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

Sci Rep. 2021 Sep 9;11(1):17980. doi: 10.1038/s41598-021-97298-0.

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood Pressure
  • Body Mass Index
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / genetics*
  • Carotid Intima-Media Thickness
  • Cognition*
  • Cohort Studies
  • Comorbidity
  • Denmark / epidemiology
  • Family*
  • Female
  • Genetic Pleiotropy*
  • Humans
  • Hypertension / epidemiology*
  • Longevity / genetics*
  • Male
  • Middle Aged
  • Obesity / epidemiology*
  • Physical Functional Performance*
  • Risk Factors
  • United States / epidemiology
  • Waist Circumference
  • Walking Speed