Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total of 5 randomized, double-blind trials in patients with hypercholesterolemia were prospectively designed to allow pooling of plasma lipid data after 12 weeks of treatment. The purpose was (1) to compare rosuvastatin 5 and 10 mg with atorvastatin 10 mg (data from 3 of the 5 trials); (2) to compare rosuvastatin 5 and 10 mg with simvastatin 20 mg and pravastatin 20 mg (data from 2 of the 5 trials); and (3) to summarize overall efficacy and subset analyses of rosuvastatin data from all 5 trials. Rosuvastatin 5 mg (n = 390) and 10 mg (n = 389) reduced low-density lipoprotein (LDL) cholesterol significantly more than did atorvastatin 10 mg (n = 393) (41.9% and 46.7% vs 36.4%, both p <0.001). Treatment with rosuvastatin 5 mg (n = 240) and 10 mg (n = 226) also resulted in significantly greater reductions in LDL cholesterol compared with both simvastatin 20 mg (n = 249) and pravastatin 20 mg (n = 252) (40.6% and 48.1% vs 27.1% and 35.7%, all p <0.001). Significant differences favoring rosuvastatin 10 mg were also observed for total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, apolipoprotein (apo) B, and apo A-I versus atorvastatin 10 mg, and for total cholesterol, HDL cholesterol, triglycerides, non-HDL cholesterol, and apo B versus simvastatin 20 mg and pravastatin 20 mg. Analyses of all the rosuvastatin 10 mg data (n = 615) from the 5 trials in subgroups defined by age > or =65 years, female sex, postmenopausal status, hypertension, atherosclerosis, type 2 diabetes, and obesity showed that rosuvastatin had consistent efficacy across patient subgroups.
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PMID:Efficacy of rosuvastatin compared with other statins at selected starting doses in hypercholesterolemic patients and in special population groups. 1264 36

Epidemiological studies identified several risk factors as cardiovascular disease correlates, including smoking, obesity, hypertension, diabetes, and increased plasma lipids. High blood cholesterol, and in particular LDL cholesterol levels, represents a major determinant of coronary artery disease, in particular when included in the context of a comprehensive risk profile. The more recent guidelines (especially NCEP ATP III in the United States, and the European Joint Task Force) have suggested the opportunity to favor treatment of those subjects with higher global cardiovascular risk, first of all of those individuals with coronary artery disease or another cardiovascular manifestation or diabetes, then of subjects with clustered risk factors or with markedly raised levels of single risk factors, eventually of other subjects. In this perspective the treatment also of slight dyslipidemias has been shown capable of reducing cardiovascular event incidence and mortality. Recent investigations, aiming at evaluating the impact of these "clinical recommendations" in the treatment of dyslipidemias or other cardiovascular risk factors within a framework of high global cardiovascular risk (EURO-ASPIRE II, L-TAP, etc.), showed inadequate attention of community-based medicine, disclosed by the insufficient number of subjects investigated and by the large number of untreated or undertreated patients. Rosuvastatin, a recently marketed inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, is an effective drug which may normalize high plasma cholesterol among high-risk subjects more often than other similar molecules, thus permitting to reach stringent guideline lipid targets. It is hoped that coronary risk charts based on Italian data will be implemented, with the purpose of better finding and treating those subjects who may benefit, at a suitable level of cardiovascular risk.
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PMID:[Dyslipidemia and global cardiovascular risk: treatment guidelines]. 1498 42

