Pleiotropic effects between cardiovascular disease risk factors and measures of cognitive and physical function in long-lived adults.

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.