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PubMed1999

Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction.

OBJECTIVES: We tested to find out whether pravastatin restores the infarct size (IS)-limiting effect of ischemic preconditioning (IP) and if it has any effect on the IP-induced activation of adenosine producing enzyme ecto-5'-nucleotidase which plays a key role in the IP-induced cardioprotection. BACKGROUND: The IS-limiting effect of IP is blunted by hypercholesterolemia. Recently, HMG-CoA reductase inhibitors are shown to have direct cytoprotective effects. METHODS: Rabbits were fed with a normal or cholesterol (1%) added diet with or without pravastatin (5 mg/kg/day) treatment. Infarct size was measured after 30 min occlusion and 3 h reperfusion of circumflex coronary artery with or without the IP procedure (5 min occlusion and 10 min reperfusion). Additionally, ecto-5'-nucleotidase activities of ischemic and nonischemic myocardium were measured immediately after IP procedure. RESULTS: This dose of pravastatin did not normalize the increased level of serum cholesterol. The IS-limiting effect of preceding IP (IS reduced from 36.7% to 9.6%, p < 0.001) was abolished by hypercholesterolemia (from 46.1% to 31.3%, p = NS) and restored by pravastatin treatment (from 35.2% to 9.4%, p < 0.001). Pravastatin treatment did not affect IS or the effect of IP under normocholesterolemia. The activation of ecto-5'-nucleotidase presented as the activity ratio of ischemic to nonischemic myocardium (3.1-fold in normocholesterolemia) was blunted by hypercholesterolemia (1.8-fold, p < 0.05) and restored by pravastatin treatment (2.9-fold). CONCLUSIONS: Pravastatin, at the dose serum cholesterol was not normalized, restored the IS-limiting effect of IP and IP-induced ecto-5'-nucleotidase activation, which were both blunted by hypercholesterolemia. The activation of ecto-5'-nucleotidase may be worth further investigation as a possible mechanism for the hypercholesterolemia-induced retardation and pravastatin-mediated restoration of the cardioprotective effect of IP.

5'-Nucleotidase↗
PubMed1997

Post acute myocardial infarction: the Fosinopril in Acute Myocardial Infarction Study (FAMIS).

Many studies have clearly documented the beneficial effects of angiotensin converting enzyme (ACE) inhibitors in patients with acute myocardial infarction (AMI). The Fosinopril in Acute Myocardial Infarction Study (FAMIS) was a 2-year randomized, double-blind, placebo-controlled multicenter study investigating the hemodynamic and clinical effects of early (< 9 h from onset of symptoms) administration of fosinopril in 285 patients with anterior AMI undergoing thrombolysis within 6 h of symptom onset. The objective of the study was twofold: 1) to estimate changes in left ventricular (LV) volumes and function over 3 months by a series of echocardiographic evaluations, and 2) to clinically assess mortality and the occurrence of congestive heart failure (CHF) over 2 years. LV volumes measured at baseline (24 to 48 h from symptom onset) were within the normal range in over two-thirds of randomized patients, and the changes in volume were comparable after 3 months of treatment with either fosinopril or placebo. However, fosinopril-treated patients showed a 30% reduction in the 2-year incidence of death or moderate-to-severe CHF (P = .04) despite having a worst prognostic profile at baseline. This benefit of fosinopril was confirmed in the subgroup of patients without CHF on admission, who showed a 34.1% reduction in the 2-year occurrence of CHF (P = .05) and a 29.1% reduction in death or CHF (P = .04). The results of the FAMIS study suggest that early treatment with fosinopril, in conjunction with thrombolysis, can significantly delay the development of CHF in patients with AMI, acting through mechanisms independent of fosinopril's impact on LV remodeling.

Adolescent↗
PubMed1999

Effects of the administration of an angiotensin-converting enzyme inhibitor during the acute phase of myocardial infarction in patients with arterial hypertension. SMILE Study Investigators. Survival of Myocardial Infarction Long-term Evaluation.

