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1.
Diagn Interv Radiol ; 24(3): 153-157, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29770768

RESUMO

PURPOSE: Debulking strategies prior to drug-coated balloon (DCB) angioplasty were suggested to improve clinical results in femoro-popliteal lesions. Currently, there are no data regarding plaque modification with a scoring balloon with subsequent DCB-angioplasty. Recently published 6-month results of the DCB-Trak registry in patients treated with scoring-balloon angioplasty and DCB-angioplasty were promising without any safety concerns. Herein, we report the 12-month follow-up data. METHODS: In a single center registry, 29 consecutive patients with 32 femoro-popliteal lesions were treated with a scoring-balloon (VascuTrak®) and a DCB subsequently. The primary endpoint was the clinically driven target lesion revascularization (TLR). Secondary endpoints were clinically driven target vessel revascularization (TVR), binary restenosis (peak systolic velocity ratio > 2.4), change in Rutherford classification and ankle-brachial-index (ABI). Safety endpoints were major cardiovascular events (cardiovascular death, myocardial infarction, stroke, death) and need for amputation. RESULTS: The procedure was successful in 29 lesions. There were no clinically driven TLRs after 12 months. Two patients required clinically driven TVR and one patient had a binary restenosis. ABI significantly increased after the procedure (0.87±0.24 to 1.04±0.18, P < 0.01) without a relevant change after 6 months (1.01±0.15, P < 0.05) or 12 months (1.01±0.20, P < 0.05). Rutherford classification improved in more than 90% of patients after 6 and 12 months. There was one major cardiovascular event at 6-month follow-up, but no amputations at 6- or 12-month follow-up. CONCLUSION: Vessel preparation with a scoring-balloon and subsequent DCB-angioplasty was safe and effective in patients with femoro-popliteal lesions. Further multicenter trials have to validate these results.


Assuntos
Angioplastia com Balão/instrumentação , Artéria Femoral/cirurgia , Doença Arterial Periférica/cirurgia , Artéria Poplítea/cirurgia , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica/métodos , Angiografia/instrumentação , Angioplastia com Balão/métodos , Índice Tornozelo-Braço/classificação , Índice Tornozelo-Braço/instrumentação , Constrição Patológica/complicações , Stents Farmacológicos/normas , Feminino , Artéria Femoral/patologia , Fluoroscopia/instrumentação , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/patologia , Artéria Poplítea/patologia , Estudos Prospectivos , Sistema de Registros , Acidente Vascular Cerebral/complicações , Resultado do Tratamento
2.
Atherosclerosis ; 251: 291-298, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27439215

RESUMO

BACKGROUND AND AIMS: The renin-angiotensin-aldosterone-system (RAAS) plays a role in endothelial dysfunction and atherosclerosis. During treatment with RAAS-inhibitors, elevated aldosterone may sustain "aldosterone escape". METHODS: We investigated the effects of treatment with the mineralocorticoid antagonist eplerenone (Ep) compared with ramipril (Rami) or the combination of both on oxidative stress, plaque formation and endothelial function, in atherosclerotic apolipoprotein E deficient mice (ApoE(-/-)-mice). ApoE(-/-)-mice were fed a cholesterol rich diet (21% fat, 19.5% casein, 1.25% cholesterol) for 8 weeks to produce mild atherosclerosis (i.e. plaque load 20-30%). ApoE(-/-)-mice (control), ApoE(-/-)-mice treated with Ep (25 mg/kg/day), Rami (2.5 mg/kg/day) and their combination were compared. Heart rate (HR) and blood pressure (BP) were measured using the tail-cuff-method. Endothelial function was measured in aortic rings and corpora cavernosal strips (CCs). Atherosclerotic plaque burden, collagen content, oxidative stress (Dihydroethidium (DHE) staining) and macrophages were determined. RESULTS: Treatments had no effects on HR and slightly reduced BP in ApoE(-/-)-mice treated with the combination of eplerenone and ramipril. Endothelium-dependent relaxation of aortic rings and CCs with carbachol was significantly improved in animals treated with Ep, Rami or their combination (p = 0.05 - p = 0.001). DHE-stained penile and aortic sections revealed a significant reduction in superoxide production in all treated groups (p = 0.035 - p = 0.001). In parallel, aortic and penile collagen content in ApoE(-/-)-mice was significantly decreased (p = 0.035 - p < 0.001) in animals treated with Ep, Rami or their combination. In agreement, there was a trend towards a reduction of aortic plaque area by treatment with Ep (-9.0 ± 3.2%) and Rami (-11.9 ± 4%). Only the treatment with the combination induced a significant reduction of the atherosclerotic plaque burden (p = 0.045). Moreover, the treatment of ApoE(-/-)-mice with Ep, Rami and their combination significantly reduced the count macrophage count in atherosclerotic plaque lesions. Ep restored endothelial function by reduction of oxidative stress, atherosclerotic macrophage content, atherosclerotic lesion size and fibrosis to the same extent as treatment with Rami or the combination. CONCLUSIONS: Mineralocorticoid antagonism provides vasculoprotective effects and should be clinically evaluated for vascular disease such as erectile dysfunction.


