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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Important novel developments in the pharmacotherapy of cardiovascular diseases are briefly summarized. New results with lipid lowering statins in secondary prevention of atherosclerosis are mentionned. Atorvastatin, introduced recently, is compared to the other statins. The extended possibilities for inhibition of platelet-aggregation in coronary disease and after interventional coronary therapy with ticlopidine, clopidogrel and specific antagonists of platelet integrin IIb/IIIa receptors (abciximab, tirofibrane) as well as fibrinolysis with reteplase are covered. Among modern trends in pharmacotherapy of heart failure studies with angiotensin-II-receptor inhibition (losartane and related compounds) or betablockers (carvedilol) are worth mentioning.
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PMID:[New cardiovascular drugs: expanded therapeutic possibilities in coronary heart disease and in heart failure]. 1040 78

Although not currently indicated for chronic heart failure (CHF), statins have been associated with improved outcome in retrospective analysis. However, statin therapy reduces plasma levels of coenzyme Q(10) (ubiquinone), which may have adverse effects on heart failure states. We hypothesized that atorvastatin treatment improves endothelial function in patients with chronic heart failure independent of LDL-cholesterol alterations. Furthermore, we assessed how reductions in coenzyme Q(10) levels impact on potentially improved endothelial function. Twenty-four patients with stable, symptomatic heart failure (New York Heart Association Class II or III) and a left ventricular ejection fraction <40% were randomised to 40 mg atorvastatin or placebo for 6 weeks and crossed over to the other treatment arm for a further 6 weeks, after a 2-week wash out. Forearm resistance vessel function was assessed by venous occlusion plethysmography during infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and N(G)-monomethyl-L-arginine (L-NMMA) into the brachial artery. Atorvastatin treatment lowered triglycerides, LDL-cholesterol and coenzyme Q(10) levels (all p<0.001) and improved endothelium-dependent vasodilatation during acetylcholine infusion (p=0.015). Endothelium-dependent forearm blood flow improvements correlated with reductions in coenzyme Q(10) levels (p=0.011), but not with LDL-cholesterol levels (p=0.084). Coenzyme Q(10) remained the significant variable predicting improvement in NO dependent endothelial function after adjusting for LDL-cholesterol levels (p=0.041). In conclusion, short-term atorvastatin therapy improved endothelial function in chronic heart failure patients. Further studies are required to determine whether coenzyme Q(10) reductions are limiting the maximum favourable effects of statin therapy on the microcirculation.
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PMID:Endothelium-ameliorating effects of statin therapy and coenzyme Q10 reductions in chronic heart failure. 1572 Oct 28

We investigated the effects of atorvastatin on inflammation and cardiac events during the inpatient period and initial 6-month follow-up in acute coronary syndrome (ACS) patients with low low-density lipoprotein (LDL) cholesterol level. One hundred and twelve consecutive ACS patients with LDL cholesterol less than 100 mg/dl were included in the study (mean 78.2+/-12.3 mg/dl). While 70 randomly selected patients received a dose of 40 mg atorvastatin within the first 24 h on top of their standard treatment as the atorvastatin group, the remaining 42 patients considered as the control group were given the standard treatment only, i.e., without any lipid-lowering drug therapy. Lipid profile, high-sensitivity C-reactive protein (hsCRP), and plasma amyloid A (SAA) levels were measured in all patients within the first 24 h of chest pain, on the 5th day, and in the 6th month. During the inpatient period and subsequent 6-month follow-up, all episodes of angina, reinfarction, revascularization, heart failure, rehospitalization, cardiac mortality, and total number of cardiac events were recorded. In the atorvastatin group, hsCRP and SAA values on the 5th day and in the 6th month compared to the first 24 h were significantly lower than those of the control group (P<0.0001). Mean LDL cholesterol level was significantly decreased in the atorvastatin group (55.7+/-17.7 mg/dl), but there was no significant change in the control group at the 6th month. The frequency of heart failure during the inpatient period and angina, unstable angina pectoris, heart failure, and revascularization in the first 6 months were also significantly reduced in the atorvastatin group. Atorvastatin started in the first 24 h reduces inflammation and improves the prognosis during both the inpatient period and the first 6 months of clinical follow-up in ACS patients with low LDL cholesterol levels.
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PMID:The effect of early statin treatment on inflammation and cardiac events in acute coronary syndrome patients with low-density lipoprotein cholesterol. 1715 16