The aim of this study was to appreciate consequences of rosuvastatin administration on hemodynamic function, vascular oxidative stress and ischemia/reperfusion disorders in normotensive and hypertensive rats. At 10 weeks of age, spontaneously hypertensive rats (SHR, n=20) and normotensive Wistar Kyoto male rats (WKY, n=20) were divided into four groups and given, either vehicle or 10 mg/kg/day of rosuvastatin by gavage for 3 weeks. Systolic blood pressure was assessed every week. At the end of these treatments, vascular NADPH oxidase activity was evaluated by chemiluminescence (lucigenin 0.5 microM). Hearts were isolated and perfused according to the Langendorff method and were subjected to 30 min of global ischemia. Reactive oxygen species (ROS) produced during reperfusion were quantified by electron spin resonance (ESR) spectroscopy using a spin probe (CP-H, 1 mM). After one week of treatment, rosuvastatin reduced the arterial pressure in SHR rats (180.3 +/- 2.1, SHR vs 169.7 +/- 2.3 mmHg, SHR+rosuvastatin; p < 0.01), without lowering plasma cholesterol levels; these effects were not observed in WKY. NADPH activity was 25% higher in control SHR rat aortas compared to control WKY, and was reduced by rosuvastatin in SHR rats. In isolated rat hearts subjected to ischemia/reperfusion sequences, there was a deterioration in functional parameters in control SHR compared to control WKY hearts. Rosuvastatin decreased post-ischemic contracture in WKY hearts by 50% (41.5 +/- 7.5, WKY control vs 18.4 +/- 4.6 mmHg, WKY+rosuvastatin; p < 0.01) and increased left ventricular developed pressure. This beneficial effect was accompanied by a decrease in ROS detected by ESR during reperfusion (312.5 +/- 45.3, WKY control; vs 219.3 +/- 22.9 AUC/mL, WKY+rosuvastatin; p < 0.05). In conclusion, these results are in accordance with the hypothesis that oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases including hypertension, and demonstrate the beneficial effects of rosuvastatin.
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PMID:[A treatment with rosuvastatin induced a reduction of arterial pressure and a decrease of oxidative stress in spontaneously hypertensive rats]. 1622 Jul 51

The pleiotropic effects of statins represent potential mechanisms for the treatment of end-organ damage in hypertension. This study has investigated the effects of rosuvastatin in a model of cardiovascular remodeling, the DOCA-salt hypertensive rat. Male Wistar rats weighing 300 to 330 g were uninephrectomized (UNX) or UNX and treated with DOCA (25 mg subcutaneously every fourth day) and 1% NaCl in the drinking water. Compared with UNX controls, DOCA-salt rats developed hypertension, cardiovascular hypertrophy, inflammation with perivascular and interstitial cardiac fibrosis, endothelial dysfunction, and prolongation of ventricular action potential duration at 28 days. Rosuvastatin-treated rats received 20 mg/kg/d of the drug in 10% Tween 20 by oral gavage for 32 days commencing 4 days before uninephrectomy. UNX and DOCA-salt controls received vehicle only. Rosuvastatin therapy attenuated the development of cardiovascular hypertrophy, inflammation, fibrosis, and ventricular action potential prolongation, but did not modify hypertension or vascular dysfunction. We conclude that the pleiotropic effects of rosuvastatin include attenuation of aspects of cardiovascular remodeling in the DOCA-salt model of hypertension in rats without altering systolic blood pressure.
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PMID:Rosuvastatin attenuates hypertension-induced cardiovascular remodeling without affecting blood pressure in DOCA-salt hypertensive rats. 1663 82

To define the effect of short-term rosuvastatin treatment on the estimated glomerular filtration rate (eGFR), the database of controlled clinical trials in the Rosuvastatin Clinical Development Program was reviewed. Thirteen studies comprising 3,956 rosuvastatin-treated patients were selected based on a serum creatinine measurement at 6 or 8 weeks after initiation of rosuvastatin treatment, randomization to approved and marketed rosuvastatin doses (5 to 40 mg), and unchanged rosuvastatin dose from treatment initiation (baseline) through 6 to 8 weeks of treatment. eGFR was determined with the Modification of Diet in Renal Disease formula. eGFR significantly increased for each dose of rosuvastatin individually and for all doses combined compared with baseline (range +0.9 to +3.2 ml/min/1.73 m2). Further analysis of 5 blinded, placebo-controlled trials comprising 525 patients showed an increase in eGFR of +0.8 ml/min/1.73 m2 (95% confidence interval +0.1 to +1.5) for all rosuvastatin-treated patients, which was significantly different from baseline (p <0.04) and from a change of -1.5 ml/min/1.73 m2 in the placebo-treated patients (95% confidence interval -2.5 to -0.5, p <0.001). The increase in eGFR for rosuvastatin-treated patients was consistent across all major demographic and clinical subgroups of interest, including patients with baseline proteinuria, baseline eGFR <60 ml/min/1.73 m2, and in patients with hypertension and/or diabetes. In conclusion, these results are consistent with previous rosuvastatin studies that showed an upward trend in eGFR with long-term treatment (> or =96 weeks) and with the hypothesis that statins may have pleiotropic mechanisms of action that include beneficial renal effects.
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PMID:Effect of short-term rosuvastatin treatment on estimated glomerular filtration rate. 1672 22

