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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 ( HF r EF ;  EF  <45%) from preserved  EF  ( HF p EF ;  EF  ≥45%). The incidence density for  HF p EF  and  HF r EF  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 μg/L, and mean ( SD )  PIIINP  was 5.48±2.04 μg/L. Among the  HF  cases, 96 were  HF r EF  and 107 were  HF p EF . Neither  ICTP  nor  PIIINP  significantly predicted incident  HF r EF . The incidence density for  HF p EF  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  HF p EF , but not  HF r EF .

Predictive Value of Collagen Biomarkers for Heart Failure With and Without Preserved Ejection Fraction: MESA (Multi‐Ethnic Study of Atherosclerosis)