Inflammation, Cholesterol, Lipoprotein(a), and 30-Year Cardiovascular Outcomes in Women.
Level 3 - non-randomized controlled study
Prospective longitudinal cohort study (30-year follow-up of trial participants)
PubMed 39216091 · doi:10.1056/NEJMoa2405182
What was done
Baseline levels of high-sensitivity C-reactive protein (hsCRP), low-density lipoprotein (LDL) cholesterol, and lipoprotein(a) were measured in 27,939 initially healthy U.S. women (mean age 54.7 years) followed prospectively for 30 years. The primary end point was a first major adverse cardiovascular event (a composite of myocardial infarction, coronary revascularization, stroke, or death from cardiovascular causes). Adjusted hazard ratios and 95% confidence intervals were calculated across quintiles of each biomarker, alongside age- and competing-risk-adjusted 30-year cumulative incidence curves.
What was found
During 30 years of follow-up, 3,662 first major cardiovascular events occurred. Comparing the top to bottom quintile, covariable-adjusted hazard ratios for the primary end point were 1.70 (95% CI, 1.52 to 1.90) for hsCRP, 1.36 (95% CI, 1.23 to 1.52) for LDL cholesterol, and 1.33 (95% CI, 1.21 to 1.47) for lipoprotein(a). Findings were consistent for coronary heart disease and stroke, each biomarker showed independent contributions, and the greatest risk spread occurred when all three biomarkers were combined.
Why it matters
A single baseline assessment of hsCRP, LDL-C, and lipoprotein(a) independently predicts cardiovascular risk over three decades in women. This supports expanding primary prevention and risk stratification strategies beyond traditional 10-year horizons.
Limits
The study was conducted entirely in U.S. women, limiting direct generalizability to men or other global populations. Biomarkers were measured only once at baseline without accounting for intra-individual variations or post-baseline treatments (e.g., lipid-lowering therapies) initiated over the 30-year span.