ABSTRACT NUMBER: ESOC2026A1967 GENETIC PREDICTORS OF ATRIAL NATRIURETIC PEPTIDES AND CIRCULATING BIOMARKERS IN THE CONTEXT OF ETIOLOGICAL DIAGNOSIS OF ISCHEMIC STROKE

Abstract Background and aims Mid-regional pro-atrial natriuretic peptide (MR-proANP) serves as a biomarker for cardioembolic stroke (CES). rs5065, a genetic variant of the Natriuretic Peptide A (NPPA)-gene encoding ANP, remains insufficiently studied in stroke etiologies. Within the PHEGAESUS-study, a phenotype-genotype association study investigating ESUS, we conducted a targeted biomarker analysis to evaluate the impact of rs5065 on MR-proANP and stroke etiology. Methods Between December 2020 and July 2023, patients with ischemic stroke were enrolled at Hannover Medical School. Genotyping was performed using Axiom myDesign Genotyping-Array. MR-proANP serum concentration was measured via fluorescence immunoassay, if samples were available more than 24 hours after stroke onset. Descriptive analyses were performed to elucidate an association between rs5065, MR-proANP-level and ESUS. Results After quality control, 1,003 patients with clinical and SNP-data were available (288 classified as ESUS, 715 as another defined etiology). In the dominant model (AG+GG vs AA), G allele carriers were more frequent in ESUS than in other stroke etiologies (69.1% vs 62.4%, p-chi2: 0.044, OR 1.35, 95%CI: 1.01-1.80). After adjustment for Essen Stroke Risk-Score, the association of rs5065 carrier status with higher odds of ESUS (aOR: 1.37, 95%CI: 1.02-1.84) remained. No differences of MR-proANP-level across the genotypes were observed (median (interquartile range): AG+GG [n=92]: 99.1 (83.8)pmol/l vs AA [n=52]: 91.5 (118.8) pmol/l, p Mann-Whitney-U: 0.8). Conclusions The dominant G allel of rs5065 does not seem to influence MR-proANP-level, but is enriched in ESUS patients. Investigation of NPPA-genomic region may improve better understanding of genetic variances, biomarkers and ESUS. Conflict of interest Rebecca Menkhaus: nothing to disclose, Gerrit M Grosse: nothing to disclose, Johannes Teller: nothing to disclose, Rieke Ringslstetter: nothing to disclose, Maria M Gabriel: nothing to disclose, Vinicius D Gastaldi: nothing to disclose, Hannelore Ehrenreich: nothing to disclose, Karin Weissenborn: nothing to disclose, Anika Grosshennig: nothing to disclose, Johanna Ernst: nothing to disclose