Blood inflammation-albumin ratio linked to early decline after ischemic stroke

A higher C-reactive protein-to-albumin ratio was associated with early neurological deterioration in a retrospective study of 1,766 patients hospitalized with acute ischemic stroke. Of the patients analyzed, 270, or 15.3%, experienced a worsening of at least two points on the National Institutes of Health Stroke Scale motor-item or total score within 72 hours of admission. The ratio, calculated by dividing C-reactive protein concentration in milligrams per liter by albumin concentration in grams per liter, remained associated with deterioration after adjustment for demographic, clinical and laboratory factors, but it did not significantly outperform C-reactive protein alone as a predictor.

The study, conducted at the Quzhou Affiliated Hospital of Wenzhou Medical University in China, included consecutive patients admitted between September 2016 and September 2022. Eligible patients had confirmed acute ischemic stroke, admission and symptom onset within 24 hours, diffusion-weighted magnetic resonance imaging showing an acute infarct within 48 hours, blood samples for C-reactive protein and albumin collected within 48 hours, and complete records needed for analysis. Of 2,150 patients screened, 215 unique patients were removed for incomplete records, missing laboratory data or loss to follow-up, and 169 more were excluded because of hemorrhagic transformation, pre-existing pneumonia, active malignancy, or severe hepatic or renal dysfunction.

Certified neurologists who were blinded to laboratory results assessed early neurological deterioration using the National Institutes of Health Stroke Scale, or NIHSS. Baseline scores were obtained within 24 hours of admission and follow-up scores during the first 72 hours. Patients whose motor-item or total score increased by at least two points were classified as having the outcome. The researchers also recorded age, sex, smoking, hypertension, diabetes, atrial fibrillation, chronic obstructive pulmonary disease, stroke severity, dysphagia, consciousness, blood counts, glucose, kidney function and other laboratory measures. Because the distribution of the C-reactive protein-to-albumin ratio was skewed, values were transformed using a base-2 logarithm before the main analyses.

Patients who deteriorated were older on average than those who did not, with mean ages of 72.3 and 68.7 years, respectively, and atrial fibrillation was more frequent in the deterioration group, affecting 26.3% compared with 14.8%. Median C-reactive protein-to-albumin ratio was 0.12 in the deterioration group, with an interquartile range of 0.05–0.44, compared with 0.07, with an interquartile range of 0.03–0.16, among patients without deterioration. The inflammation marker C-reactive protein and white blood cell count were also higher in the deterioration group, while mean albumin concentration was lower. These differences describe the groups at baseline and do not by themselves establish that the ratio caused neurological worsening.

The pattern was evident when the cohort was divided into quartiles of the log-transformed ratio. Early deterioration occurred in 50 of 508 patients, or 9.84%, in the lowest quartile; 44 of 396, or 11.11%, in the second; 74 of 431, or 17.17%, in the third; and 102 of 431, or 23.67%, in the highest. Patients in the highest quartile had 2.90 times the unadjusted odds of deterioration compared with those in the lowest. After adjustment for age and sex, the odds ratio was 2.66, and the fully adjusted estimate was 1.95 with a 95% confidence interval of 1.27–2.88. A significant trend across quartiles remained in the adjusted analysis.

The fully adjusted model accounted for age, sex, smoking, hypertension, diabetes, atrial fibrillation, chronic obstructive pulmonary disease, baseline NIHSS score, dysphagia, Glasgow Coma Scale score, white blood cell count, fasting plasma glucose and estimated glomerular filtration rate. When the logarithm of the ratio was analyzed continuously, each one-unit increase was associated with an adjusted odds ratio of 1.12 for deterioration, with a 95% confidence interval of 1.03–1.21. Variance inflation factors for the model variables ranged from 1.05 to 2.69, indicating no substantial multicollinearity under the investigators’ criteria. Subgroup estimates were generally positive, but several confidence intervals included no association, and no interaction test was significant; the results therefore did not show that the relationship differed across the examined clinical strata.

As a stand-alone classifier, the ratio showed only modest discrimination for early deterioration, with an area under the receiver operating characteristic curve, or AUC, of 0.627. It performed significantly better than the Age-Atrial fibrillation-Dysphagia-Sex-Stroke severity score, known as A2DS2, whose AUC was 0.520. However, its performance was not significantly different from that of C-reactive protein alone, which had an AUC of 0.624; the comparison between them gave a p-value of 0.111. The ratio also did not differ significantly from neutrophil count, with an AUC of 0.616, or white blood cell count, with an AUC of 0.606.

Adding the ratio to A2DS2 raised the AUC from 0.520 to 0.591, a difference of 0.071 that was statistically significant according to the study’s analysis. Smaller increases were seen when it was added to models containing white blood cell count or neutrophil count. In contrast, adding it to C-reactive protein increased the AUC from 0.624 to only 0.626, and that change was not statistically significant. The findings therefore support the ratio as a potentially inexpensive adjunct derived from routine blood tests, particularly alongside clinical risk assessment, but not as a replacement for C-reactive protein or as a marker with demonstrated superior predictive performance.

Generalized additive and two-piecewise regression models were used to explore whether the relationship changed at a particular value. The models suggested a possible change in slope near a log-transformed ratio of −5.64, corresponding to a raw ratio of approximately 0.020. Below that candidate value, the adjusted odds ratio was 2.35, with a 95% confidence interval of 0.99–5.58; at or above it, the odds ratio was 1.15, with a confidence interval of 1.05–1.26. However, the difference between the two slopes was not statistically significant, and the threshold model did not significantly improve fit over a linear model in a likelihood-ratio comparison. The value of approximately 0.020 is therefore hypothesis-generating rather than a validated biological or clinical cutoff.

Several limitations constrain how the results should be interpreted. The retrospective, single-center design cannot establish causation and may limit generalizability. C-reactive protein and albumin were measured only once within 48 hours, so the analysis could not capture changes in inflammation or nutritional status over time, and residual confounding remains possible despite extensive adjustment. The NIHSS-based definition may not capture every aspect of neurological decline. Patient-level overlap with earlier cohorts from the institutional registry was not quantified, long-term outcomes were not evaluated, and prospective multicenter validation is still required. The findings identify an association between a readily available blood-test ratio and early deterioration after acute ischemic stroke, but they do not show that lowering inflammation or increasing albumin would prevent deterioration, nor do they establish a value at which monitoring or treatment should change.

Subject of Research: Association between the C-reactive protein-to-albumin ratio and early neurological deterioration in acute ischemic stroke

Article Title: Elevated C-reactive protein-to-albumin ratio is associated with early neurological deterioration in acute ischemic stroke: a retrospective cohort study

Article References: Zhou, Z., Xu, W., Wu, Z., Duan, T., Yang, M., Xu, Y., & Ye, J. (2026). Elevated C-reactive protein-to-albumin ratio is associated with early neurological deterioration in acute ischemic stroke: a retrospective cohort study. Frontiers in Neurology, 17, Article 1880425. https://doi.org/10.3389/fneur.2026.1880425

Image Credits: AI Generated

DOI: 10.3389/fneur.2026.1880425

Keywords: acute ischemic stroke, early neurological deterioration, C-reactive protein, albumin, inflammation, blood biomarkers, retrospective cohort, risk prediction, NIHSS, stroke outcome, Elevated, C-reactive