Serum levels of fetuin-A, osteoprotegerin and osteopontin in patients with coronary artery disease: effects of statin (HMGCoA-reductase inhibitor) therapy.

BACKGROUND AND OBJECTIVES

Statins (HMGCoA-reductase inhibitors) produce numerous non-lipid related, 'pleiotropic' effects. Our aim was to investigate whether simvastatin treatment affects serum levels of vascular calcification inhibitors, such as fetuin-A, osteoprotegerin (OPG) and osteopontin (OPN), in patients with coronary artery disease (CAD).

METHODS

A total of 98 statin-free patients with angiographically proven, newly diagnosed CAD were treated with simvastatin (20-40 mg daily) for 6 months to target a low-density lipoprotein (LDL) level <100 mg/dL (the statin group [SG]). Thirty-five age- and sex-matched healthy individuals without any chronic metabolic or cardiovascular disease at baseline served as a healthy control group (HCG). Clinical, anthropometrical and metabolic parameters and serum fetuin-A, OPG, OPN and high-sensitivity C-reactive protein (hsCRP) levels were assayed at baseline in all participants and after 6 months only in SG patients.

RESULTS

Compared with HCG subjects at baseline, SG patients exhibited higher serum levels of OPG (7.39 ± 2.94 pmol/L vs 2.47 ± 1.15 pmol/L, p < 0.001), OPN (60.99 ± 17.52 ng/mL vs 45.45 ± 10.26 ng/mL, p = 0.005) and hsCRP (4.66 ± 1.74 mg/L vs 1.58 ± 0.56 mg/L, p < 0.001) as well as lower serum levels of fetuin-A (0.222 ± 0.036 μg/L vs 0.839 ± 0.092 μg/L, p < 0001). Apart from significantly reducing plasma total cholesterol and LDL, simvastatin also reduced serum levels of fetuin-A (by ~62.6 %), OPG (by ~47.2 %), OPN (by ~44.6 %) and hsCRP (by ~45.3 %) (p < 0.05) in SG patients. In standard multiple regression analysis, the simvastatin-induced reduction in fetuin-A was independently associated with changes in total cholesterol (β = -0.289, p = 0.048) and LDL (β = -0.302, p = 0.032) (R (2) = 0.305, p = 0.040).

CONCLUSION

Patients with CAD showed derangements in serum levels of all vascular calcification inhibitors compared with those in healthy controls. Simvastatin treatment for 6 months significantly decreased serum fetuin-A, OPG and OPN levels, but the clinical relevance of this requires further investigation.