Low-density lipoprotein cholesterol, C-reactive protein, and lipoprotein(a) universal one-time screening in primary prevention: the EPIC-Norfolk study

Abstract Background and Aims Recent data from a large American cohort of women strongly support universal one-time screening for LDL cholesterol, high-sensitivity C-reactive protein (hsCRP), and lipoprotein(a) [Lp(a)] in primary prevention. This study addresses the validity and generalizability of this novel primary prevention strategy in a large prospective European cohort of initially healthy men and women. Methods Plasma levels of LDL cholesterol, hsCRP, and Lp(a) were measured at study entry in 17 087 participants from the EPIC-Norfolk study who were subsequently followed over a period of 20 years for major adverse cardiovascular events (MACEs). Competing risk- and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MACE across quintiles of each biomarker and sought evidence of independent as well as additive effects over time were calculated. Results During the 20-year follow-up, a total of 3249 MACEs occurred. Increasing quintiles of baseline LDL cholesterol, hsCRP, and Lp(a) all predicted 20-year risks; the multivariable-adjusted HRs in a comparison of the top to bottom quintile were 1.78 (95% CI: 1.57–2.00) for LDL cholesterol, 1.55 (95% CI: 1.37–1.74) for hsCRP, and 1.19 (95% CI: 1.07–1.33) for Lp(a). Compared with individuals with no biomarker elevations, the multivariable-adjusted HRs for incident MACE were 1.33, 1.68, and 2.41 for those with one, two, or three biomarkers in the top quintile, respectively (all P < .001). Each biomarker demonstrated independent contributions to overall risk and findings were consistent in analyses stratified by sex. Conclusions A single combined measure of LDL cholesterol, hsCRP, and Lp(a) among initially healthy European men and women was predictive of incident MACE during a 20-year period. These data replicate findings from a recent American cohort and strongly support universal screening for all three biomarkers in primary prevention.