The Effects Of Different Dose Of Statins On Serum Markers Of Inflammation In Patients With Chronic Heart Failure

Objective: Hydroxymethylglutaryl CoA reductase inhibitors ( statins), as effective lipid-lowering agents are used extensively in clinic. An extensive research has showed that statins cause a marked decrease in mortality and morbidity in coronary artery disease primarily by lowering cholesterol. Recently they were found playing a role of antioxidant , anti-inflammatory, regulating immunity, improving vascular endothelial function,and inhibiting of ventricular remodeling ,which is called the pleiotropic of statins. However, their roles and cruative effects on patients with chronic heart failure remains unclear. In recent years, Many researches indicate that the neurohumoral activation and an abnormal in?ammatory response plays an important role in the pathogenesis of heart failure. The large number of neurohormones and proinflammatory cytokines were activated in patients with heart failure .Such as tumor necrosis factor-α(TNF-α), interleukin (IL) -6, and high sensitive C-reactive protein (hs-CRP) , which can be the independent predictors of the severity of patients with heart failure.These proinflammatory cytokines were shown to trigger apoptosis, pathological fibrosis and the left ventricular remodeling and have negative inotropic effects on myocardium,and finally accelerated the aggravation of cardiac function.But so far ,the beneficial potential of statins other than their lipid lowering effects has not been studied widely in patients with HF,especially the effects of different dose statins.And there is few information available on relations of antiinflammatory with better cardiac function in HF.We aimed to investigate the effects of 12-month of atorvastatin treatment in patients with chronic heart failure secondary to coronary artery disease by evaluating the serum inflammatory markers, in order to provide new ideas and direction for the clinical treatment of chronic congestive heart failure and make a further guidance on statins in heart failure in the application.Methods:119 patients with chronic heart failure secondary to coronary artery disease were included to this prospective case-controlled trial. 40 were randomized to receive atorvastatin 10 mg/d (group of 10mg statin), 38 receiving atorvastatin 20 mg/d ( group of 20mg statin) and 41 served as controls . At baseline and 6, 12 months after treatment, hs-CRP,TNF-αand LVEF were measured.Results:After a 6-month treatment, there were significant reductions in serum levels of high-sensitivityC-reactiveprotein and tumor necrosis factor-alpha in the statin groups compared with those in controls(P<0.05). The changes between group of 20mg statin and group of 10mg statin was also distinct(P<0.05). There was an significant increase in left ventricular ejection fraction(LVEF%) in the statin groups compared with those in controls(P<0.05). And the group of 20mg statin showed a tendency of improvement compared with those in the group of 10mg statin. After a 12-month treatment, there was significant reductions in serum levels of hs-CRP and TNF-αin the group of 20mg statin compared with those in controls(P<0.05). There was a significant reductions in serum levels of hs-CRP in the group of 10mg statin compared with those in controls(P<0.05).The changes between group of 20mg statin and group of 10mg statin was also distinct(P<0.05). There was an significant increase in left ventricular ejection fraction(LVEF%) in the statin groups compared with those in controls(P<0.05). The changes between group of 20mg statin and group of 10mg statin was also distinct(P<0.05). After a 12-month treatment ,the trial showed that the decrease of hs-CRP (Δhs-CRP) was negatively correlated with the increase of LVEF (ΔLVEF) ( r= -0.256, P<0.005), the decrease of TNF-α(ΔTNF-α) was also negatively correlated with the increase of LVEF (ΔLVEF) ( r= -0.221, P<0.005).Conclusion:After a 12-month treatment of atorvastatin in patients with chronic heart failure secondary to coronary artery disease could decrease the serum levels of hs-CRP and TNF-αand improve cardiac function. These effects were becoming more distinct as the dose of atorvastatin used was increased. And the decrease of hs-CRP (Δhs-CRP)and TNF-α(ΔTNF-α) were negatively correlated with the increase of LVEF (ΔLVEF).