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.
| Discipline Area | Score |
|---|---|
| Public Health |  |
| Internal Medicine |  |
| Cardiology | |
| Family Medicine (FM)/General Practice (GP) | |
| General Internal Medicine-Primary Care(US) | |
Nice "validation" of the Women's Health Study 30-year follow-up findings published last year, with consistent findings regardless of sex. This argues for routine "screening" with LDL-C, CRP, and Lp(a), which arguably should be undertaken at least once in a lifetime in the primary prevention setting.
So the combination of LDL-C, HsCRP, and lipoprotein predict a 20-year risk for MACE. Will this information make it more likely that providers and patients will start and continue effective lifestyle and pharmacological measures? Will this result in decreased CV mortality and morbidity compared with current practice? Still to be determined.
I'm not sure how important this study is. Demonstrating a graded relationship with risk is an important attribute of a proposed screening test, but it is not sufficient. There needs to be the demonstration that interventions based on these risk predictions lower subsequent outcome events. Until that is known, I don't see proven value for this screening test and some possibility of harm.
CRP and LPa appear to add more information about CV risk than LDL alone. However, we need to know if getting these additional labs add more information than what is known from the AHA (Framingham) CV Risk Calculator or the AHA PREVENT Calculator for this to be useful.
Obtaining lipid measures for cardiovascular disease screening is currently standard of care in addition to other Framingham/AHA risk factors. Adding hsCRP and Lp(a) to standard risk assessment is not new. It appears that when added to LDL, these additional factors add value. However, it still remains to be seen whether they also contribute when added to these other established risk factors.
I agree with the findings that primary screening for hyperlipidemia and major adverse cardiovascular events should involve 3 parameters: LDL-C, high sensitivity-CRP, and lipoprotein(a) because of the statistically significant result obtained with the EPIC NORFOLK study.
