Midregional proatrial natriuretic peptide improves risk stratification after ischemic stroke

Abstract

ObjectiveTo validate midregional proatrial natriuretic peptide (MR-proANP) for outcome prediction and diagnosis of cardioembolic stroke etiology compared to established clinical variables.MethodsIn this prospective multicenter cohort study, we quantified MR-proANP levels in ischemic stroke patients within 24 hours of onset. Primary outcome measures were 90-day mortality, unfavorable functional outcome (modified Rankin Scale score >2), and cardioembolic stroke etiology diagnosed during hospitalization.ResultsOf 788 included patients, 783 completed their 90-day follow-up, and 118 patients (15%) died. After full adjustment, MR-proANP levels were associated with 90-day mortality (adjusted hazard ratio 6.12, 95% confidence interval [CI] 2.36–15.84, p = 0.01) and functional outcome (adjusted odds ratio [aOR] 2.46, 95% CI 1.05–5.74, p = 0.038). For mortality prediction, adding MR-proANP to the regression model increased its discriminatory accuracy, and the continuous net reclassification index (cNRI) was 49% (95% CI 26%–78%, p < 0.001). For functional outcome, there was no significant improvement in discrimination or reclassification. Cardioembolic stroke etiology and the diagnosis of atrial fibrillation at hospital discharge were associated with MR-proANP with an aOR of 2.10 (95% CI 1.11–3.97, p = 0.02) and 18.35 (95% CI 7.94–42.45, p < 0.001), respectively. The cNRI of MR-proANP for cardioembolic stroke etiology was not significant, as opposed to atrial fibrillation (78%, 95% CI 60%–89%, p < 0.001). MR-proANP levels ≥289 pmol/L had a specificity of 86% and sensitivity of 48% for the diagnosis of atrial fibrillation.ConclusionMR-proANP is a newly validated blood biomarker providing additional prognostic information for mortality after stroke. Higher MR-proANP levels were associated with cardioembolic stroke etiology and, even more strongly, atrial fibrillation.