Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials.
Level 3 - non-randomized controlled study
Collaborative observational cohort analysis evaluating prognostic biomarker associations across three randomized clinical trial populations
PubMed 36893777 · doi:10.1016/S0140-6736(23)00215-5
What was done
Researchers conducted a collaborative pooled cohort analysis of 31,245 patients with or at high risk of atherosclerotic disease receiving contemporary statin therapy across three multinational randomized trials: PROMINENT (n=9,988), REDUCE-IT (n=8,179), and STRENGTH (n=13,078). Baseline high-sensitivity C-reactive protein (hsCRP) and low-density lipoprotein cholesterol (LDLC) were categorized into quartiles. Multivariable Cox models adjusted for age, sex, BMI, smoking, blood pressure, prior cardiovascular disease history, and randomized treatment assignment evaluated associations with major adverse cardiovascular events (MACE), cardiovascular death, and all-cause death.
What was found
Residual inflammation strongly predicted outcomes: comparing the highest to lowest hsCRP quartile, adjusted hazard ratios were 1.31 (95% CI 1.20-1.43; p<0.0001) for MACE, 2.68 (95% CI 2.22-3.23; p<0.0001) for cardiovascular mortality, and 2.42 (95% CI 2.12-2.77; p<0.0001) for all-cause mortality. By contrast, residual cholesterol was not significantly associated with MACE (highest vs lowest LDLC quartile adjusted HR 1.07, 95% CI 0.98-1.17; p=0.11) and showed smaller associations with cardiovascular mortality (HR 1.27, 95% CI 1.07-1.50; p=0.0086) and all-cause mortality (HR 1.16, 95% CI 1.03-1.32; p=0.025).
Why it matters
Among statin-treated patients, residual systemic inflammation measured by hsCRP is a more potent driver of recurrent cardiovascular events and mortality than residual LDL cholesterol. This highlights residual inflammatory risk as a primary target for future combination therapies.
Limits
This is an observational biomarker analysis within clinical trial cohorts and cannot establish whether pharmacologically lowering hsCRP directly improves clinical outcomes. The constituent trials (PROMINENT, REDUCE-IT, STRENGTH) selected for specific cardiometabolic and dyslipidemic risk profiles, potentially limiting generalizability to all statin-treated populations. The abstract does not provide details on longitudinal biomarker changes or specific statin dosing regimens.