Assuntos
Aterosclerose/metabolismo , Colesterol/administração & dosagem , Endotélio Vascular/fisiologia , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Aorta/metabolismo , Pressão Sanguínea , Disfunção Erétil/metabolismo , Frequência Cardíaca , Masculino , Camundongos , Camundongos Knockout para ApoE , Mineralocorticoides , Estresse Oxidativo
3.
J Pharmacol Exp Ther ; 343(2): 253-7, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22837011

RESUMO

The recently developed oral anticoagulant dabigatran (Dabi) etexilate directly inhibits thrombin after activation by plasma esterases to dabigatran. Thrombin is involved in the pathogenesis of atherosclerosis. We investigated the effects of direct thrombin inhibition on atherosclerosis and endothelial function in a hypercholesterolemic mouse model with accelerated atherosclerosis {[apolipoprotein E-deficient (ApoE(-/-)] mice}. ApoE(-/-) mice were treated with a cholesterol-rich diet for 12 weeks and either dabigatran etexilate (900 mg/kg body weight) or vehicle. Wild-type (C57/B6) mice served as control. Endothelial function was assessed with carbachol (endothelium dependent) by using glyceroltrinitrate (endothelium independent) as control in aortic rings. Atherosclerotic lesion formation was evaluated with Oil Red staining, and vascular collagen content was determined by Sirius Red staining. Reactive oxygen species (ROS) production was determined by semiquantitative immunohistochemical staining. Measurement of dabigatran plasma levels (622.3±169 ng/ml) and a performed coagulation test (diluted thrombin time) revealed a relevant anticoagulatory concentration. Dabigatran etexilate attenuated increased atherosclerotic plaque formation [ApoE(-/-) Dabi: 16.1±3.8% of ApoE(-/-) control; p<0.001], decreased collagen content [ApoE(-/-) Dabi: 49.1±10% of ApoE(-/-) control; p=0.01], and ROS production in dihydroethidium staining [ApoE(-/-) Dabi: 46.3±5.4% of ApoE(-/-) control; p=0.005] in parallel to an improvement of endothelial function [ApoE(-/-) control 42.6±2.7 versus ApoE(-/-) Dabi 62.9±3.3% of phenylephrine-induced contraction; p=0.001] at 100 µmol carbachol. These data suggest that direct thrombin inhibition in a relevant dosage improved endothelial function and reduced atherosclerotic lesion size, collagen content, and oxidative stress in hypercholesterolemic atherosclerosis. Interference with the coagulation system might provide a therapeutic target to modify atherosclerotic disease progression.


Assuntos
Antitrombinas/farmacologia , Apolipoproteínas E/fisiologia , Benzimidazóis/farmacologia , Endotélio Vascular/efeitos dos fármacos , Placa Aterosclerótica/genética , Placa Aterosclerótica/prevenção & controle , Trombina/antagonistas & inibidores , beta-Alanina/análogos & derivados , Animais , Apolipoproteínas E/genética , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Colágeno/metabolismo , Dabigatrana , Etídio/análogos & derivados , Corantes Fluorescentes , Frequência Cardíaca/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Microscopia de Fluorescência , Estresse Oxidativo/efeitos dos fármacos , beta-Alanina/farmacologia
4.
Clin Cardiol ; 35(4): 255-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22278395

RESUMO

BACKGROUND: Optimal revascularization strategy is still under debate in patients with coronary artery disease, particularly due to the results of the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial. Although medical prevention has been clearly shown to be beneficial in coronary artery disease, it has been suggested that patients were significantly undertreated with evidence-based medications for cardiovascular protection. HYPOTHESIS: The purpose of the study was to evaluate concomitant medical treatment in cardiovascular interventional head-to-head trials comparing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). METHODS: A systematic search of the literature regarding documentation and reports of medical treatment in cardiovascular interventional head-to-head trials with more than 500 patients comparing CABG and PCI was performed. RESULTS: Systematic research of the literature identified 2106 articles of potential interest. After review and selection, only 3 trials reported on medical treatment. Baseline medication was reported in the RITA (Randomized Intervention Treatment of Angina), CABRI (Coronary Angioplasty versus Bypass Revascularisation Investigation), and SYNTAX trials, and follow-up data were provided by the CABRI and SYNTAX 3-year trials only. CONCLUSIONS: Poor reporting of medical treatment at discharge might reflect an underestimation of secondary prevention in patients undergoing cardiac surgery or interventional procedures in head-to-head interventional trials. Thus, discussion of optimal revascularization procedure has to remain open, even in terms of concomitant medical treatment of patients.


