Plasma levels of matrix metalloproteinases and their inhibitors in hypertension: a systematic review and meta-analysis.

Background: Hypertension is a major cause of cardiovascular remodeling. In the cardiovascular system, the remodeling of the extracellular matrix is controlled by the matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs). The aim of this meta-analysis is to elucidate the behavior of plasma MMP and TIMP levels in hypertension and their relationship to cardiovascular remodeling.

Methods: MEDLINE and EMBASE databases were searched up to July 2011. Studies were considered eligible if they provided values of plasma MMPs and TIMPs in hypertensive patients. Given the high variability of the plasma biomarker values among studies, the standardized mean difference (SMD) was calculated.

Results: Ten studies provided plasma MMP-9; the SMD between 778 hypertensive patients and 669 controls was 1.95 units (P < 0.05). Thirteen studies provided plasma TIMP-1; the SMD between 851 hypertensive patients and 646 normotensive individuals was 1.92 units (P < 0.01). Three studies investigated whether plasma TIMP-1 predicted left ventricular (LV) remodeling; the SMD between 92 hypertensive patients with and 88 hypertensive patients without LV hypertrophy was 5.81 units (P < 0.05). As for diastolic heart failure (HF), five studies provided data for plasma MMP-2; the SMD between 321 hypertensive patients with and 334 hypertensive patients without HF was 2.36 units (P < 0.01). The heterogeneity among studies was high.

Conclusions: These results suggest that MMP-2, MMP-9 and TIMP-1 may have a role as biomarkers of cardiovascular remodeling in hypertension. If these results are confirmed in prospective clinical studies, they could provide new tools to stratify cardiovascular risk in hypertensive patients.