Statins have pleiotropic effects such as anti-inflammatory and vascular protective effects that would be beneficial for patients with chronic heart failure. This report describes a patient with idiopathic dilated cardiomyopathy and a long-standing history of heart failure that was treated with atorvastatin in addition to conventional therapy that included beta-blockers. Atorvastatin therapy for 12 months was associated with an improvement in cardiac function and improved left ventricular remodeling and peak oxygen consumption. This result suggests that statin therapy may be a potential novel treatment strategy for patients with chronic heart failure.
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PMID:Atorvastatin therapy associated with improvement in left ventricular remodeling in a case of idiopathic dilated cardiomyopathy. 1717 Jun 29

LV (left ventricular) remodelling is the basic mechanism of HF (heart failure) following MI (myocardial infarction). Although there is evidence that pro-inflammatory cytokines [including TNF-alpha (tumour necrosis factor-alpha) and IL-6 (interleukin-6)] are involved in the remodelling process, only little is known about the role of anti-inflammatory cytokines, such as IL-10. As accumulating evidence has revealed that statins possess anti-inflammatory properties, the aim of the present study was to elucidate the effect of atorvastatin on the modulation of the anti-inflammatory cytokine IL-10 and its effect on LV function in rats with HF subsequent to MI. Rats with MI, induced by permanent LAD (left anterior descending) branch coronary artery ligation, were treated for 4 weeks with atorvastatin (10 mg x kg(-1) of body weight x day(-1) via oral gavage) starting on the first day after induction of MI. Cardiac function was assessed by echocardiography and cardiac catheterization 4 weeks after MI induction. Membrane-bound and soluble fractions of TNF-alpha, IL-6 and IL-10 protein, the TNF-alpha/IL-10 ratio, serum levels of MCP-1 (monocyte chemoattractant protein-1) as well as myocardial macrophage infiltration were analysed. Treatment with atorvastatin significantly improved post-MI LV function (fractional shortening, +120%; dP/dt(max), +147%; and LV end-diastolic pressure, -27%). Furthermore atorvastatin treatment markedly decreased the levels of TNF-alpha, IL-6 and MCP-1, reduced myocardial infiltration of macrophages and significantly increased myocardial and serum levels of the anti-inflammatory cytokine IL-10. Thus the balance between pro-inflammatory and anti-inflammatory cytokines was shifted in the anti-inflammatory direction, as shown by a significantly decreased TNF-alpha/IL-10 ratio. Atorvastatin ameliorated early LV remodelling and improved LV function in rats with HF subsequent to MI. Our study suggests that the modulation of the balance between pro- and anti-inflammatory cytokines towards the anti-inflammatory cytokine IL-10 is one salutary mechanism underlying how atorvastatin influences post-MI remodelling and thus improves LV function.
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PMID:Atorvastatin enhances interleukin-10 levels and improves cardiac function in rats after acute myocardial infarction. 1897 70

