Effects of atorvastatin 80 mg daily on indices of matrix remodelling in 'high-risk' patients with ischemic heart disease

Recent evidence suggests that higher doses of statins could improve clinical outcomes compared to conventional doses, but whether this benefit is due to "additional" pleiotropic effects is uncertain. We tested the hypothesis that atorvastatin 80 mg/day would have beneficial effects on indices of matrix remodelling (matrix metalloproteinase-1, MMP-1, and its tissue inhibitor, TIMP-1) in high-risk cardiovascular disease. We studied 27 "high-risk" patients (inclusion criteria: severe triple vessel but rejected for by-pass for extensive coronary disease, severe effort angina after coronary artery by-pass and premature coronary disease with >/=3 risk factors) with an abnormal lipid profile despite atorvastatin 40 mg/day, at baseline and at 3 months after increasing the statin dose to 80 mg/day. Baseline results in patients were compared to 22 healthy controls. At baseline, patients had lower levels of MMP-1 compared to controls. When atorvastatin was increased to 80 mg/day, significant reduction in LDL-cholesterol was observed, whereas MMP-1 and TIMP-1 levels were increased. These, despite of atorvastatin 40 mg daily, 'high-risk' patients still demonstrated abnormal extracellular remodelling indices. Doubling the dose of atorvastatin resulted in significant improvement in extracellular remodelling indices.