# Association of alkaline-phosphatase/albumin ratio with all-cause mortality in critically ill patients with ischemic stroke: a retrospective study

**Authors:** Tao Zheng, Mengmeng Guo, Yating Han, Guanglu Li, Xianhua Wang, Shenjie Li, Yuting Gao, Wenxiong Tang, Zunjing Liu

PMC · DOI: 10.3389/fneur.2025.1567767 · Frontiers in Neurology · 2025-04-30

## TL;DR

This study found that a higher alkaline phosphatase to albumin ratio (APAR) is linked to increased risk of death in critically ill patients with ischemic stroke.

## Contribution

The study is the first to show that APAR is a significant predictor of mortality in critically ill ischemic stroke patients.

## Key findings

- Higher APAR was significantly associated with all-cause mortality at 28, 90, and 365 days after admission.
- APAR showed a linear relationship with 28-day and 365-day mortality, but a nonlinear one with 90-day mortality.
- The association between APAR and mortality was consistent across subgroups without hypertension, diabetes, or other comorbidities.

## Abstract

Recent studies have shown that alkaline phosphatase to albumin ratio (APAR) is a prognostic biomarker for coronary heart disease and cancer. However, the effect of APAR on the prognosis of ischemic stroke (IS) remains unclear. We aimed to assess the association of APAR with all-cause mortality in critically ill patients with IS.

Critically ill patients with IS were identified from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) Version 3.0 database, and classified into quartiles based on APAR index levels. Clinical outcomes included all-cause mortality at 28-days, 90-days and 365-days after admission. Cox proportional hazards regression analysis and restricted cubic spline method were used to clarify the relationship between APAR index and clinical outcomes in critically ill patients with IS.

A total of 1,690 critically ill patients with IS were selected from the MIMIC-IV database. Multivariate Cox proportional hazard analysis showed that increased APAR index was significantly associated with all-cause mortality. After adjusting for potential confounding factors, patients with higher APAR (Q4: 1.524–2.794) had significantly increased all-cause mortality at 28-days, 90-days, and 365-days after admission (HR 2.05, 95%CI 1.47–2.86, p = 0; HR 2.09, 95%CI 1.53–2.85, p = 0; HR 2.11, 95%CI 1.55–2.87, p = 0). APAR had a linear relationship with 28-days and 365-days mortality (P for non-linearity: 0.098 and 0.051), but a nonlinear relationship with 90-days mortality (P for non-linearity: 0.042). Subgroup analyses further revealed that higher APAR was also associated with increased long-term mortality in IS patients without hypertension, DM, cardiovascular disease, liver disease or CKD. In addition, we did not observe any interaction between subgroup variables and APAR.

A higher APAR index was significantly associated with increased all-cause mortality at 28-days, 90-days and 365-days after admission for critically ill patients with IS. The APAR index may help identify patients with IS at high risk of all-cause death.

## Linked entities

- **Diseases:** ischemic stroke (MONDO:1060198), diabetes mellitus (MONDO:0005015), cardiovascular disease (MONDO:0004995), liver disease (MONDO:0005154), chronic kidney disease (MONDO:0005300)

## Full-text entities

- **Genes:** ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, SH2B2 (SH2B adaptor protein 2) [NCBI Gene 10603] {aka APS}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** death (MESH:D003643), inflammation (MESH:D007249), cirrhosis (MESH:D005355), liver cirrhosis (MESH:D008103), neuroinflammatory (MESH:D000090862), Hypertension (MESH:D006973), coronary heart disease (MESH:D003327), Stroke (MESH:D020521), acute ischemic stroke (MESH:D000083242), vascular calcification (MESH:D061205), protein-energy malnutrition (MESH:D011502), cerebral edema (MESH:D001929), cancer (MESH:D009369), uremia (MESH:D014511), white matter (MESH:D056784), MI (MESH:D009203), disability (MESH:D009069), heart failure (MESH:D006333), pneumonia (MESH:D011014), brain injury (MESH:D001930), neurological deterioration (MESH:D009422), Organ Failure (MESH:D009102), DM (MESH:D003920), hypoalbuminemia (MESH:D034141), peripheral artery disease (MESH:D058729), atrial fibrillation (MESH:D001281), Alzheimer (MESH:D000544), atherosclerosis (MESH:D050197), ventricular arrhythmias (MESH:D001145), APS III (MESH:D016884), acute (MESH:D000208), lacunar infarction (MESH:D059409), CCI (MESH:C566784), hemorrhagic stroke (MESH:D000083302), hepatitis (MESH:D056486), hyperlipidemia (MESH:D006949), CVD (MESH:D002318), pulmonary edema (MESH:D011654), neurological diseases (MESH:D020271), small cerebral vascular disease (MESH:D059345), epilepsy (MESH:D004827), vascular disease (MESH:D014652), physiology (MESH:D012735), IS (MESH:D002544), deep vein thrombosis (MESH:D020246), neuronal damage (MESH:D009410), APAR (MESH:C562645), Critically ill (MESH:D016638), liver disease (MESH:D008107), ill (MESH:D002908), calcification (MESH:D002114), coma (MESH:D003128), traumatic brain injury (MESH:D000070642), dysphagia (MESH:D003680), CKD (MESH:D051436)
- **Chemicals:** pyrophosphate (MESH:C107241), reactive oxygen species (MESH:D017382), creatinine (MESH:D003404), K (MESH:D011188), glucose (MESH:D005947), Na (MESH:D012964), oxygen (MESH:D010100), TC (MESH:D013667), APAR (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC12074950/full.md

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Source: https://tomesphere.com/paper/PMC12074950