Collagen biomarkers predict new onset of hypertension in normotensive participants: The Multi-Ethnic Study of Atherosclerosis

Objective: Vascular remodeling associated with increased extracellular matrix (ECM) may precede hypertension. Procollagen type III N-terminal propeptide (PIIINP) and collagen type I carboxy-terminal telopeptide (ICTP) reflect collagen turnover and are important in ECM remodeling. PIIINP and ICTP are increased in cardiovascular diseases (CVD). We hypothesized that PIIINP and ICTP among normotensives predict incident hypertension. Methods: We included 1252 Multi-Ethnic Study of Atherosclerosis participants with mean age 58.1-12.4 years, 48% men, free of overt CVD, having SBP and DBP less than 130/85mmHg and not using any antihypertensive medication, and having plasma PIIINP and ICTP measurements, all assessed at baseline. We studied the association of baseline PIIINP and ICTP with the relative incidence density (RID) of incident hypertension, defined as SBP/DBP at least 140/90 mmHg, or antihypertensive therapy use during follow-up (four examinations over median 9.4 years). Results: Baseline mean SBP/DBP was 110.9-14.0/ 67.9-10.4 mmHg. Mean concentration of PIIINP was 5.39-1.95mg/l and ICTP was 3.18-1.39mg/l. During follow-up visits, 35.9% of the participants developed hypertension. After adjustment for age, race, and sex there was a significant RID for new onset of hypertension of 1.16 (1.06, 1.28), P=0.0017 for PIIINP and 1.20 (1.08,1.33) for ICTP, P=0.0008. After additional adjustment for renal function, CVD risk factors and inflammatory variables, RID for new onset hypertension was 1.28 (1.15,1.42), P<0.001 for PIIINP and 1.29 (1.15,1.44) for ICTP, P<0.0001. Conclusion: Biomarkers of ECM remodeling predicted the development of hypertension in normotensive participants free of overt CVD.