Laila Staerk1,2, Sarah R Preis3, Honghuang Lin1,4, Steven A Lubitz5, Patrick T Ellinor5, Daniel Levy1, Emelia J Benjamin1,6,7,8, Ludovic Trinquart1,3. 1. National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, MA (L.S., H.L., D.L., E.J.B., L.T.). 2. Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Helleup, Denmark (L.S.). 3. Department of Biostatistics (S.R.P., L.T.), Boston University School of Public Health, MA. 4. Section of Computational Biomedicine (H.L.), Department of Medicine, Boston University School of Medicine, MA. 5. Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., P.T.E.). 6. Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA. 7. Cardiology and Preventive Medicine Sections (E.J.B.), Department of Medicine, Boston University School of Medicine, MA. 8. Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (E.J.B.).
Abstract
BACKGROUND: Identification of protein biomarkers associated with incident atrial fibrillation (AF) may improve the understanding of the pathophysiology, risk prediction, and development of new therapeutics for AF. We examined the associations between 85 protein biomarkers and incident AF. METHODS: We included participants ≥50 years of age from the FHS (Framingham Heart Study) Offspring and Third Generation cohorts, who had 85 fasting plasma proteins measured using Luminex xMAP platform. Hazard ratios (per 1 SD increment of rank-normalized biomarker [hazard ratio]) and 95% CIs for incident AF were calculated using Cox regression models adjusted for age, sex, height, weight, current smoking, systolic blood pressure, diastolic blood pressure, hypertension treatment, diabetes mellitus, valvular heart disease, prevalent myocardial infarction, and prevalent heart failure. We used the false discovery rate to account for multiple testing. RESULTS: The study sample comprised 3378 participants (54% women) with mean (SD) age of 61.5 (8.4) years. In total, 401 developed AF over a mean follow-up of 12.3±3.8 years. We observed lower hazard of incident AF associated with higher mean levels of IGF1 (insulin-like growth factor 1; hazard ratio per 1 SD increment in protein level, 0.84 [95% CI, 0.76-0.93]), and higher hazard of incident AF associated with higher mean levels of both IGFBP1 (insulin-like growth factor-binding protein 1; hazard ratio, 1.24 [95% CI, 1.1-1.39]) and NT-proBNP (N-terminal pro-B-type natriuretic peptide; hazard ratio, 1.73 [95% CI, 1.52-1.96]). CONCLUSIONS: Decreased levels of IGF1 and increased levels of IGFBP1 and NT-proBNP were associated with higher risk of incident AF.
BACKGROUND: Identification of protein biomarkers associated with incident atrial fibrillation (AF) may improve the understanding of the pathophysiology, risk prediction, and development of new therapeutics for AF. We examined the associations between 85 protein biomarkers and incident AF. METHODS: We included participants ≥50 years of age from the FHS (Framingham Heart Study) Offspring and Third Generation cohorts, who had 85 fasting plasma proteins measured using Luminex xMAP platform. Hazard ratios (per 1 SD increment of rank-normalized biomarker [hazard ratio]) and 95% CIs for incident AF were calculated using Cox regression models adjusted for age, sex, height, weight, current smoking, systolic blood pressure, diastolic blood pressure, hypertension treatment, diabetes mellitus, valvular heart disease, prevalent myocardial infarction, and prevalent heart failure. We used the false discovery rate to account for multiple testing. RESULTS: The study sample comprised 3378 participants (54% women) with mean (SD) age of 61.5 (8.4) years. In total, 401 developed AF over a mean follow-up of 12.3±3.8 years. We observed lower hazard of incident AF associated with higher mean levels of IGF1 (insulin-like growth factor 1; hazard ratio per 1 SD increment in protein level, 0.84 [95% CI, 0.76-0.93]), and higher hazard of incident AF associated with higher mean levels of both IGFBP1 (insulin-like growth factor-binding protein 1; hazard ratio, 1.24 [95% CI, 1.1-1.39]) and NT-proBNP (N-terminal pro-B-type natriuretic peptide; hazard ratio, 1.73 [95% CI, 1.52-1.96]). CONCLUSIONS: Decreased levels of IGF1 and increased levels of IGFBP1 and NT-proBNP were associated with higher risk of incident AF.
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