High systemic inflammation response index and increased cardiovascular risk and mortality in MASLD: A prospective cohort study
Haixiang Zheng, Kuangyi Wu, Hong Zheng, Guanlin Chen, Yulong Lan, Shuohua Chen, Gavino Casu, Leonardo A. Sechi, Shouling Wu, Gianpaolo Vidili, Youren Chen
Abstract
Background & Aims The correlation between systemic inflammation response index(SIRI) and both cardiovascular disease(CVD, including myocardial infarction and total stroke) and mortality in individuals with metabolic dysfunction-associated steatotic liver disease(MASLD, hepatic steatosis with metabolic dysfunction) remains unclear. Here, we examine this relevance in a substantial Chinese cohort. Methods 24,340 MASLD population from the Kailuan study were observed over a median of 16.0 years. SIRI was calculated using counts of neutrophil, monocyte, and lymphocyte. Cox proportional hazards models estimated hazard ratios(HRs) for CVD and mortality across SIRI quartiles. Net reclassification improvement assessed SIRI's predictive value versus hs-CRP and other indices. Mediation analysis assessed the roles of platelet count(PLT), Chinese visceral adiposity index(CVAI) and triglyceride-glucose index(TyG). Results During follow-up, 4,171 CVD events and 4,510 deaths occurred. Elevated SIRI was significantly linked to higher risks of CVD (HR for Q4 vs. Q1: 1.21; 95% CI: 1.10–1.31, P<0.001), including myocardial infarction (HR: 1.22; 95% CI: 1.01–1.48, P=0.045), total stroke (HR: 1.18; 95% CI: 1.06–1.31, P=0.003), and mortality (HR: 1.34; 95% CI: 1.24–1.46, P<0.001) in MASLD. Associations were stronger among women (HR: 1.17; 95% CI: 1.07–1.29, P<0.01) and physically inactive individuals (HR: 1.09; 95% CI: 1.05–1.13, P<0.01). SIRI improved outcome prediction over hs-CRP and others, with significant reclassification gains(5.84;95% CI: 2.57–9.12; P < 0.001). TyG partially mediated these associations(5.3% for CVD, P=0.006; 2.9% for mortality, P=0.003), whereas PLT exhibited slight inverse mediation on mortality(-3.3%, P=0.032). Conclusions High SIRI independently correlates with a heightened risk of CVD and mortality in MASLD. The findings underscore systemic inflammation's role and propose SIRI as an effective biomarker for risk stratification in this individuals. Clinical trial number ChiCTR-TNC-11001489 Impact and implications This study provides important evidence linking systemic inflammation, as measured by the systemic inflammation response index (SIRI), to increased CVD and mortality in individuals with MASLD, a prevalent condition with rising global burden. The findings underscore the clinical relevance of inflammation markers in cardiovascular risk stratification, particularly for patients and healthcare providers managing MASLD. Physicians and policymakers could incorporate SIRI into routine assessments to identify MASLD patients at higher risk of cardiovascular events, potentially guiding targeted interventions aimed at mitigating systemic inflammation and metabolic dysfunction. Nonetheless, due to the predominantly male, community-based cohort from northern China, further research across diverse populations is warranted to confirm these associations before widespread clinical implementation.