Smoking, apolipoprotein E genotypes, and mortality (the Ludwigshafen RIsk and Cardiovascular Health study).

Aims The genetic polymorphism of apolipoprotein E (APOE) has been suggested to modify the effect of smoking on the development of coronary artery disease (CAD) in apparently healthy persons. The interaction of these factors in persons undergoing coronary angiography is not known. Methods and results We analysed the association between the APOE-genotype, smoking, angiographic CAD, and mortality in 3263 participants of the LUdwigshafen RIsk and Cardiovascular Health study. APOE-genotypes were associated with CAD [ɛ22 or ɛ23: odds ratio (OR) 0.56, 95% confidence interval (CI) 0.43–0.71; ɛ24 or ɛ34 or ɛ44: OR 1.10, 95% CI 0.89–1.37 compared with ɛ33] and moderately with cardiovascular mortality [ɛ22 or ɛ23: hazard ratio (HR) 0.71, 95% CI 0.51–0.99; ɛ33: HR 0.92, 95% CI 0.75–1.14 compared with ɛ24 or ɛ34 or ɛ44]. HRs for total mortality were 1.39 (95% CI 0.39–0.1.67), 2.29 (95% CI 1.85–2.83), 2.07 (95% CI 1.64–2.62), and 2.95 (95% CI 2.10–4.17) in ex-smokers, current smokers, current smokers without, or current smokers with one ɛ4 allele, respectively, compared with never-smokers. Carrying ɛ4 increased mortality in current, but not in ex-smokers (HR 1.66, 95% CI 1.04–2.64 for interaction). These findings applied to cardiovascular mortality, were robust against adjustment for cardiovascular risk factors, and consistent across subgroups. No interaction of smoking and ɛ4 was seen regarding non-cardiovascular mortality. Smokers with ɛ4 had reduced average low-density lipoprotein (LDL) diameters, elevated oxidized LDL, and lipoprotein-associated phospholipase A2. Conclusion In persons undergoing coronary angiography, there is a significant interaction between APOE-genotype and smoking. The presence of the ɛ4 allele in current smokers increases cardiovascular and all-cause mortality. [ABSTRACT FROM PUBLISHER]