ramipril and Angina-Pectoris

Acute coronary syndrome (ACS) is a clinical syndrome caused by acute myocardial ischemia and a severe stage of coronary atherosclerosis heart disease. The aim of this study was to clarify whether ramipril was a therapeutic agent against monocyte chemoattractant protein 1 (MCP-1), interleukin 18 (IL-18), and interleukin 10 (IL-10) in elderly patients with ACS. A total of 190 subjects including 72 elderly patients with ACS (78.1% male, mean age 67.12 +/- 5.06 years), 60 elderly patients with stable angina pectoris (76.9% male, mean age 68.00 +/- 4.52 years), and 58 healthy volunteers (77.8% male, mean age 65.96 +/- 4.18 years) were recruited into the study. Serum MCP-1, IL-10, and IL-18 were determined in 132 elderly patients by enzyme-linked immunosorbent assay (ELISA) before and after treatment with low doses of ramipril (2.5-5 mg/day), and were determined in 58 healthy volunteers. The levels of serum MCP-1 and IL-18 were much higher in elderly patients with ACS than those in elderly patients with SAP and healthy volunteers. After treating with ramipril, the levels of MCP-1 and IL-18 were decreased in elderly patients with ACS. Moreover, ramipril significantly increased serum IL-10 in elderly patients with ACS. Ramipril plays an important role in elderly patients with ACS. With decreasing MCP-1 and IL-18, it can ameliorate cytokine-associated cardiac damage. This study may provide a new recognition of angiotensin-converting enzyme inhibitor for the treatment of ACS.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Biomarkers; Chemokine CCL2; China; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation Mediators; Interleukin-10; Interleukin-18; Male; Middle Aged; Ramipril; Treatment Outcome

To investigate the hypothesis that prior angina pectoris confers protection from remodeling occurring after myocardial infarction (MI), we analyzed echocardiograms from the Healing and Early Afterload Reducing Therapy (HEART) trial.. Ischemia occurring before MI has been shown to reduce infarct size in experimental models and to improve outcomes in patients. The extent to which ischemia occurring before MI influences subsequent changes in ventricular size and function is unclear.. We studied 283 patients enrolled in the HEART trial who had echocardiograms at days 1 and 90 after MI. Left ventricular (LV) dilation from days 1 to 90 was used as a measure of LV remodeling. We explored the relationship between symptomatic angina occurring before infarction and subsequent LV remodeling.. In patients who reported angina (n = 111) during the three months preceding MI, LV volume change was -0.73 +/- 2.6 ml over the 90-day post-MI period, compared with 6.8 +/- 2.6 ml for patients (n = 172) without angina (p = 0.017). In contrast, there were no differences in changes in ejection fraction based on prior angina. Maximal creatine kinase was significantly lower in patients with prior angina (2,119 +/- 1,729 vs. 2,701 +/- 2,088, p = 0.016). In a multivariate model, prior angina remained protective for ventricular remodeling after adjusting for age, gender, baseline ejection fraction, Killip class, baseline end-diastolic volume, and drug treatment group (p = 0.042). However, the protective effect of pre-infarction angina appeared to be attenuated in diabetic patients.. Ischemic symptoms occurring before MI may protect against LV remodeling. These protective effects may be secondary to recruitment of collaterals or ischemic preconditioning of the myocardium, and they appear to be attenuated in diabetic patients.

Topics: Aged; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Creatine Kinase; Diabetes Mellitus; Double-Blind Method; Echocardiography; Female; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Predictive Value of Tests; Prevalence; Ramipril; Stroke Volume; Ventricular Remodeling

