Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events.
Level 3 - non-randomized controlled study
Prospective cohort study assessing prognostic biomarkers.
PubMed 12432042 · doi:10.1056/NEJMoa021993
What was done
Baseline levels of C-reactive protein (CRP) and low-density lipoprotein (LDL) cholesterol were measured in 27,939 apparently healthy American women. Participants were followed prospectively for a mean of 8 years for the occurrence of first cardiovascular events, defined as myocardial infarction, ischemic stroke, coronary revascularization, or cardiovascular death. Risk prediction was evaluated using multivariable models adjusted for age, smoking status, diabetes, blood pressure categories, hormone-replacement therapy use, and Framingham risk score components.
What was found
CRP and LDL cholesterol were minimally correlated (r = 0.08). Across increasing quintiles compared with the lowest quintile, the adjusted relative risks for first cardiovascular events were 1.4, 1.6, 2.0, and 2.3 for CRP (P < 0.001), compared to 0.9, 1.1, 1.3, and 1.5 for LDL cholesterol (P < 0.001). Overall, 77% of cardiovascular events occurred among women with baseline LDL cholesterol levels below 160 mg/dL (4.14 mmol/L), and 46% occurred in women with LDL below 130 mg/dL (3.36 mmol/L). CRP and LDL tended to identify different high-risk subsets, and assessing both biomarkers provided superior prognostic stratification compared to either alone.
Why it matters
This study shows that systemic inflammation measured by CRP is a strong, independent predictor of incident cardiovascular events in women, adding meaningful prognostic information beyond standard lipid profiles and traditional Framingham risk scores.
Limits
The study was restricted to American women, limiting direct generalizability to men and other demographic groups. Biomarkers were measured only at baseline, leaving potential temporal variation unaddressed. The observational design assesses prognostic association rather than a causal role of CRP in atherogenesis.
Cited by
- contradicts The JUPITER trial and related studies showed that patients with high LDL cholesterol but low C-reactive protein have a negligible risk of cardiovascular disease compared to those with both high LDL and high CRP.