BackgroundInflammation plays an essential role in the pathogenesis of hypertension. A novel inflammatory biomarker systemic inflammatory response index (SIRI) is related with all-cause and cardiovascular (CVD) mortality, while the role of SIRI in hypertension patients is unclear. MethodsA total of 21,506 participants with hypertension were recruited in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. SIRI was calculated as the neutrophil count * monocyte count/lymphocyte count. Hypertension was defined according to the examination of blood pressure, prescription, and self-reported physician diagnosis. Survival status was followed through 31 December 2019. The non-linear relationship was assessed using restricted cubic spline analysis. The association of all-cause mortality with SIRI was evaluated using the Kaplan-Meier curve and the weighted Cox regression analysis. The predictive abilities were assessed with Receiver operating curve. ResultsDuring 189,063 person-years of follow-up, 5,680 (26.41%) death events were documented, including 1,967 (9.15%) CVD related deaths. A J-shaped association was observed between SIRI and all-cause and CVD mortality. The Kaplan-Meier curve indicated the all-cause and CVD mortality risks were higher in high SIRI quartiles compared with lower SIRI quartiles. After adjusting for all covariates, the SIRI was positively associated with the all-mortality risk with HR = 1.19 (1.15, 1.22), and CVD mortality with HR = 1.19 (1.15, 1.24). The result was robust in subgroup analysis and sensitivity analysis. ConclusionElevated SIRI level is associated with increased all-cause and CVD mortality among patients with hypertension. SIRI is considered as a potential inflammatory biomarker in the clinical practice. Further large-scale cohort studies are required to confirm our findings.