Assuntos
Angioplastia Coronária com Balão , Ponte de Artéria Coronária , Doença da Artéria Coronariana/terapia , Medicina Baseada em Evidências , Disseminação de Informação/métodos , Prevenção Secundária , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/cirurgia , Humanos , Medição de Risco/métodos , Fatores de Tempo
5.
Eur Heart J ; 33(10): 1223-31, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21821843

RESUMO

AIMS: Collateral arteries protect tissue from ischaemia. Heart rate correlates with vascular events in patients with arterial obstructive disease. Here, we tested the effect of heart-rate reduction (HRR) on collateral artery growth. METHODS AND RESULTS: The I(f)-channel inhibitor ivabradine reduced heart rate by 11% in wild-type and 15% in apolipoprotein E (ApoE)(-/-) mice and restored endothelium-dependent relaxation in aortic rings of ApoE(-/-) mice. Microsphere perfusion and angiographies demonstrated that ivabradine did not change hindlimb perfusion in wild-type mice but improved perfusion in ApoE(-/-) mice from 40.5 ± 15.8-60.2 ± 18.5% ligated/unligated hindlimb. Heart rate reduction (13%) with metoprolol failed to improve endothelial function and perfusion. Protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS, and eNOS activity were increased in collateral tissue following ivabradine treatment of ApoE(-/-) mice. Co-treatment with nitric oxide-inhibitor N (G)-nitro-L-arginine methyl ester abolished the effects of ivabradine on arteriogenesis. Following ivabradine, classical inflammatory cytokine expression was lowered in ApoE(-/-) circulating mononuclear cells and in plasma, but unaltered in collateral-containing hindlimb tissue, where numbers of perivascular macrophages also remained unchanged. However, ivabradine reduced expression of anti-arteriogenic cytokines CXCL10and CXCL11 and of smooth muscle cell markers smoothelin and desmin in ApoE(-/-) hindlimb tissue. Endothelial nitric oxide synthase and inflammatory cytokine expression were unchanged in wild-type mice. Ivabradine did not affect cytokine production in HUVECs and THP1 mononuclear cells and had no effect on the membrane potential of HUVECs in patch-clamp experiments. CONCLUSION: Ivabradine-induced HRR stimulates adaptive collateral artery growth. Important contributing mechanisms include improved endothelial function, eNOS activity, and modulation of inflammatory cytokine gene expression.


Assuntos
Antiarrítmicos/farmacologia , Aterosclerose/fisiopatologia , Benzazepinas/farmacologia , Circulação Colateral/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipercolesterolemia/fisiopatologia , Animais , Apolipoproteínas E/metabolismo , Artérias/efeitos dos fármacos , Capilares/efeitos dos fármacos , Canais de Cátion Regulados por Nucleotídeos Cíclicos/antagonistas & inibidores , Citocinas/efeitos dos fármacos , Ivabradina , Ligadura , Camundongos , Óxido Nítrico Sintase Tipo III/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico
6.
Vasc Health Risk Manag ; 7: 391-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21796253

RESUMO

Activation of the renin-angiotensin system plays a major role in cardiovascular morbidity and mortality. Recently, angiotensin II receptor blockers (ARBs) have been the subject of a number of large clinical cardiovascular outcome trials, indicating beneficial effects of ARBs with more than 384,000 patient-years of data in different cardiovascular diseases along the cardiovascular continuum, from patients with risk factors, through high cardiovascular risk, to patients with heart failure. This article reviews the implications of these trials for the optimal management of cardiovascular risk.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Ensaios Clínicos como Assunto , Sistema Renina-Angiotensina/efeitos dos fármacos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Doenças Cardiovasculares/metabolismo , Progressão da Doença , Medicina Baseada em Evidências , Humanos , Resultado do Tratamento
7.
J Am Coll Cardiol ; 56(24): 1973-83, 2010 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-21126638

RESUMO

This review summarizes the current literature and the open questions regarding the physiology and pathophysiology of the mechanical effects of heart rate on the vessel wall and the associated molecular signaling that may have implications for patient care. Epidemiological evidence shows that resting heart rate is associated with cardiovascular morbidity and mortality in the general population and in patients with cardiovascular disease. As a consequence, increased resting heart rate has emerged as an independent risk factor both in primary prevention and in patients with hypertension, coronary artery disease, and myocardial infarction. Experimental and clinical data suggest that sustained elevation of heart rate-independent of the underlying trigger-contributes to the pathogenesis of vascular disease. In animal studies, accelerated heart rate is associated with cellular signaling events leading to vascular oxidative stress, endothelial dysfunction, and acceleration of atherogenesis. The underlying mechanisms are only partially understood and appear to involve alterations of mechanic properties such as reduction of vascular compliance. Clinical studies reported a positive correlation between increased resting heart rate and circulating markers of inflammation. In patients with coronary heart disease, increased resting heart rate may influence the clinical course of atherosclerotic disease by facilitation of plaque disruption and progression of coronary atherosclerosis. While a benefit of pharmacological or interventional heart rate reduction on different vascular outcomes was observed in experimental studies, prospective clinical data are limited, and prospective evidence determining whether modulation of heart rate can reduce cardiovascular events in different patient populations is needed.


