Multiple Blood Biomarkers and Stroke Risk in Atrial Fibrillation: The REGARDS Study.

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  • Additional Information
    • Source:
      Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101580524 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2047-9980 (Electronic) Linking ISSN: 20479980 NLM ISO Abbreviation: J Am Heart Assoc Subsets: MEDLINE
    • Publication Information:
      Original Publication: Oxford : Wiley-Blackwell
    • Subject Terms:
      Decision Support Techniques*; Atrial Fibrillation/*blood ; Biomarkers/*blood ; Ischemic Stroke/*blood; Black or African American ; Aged ; Aged, 80 and over ; Atrial Fibrillation/diagnosis ; Atrial Fibrillation/ethnology ; Atrial Fibrillation/therapy ; Case-Control Studies ; Cystatin C/analysis ; Factor VIII/analysis ; Female ; Humans ; Incidence ; Interleukin-6/blood ; Ischemic Stroke/diagnosis ; Ischemic Stroke/ethnology ; Ischemic Stroke/prevention & control ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Peptide Fragments/blood ; Predictive Value of Tests ; Prognosis ; Proof of Concept Study ; Prospective Studies ; Risk Assessment ; Risk Factors ; United States/epidemiology ; White People
    • Abstract:
      Background Atrial fibrillation is associated with increased stroke risk; available risk prediction tools have modest accuracy. We hypothesized that circulating stroke risk biomarkers may improve stroke risk prediction in atrial fibrillation. Methods and Results The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a prospective cohort study of 30 239 Black and White adults age ≥45 years. A nested study of stroke cases and a random sample of the cohort included 175 participants (63% women, 37% Black adults) with baseline atrial fibrillation and available blood biomarker data. There were 81 ischemic strokes over 5.2 years in these participants. Adjusted for demographics, stroke risk factors, and warfarin use, the following biomarkers were associated with stroke risk (hazard ratio [HR]; 95% CI for upper versus lower tertile): cystatin C (3.16; 1.04-9.58), factor VIII antigen (2.77; 1.03-7.48), interleukin-6 (9.35; 1.95-44.78), and NT-proBNP (N-terminal B-type natriuretic peptide) (4.21; 1.24-14.29). A multimarker risk score based on the number of blood biomarkers in the highest tertile was developed; adjusted HRs of stroke for 1, 2, and 3+ elevated blood biomarkers, compared with none, were 1.75 (0.57-5.40), 4.97 (1.20-20.5), and 9.51 (2.22-40.8), respectively. Incorporating the multimarker risk score to the CHA 2 DS 2 VASc score resulted in a net reclassification improvement of 0.34 (95% CI, 0.04-0.65). Conclusions Findings in this biracial cohort suggested the possibility of substantial improvement in stroke risk prediction in atrial fibrillation using blood biomarkers or a multimarker risk score.
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    • Grant Information:
      K08 HL096841 United States HL NHLBI NIH HHS; P20 GM135007 United States GM NIGMS NIH HHS; R01 HL111362 United States HL NHLBI NIH HHS; U01 NS041588 United States NS NINDS NIH HHS
    • Contributed Indexing:
      Keywords: atrial fibrillation; biomarkers; prospective studies; risk factors; stroke
    • Accession Number:
      0 (Biomarkers)
      0 (CST3 protein, human)
      0 (Cystatin C)
      0 (IL6 protein, human)
      0 (Interleukin-6)
      0 (Peptide Fragments)
      0 (pro-brain natriuretic peptide (1-76))
      114471-18-0 (Natriuretic Peptide, Brain)
      839MOZ74GK (F8 protein, human)
      9001-27-8 (Factor VIII)
    • Publication Date:
      Date Created: 20210730 Date Completed: 20211029 Latest Revision: 20230701
    • Publication Date:
      20240628
    • Accession Number:
      PMC8475705
    • Accession Number:
      10.1161/JAHA.120.020157
    • Accession Number:
      34325516