Comparison Of40Mg Versus10mg Atorvastatin On Circulating EMPs,EPCs,MEE And Left Ventricular Function In Patients With Ischemic Cardiomyopathy

BackgroundStatins, serving as an anti-atherosclerosis drug, can significantly decrease the rates of cardiovascular events in patients with coronary heart disease (CHD), and were extensively administrated in secondary prevention of CHD. At present, consensus on the possible effects of statins on cardiac function in patients with ischemic cardiomyopathy(ICM) have not been achieved, although the safety of statins in patients with heart failure has been demonstrated by the CORONA and UNIVERSE trials. Small prospective clinical studies using atorvastatin and simvastatin for systolic heart failure (HF) have suggested that statins could be beneficial in patients with congestive heart failure(CHF) Conversely, subsequent studies indicated that rosuvastatin couldn’t improve the prognosis in patients with ischemic or nonischemic, systolic HF. The incomplete agreement existing on the role of statins in HF may in part be due to the different class and dose of statins administration and different race in these studies. Several clinical trials administrating statins for CHF have documented an improved LV function, but the mechanisms in patients with CHF are still not completely known.At present, the level of circulating EPCs(cEPCs) not only correlates with cumulative cardiovascular risk and vascular function7, but also predicts future cardiovascular events and atherosclerotic disease progression in patients with coronary artery disease (CAD). Recently, advanced stages of heart failure were shown to be associated with reduced levels of cEPCs. Study showed ICM was associated with selective impairment of progenitor cell function in the bone marrow and in the peripheral blood.Endothelial cells could release microparticles after inflammatory stimulation, and 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. Currently, stabilizing cellular membranes to decrease the release of EPMs was considered a target of vascular therapy.Matrix metalloproteinase(MMPs), which are present in the myocardium and capable of degrading all the matrix components of the heart, are the driving force behind myocardial matrix remodeling. MMP-9is well-known for its ability to degrade gelatins. The particular importance of MMP-9activity during LV remodeling has recently been demonstrated in several studies. Furthermore, MMP-9may be one of the candidates for selective inhibition after myocardial infarction(MI), because the deficiency in MMP-9alone could reduce LV chamber enlargement after infarction.LV hypertrophy, remodeling would lead to myocardial energy metabolic imbalance. In present, myocardial energy expenditure (MEE) derived from standard echocardiographic measurements was regarded as an effective indicator for myocardial bioenergetics and significantly correlated with cardiac function in CHF patients, especially in CHF patients with reduced LV ejection fraction(LVEF). Previous study demonstrated depressed EF was independently associated with higher MEE and increased MEE could predict cardiac death.However, currently, there were few data to delineate the effect of different doses statins on cEPCs and cEPMs. Thus, the present study was designed to investigate the differences of40mg versus10mg atorvastatin on cEPCs, cEMPs, MEE and LV function in patients with ICM.Part one Comparison of40mg versus10mg atorvastatin on oxLDL, hsCRP, circulating endothelial-derived microparticles and endothelial progenitor cells in patients with ischemic cardiomyopathyObjective This study was designed to investigate the differences of40mg versus lOmg atorvastatin on oxLDL, hsCRP, circulating endothelial-derived microparticles(EMPs) and endothelial progenitor cells(EPCs) in patients with ischemic cardiomyopathy (ICM).Methods100patients with ICM and100healthy examined people as normal control group were recruited to this study. Patients were randomly divided into two groups:10mg atorvastatin group (n=50) and40mg atorvastatin group (n=50).All subjects were followed up for1year. The levels of serum lipids, oxLDL, hsCRP, circulating EPCs and EMPs were examined in all subjects. The incidences of adverse reactions in two study groups were taken down.Results3,2and3patients