New Biomarkers Associated With Cardiovascular Death In Patients With Atrial Fibrillation Using Multimarker Screening : Insights From The Aristotle Trial

• BackgroundAtrial fibrillation (AF) is associated with significant mortality. Biomarkers have shown to add predictive value and could facilitate the understanding of key pathophysiologic mechanisms in AF. Using proximity extension assay (PEA), a new multiplex analytic technique enabling analysis of hundreds of plasma biomarkers, we explored the association between 255 cardiovascular and inflammatory biomarkers with cardiovascular death in patients with AF on oral anticoagulation.MethodsFrom the ARISTOTLE trial of patients with AF, 517 cases of cardiovascular death and 4057 randomly selected controls were included in an unstratified case-control cohort study. Plasma obtained at randomization was analyzed with conventional immunoassays or the OLINK PEA- panels CVDII, CVDIII, and inflammation panel. Median follow-up time was 1.8 years. The association between biomarkers and cardiovascular death was evaluated using Random Forest and individual Cox-regression analyses adjusted for clinical characteristics, renal function, and cardiac biomarkers (NT-proBNP and cTnT-hs), with adjustment for multiple testing.ResultsOf the 255 studied biomarkers, NT-proBNP, cTnT-hs, interleukin-6 (IL-6), transferrin receptor protein 1 (TfR1) and fibroblast growth factor 23 (FGF-23) remained statistically significantly associated with cardiovascular death according to both the Random Forest and the adjusted Cox-regression analysis. In the adjusted Cox analysis, the hazard ratio (95% confidence intervals) per interquartile range was 1.58 (1.38 - 1.83) for NT-proBNP, 1.56 (1.40 -1.75) for cTnT-hs, 1.28 (1.14 - 1.44) for IL-6, 1.27 (1.14 - 1.41) for TfR1 and 1.18 (1.09 -1.28) for FGF-23.ConclusionAmong a vast number of biomarkers, NT-proBNP, cTnT-hs, IL-6, TfR1 and FGF-23 had an independent association with cardiovascular death in patients with AF. The associations of TfR1 and FGF-23 with cardiovascular death in AF are novel and the role of iron regulation (TfR1), and phosphate metabolism (FGF-23), warrants further investigation.

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

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