Prognostic Value of Natriuretic Peptides for Delayed Cerebral Ischemia and Outcomes After Aneurysmal Subarachnoid...

Aneurysmal subarachnoid hemorrhage (aSAH) is a type of hemorrhagic stroke with high morbidity and mortality, with life-threatening secondary complications including delayed cerebral ischemia (DCI). Biomarkers capable of improving early risk of DCI remain understudied. DCI frequently triggers neurogenic cardiac injury, manifested through left ventricular dysfunction and wall strain. Natriuretic peptides (NP), including brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP), have been implicated in the cardiac stress responses after aSAH, but their prognostic utility for DCI remains uncertain.

The objective was to systematically review and meta-analyze observational studies evaluating the association of NP with DCI, mortality, and functional outcome in patients with aSAH.

Following PRISMA guidelines, five databases were searched up to September 2025. Eligible studies included adult patients with confirmed aSAH and measured NP levels within 7 days, reporting outcomes of interest. Data were synthesized using random-effects models, with effect sizes expressed as odds ratios (ORs) or standardized mean differences (SMDs). Risk of bias was assessed with the ROBINS-I tool.

In total, 17 studies (n = 3172 patients) were included, with 12 proving data for quantitative synthesis. Elevated NP levels were significantly associated with DCI in dichotomous (OR 2.66, 95% CI 1.16-6.10) adjusted models (adjusted OR (aOR) 1.84, 95% CI 1.01-3.35), and continuous analyses (SMD 0.94, 95% CI 0.20-1.68). Admission NP demonstrated moderate diagnostic accuracy for DCI prediction (pooled area under the curve, AUC, 0.76). In contrast, no statistically significant associations were observed for mortality (OR 2.37, 95% CI 0.66-8.50) or unfavorable functional outcomes (OR 1.90, 95% CI 0.65-5.52). Heterogeneity across studies was substantial.

Elevated NP levels are significantly associated with DCI in patients with aSAH. These findings support the use of NP as useful prognostic biomarkers. However, their utility in predicting mortality and functional outcomes remains inconclusive. Large prospective studies with standardized methodologies are required to validate their clinical applicability.