Tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 levels in patients with hypertension: Relationship to tissue Doppler indices of diastolic relaxation

Background Hypertension, hypertensive heart disease, and left ventricular (LV) hypertrophy are integral to symptomatic diastolic heart failure. Tissue inhibitor of metalloproteinase-1 (TIMP-1) is linked to extracellular matrix fibrosis and is elevated in hypertension. We hypothesized a link between circulating TIMP-1, matrix metalloproteinase-9 (MMP-9), and resting echocardiographic LV filling parameters using tissue Doppler parameters of diastolic (dys)function. Methods Circulating MMP-9 and TIMP-1 levels were measured in citrated plasma by ELISA in 74 patients with hypertension (58 men, mean age 58 ± 11 years) and 34 controls (23 men, mean age 53 ± 13 years). All had confirmed normal short axis systolic contractility, with no significant wall motion abnormalities; the LV mass and standard resting tissue Doppler echocardiographic indices of diastolic function were also recorded. Results Both MMP-9 and TIMP-1 levels were higher in the hypertensive group (P = .0039 andP = .0054, respectively). When compared to controls, hypertensive patients had a greater LV mass (P = .0054), and differences in many of the parameters reflecting diastolic dysfunction (controls versus hypertensives: E: 0.71 ± 0.15 v 0.81 ± 0.15 m/sec, P = .004; A: 0.66 ± 0.12 v 0.81 ± 0.16 m/sec, P< .0001; e′: 0.12 (0.09–0.14) v 0.09 (0.07–0.10) m/sec, P = .0017; e′/a′: 1.20 (1.00–1.80) v 0.88 (0.71–1.05), P< .0001; E/e′: 6.54 (4.75–7.14) v 8.89 (7.55–10.75), P< .0001, respectively). Within the hypertensive cohort, only TIMP-1 levels correlated with LV mass (r = 0.271, P = .024), LV mass index (r = 0.323, P = .007), and tissue Doppler parameters of diastolic dysfunction, including e′ (r = −0.338, P = .005), a′ (r = −0.350, P = .005), and E/e′ (r = 0.334, P = .005). Conclusions TIMP-1 is thought to increase tissue concentrations of collagen type I by preventing its breakdown by MMPs. Our findings therefore add weight to a hypothesis suggesting that TIMP-1 may be a key mediator of LV diastolic dysfunction through definition of ventricular matrix composition.