Association of MR-proANP Circulating Levels with Ischemic Stroke of Cardioembolic Etiology: A Systematic Review and Meta-Analysis.

Abstract

The accurate identification of acute ischemic stroke (AIS) etiology is fundamental for its management. Midregional pro-atrial natriuretic peptide (MR-proANP) shows potential as a biomarker of cardioembolic (CE) etiology. We aimed to review and synthesize all data on the association between MR-proANP and CE stroke. Articles were searched in Scopus, Web of Science, and Medline databases up to March 2025. Search terms included the free-text words to identify "stroke" and "MR-pro-ANP" and the Mesh term "Stroke." A meta-analysis was performed using the random-effects model. ROBINS-E Tool was used for quality assessment. Eight studies were included, from which six evaluated the association between MR-proANP and CE etiology in patients with AIS and two evaluated MR-proANP levels in the general population and their association with the risk of future CE stroke. All studies were consistent in describing significantly higher levels of MR-proANP in patients with CE stroke when compared to non-CE stroke. Four studies were included in the meta-analysis, confirming a significant association between MR-proANP and CE etiology (OR 6.04, 95% CI 2.79-13.07). Also, MR-proANP showed moderate to high discriminative ability in identifying CE strokes, significantly improving the discriminative capacity of clinical models, and a strong association with atrial fibrillation (AF). Finally, higher MR-proANP levels were associated with an increased risk of future CE stroke. MR-proANP circulating levels were consistently associated with CE etiology of ischemic stroke, improving the discriminative ability of clinical models, suggesting a role for this biomarker in the accurate classification of AIS etiology.