Collagen Biomarkers and Incidence of New Onset of Atrial Fibrillation in Subjects With No Overt Cardiovascular Disease at Baseline: The Multi-Ethnic Study of Atherosclerosis

Background Atrial fibrosis is a hallmark of structural remodeling in atrial fibrillation (AF). Plasma procollagen type III N-terminal propeptide (PIIINP) reflects collagen synthesis and degradation while collagen type I carboxy-terminal telopeptide (ICTP) reflects collagen degradation. We aimed to study baseline plasma PIIINP and ICTP and their associations with incident AF in participants initially free of overt cardiovascular disease. Methods In a stratified sample of the Multi-Ethnic Study of Atherosclerosis, initially aged 45–84 years, 3071 participants had both PIIINP and ICTP measured at baseline. Incident AF in 10-year follow-up was based on a hospital International Classification of Diseases code for AF or atrial flutter, in- or outpatient Medicare claims through 2011 (primarily in those aged 65–84 years), or ECG 10 years after baseline (n=357). The associations of PIIINP and ICTP with incident AF were estimated using Poisson regression with follow-up time offset. Results Baseline PIIINP (5.50±1.55 µg/L) and ICTP (mean±SD, 3.41±1.37 µg/L) were positively related (both P<0.0001) to incident AF in a model adjusting for age, race/ethnicity, and sex, with an apparent threshold (relative incidence density 2.81 [1.94–4.08] for PIIINP ≥8.5 µg/L [3.5% of the sample] and 3.46 [2.36–5.07] for ICTP ≥7 µg/L [1.7% of the sample]). Findings were attenuated but remained statistically significant after further adjustment for systolic blood pressure, height, body mass index, smoking, and renal function. Additional adjustment for other risk factors and biomarkers of inflammation did not alter conclusions. Conclusions Plasma collagen biomarkers, particularly at elevated levels, were associated with excess risk for AF.