血管紧张素转换酶抑制剂对无左心室功能不全的冠心病患者预后的影响

目的采用meta分析评价长期应用血管紧张素转换酶抑制剂(ACEI)是否减少无左心室功能不全的冠心病患者主要心血管事件的发生风险。方法检索MEDLINE、EMBASE数据库、IPA数据库、Cochrane图书馆。检索词:angiotensin-converting enzyme inhibitors,coronary artery disease,coronary heart disease randomi(s)zed controlled trials,clinical trials,myocardial infarction。入选试验满足条件:试验为随机对照试验,研究对象为无左心室功能不全的冠心病患者,随访时间不少于2年。在检索到的文章中共有7个试验(HOPE、PART-2、QUIET、EOROPA、PEACE、CAMELOT、IMAGINE)满足条件,总计36 053例患者。采用比值比OR和95%置信区间(CI)作为评价ACEI和安慰剂治疗差异有无统计学意义的指标。应用RevMan5.0软件行统计学分析。结果采用ACEI治疗可明显减少总病死率(OR=0.86,95%CI为0.80～0.94)、心血管病死率(OR=0.82,95%CI为0.74～0.91)、非致死性心肌梗死的发生率(OR=0.85,95%CI为0.76～0.95)及脑卒中或短暂性脑缺血发作的发生率(OR=0.78,95%CI为0.67～0.91),其他事件如心脏停搏后复苏、血管成形术、心力衰竭入院等发生率也减少。结论 ACEI可明显降低无左心室功能不全的冠心病患者的总病死率和心血管事件发生率。     

Comparison between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the risk of myocardial infarction, stroke and death: a meta-analysis

OBJECTIVES: To compare the effects of angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors on the risk of myocardial infarction, stroke, cardiovascular mortality and total mortality. METHODS: We conducted a meta-analysis of randomized comparative trials between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors. Inclusion criteria were publication in peer-reviewed journals indexed in Medline, randomized comparison of angiotensin II receptor blockers vs. angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers + angiotensin-converting enzyme inhibitors vs. angiotensin-converting enzyme inhibitors, report of major complications including myocardial infarction, stroke, cardiovascular mortality or all-cause mortality; average follow-up of at least 1 year in at least 200 patients. RESULTS: Six trials fulfilled the inclusion criteria, for a total of 49 924 patients. In the pooled estimate, there were no significant differences between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors on the risk of myocardial infarction (odds ratio 1.01; 95% confidence interval 0.95-1.07; P = 0.75), cardiovascular mortality (odds ratio 1.03; 95% confidence interval 0.98-1.08; P = 0.23) and total mortality (odds ratio 1.03; 95% confidence interval 0.97-1.10; P = 0.20). This was the case also when the analysis involved only the comparison between angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Overall, the risk of stroke was slightly lower with angiotensin II receptor blockers than angiotensin-converting enzyme inhibitors (odds ratio 0.92; 95% confidence interval 0.85-0.99; P = 0.037), the direct angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers comparison showing a nonsignificant trend in a similar direction. Statistical heterogeneity among trials was not significant, with a low to null inconsistency statistic, for stroke (P = 0.67), myocardial infarction (P = 0.86), cardiovascular mortality (P = 0.14) and total mortality (P = 0.12). CONCLUSION: This overview suggests that angiotensin II receptor blockers are as effective as angiotensin-converting enzyme inhibitors on the risk of myocardial infarction, cardiovascular mortality and total mortality. Angiotensin II receptor blockers may be slightly more protective than angiotensin-converting enzyme inhibitors on the risk of stroke.     