Atherosclerosis, especially when manifested as coronary artery disease (CAD), continues to be the number one cause of mortality and morbidity in developed nations and will soon become so in developing countries. Survivors of an acute heart attack have an increased risk of illness and death that is 1.5-15 times greater than in the general population. Sudden death occurs in myocardial infarction (MI) survivors at a rate 4-6 times greater than in the general population. After an initial recognized MI, 25% of male and 38% of female survivors die within 1 year. Within 6 years after a recognized MI, 18% of men and 35% of women will have a second MI, 7% of men and 6% of women will suffer sudden death, and 22% of men and 46% of women will be disabled with heart failure. Aggressive secondary prevention, therefore, is the key to containing and reversing the "malignant" natural history of CAD, since patients with CAD or CAD risk equivalents are already in the "high risk" category according to the Adult Treatment Panel III (ATP III) of the National Cholesterol Education rogram (NCEP). Treatment of dyslipidemia, especially the reduction of low-density lipoprotein (LDL) cholesterol levels to below 100 mg/dl, was recommended by the 2001 NCEP-ATP Guidelines. In 2004, based on the increasing evidence from several major clinical trials between 2001 and 2004, the NCEP-ATP reaffirmed its LDL goal of < 100 mg/dl in patients with CAD or coronary disease risk equivalents (including multiple risk factors), with an optional LDL goal of < 70 mg/dl in very-high-risk patients (including patients with established coronary heart disease plus other highrisk conditions) Findings from major studies, such as the Treating to New Targets (TNT) study, the Scandinavian Simvastatin Survival Study (4S), the Collaborative Atorvastatin Diabetes Study (CARDS), the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial and, more recently, the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LAA), lend support to the idea that greater LDL cholesterol lowering than that achieved with standard doses of statins may be warranted in patients with CAD and metabolic syndrome, CAD and diabetes, CAD and congestive heart failure, and CAD and renal insufficiency. On the other hand, additional lipid reduction may also be warranted in patients with risk factors such as diabetes, hypertension or a history of stroke, but without manifest CAD and despite relatively normal cholesterol levels. These newer indications for statins, atorvastatin in particular, as part of more aggressive secondary and primary prevention, are reviewed in this paper.
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PMID:Expanding roles for atorvastatin. 1859 99

Although some data suggest that statins can improve cardiac mechanical function in some patients with chronic heart failure (CHF), the effects of long-term statin therapy on cardiac electrical instability remain unclear. We performed a randomized perspective analysis of the effects of 10 mg/d (statin group 1, n=40), 20 mg/d (statin group 2, n=38) of atorvastatin and controls (control group, n=41) on corrected QT intervals (QTc), corrected QT dispersion (QTcd) and cardiac function in patients with CHF secondary to coronary artery disease (CAD) for one year. At 6 and 12 months, the statin groups displayed lower QTc and QTcd compared with controls. The changes were becoming more distinct in statin group 2, (P<0.05). In statin groups, the changes of QTc and QTcd were independent of changes of plasma low-density lipoprotein cholesterol and total cholesterol levels, and the decrease of QTcd was correlated with the increase of LVEF within 12 months. Atorvastatin shortens QTc, QTcd and improves cardiac function, and might thereby be parts of the mechanisms which atorvastatin benefited CHF patients secondary to CAD.
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PMID:Statin therapy shortens QTc, QTcd, and improves cardiac function in patients with chronic heart failure. 1904 44

We investigated whether intensive cholesterol lowering could more effectively prevent heart failure (HF) in secondary prevention. The IDEAL study was a 4.8-year prospective, randomized trial comparing "usual" simvastatin treatment (20 to 40 mg/day, n = 4,449) with high-dose atorvastatin (80 mg/day, n = 4,439) in patients with a history of myocardial infarction (MI). At baseline, 94% of patients (n = 8,351) had no history of HF. During the course of the trial, there were 222 new or recurrent hospitalizations for HF (57 and 165 in those with and without HF at baseline, respectively), 123 (2.8%) in the simvastatin group and 99 (2.2%) in the atorvastatin group (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.62 to 1.05, p = 0.11). After adjustments, atorvastatin 80 mg was associated with a 26% decrease of new HF events compared with simvastatin 20 to 40 mg (HR 0.74, 95% CI 0.57 to 0.97, p = 0.03). Atorvastatin tended to be associated with fewer HF events in those with HF at baseline (n = 537, HR 0.65, 95% CI 0.38 to 1.11, p = 0.11) and those without HF at baseline (n = 8,351, HR 0.80, 95% CI 0.59 to 1.09, p = 0.15). Also, HF without preceding MI (n = 187) was decreased (HR 0.73, 95% CI 0.54 to 0.97, p = 0.03). In conclusion, atorvastatin 80 mg was more efficient than simvastatin 20 to 40 mg in preventing development of HF in patients with previous MI.
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PMID:Comparative effect of atorvastatin (80 mg) versus simvastatin (20 to 40 mg) in preventing hospitalizations for heart failure in patients with previous myocardial infarction. 1942 32

