Prognostic impact of residual inflammatory and triglyceride risk in statin-treated patients with well-controlled LDL cholesterol and atherosclerotic cardiovascular disease

AIMS: Identifying alternative contributors to the residual risk of atherosclerotic cardiovascular disease (ASCVD) beyond LDL cholesterol (LDL-C) levels is crucial. We investigated the relative impact of triglycerides (TGs) and high-sensitivity C-reactive protein (hs-CRP) on outcomes in statin-treated patients with well-controlled LDL-C undergoing percutaneous coronary intervention (PCI) for established ASCVD. METHODS AND RESULTS: We included 9446 statin-treated patients with LDL-C < 70 mg/dL undergoing PCI between 2012 and 2022, stratified into four groups: (i) no residual risk (TG <150 mg/dL + hs-CRP <2 mg/L); (ii) residual TG risk (TG ≥150 mg/dL + hs-CRP <2 mg/L); (iii) residual inflammatory risk (TG <150 mg/dL + hs-CRP ≥2 mg/L); and (iv) residual TG and inflammatory risk (TG ≥150 mg/dL + hs-CRP ≥2 mg/L). The primary endpoint was major adverse cardiovascular events (MACE) at 1 year, consisting of all-cause mortality, myocardial infarction, or stroke. Cox regression analysis was performed, using the no residual risk group as a reference. Of the total population, 5339 (56.5%) had no residual risk, 555 (5.9%) presented residual TG risk, 3009 (31.9%) had residual inflammatory risk, and 543 (5.7%) exhibited residual combined risk. After multivariable adjustment, patients with residual inflammatory or combined risk showed a significantly higher hazard of MACE, mainly driven by all-cause mortality. No significant difference was observed between patients with residual TG risk and those with no residual risk. CONCLUSION: In statin-treated patients with well-controlled LDL-C undergoing PCI, residual inflammatory risk-alone or in combination with residual TG risk-was associated with a higher incidence of MACE, highlighting the need for targeted preventive strategies beyond LDL-C lowering.