A positive history of arterial hypertension (HBP) is present in as many as 30% of patients with acute myocardial infarction (AMI) and their clinical outcome could be greatly improved by drugs enhancing blood pressure control and preserving ventricular function. The aim of the present study was to evaluate the importance of a history of HBP on the clinical efficacy of early treatment with the angiotensin-converting enzyme (ACE) inhibitor zofenopril in patients with anterior AMI. We summarize the results of a post-hoc analysis of data from the Survival of Myocardial Infarction Long-term Evaluation (SMILE) study, which randomly evaluated the efficacy of zofenopril given within 24 h of symptom onset to patients with anterior AMI not undergoing thrombolysis. Of 1441 patients who entered the study, 565 (39.2%) had a history of HBP. The mean follow-up time was 12 months and the main outcome measures were 6-week combined occurrence of death and severe congestive heart failure (CHF) and 1-year mortality. After 6-week of treatment with zofenopril the relative risk of death or severe CHF was 0.60 (95% confidence interval [CI]: 0.45-0.81; 2P < .05) in the hypertensive group and 0.89 (0.74-1.08; 2P = .62) for normotensive patients, whereas the 1-year risk of death was 0.61 (95% CI: 0.23,0.89; 2P < .05) and 0.77 (95% CI: 0.52-1.17; 2P = .22), respectively. The 6-week prevalence of mild-to-moderate CHF was also significantly reduced by zofenopril in the hypertensive population (14.1% v 9.4%; 2P < .05). The present data suggest that treatment with zofenopril started within 24 h of the onset of anterior AMI could be highly beneficial in patients with a history of HBP.

Adolescent↗
PubMed1999

The effect of verapamil on left ventricular remodelling and diastolic function after acute myocardial infarction (the Verapamil Infarction Study on Remodelling and Relaxation--VISOR).

The VISOR is a double blind, randomized, placebo-controlled study aimed to assess the effects of early and prolonged administration of verapamil on the left ventricular geometry and diastolic function in patients with anterior acute myocardial infarction treated with thrombolysis. Patients with heart failure or ejection fraction < 45% were excluded. Within 12 hours from starting thrombolysis, 70 patients were given verapamil (5 mg/hour intravenously for the first 24 hours, followed by 120 mg t.i.d. perorally for 6 months) or equivalent placebo. Echocardiograms were performed on admittance, before discharge, after 3 months and 6 months. The following parameters were calculated: left ventricular volumes, ejection fraction, sphericity index, early (E) and late (A) transmitral peak flow velocities and time-velocity integrals with their ratios, deceleration time and half-time of E, isovolumic relaxation time (IVRT), and non-invasive time constant of ventricular relaxation (tau). The basal and the last available parameters were considered for statistical analysis. The effects of the treatment on the left ventricular volumes, ejection fraction, and sphericity index were not statistically relevant. Conversely, a reduction of E/A ratio (P < .05) and increases of A integral (P < .01), deceleration time and half-time of E, IVRT and tau (P < .05) were found in the placebo group and not in the verapamil group. No significant changes in the blood pressure, heart rate, PQ interval, and biochemical parameters were observed in the two groups. In conclusion, in patients with a thrombolysed anterior acute myocardial infarction and preserved systolic function, verapamil can prevent alterations of the diastolic function in absence of effect on ventricular remodelling, and has a good safety profile.

Calcium Channel Blockers↗
PubMed1997

Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival--4.

In a randomized, placebo-controlled trial, the effects of treatment with fish oil (eicosapentaenoic acid, 1.08 g/day) and mustard oil (alpha-linolenic acid, 2.9 g/day) were compared for 1 year in the management of 122 patients (fish oil, group A), 120 patients (mustard oil, group B), and 118 patients (placebo, group C) with suspected acute myocardial infarction (AMI). Treatments were administered about (mean) 18 hours after the symptoms of AMI in all three groups. The extent of cardiac disease, rise in cardiac enzymes, and lipid peroxides were comparable among the groups at entry into the study. After 1 year total cardiac events were significantly less in the fish oil and mustard oil groups compared with the placebo group (24.5% and 28% vs. 34.7%, p < 0.01). Nonfatal infarctions were also significantly less in the fish oil and mustard oil groups compared with the placebo group (13.0% and 15.0% vs. 25.4%, p < 0.05). Total cardiac deaths showed no significant reduction in the mustard oil group; however, the fish oil group had significantly less cardiac deaths compared with the placebo group (11.4% vs. 22.0%, p < 0.05). Apart from the decrease in the cardiac event rate, the fish oil and mustard oil groups also showed a significant reduction in total cardiac arrhythmias, left ventricular enlargement, and angina pectoris compared with the placebo group. Reductions in blood lipoproteins in the two intervention groups were modest and do not appear to be the cause of the benefit in the two groups. Diene conjugates showed a significant reduction in the fish oil and mustard oil groups, indicating that a part of the benefit may be caused by the reduction in oxidative stress. The findings of this study suggest that fish oil and mustard oil, possibly due to the presence of n-3 fatty acids, may provide rapid protective effects in patients with AMI. However, a large study is necessary to confirm this suggestion.

