AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Nonlinear Dose Response Meta Analysis of the Red Blood Cell Distribution Width to Albumin Ratio (RAR) and Cardiovascular Mortality Evidence from Restricted Cubic Splines
By J KJ, Keswani K, Haq NU et al.
Background: The red blood cell distribution width-to-albumin ratio (RAR) has emerged as a novel prognostic biomarker in cardiovascular disease, integrating inflammatory burden and nutritional status. However, the dose-response relationship between RAR and cardiovascular mortality remains incompletely characterized. We performed a nonlinear dose-response meta-analysis using restricted cubic splines (RCS) to quantify the shape and magnitude of this association. Methods: We conducted a systematic review across Google Scholar, Embase Scopus and PubMed from inception to March 31st 2026 following PRISMA 2020 guidelines.We conducted a systematic review and dose-response meta-analysis of studies examining RAR and cardiovascular mortality. Restricted cubic splines with knots positioned at the 10th, 50th, and 90th percentiles (1.5, 3.5, and 7.0 ml/g, respectively) were fitted to model nonlinear relationships. Nonlinearity was assessed using Akaike Information Criterion (AIC) and Wald tests. Random-effects models were employed, with subgroup analyses stratified by cardiovascular disease type. Publication bias was evaluated using Egger's regression test. Results: Sixteen studies encompassing 30,933 patients were included. The pooled analysis demonstrated a significant nonlinear dose-response relationship between RAR and cardiovascular mortality (P-nonlinearity <0.001, χ ² =53). Compared with the reference value (RAR=3 ml/g), the pooled hazard ratio for highest versus lowest RAR categories was 1.88 (95% CI 1.59-2.23). Per 1 ml/g increase in RAR, the hazard ratio was 1.27 (95% CI 1.16-1.39). Specific RAR thresholds yielded escalating risks: RAR=4 ml/g (HR=1.53, 95% CI 1.29-1.80), RAR=5 ml/g (HR=1.97, 95% CI 1.54-2.53), and RAR=10 ml/g (HR=2.93, 95% CI 2.19-3.91). The dose-response curve revealed an inflection point at approximately 4.2 ml/g, with steeper risk acceleration below this threshold. Subgroup analyses showed stronger associations in acute myocardial infarction (HR=2.43, 95% CI 1.52-3.87) compared with heart failure (HR=1.78, 95% CI 1.13-2.81). Substantial heterogeneity was observed (I ² =91%). Egger's test indicated no significant publication bias (p=0.14). Conclusions: This dose-response meta-analysis demonstrates a significant nonlinear relationship between RAR and cardiovascular mortality, with accelerated risk at RAR values exceeding 4.2 ml/g. The RAR represents a readily available, cost-effective prognostic tool that mayfacilitate risk stratification in diverse cardiovascular populations. Future prospective studies should validate optimal RAR thresholds for clinical decision-making.