P4.13 HERITABILITY AND OTHER DETERMINANTS OF LEFT VENTRICULAR DIASTOLIC FUNCTION IN THE FAMILY-BASED POPULATION STUDY

Abstract

Background: Understanding to what extent genetic factors influence diastolic Doppler indexes is an important issue in view of the relation of left ventricular (LV) diastolic dysfunction with outcome. We, therefore, investigated in nuclear families recruited from the general population the heritability of LV diastolic traits and the composite diastolic score. Methods and results: A random sample of 316 nuclear families (452 parents and 600 offspring, mean age, 58.5 and 33.3 years) was recruited in Belgium, Poland, Italy and Russia. We measured transmitral early and late diastolic velocities (E and A) by pulsed wave Doppler, and mitral annular velocities (E′ and A′) by tissue Doppler. Using principle component analysis, we summarized 5 Doppler indexes – namely, E, A, E′ and A′ velocities, and E/E′ – into a single diastolic score. To calculate the heritability of diastolic indexes, we used (1) the regression slope of offspring on mid-parent residual values, (2) variance decomposition in siblings. The parent-offspring concordances of all diastolic indexes were significant and ranged from 0.17 for A (P=0.009) to 0.42 for E′ (P<0.0001). In variance decomposition analyses in sibships, the abovementioned traits with adjustment for covariables had moderate heritability in a range of 0.12-0.31 (P≤0.01). Among the parent-offspring pairs and sibships, the heritability estimates of the composite diastolic score were 0.39 and 0.27, respectively (P<0.0001). Conclusions: Our study demonstrated moderate heritability of various indexes reflecting LV diastolic function in nuclear families. The observation highlights the necessity of further research into the genes that affect LV diastolic function.