Comparative associations of LDL-C, Lp(a), hsCRP, and IL-6 with cardiovascular risk: Insights from the United Kingdom (UK) biobank and the multi-ethnic study of atherosclerosis (MESA).
Level 3 - non-randomized controlled study
Prospective observational cohort study analysis across two independent cohorts.
PubMed 42173333 · doi:10.1016/j.pcad.2026.05.005
What was done
Researchers evaluated participants from the UK Biobank and the Multi-Ethnic Study of Atherosclerosis (MESA) who had baseline measurements of low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6). The primary outcome was incident atherosclerotic cardiovascular disease (ASCVD), defined as myocardial infarction, stroke, or cardiovascular death. Multivariable Cox proportional hazards models were fitted to estimate hazard ratios comparing top to bottom quartiles of each biomarker, adjusting for traditional cardiovascular risk factors and mutually adjusting for the other biomarkers.
What was found
The mean age was 56.8 years (SD 8.1) in UK Biobank and 62.2 years (SD 10.2) in MESA. Comparing the highest to lowest quartiles in fully adjusted models, hazard ratios for incident ASCVD were: - UK Biobank: LDL-C 1.10 (95% CI: 0.97–1.25), Lp(a) 1.15 (95% CI: 1.03–1.29), hsCRP 1.19 (95% CI: 1.04–1.37), and IL-6 1.67 (95% CI: 1.44–1.93). - MESA: LDL-C 1.26 (95% CI: 1.02–1.56), Lp(a) 1.23 (95% CI: 0.99–1.53), hsCRP 1.13 (95% CI: 0.88–1.44), and IL-6 1.60 (95% CI: 1.24–2.07).
Why it matters
This study directly benchmarks inflammatory and lipid biomarkers against one another, highlighting IL-6 as a potentially stronger independent marker of residual cardiovascular risk in primary prevention than hsCRP or traditional lipid metrics.
Limits
The total sample size, event counts, and follow-up duration were not reported in the abstract. As an observational study, residual confounding remains possible, and single baseline biomarker measurements do not account for variation over time or baseline lipid-lowering therapies.