Influence Of Aging On The Effect Of Atorvastatin Improving Left Ventricular Remodeling、Heart Function And Myocardial Energy Expenditure In Patients With Ischemic Cardiomyopathy

BackgroundStatins are effective cholesterol lowering agents, and commonly prescribed for the primary and secondary prevention against coronary heart disease (CHD), because they can reduce CHD incidence and motality obviously. Statins have been shown to possess several favorable effects, including improving endothelial function, anti-inflammation, anti-oxidant effect and reversing pathologic myocardial remodeling. All these effects mentioned above may contribute to prevent the progression of chronic heart failure (CHF), and it is confirmed by several small endpoint studies. However, recently, the result from universal study has indicated rosuvastatin could not improve ventricular remodeling and heart function in patients with CHF. Furthermore, the conclusions from two large-scale controlled studies are disappointing. Both studies showed that CHF patients have not gained any benefit from statin therapy in improving clinical outcomes. Hence, it is a matter of debate that whether statins can improve ventricular remodeling, heart function and clinical prognosis in patients with CHF. Most of experts have the opinion that the different type and dose of statins administration and different populations in these studies may contribute to these controversial results. The result from one meta-analysis showed that statins improved ventricular remodeling, heart function and clinical pronosis in patients with CHF, but not in patients treated with rosuvastatin. Rencently, one randomized study demonstrates that compared to the low dose of atorvastatin, the high dose of atorvastatin might make ventricular remodeling and heart function improved in in patients with ICM. Notably, almost all the favorable effects of statin therapy have been verified by using in vitro techniques, or in younger patients and healthy control, whereas the majority of patients enrolled in these two studies were advanced age (>65years) with multiple comorbidities. Therefore, age might affect the efficacy of statin in patients with ICM.Although it is still unclear that the exact mechanism of statins works in the treatment of CHF, a growing body of evidences displays that statin can increase mobilization of EPCs from bone marrow and impore endothelial function. Advanced stages of heart failure were shown to be related with reduced levels of cEPCs, and impaired functions of progenitor cells in the peripheral blood in patient with ICM. Hence, this effect might make contribution to improve ventricular remodeling, heart function and clinical pronosis in patients with CHF. However, the age-related changes in cEPCs number and dysfunction and endothelial dysfunction may lead to the impairment of statins repair mechanisms in the aging cardiovascular system. At the same time, Aging plays a negative role on cardiac structure, function and myocardial energy expendicture, including cardiac hyperotrophy, function degeneration and imbalance of myocardial energy expendicture. This aged-related change makes it difficult that statins reverse myocardial remodeling, function degeneration and imbalance of myocardial energy expendicture.A high incidence of thrombotic complications has been associated with patients with ICM. The platelet-related factors is prone to be activated by inflammatory factors, then the activated platelets were accumulated and enhanced the forming of thrombosis, which at last lead to the incidences of cardiacarrhythmia and clinical events. Statins have been shown to possess positive effects, including anti-inflammation, anti-oxidant effect, which may inhibit the platelet-related factor activated. This effect may contribute to the improvement of clinical prognosis.The presence of increased levels of circulating endothelial-derived microparticles (cEMP) have been documented in various pathological conditions including coronary syndromes, in which they reflect endothelial dysfunction and are associated with a poor clinical outcome.Our group and other researchers have found that myocardial energy expenditure derived from standard echocardiographic measurements were considered as an effective indicator for myocardial bioenergetics. In patients with heart failure, the absolute change of MEE is inversely correlated with that of LVEF, indicating that MEE might be an effective index for assessing engegy metabolism and heart function.There were few data to investigated the influence of aging on the effect of atorvastatin improving cEPCs mobilization、endothelial function、left ventricular remodeling、LVEF and MEE in Patients with ICM, and to compare the effect of different dose of atorvastatin on serum prostacyclin and platelet activation.Objective This study was designed to compare the efficacy of atorvastatin therapy in the mobilization of EPCs, the improvement of endothelial dysfunction, left ventricular remodeling, LVEF and MEE in young and elderly patients with ICM, and to investigate the effect of different dose of atorvastatin on serum prostacyclin and platelet activation.Subjects and MethodSubjects we included patients with ICM (required to have angiographic evidence of coronary artery disease or a previous MI at least3months prior to inclusion into the study), LVEF<45%, LV end-diastolic dimension>50mm and NYHA class Ⅱ-Ⅳ. The exclusion criteria included individuals with previous statin-induced myopathy or a hypersensitivity reaction, acute infection, chronic inflammatory disease, autoimmune disease, thyroid disease, liver disease, acute or chronic heart failure due to other cardiovascular diseases other than ICM, stroke within3months, renal failure, lung disease and a life expectancy less than1year. Groups157ICM patients in Cardiovascular Department were assigned into this study from March2007to March2011. In accordance with the hospitalization order, Young (...