Assuntos
Vasos Sanguíneos/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Frequência Cardíaca , Endotélio Vascular/fisiopatologia , Humanos
8.
J Am Coll Cardiol ; 56(25): 2067-76, 2010 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-21144965

RESUMO

Atrial fibrillation (AF) is the most common cardiac rhythm disorder and a major risk factor for ischemic stroke. Antithrombotic therapy using aspirin or vitamin K antagonists (VKA) is currently prescribed for prevention for ischemic stroke in patients with AF. A narrow therapeutic range and the need of regular monitoring of its anticoagulatory effect impair effectiveness and safety of VKA, causing a need for alternative anticoagulant drugs. Recently developed anticoagulants include direct thrombin antagonists such as dabigatran or factor Xa inhibitors such as rivaroxaban, apixaban, betrixaban, and edoxaban. Currently, data from a phase III clinical trial are available for dabigatran only, which show the direct thrombin antagonist to be at least noninferior in efficacy to VKA for the prevention of stroke and systemic embolism in patients with AF. This review focuses on current advances in the development of directly acting oral anticoagulant drugs and their potential to replace the VKA class of drugs in patients with AF.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Anticoagulantes/farmacologia , Ensaios Clínicos Fase III como Assunto , Drogas em Investigação , Inibidores do Fator Xa , Humanos , Acidente Vascular Cerebral/etiologia , Trombina/fisiologia
9.
Cardiology ; 117(3): 163-73, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21051889

RESUMO

Clinical trials have shown the efficacy of angiotensin II receptor blockers (ARBs) in patients with hypertension and have suggested that ARBs are noninferior to angiotensin-converting enzyme (ACE) inhibitors in patients with ischemic heart disease and heart failure. The Heart Outcomes Prevention Evaluation (HOPE), a landmark study in high cardiovascular risk management, demonstrated the cardioprotection of the ACE inhibitor ramipril. Thus, in the recent Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET®) ramipril was selected as a comparator when exploring the cardioprotective potential of telmisartan in the first head-to-head comparison of an ACE inhibitor and an ARB in a broad cross-sectional cohort of cardiovascular high-risk patients. ONTARGET showed that telmisartan is as effective as ramipril in the management of these patients but is better tolerated. The combination of ramipril and telmisartan did not confer a further benefit but did bring about an increased rate of adverse events such as renal dysfunction. In previous ARB outcome trials, cardiovascular risk profile, nature and severity of the underlying cardiovascular disease, dosing regimens and concomitant therapies, follow-up, and endpoints have varied greatly so that caution is warranted in extrapolating evidence gained from high-risk patients to other conditions such as acute myocardial infarction or chronic heart failure.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Benzoatos/farmacologia , Benzoatos/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/efeitos dos fármacos , Progressão da Doença , Humanos , Ramipril/farmacologia , Ramipril/uso terapêutico , Fatores de Risco , Telmisartan , Resultado do Tratamento
10.
Vasc Health Risk Manag ; 6: 207-14, 2010 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-20407628

RESUMO

Raynaud's phenomenon is a clinical disorder with episodic digital ischemic vasospasm triggered by cold- or emotional-stress. It was first mentioned by Maurice Raynaud in 1862 describing "a local asphyxia of the extremities" and was further divided into primary Raynaud's disease and secondary Raynaud's phenomenon, which is often related to connective tissue diseases, but also physical or chemical strain. Though pathophysiology of Raynaud's phenomenon is still poorly understood, systemic and local vascular effects are most likely to be involved in primary Raynaud's disease. In secondary Raynaud's phenomenon additional abnormalities in vascular structure and function may play the major role. Thus, medical treatment of Raynaud's phenomenon remains unsatisfactory, due to limited understanding of pathophysiological mechanisms. This review addresses current evidence for medical treatment of primary and secondary Raynaud's phenomenon with regard to pathophysiological mechanisms as well as future perspectives.


Assuntos
Doença de Raynaud/terapia , Antagonistas Adrenérgicos alfa/uso terapêutico , Algoritmos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas dos Receptores de Endotelina , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Doença de Raynaud/etiologia , Doença de Raynaud/fisiopatologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Vasoconstrição/fisiologia , Vasodilatação/fisiologia , Vasodilatadores/uso terapêutico , Quinases Associadas a rho/antagonistas & inibidores
11.
Atherosclerosis ; 212(1): 55-62, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20347444