Outcomes of preoperative Angiotensin-converting enzyme inhibitor therapy in patients undergoing isolated coronary artery bypass grafting

The association between preoperative use of angiotensin-converting enzyme (ACE) inhibitors and outcomes after coronary artery bypass grafting (CABG) remain controversial. Our aim was to study in-hospital outcomes after isolated CABG in patients on preoperative ACE inhibitors. A retrospective analysis of 8,889 patients who underwent isolated CABG from 2000 through 2011 was conducted. The primary outcome of interest was the incidence of major adverse events (MAEs) defined as a composite of mortality, postoperative renal dysfunction, myocardial infarction, stroke, and atrial fibrillation during index hospitalization. The secondary outcome was the incidence of individual outcomes included in MAEs. Logistic regression analyses were performed. Of 8,889 patients, 3,983 (45%) were on preoperative ACE inhibitors and 4,906 (55%) were not. Overall incidence of MAEs was 38.1% (n = 1,518) in the ACE inhibitor group compared to 33.6% (n = 1,649) in the no-ACE inhibitor group. Preoperative use of ACE inhibitors was independently associated with MAEs (odds ratio 1.13, 95% confidence interval 1.03 to 1.24), most of which was driven by a statistically significant increase in postoperative renal dysfunction (odds ratio 1.18, 95% confidence interval 1.03 to 1.36) and atrial fibrillation (odds ratio 1.15, 95% confidence interval 1.05 to 1.27). In-hospital mortality, postoperative myocardial infarction, and stroke were not significantly associated with preoperative ACE inhibitor use. Analyses performed after excluding patients with low ejection fractions yielded similar results. In conclusion, preoperative ACE inhibitor use was associated with an increased risk of MAEs after CABG, in particular postoperative renal dysfunction and atrial fibrillation.     

Tissue angiotensin-converting enzyme inhibitors for the prevention of cardiovascular disease in patients with diabetes mellitus without left ventricular systolic dysfunction or clinical evidence of heart failure: a pooled meta-analysis of randomized placebo-controlled clinical trials

Aim:  The aim of this study was to determine the role of tissue angiotensin-converting enzyme (ACE) inhibitors in the prevention of cardiovascular disease in patients with diabetes mellitus without left ventricular systolic dysfunction or clinical evidence of heart failure in randomized placebo-controlled clinical trials using pooled meta-analysis techniques.
Methods:  Randomized placebo-controlled clinical trials of at least 12 months duration in patients with diabetes mellitus without left ventricular systolic dysfunction or heart failure who had experienced a prior cardiovascular event or were at high cardiovascular risk were selected. A total of 10 328 patients (43 517 patient-years) from four selected trials were used for meta-analysis. Relative risk estimations were made using data pooled from the selected trials and statistical significance was determined using the Chi-squared test (two-sided alpha error <0.05). The number of patients needed to treat was also calculated.
Results:  Tissue ACE inhibitors significantly reduced the risk of cardiovascular mortality by 14.9% (p = 0.022), myocardial infarction by 20.8% (p = 0.002) and the need for invasive coronary revascularization by 14% (p = 0.015) when compared to placebo. The risk of all-cause mortality also tended to be lower among patients randomized to tissue ACE inhibitors, whereas the risks of stroke and hospitalization for heart failure were not significantly affected. Treating about 65 patients with tissue ACE inhibitors for about 4.2 years would prevent one myocardial infarction, whereas treating about 85 patients would prevent one cardiovascular death.
Conclusion:  Pooled meta-analysis of randomized placebo-controlled trials suggests that tissue ACE inhibitors modestly reduce the risk of myocardial infarction and cardiovascular death and tend to reduce overall mortality in diabetic patients without left ventricular systolic dysfunction or heart failure.     

