Association of MR-proANP circulating levels with ischemic stroke of cardioembolic etiology: a systematic review and meta-analysis

Abstract

Background: While accurate identification of acute ischemic stroke (AIS) etiology is fundamental for its appropriate management, in a significant proportion of patients, etiology remains undetermined despite extensive work-up. Midregional pro-atrial natriuretic peptide (MR-proANP) shows potential as a biomarker of cardioembolic (CE) etiology and could contribute to these patients' reclassification. We aimed to review and synthesize all data on the association between MR-proANP and CE stroke. Methods: We systematically reviewed clinical studies reporting an association between MR-proANP and CE stroke in adults. Data were extracted, and a meta-analysis was performed using the random-effects model. Results: 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 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, along with a strong association with atrial fibrillation (AF). Finally, higher MR-proANP levels were associated with an increased risk of future stroke of CE origin. Discussion: 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.