Heritability of Vascular Structure and Function: A Parent–Child Study

Abstract

BackgroundUnderstanding the heritable contribution of vascular measures, from parent to offspring, may aid in risk stratification and atherosclerosis prevention efforts. We hypothesized that measures of vascular structure and function would be heritable in this cohort of parents and their adolescent offspring.Methods and ResultsHigh‐resolution ultrasound scans of the brachial and carotid arteries were obtained in parents (n=558) and their offspring (n=369). Lumen diameter and flow‐mediated dilation were measured in the brachial artery. Intima‐media thickness, lumen diameter, incremental elastic modulus, diameter distensibility, and cross‐sectional distensibility were measured, and carotid cross‐sectional compliance was measured in the carotid artery. Carotid–radial pulse wave velocity was obtained using SphygmoCor®. Heritability analysis (h2, expressed as %) using Sequential Oligogenic Linkage Analysis Routines was performed on the entire cohort and adjusted for age, sex, race, body–mass index, smoking, and mean arterial pressure. Data are presented as mean±SE. Measures of brachial artery diameter (h2=25±9%, P=0.001), lumen diameter (h2=55±9%, P<0.001), intima‐media thickness (h2=29±13%, P=0.014), diameter distensibility (h2=28±7%, P<0.001), cross‐sectional distensibility (h2=27±7%, P<0.001), and pulse wave velocity (h2=26±9%, P<0.001) were significantly heritable. Flow‐mediated dilation and incremental elastic modulus were not significantly heritable. Similar associations were observed in analysis restricted to siblings and complete Trios (mother, father, and child).ConclusionsThese data show that the majority of noninvasive measures of vascular structure and function are heritable, suggesting that measurement of these subclinical risk factors in parents may be helpful in assessing childhood risk for future cardiovascular disease.

Carotid artery intima–media thickness, distensibility and elasticity: population epidemiology and concordance in Australian children aged 11–12 years old and their parents

“…Given the direction and magnitude of the point estimates, we think (2) is most likely, but this can only be verified in further studies with larger numbers of fathers. Despite their similar number of fathers (n=186), Ryder et al ’s findings29 did contrast with ours in reporting a higher heritability statistic (h 2 =41.5%) in father–offspring dyads than mother-offspring dyads (h 2 =23.4%) in distensibility measures, which would also imply a higher correlation coefficient.…”

“…In particular, our results almost exactly approximate those reported by Ryder et al of parent–offspring correlations in a US population (r=0.08 for carotid IMT, online supplementary table 2). 29 Ryder’s sibling–sibling correlations were marginally higher within the same cohort (r=0.11), and were higher again, according to another study, in late middle age (r=0.36) 28. This higher concordance between mid-life siblings may reflect smaller relative measurement error, because a fixed absolute measurement error becomes a smaller relative proportion of a measurement as IMT increases with age.…”

“…Carotid IMT is known to be modestly heritable, however, the estimates are largely derived from studies of twins26 or older participants 27 28. One study reported modest parent–child heritability (h 2 <30%) 29. Understanding parent–child concordance in a larger population-based cohort could clarify sex differences and examine the generalisability of earlier findings.…”

Relation of the Ankle Brachial Index to Left Ventricular Ejection Fraction in Patients Without Coronary Artery Disease

“…We measured carotid-radial PWV rather than carotid-femoral PWV. Although carotid-femoral PWV is strongly predictive of cardiovascular outcomes, carotid to radial PWV has been frequently used for various applications [35].…”

Carotid Artery Atherosclerosis: A Review on Heritability and Genetics

“…Although twin studies are the focus of this article, family studies in regard to CAS also have to be mentioned in brief. In family studies, the heritability of CIMT varied between 16% and 66% (Fox et al, 2003; Juo et al, 2005; Kao et al, 2005; Kuipers et al, 2013; Mayosi et al, 2005; Moskau et al, 2005; Ryder et al, 2017; Sayed-Tabatabaei et al, 2005; Xiang et al, 2002). There were two findings for heritability of plaque presence of 23% (Hunt et al, 2002) and 15% (Dong et al, 2010).…”