Frontiers in Cardiovascular Medicine (Jul 2022)

Blood-Based Biomarkers to Search for Atrial Fibrillation in High-Risk Asymptomatic Individuals and Cryptogenic Stroke Patients

  • Elena Palà,
  • Alejandro Bustamante,
  • Alejandro Bustamante,
  • Jorge Pagola,
  • Jesus Juega,
  • Jaume Francisco-Pascual,
  • Jaume Francisco-Pascual,
  • Anna Penalba,
  • Maite Rodriguez,
  • Mercedes De Lera Alfonso,
  • Juan F. Arenillas,
  • Juan Antonio Cabezas,
  • Soledad Pérez-Sánchez,
  • Francisco Moniche,
  • Reyes de Torres,
  • Teresa González-Alujas,
  • Teresa González-Alujas,
  • Josep Lluís Clúa-Espuny,
  • Josep Lluís Clúa-Espuny,
  • Juan Ballesta-Ors,
  • Domingo Ribas,
  • Juan Acosta,
  • Alonso Pedrote,
  • Felipe Gonzalez-Loyola,
  • Felipe Gonzalez-Loyola,
  • Delicia Gentile Lorente,
  • Delicia Gentile Lorente,
  • Miguel Ángel Muñoz,
  • Miguel Ángel Muñoz,
  • Carlos A. Molina,
  • Joan Montaner

DOI
https://doi.org/10.3389/fcvm.2022.908053
Journal volume & issue
Vol. 9

Abstract

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BackgroundAtrial fibrillation (AF) increases the risk of ischemic stroke in asymptomatic individuals and may be the underlying cause of many cryptogenic strokes. We aimed to test the usefulness of candidate blood-biomarkers related to AF pathophysiology in two prospective cohorts representative of those populations.MethodsTwo hundred seventy-four subjects aged 65–75 years with hypertension and diabetes from the AFRICAT cohort, and 218 cryptogenic stroke patients aged >55 years from the CRYPTO-AF cohort were analyzed. AF was assessed by 4 weeks of monitoring with a wearable Holter device (NuuboTM™). Blood was collected immediately before monitoring started. 10 candidate biomarkers were measured by automated immunoassays (Roche, Penzberg) in the plasma of all patients. Univariate and logistic regression analyses were performed in each cohort separately.ResultsAtrial fibrillation detection rate was 12.4% (AFRICAT cohort) and 22.9% (CRYPTO-AF cohort). 4 biomarkers were significantly increased in asymptomatic individuals with AF [Troponin-T, Angiopoietin-2 (Ang-2), Endocan, and total N-terminal pro-B type natriuretic peptide (NT-proBNP)] and 7 biomarkers showed significantly higher concentrations in cryptogenic stroke patients with AF detection [growth differentiation factor 15, interleukin 6, Troponin-T, Ang-2, Bone morphogenic protein 10, Dickkopf-related protein 3 (DKK-3), and total NT-proBNP]. The models including Ang-2 and total NT-proBNP [AUC 0.764 (0.665–0.863)], and Ang-2 and DKK-3 [AUC = 0.733 (0.654–0.813)], together with age and sex, showed the best performance to detect AF in high-risk asymptomatic individuals, and in cryptogenic stroke patients, respectively.ConclusionBlood-biomarkers, in particular, total NT-proBNP, DKK-3, and Ang-2, were associated with AF reflecting two mechanistically different pathways involved in AF pathophysiology (AF stretch and vascular changes). The combination of these biomarkers could be useful in AF screening strategies in the primary care setting and also for searching AF after cryptogenic stroke.

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