Elevated serum markers for collagen synthesis in patients with hypertrophic cardiomyopathy and diastolic dysfunction

Abstract

Objectives: The hypothesis of impaired collagenolysis in patients with hypertrophic cardiomyopathy (HCM) was tested by measuring serum markers of type-I collagen metabolism. These markers were correlated with echocardiographic parameters of diastolic function.

Background: HCM is a common disease in the adult population with a wide range of clinical manifestations. Left ventricular hypertrophy and increased intramyocardial collagen content are known to cause diastolic dysfunction in patients with HCM.

Methods: In 26 patients with HCM and 38 control subjects (aged: 57+/-3 and 54+/-2 years, p=n.s.) serum levels of collagenolytic matrixmetalloproteinase-1 (MMP-1) and its inhibitor TIMP-1, the markers for collagen type-I synthesis (PICP) and degradation (ICTP) were determined by ELISA and RIA. Diastolic function were determined by Doppler echocardiography.

Results: Free TIMP-1 was elevated in HCM compared to controls (216,78+/-9,89 vs 183.77+/-7.57 ng/ml ; p=0.006) as well as PICP (165.92+/-10.26 vs 114.57+/-6.38 mug/l; p<0.001). Free MMP-1 was significantly lower in HCM (1.13+/-0.20 vs 2.33+/-0.34; p=0.01). ICTP did not differ. The MMP-1/TIMP-1 ratio was significantly lower in HCM (0.006+/-0.001 vs 0.012+/-0.001, p=0.003). PICP correlated positively with diastolic E/A ratio (r=0.389; p=0.05) and septal thickness (r=0.484; p=0.01).

Conclusions: Serum marker of collagen synthesis (PICP) is increased in patients with HCM. Increased marker for inhibition of collagenolysis (TIMP-1) and a disturbed balance of collagen synthesis and degradation (ratio) with a predominance of inhibition of collagenolysis indicates collagen accumulation (fibrosis), which explains passive diastolic dysfunction in patients with HCM.