APOE4 POLYMORPHISM INCREASES THE RISK FOR EXERCISE-INDUCED SILENT-MYOCARDIAL-ISCHEMIA IN OLDER MEN

The apolipoprotein (apo) E4 polymorphism is associated with increased risk for symptomatic coronary artery disease (CAD). This study examine s whether the apoepsilon4 allele is associated with an increased risk for exercise-induced silent myocardial ischemia (SI) in healthy, older (62 +/- 7 years; mean +/- SD), normocholesterolemic, nonsmoking male volunteers. The apoepsilon4 allele was present in 20 of 45 (44%) men w ith SI on graded exercise treadmill testing compared with 22 of 127 (1 7%) men of comparable age with normal exercise tests (P<.001), resulti ng in a crude relative risk of 2.57 (95% confidence limits, 1.57 to 4. 23) for SI in men with the apoepsilon4 allele compared with those with out the epsilon4 allele. Although the lipoprotein lipid levels did not differ between men with normal exercise tests and those with SI, the men with the apoE 4/3 phenotype had higher total cholesterol and low-d ensity lipoprotein cholesterol (LDL-C) levels than those with the apoE 2/3 and 313 phenotypes (P<.05). Men with SI and the apoE 4/3 phenotyp e were older (64 +/- 5 versus 57 +/- 8 years, P<.01) and leaner (P<.01 ) than the normal non-SI men with the apoE 4/3 phenotype. The older ag e of the men with SI and the apoE 413 phenotype is consistent with a p rogression of atherosclerosis over time. Men with SI and the apoE 313 phenotype were of comparable age and body composition to apoE 313 phen otype men with normal exercise tests. Thus, even in the presence of no rmal LDL-C levels, the apoepsilon4 allele may predispose older men to SI.