Angiotensin (Ang) II is now recognized to be a mediator of a wide variety of inflammatory processes. This study investigated renin-angiotensin system (RAS) components and a number of inflammatory mediators in left ventricular biopsies from 2-vessel disease unstable angina (UA) (n=43) and stable angina (SA) (n=15) patients undergoing coronary bypass surgery. Biopsy samples from 6 patients undergoing valve replacement for mitral stenosis served as controls. UA patients were randomly assigned to angiotensin-converting enzyme (ACE)-inhibitor (ramipril), AT1 antagonist (valsartan), or placebo and treated during the 5 days preceding coronary bypass surgery, performed from 6 to 9 days after coronary angiography. During coronary angiography coronary blood flow was measured and samples were obtained from aorta and coronary sinus for determination of Ang I and Ang II gradients. The hearts of UA patients produced Ang II in a greater amount than in SA patients (P<0.01). UA biopsy samples showed numerous DR+ cells, identified as lymphocytes, macrophages, and endothelial cells. Reverse-transcriptase polymerase chain reaction showed overexpression of AGTN, ACE, and AT1-R genes, as well as upregulation of TNF-alpha, IL-6, IFN-gamma, and iNOS genes (P<0.01), with no differences between nonischemic and potentially ischemic areas. AGTN, ACE, and cytokine genes were mainly localized on endothelial cells. Ramipril and valsartan markedly decreased the expression levels of TNF-alpha, IL-6, and iNOS, and, to a lesser extent, of IFN-gamma genes, but did not affect the number of DR+ cells, with no significant difference between the 2 treatments. These results show that locally generated Ang II amplifies the immunomediated inflammatory process of coronary microvessels occurring in unstable angina.

Topics: Adult; Aged; Angina Pectoris; Angina, Unstable; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Chymases; Combined Modality Therapy; Coronary Angiography; Coronary Artery Bypass; Coronary Circulation; Cytokines; Female; Gene Expression Profiling; Humans; Male; Microcirculation; Middle Aged; Mitral Valve Stenosis; Myocardium; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Preoperative Care; Ramipril; Renin-Angiotensin System; RNA, Messenger; Serine Endopeptidases; Tetrazoles; Valine; Valsartan; Vasculitis

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 30+/-5% and 53+/-6%, respectively (P<0.001), and reduced plasma levels of malondialdehyde by 4+/-7% (P=0.026) and 25+/-4% (P<0.001), respectively. Monocyte chemoattractant protein-1 levels decreased by 3+/-3% and 12+/-2%, respectively (P=0.049 and P=0.001, respectively), C-reactive protein levels changed by 0% and 18%, respectively (P=0.036 and P<0.001, respectively), and plasminogen activator inhibitor-1 antigen levels changed by -7+/-7% and 17+/-5%, respectively (P=0.828 and P<0.001, 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 (P<0.001 and P=0.048 by ANOVA, respectively). Ramipril alone or simvastatin combined with ramipril significantly improved the percent flow-mediated dilator response to hyperemia (both P<0.001), however, simvastatin combined with ramipril showed significantly more improvement than ramipril alone (P<0.001 by ANOVA). Simvastatin combined with ramipril significantly improved endothelium-dependent vasodilation and fibrinolysis potential and reduced plasma levels of oxidant stress and inflammation markers in hypercholesterolemic patients.

Topics: Angina Pectoris; Biomarkers; C-Reactive Protein; Chemokine CCL2; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Diabetes Complications; Double-Blind Method; Drug Therapy, Combination; Endothelium, Vascular; Female; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Nitric Oxide; Plasminogen Activator Inhibitor 1; Ramipril; Simvastatin; Triglycerides; Vasodilation

