Lipoprotein (a), Lipids, Aspirin, and Risk of Myocardial Infarction in the Physician's Health Study

BACKGROUND: Previously reported data from the Physicians' Health Study indicate that there is no association between lipoprotein (a) level and subsequent risk of myocardial infarction among members of a large cohort of middle-aged men followed up prospectively for an average of 60.2 months. OBJECTIVE: To investigate whether this null finding is related to the generally favorable lipid profile of the cohort or to randomized assignment of aspirin. METHODS: In a follow-up analysis of 296 confirmed cases of myocardial infarction and 296 controls, we evaluated the association between lipoprotein (a) level and cardiovascular risk for those with and without hyperlipidemia as well as for those randomly allocated aspirin treatment and placebo. RESULTS: For those with total cholesterol levels > or = 200 mg/dl, the age-adjusted smoking-adjusted relative risks of a first myocardial infarction associated with lipoprotein (a) levels above the 25th, 50th, 75th, 90th, and 95th percentiles of the control distribution were 0.9, 1.1, 1.6, 1.7 and 1.0 (all NS; P for trend 0.5). Among those with total cholesterol levels < 200 mg/dl, the adjusted relative risks of myocardial infarction associated with these cutoff points were 0.9, 0.7, 1.2, 0.7, and 1.4 (all NS; P for trend 0.7). Analyses limited to those with total cholesterol levels > or = 240 mg/dl or to men with higher than normal total cholesterol: high-density lipoprotein ratios revealed similar null findings. We observed no significant interaction between total cholesterol and lipoprotein (a) levels for these groups. For those randomly allocated aspirin, the age-adjusted and smoking-adjusted relative risks of myocardial infarction associated with lipoprotein (a) levels above the 25th, 50th, 75th, 90th, and 95th percentile cutoff points were 0.9, 0.9, 1.5, 1.5, and 1.0 (all NS; P trend 0.9). For those randomly allocated placebo, the age-adjusted and smoking-adjusted relative risks of myocardial infarction associated with lipoprotein (a) levels were 0.8, 0.9, 1.4, 1.5, and 1.3 (all NS; P trend 0.9). There was no significant interaction between aspirin and lipoprotein (a) level for any of these groups. Similar null findings were observed in analyses evaluating evidence for there being a trend across increasing quartiles of lipoprotein (a). CONCLUSION: These prospective data indicate that neither levels of lipids nor aspirin treatment modified the lack of overall effect of lipoprotein (a) on the risk of a first myocardial infarction in the Physicians' Health Study.