Adult↗
PubMed2002

Development and validation of a short measure of health status for individuals with acute myocardial infarction: the myocardial infarction dimensional assessment scale (MIDAS).

The purpose of this study was to develop and validate a disease-specific health status measure for individuals with myocardial infarction (MI). The development of the myocardial infarction dimensional assessment scale (MIDAS) followed three main stages. Stage 1 consisted of in-depth, semi-structured, exploratory interviews conducted on a sample of 31 patients to identify areas of salience and concern to patients with MI. These interviews generated 48 candidate questions. In stage 2 the 48-item questionnaire was used in a postal survey to identify appropriate rephrasing/shortening, to determine acceptability and to help identify sub-scales of the instrument addressing different dimensions of MI. Finally, in stage 3 the construct validity of MIDAS subscales was examined in relation to clinical and other health outcomes. A single centre (district general hospital) in England was used for stages 1 and 3 and a national postal survey was conducted for stage 2. A total of 410 patients were recruited for the national survey (stage 2). Full data were available on 348 (85%) patients. One hundred and fifty-five patients were recruited to test construct validity (stage 3). The MIDAS contains 35 questions measuring seven areas of health status: physical activity, insecurity, emotional reaction, dependency, diet, concerns over medication and side effects. The measure has high face, internal and construct validity and is likely to prove useful in the evaluation of treatment regimes for MI.

Activities of Daily Living↗
PubMed1998

Identification of post acute myocardial infarction patients with potential benefit from prophylactic treatment with amiodarone. A substudy of EMIAT (the European Myocardial Infarct Amiodarone Trial).

AIMS: To perform a retrospective analysis of subgroups of patients enrolled into the European Myocardial Infarct Amiodarone Trial (EMIAT) in order to identify patients who might benefit from prophylactic amiodarone treatment and patients in whom amiodarone might be harmful. METHODS: Baseline characteristics of the 1486 patients enrolled in EMIAT were used to investigate the all-cause mortality effect of amiodarone (intention-to-treat) in patients with a left ventricular ejection fraction 30-40% and < 30%, in patients with and without arrhythmia signs on Holter recordings, in patients with high and low baseline resting heart rate, in patients on and off beta-blocker treatment, and in a combination of these groups. RESULTS: A univariate analysis suggested that all-cause mortality is reduced on amiodarone in patients with an ejection fraction < 30%, with arrhythmia on the initial Holter, on beta-blocker treatment, and with an increased initial heart rate. A trend towards an increase of all-cause mortality was noted in patients with an ejection fraction 30-40%, without arrhythmia on Holter, off beta-blockers, and with a low baseline heart rate. A multivariate analysis suggested that the univariate observations are mutually additive. CONCLUSIONS: The study might serve as a basis for future prospective trials where amiodarone could be tested in patients with a recent myocardial infarction, having a reduced left ventricular ejection fraction, a high initial heart rate, and taking beta-blockers.

Adrenergic beta-Antagonists↗
PubMed1983

[Relation between multiple infarcts and vascular (multi-infarct) dementia].

77 patients with multiple infarcts in computerized tomography have been investigated. In 10 patients no definitive stroke could be found in the history, 2 had TIAs only. In 20 cases a PRIND and in 45 a completed stroke could be observed. More than one stroke was only present in 28 patients. In 68 of the patients without remarkable aphasia or decreased level of consciousness the psychiatric findings showed 37 patients with and 31 without a dementia. The CT findings showed in the patients with dementia significantly more often infarcts in the dominant hemisphere, whereas atrophy was found in a similar distribution in both groups.

