Routine Hematologic Indices as Scalable Biomarkers for Frailty: A Comprehensive Systematic Review and Meta-Analysis.

OBJECTIVES: To systematically evaluate the associations of albumin-based biomarkers, including the C-reactive protein-to-albumin ratio (CAR/hsCAR), neutrophil percentage-to-albumin ratio (NPAR), lactate-to-albumin ratio (LAR), and C-reactive protein-albumin-lymphocyte (CALLY) index, with mortality and major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD), and to compare their prognostic and discriminative performance. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Thirty-four studies involving 47,763 patients with CAD were included, encompassing predominantly acute coronary syndrome (ACS)-related populations as well as broader coronary and cardiovascular cohorts. METHODS: We systematically evaluated albumin-based biomarkers, including CAR/hsCAR, NPAR, LAR, and CALLY. Pooled associations with mortality and MACE were estimated using effect measures reported by the original studies. Discriminative performance and potential clinical utility were also evaluated where data were available. RESULTS: Higher CALLY values were associated with lower all-cause mortality (HR 0.46, 95% CI 0.24-0.87) and showed a directionally protective but nonsignificant association with MACE (HR 0.44, 95% CI 0.18-1.08). Elevated CAR/hsCAR was associated with increased mortality (OR 1.61, 95% CI 1.09-2.38) and MACE (HR 1.37, 95% CI 1.21-1.56) in ACS-related cohorts. NPAR showed the most consistent association with mortality (HR 1.88, 95% CI 1.71-2.08; I² = 4.8%), whereas its association with MACE was less stable (HR 1.86, 95% CI 0.56-6.13). LAR showed the largest pooled effect estimate for mortality (HR 2.50, 95% CI 1.78-3.51). In discriminative analyses, CAR showed the most balanced performance for long-term MACE, NPAR showed the strongest rule-in profile for long-term MACE, and CAR and CALLY showed the best discrimination for mortality. CONCLUSIONS AND IMPLICATIONS: Albumin-based biomarkers are associated with adverse outcomes in CAD, particularly in ACS-related populations, with distinct prognostic patterns across biomarkers and clinical endpoints. These routinely available indices may provide complementary information for risk stratification; however, prospective studies are needed to determine their incremental prognostic value and clinical utility beyond established risk assessment approaches.