Endothelium-dependent responses in patients with hypercholesterolemic coronary artery disease under the effects of simvastatin and enalapril, either separately or combined

Esper, Ricardo J.; Machado, Rogelio A.; Vilariño, Jorge; Cacharrón, José L.; Ingino, Carlos A.; Guiñazú, Carlos A. Garcı́a; Bereziuk, Eulalio; Bolaño, Alberto L.; Suárez, Daniel

doi:10.1067/mhj.2000.109649

Cited by 32 publications

(24 citation statements)

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“…15 Therefore, simvastatin combined with ramipril may reduce LDL cholesterol levels and angiotensin II expression, which would be predicted to improve flow-mediated dilation. Indeed, consistent with other studies, 16,25 we observed that simvastatin combined with ramipril significantly improved the percent flow-mediated dilator response to hyperemia to greater extent than simvastatin or ramipril alone. One recent study reported no additional benefits on coronary atherosclerosis progression measured by quantitative coronary angiogram when simvastatin was combined with enalapril.…”

Section: Discussionsupporting

confidence: 80%

Simvastatin Combined With Ramipril Treatment in Hypercholesterolemic Patients

et al. 2004

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Abstract-Mechanisms underlying biological effects of statin and angiotensin-converting enzyme inhibitor therapies differ. Thus, we studied vascular responses to combination therapy in hypercholesterolemic patients. A randomized, double-blind, placebo-controlled, crossover trial was conducted with 50 hypercholesterolemic patients with simvastatin and either placebo or ramipril (study I) and in 45 hypercholesterolemic diabetic patients with simvastatin or ramipril with placebo or simvastatin combined with ramipril (study II) for 2 months with 2 months washout. In study I simvastatin combined with ramipril significantly reduced blood pressure after 2 months. Simvastatin alone or combined with ramipril significantly changed lipoproteins, improved percent flow-mediated dilator response to hyperemia by 30Ϯ5% and 53Ϯ6%, respectively (PϽ0.001), and reduced plasma levels of malondialdehyde by 4Ϯ7% (Pϭ0.026) and 25Ϯ4% (PϽ0.001), respectively. Monocyte chemoattractant protein-1 levels decreased by 3Ϯ3% and 12Ϯ2%, respectively (Pϭ0.049 and Pϭ0.001, respectively), C-reactive protein levels changed by 0% and 18%, respectively (Pϭ0.036 and PϽ0.001, respectively), and plasminogen activator inhibitor-1 antigen levels changed by Ϫ7Ϯ7% and 17Ϯ5%, respectively (Pϭ0.828 and PϽ0.001, respectively). In study II ramipril alone did not significantly change lipoproteins and C-reactive protein levels, however, simvastatin combined with ramipril significantly changed lipoproteins and C-reactive protein levels more than ramipril alone (PϽ0.001 and Pϭ0.048 by ANOVA, respectively). Ramipril alone or simvastatin combined with ramipril significantly improved the percent flow-mediated dilator response to hyperemia (both PϽ0.001), however, simvastatin combined with ramipril showed significantly more improvement than ramipril alone (PϽ0.001 by ANOVA). Simvastatin combined with ramipril significantly improved endotheliumdependent vasodilation and fibrinolysis potential and reduced plasma levels of oxidant stress and inflammation markers in hypercholesterolemic patients. Key Words: angiotensin-converting enzyme Ⅲ atherosclerosis Ⅲ endothelial growth factors Ⅲ hypercholesterolemia Ⅲ blood pressure L arge-scale clinical studies demonstrate that statins and angiotensin-converting enzyme (ACE) inhibitor prevent or retard the progression of coronary heart disease. 1,2 The mechanisms of this apparent benefit of these therapies may include vascular effects. Statins reduce LDL cholesterol and improve endothelial function, consistent with enhanced NO bioactivity. 3-5 ACE inhibition also improves endothelial function. 6,7 A potential mechanism of this effect is augmented NO bioactivity via diminished bradykinin degradation by ACE with activation of endothelial B 2 kinin receptors and stimulation of NO synthase activity. 8 Alternatively, ACE inhibition may diminish intracellular production of superoxide anions via reduced activity of angiotensin II-dependent oxidases in the endothelium and vascular smooth muscle, 9,10 thus protecting NO from oxidant degradatio...

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Section: Discussionsupporting

confidence: 80%

Simvastatin Combined With Ramipril Treatment in Hypercholesterolemic Patients

et al. 2004

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“…In contrast to SCAT, another study showed a synergistic effect of simvastatin and enalapril in increasing the response to postischaemic vasodilatation in hypercholesterolaemic patients. 30 It is likely that the synergistic/additive effect of statins and ACEI we found could be attributed to the complementary pleiotropic effects of these drugs. 31,32 For example, ACEIs and statins can have beneficial effects on haemostatic and other factors.…”

Section: Discussionmentioning

confidence: 90%

“…A significant additive effect on structural vascular damage, blood pressure, and vascular resistance was also shown during combination treatment of simvastatin and enalapril in hypertensive subjects. 30,32 We reported that quinapril 41 and atorvastatin 42,43 have a beneficial effect on heart rate variability and aortic elasticity, left ventricular ejection fraction and left ventricular mass index. 43 All these factors could account for an increased event rate.…”

