Other factors may override E4 inverse association with longevity

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Julie G
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Other factors may override E4 inverse association with longevity

Postby Julie G » Sun Oct 06, 2019 1:48 pm

I skimmed full text and have to say the abstract doesn't quite do the paper justice. ApoE4 men, not women, appear to be at a higher risk of cardiovascular mortality but specific factors (different for each gender) appear to override our APOE status. For men, lack of physical exercise, low HDL, hypertension, diabetes and current use of lipid-lowering medication were all associated with a higher prevalence of CVD. For women, older age, diabetes, high triglycerides and lipid lowering medication were associated with CVD. Low HDL is associated with greater all cause mortality. Interestingly, for E4 carriers only, being sedentary was associated with a reduced risk of all cause mortality. I suggest taking that last correlation with a grain of salt as the dataset was comprised of elderly folks, 70-85 y/o. I suspect we should try to control as many risk factors as possible (including exercise!) to counteract our E4 status. I'd love to hear others thoughts on this one.

ApoE genotype, lipid profile, exercise, and the associations with cardiovascular morbidity and 18-year mortality.
Studies of longevity examined apolipoprotein E (ApoE), a gene involved in lipoprotein metabolism, which interacts with susceptibility to age-related diseases, and with mortality. We evaluated the association of ApoE isoforms with cardiovascular disease (CVD) and all-cause mortality.
A prospective cohort of 949 survivors of the Israel Study of Glucose Intolerance, Obesity, and Hypertension, examined during 1999-2004, mean age 72 years, was followed for mortality until 2017. Participants were interviewed for lifestyle habits and medical history. Anthropometrics and biochemical markers were taken. Logistic regression was used to assess CVD morbidity and Cox proportional-hazard model for mortality.
The most common genotype in the cohort was ApoE E3 (76.3%), with the other two almost equally distributed (ApoE E2 11.2% and ApoE E4 12.5%). In men only, ApoE E4 associated with CVD (adjusted OR (aOR)=1.46, 95%CI 0.76, 2.80) and with 18-year mortality (adjusted HR (aHR) =1.47, 95%CI 0.95, 2.26), adjusting for age, ethnicity, physical activity, hypertension, diabetes, LDL-cholesterol, HDL-cholesterol, triglycerides and lipid-lowering medications. Low levels of HDL cholesterol, adjusted for ApoE and the above mentioned variables, associated with higher prevalence of CVD (aOR=1.35, 95%CI 1.00, 1.83) and all-cause mortality (aHR=1.42, 95%CI 1.14, 1.78). ApoE E3 and E2 conferred a lower 18-year mortality risk in the physically active individuals, compared to the sedentary (aHR=0.57, 95%CI 0.44, 0.74, and aHR=0.53, 95%CI 0.78, 1.02, respectively).
In community dwelling older adults, sociodemographic characteristics and physical activity, blood pressure and HDL-cholesterol levels, may outweigh the impact of ApoE polymorphisms on CVD morbidity and all-cause mortality.

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Re: Other factors may override E4 inverse association with longevity

Postby Saskia » Tue Oct 08, 2019 11:13 am

That's very interesting. Anything where APOE4 is looked at individually against factors we can control is interesting I guess :)
Do you know if there's a public version of the full research doc? I couldn't find it.
45 years old, E4/E4 and strangely no AD in (large) family. Mother (73 yo) E4/E4, father (87 yo) E4/E3, both symptom free. Recently started 16h fasts, taking resveratrol/B12/curcumin/krill oil/folic acid. Working on minimizing sugar & refined carbs

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Re: Other factors may override E4 inverse association with longevity

Postby aphorist » Wed Oct 09, 2019 3:27 pm


I have a real hard time putting any stock in Table 3. Non-significant confidence intervals. ApoE4 Men who physically exercise having 3.26x the hazard incidence rate than those who are sedentary. Can't simultaneously suggest that low HDL is a biomarker for mortality and that exercising will also put one at a greater hazard rate for death.

And if the sedentary E4 men are living longer, then the 1.65 - 1.55 hazard rates for all men in Table 2, suggests that the non-E4's must have been really at risk, but that doesn't really match up w/ Table 3 data for Non-E4's.

IDK what's going on w/ that table 3 or if I'm not seeing something here.

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