Predictive value of collagen biomarkers for heart failure with and without preserved ejection fraction: MESA (Multi-Ethnic Study of Atherosclerosis)

Background--Collagen biomarkers may correlate with incident heart failure (HF) and its subtypes. We hypothesized that circulating procollagen type III N-terminal propeptide (PIIINP) and collagen type I carboxy-terminal telopeptide (ICTP) predict incident HF. Methods and Results--We used a stratified sampling design in a multiethnic sample of 3187 subjects, initially aged 45 to 84 years and free of cardiovascular disease. We assayed baseline serum PIIINP and ICTP concentrations using radioimmunoassay. Incident HF was adjudicated, distinguishing reduced ejection fraction (HFrEF; EF < 45%) from preserved EF (HFpEF; EF =45%). The incidence density for HFpEF and HFrEF was computed using Poisson regression per SD for each of PIIINP and ICTP, adjusting in model 1 for age, race, sex, and renal function or in model 2 for these variables plus blood pressure and medication. Mean (SD) ICTP was 3.38±1.77 lg/L, and mean (SD) PIIINP was 5.48±2.04 lg/L. Among the HF cases, 96 were HFrEF and 107 were HFpEF. Neither ICTP nor PIIINP significantly predicted incident HFrEF. The incidence density for HFpEF per 100 people observed for 13 years was 1.65 for low PIIINP (lower 6 octiles) versus 3.00 for higher PIIINP (P=0.002) in model 1 and correspondingly 1.45 versus 2.59 (P=0.003) in model 2. For low ICTP (lower 7 octiles) versus higher ICTP (octile 8), incidence densities were 1.79 versus 3.64 (P=0.002) in model 1 and 1.58 versus 3.12 (P=0.002) in model 2. Conclusions--High levels of circulating ICTP and PIIINP as collagen biomarkers appear to be associated with incident HFpEF, but not HFrEF.