and 0.69 [95% CI: 0.38–1], respectively) when adjusted for age and sex. Hypoechoic plaques in the carotid and femoral arteries showed no heritability, while mixed plaques showed intermediate heritability (0.50 [95% CI: 0–0.76]). Age and sex-adjusted phenotypic correlation between CAC and 4segm_hyper was 0.48 [95% CI: 0.30–0.63] and the underlying genetic correlation was 0.86 [95% CI: 0.42–1]. Conclusions: Calcification of atherosclerotic plaques is moderately heritable in all investigated arteries and significant overlapping genetic factors can be attributed to the phenotypical resemblance of coronary and carotid or femoral atherosclerotic calcification. Our findings support the idea of screening extracoronary arteries in asymptomatic individuals. We also propose a hypothesis about primarily carotid-coronary and femoral-coronary atherosclerosis as two distinct genetic predispositions to co-localization.

Keywords

• atherosclerosis
• multivessel
• heritability
• genetic correlation
• plaque calcification
• twin study