RESUMO

OBJECTIVE: To determine the effect of heart rate reduction with ivabradine on atherosclerotic lesions and erectile dysfunction. METHODS: Two different treatment regimes with ivabradine were applied in wild-type (C57/B6) and ApoE(-/-)-mice to study effects of ivabradine on erectile function and atherosclerosis in animals with and without present endothelial dysfunction. Preventive effects of ivabradine were evaluated in animals fed a high-cholesterol diet in parallel to treatment with ivabradine (orally via chow, 10 mg/kg per day). The other treatment regime started treatment with a high-cholesterol diet for 4 weeks to induce endothelial dysfunction. Thereafter, treatment with ivabradine (orally via chow, 15 mg/kg per day) was started in ApoE(-/-) mice for 3 months. Vital parameters were measured using the tail-cuff method. Erectile function was assessed by pharmacological stimulation of corpora cavernosa in organ bath chambers. Atherosclerotic plaque formation, oxidative stress, eNOS and collagen content were determined. RESULTS: Treatment with ivabradine significantly reduced heart rate (p<0.01), with no effect on blood pressure. Aortic atherosclerotic lesion size decreased with ivabradine in both treatment regimes (p<0.05). Endothelium-dependent relaxation of corpora cavernosa significantly decreased in ApoE(-/-)-mice with a restoration by ivabradine in prevention and reversal. Dihydroethidium-stained penile sections (p<0.05) and lipid peroxidase assay (p<0.05) revealed a reduction in superoxide production in ivabradine-treated animals. Penile eNOS-expression increased and collagen content significantly decreased (p<0.01) in ivabradine-treated animals. CONCLUSION: Ivabradine improves penile endothelial function by reduction of oxidative stress and penile fibrosis. Beneficial effects were achieved in prevention and manifest endothelial dysfunction.


Assuntos
Antiarrítmicos/farmacologia , Apolipoproteínas E/deficiência , Aterosclerose/prevenção & controle , Benzazepinas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Impotência Vasculogênica/prevenção & controle , Ereção Peniana/efeitos dos fármacos , Pênis/efeitos dos fármacos , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Apolipoproteínas E/genética , Aterosclerose/etiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Pressão Sanguínea , Colesterol na Dieta , Colágeno/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Fibrose , Impotência Vasculogênica/etiologia , Impotência Vasculogênica/metabolismo , Impotência Vasculogênica/fisiopatologia , Ivabradina , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pênis/irrigação sanguínea , Pênis/fisiopatologia , Superóxidos/metabolismo , Fatores de Tempo , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia
12.
Circulation ; 121(12): 1439-46, 2010 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-20231536

RESUMO

BACKGROUND: Although erectile dysfunction (ED) is associated with cardiovascular risk factors and atherosclerosis, it is not known whether the presence of ED is predictive of future events in individuals with cardiovascular disease. We evaluated whether ED is predictive of mortality and cardiovascular outcomes, and because inhibition of the renin-angiotensin system in high-risk patients reduces cardiovascular events, we also tested the effects on ED of randomized treatments with telmisartan, ramipril, and the combination of the 2 drugs (ONTARGET), as well as with telmisartan or placebo in patients who were intolerant of angiotensin-converting enzyme inhibitors (TRANSCEND). METHODS AND RESULTS: In a prespecified substudy, 1549 patients underwent double-blind randomization, with 400 participants assigned to receive ramipril, 395 telmisartan, and 381 the combination thereof (ONTARGET), as well as 171 participants assigned to receive telmisartan and 202 placebo (TRANSCEND). ED was evaluated at baseline, at 2-year follow-up, and at the penultimate visit before closeout. ED was predictive of all-cause death (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.21 to 2.81, P=0.005) and the composite primary outcome (HR 1.42, 95% CI 1.04 to 1.94, P=0.029), which consisted of cardiovascular death (HR 1.93, 95% CI 1.13 to 3.29, P=0.016), myocardial infarction (HR 2.02, 95% CI 1.13 to 3.58, P=0.017), hospitalization for heart failure (HR 1.2, 95% CI 0.64 to 2.26, P=0.563), and stroke (HR 1.1, 95% CI 0.64 to 1.9, P=0.742). The study medications did not influence the course or development of ED. CONCLUSIONS: ED is a potent predictor of all-cause death and the composite of cardiovascular death, myocardial infarction, stroke, and heart failure in men with cardiovascular disease. Trial treatment did not significantly improve or worsen ED. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00153101.