Adult↗
PubMed1993

The association between on-site cardiac catheterization facilities and the use of coronary angiography after acute myocardial infarction. Myocardial Infarction Triage and Intervention Project Investigators.

BACKGROUND: During the past decade the use of coronary angiography after acute myocardial infarction has substantially increased. Among the possible contributing factors, the increasing availability of cardiac catheterization facilities was the focus of our investigation. METHODS: We investigated whether the availability of cardiac catheterization facilities at an admitting hospital was associated with the likelihood that a patient would undergo coronary angiography. After adjusting for age, sex, cardiac history, and cardiac complications during hospitalization, we evaluated this association in 5867 consecutive patients with acute myocardial infarction admitted to 19 Seattle-area hospitals. We also assessed the association between the presence of on-site cardiac catheterization facilities and in-hospital mortality. RESULTS: Patients admitted to hospitals with on-site cardiac catheterization facilities were far more likely to undergo coronary angiography (odds ratio, 3.21; 95 percent confidence interval, 2.81 to 3.67) than patients admitted to hospitals where transfer to another institution would be required to perform cardiac catheterization. Admission to a hospital with on-site facilities was more strongly associated with the use of coronary angiography than any characteristic of the patient. Although our study had limited power to detect differences in mortality, the availability of coronary angiography had no discernible association with in-hospital mortality rates (odds ratio for mortality among patients admitted to hospitals with on-site facilities vs. patients admitted to hospitals without such facilities, 0.88; 95 percent confidence interval, 0.71 to 1.09). CONCLUSIONS: In this community-wide study, the availability of on-site cardiac catheterization facilities was associated with a higher likelihood that a patient would undergo coronary angiography. However, admission to hospitals with these facilities did not appear to be associated with lower short-term mortality.

Aged↗
PubMed2001

Infarct artery reocclusion after primary angioplasty, stent placement, and thrombolytic therapy for acute myocardial infarction.

BACKGROUND: The benefits of thrombolytic therapy for acute myocardial infarction (AMI) are limited by reocclusion of the infarct-related artery, which occurs in 25% to 30% of patients after successful reperfusion. The frequency of reocclusion after balloon angioplasty and stenting in this setting is less well documented. The aim of this study was to analyze the frequency and timing of reocclusion after percutaneous transluminal coronary angioplasty (PTCA) and stent placement during AMI from all available studies compared with previously published reocclusion rates after thrombolysis. METHODS AND RESULTS: The previously published thrombolysis data included 4231 patients in 19 studies with > or = 75 patients. Only PTCA studies with > or = 50 patients and stent studies with > or = 30 patients, in which routine angiographic follow-up was obtained in > or = 60% of patients, were included. Ten PTCA studies with a total of 1943 patients were analyzed, with follow-up angiography in 1391 (72%). Reocclusion rates ranged from 5% to 16.7%. The stent studies included 698 patients from 7 studies, with follow-up angiography in 92%. Reocclusion rates ranged from 0% to 6%. With the use of logistic regression analysis with allowance for overdispersion, there was a significantly lower rate of reocclusion after PTCA (odds ratio, 0.38; confidence interval, 0.24 to 0.57; P <.0001) and stent placement (odds ratio, 0.11; confidence interval, 0.05 to 0.22; P <.0001) compared with thrombolysis. Reocclusion after stent placement was lower than after PTCA (odds ratio, 0.28; confidence interval, 0.13 to 0.6; P <.0001). CONCLUSIONS: Reocclusion after PTCA and stent placement during AMI is less frequent than after thrombolysis. This may contribute to the superior outcome of patients treated with PTCA and stent placement in this setting.

Angioplasty, Balloon, Coronary↗
PubMed2002

Bivalirudin as a replacement for unfractionated heparin in unstable angina/non-ST-elevation myocardial infarction: observations from the TIMI 8 trial. The Thrombolysis in Myocardial Infarction.

