Association of RDW and RAR with All-Cause and Cardiovascular Mortality in NAFLD/MASLD: A Population-Based Study

Abstract

Background: Red blood cell distribution width (RDW) is associated with prognosis in chronic liver disease. The RDW-to-albumin ratio (RAR) is a novel biomarker that reflects inflammation and nutritional status. However, the associations of RDW and RAR with mortality in non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. Objectives: This study examined the associations of RDW and RAR with all-cause and cardiovascular disease (CVD) mortality among US adults with NAFLD and MASLD, separately. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 1999 - 2018 were linked to National Death Index records through 2019. Parallel analyses were conducted in 2 independent cohorts: patients with NAFLD (n = 5519) and patients with MASLD (n = 5387). The exposures were RDW and RAR. The primary outcomes were all-cause mortality and CVD mortality. Multivariable Cox proportional hazards models were used to evaluate the associations of RDW and RAR with all-cause and CVD mortality. Restricted cubic splines (RCS) were used to assess nonlinearity, and threshold-effect analyses were performed when significant nonlinearity was detected. Subgroup analyses were conducted according to sex, age, education, race, poverty-income ratio (PIR), and Fibrosis-4 (FIB-4) index. Results: After full adjustment, elevated RDW and RAR levels were significantly associated with increased risks of all-cause and CVD mortality (all P < 0.05). Significant dose–response trends were observed across quartiles (all P-trend < 0.001), with the highest quartile showing a markedly higher risk than the lowest quartile. Subgroup analyses indicated effect modification by several stratification factors. Conclusions: RDW and RAR were independently associated with an increased mortality risk in individuals with NAFLD and MASLD, supporting their potential utility as convenient prognostic biomarkers in this population.