Angiotensin-converting enzyme inhibitors in coronary artery disease and preserved left ventricular systolic function: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study sought to assess the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in patients with coronary heart disease and preserved left ventricular (LV) function. BACKGROUND: The ACEIs have been shown to improve outcomes in patients with heart failure and myocardial infarction (MI). However, there is conflicting evidence concerning the benefits of ACEIs in patients with coronary artery disease (CAD) and preserved LV systolic function. METHODS: An extensive search was performed to identify randomized, placebo-controlled trials of ACEI use in patients with CAD and preserved LV systolic function. Of 61 potentially relevant articles screened, 6 trials met the inclusion criteria. They were reviewed to determine cardiovascular mortality, nonfatal MI, all-cause mortality, and revascularization rates. We performed random-effect model meta-analyses and quantified between-studies heterogeneity with I(2). RESULTS: There were 16,772 patients randomized to ACEI and 16,728 patients randomized to placebo. Use of ACEIs was associated with a decrease in cardiovascular mortality (relative risk [RR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01), nonfatal MI (RR 0.84, 95% CI 0.75 to 0.94, p = 0.003), all-cause mortality (RR 0.87, 95% CI 0.81 to 0.94, p = 0.0003), and revascularization rates (RR 0.93, 95% CI 0.87 to 1.00, p = 0.04). There was no significant between-studies heterogeneity. Treatment of 100 patients for an average duration of 4.4 years prevents either of the adverse outcomes (one death, or one nonfatal myocardial infarction, or one cardiovascular death or one coronary revascularization procedure). CONCLUSIONS: The cumulative evidence provided by this meta-analysis shows a modest favorable effect of ACEIs on the outcome of patients with CAD and preserved LV systolic function.     

Effects of early and late administration of angiotensin-converting enzyme inhibitors on mortality after myocardial infarction

BACKGROUND: Clinical trials demonstrating that angiotensin-converting enzyme (ACE) inhibitors reduce mortality when prescribed following myocardial infarction have focused on either early or late administration. It is unclear what the overall mortality benefits are and how long they last. METHODS: We identified trials of ACE inhibitor therapy after myocardial infarction that were published between 1987 and 2002. Studies were included if they were randomized placebo-controlled trials with follow-up of at least 1 month. Separate analyses were performed for trials of therapy initiated within 48 hours of infarction (early administration) or initiated more than 48 hours after infarction (late administration). The Yusuf-Peto modification of the Mantel-Haenszel method was used to obtain summary odds ratios for mortality. RESULTS: Twenty-two trials (14 early administration, 8 late administration) met the inclusion criteria. Early administration of ACE inhibitors was associated with a slight reduction in 1-month mortality (odds ratio [OR] = 0.93; 95% confidence interval [CI]: 0.88 to 0.97) and a much larger reduction in 1-year mortality (OR = 0.68; 95% CI: 0.54 to 0.87). Late therapy was associated with significant reductions in 1-year mortality (OR = 0.84; 95% CI: 0.73 to 0.97), 2-year mortality (OR = 0.75; 95% CI: 0.67 to 0.85), and 3-year mortality (OR = 0.74; 95% CI: 0.65 to 0.84). CONCLUSION: Both early and late administration of ACE inhibitor therapy are associated with lower mortality following myocardial infarction, with the largest benefits observed with long-term mortality.     

The Angiotensin-converting Enzyme Inhibition Post Revascularization Study (APRES)

OBJECTIVE: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Usefulness of myocardial contrast echocardiography in predicting late mortality in patients with anterior wall acute myocardial infarction

We investigated whether myocardial contrast echocardiography (MCE) performed soon after acute myocardial infarction (AMI) improves risk stratification for late mortality. MCE after AMI identifies microvascular "no-reflow" and predicts early outcomes; however, the predictive value of MCE for late mortality is unknown. One hundred sixty-seven patients with anterior AMI and left ventricular dysfunction underwent MCE 2 days after admission, and a perfusion score index (PSI) was calculated. Long-term follow-up (mean 39 months) was available for all patients. Patients with normal and abnormal perfusion had similar baseline characteristics. Myocardial contrast echocardiographic PSI was a predictor of mortality as a continuous variable (odds ratio 3.2 for each 1.0 increase in PSI, 95% confidence interval 1.1 to 9.7, p = 0.04). In a logistic regression model, age (odds ratio 2.6 per decade, 95% confidence interval 1.6 to 4.4, p = 0.0002) and PSI (odds ratio 4.5 for each 1.0 increase in PSI, 95% confidence interval 1.3 to 15.4, p = 0.02) were the only significant predictors of mortality. In a subanalysis comparing patients >70 years old with abnormal PSI with all other patients, Kaplan-Meier estimates showed a marked difference in survival over a mean follow-up of 39 months (24% vs 4% mortality, p = 0.0002). In conclusion, MCE refines risk stratification soon after anterior AMI in patients with left ventricular dysfunction. Patients at very high and very low risk of mortality can be identified, and myocardial contrast echocardiographic data are incrementally useful compared with existing clinical and angiographic variables.     

Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race,gender, and diabetic status: a meta-analysis of major clinical trials

OBJECTIVES: This study sought to assess the effect of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers on all-cause mortality in patients with left ventricular (LV) systolic dysfunction according to gender, race, and the presence of diabetes. BACKGROUND: Major randomized clinical trials have established that ACE inhibitors and beta-blockers have life-saving benefits in patients with LV systolic dysfunction. Most patients enrolled in these trials were Caucasian men. Whether an equal effect is achieved in women, non-Caucasians, and patients with major comorbidities has not been established. METHODS: The authors performed a meta-analysis of published and individual patient data from the 12 largest randomized clinical trials of ACE inhibitors and beta-blockers to produce random effects estimates of mortality for subgroups. RESULTS: Data support beneficial reductions in all-cause mortality for the use of beta-blockers in men and women, the use of ACE inhibitors and some beta-blockers in black and white patients, and the use of ACE inhibitors and beta-blockers in patients with or without diabetes. Women with symptomatic LV systolic dysfunction probably benefit from ACE inhibitors, but women with asymptomatic LV systolic dysfunction may not have reduced mortality when treated with ACE inhibitors (pooled relative risk = 0.96; 95% confidence interval: 0.75 to 1.22). The pooled estimate of three beta-blocker studies supports a beneficial effect in black patients with heart failure, but one study assessing bucindolol reported a nonsignificant increase in mortality. CONCLUSIONS: Angiotensin-converting enzyme inhibitors and beta-blockers provide life-saving benefits in most of the subpopulations assessed. Women with asymptomatic LV systolic dysfunction may not achieve a mortality benefit when treated with ACE inhibitors.     

Effect of use of combination evidence-based medical therapy after acute coronary syndromes on long-term outcomes

Several medications have individually been shown to reduce mortality in patients with acute coronary syndromes (ACS), but data on long-term outcomes related to the use of combinations of these medications are limited. For 2,684 consecutive patients admitted with ACS from January 1999 and January 2007, a composite score was calculated correlating with the use upon discharge of indicated evidence-based medications (EBMs): aspirin, β blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and lipid-lowering agents. Multivariate models were used to examine the impact of EBM score on 2-year events with adjustment for components of the Global Registry of Acute Coronary Events (GRACE) risk score, thienopyridine use, and year of discharge. Women were older, had more co-morbidities, and were less likely to receive all 4 EBMs (53% vs 64%, p < 0.0001) than men. Patients who received all 4 indicated EBMs had a significant 2-year survival benefit compared to patients who received ≤1 EBM (odds ratio 0.25, 95% confidence interval 0.15 to 0.41), which was observed when men and women were examined separately (for men, odds ratio 0.22, 95% confidence interval 0.11 to 0.44; for women, odds ratio 0.3, 95% confidence interval 0.15 to 0.63). A modest benefit, in terms of cardiovascular disease events (myocardial infarction, rehospitalization, stroke, and death), was observed only for men who received all 4 EBMs. In conclusion, a combination of cardiac medications at the time of ACS discharge is strongly associated with 2-year survival in men and women, suggesting that discharge is an important time to prescribe secondary preventative medications.     

Is ramipril really better than other angiotensin-converting enzyme inhibitors after acute myocardial infarction?

Whether angiotensin-converting enzyme (ACE) inhibitors are interchangeable and equally efficacious after acute myocardial infarction (AMI) is controversial. We assessed whether ramipril was superior to other ACE inhibitors after AMI as suggested by a previously published study. We performed a retrospective cohort study using linked administrative databases on >1.4 million elderly residents in the province of Ontario who were admitted to the hospital for AMI, survived >or=30 days after discharge, and were initiated on an ACE inhibitor after AMI and remained on the same ACE inhibitor from April 1, 1997 to March 31, 2000. We followed patients for 2 years and measured readmission for AMI or mortality, together or alone. Our cohort included 5,408 elderly patients. Compared with patients on enalapril, there was no significant difference for the combined end points of readmission for AMI or mortality across users of ramipril (adjusted hazard ratio 0.95, 95% confidence interval 0.79 to 1.15), lisinopril (adjusted hazard ratio 1.02, 95% confidence interval 0.84 to 1.25), or other ACE inhibitors (adjusted hazard ratio 1.08, 95% confidence interval 0.88, 1.32). In conclusion, the findings of this study support a class effect among ACE inhibitors in treatment after AMI.     

Effect of statins, angiotensin-converting enzyme inhibitors, and beta blockers on survival in patients >or=65 years of age with heart failure and preserved left ventricular systolic function

About half of all patients with heart failure (HF) have preserved left ventricular systolic function. Statins, angiotensin-converting enzyme inhibitors, and beta blockers have been shown to improve survival in patients with HF and low ejection fraction. However, no large national study has investigated these agents in patients with HF and preserved left ventricular ejection fraction. We evaluated a nationwide sample of 13,533 eligible Medicare beneficiaries aged >or=65 years who were hospitalized with a primary discharge diagnosis of HF and had chart documentation of preserved left ventricular ejection fraction between April 1998 and March 1999 or between July 2000 and June 2001. In Cox proportional hazard model accounting for demographic profile, clinical characteristics, treatments, physician specialty, and hospital characteristics, discharge statin therapy was associated with significant improvements in 1- and 3-year mortality (RR 0.69, 95% confidence interval [CI] 0.61 to 0.78; RR 0.73, 95% CI 0.68 to 0.79, respectively). Irrespective of total cholesterol level or coronary artery disease status, diabetes, hypertension, and age, statin therapy was associated with significant differences in mortality rates. Similarly, angiotensin-converting enzyme inhibitors were associated with better survival at 1 year (RR 0.88, 95% CI 0.82 to 0.95) and 3 years (RR 0.93, 95% CI 0.89 to 0.98). Beta-blocker therapy was associated with a nonsignificant trend at 1 year (RR 0.93, 95% CI 0.87 to 1.10) and significant survival benefits at 3 years (RR 0.92%, 95% CI 0.87 to 0.97). In conclusion, our data demonstrate that statins, angiotensin-converting enzyme inhibitors, and beta blockers are associated with better short- and long-term survival in patients >or=65 years with HF and preserved left ventricular ejection fraction.     

Relative efficacy of angiotensin converting enzyme inhibitors on mortality of patients with congestive heart failure: implications of randomized trials and role of the aetiology (ischaemic or non-ischaemic) of heart failure.

We examined the influence of angiotensin converting enzyme inhibitors (ACE inhibitors) on mortality in patients with heart failure of both ischaemic or non-ischaemic origin. Eleven, randomized, placebo-controlled trials of ACE inhibitors involving 1266 patients were selected. The follow-up period varied from 3 to 6 months. Four different ACE inhibitors were used in the 11 clinical trials. A total of 679 patients presented with an ischaemic heart failure and 587 with a non-ischaemic heart failure. Meta-analysis, performed for both subgroups, showed that mortality was significantly decreased in the ischaemic subgroup only (ischaemic group: odds ratio 0.45; 95% confidence interval 0.28 to 0.71; non-ischaemic subgroup: odds ratio 0.7; 95% confidence interval 0.4 to 1.5). Although the two odds ratio are not significantly different, further randomized, placebo-controlled trials with ACE inhibitors are required in order to determine more precisely the benefit/risk ratio in patients with non-ischaemic heart failure.     