BACKGROUND: The Thrombolysis in Myocardial Infarction (TIMI) 8 trial was undertaken to compare the efficacy and safety of bivalirudin versus unfractionated heparin in a double-blind phase III trial of patients with unstable angina/non-ST-elevation myocardial infarction (MI). METHODS: All patients received aspirin and were randomized either to unfractionated heparin (bolus of 70 U/kg followed by an infusion of 15 U/kg/h) or bivalirudin (bolus of 0.1 mg/kg followed by an infusion of 0.25 mg/kg/h) for a minimum of 72 hours. The primary efficacy end point was a composite of all cause mortality or nonfatal recurrent MI. RESULTS: A total of 133 of the planned 5320 patients were enrolled, at which point the study was terminated by the sponsor because of a decision at the time to suspend further development of bivalirudin. Through 14 days, the incidence of death or nonfatal MI was 9.2% in the 65 patients in the unfractionated heparin group and was 2.9% in the 68 patients in the bivalirudin group, odds ratio (95% CI) 0.30 (0.06-1.53). Major hemorrhage occurred in 3 patients in the unfractionated heparin group (4.6%) but in none of the patients in the bivalirudin group (P =.11). CONCLUSIONS: The trend toward a lower rate of death or nonfatal MI in the bivalirudin group is consistent with a therapeutic effect of the drug and is consistent with other trials of bivalirudin in patients with acute coronary syndromes. The potential for clinically meaningful antithrombotic activity without an increased risk of bleeding and availablility of an alternative anticoagulation strategy in patients who cannot tolerate unfractionated heparin are particularly attractive and underscore the need for further evaluation of bivalirudin.

Aged↗
PubMed2002

Abciximab therapy improves 1-month survival rate in unselected patients with acute myocardial infarction undergoing routine infarct artery stent implantation.

BACKGROUND: The impact of abciximab therapy on mortality in unselected patients with acute myocardial infarction (AMI) undergoing routine primary infarct-related artery (IRA) stent implantation is not yet defined, and previous randomized studies have produced conflicting results. METHODS: A strategy of IRA stenting alone as opposed to IRA stenting plus abciximab was compared in a series of 561 consecutive unselected patients with AMI. Abciximab treatment was strongly encouraged for all patients. The contraindication for abciximab therapy was a high risk of major bleeding as assessed by the operator before mechanical intervention. RESULTS: Of 561 patients, 348 patients underwent abciximab therapy and 213 underwent primary IRA stenting alone. The 1-month overall mortality rate was 2.9% in the abciximab group and 10.8% in the stent alone group (P <.001). The relative reduction in mortality rate was 73% for patients overall, 77% in the subset of patients aged < or =70 years (mortality rate, 1.2% vs 5.2%, P =.020), 57% in patients aged >70 years (7.7% vs 18%, P =.043), 63% in patients with cardiogenic shock (17% vs 46%, P =.022), and 77% in patients without cardiogenic shock (1.3% vs 5.6%, P =.002). Multivariate analyses on the basis of all patients, and on the subset of patients aged < or =70 years, showed that abciximab therapy was independently related to the risk of death at 1 month. No differences were seen between groups in the procedural success rate (99.1% vs 98.1%) or in the incidence rates of nonfatal reinfarction (0.3% vs 1.9%) or repeat target vessel revascularization (1.7% vs 1.9%). CONCLUSION: The results of this study strongly support the use of abciximab therapy in nonselected patients with AMI undergoing routine IRA stent implantation. The mechanism of the clinical benefit of abciximab was not related to the patency of the IRA.

Abciximab↗
PubMed2003

Relationship between initial white blood cell counts, stage of acute myocardial infarction evolution at presentation, and incidence of Thrombolysis In Myocardial Infarction-3 flow after streptokinase.

