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Matrix metalloproteinase‐1 and its inhibitor, TIMP‐1, in systolic heart failure: relation to functional data and prognosis
Author(s) -
Jordán A.,
Roldán V.,
García M.,
Monmeneu J.,
De Burgos F. G.,
Lip G. Y. H.,
Marín F.
Publication year - 2007
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/j.1365-2796.2007.01823.x
Subject(s) - medicine , heart failure , matrix metalloproteinase , cardiology , ventricle , heart transplantation , ejection fraction , gastroenterology
. Background. Structural remodelling of left ventricle is a common feature in the progression of congestive heart failure (CHF). Matrix metalloproteinases (MMPs) have been directly implicated as they degrade extracellular proteins. To test the hypothesis that MMP‐and its inhibitor, tissue type inhibitor of matrix metalloproteinases (TIMP‐1), could be related to functional status and prognosis in CHF, we examined the relationship of MMP‐1 and TIMP‐1 to peak oxygen consumption (VO 2 ) and peak minute ventilation/carbon dioxide production relationship (VE/VCO 2 ), and assessed their prognostic value. Methods. We studied 50 patients with CHF, who were compared with 53 controls echocardiogram and ergoespirometry were performed, and serum levels of MMP‐1 and TIMP‐1 were assayed by ELISA. Patients were followed up for 17.5 ± 8.9 months, and total mortality, readmissions for heart failure and cardiac transplantation were recorded. Results. Patients with CHF had lower levels of MMP‐1 ( P = 0.027), and higher levels of TIMP‐1 and TIMP‐1/MMP‐1 ratio (both P < 0.01) than controls. TIMP‐1 levels and the TIMP‐1/MMP‐1 ratio correlated negatively with peak VO 2 (Spearman, r :−0.51; P = 0.001 and r : −0.42; P = 0.030, respectively). During the follow‐up period, 23 patients (47.9%) suffered endpoints – these patients had higher baseline peak VE/VCO 2 ( P = 0.001), TIMP‐1 ( P = 0.004), and TIMP‐1/MMP‐1 ratio values ( P = 0.002), whereas MMP‐1 levels were lower ( P = 0.027). On multivariate analysis, VE/VCO 2 , MMP‐1 levels and age were the only variables independently related to prognosis (all P < 0.05). Conclusion. Poor functional capacity in CHF can be related to abnormal extracellular matrix turnover. Patients who suffered endpoints had more abnormal indices of matrix turnover, where MMP‐1 levels showed independent prognostic value.