Modifiable Characteristics may Outweigh ApoE Genotype Impact on Cardiovascular Morbidity and 18-year Mortality in Community Dwelling Older Israelis

BACKGROUND: Studies of longevity often examine apolipoprotein E (ApoE), a gene involved in lipoprotein metabolism, which interacts with susceptibility to age-related diseases, such as cardiovascular disease (CVD) and Alzheimer’s disease, and with mortality.

OBJECTIVE: To evaluate the association of ApoE allele frequencies, plasma lipids, lipoproteins profile, and selected patient characteristics with CVD morbidity and all-cause mortality.

DESIGN: Prospective cohort study, with follow up until 2017 of survivors of the Israel Study of Glucose Intolerance, Obesity, and Hypertension who were examined during 1999-2004.

PARTICIPANTS: 949 participants, with mean age of 72 years.

MEASUREMENTS: Participants were interviewed for lifestyle habits, medical history and medication use. Anthropometrics and biochemical markers were assessed. Using logistic regression and Cox proportional hazard models, interactions between ApoE and selected patient characteristics were examined.

RESULTS: The most common isoform in the cohort was ApoE ε3 (76.3%), with the other two isoforms almost equally distributed (ApoE ε2 11.2% and ApoE ε4 12.5%), but distributed differently between the population`s four ethnic origins. Lack of physical exercise and hypertension associated with higher CVD morbidity prevalence and higher 18-year mortality. In males only, ApoE ε4 associated with CVD (OR=1.46, 95%CI 0.76, 2.81) and with 18-year mortality (HR=1.52, 95%CI 0.98, 2.34), controlling for age, ethnicity, physical activity, hypertension, LDL-cholesterol, HDL-cholesterol, triglycerides and lipid-lowering medications. Low levels of HDL cholesterol, adjusted for the ApoE allele and the above mentioned variables associated with higher risk of both CVD morbidity (adjusted OR=1.39, 95%CI 1.02, 1.87) and all-cause mortality (adjusted HR=1.44, 95%CI 1.16, 1.79) in the total cohort. A significant interaction was observed between physical activity and ApoE on 18-year mortality.

CONCLUSIONS: In community dwelling older adults, sociodemographic characteristics and physical activity, blood pressure and HDL-cholesterol levels, may outweigh the impact of ApoE gene polymorphisms on cardiovascular risk and all-cause mortality.