Abstract 20701: Genetics or Environment - The First Twin Study of Coronary Endothelial Shear Stress

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Abstract

Introduction: There is a robust evidence to show a genetic disposition in the development of coronary artery disease. Several twin studies have examined the association between systemic risk factors such as hypertension or hypercholesterolemia and heritability but there is no previous work concerning the effect of genetics on local intracoronary hemodynamic forces.

Hypothesis: Investigation of the heritability of endothelial shear stress (ESS) across the coronary artery systems of twins will shed light on the relative contribution of genetics and biomechanical factors (environment) to local coronary atherosclerotic lesions.

Methods: Coronary CT angiograms were acquired from 10 twin pairs: 6 monozygotic (MZ) and 4 dizygotic (DZ). In the acquired images, the lumen borders were segmented in the main epicardial arteries and their side branches. The annotated borders were used to reconstruct coronary anatomy and estimate the ESS using computational fluid dynamics. The flow conditions of simulations were personalised based on patient metrics such as blood pressure and ventricular mass. ESS values were taken from the simulated coronary artery per segment of the vessels and segmental ESS values were compared. Subsequently, broad heritability (h2) estimates of the ESS were calculated.

Results: Mean ESS were LM-proximal LAD: 2.5 ± 1.6 Pa, mid LAD: 3.2 ± 1.7 Pa, distal LAD 4.8 ± 2.5 Pa, proximal LCx: 2.2 ± 1.0 Pa, mid-distal LCx: 3.6 ± 1.6 Pa, RCA: 2.7 ± 1.6 Pa, respectively. Across the dataset, there is a noticeable heritability in the ESS distribution in the proximal of the LCx and LAD, h2 of 0.73 and 1.08 while we did not observe genetic determination of the other segments.

Conclusions: Genetic profile appears to be an important determinant of local intracoronary hemodynamic forces. Further research is needed to explore the interplay between ESS and genetic profile in the atherosclerotic evolution.

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