The prevalence of angina after invasive revascularization is not negligible and impacts on quality of life. It has not been clarified whether potential anti-ischemic actions of angiotensin-converting enzyme inhibitors (1) may apply to non high-risk patients and (2) may reduce the prevalence of angina. We sought to test the hypothesis that ramipril, an angiotensin-converting enzyme inhibitor, may reduce the postrevascularization prevalence of angina pectoris and improve quality of life.. In the Angiotensin-converting enzyme Post-Revascularization Study (APRES), 159 patients who underwent invasive revascularization for chronic angina and who had not had heart failure, acute myocardial infarction (AMI), or severe left ventricular dysfunction were randomized to receive 10 mg of ramipril or placebo. During the 12- to 46-month follow-up, the Specific Activity Scale class, exercise tests, and SF-36 quality of life scores were serially assessed.. The average prevalence of angina of Specific Activity Scale class II or worse was 26.6% in the ramipril group and 19.9% in the placebo group (p=0.16). The average prevalence of exercise-inducible ischemia was 30.8% in the ramipril group and 25.2% in the placebo group (p=0.39). There were no significant differences between the two treatment groups in the SF-36 quality of life scores or in the Duke treadmill score. Post-hoc power calculations revealed that the power to rule out a clinical significant benefit of ramipril on the prevalence of angina, quality of life, and Duke treadmill score was >90%.. These data do not suggest that ramipril reduces the prevalence of angina pectoris or improves quality of life after invasive revascularization in such patients

Topics: Analysis of Variance; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Denmark; Exercise; Female; Humans; Male; Middle Aged; Myocardial Revascularization; Postoperative Complications; Prevalence; Quality of Life; Ramipril

We hypothesized that the benefit from ramipril on cardiac events and on left ventricular end-systolic volume (ESVI) in the Angiotensin-converting enzyme inhibition Post-revascularization Study (APRES) randomized controlled trial (RCT) was associated with long-term improvement.. For the 3.2 years after the end of the RCT, we obtained information from a national database regarding date and cause of death and hospitalization for the 159 enrolled patients.. Assignment to ramipril in the RCT resulted in a lower rate of cardiac death or hospitalization with heart failure up to the time of complete follow-up of all patients at 4.3 years (relative risk [RR], 0.28; P =.018) and up to 1.5 years after the end of the RCT (RR, 0.35; P =.042) but not up to the complete extended follow-up time at 6.9 years (RR, 0.65; P =.27). Independent predictors for risk of future cardiac death or hospitalization with heart failure were (a) left ventricular dilation (LVD) (RR, 2.84; P =.031), defined as an increase in ESVI greater than the reproducibility coefficient, and (b) composite event of acute myocardial infarction or development of heart failure or LVD (RR, 12.44; P <.001). Ramipril significantly reduced events (a) (P =.046) and (b) (P =.015) during the RCT.. There is congruence between the beneficial effect of ramipril on LVD, acute myocardial infarction, or heart failure and the prognostic importance of these factors and on cardiac death and hospitalization with heart failure. This observation supports and reinforces conclusions from previous APRES reports that ramipril benefits non-high-risk patients after revascularization.

Topics: Analysis of Variance; Angina Pectoris; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Bypass; Follow-Up Studies; Heart Diseases; Heart Failure; Hospitalization; Humans; Myocardial Infarction; Proportional Hazards Models; Ramipril; Risk; Ventricular Dysfunction, Left

OBJECTIVES We sought to assess the effect of ramipril on left ventricular (LV) volumes, and the clinical significance thereof, in patients with moderate LV dysfunction and no clinical heart failure undergoing invasive revascularization for chronic stable angina.. It is unsettled whether treatment with an angiotensin-converting enzyme inhibitor has an impact on LV volumes in this patient group, and, if so, whether this is associated with the clinical outcome.. A total of 133 patients with a left ventricular ejection fraction (LVEF) between 0.30 and 0.50 and no clinical heart failure undergoing invasive revascularization for chronic stable angina were randomized to receive ramipril 10 mg once daily or placebo and were followed for a median of 33 months with echocardiography at baseline and 3, 12 and 24 months postoperatively.. Repeated measures analysis of all time points showed that ramipril significantly reduced the end-diastolic volume index (EDVI) (p = 0.032) and end-systolic volume index (ESVI) (p = 0.006) as compared with placebo. Ramipril also reduced the incidence of the triple composite end point of cardiac death, acute myocardial infarction or development of heart failure (p = 0.046). Cox regression analysis, controlling for baseline LVEF and assignment to ramipril, revealed: 1) that increases in EDVI and ESVI up to three months predicted an increasing risk of a future adverse clinical outcome; and 2) that the benefit with ramipril on clinical outcome was partly dependent on a reduction in LV volumes.. Even in this patient group, LV dilation may supervene and lead to an adverse clinical outcome. Ramipril reduces the postoperative increase in LV volumes and may thereby improve clinical outcome.

