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January 21, 2004

Novel Risk Factors for Atherosclerosis—Reply

Author Affiliations

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2004;291(3):301. doi:10.1001/jama.291.3.301-c

In Reply: In response to Dr von Eckardstein, in the study he cites,1 a serum Lp(a) level of 0.2 g/L or greater was associated with an increased risk of incident nonfatal myocardial infarction, fatal myocardial infarction, or sudden-death cardiovascular disease in patients with an already high predicted risk of cardiovascular disease using conventional risk factors. In this nested case-control study, in which there were 44 incident cardiovascular events, an elevated Lp(a) level did not add predictive value among patients within the first 3 quintiles of predicted global risk, and in the highest quintile the increase in risk of elevated Lp(a) level was of marginal statistical significance (relative risk, 2.8; 95% confidence interval, 1.1-7.2; P = .03). Therefore, while their analysis was suggestive of additive predictive value of elevated Lp(a) level to global risk scores, this study had relatively low statistical power to study this relationship rigorously. Moreover, surprising findings such as the absence of interactions between elevated Lp(a) level and smoking, hypertriglyceridemia, or diabetes emphasize the possibility of spurious results when multiple interactions are tested in studies with low statistical power. Therefore, while the analysis by von Eckardstein and colleagues lends some support for the additive risk conferred by elevated Lp(a) levels in patients with multiple conventional cardiovascular risk factors, more investigations are required to confirm or refute the interactions that were observed as well as the notable ones that were absent.

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