Ventricular Matrix Remodeling: Correlates and Prognosis

BACKGROUND:

Recent studies have established that cardiac extracellular matrix (ECM) remodeling is a major determinant of pathologic left ventricular hypertrophy (LVH) and progressive left ventricular dilatation, and as a result, contributes to the development of left ventricular dysfunction and overt congestive heart failure (CHF). The recent development of reliable serologic assays for procollagen peptides, metalloproteinases (MMP) and their tissue inhibitors (TIMP), and cytokines permits the in vivo assessment of LV ECM remodeling, and raises the possibility of expanding the utility of these markers 'from the bench to the bedside.' Prior studies of ECM biomarkers in congestive heart failure have been limited to cross-sectional investigations of small samples of highly selected patients with advanced disease. The fundamental question whether serum markers of ECM remodeling are important correlates of left ventricular dilatation or left ventricular hypertrophy, or are independent predictors of incident congestive heart failure in the community remains unanswered.

DESIGN NARRATIVE:

The aims of the study are to: determine the relationships between serum markers of ECM remodeling and traditional congestive heart failure risk factors; analyze the cross-sectional relations between markers of ECM remodeling and echocardiographic left ventricular hypertrophy and left ventricular dilatation, Doppler indices of left ventricular filling and serum natriuretic peptides; investigate prospectively the relationships between ECM remodeling markers and progressive left ventricular dilatation and left ventricular hypertrophy and congestive heart failure incidence, adjusting for standard risk factors. Stored samples from the Framingham Offspring and Omni cohorts will be used. Participants at the extremes of the joint distributions of left ventricular wall thickness and left ventricular internal dimension from echocardiograms performed at earlier Framingham exams will be sampled.