Assuntos
Benzimidazóis/administração & dosagem , Benzoatos/administração & dosagem , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Disfunção Erétil , Valor Preditivo dos Testes , Ramipril/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II , Inibidores da Enzima Conversora de Angiotensina , Método Duplo-Cego , Quimioterapia Combinada , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Humanos , Masculino , Mortalidade , Telmisartan , Resultado do Tratamento
13.
Expert Opin Pharmacother ; 10(18): 3113-7, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19925045

RESUMO

The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) was a 25,620 patient study program comparing telmisartan with ramipril or the combination thereof in patients at increased cardiovascular risk. Ramipril had previously been proven to prevent cardiovascular events in a similar population within the HOPE-trial. However, ramipril and other ACE inhibitors (ACE-Is) may have limited tolerability that might restrict their use in patients requiring secondary prevention, whereas angiotensin receptor blockers (ARBs) are suggested to be better tolerated. However, no ARB had been compared with the standard treatment, ramipril, in these cardiovascular patients at increased risk. ONTARGET showed that telmisartan was as effective as ramipril in preventing cardiovascular events, but was better tolerated. The combination of ramipril and telmisartan was not superior to either monotherapy. Taken together, ONTARGET demonstrated that telmisartan is as effective as ramipril in a broad cardiovascular increased-risk population in the middle of the cardiovascular continuum. In these patients who are intolerant to ACE-Is or who do not achieve blood pressure control, the ARB with the best evidence for secondary prevention is telmisartan according to the results of the ONTARGET trial.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Benzimidazóis/uso terapêutico , Benzoatos/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Benzimidazóis/efeitos adversos , Benzoatos/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Doenças Cardiovasculares/prevenção & controle , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ramipril/efeitos adversos , Ramipril/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Telmisartan , Resultado do Tratamento
14.
Clin Res Cardiol ; 98(6): 345-52, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19430713

RESUMO

The article summarizes the results of clinical trials in the field of cardiovascular medicine, which were presented during the Hotline Sessions at the annual meeting of the American College of Cardiology in Orlando, USA, from 28th March to 31st March 2009. The data were presented by leading experts in the field with relevant positions within the trials. Unpublished reports should be considered as preliminary data as the analysis may change in the final publications. The summaries presented in the manuscript were generated from the oral presentations and provide the readers with the comprehensive information on the results of the latest clinical trials in cardiovascular medicine.


Assuntos
Pesquisa Biomédica/tendências , Cardiologia/tendências , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/terapia , Ensaios Clínicos como Assunto , Humanos , Estados Unidos
15.
Med Klin (Munich) ; 104(4): 309-13, 2009 Apr 15.
Artigo em Alemão | MEDLINE | ID: mdl-19399390

RESUMO

Prevalence of erectile dysfunction (ED) amounts to 20-30% in a general population and increases to 50-70% in cardiovascular high-risk patients. Association of ED with known cardiovascular risk factors is causal with endothelial function of penile vessels and corpora cavernosa playing a crucial role in physiology of erection. Moreover, severity of ED correlates with cardiovascular risk of patients and represents an early symptom of generalized atherosclerosis. Hence, cardiovascular risk factors and diseases are sooner diagnosed in patients with ED with the opportunity of risk-adjusted prevention. Furthermore, different trials suggest erectile function as a strong predictor of cardiovascular events like myocardial infarction or stroke.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Impotência Vasculogênica/fisiopatologia , Idoso , Animais , Aterosclerose/epidemiologia , Aterosclerose/fisiopatologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Infarto Cerebral/epidemiologia , Infarto Cerebral/fisiopatologia , Estudos Transversais , Modelos Animais de Doenças , Humanos , Impotência Vasculogênica/epidemiologia , Masculino , Programas de Rastreamento , Camundongos , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/fisiopatologia , Estresse Oxidativo/fisiologia , Prognóstico , Fatores de Risco , Estatística como Assunto
16.
Eur J Heart Fail ; 11(3): 299-303, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19158153

RESUMO

AIMS: Clinical outcomes of patients with chronic heart failure (CHF) have improved, but evidence-based treatment appears to be imbalanced depending on patients' and physicians' gender. We aimed to determine the interactions of gender with medical treatment of CHF. METHODS AND RESULTS: Consecutive patients with CHF (n = 1857) were evaluated regarding co-morbidities, New York Heart Association classification, current medical treatment, and dosage of angiotensin-converting enzyme-inhibitors (ACE-Is) and beta-blockers. Gender of patients and treating physicians was recorded. Baseline characteristics of patients and physicians were comparable for males and females. Female patients were less frequently treated with ACE-Is, angiotensin-receptor blockers, or beta-blockers. Achieved doses were lower in female compared with male patients. Guideline-recommended drug use and achieved target doses tended to be higher in patients treated by female physicians. There was no different treatment for male or female patients by female physicians, whereas male physicians used significantly less medication and lower doses in female patients. In multivariable analysis, female gender of physicians was an independent predictor of use of beta-blockers. CONCLUSION: Treatment of CHF is influenced by patients', but also physicians' gender with regard to evidenced-based drugs and their dosage. Physicians should be aware of this problem in order to avoid gender-related treatment imbalances.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Fidelidade a Diretrizes , Insuficiência Cardíaca/epidemiologia , Médicos/estatística & dados numéricos , Guias de Prática Clínica como Assunto/normas , Idoso , Estudos Transversais , Medicina Baseada em Evidências/métodos , Feminino , Seguimentos , Alemanha/epidemiologia , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Cooperação do Paciente , Estudos Retrospectivos , Fatores Sexuais , Resultado do Tratamento
17.
J Cardiovasc Med (Hagerstown) ; 9(11): 1095-7, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18852579

