Protein Biomarkers and Risk of Atrial Fibrillation: The Framingham Heart Study


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.


We included participants Ȧ5;50 years of age from the Framingham Heart Study Offspring and Third Generation cohorts, who had 85 fasting plasma proteins measured using Luminex xMAP platform. Hazard ratios (per 1 standard deviation increment of rank normalized biomarker [HR]) and 95% confidence intervals (CI) 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, valvular heart disease, prevalent myocardial infarction, and prevalent heart failure. We used the False Discovery Rate to account for multiple testing.


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 insulin-like growth factor 1 (IGF1) (HR per 1 standard deviation 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 insulin-like growth factor-binding protein 1 (IGFBP1) (HR = 1.24; 95% CI, 1.1-1.39) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (HR = 1.73; 95% CI, 1.52-1.96).


Decreased levels of IGF1 and increased levels of IGFBP1 and NT-proBNP were associated with higher risk of incident AF.