Plasma tissue inhibitor of metalloproteinase-1 levels are elevated in essential hypertension and related to left ventricular hypertrophy

Essential hypertensive patients have an increased heart and arterial collagen concentration. Increased collagen synthesis can be assessed using procollagen III N peptide (PIIINP) and reduced collagen degradation measured using tissue inhibitor of metalloproteinase-1 (TIMP-1). Plasma TIMP-1 and PIIINP levels were measured in 31 patients with essential hypertension and in 17 normotensive control subjects. The hypertensive patients were either treatment naive ( n = 18) or had been without treatment for 1 month ( n = 13). Both groups of patients were screened to exclude other fibrotic diseases. In the hypertensive patients, TIMP-1 levels were significantly ( P < .0002) elevated (median 380 ng/mL, range 160 to 1560 ng/mL) compared with those of the normotensive control subjects (median 178 ng/mL, range 99 to 330 ng/mL). In hypertensive subjects who had never received antihypertensive therapy there were significant correlations between TIMP-1 and left ventricular posterior wall thickness in diastole (LVPWd) (r = 0.58) ( P < .02) and left ventricular mass index (r = 0.58) ( P < .02). There was no difference in PIIINP levels (mean ± 2 SD) between the hypertensive (0.56 U/mL ± 0.3) and normotensive groups (0.52 U/mL ± 0.2). The increased tissue collagen III levels found in the heart and vessels of hypertensive patients is due to a reduction in collagen degradation because of high TIMP-1 levels, rather than an increase in synthesis of collagen type III. The tissue source of this TIMP-1 is unclear.