Interaction between high-sensitivity C-reactive protein and mean platelet volume for 1-year major adverse cardiovascular events in stable coronary artery disease

Residual cardiovascular risk remains substantial in patients with stable coronary artery disease (CAD) despite guideline-based secondary prevention. We investigated whether systemic inflammation and platelet size jointly influence 1-year major adverse cardiovascular events (MACE) in 1463 patients with stable CAD. Using high-sensitivity C-reactive protein (hs-CRP) and mean platelet volume (MPV), we defined four joint phenotypes. Multivariable logistic regression was used to examine associations with MACE, with interaction assessed on multiplicative and additive scales. During 1-year follow-up, 71 events occurred. Compared with patients with low hs-CRP and low MPV, those with concurrent elevation of hs-CRP (> 3.0 mg/L) and MPV (≥ 10.1 fL) had a significantly higher risk of MACE (adjusted OR 2.23, 95% CI 1.15–4.25), whereas isolated elevation of either marker alone was not associated with increased risk. Positive interaction was observed on both multiplicative (P = 0.047) and additive scales (Relative Excess Risk due to Interaction 1.49, 95% CI 0.17–3.14). These findings were consistent across sensitivity and subgroup analyses. In stable CAD, combined elevation of hs-CRP and MPV identifies a subgroup at higher short-term risk, suggesting that joint assessment of inflammation and platelet size may improve stratification of residual thrombo-inflammatory risk.