BACKGROUND: The initial white cell counts in patients with acute myocardial infarction (AMI) may reflect the stage of AMI evolution, and may also be related to the efficacy of thrombolytic agents in recanalizing occluded epicardial arteries. METHODS: In 312 patients with a first AMI, we divided the initial white cell counts into quartiles and investigated their relationship with the time to treatment and the incidence of Thrombolysis In Myocardial Infarction (TIMI)-3 flow at 90 minutes after commencement of streptokinase. RESULTS: A longer time from symptom onset to treatment was independently associated with a higher neutrophil count and a lower non-neutrophil count. These times were 2.6, 2.9, and 3.8 hours, respectively, in the lowest, combined second and third (ie, middle), and highest neutrophil quartiles (P =.003), and 4.3, 3, and 1.9 hours, respectively, in the lowest, combined middle, and highest non-neutrophil quartiles (P <.0001). TIMI-3 flow was achieved in 44% of the lowest total white cell quartile, 41% of the combined middle quartile, and 60% of the highest quartile (P =.05). The corresponding figures were 47%, 49%, and 46% (P =.657) for the neutrophil quartiles, and 32%, 46%, and 68% for the non-neutrophil quartiles (P =.001). On multivariable analysis, the incidence of TIMI-3 flow was independently and positively associated with the initial non-neutrophil count. Patients with non-neutrophil counts in the highest quartile had a higher incidence of TIMI-3 flow than those in the lowest quartile (odds ratio 2.86, 95% CI 1.32-6.23, P =.008). CONCLUSIONS: A longer time from symptom onset to thrombolysis for AMI is associated with a higher neutrophil count and a lower non-neutrophil count at presentation. A higher neutrophil count is not associated with worse epicardial blood flow at 90 minutes after streptokinase, and a higher non-neutrophil count predicts a greater likelihood of achieving TIMI-3 flow.

Aged↗
PubMed2005

Candidate genes of cerebral infarction and traditional classification in Koreans with cerebral infarction.

Sasang constitutional medicine is a major branch of Korean traditional Oriental medicine. The differences of disease susceptibility to be shown in Sasang constitution may be due to genetic factors. Therefore, the authors examined relationship between candidate genes of cerebral infarction (CI) and Sasang constitution. The homozygous deletion allele of the angiotensin converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the e4 allele of the apolipoprotein E gene (ApoE/e4) are reported to be associated with ischemic heart disease. CI is another atherosclerotic disease; and the effects of these polymorphisms on CI have been confusing. This study investigated whether ACE/DD, AGN/TT, and ApoE/e4 genotypes are associated with CI and whether genetic risk is enhanced by Sasang constitutional classification. The authors ascertained these genotypes in patients with CI (N=211), diagnosed by brain computed tomography. Control subjects for the infarction group were randomly selected from 319 subjects matched for age, sex, and history of hypertension with patients. The ACE/DD genotype was not associated with CI. However, there was significant association between ApoE polymorphism and CI (chi2=15.089, p<.05). Furthermore, frequency of AGN/TT genotype was higher in the patients with CI than in the controls (chi2=20.072, p<.05). The frequency of T allele was 0.91 in patients and 0.82 in controls (chi2=17.237, p<.05). However, Sasang constitutional classification did not increase the relative risk for CI in the subjects with ApoE/e4 or AGN/T allele. These results suggest that ApoE and AGN polymorphism predict CI, but Sasang constitutional classification does not enhance the risk for CI associated with ApoE/e4 or AGN/TT in a Korean population.

Angiotensinogen↗
PubMed2002

Smoking and mortality following acute myocardial infarction: results from the National Registry of Myocardial Infarction 2 (NRMI 2).

BACKGROUND: Current smokers have lower mortality following acute myocardial infarction (AMI) than non-smokers. This is often referred to as the "smokers' paradox". Our study explored possible explanations of this phenomenon. METHODS: From the 510,044 cases of AMI in the NRMI 2 from 1 June 1994, through 30 April 1997, 297,458 cases without hospital transfer were analyzed. Characteristics and treatments of tobacco smokers and non-smokers were compared before and after age-standardization. Multivariate logistic models investigated possible associations with in-hospital mortality using clinically relevant variables and interaction terms. RESULTS: Twenty-four per cent of AMI cases were current smokers. Smokers were 14 years younger than non-smokers (mean age 58 vs. 72 years, p<0.001) and had lower in-hospital mortality (8.0% vs. 16.4%, p<0.001). After age-standardization, smokers were more likely than non-smokers to suffer a Q-wave type of infarction, and were less likely to have a prior history of diabetes, hypertension, AMI, angina, cardiac failure, and coronary interventions. The unadjusted odds ratio (OR) for smoking and mortality was 0.44 (95% confidence interval, CI 0.43-0.45). After adjustment for age the OR was 0.81 (95% CI 0.78-0.83). Additional adjustment for previous medical history/cardiovascular risk factors changed the OR to 0.86 (95% CI 0.83-0.89). Adjustment for additional covariates and interaction terms had little effect. CONCLUSIONS: Smokers with AMI were on average 14 years younger than non-smokers, explaining most of the apparent association of smoking with differences in presentation and treatment, and lower in-hospital mortality. The residual association of smoking and better prognosis, the "smoker's paradox", was not fully explained by measured covariates.

