July 21, 2020Open Access
Cardiovascular health, genetic risk, and risk of dementia in the Framingham Heart Study
Key Result
Favorable cardiovascular health was associated with a 0.45-fold lower risk of incident dementia compared to unfavorable cardiovascular health, independent of genetic risk.
Study Design
Type
Cohort (n=1,211)
Multicenter
No
Structured PICO
Does ideal cardiovascular health and genetic risk affect the risk of incident all-cause dementia in the Framingham Heart Study offspring cohort?
P
Population
1,211 Framingham Heart Study (FHS) offspring cohort participants
I
Intervention
Ideal cardiovascular health (CVH) based on the American Heart Association Ideal CVH Index and genetic risk score (GRS) of common genetic variants and the APOE ε4 genotype
C
Comparator
Unfavorable CVH, low GRS (<20th percentile), and not carrying an APOE ε4 allele
O
Outcome
Incident all-cause dementia with up to 10 years of follow-up (mean 8.4 years)hard clinical
Both genetic risk and ideal cardiovascular health contribute additively to the risk of incident all-cause dementia.
Main Result
Effect estimate: HR 0.45 (95% CI 0.20-1.01)
p-value: p=0.0527
Limitations
- The Framingham Heart Study is composed of individuals of European descent, so results may not be generalizable to non-European populations.
- Small sample size, which leads to large error bars in the estimates of cumulative hazards.
- Some of the genetic markers may influence both cardiovascular health and dementia.
Abstract
Objective To determine the joint role of ideal cardiovascular health (CVH) and genetic risk on risk of dementia. Methods We categorized CVH on the basis of the American Heart Association Ideal CVH Index and genetic risk through a genetic risk score (GRS) of common genetic variants and the APOE ε4 genotype in 1,211 Framingham Heart Study (FHS) offspring cohort participants. We used multivariable Cox proportional hazards regression models to examine the association between CVH, genetic risk, and incident all-cause dementia with up to 10 years of follow-up (mean 8.4 years, 96 incident dementia cases), adjusting for age, sex, and education. Results We observed that a high GRS (>80th percentile) was associated with a 2.6-fold risk of dementia (95% confidence interval CI of hazard ratio HR 1.23–5.29; p = 0.012) compared with having a low GRS (APOE ε4 allele was associated with a 2.3-fold risk of dementia compared with not carrying an APOE ε4 allele (95% CI of HR 1.49–3.53; p = 0.0002), and having a favorable CVH showed a 0.45-fold lower risk of dementia (95% CI of HR 0.20–1.01; p = 0.0527) compared to having an unfavorable CVH when all 3 components were included in the model. We did not observe an interaction between CVH and GRS (p = 0.99) or APOE ε4 (p = 0.16). Conclusions We observed that both genetic risk and CVH contribute additively to dementia risk.