Dataset Information

Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105?949 individuals from a white general population cohort.

ABSTRACT: AIMS:To determine whether plasma apoE levels and APOE genotype are associated with all-cause and cause-specific mortality. METHODS AND RESULTS:Using a prospective cohort design with 105 949 white individuals from the general population, we tested the association between plasma apoE at study enrolment and death during follow-up, and whether this was independent of APOE genotype. We confirmed the well-known association between APOE genotypes and mortality. For all-cause, cardiovascular, and cancer mortality, high levels of apoE were associated with increased risk, while for dementia-associated mortality low levels were associated with increased risk. For the highest vs. the fifth septile of plasma apoE, hazard ratios (HRs) were 1.20 (95% confidence interval 1.12-1.28) for all-cause mortality, 1.28 (1.13-1.44) for cardiovascular mortality, and 1.18 (1.05-1.32) for cancer mortality. Conversely, for the lowest vs. the fifth septile the HR was 1.44 (1.01-2.05) for dementia-associated mortality. Results were similar in analyses restricted to APOE ?33 carriers. Examining genetically determined plasma apoE, a 1?mg/dL increase conferred risk ratios of 0.97 (0.92-1.03) for cardiovascular mortality and 1.01 (0.95-1.06) for cancer mortality, while a 1?mg/dL decrease conferred a risk ratio of 1.70 (1.36-2.12) for dementia-associated mortality. CONCLUSION:High plasma levels of apoE were associated with increased all-cause, cardiovascular, and cancer mortality, however of a non-causal nature, while low levels were causally associated with increased dementia-associated mortality.

SUBMITTER: Rasmussen KL

PROVIDER: S-EPMC6735871 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort.

Rasmussen Katrine L KL Tybjærg-Hansen Anne A Nordestgaard Børge G BG Frikke-Schmidt Ruth R

European heart journal 20190901 33

<h4>Aims</h4>To determine whether plasma apoE levels and APOE genotype are associated with all-cause and cause-specific mortality.<h4>Methods and results</h4>Using a prospective cohort design with 105 949 white individuals from the general population, we tested the association between plasma apoE at study enrolment and death during follow-up, and whether this was independent of APOE genotype. We confirmed the well-known association between APOE genotypes and mortality. For all-cause, cardiovascu ...[more]

PMID: 31236578

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Project description:The omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mediate inflammation in large part by affecting pro-inflammatory and anti-inflammatory/pro-resolving oxylipin concentrations. Common gene variants are thought to underlie the large inter-individual variation in oxylipin levels in response to n-3 PUFA supplementation, which in turn is likely to contribute to the overall heterogeneity in response to n-3 PUFA intervention. Given its known role in inflammation and as a modulator of the physiological response to EPA and DHA, here we explore, for the first time, the differential response of plasma hydroxy-, epoxy- and dihydroxy-arachidonic acid, EPA and DHA oxylipins according to apolipoprotein E (APOE) genotype using samples from a dose-response parallel design RCT. Healthy participants were given doses of EPA+DHA equivalent to intakes of 1, 2, and 4 portions of oily fish per week for 12 months. There was no difference in the plasma levels of EPA, DHA or ARA between the wildtype APOE3/E3 and APOE4 carrier groups after 3 or 12 months of n-3 PUFA supplementation. At 12 months, hydroxy EPAs (HEPEs) and hydroxy-DHAs (HDHAs) were higher in APOE4 carriers, with the difference most evident at the highest EPA+DHA intake. A significant APOE*n-3 PUFA dose effect was observed for the CYP-ω hydroxylase products 19-HEPE (p = 0.027) and 20-HEPE (p = 0.011). 8-HEPE, which, along with several other plasma oxylipins, is an activator of peroxisome proliferator activated receptors (PPARs), showed the highest fold change in APOE4 carriers (14-fold) compared to APOE3/E3 (4-fold) (p = 0.014). Low basal plasma EPA levels (EPA < 0.85% of total fatty acids) were associated with a greater change in 5-HEPE, 9-HEPE, 11-HEPE, and 20-HEPE compared to high basal EPA levels (EPA > 1.22% of total fatty acids). In conclusion, APOE genotype modulated the plasma oxylipin response to increased EPA+DHA intake, with APOE4 carriers presenting with the greatest increases following high dose n-3 PUFA supplementation for 12 months.

Dataset Information

Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105?949 individuals from a white general population cohort.

Publications

Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort.

Similar Datasets

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