Smoking-driven systemic inflammation elevates mortality risk in hypertensive patients: A cross-sectional study using insights from NHANES 1999–2018

INTRODUCTION: Existing evidence on the association between smoking and hypertension (HTN) remains conflicting, and the potential role of systemic inflammation in mediating smoking-related mortality among hypertensive patients is poorly understood. This study aimed to investigate the association between smoking status, smoking volume, and HTN risk in a large, nationally representative sample. Furthermore, we sought to determine whether systemic inflammation, measured by the systemic inflammation index (SII), mediates the association between smoking and all-cause mortality in hypertensive individuals. METHODS: This cross-sectional, pooled secondary data analysis study utilized data from 10 cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Data on smoking, covariates, and hypertension status were collected through standardized interviews, questionnaires, and laboratory/physical examinations. A total of 28967 participants were included after excluding those with incomplete data. Propensity score matching (PSM) analysis was employed to adjust for confounding factors such as age, gender, BMI, race, and other sociodemographic variables. Logistic regression and restricted cubic spline regression were used to assess the dose-response relationship between smoking and HTN. Mediation analysis was performed to evaluate the role of systemic inflammation, as measured by the systemic inflammation index (SII), in the increased mortality risk among hypertensive smokers. RESULTS: Smoking significantly increased the likelihood of HTN after adjusting for confounders (adjusted odds ration, AOR=1.18; 95% CI: 1.10-1.27). A dose-response relationship was observed, with individuals smoking >30 cigarettes/day having the highest likelihood of HTN (AOR=1.37; 95% CI: 1.07-1.75). PSM analysis confirmed these findings, showing a significant increase in HTN prevalence among smokers (p=0.045). Smoking was also associated with increased overall mortality in hypertensive patients (HR=1.993; 95% CI: 1.766-2.249). Mediation analysis revealed that systemic inflammation, as measured by SII, accounted for 87.70% of the increased mortality in hypertensive smokers (ACME=0.068, p<0.001). CONCLUSIONS: This study establishes a significant association between smoking, HTN and mortality. The findings underscore a potential dose-response trend between cigarette consumption and HTN, with systemic inflammation playing a key role in mediating the higher mortality observed in hypertensive smokers. Interventions targeting smoking cessation and systemic inflammation may significantly reduce the burden of HTN-related morbidity and mortality.