Routine inflammatory indices modify clonal hematopoiesis-related prognostic risk in patients undergoing percutaneous...

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.

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.

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 P_interaction < 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%).

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.