Objective: To assess prospectively the risk of myocardial infarction (MI) associated with elevated levels of lipoprotein(a) (Lp[a]).
Design: Nested case-control study using prospectively collected plasma samples.
Setting: Participants in the Physicians' Health Study.
Participants: A total of 14,916 male physicians aged 40 to 84 years with no prior history of MI or stroke provided plasma samples at baseline and were followed up prospectively for an average period of 60.2 months. Samples from 296 physicians who subsequently developed MI were analyzed for Lp(a) level together with paired controls, matched for smoking status and age.
Main outcome measure: Fatal or nonfatal acute MI.
Results: The distribution of Lp(a) level among cases was virtually identical to that of controls (P = .88), and there was no significant difference between groups for median Lp(a) levels (103.0 mg/L vs 102.5 mg/L; P = .73). In analyses controlling for age and smoking status, we found no evidence of association between increasing level of Lp(a) and risk of MI (relative risks from lowest to highest quintiles of Lp(a): 1.00, 0.97, 0.83, 0.88, and 1.07; P for trend = .93) or a threshold effect at any prespecified cutoff of Lp(a) level (relative risks associated with Lp[a] levels above the 25th, 50th, 75th, 90th, and 95th percentiles of the control distribution, respectively: 1.04, 1.00, 1.19, 1.00, and 1.07; all P values nonsignificant). Further adjustment for both lipid and nonlipid cardiovascular risk factors had no material impact.
Conclusions: In this prospective study of predominantly middle-aged white men, we found no evidence of association between Lp(a) level and risk of future MI. These data do not support the use of Lp(a) level as a screening tool to define cardiovascular risk among this population.