Age and Duration of Follow-up as Modulators of the Risk for Ischemic Heart Disease Associated With High Plasma C-Reactive Protein Levels in Men

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Abstract
ACCUMULATING evidence suggests that inflammation may be etiologically important in the development of atherosclerosis.1 In this respect, plasma C-reactive protein (CRP), a marker of low to moderate systemic inflammation, has received much attention in recent years. Results from cross-sectional and prospective studies2 have indicated that raised plasma CRP levels were associated with an increased risk for future cardiovascular events among apparently healthy subjects3,4 as well as in individuals with stable and unstable angina5 or with previous myocardial infarction.6 Moreover, results from the Physicians' Health Study disclosed that baseline plasma CRP concentration added to the predictive value of traditional lipid risk factors in determining risk for first myocardial infarction.7 Although these data suggest that adding plasma CRP levels to the list of cardiovascular risk factors commonly assessed in the clinical practice would improve our ability to predict future cardiovascular events, critical issues remain to be specifically addressed. First, our current interpretation of the relationship between plasma CRP level and the risk for ischemic heart disease (IHD) in middle-aged men is based almost exclusively on data derived from cross-sectional or prospective nested case-control studies,8 with only 1 population-based study9 conducted in a relatively small cohort of subjects. Second, the ability of plasma CRP levels to predict an increased risk for IHD has yet to be tested while considering a comprehensive number of lipid and nonlipid cardiovascular risk factors as confounders. Third, the CRP prognostic value of IHD risk showed a strong time-to-event dependency in the elderly,10 whereas it appeared to be stable during follow-ups of varying lengths in a nested case-control study in middle-aged men.3 Thus, the chronological relationship between plasma CRP levels and the risk for future IHD events remains to be fully elucidated using population-based, prospective data.