Section: Discussionmentioning

confidence: 98%

Effect of statins and ACE inhibitors alone and in combination on clinical outcome in patients with coronary heart disease

et al. 2004

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We assessed the 'synergy' of statins and angiotensinconverting enzyme inhibitors (ACEI) in reducing vascular events in patients with coronary heart disease (CHD). The GREek Atorvastatin and CHD Evaluation (GREACE) Study, suggested that aggressive reduction of low density lipoprotein cholesterol to 2.59 mmol/l (o100 mg/dl) significantly reduces morbidity and mortality in CHD patients, in comparison to undertreated patients. In this post hoc analysis of GREACE the patients (n ¼ 1600) were divided into four groups according to long-term treatment: Group A (n ¼ 460 statin þ ACEI), B (n ¼ 420; statin, no ACEI), C (n ¼ 371;no 371;no statin, on ACEI), and D (n ¼ 349; no statin, no ACEI). Analysis of variance was used to assess differences in the relative risk reduction (RRR) in 'all events' (primary end point) between groups. During the 3-year follow-up there were 292 cardiovascular events; 45 (10% of patients) in group A, 61 (14.5%) in group B, 91 in group C (24.5%) and 95 events in group D (27%). The RRR (95% confidence interval (CI) in the primary end point in group A was 31%, (95% CI À48 to À6%, P ¼ 0.01) in comparison to group B, 59% (95% CI À72 to À48%, Po0.0001) to group C and 63% (95% CI À74 to À51%, Po0.0001) to group D. There was no significant difference in RRR between groups C and D (9%, CI À27-10%, P ¼ 0.1). Other factors (eg the blood pressure) that can influence clinical outcome did not differ significantly between the four treatment groups. In conclusion, the statin þ ACEI combination reduces cardiovascular events more than a statin alone and considerably more than an ACEI alone. Aggressive statin use in the absence of an ACEI also substantially reduced cardiovascular events. Treatment with an ACEI in the absence of a statin use reduced clinical events in comparison to patients not treated with an ACEI but not significantly, at least in these small groups of patients.

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“…78) Further, enalapril has significantly increased the postischemic vasodilator response in patients with coronary hypercholesterolemia. 81) In healthy volunteers, triglyceride-rich lipoproteins-induced endothelial dysfunction was prevented by losartan and quinapril and the preventive effect was more pronounced with quinapril. 79) In mildly hypertensive patients without organ damage, zofenopril, beyond its blood pressure lowering effect and through its sustained antioxidant activity has markedly improved endothelial function.…”

Section: Primary Hypercholesterolemia Pitavastatin Atorvastatinmentioning

confidence: 99%

“…70,[75][76][77][78][79][80][81][82][83] In the Trial on Reversing ENdothelial Dysfunction (TREND) study, normotensive patients with angiographically demonstrated coronary atherosclerosis were treated chronically with quinapril, an ACE inhibitor with high tissuebinding affinity. These patients had restoration of endothelium-dependent vasodilation of coronary vessels in absence of significant reduction in blood pressure.…”

Section: Primary Hypercholesterolemia Pitavastatin Atorvastatinmentioning

confidence: 99%

Pharmacological Interventions to Prevent Vascular Endothelial Dysfunction: Future Directions

Balakumar¹,

Koladiya

Ramasamy

et al. 2008

JOURNAL OF HEALTH SCIENCE

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Endothelium forms an innermost lining of blood vessel and it regulates the vascular tone and permeability. A healthy vascular endothelium is antiatherogenic in nature because of its properties such as inhibition of platelet aggregation, adhesion cascades, smooth muscle cell proliferation and leukocyte adhesion. Vascular endothelial dysfunction (VED) is associated with reduced synthesis and release of nitric oxide, proinflammatory and prothrombotic properties followed by diminished vasodilation. VED has been implicated in the pathogenesis of artherosclerosis, hypertension, myocardial infarction, heart failure, renal failure and stroke. Various pharmacological interventions such as angiotensin converting enzyme (ACE) inhibitors, statins, insulin sensitizers, L-arginine as well as agents that target endothelial nitric oxide synthase (eNOS) "coupling" such as folates or tetrahydrobiopterin (BH4) have been noted to improve the function of vascular endothelium. In this review, we discussed various recently developed pharmacological interventions to improve the function of endothelium. Moreover, the novel targets sites involved in the pathogenesis of vascular endothelial dysfunction have been delineated.

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Endothelium-dependent responses in patients with hypercholesterolemic coronary artery disease under the effects of simvastatin and enalapril, either separately or combined

Cited by 32 publications

References 0 publications

Simvastatin Combined With Ramipril Treatment in Hypercholesterolemic Patients

Simvastatin Combined With Ramipril Treatment in Hypercholesterolemic Patients

Effect of statins and ACE inhibitors alone and in combination on clinical outcome in patients with coronary heart disease

Pharmacological Interventions to Prevent Vascular Endothelial Dysfunction: Future Directions

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