PURPOSE: Interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) aggravate atherosclerosis. Interleukin-6 (IL-6) increases and anti-inflammatory IL-4 decreases CRP. Patients with diabetes have increased inflammatory cytokine levels and are at increased risk for coronary artery disease (CAD). Medication that decreases inflammatory cytokines, and CRP, or increases IL-4, may protect the endothelial integrity and regress atherosclerosis. Statins have been shown to decrease inflammatory cytokines and CRP, and TZD increases IL-4 and decreases CRP. The purpose of this study is to evaluate the effects of rosuvastatin, pioglitazone, and rosuvastatin + pioglitazone combination on IFN-γ, TNF-α, IL-6, CRP, and IL-4 levels in diabetic patients with CAD.
METHODS: Twenty diabetic subjects with CAD were divided in group R (rosuvastatin 20 mg mg/d) and group P (pioglitazone 45 mg/d). At 6 months, pioglitazone was added to group R, and rosuvastatin was added to group P. The lipid profile and cytokine levels were measured at baseline and every 2 months.
RESULTS: IFN-γ, TNF-α, IL-6, and CRP were above normal, but IL-4 was suppressed, in all diabetic subjects before treatment. In group R, rosuvastatin decreased LDL cholesterol at 2 mo and increased HDL cholesterol at 4 mo; decreased IFN-γ, TNF-α, and IL-6 at 4 mo, and CRP at 6 mo. In group P, pioglitazone decreased LDL and increased HDL cholesterol at 4 mo; decreased IFN-γ, TNF-α, and increased IL-4 at 2 mo, and decreased CRP at 4 mo. When pioglitazone was added to group R, and rosuvastatin was added to group P, additive changes in cytokines and CRP levels occurred. Rosuvastatin lowered LDL cholesterol and increased HDL cholesterol synergistically when added to group P. Pioglitazone increased IL-4 when added to group R.
CONCLUSION: Rosuvastatin and pioglitazone combination lower inflammatory IFN-γ, TNF-α, IL-6, and increased anti-inflammatory IL-4 cytokines, and decrease CRP levels additively, and optimize patients’ lipid profiles.
CLINICAL IMPLICATIONS: These beneficial effects of rosuvastatin and pioglitazone combination may provide cardiovascular protection for diabetic patients with hyperlipidemia and coronary artery disease.
DISCLOSURE: Linda Tan, Consultant fee, speaker bureau, advisory committee, etc. Stanley Tan is on speaker bureau of AstraZeneca and Lilly.