RESUMO

BACKGROUND: Noncompaction of left ventricular myocardium is a rare congenital cardiomyopathy resulting from an incomplete myocardial morphogenesis that leads to the persistence of the embryonic myocardium. This condition is characterized by a thin compacted epicardial and an extremely thickened endocardial layer with prominent trabeculations and deep intertrabecular recesses. It is not clear, in noncompaction of myocardium, whether intertrabecular recesses could be responsible for thrombi formation and thromboembolic complications. METHODS: The prevalence of stroke and echocardiographic finding of thrombus was evaluated in a continuous series of 229 patients (men and women) affected by noncompaction of the left ventricular myocardium, who were included in the SIEC registry. We excluded patients affected by atrial fibrillation. RESULTS: The mean age of the patients was 49.5 years. Fifty percent of the patients were affected by a ventricular systolic dysfunction. The mean period of follow-up was 7.3 years. Only four patients had a history of ischemic stroke. A large thrombus into the left ventricular chamber was observed in a 1-year-old child affected by Behcet's disease (high risk of thrombi formation). CONCLUSION: Noncompaction of the left ventricular myocardium, by itself, does not seem to be a risk factor for stroke or embolic results, so there is no indication for oral anticoagulant therapy.


Assuntos
Anticoagulantes/uso terapêutico , Cardiomiopatias/tratamento farmacológico , Cardiopatias Congênitas/tratamento farmacológico , Ventrículos do Coração/efeitos dos fármacos , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/prevenção & controle , Administração Oral , Adulto , Anticoagulantes/administração & dosagem , Cardiomiopatias/complicações , Cardiomiopatias/congênito , Feminino , Cardiopatias Congênitas/complicações , Ventrículos do Coração/anormalidades , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Tromboembolia/etiologia , Fatores de Tempo
18.
J Pharmacol Exp Ther ; 327(3): 692-8, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18812494

RESUMO

Angiotensin receptor blockers enhance endothelial function and are suggested to improve erectile function. The effects and underlying mechanisms of treatment with the angiotensin receptor blocker irbesartan on penile endothelial function in apolipoprotein E (ApoE)(-/-) mice were determined. Wild-type (C57/B6) and ApoE(-/-) mice were fed with a high-fat, cholesterol-rich diet for 7 weeks and treated with irbesartan (50 mg/kg . day) or hydralazine (250 mg/l). Vital parameters were measured with the tail-cuff method. Endothelial (aortic rings) and erectile function (corpora cavernosa) were assessed by pharmacological stimulation in an organ bath chamber. Oxidative stress and angiotensin receptor expression were determined. Blood pressure was significantly decreased in irbesartan- and hydralazine-treated ApoE(-/-) mice (p < 0.05) compared with controls and wild-type mice. Endothelial function of the aorta and corpus cavernosum was significantly impaired in ApoE(-/-) mice (p < 0.05) and could be restored by treatment with irbesartan (p < 0.05). Consistently, nitric oxide production of corpora cavernosa was impaired in ApoE(-/-) mice (p < 0.01), with a restoration in irbesartan- but not hydralazine-treated mice. Dihydroethidium-stained sections and lipid peroxidase assay revealed a reduction of superoxide production in irbesartan (p < 0.05) compared with hydralazine-treated and control ApoE(-/-) mice. In summary, irbesartan improves penile endothelial function in ApoE(-/-) mice by reduction of vascular and cavernosal oxidative stress. This result emphasizes the beneficial effect of inhibition of the renin-angiotensin system even in terms of erectile function.


Assuntos
Compostos de Bifenilo/farmacologia , Endotélio/efeitos dos fármacos , Ereção Peniana/efeitos dos fármacos , Pênis/efeitos dos fármacos , Tetrazóis/farmacologia , Animais , Aorta , Apolipoproteínas E/deficiência , Pressão Sanguínea , Endotélio/fisiologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Hidralazina/farmacologia , Irbesartana , Masculino , Camundongos , Camundongos Knockout , Óxido Nítrico , Estresse Oxidativo , Pênis/citologia , Receptores de Angiotensina , Sistema Renina-Angiotensina
19.
Clin Res Cardiol ; 97(7): 418-31, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18454336

