Changes of matrix metalloproteinase-9 level is associated with left ventricular remodeling following acute myocardial infarction among patients treated with trandolapril, valsartan or both.

BACKGROUND: Inhibition of the renin-angiotensin system (RAS) with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) can suppress left ventricular (LV) remodeling after acute myocardial infarction (AMI), possibly through the modifications of matrix metalloproteinase (MMP)-9. Whether LV remodeling is suppressed in association with MMP-9 suppression in post-AMI/-percutaneous coronary intervention (PCI) patients treated with ACE inhibitor and/or ARB was examined. The presence of any differences in LV remodeling and MMP-9 levels across the groups was also investigated. METHODS AND RESULTS: Sixty-five patients were initiated into each of 3 treatments; trandolapril, valsartan or a combination of both (half-dose-trandolapril plus half-dose-valsartan). Changes in MMP-9, LV end-diastolic and end-systolic volume index (LVEDVI and LVESVI) after 12 months were assessed. Overall, MMP-9 significantly decreased, although neither LVEDVI nor LVESVI increased significantly. DeltaMMP-9 was significantly correlated with DeltaLVEDVI (r=0.36) or DeltaLVESVI (r=0.39). In comparison, across groups, it was found that MMP-9, LVEDVI and LVESVI at 12 months were significantly lower in the combination therapy group than in the trandolapril group. There were no significant differences between the valsartan group and combination therapy group, or between the valsartan group and the trandolapril group. CONCLUSIONS: LV remodeling might be suppressed in association with MMP-9 suppression in AMI patients treated with PCI and regular dose or half-dose-combination of RAS inhibitors. Furthermore, a half-dose-combination might suppress LV remodeling more effectively than trandolapril alone.

Long-term efficacy of pravastatin therapy in diabetic patients undergoing complete coronary revascularization.

AIM: The long-term effect of statin therapy in diabetic patients after coronary revascularization is not well established. Accordingly, we sought to determine if whether statin therapy initiated at the time of complete revascularization including percutaneous coronary intervention (PCI) and/or bypass surgery reduces total and cardiac mortality among diabetic patients. METHODS: We collected data from 1,138 consecutive patients who underwent complete revascularization (PCI and/or bypass surgery). We then compared all-cause and cardiac mortality rates in 499 patients with diabetes mellitus of whom 149 (29.9%) were treated with statin at the time of revascularization. To adjust the variables that would have been related to the decision regarding statin administration, a propensity score was computed and multivariate Cox regression was carried out. RESULTS: During follow-up (8.8+/-2.6 years), 103 patients died (including 43 who died of cardiac causes). The Multivariate analysis showed statin therapy to be significantly associated with reduced cardiac mortality (HR 0.39, 0.16-0.95; p=0.039), but not with all-cause mortality. CONCLUSION: Statin therapy was associated with a significantly reduced risk of cardiac mortality in patients with diabetes mellitus and coronary artery disease after complete revascularization.

Effectiveness of statin-eluting stent on early inflammatory response and neointimal thickness in a porcine coronary model.

BACKGROUND: Drug-eluting stent (DES) implantation is routine during coronary revascularization because DES significantly reduce rates of restenosis and target lesion revascularization compared with bare metal stent (BMS). However, available DES have limitations, such as late thrombosis because of delayed healing with poorer endothelialization and persistent local inflammation. Statins can inhibit cell proliferation, inflammation, and restore endothelial function. The present study evaluated the ability of stent-based cerivastatin delivery to reduce stent-induced inflammatory responses and adverse effects on endothelial function, and to inhibit neointimal hyperplasia in a porcine coronary model. METHODS AND RESULTS: Pigs were randomized into groups in which the coronary arteries (9 pigs, 18 coronaries in each group) had either a cerivastatin-eluting stent (CES) or a BMS. All animals survived without any adverse effects. Inflammatory cell infiltration evaluated using scanning electron microscopy on day 3 after stenting was significantly decreased in the treated vessels (inflammation score: 1.15+/-0.12 vs 2.43+/-0.34, p<0.0001). At day 28, endothelial function with intracoronary infusion of bradykinin was preserved in both the CES and BMS groups. Volumetric intravascular ultrasound images revealed decreased intimal volume in the CES group (28.3+/-5.4 vs 75.9+/-4.2 mm3, p<0.0001). Histomorphometric analysis showed reduced neointimal area (1.74+/-0.45 vs 3.83+/-0.51 mm2, p<0.0001) in the CES group despite similar injury scores (1.77+/-0.30 vs 1.77+/-0.22, p=0.97). CONCLUSION: In porcine coronary arteries CES significantly decreased neointimal hyperplasia with a decreased early inflammatory response and without endothelial dysfunction.

Efficacy of peroxisome proliferative activated receptor (PPAR)-alpha ligands, fenofibrate, on intimal hyperplasia and constrictive remodeling after coronary angioplasty in porcine models.

Constrictive remodeling and intimal hyperplasia play a prominent role in restenosis after angioplasty. It has been reported that the severity of constrictive remodeling and intimal hyperplasia correlate with adventitial angiogenesis and inflammation. Experimental evidence indicates that inflammation participates in angiogenesis, and therefore inhibition of inflammation may impair neovascularization. We tested whether fenofibrate, peroxisome proliferative activated receptors (PPAR)-alpha specific ligand, inhibits the early inflammation, adventitial angiogenesis, constrictive remodeling and intimal hyperplasia after angioplasty using porcine coronary arteries. Fenofibrate was tested in vivo, in 30 coronary arteries of 10 pigs (1g/day, orally) and was compared to placebo. Quantitative intravascular ultrasound and histopathologic assessment showed that fenofibrate increased lumen (6.28 mm(2) versus 5.15 mm(2)), vessel area (7.34 mm(2) versus 6.69 mm(2)) and inhibited constrictive remodeling. Inflammatory cell infiltration was evaluated with scanning electron microscopy 3 days after angioplasty and was significantly decreased in the treated vessels compared to control. Adventitial angiogenesis 3 days after angioplasty was significantly reduced in the injured vessels derived from the fenofibrate treated group compared to placebo. In conclusion, pharmacological activation of PPAR-alpha inhibited constrictive remodeling and neointimal hyperplasia after angioplasty through inhibition of inflammation and adventitial neovascularization.