Editors' ChoiceAging

Biomarking Bad Outcomes

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Science Translational Medicine  28 Sep 2011:
Vol. 3, Issue 102, pp. 102ec156
DOI: 10.1126/scitranslmed.3003235

The knights of cardiovascular research are on a quest for their holy grail: knowing who is at the greatest risk for heart disease and how to modify that risk. Heart tissue undergoes age-related changes, including increased fibrosis—the infiltration of fibrous connective tissue—which may make a person more vulnerable to cardiovascular mayhem. Because collagen deposition is an integral part of fibrosis, Barasch et al. asked whether biomarkers of collagen turnover are associated with cardiovascular outcomes in older adults who were part of a large prospective community-based observational study: The Cardiovascular Health Study (CHS).

As people age, collagen is deposited in the extracellular matrix that surrounds cardiac muscle cells and has adverse effects on the heart’s mechanics and electrical system. Using a subcohort of the CHS (n = 880 study participants) in a case-control design, participants were divided into four groups: (i) heart failure with low ejection fraction, (ii) heart failure with normal ejection fraction, (iii) controls with cardiovascular disease risk factors but no heart failure, and (iv) healthy controls without cardiovascular disease. Frozen serum was assessed for biomarkers of collagen synthesis [carboxy-terminal propeptide of type I procollagen (PIP) and amino-terminal propeptide of type III procollagen (PIIINP)] and degradation [carboxy-terminal telopeptide of collagen type I (CITP)]. Outcomes were measured for a mean follow-up period of 12.4 years. The primary outcome was cardiovascular events (for example, myocardial infarction, stroke, or heart failure hospitalization), but all-cause death and incident heart failure were also assessed for the control groups. Elevated serum concentrations of CITP and PIIINP were associated with myocardial infarction, heart failure, and death in all groups, including the controls, even when adjusted for age, gender, race, hypertension, diabetes, and hyperlipidemia. PIP had only a weak association, confirming what the authors had found in a previous study.

These results support the theory that myocardial fibrosis is associated with adverse cardiovascular outcomes; suggest that therapies to decrease collagen deposition may be beneficial; and pinpoint markers of collagen turnover that identify those at risk for adverse cardiovascular outcomes. Clinical trials to oppose collagen formation in those with cardiac disease are under way. Such trials will reveal whether therapies that change collagen biomarker concentrations also decrease adverse cardiovascular outcomes in patients.

E. Barasch et al., The relationship between serum markers of collagen turnover and cardiovascular outcome in the elderly: The Cardiovascular Health Study. Circ. Heart Failure, 7 September 2011 (10.1161/circheartfailure.111.962027). [Abstract]

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