Gina M Peloso1, Alexa S Beiser2, Claudia L Satizabal2, Vanessa Xanthakis2, Ramachandran S Vasan2, Matthew P Pase2, Anita L Destefano2, Sudha Seshadri1. 1. From the Departments of Biostatistics (G.M.P., A.S.B., V.X., A.L.D.) and Epidemiology (R.S.V.), Boston University School of Public Health; Boston University and NHLBI's Framingham Heart Study (A.S.B., C.L.S., V.X., R.S.V., A.L.D., S.S.), Framingham; Department of Neurology (A.S.B., C.L.S., A.L.D., S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; Sections of Preventive Medicine & Epidemiology and Cardiology (V.X., R.S.V.), Department of Medicine, Boston University, MA; Melbourne Dementia Research Centre (M.P.P.), The Florey Institute for Neuroscience and Mental Health; Faculty of Medicine, Dentistry, and Health Sciences (M.P.P.), University of Melbourne, Parkville; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Hawthorn, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA. gpeloso@bu.edu seshadri@uthscsa.edu. 2. From the Departments of Biostatistics (G.M.P., A.S.B., V.X., A.L.D.) and Epidemiology (R.S.V.), Boston University School of Public Health; Boston University and NHLBI's Framingham Heart Study (A.S.B., C.L.S., V.X., R.S.V., A.L.D., S.S.), Framingham; Department of Neurology (A.S.B., C.L.S., A.L.D., S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), University of Texas Health Sciences Center, San Antonio; Sections of Preventive Medicine & Epidemiology and Cardiology (V.X., R.S.V.), Department of Medicine, Boston University, MA; Melbourne Dementia Research Centre (M.P.P.), The Florey Institute for Neuroscience and Mental Health; Faculty of Medicine, Dentistry, and Health Sciences (M.P.P.), University of Melbourne, Parkville; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Hawthorn, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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 (<20th percentile); carrying at least 1 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.
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 (<20th percentile); carrying at least 1 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.
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