withdrew in lOmg atorvastatin group,40mg atorvastatin group and control group respectively because of moving to other provinces. The incidences of cardiovascular events in10mg atorvastatin group and in40mg atorvastatin group were10.6%(5/47) and6.25%(3/48) during the period of follow-up. There were no significant differences in the rates of cardiovascular events between the two study groups. There was no rhabdomyolysis and drug-induced hepatitis in the two study groups during the follow-up. No excessive episodes of adverse reactions occurred in the40mg atorvastatin group. Subjects did not differ in CK and ALT between the two study groups at the end of study.Subjects did not differ in lipids, oxLDL, hsCRP, cEMPs, cEPCs, MEE, cardiac function, CK, ALT, fibrinogen, urine acid, age, gender, family medical history, index weight, number with hypertension, number with diabetes, number ever smoking, drugs, echocardiographic indices and the rate of stent implanted between the two study groups. At the end of the study, the levels of serum TC(F=11.586,P=0.001), LDL(F=7.459,P=0.008), oxLDL(F=l6.106,P=0.000) and hsCRP(F=29.497,P=0.000) significantly decreased in40mg atorvastatin group in contrast to1Omg atorvastatin group. At the end of the study, the levels of cEMPs(F=24.252,P=0.000) significantly decreased but the levels of cEPCs(F=4.969,P=0.028)significantly increased in40mg atorvastatin group in contrast to10mg atorvastatin group.Conclusions40mg atorvastatin might decrease the levels of circulating EMPs and increase the number of circulating EPCs in patients with ICM in comparison with lOmg atorvastatin. Furthermore, atorvastatin might have the beyond lipids-decreased effects. Part two Comparison of40mg versus10mg atorvastatin on myocardial energy expenditure level and left ventricular function in patients with ischemic cardiomyopathyObjectives The present study was to investigate the differences of40mg versus10mg atorvastatin on myocardial energy expenditure (MEE) and E/E’ in patients with ischemic cardiomyopathy (ICM).Methods100patients with ICM and100healthy examined people as normal control group were recruited to this study. Patients were randomly divided into two groups:10mg atorvastatin group (n=50) and40mg atorvastatin group (n=50).All subjects were followed up for1year. The levels of B-type natriuretic peptide(BNP), circumferential end-systolic wall stress(cESS), MEE, E/E’ and echocardiography were examined in all subjects.Results At the end of this study, the decrease in LVMI(F=3.014,P=0.390)was observed in40mg atorvastatin group in contrast to10mg atorvastatin group although there were no significant differences between the two study groups. At the end of the study, the levels of MEE (F=5.319,P=0.023)significantly decreased in40mg atorvastatin group in contrast to10mg atorvastatin group.At the end of the study, the levels of serum BNP(F=4.845,P=0.032)and E/E’(F=10.330,P=0.002) significantly decreased in40mg atorvastatin group in contrast to10mg atorvastatin group,P<0.05. Subjects did not differ in LVEF(F=0.385,P=0.536) between the two study groups at the end of the study.Conclusions40mg atorvastatin might significantly decrease the levels of MEE and E/E’obtained from Doppler echocardiography in comparison with10mg atorvastatin in patients with ICM. Moreover the effect might be independent of the decrease of lipids. Part three Comparison of40mg versus10mg atorvastatin on the levels of serum matrix metalloproteinase-9in patients with ischemic cardiomyopathyObjectives The present study was to investigate differences of40mg versus10mg atorvastatin on the levels of serum matrix metalloproteinase-9(MMP-9) in patients with ischemic cardiomyopathy (ICM).Methods100patients with ICM and100healthy examined people as normal control group were recruited to this study. Patients were randomly divided into two groups:10mg atorvastatin group (n=50) and40mg atorvastatin group (n=50).All subjects were followed up for1year. The levels of serum MMP-9were examined in all subjects.Results At the end of this study, the levels of MMP-9(F=5.016,P=0.026) significantly decreased in40mg atorvastatin group in contrast to10mg atorvastatin group.Conclusions40mg atorvastatin might significantly decrease the levels of serum MMP-9in comparison with10mg atorvastatin in patients with ICM.