Associations between neutrophil-percentage-to-albumin ratio level and all-cause mortality and cardiovascular disease-cause mortality in general population: evidence from nhanes 1999-2010

Abstract Introduction Chronic inflammation is a recognized independent risk factor for cardiovascular disease (CVD), highlighting the need for reliable inflammatory indicators to predict CVD(1). As an inflammatory indicator which has been proved to have predictive value for the prognosis of CVDs, neutrophil percentage-to-albumin ratio (NPAR) has obtained increasing attention(2,3), but further research is needed to confirm the relationship with mortality in general population. Purpose To explore whether NPAR can serve as a predictive inflammatory indicator for CVD-cause and all-cause mortality in general population. Methods This prospective cohort study included 21317 individuals who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. The baseline NPAR level was calculated as Neutrophil percentage (%) * 100/Albumin (g/dl). Data for CVD and all-cause mortality were acquired by linking the cohort database with the National Death Index through December 31, 2019.Weighted Kaplan–Meier curves with log-rank tests were conducted to access cumulative survival differences across different NPAR results. Restricted cubic spline analyses were employed to examine the nonlinear association. Multivariable Cox proportional hazards regression models were used to compute hazard ratios and 95% CIs. Receiver Operating Characteristic (ROC) curves were used to compare predictive value of NPAR with systemic immune inflammation index (SII) and neutrophils percent. Results In this cohort study, during 270014 person-years of follow-up, 4074 all-cause deaths and 1116 CVD-cause deaths were documented. We found significant associations between elevated NPAR and both CVD-cause and all-cause mortality in Kaplan–Meier curves (both P for log-rank test<0.001). Restricted cubic splines revealed non-linear associations between NPAR level and both CVD-cause (P=0.018 for nonlinearity) and all-cause mortality (P<0.001 for nonlinearity) (Figure 1A and 1B). After adjusting for confounding factors, participants in the highest NPAR tertile had a significantly increased risk of all-cause mortality (HR: 1.46, 95% CI: 1.33-1.61) and CVD-cause mortality (HR: 1.54, 95% CI: 1.32-1.80) compared to those in the lowest tertile, while no association was detected for individuals in the middle tertile (Figure 2). The effect of NPAR was consistent across most subgroups, with no significant interaction with most covariates except for high cholesterol (CVD-cause mortality: P=0.014, all-cause mortality: P=0.022). Further ROC analysis confirmed that NPAR had higher predictive value than neutrophil percent and SII. Conclusions Elevated NPAR level was significantly associated with an increased risk of all-cause and CVD-cause mortality in general population.Given its easy-to-calculate nature and high predictive value, NPAR index, with implications in public health, deserves greater attention in inflammatory assessment and cardiovascular prevention.Figure 1 Nonlinear associationFigure 2 Cox regression table