Abstract
Cardiovacular disease (CVD) is the leading cause of death among older adults and is often accompanied by functional decline. It is unclear what is driving this co-occurrence, but it may be behavioral, environmental and/or genetic. We used a family-based study to estimate the phenotypic and shared genetic correlation between CVD risk factors and physical and cognitive functional measures. Participants (n = 1,881) were from the Long Life Family Study, which enrolled families based on their exceptional longevity (sample mean age = 69.4 years, 44% female). Cardiovascular disease risk factors included carotid vessel measures [intima-media thickness and inter-adventitial diameter], obesity [body mass index (BMI) and waist circumference], and hypertension [systolic and diastolic blood pressures]. Function was measured in the physical [gait speed, grip strength, chair stand] and cognitive [digital symbol substitution test, retained and working memory, semantic fluency, and trail making tests] domains. We used SOLAR to estimate the genetic, environmental, and phenotypic correlation between each pair adjusting for age, age2, sex, field center, smoking, height, and weight. There were significant phenotypic correlations (range |0.05–0.22|) between CVD risk factors and physical and cognitive function (all P < 0.05). Most significant genetic correlations (range |0.21–0.62|) were between CVD risk factorsand cognitive function, although BMI and waist circumference had significant genetic correlation with gait speed and chair stand time (range |0.29–0.53|; all P < 0.05). These results suggest that CVD risk factors may share a common genetic-and thus, biologic-basis with both cognitive and physical function. This is particularly informative for research into the genetic determinants of chronic disease.
Highlights
Cardiovacular disease (CVD) is the leading cause of death among older adults and is often accompanied by functional decline
Waist circumference was phenotypically correlated with the same functional measures as body mass index (BMI) (Supplemental Table S1)
inter-adventitial diameter (IAD) was inversely correlated with digit symbol substitution test (DSST) and gait speed (ρ = − 0.05 for both) but positively correlated with chair stand time (ρ = 0.05)
Summary
Cardiovacular disease (CVD) is the leading cause of death among older adults and is often accompanied by functional decline. Most of the studied confounders or mediators of the relationship between CVD and function are biologic and/or behavioral, such as age, sex, excess weight, smoking, depression, education level and inactivity Each of these conditions is heritable in families, with specific estimates ranging from 0.21 for IMT17 to 0.68 for inter-adventitial diameter (IAD)[18], and estimates of heritability of BMI are 0.4–0.919–23. The purpose of this study was to determine the extent to which CVD risk factors, including measures of subclinical carotid vessel disease, obesity, and hypertension, are phenotypically correlated, and genetically correlated with cognitive and physical function in adults from families with exceptional longevity from the Long Life Family Study (LLFS). We hypothesized that CVD risk factors will demonstrate an inverse genetic correlation with measures of cognitive and physical function, adjusting for demographic and environmental covariates
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