Residual inflammatory versus lipid risk after STEMI in statin-treated patients: impact on early recurrent events
V B Halatiu, I Benedek, I P Rodean, T BenedekAbstract
Background
Residual cardiovascular risk remains high in STEMI survivors despite guideline-directed high-intensity statins, driven by persistent dyslipidaemia and low-grade inflammation. Evidence in statin-treated coronary patients suggests inflammatory residual risk may outweigh cholesterol risk, but this is poorly studied in contemporary, intensively treated STEMI cohorts.
Purpose
To compare the prognostic impact of residual lipid versus inflammatory risk on early events in STEMI patients on high-intensity statins.
Methods
We conducted a single-centre prospective cohort study including 428 consecutive STEMI patients who underwent primary PCI and were discharged on maximally tolerated high-intensity statin therapy between 2020 and 2025. Residual lipid profile was assessed at 3 months (LDL-C, non-HDL-C, triglycerides, apolipoprotein B); residual lipid risk was defined as LDL-C ≥55 mg/dL and/or non-HDL-C ≥85 mg/dL. Residual inflammatory risk was evaluated using high-sensitivity C-reactive protein (hsCRP) and neutrophil-to-lymphocyte ratio (NLR), defined as hsCRP ≥2 mg/L or NLR in the upper tertile. Patients were categorized into four groups (no residual risk, isolated lipid risk, isolated inflammatory risk, combined risk) and followed 6–12 months for a composite endpoint of MACE, unplanned revascularization, or heart-failure hospitalization. Multivariable Cox regression provided adjusted hazard ratios for each group.
Results
Of 428 STEMI patients (mean age 61±11 years, 29% women), LDL-C <55 mg/dL was achieved in 177 (41.4%). Overall, 77 patients (18.0%) had no residual risk, 88 (20.6%) isolated lipid risk, 118 (27.6%) isolated inflammatory risk, and 145 (33.9%) combined residual risk. During a median follow-up of 9.2 months, 74 patients (17.3%) experienced the composite endpoint. Event rates were 6.5% (no residual risk), 10.2% (isolated lipid), 21.2% (isolated inflammatory), and 25.5% (p<0.001). In multivariable analysis, isolated inflammatory risk (adjusted HR 1.82; p=0.03) and combined risk (HR 2.11; p=0.003) independently predicted events, whereas isolated lipid risk did not (HR 1.14; p=0.71). Among patients with LDL-C <55 mg/dL, elevated hsCRP/NLR identified higher risk (22.4% vs 8.1%; HR 2.36; p=0.03), while LDL-C quartiles within target were not predictive (p for trend=0.48). Adding hsCRP and NLR improved discrimination (C-statistic 0.72 to 0.79; p=0.01), whereas adding LDL-C/non-HDL-C did not (p=0.45).
Conclusion(s)
Residual inflammatory risk was a more powerful determinant of early recurrent cardiovascular events than residual lipid risk. These data support systematic post-STEMI assessment of hsCRP and NLR and indicate that risk stratification based solely on LDL-C underestimates residual vulnerability. Our findings suggest that targeted anti-inflammatory strategies, in addition to aggressive lipid lowering, may be necessary to meaningfully reduce residual cardiovascular risk in this very-high-risk population.