[The effects after withdrawal of simvastatin on brachial artery endothelial function in patient with coronary heart disease or risk factors].
OBJECTIVE
Landmark trials have demonstrated that statins can reduce the risk of coronary events. Despite the widespread use of statins in the settings of primary and secondary prevention of CHD, withdrawal of statins is a frequent problem in clinical practice. Several recent clinical studies have suggested that withdrawal of statin therapy might be associated with an increase in thrombotic vascular events and the onset of acute coronary syndromes. However, the effects of discontinuing of statins treatment on endothelial function and underlying mechanism are unknown. Objectives We investigated the effects after withdrawal of simvastatin on brachial artery endothelial function in patients unreached cholesterol target with coronary heart disease (CHD) or CHD risk factors.


METHODS
We included 33 patients with established CHD or CHD risk factors, whose serum cholesterol did not achieve NCEP target level. They were administered simvastatin (20 mg) for 4 weeks. Endothelial dependent flow-mediated vasodilation (FMD) was assessed in the brachial artery using high-resolution ultrasound at baseline, after 4 weeks of simvastatin and after termination of therapy 1 week. We evaluated fasting serum lipid profiles and vasoactive substances simultaneously, included nitric oxide (NO), endothelin (ET), 6-keto-PGF1(alpha) and thromboxane B(2) (TXB(2)), which were measured as plasma prostacyclin and TXA(2) respectively.


RESULTS
Simvastatin treatment reduced low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels and improved endothelial-dependent vasodilation in patients after 4 weeks. Withdrawal of simvastatin, however, FMD showed a significant reduction [(4.82 +/- 0.71)% vs (11.51 +/- 0.87)%, P < 0.01], that remained in low level after 1 week, and the FMD were even lower than the baseline values [(4.82 +/- 0.71)% vs (5.89 +/- 0.65)%, P < 0.01]. After terminating simvastatin treatment, serum NO and plasma 6-keto-PGF1(alpha) levels decreased, as well as plasma ET and serum LDL-C levels increased. But there was no significant difference between plasma TXB(2) levels before and after withdrawal of simvastatin (P > 0.05). Overall, there were significant positive correlations between withdrawal-induced changes in FMD and serum NO level (r = 0.674, P = 0.004), whereas no correlations were shown between the changes in FMD and serum LDL-C level (r = -0.414, P = 0.083).


CONCLUSIONS
Abrupt withdrawal of simvastatin therapy resulted in the significant adverse impact on brachial artery endothelial function in patients unreached cholesterol target with CHD or CHD risk factors. Termination of therapy may suppress endothelial NO production and impair endothelial function that is independent of lipid-lowering effect.
Chen
Hong
H
Department of Cardiology, People's Hospital of Peking University, Beijing 100044, China. chenhong0418@yahoo.com.cn
Ren
Jing-yi
JY
Wu
Bei
B
Liu
Xin
X
Wang
Ruo-jie
RJ
Li
Li-jun
LJ
Luo
Yu
Y
D000368:Aged; D001916:Brachial Artery / Q000187:drug effects*; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D012307:Risk Factors; D019821:Simvastatin / Q000008:administration & dosage*; D014664:Vasodilation
D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D009569:Nitric Oxide; D019821:Simvastatin