Stimulus for Myocardial Fibrosis Early Sign of Cardiomyopathy
Serum-C terminal propeptide of type I procollagen levels elevated in mutation carriers
WEDNESDAY, Aug. 4 (HealthDay News) -- Elevated levels of serum C-terminal propeptide of type I procollagen (PICP) are indicative of increased myocardial collagen synthesis in sarcomere-mutation carriers without overt hypertrophic cardiomyopathy, and often precede the development of left ventricular hypertrophy or fibrosis that is visible on imaging, according to a study in the Aug. 5 issue of the New England Journal of Medicine.
Carolyn Y. Ho, M.D., of Brigham and Women's Hospital in Boston, and colleagues evaluated 38 patients with pathogenic sarcomere mutations and overt hypertrophic cardiomyopathy, 39 patients with mutations but no left ventricular hypertrophy, and 30 controls without mutations.
Compared to patients without mutations, the researchers found that PICP levels were significantly higher in mutation carriers without left ventricular hypertrophy and in those with overt hypertrophic cardiomyopathy (31 and 69 percent higher, respectively). The ratio of PICP to C-terminal telopeptide of type I collagen was only elevated in patients with overt hypertrophic cardiomyopathy. In addition, cardiac imaging studies revealed late gadolinium enhancement in 71 percent of patients with overt hypertrophic cardiomyopathy, which indicated myocardial fibrosis, but in none of the patients with mutations but no left ventricular hypertrophy.
"Elevated serum PICP levels in mutation carriers with normal cardiac morphologic features constitute a potentially useful phenotype for sarcomere mutations and a serologic marker of genetic risk that can be detected before clinical diagnosis," the authors write. "These observations offer insights into the pathophysiology of hypertrophic cardiomyopathy, suggesting that the stimulus for myocardial fibrosis is an early manifestation of sarcomere gene mutations."
The study was funded in part by the GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease.