Treatment benefit by perindopril in patients with stable coronary artery disease at different levels of risk.

AIMS: Patients with stable coronary artery disease (CAD) are at increased risk. Estimation of individual risk is difficult. We developed a cardiovascular risk model based on the EUROPA study population and investigated whether benefit of long-term administration of the angiotensin-converting enzyme (ACE)-inhibitor perindopril was modified by risk level. METHODS AND RESULTS: A total of 12 218 patients with stable CAD were treated with 8 mg perindopril or placebo. Baseline patient characteristics were assessed for association with 1091 cardiovascular deaths or non-fatal myocardial infarction (MI). Risk factors were age over 65 years, male gender [hazard ratio (HR) 1.2], previous MI (HR 1.5), previous stroke and/or peripheral vascular disease (HR 1.7), diabetes, smoking, angina (all HR 1.5), and high serum cholesterol and systolic blood pressure. Treatment benefit by perindopril was consistent among high, intermediate, and low risk patients (HRs 0.88, 0.68, and 0.83, respectively). Risk reduction was thus not modified by absolute risk level. CONCLUSION: Risk factors such as age, male gender, smoking, total cholesterol, and blood pressure continue to play an important role once clinical sequellae of coronary heart disease have developed. Patients at moderate-to-high risk because of uncontrolled risk factors and those with other indications for ACE-inhibitors have the most to gain from ACE-inhibition.     

Evaluation of the effects of aspirin combined with angiotensin-converting enzyme inhibitors in patients with coronary artery disease

BACKGROUND: Several studies have suggested that there may be an interaction between angiotensin-converting enzyme (ACE) inhibitors and aspirin in patients with congestive heart failure, such that their benefits are attenuated when used in combination. Whether this interaction exists in patients with coronary artery disease is not known. SUBJECTS AND METHODS: Patients enrolled in two large trials, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) and Evaluation in PTCA to Improve Long-Term Outcome with Abciximab GP IIb/IIIa Blockade (EPILOG), were stratified according to use of aspirin and ACE inhibitors on discharge from the hospital. In the EPILOG trial, left ventricular systolic function was assessed by contrast ventriculography. The primary endpoint was all-cause mortality at 1 year. EPILOG patients, all of whom were receiving aspirin, were also examined for the combined endpoint of death or nonfatal myocardial infarction. Stratified and multivariate analyses were used to adjust for baseline differences in patient characteristics. RESULTS: We studied 31,622 patients in the GUSTO-I trial and 2,619 patients in the EPILOG trial. There were 615 deaths among the GUSTO-I patients and 45 deaths among the EPILOG patients at 1 year. Unadjusted mortality was greater among patients treated with both ACE inhibitors and aspirin than among patients treated with aspirin alone (3.3% versus 1.6%, P <0.001 for GUSTO-I; and 3.7% versus 1.2%, P <0.001 for EPILOG). Similarly, the composite endpoint of death or nonfatal myocardial infarction was more frequent among EPILOG patients who were taking ACE inhibitors (6.3% versus 3.3%, P = 0. 001). After adjusting for confounders, combined use of aspirin and ACE inhibitors was associated with increased mortality in GUSTO-I patients (hazard ratio [HR] = 2.2, 95% confidence interval [CI]: 1.1 to 4.3, P = 0.03) compared with aspirin alone. In EPILOG patients, after adjusting for clinical factors and extent of left ventricular dysfunction, the combination of aspirin and ACE inhibitors was associated with an increased risk of death (HR = 2.1, 95% CI: 1.1 to 3.8, P = 0.02) and of death or nonfatal myocardial infarction (HR = 1.5, 95% CI: 1.1 to 2.5, P = 0.02) compared with aspirin alone. CONCLUSION: These observational findings suggest the possibility of an interaction between aspirin and ACE inhibitors among patients with ischemic heart disease. Further study of this issue is warranted.     

Five year clinical effect of coronary stenting and coronary artery bypass grafting in renal insufficient patients with multivessel coronary artery disease: insights from ARTS trial.

AIMS: To compare coronary stent implantation and bypass surgery for multivessel coronary disease in patients with renal insufficiency. METHODS AND RESULTS: In the ARTS trial, 142 moderate renal insufficient patients (Ccr<60 mL/min) with multivessel coronary disease were randomly assigned to stent implantation (n=69) or CABG (n=73). At 5 years, there was no significant difference between the two groups in terms of mortality (14.5% in the stent group vs. 12.3% in the CABG group, P=0.81), or combined endpoint of death, cerebrovascular accident (CVA), or myocardial infarction (MI) (30.4% in the stent group vs. 23.3% in the CABG group, P=0.35). Among patients who survived without CVA or MI, 18.8% in the stent group underwent a second revascularization procedure when compared with 8.2% in the surgery group (P=0.08). The event-free survival at 5 years was 50.7% in the stent group and 68.5% in the surgery group (P=0.04). CONCLUSION: At 5 years, the differences in mortality and combined incidence of death, CVA, and MI between coronary stenting and surgery did not reach statistically significant level. However, the occurrence of MACCE in the stent group was higher than in the CABG group, mainly driven by the higher incidence of repeat revascularization in the stent group.     

Angiotensin-converting enzyme inhibitor promotes coronary collateral circulation in patients with coronary artery disease.

Previous studies have suggested that angiotensin-converting enzyme inhibitors (ACEI) promote collateral circulation in ischemic limbs of rabbits. The present study was designed to determine the association between treatment with ACEI and the development of coronary collateral circulation, as assessed by the Rentrop Score, in patients with coronary artery disease (CAD) in a case - control study. Subjects included 456 patients with angina who underwent coronary angiography. Those who had one (1-V), two (2-V) or three (3-V) significantly stenosed vessels, and who received only ACEI without any other anti-hypertensive medication were defined as cases (n=33), and age, sex and body mass index-matched subjects (n=56) were selected as controls. Among 1-V patients, but not 2-V or 3-V patients, the cases included a higher percentage of patients with Rentrop Score of at least 1 than the controls, suggesting that ACEI was associated with coronary collateral circulation. Patients with 1-V disease who were treated with ACEI were most likely [odds ratio (confidence interval): 6.1 (1.4-30.1)] to develop collateral circulation, as assessed by a multiple logistic regression analysis. Therefore, treatment with ACEI was associated with the development of collateral circulation in patients with CAD, suggesting that such an action is associated with bradykinin production by ACEI.     

Circadian activity of the endogenous fibrinolytic system in stable coronary artery disease: effects of beta-adrenoreceptor blockers and angiotensin-converting enzyme inhibitors

Objectives. To examine circadian changes in the sympathovagal balance, the activity of the renin-angiotensin system and hemostatic variables in patients with stable coronary artery disease, and the effects of beta-adrenoceptor blockade and angiotensin-converting enzyme inhibition.

Background. Sympathovagal balance and key components of the fibrinolytic system show circadian variability. The effects of beta-adrenergic blocking agents and angiotensin-converting enzyme inhibitors on these autonomic and hemostatic rhythms are not well defined.

Methods. Twenty patients with coronary artery disease underwent 24-h Holter monitoring for heart rate variability and blood sampling (6 hourly for 24 hours) after three consecutive treatment phases, (firstly with placebo, then bisoprolol, and finally quinapril). The effects on sympathovagal balance, hemostatic variables and the renin-angiotensin system activity were measured.

Results. The fibrinolytic capacity showed marked circadian variation at the end of the placebo phase (p = 0.002), plasminogen activator inhibitor-1 (PAI-1) activity peaking at 06.00 am when tissue plasminogen activator (tPA) activity was at its nadir. Sympathovagal balance showed a sharp increase at approximately the same time but plasma renin activity did not rise until later in the day. Inspection of the 24-h profiles suggested that bisoprolol reduced sympathovagal balance and the morning peak of PAI-1 activity and antigen, with a small increase in tPA activity, although these changes were not significant. Quinapril produced a substantial rise in renin (p = 0.01) but did not significantly affect either PAI-1 or tPA. Sympathovagal balance was unaffected by quinapril.

Conclusions. In patients with stable coronary artery disease, angiotensin-converting enzyme inhibition with quinapril does not affect either sympathovagal balance or the endogenous fibrinolytic system. Our data suggest that the sympathoadrenal system may modify fibrinolytic activity, judged by the response to beta-adrenoreceptor blockade with bisoprolol.     

Adverse prognosis associated with the metabolic syndrome in established coronary artery disease: data from the EUROPA trial

Objective

To assess the prevalence of metabolic syndrome, and its effect on cardiovascular morbidity and mortality in patients with established coronary disease and to explore the inter‐relationships between metabolic syndrome, diabetes, obesity and cardiovascular risk.

Methods

The presence of metabolic syndrome was determined in 8397 patients with stable coronary disease from the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease, with mean follow‐up of 4.2 years. Metabolic syndrome was defined using a modified version of the National Cholesterol Education Programme criteria.

Results

Metabolic syndrome was present in 1964/8397 (23.4%) of the population and significantly predicted outcome; relative risk (RR) of cardiovascular mortality  =  1.82 (95% CI 1.40 to 2.39); and fatal and non‐fatal myocardial infarction RR = 1.50 (95% CI 1.24 to 1.80). The association with adverse outcomes remained significant after adjustment, RR of cardiovascular mortality after adjustment for conventional risks and diabetes  =  1.39 (95% CI 1.03 to 1.86). In comparison with normal weight subjects without diabetes or metabolic syndrome, normal weight dysmetabolic subjects (with either diabetes or metabolic syndrome) were at substantially increased risk of cardiovascular death (RR = 4.05 (95% CI 2.38 to 6.89)). The relative risks of cardiovascular death for overweight and obese patients with dysmetabolic status were nominally lower (RR = 3.01 (95% CI 1.94 to 4.69) and RR = 2.35 (95% CI 1.50 to 3.68), respectively).

Conclusions

Metabolic syndrome is associated with adverse cardiovascular outcome, independently of its associations with diabetes and obesity. A metabolic profile should form part of the risk assessment in all patients with coronary disease, not just those who are obese.     

透析在慢性肾功能不全冠心病患者介入治疗中的作用

目的 探讨透析在合并慢性肾功能不全的冠心病患者行介入治疗时的有效性和安全性.方法 选择合并慢性肾功能不全的冠心病患者,PCI术前给予水化和碱化：连续口服碳酸氢钠片1g,3次/d×3d,术前3～12h内静脉缓慢输入氯化钠1000～1500ml,3～10ml/（ kg·h）.PCI术后留置动脉穿刺鞘管,立即进行4h的透析治疗保护肾功能,观察手术前后肾功能的变化.结果 所有患者均成功进行了冠状动脉介入治疗,术后1个月内无明显手术并发症,未出现支架内血栓.58例患者中有56例血浆肌酐水平与术前比较无明显变化,1例患者血浆肌酐升高,1例患者术后需要永久性透析.结论 合并肾功能不全的冠心病患者并非是介入治疗的禁忌症.透析可以有效的预防造影剂相关性肾病的发生,安全地进行介入治疗.     

Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease

Several beneficial effects of resveratrol (RES), a natural antioxidant present in red wine have already been described. The aim of our study was to investigate if RES had a clinically measurable cardioprotective effect in patients after myocardial infarction. In this double-blind, placebo controlled trial 40 post-infarction Caucasian patients were randomized into two groups. One group received 10 mg RES capsule daily for 3 months. Systolic and diastolic left ventricular function, flow-mediated vasodilation (FMD), several laboratory and hemorheological parameters were measured before and after the treatment. Left ventricular ejection fraction showed an increasing tendency (ns) by RES treatment. However, left ventricular diastolic function was improved significantly (p < 0.01) by RES. A significant improvement in endothelial function measured by FMD was also observed (p < 0.05). Low-density lipoprotein (LDL) level significantly decreased (p < 0.05) in the RES treated group. Red blood cell deformability decreased and platelet aggregation increased significantly in the placebo group (p < 0.05), while resveratrol treatment has prevented these unfavourable changes. Concerning other measured parameters no significant changes were observed neither in placebo nor in RES group. Our results show that resveratrol improved left ventricle diastolic function, endothelial function, lowered LDL-cholesterol level and protected against unfavourable hemorheological changes measured in patients with coronary artery disease (CAD).     

肾素-血管紧张素系统基因多态性对血管紧张素转换酶抑制剂治疗慢性肾功能不全疗效的影响

目的 :探讨血管紧张素原 (AGT)及血管紧张素转换酶 (ACE)基因多态性对血管紧张素转换酶抑制剂(ACEI)延缓慢性肾功能不全进展疗效的影响。　 方法 :利用苯那普利前瞻性治疗 42例慢性肾功能不全早期的IgA肾病或局灶节段硬化性肾炎 ,治疗时间 12个月。利用PCR方法测定患者ACE、AGT基因型 ,并据此分组 ,比较苯那普利治疗后不同基因型组肌酐清除率 (Ccr)及尿蛋白定量下降程度的差异。　 结果 :苯那普利治疗 12个月后 ,ACE基因DD、DI型组Ccr下降速度较II型组略快 ,分别为 0 2 2 4、0 172及 0 113ml·min-1·month-1,但无显著性差异 (P >0 0 5 ) ,DD、DI型组尿蛋白下降幅度显著高于II型组 (48 93%、32 5 6 %vs 9 0 9%,P <0 0 5 ) ;AGT基因TT、MT型组Ccr下降速度较MM型组快 (0 179、0 16 4vs 0 0 96ml·min-1·month-1,P >0 0 5 ) ,TT、MT型组尿蛋白降幅显著高于MM型组 (2 1 97%、37 78%vs 2 74%,P <0 0 5 )。　 结论 :苯那普利治疗慢性肾功能不全早期的原发性肾炎 ,含ACE基因D等位基因及AGT基因T等位基因的患者Ccr下降速度较其他基因型略快。尚需进行前瞻性对照研究以探讨ACE、AGT基因多态性对ACEI延缓慢性肾功能不全疗效的确切影响。苯那普利降低尿蛋白的疗效明显受基因多态性影响。     

Anti-ischemic effect of angiotensin-converting enzyme inhibitor, but not vitamin C, in patients with coronary artery disease treated with beta-blockers and nitrates. Randomized, cross-over, double-blind comparison

Anti-ischemic effect of angiotensin-converting enzyme inhibitor--chinapril was examined by exercise tolerance test [ETT] in randomised, cross-over double blind comparison in 20 pts with coronary artery disease treated with beta-blockers and nitrates. After 8 weeks of chinapril treatment maximal work capacity and exercise duration were significantly greater in comparison with baseline values, respectively: 7,8 vs 6,7 METs (p < 0,05) and 416 vs 335 s (p < 0,05). Time to ST segment depression was significantly longer after chinapril treatment: 394 vs 298 s (placebo) p = 0,01) vs 277 s (baseline), p = 0,008. The number of patients with exercise ST depression was significantly lower (63% vs 100%). Rate pressure product wasn't changed after chinapril treatment. Vitamin C therapy did not have influence on ischemia signs in exercise tolerance test.     

Effects of aliskiren on the fibrinolytic system in patients with coronary artery disease receiving angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker

Aliskiren is a novel blood pressure-lowering agent acting as an oral direct renin inhibitor. We evaluated the effects of aliskiren on the fibrinolytic system in patients with coronary artery disease who were receiving angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs). We studied 17 patients with coronary artery disease whose systolic blood pressure was more than 130 mmHg despite treatment with ACEIs or ARBs. Aliskiren (150 mg) was added to ACEIs or ARBs, and was continued for 6 weeks. Aliskiren significantly decreased systolic blood pressure (140 ± 6–128 ± 8 mmHg, P < 0.001) and plasma renin activity (1.8 ± 2.3–0.6 ± 0.9 ng/ml/h, P < 0.01) after 6 weeks. However, it did not affect plasminogen activator inhibitor-1 (28.8 ± 14.5–30.6 ± 13.6 ng/ml, P = 0.84), fibrinogen (305 ± 72 vs 301 ± 71 mg/dl, P = 0.33), or D-dimer (0.49 ± 0.24–0.51 ± 0.28 μg/ml, P = 0.70) levels. Our data suggested that patients receiving ACEIs or ARBs would not be expected to have any changes in biomarkers of the fibrinolytic system with additional pharmacologic inhibition of the renin–angiotensin–aldosterone system.     

Olmesartan reduces inflammatory biomarkers in patients with stable coronary artery disease undergoing percutaneous coronary intervention: results from the OLIVUS trial

The OLmesartan on the progression of coronary atherosclerosis: evaluation by IntraVascular UltraSound (OLIVUS) trial demonstrated that an angiotensin II receptor blocker, olmesartan, reduces the rate of coronary atheroma progression as evaluated by intravascular ultrasound in patients with stable angina pectoris undergoing percutaneous coronary intervention. This substudy examined the impact of olmesartan on serum biomarkers and the relationship between biomarker changes and atheroma progression. Patients in the OLIVUS trial (n = 247) were randomly assigned to a control group or the olmesartan group. A subgroup of these patients (n = 135, 55 %) was analyzed at baseline and at 14 months. Patients’ characteristics and blood-pressure control were identical between the control group (n = 65) and the olmesartan group (n = 70), and also between the subpopulation and total population. The change in the level of high-sensitivity C-reactive protein (hs-CRP) (mg/l) and adiponectin (μg/ml) was significantly greater in the olmesartan group than in the control group (between-group differences: 0.5 and ?0.7; 95 % confidence interval: 0.2–0.8 and ?1.3 to ?0.1; P = 0.001 and 0.02, respectively). Multiple regression analysis revealed that the nominal changes in total atheroma volume and percent atheroma volume were significantly associated with the nominal change in hs-CRP in the olmesartan group but not in the control group. Olmesartan reduced hs-CRP in patients with stable angina, and this correlated with the change in coronary atheroma.