Abstract 2373: The Effects of Statin Therapy on MMP Families in Patients with Acute Heart Failure

Abstract

Introduction: It is known that increased matrix metalloprotease (MMP) accelerated cardiac remodeling in chronic heart failure (HF). Although roles of MMPs in acute HF have not been well clarified, we also found that MMPs increased in acute HF and decreased in the improvement of HF with conventional therapy. Pharmacological modification of MMPs may be beneficial for a treatment of acute HF. Therefore we assessed the hypothesis that a statin decreased MMPs in acute HF. Methods: Serum levels of MMP-2,-3, and -9 were measured on admission (Day 1), Day 3, and Day 14 in 38 acute HF patients. The patients were randomized to either atorvastatin group (n = 20) or control group (n = 18). Atorvastatin (10 –20mg per day) was started within 12 hours after their admission and continued for two weeks. There was no limitation in HF treatment and the treatment was not different between the two groups except atorvastatin. Patient characteristics including an etiology of HF and cardiac function were also not different between the groups. Results: There were no differences in serum levels of MMP-2, -3, and-9 on Day 1 between atorvastain group (1435.3 ± 292.6 ng/ml, 72.2 ± 40.4 ng/ml, 132.9 ± 85.5 ng/ml, respectively) and control group(1284.5 ± 399.6 ng/ml, 142.0 ± 139.7 ng/ml, 88.4 ± 51.2 ng/ml, respectively). MMP-2 significantly decreased in both atorvastatin and control group on Day 3 and Day 14. But, decreases of MMP-2 on Day 3 and Day 14 from Day 1 were significantly greater in atorvastatin group (− 581.3 ± 237.3 ng/ml and − 447.7 ± 228.3 ng/ml, respectively) than in control group (− 321.3 ± 257.8 ng/ml and − 275.0 ± 179.4 ng/ml, respectively). MMP-9 significantly decreased in atorvastatin group on Day 3 and Day 14 (132.9 ± 85.5 ng/ml on Day1, 71.4 ± 48.6 ng/ml on Day 3, 53.0 ± 28.5 ng/ml on Day 14; p < 0.05), but did not change significantly in control group. MMP-3 did not significantly change in both groups. Conclusion: MMP-2 decreased with conventional HF treatment, but MMP-3 and -9 did not. Interestingly, early start of statin treatment significantly decreased both MMP-2 and -9, but not MMP-3 in acute HF. This is the first report demonstrating the effects of statin on MMPs in acute HF.