We recently reported that increased vascular endothelial nitric oxide production could protect against the development of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and right ventricular hypertrophy (RVH) in rats (32). The present study investigated whether the pleiotropic action of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in upregulating endothelial function could also protect against the MCT-induced end-organ damages. Rosuvastatin (2 mg kg(-1) day(-1) via oral gavage) or placebo was initiated 1 wk before or 1 wk after MCT (60 mg/kg ip) administration. One month after MCT, significant PAH developed in the placebo rats, which were accompanied by histological evidence of pulmonary vascular thickening and right ventricular hypertrophy. The coronary endothelial vasodilatory function, assessed with endothelial/nitric oxide-dependent responses to acetylcholine and N(G)-nitro-L-arginine methyl ester (L-NAME), was depressed, while the constrictory responses to known coronary constrictors was enhanced. In rats that received rosuvastatin treatment 1 wk before MCT administration, a significantly reduced PAH and RVH was observed, as well as reduced pulmonary vascular and right ventricular remodelings. Rosuvastatin 1-wk posttreatment had no effect on PAH, but inhibited RVH. Right coronary endothelial dysfunction, which was shown in placebo rats, was effectively prevented by both pre- and postrosuvastatin treatment, while this effect was more dramatic in the pretreated group. Left coronary endothelial function, which was not affected by MCT, also showed an upregulation by rosuvastatin. Taken together, our results demonstrated the pleiotropic protection of rosuvastatin against the development of PAH and RVH and confirmed our previous finding that the targeted preservation of coronary endothelial function and vasoactivity may provide a novel approach to protect against cardiac remodeling.
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PMID:Rosuvastatin provides pleiotropic protection against pulmonary hypertension, right ventricular hypertrophy, and coronary endothelial dysfunction in rats. 1805 12

Calcific aortic stenosis (AS) is a progressive disease that has, until recently, been considered to be a degenerative and unmodifiable process induced by long-lasting mechanical stress. However, histopathologic studies have now demonstrated that the development and progression of calcific AS is based on an active process, sharing a number of similarities with atherosclerosis. Inflammation, lipid infiltration, dystrophic calcification, ossification, platelet deposition and endothelial dysfunction have been observed in both diseases. In addition, several studies have suggested that AS and atherosclerosis share a number of risk factors, such as hypercholesterolemia, elevated lipoprotein (a), smoking, hypertension and diabetes. These findings suggest that statin therapy could be beneficial in AS by its lipid-lowering and/or anti-inflammatory effects, as is the case in atherosclerosis. Although this concept has been supported by experimental work and by four retrospective clinical studies observing significantly slower rates of hemodynamic progression in statin-treated patients, a prospective randomized trial (Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression [SALTIRE]; 80mg of atorvastatin vs placebo) yielded a negative result. In contrast to the retrospective analyses, according to the study protocol, patients with hyperlipidemia had to be excluded in this trial. A recent prospective study (Rosuvastatin Affecting Aortic Valve Endothelium [RAAVE]) treating hypercholesteremic patients with rosuvastatin, found a significantly slower rate of progression in these patients compared with patients with normal cholesterol levels who were left untreated, suggesting that statin therapy may only be beneficial in patients with hyperlipidemia. Lipid-lowering therapy with statins can, therefore, currently only be recommended in this subgroup of patients with AS.
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PMID:Aortic sclerosis, aortic stenosis and lipid-lowering therapy. 1832 97

