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Impact of APOE4 and future family history on early adulthood cardiovascular risk: Results from a 30‐year cohort study
Author(s) -
Koychev Ivan,
Vaci Nemanja,
Moonen Justine E,
Yaffe Kristine,
Nasrallah Ilya M,
Sidney Stephen,
Jindra Christoph,
Gallacher John,
Launer Lenore J
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.040454
Subject(s) - apolipoprotein e , medicine , family history , dementia , blood pressure , cohort , genetic predisposition , gerontology , disease
Background Selected cardiovascular factors, APOE ε4 allele carriership and family history of dementia (FHD) are robust risk factors for late‐onset dementia. While it is recognised that cardiovascular factors exert their influence from mid‐age, it is unclear whether APOE ε4 carriership and a future FHD impact the process. Here we test the hypothesis that genetic and familial susceptibility for dementia are associated with an unfavourable cardiovascular risk profile starting from early adulthood. Method We used data from the CARDIA study which followed‐up 5116 individuals aged 18‐30 starting in 1984. Data from 2,497 30‐year visit attendees (mean age 55) was used to assess the associations of APOE ε4 carriership and future FHD with baseline and 30‐year measures of cardiovascular risk factors (LDL, HDL, glucose, blood pressure, BMI) suggested to be associated with late‐life cognitive impairment. Result APOE ε4 carriers, compared to non‐carriers, had higher LDL and lower HDL levels in early adulthood. Future FHoD was associated with worse late‐life but not baseline lipid profile. Compared to those with neither or one, persons having both FHD and APOE ε4 had the lowest baseline mean HDL and highest mean LDL (52 and 117 mg/dL for APOE ε4+/FHD+ versus 54 and 107 mg/dL for APOE‐/FHD‐ respectively). Interestingly, APOE ε4+/FHoD+ was associated with lower systolic and diastolic blood pressure relative to the APOE ε4‐/FHD‐ group in early adulthood but not year 30. Neither family history nor APOE ε4 were associated with early or late‐life levels of blood glucose or, BMI. Conclusion Our results indicate that APOE ε4 allele carriership associates with an unfavourable lipid profile (low HDL, high LDL) starting from early adulthood continuing into later life. Of the two factors, APOE ε4 allele carriership was more strongly associated with lipid levels, but family history of dementia does add some additional explanatory value to the association. Recent GWAS have identified cholesterol metabolism as a component of risk for dementia, and these results indicate that APOE ε4 allele effects peripherally measured lipids, starting at the latest in early adulthood. The relation between these levels and brain structure and function needs further evaluation.