BMC Medicine · Feb 25, 2026

Routine inflammatory indices modify clonal hematopoiesis-related prognostic risk in patients undergoing percutaneous coronary intervention: a real-world cohort study

By Shen X, Song Y, Zhao H et al.

BACKGROUND: Patients undergoing percutaneous coronary intervention (PCI) remain at substantial residual inflammatory risk, potentially driven by clonal hematopoiesis of indeterminate potential (CHIP), a novel pro-inflammatory contributor to atherogenesis. However, the clinical implications of CHIP-inflammation interplay in secondary prevention remain insufficiently understood. We aimed to investigate the joint impact of CHIP and systemic inflammation on prognosis among PCI patients. METHODS: This cohort included PCI patients receiving guideline-directed lipid-lowering and dual antiplatelet therapies. CHIP mutations were identified by targeted sequencing with a mean sequencing depth of 985 × . Systemic inflammation was assessed using 12 routine inflammatory indices. Cox proportional hazards models were used to assess the impact of CHIP and inflammatory indices on 5-year all-cause mortality, the primary outcome. Major adverse cardiac and cerebrovascular events (MACCE) comprised all-cause mortality, nonfatal myocardial infarction, ischemic stroke, stent thrombosis, and unplanned revascularization. RESULTS: Among 3640 PCI patients, 799 (21.95%) carried CHIP mutations. During a median follow-up of 5.06 years, CHIP was independently associated with increased risks of all-cause (hazard ratio (HR), 1.76; 95% confidence interval (CI), 1.20-2.57) and cardiac mortality (HR, 2.19; 95% CI, 1.31-3.65). Notably, this association was significantly modified by systemic inflammatory burden, as reflected by aggregate index of systemic inflammation (AISI), monocyte-lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), and systemic inflammatory response index (SIRI) (adjusted Pinteraction < 0.05). Specifically, CHIP conferred no excess mortality risk in low-inflammatory states, as reflected by SII (HR, 0.92; 95% CI, 0.52-1.66), whereas elevated inflammation significantly amplified CHIP-related mortality risk (HR, 3.36; 95% CI, 1.94-5.82), even among small-clone carriers (variant allele fraction 0.5-2%). Although no overall association was observed between CHIP and 5-year MACCE, significant associations emerged under elevated levels of SII (HR, 1.31; 95% CI, 1.05-1.64) and SIRI (HR, 1.38; 95% CI, 1.10-1.72). Moreover, incorporating CHIP into the GRACE score, a traditional risk assessment tool, yielded a modest yet significant improvement in long-term mortality prediction after PCI (ΔC-index, 3%; 95% CI, 0.9-6.6%). CONCLUSIONS: Hematopoiesis-related genetic alterations conferred excess prognostic risk, primarily in the presence of elevated hematological inflammation, underscoring the potential benefit of inflammatory burden management in PCI patients harboring CHIP.

doi.org/10.1186/s12916-026-04711-4 Open access PubMed 41742215 Mechanisms