Hypertensive patients with left ventricular hypertrophy (LVH) are the most common high-risk group to develop heart failure with preserved ejection fraction. Recent reports have noted the favorable effect of statins on LVH. We evaluated the effect of rosuvastatin on cardiac remodeling, function, and progression to heart failure in a hypertensive rat model with established LVH. Dahl salt-sensitive rats were fed a high-salt diet until 13 weeks of age. After LVH was confirmed by echocardiography, rats were randomly assigned to control and statin treatment (n=18 each group). The statin-treated group was treated with rosuvastatin until 21 weeks of ages. Serial echocardiography, blood pressure monitoring, and miniaturized conductance catheter hemodynamic monitoring were performed at 21 weeks. Echocardiographic parameters were not significantly different between the groups. On hemodynamic monitoring, systolic performance parameters were similar between the groups, whereas end diastolic pressure-volume relationships were lower in the statin-treated group (0.014+/-0.008 versus 0.008+/-0.004 mm Hg/muL, P<0.05), suggesting improvement in myocardial stiffness. Pathological analysis showed attenuation of perivascular and interstitial fibrosis in the statin-treated group (P<0.02). Rosuvastatin therapy did not alleviate LVH in hypertensive rats with established LVH, but it attenuated myocardial fibrosis and LV stiffness. It seems that rosuvastatin has limited therapeutic value when used to prevent progression from LVH to heart failure in hypertensive hearts.
Hypertension 2009 Sep
PMID:Effect of rosuvastatin on cardiac remodeling, function, and progression to heart failure in hypertensive heart with established left ventricular hypertrophy. 1956 47

Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) was a placebo-controlled trial undertaken on "apparently healthy" subjects selected primarily on the basis of high-sensitivity C-reactive protein concentrations >or=2.0 mg/L. JUPITER showed that rosuvastatin reduced the incidence of cardiac events compared to a control group. The study population (median age 66 years) included men and women with the metabolic syndrome (about 41%), median blood pressures in the prehypertensive range, current smoking (about 15%), median body mass indexes higher than normal, and Framingham 10-year risk >10% (about 50%). The presence of these risk factors indicates that a significant proportion of subjects were not "healthy" and warranted aggressive management under current guidelines, without the measurement of high-sensitivity C-reactive protein. Furthermore, <17% of the trial participants were taking guidelines-recommended aspirin, and 25% had systolic blood pressures >145 mm Hg and would have merited treatment for hypertension. It is likely that many of the participants did not receive care consistent with current standards. Thus, the benefit of statin therapy would have been more difficult to demonstrate if standard therapeutic recommendations had been followed. In conclusion, these considerations cast doubt on the contention that statin therapy should be initiated in apparently healthy individuals on the basis of elevated high-sensitivity C-reactive protein levels.
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PMID:Another look at the results of the JUPITER trial. 1993

Statins have been shown to reduce cardiovascular events across a broad spectrum of patients at risk, irrespective of baseline LDL-cholesterol levels. In a meta-analysis of 14 statin trials involving more than 90,000 participants, statin therapy reduced the 5-year incidence of cardiovascular events by about 20% for each mmol/L of LDL-cholesterol reduction. The results of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) study suggest that the degree of reduction in Japanese subjects may be greater than this for the same degree of LDL-cholesterol reduction. Given the success of statins in preventing cardiovascular events, it is not surprising that they have been tested in a variety of related conditions, three of which are discussed in this article. Heart failure is characterized by inflammation, endothelial dysfunction and neurohumeral activation, conditions that are ameliorated by statin therapy. The Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) showed no significant benefit of rosuvastatin upon the primary endpoint, cardiovascular death, myocardial infarction and stroke. However, subgroups identified by the biomarkers plasma amino-terminal pro-brain natriuretic and C-reactive protein showed a reduction in events. Aortic stenosis and atherosclerosis share common risk factors, including hypertension and hypercholesterolemia. Although non-randomized cohort studies have suggested that statins slow the progression of aortic stenosis, this was not shown in either of the two randomized placebo-controlled trials testing this hypothesis. Similarly, Alzheimer's disease shares many risk factors with atherosclerosis, and several observational studies have reported a lower risk of developing this condition in patients taking statins. However, two recently completed clinical trials indicate that neither atorvastatin nor simvastatin slow the progression of early Alzheimer's disease. In conclusion, although statins are effective, established therapy for the prevention of vascular events in patients at risk, they have as yet not proven to be successful for these newer indications.
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PMID:Exploring new indications for statins beyond atherosclerosis: Successes and setbacks. 2020 67


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