High-sensitivity C-reactive protein and silent myocardial ischemia in Chinese with type 2 diabetes mellitus

Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients with type 2 diabetes mellitus. When diabetes exists in patients with established CAD, absolute risk for future events is very high. Diabetic patients often have severe, yet asymptomatic, CAD. Although high-sensitivity C-reactive protein (hsCRP) is a strong independent risk factor for cardiovascular events, there is an unclear association between it and silent myocardial ischemia in diabetic patients. In this study, we assess the relationship between hsCRP and silent myocardial ischemia in Chinese with type 2 diabetes mellitus. We designed a cross-sectional study with 225 asymptomatic diabetic patients having no known CAD. Ischemia was assessed by myocardial perfusion imaging. A total of 109 patients (48.4%) was found to have silent myocardial ischemia. Logistic regression analysis revealed age (odds ratio = 4.01, P = .002) (95% confidence interval, 1.98-7.44) and hsCRP (odds ratio = 2.58, P = .005) (95% confidence interval, 1.33-5.01) to be associated with greater risk of silent myocardial ischemia. Using the American Diabetes Association screening guidelines to evaluate risk, we found silent myocardial ischemia to be equally distributed between diabetic patients with 2 or more cardiac risk factors and those with less than 2 risk factors. Twenty-seven (24.8%) patients with silent myocardial ischemia were missed when the American Diabetes Association guidelines were used alone. High-sensitivity C-reactive protein was associated with silent myocardial ischemia in our study. High-sensitivity C-reactive protein might help detect silent myocardial ischemia in diabetic Chinese who may need aggressive treatment to reduce future CAD morbidity and mortality in Taiwan.     

Relation of growth-differentiation factor 15 to left ventricular remodeling in ST-segment elevation myocardial infarction

The development of left ventricular remodeling (LVR) after myocardial infarction is associated with a high risk of heart failure and death. LVR is difficult to predict, and limited information is available on the association of cardiac biomarkers and LVR. Growth-differentiation factor-15 (GDF-15) is induced during heart failure development and, in animals models, might influence the different processes involved in cardiac remodeling. The aim of the present investigation was to assess the association between the serum levels of GDF-15 within the first 24 hours of ST-segment elevation myocardial infarction and the development of subsequent LVR at 12 months of follow-up. This prospective study included 97 patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Echocardiography was performed in all patients within the first 96 hours of admission and at 12 months of follow-up. LVR was defined as a >20% increase in the left ventricular end-diastolic volume at 12 months of follow-up compared to baseline. Blood samples for the determination of GDF-15 and brain natriuretic peptide were obtained within the first 24 hours after symptom onset. According to the pre-established criteria, 21 patients (22%) had LVR. Patients with LVR had greater levels of GDF-15 at study entry (median 3,439 pg/ml, interquartile range 2,391 to 6,168 vs median 1998 pg/ml, interquartile range 1,204 to 3,067, respectively; p <0.001). Multivariate analysis showed that GDF-15 (odds ratio 10.1, 95% confidence interval 2.5 to 40.1, p <0.001) and treatment with angiotensin-converting enzyme inhibitors (odds ratio 3.9, 95% confidence interval 1.2 to 12.3, p <0.01) were independents predictors of LVR. Receiving operating characteristics analysis showed an area under the curve of 0.77 for GDF-15 (95% confidence interval 0.67 to 0.84, p <0.001). In conclusion, the results of the present study have identified GDF-15 as an independent marker of LVR in patients with ST-segment elevation myocardial infarction.     

Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphism in coronary disease and malignant ventricular arrhythmias