Topics: Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Coronary Artery Bypass; Diastole; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Postoperative Complications; Ramipril; Stroke Volume; Survival Rate; Systole; Ventricular Dysfunction, Left

This study was performed to assess the effect of treatment with ramipril on the incidence of cardiac events after invasive revascularization in patients with asymptomatic moderate left ventricular dysfunction.. In patients with angina pectoris and left ventricular dysfunction, both invasive revascularization and treatment with angiotensin-converting enzyme inhibitors reduce cardiac mortality and morbidity. Whether there is a benefit from combining the two treatment strategies has never been evaluated prospectively.. After invasive revascularization, 159 patients with preoperative chronic stable angina pectoris, left ventricular ejection fraction between 0.30 and 0.50 and no clinical heart failure were randomly assigned to receive double-blind treatment with either ramipril or placebo and subsequently followed for a median of 33 months.. Ramipril reduced the incidence of the triple-composite end point of cardiac death, acute myocardial infarction or clinical heart failure (risk reduction 58%; 95% confidence interval 7% to 80%, p = 0.031). The incidence of the quadruple-composite end point of cardiac death, acute myocardial infarction, clinical heart failure or recurrent angina pectoris was not altered with ramipril. These findings were consistent across subgroups with respect to left ventricular ejection fraction below or above 0.40, and whether coronary artery bypass grafting or percutaneous transluminal coronary angioplasty was performed.. In patients with angina pectoris and asymptomatic moderate left ventricular dysfunction, long-term treatment with ramipril after invasive revascularization significantly reduced the incidence of the composite end point of cardiac death, acute myocardial infarction or clinical heart failure, indicating that the beneficial effects of angiotensin-converting enzyme inhibitor treatment may be extended to include treatment of this patient group.

Topics: Adult; Aged; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Double-Blind Method; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Ramipril; Stroke Volume; Survival Rate; Treatment Outcome; Ventricular Dysfunction, Left

Invasive revascularization improves prognosis, functional status and quality of life in patients with severe angina pectoris and impaired left ventricular function, and treatment with ACE-I reduces the development of cardiac events and left ventricular dysfunction in patients without or with mild angina pectoris. However, the effects of a combined treatment strategy with invasive revascularization and subsequent long-term ACE-I therapy in patients with limiting angina pectoris and impaired left ventricular function have not previously been investigated. APRES is a long-term, prospective, randomized double-blind study that evaluates the effects of ramipril 10 mg o.d. on the long-term development of cardiac events, left ventricular function, functional status and quality of life following invasive revascularization in patients without recent AMI or clinical heart failure and with preoperative ejection fraction in the range 0.30-0.50. The rationale, design and power of APRES and the choice and relevance of outcome measures are discussed. Based on experience and results from the first year of the study for screening procedure, inclusion rate, patient compliance, reproducibility analyses and the magnitude of outcome measures, we conclude that the study is feasible and safe. The included patients match with the target population, the outcome measures seem appropriate and the power considerations valid for the majority of the outcome measures.

Topics: Adolescent; Adult; Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Bypass; Double-Blind Method; Exercise Test; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Revascularization; Postoperative Complications; Postoperative Period; Prognosis; Prospective Studies; Quality of Life; Ramipril; Survival Rate; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Coronary Disease; Humans; Ischemic Preconditioning, Myocardial; Myocardial Infarction; Ramipril; Stroke Volume; Ventricular Remodeling

Topics: Acute Disease; Angina Pectoris; Angina, Unstable; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Electrocardiography; Humans; Male; Middle Aged; Models, Cardiovascular; Myocardium; Ramipril; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Tetrazoles; Valine; Valsartan

Topics: Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Clinical Trials as Topic; Coronary Disease; Drug Therapy, Combination; Humans; Perindopril; Ramipril; Survival Rate