Dataset Information

A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease.

ABSTRACT:

Background

Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD).

Methods and results

We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test. In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (P-value for heterogeneity = 0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification.

Conclusions

In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD.

SUBMITTER: Holmes MV

PROVIDER: S-EPMC4232362 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease.

Holmes Michael V MV Frikke-Schmidt Ruth R Melis Daniela D Luben Robert R Asselbergs Folkert W FW Boer Jolanda M A JM Cooper Jackie J Palmen Jutta J Horvat Pia P Engmann Jorgen J Li Ka-Wah KW Onland-Moret N Charlotte NC Hofker Marten H MH Kumari Meena M Keating Brendan J BJ Hubacek Jaroslav A JA Adamkova Vera V Kubinova Ruzena R Bobak Martin M Khaw Kay-Tee KT Nordestgaard Børge G BG Wareham Nick N Humphries Steve E SE Langenberg Claudia C Tybjaerg-Hansen Anne A Talmud Philippa J PJ

Atherosclerosis 20140815 1

<h4>Background</h4>Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD).<h4>Methods and results</h4>We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD ...[more]

PMID: 25173947

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Project description:Background and Purpose- The role of dietary fat on cardiovascular health and mortality remains under debate. Because the APOE is central to the transport and metabolism of lipids, we examined associations between plasma fatty acids and the risk of stroke, coronary heart disease, and mortality by APOE-ε4 genotype. Methods- We included 943 FHS (Framingham Heart Study) and 1406 3C (Three-City) Bordeaux Study participants. Plasma docosahexaenoic, linoleic, arachidonic, and palmitic fatty acids were measured at baseline by gas chromatography. All-cause stroke, ischemic stroke, coronary heart disease, and all-cause mortality events were identified prospectively using standardized protocols. Each cohort used Cox models to separately relate fatty acid levels to the risk of developing each event during ≤10 years of follow-up adjusting for potential confounders and stratifying by APOE genotype (ε4 carriers versus noncarriers). We then meta-analyzed summary statistics using random-effects models. Results- On average, participants had a mean age of 74 years, 61% were women, and 21% (n=483) were APOE-ε4 carriers. Meta-analysis results showed that, only among APOE-ε4 carriers, every SD unit increase in linoleic acid was associated with a reduced risk of all-cause stroke (hazard ratio [HR], 0.54 [95% CI, 0.38-0.78]), ischemic stroke (HR, 0.48 [95% CI, 0.33-0.71]), and all-cause mortality (HR, 0.70 [95% CI, 0.57-0.85]). In contrast, every SD unit increase in palmitic acid was related to an increased risk of all-cause stroke (HR, 1.58 [95% CI, 1.16-2.17]), ischemic stroke (HR, 1.76 [95% CI, 1.26-2.45]), and coronary heart disease (HR, 1.48 [95% CI, 1.09-2.01]), also in APOE-ε4 carriers only. Results for docosahexaenoic acid and arachidonic acid were heterogeneous between cohorts. Conclusions- These exploratory results suggest that APOE-ε4 carriers may be more susceptible to the beneficial or adverse impact of fatty acids on cardiovascular disease and mortality. In this subgroup, higher linoleic acid was protective for stroke and mortality, whereas palmitic acid was a risk factor for stroke and coronary heart disease. The mechanisms underlying these novel findings warrant further investigation.

Dataset Information

A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease.

Background

Methods and results

Conclusions

Publications

A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease.

Similar Datasets

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