OBJECTIVES: It has been reported that patients carrying the angiotensin-converting enzyme (ACE) deletion DD genotype with the angiotensin II type 1 (AT1) C allele are at increased risk for myocardial infarction. The frequency distribution of the ACE and AT1 receptor gene polymorphism and their possible relation regarding malignant ventricular arrhythmias in patients with coronary artery disease (CAD) and left ventricular dysfunction was determined. METHODS: The ACE I/D and AT1 A/C polymorphisms (using polymerase chain reaction) in 100 Caucasian patients suffering from CAD with a history of malignant ventricular arrhythmias treated with an implantable cardioverter defibrillator (ICD group) was compared to 127 age-matched Caucasian patients with CAD and no history of malignant ventricular arrhythmias (control group). All patients had reduced left ventricular ejection fraction of < 40% and were comparable regarding sex distribution, body mass index, ACE-inhibitor treatment, lipid status and duration of CAD. RESULTS: The prevalence of DD/CC in the ICD group was significantly higher (19% versus 10%, p < 0.0001). The risk for malignant ventricular arrhythmias was associated with the combination of ACE D and AT1 C alleles (odds-ratio: 2.4, 95% confidence interval 1.41 to 3.94, p < 0.001). The distribution of ACE and AT1 genotypes was not different between the two group. CONCLUSIONS: Patients with coronary artery disease and left ventricular dysfunction carrying ACE D and AT1 C alleles are at increased risk for development of malignant ventricular arrhythmias. Because of available pharmacological inhibitors, these results may have clinical implications for the prevention of sudden cardiac death.     

Electrocardiographic predictors of out-of-hospital sudden cardiac arrest in patients with coronary artery disease

Sudden cardiac arrest (SCA), due mainly to coronary artery disease (CAD), is a leading cause of death. To identify electrocardiographic and clinical differences between patients with CAD with and without SCA, 87 victims of SCA with CAD were compared with 131 patients with CAD without SCA. Patients' latest routine electrocardiograms and clinical variables were compared. Patients with CAD with and without previous myocardial infarctions (MIs) were included. Patients with SCA had a higher incidence of echocardiographic evidence of left ventricular hypertrophy and/or heart failure than controls. The median left ventricular ejection fractions for patients with SCA with and without previous MIs were 0.30 (interquartile range 0.24 to 0.41) and 0.41 (interquartile range 0.25 to 0.56). The median time between the last electrocardiographic assessment and SCA was 59 days (interquartile range 29 to 137). Regarding electrocardiographic characteristics, in patients with and without previous MIs, QRS width (odds ratio 1.032, 95% confidence interval 1.012 to 1.053, p = 0.002, and odds ratio 1.035, 95% confidence interval 1.015 to 1.056, p = 0.001) was the only significant predictor of SCA. In conclusion, in patients with CAD, regardless of a previous MI, a longer QRS width and echocardiographic parameters consistent with heart failure are associated with SCA, even in patients with ischemic cardiomyopathy currently not eligible for an implantable cardioverter-defibrillator.     

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.     

Bayesian meta-analysis of tissue angiotensin-converting enzyme inhibitors for reduction of adverse cardiovascular events in patients with diabetes mellitus and preserved left ventricular function

The role of angiotensin-converting enzyme (ACE) inhibitors in diabetic patients with preserved ventricular function is uncertain. Tissue ACE inhibitors have been defined by increased lipophilicity and structural characteristics that result in greater tissue-specific ACE binding when compared with plasma ACE inhibitors. A Bayesian meta-analysis of randomized trials was conducted to evaluate tissue ACE inhibitors in prevention of cardiovascular disease among patients with diabetes mellitus and preserved left ventricular function. Four trials were selected that evaluated 2 different ACE inhibitors and included 10,328 patients (43,517 patient-years). The Perindopril Substudy in Coronary Artery Disease and Diabetes (PERSUADE) and the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) compared the effects of perindopril vs a placebo, and the Heart Outcomes Prevention Evaluation (HOPE) and the Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) study investigated the impact of ramipril vs a placebo. Bayesian meta-analysis of sequential trials and sensitivity analysis of therapeutic response were subsequently computed. Bayesian meta-analysis determined reduced risk of cardiovascular mortality (PB=.991), myocardial infarction (PB=.999), and the need for invasive coronary revascularization (PB=.995) when compared with placebo. Total mortality was also decreased (PB=.967), while the risk of stroke (PB=.907) and hospitalization for heart failure (PB=.923) were impacted. Bayesian meta-analysis of randomized trials suggests that tissue ACE inhibitors decrease the probability that diabetic patients with preserved left ventricular function will experience myocardial infarctions and cardiovascular death and reduce overall mortality.