Aims There is increasing evidence that immune mechanisms are involved in the pathogenesis of heart failure (HF). The relationship between neopterin and the risk of HF has yet to be investigated on a large scale. We assessed the relationship between neopterin, a novel marker of monocyte activation, and risk of hospitalization for HF. Methods and results Among the subjects of Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trial, 3946 had neopterin levels measured at study entry, on average 7 days after acute coronary syndrome (ACS). We assessed the relationship between neopterin and hospitalization for HF, and for death or HF over 2 years mean follow-up in a post hoc analysis using Cox regression models. Unadjusted hospitalization rates for HF increased across quartiles of neopterin, from 0.66 to 3.97 per 100 person-years. Per 1SD increment in log (neopterin), the adjusted risk of HF increased by 34% [hazard ratio (HR) 1.34, CI 1.10-1.64; P = 0.004]. Even after excluding individuals with a prior history of HF or recurrent ischaemic events, the relationship between neopterin and HF hospitalization remained significant. When added to a multivariable Cox model of HF-risk containing traditional risk factors, C-reactive protein and brain natriuretic protein (BNP), the further addition of neopterin significantly improved the HF-risk prediction model by likelihood ratio test analysis (P = 0.005), C-statistic (increasing from 0.743 to 0.773; P = 0.027), integrated discrimination improvement (IDI) analysis (P = 0.001), but not net reclassification improvement (NRI) analysis (P = 0.406). Similar results were obtained for the endpoint of death or HF. Conclusion Neopterin levels are an independent predictor of HF hospitalization, and improve risk prediction over and above conventional biomarkers.
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PMID:Prognostic utility of neopterin and risk of heart failure hospitalization after an acute coronary syndrome. 2134 49

The NADPH oxidases (Noxes) are a family of ROS (reactive oxygen species)-generating enzymes which play a critical role in the development of cardiac remodeling associated with heart failure. The Noxes of their catalytic isoforms include multiple homologues in cardiovascular cells with wide range tissue distribution. It is still unclear which Noxes represent the major enzymatic source of ROS in the heart and play a predominant role in cardiac hypertrophy. In this study we investigated the differential expression changes of NAD(P)H oxidase P47phox isoform and Nox homologues in left ventricle and the effects of atorvastatin on cardiac remodeling in two-kidney two-clip(2K2C) hypertensive rats. The mRNA and protein expression of Nox2, Nox4 and P47phox showed a sustained increase at 4, 8, 12 weeks after surgery in 2K2C rats. Administration of atorvastatin attenuated cardiac dysfunction, hypertrophy and fibrosis of 2K2C rats. However, atorvastatin treatment had no effects on BP regulation. Further studies revealed that atorvastatin inhibited the increased expression of Nox2, Nox4, P47phox as well as 02"- production in 2K2C hypertensive rats. These findings indicate that Nox2, Nox4 and P47phox play a crucial role in the development of cardiac remodeling in the 2K2C hypertensive rats. Atorvastatin, independent of BP control, exerts anti-remodeling effects partially by inhibition of NAD(P)H oxidase-mediated cardiac oxidative stress.
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PMID:Differential expression of Nad(P)H oxidase isoforms and the effects of atorvastatin on cardiac remodeling in two-kidney two-clip hypertensive rats. 2370 Jul 92


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