RESUMO

Cardiovascular disease represents a continuum that starts with risk factors such as hypertension and progresses to atherosclerosis, target organ damage, and ultimately to myocardial infarction, heart failure, stroke or death. Renin-angiotensin system (RAS) blockade with angiotensin converting enzyme (ACE) inhibitors or angiotensin AT(1)-receptor blockers (ARBs) has turned out to be beneficial at all stages of this continuum. Both classes of agent can prevent or reverse endothelial dysfunction and atherosclerosis, thereby reducing the risk of cardiovascular events. Such a reduction has been shown mainly for ACE inhibitors in patients with coronary artery disease, but recent studies revealed that ARBs are not inferior in this respect. However, no such data are currently available on the combination of these drugs. Both ACE inhibitors and ARBs have been shown to reduce target organ damage in organs such as the kidney, brain and heart, and to decrease cardiovascular mortality and morbidity in patients with congestive heart failure. Experimental data point to an influence of ACE inhibitors and ARBs on the number and function of endothelial progenitor cells revealing additional mechanisms of action of these drugs. The VALIANT trial has shown equivalent effects of ARB valsartan and the ACE-inhibitor captopril in patients post myocardial infarction, but the dual RAS-blockade, compared to monotherapy, did not further reduce events. In secondary prevention, the most-recently published ONTARGET study provides evidence that on top of a better tolerability AT(1)-receptors antagonists are equal to ACE inhibitors in the prevention of clinical endpoints like cardiovascular mortality and morbidity, myocardial infarction and stroke. The combined RAS blockade, however, achieved no further benefits in vascular high-risk patients and was associated with more adverse events. In chronic heart failure, ValHeFT and CHARM-ADDED have shown that combined RAS inhibition with ACE inhibitor and valsartan or candesartan reduced morbidity and mortality in certain patient subgroups. Accumulating evidence also points to benefits of the combination therapy in individuals with proteinuric nephropathies. In conclusion, while combined RAS-inhibition is not generally indicated in patients along the cardio-reno-vascular continuum, it has already proven to be effective in heart failure patients with incomplete neuroendocrine blockade. In secondary prevention, monotherapy with either RAS inhibitor is equally efficacious. Furthermore, novel pharmacologic agents such as renin inhibitors may prove useful in preventing common side effects of RAS blockade such as angiotensin escape and AT(1)-receptor upregulation, giving clinicians additional therapeutic tools to optimally treat the individual patient.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Seleção de Pacientes , Sistema Renina-Angiotensina/efeitos dos fármacos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Endotélio/efeitos dos fármacos , Endotélio/fisiologia , Humanos , Rim/fisiologia , Metanálise como Assunto , Sistema Renina-Angiotensina/fisiologia , Fatores de Risco
20.
Circulation ; 117(18): 2377-87, 2008 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-18443241

RESUMO

BACKGROUND: Elevated heart rate is associated with increased cardiovascular morbidity. We hypothesized that selective heart rate reduction may influence endothelial function and atherogenesis and tested the effects of the I(f) current inhibitor ivabradine in apolipoprotein E-deficient mice. METHODS AND RESULTS: Male apolipoprotein E-deficient mice fed a high-cholesterol diet were treated with ivabradine (10 mg . kg(-1) . d(-1)) or vehicle for 6 weeks (n=10 per group). Ivabradine reduced heart rate by 13.4% (472+/-9 versus 545+/-11 bpm; P<0.01) but did not alter blood pressure or lipid levels. Endothelium-dependent relaxation of aortic rings was significantly improved in ivabradine-fed animals (P<0.01). Ivabradine decreased atherosclerotic plaque size in the aortic root by >40% and in the ascending aorta by >70% (P<0.05). Heart rate reduction by ivabradine had no effect on the number of endothelial progenitor cells and did not alter aortic endothelial nitric oxide synthase, phosphorylated Akt, vascular cell adhesion molecule-1, or intercellular adhesion molecule-1 expression but decreased monocyte chemotactic protein-1 mRNA and exerted potent antioxidative effects. Ivabradine reduced vascular NADPH oxidase activity to 48+/-6% and decreased markers of superoxide production and lipid peroxidation in the aortic wall (P<0.05). The in vivo effects of ivabradine were absent at a dose that did not lower heart rate, in aortic rings treated ex vivo, and in cultured vascular cells. In contrast to ivabradine, treatment with hydralazine (25 mg . kg(-1) . d(-1) for 6 weeks) reduced blood pressure (-15%) but increased heart rate (37%) and did not improve endothelial function, atherosclerosis, or oxidative stress. CONCLUSIONS: Selective heart rate reduction with ivabradine decreases markers of vascular oxidative stress, improves endothelial function, and reduces atherosclerotic plaque formation in apolipoprotein E-deficient mice.


Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/prevenção & controle , Benzazepinas/farmacologia , Endotélio Vascular/fisiologia , Frequência Cardíaca/fisiologia , Estresse Oxidativo/fisiologia , Animais , Apolipoproteínas E/sangue , Aterosclerose/sangue , Aterosclerose/fisiopatologia , Benzazepinas/uso terapêutico , Células Cultivadas , Colesterol na Dieta/efeitos adversos , Endotélio Vascular/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Ivabradina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Estresse Oxidativo/efeitos dos fármacos , Taquicardia/sangue , Taquicardia/tratamento farmacológico , Taquicardia/fisiopatologia
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