Heritability of haemodynamics in the ascending aorta

Abstract

Blood flow in the vasculature can be characterised by dimensionless numbers commonly used to define the level of instabilities in the flow, for example the Reynolds number, Re. Haemodynamics play a key role in cardiovascular disease (CVD) progression. Genetic studies have identified mechanosensitive genes with causal roles in CVD. Given that CVD is highly heritable and abnormal blood flow may increase risk, we investigated the heritability of fluid metrics in the ascending aorta calculated using patient-specific data from cardiac magnetic resonance (CMR) imaging. 341 participants from 108 British Caucasian families were phenotyped by CMR and genotyped for 557,124 SNPs. Flow metrics were derived from the CMR images to provide some local information about blood flow in the ascending aorta, based on maximum values at systole at a single location, denoted max, and a 'peak mean' value averaged over the area of the cross section, denoted pm. Heritability was estimated using pedigree-based (QTDT) and SNP-based (GCTA-GREML) methods. Estimates of Reynolds number based on spatially averaged local flow during systole showed substantial heritability ([Formula: see text], [Formula: see text]), while the estimated heritability for Reynolds number calculated using the absolute local maximum velocity was not statistically significant (12-13%; [Formula: see text]). Heritability estimates of the geometric quantities alone; e.g. aortic diameter ([Formula: see text], [Formula: see text]), were also substantially heritable, as described previously. These findings indicate the potential for the discovery of genetic factors influencing haemodynamic traits in large-scale genotyped and phenotyped cohorts where local spatial averaging is used, rather than instantaneous values. Future Mendelian randomisation studies of aortic haemodynamic estimates, which are swift to derive in a clinical setting, will allow for the investigation of causality of abnormal blood flow in CVD.

Figure 1

Laminar (left), transitional (middle) and turbulent (right) blood flow: arrows indicate direction of fluid flow. During laminar flow fluid moves in parallel layers without disruption between the layers. During turbulent flow mixing occurs between the layers creating chaotic flow velocities with variations in gradient. The right side of each figure show the velocity profile across the diameter, averaged in time and at a given instance in time.

Figure 2

Part a: (A) Mean (black) and maximum (red) blood flow velocity across a cardiac cycle. (B) $U_{\mathit{max}}$ is the maximum value of instantaneous velocity (solid line) at any location of the imaging plane whereas $U_{\mathit{pm}}$ is the maximum mean velocity (dashed line). Part b: Magnitude image demonstrating contouring of ascending aorta (red outline).

Figure 3

Heritability estimates for the haemodynamic metrics in the ascending aorta. Metrics are classified based on the type measurements used to calculate each: geometry based, spatially averaged flow based and single point flow based. The size of each marker is representative of the confidence level (P value) as presented in Table 5 where CSA is the cross sectional and D is the diameter.