Abstract 4862: Structural, Functional, and Clinical Manifestations of Hypertensive Heart Disease: Predicted by Determinants of Myocardial Extracellular Matrix (ECM) Composition
Chronic arterial hypertension (HTN) may cause left ventricular (LV) remodeling, alterations in cardiac function, and the development of chronic heart failure (CHF). Changes in the composition of the myocardial extracellular matrix (ECM) are causally related to these structural, functional, and clinical outcomes and may be determined by the balance between matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs (TIMPs). The purpose of this study was to test the hypothesis that the structural and functional manifestations of HTN are associated with a specific pattern of plasma MMP and TIMP expression. Plasma concentration of MMP-2, 3, 7, 8, 9, and TIMP-1, 2, 3, 4, an echocardiogram, and 6-minute walk test (6MWT) were performed on 88 subjects with controlled HTN (requiring medication and meeting JNCVII guidelines but without non-cardiac organ disease, valvular or ischemic heart disease, recent surgery, or an ejection fraction < 45%) and 62 age and gender matched control subjects (CTL) with no evidence of cardiovascular disease. Multivariable regression models were developed to predict echo determined LV mass (g/m2), LV end diastolic volume/mass ratio (V/M), pulmonary capillary wedge pressure (PCWP) and 6 MWT. The presence of LV hypertrophy (increased LV Mass), concentric remodeling (decreased V/M), increased PCWP and decreased 6MWT were associated with an increase in MMP-7,8,9 and an increase in TIMP-1,2,4 in a univariate analysis. In addition, a multivariate analysis based on specific patterns of MMP/TIMP expression (Table⇓) was highly predictive of the structural and functional manifestations of HTN. These data support the hypothesis that the structural and functional manifestations of HTN are associated with a specific pattern of plasma MMP and TIMP expression.