Aged↗
PubMed1994

ACE inhibition, atherosclerosis and myocardial infarction--the AIRE Study in practice. Acute Infarction Ramipril Efficacy Study.

Unlike most cell-types in the body, cardiomyocytes do not replicate in adult life. Consequently myocardial infarction produces irreparable damage to the heart which in turn increases the likelihood of premature death. Recent trials indicate that immediate aspirin and thrombolytic therapy beneficially modify the natural history of myocardial infarction, reducing both short- and long-term mortality rates. However, the occurrence of early heart failure in as many as one third of patients continues to carry with it a particularly poor prognosis. Recent trials with ACE inhibitors indicate that delayed initiation (beyond 24 h) and long-term maintenance treatment of patients selected on the basis of either heart failure (AIRE Study) or an ejection fraction of less than 40% (SAVE Study) result in large reductions in all-cause mortality. Although the exact mechanism of this benefit remains uncertain the reduction of further myocyte death due to reinfarction or gradual toxic attrition has been suggested. The currently unreported ISIS-4 and GISSI-3 should provide additional information as to whether the clinical indications for ACE-inhibitor therapy should be extended to other patient groups.

Coronary Artery Disease↗
PubMed1996

Effects of beta receptor antagonists on left ventricular function in patients with clinical evidence of heart failure after myocardial infarction. A double-blind comparison of metoprolol and xamoterol. Echocardiographic results from the Metoprolol and Xamoterol Infarction Study (MEXIS).

Two hundred and ten patients with clinical evidence of heart failure, developing after an acute myocardial infarction, were randomized to treatment with the beta 1-receptor antagonist metoprolol 50-100 mg b.i.d. (n = 106) or the beta 1-receptor partial agonist xamoterol 100-200 mg b.i.d. (n = 104). Left ventricular systolic and diastolic function were assessed with echocardiography and transmitral Doppler cardiography before and after 3 and 12 months of double-blind treatment. E-point septal separation and percent left ventricular fractional shortening were used as indices of systolic function. The ratio between peak early and late mitral diastolic flow (E/A ratio) and isovolumic relaxation time were used as indices of diastolic function. In the xamoterol group, there was a deterioration in E-point septal separation (P < 0.05). A difference between the treatment groups was present both at 3 months (E-point septal separation 11.4 vs 13.0 mm, P < 0.01, fractional shortening 27.1 vs 25.2%, P < 0.05) and 12 months (E-point septal separation 11.1 vs 13.2 mm. P < 0.005, fractional shortening 26.9 vs 25.0%, P < 0.05). E/A ratio increased in the metoprolol group (P < 0.05) but not in the xamoterol group. At 3 months there was a significant difference (0.85 vs 0.67, P < 0.005) between the groups but not at 12 months. In comparison with the beta 1-receptor antagonist metoprolol, the beta 1-receptor partial agonist xamoterol impaired left ventricular systolic function in patients with clinical evidence of heart failure after an acute myocardial infarction.

Adrenergic beta-Antagonists↗
PubMed1990

Importance of quantitative analysis of ventricular arrhythmias for predicting the prognosis in low-risk postmyocardial infarction patients. European Infarction Study Group.

In 378 placebo patients enrolled in the European Infarction Study (EIS), a secondary prevention study after acute myocardial infarction, 24-h baseline Holter monitoring was done 14 to 31 days after MI, and the relationship of electrical (ventricular arrhythmias) and mechanical (clinical signs of ventricular dysfunction) risk factors was analysed on the basis of mortality during the subsequent 2 years of follow-up. There was a rather low overall 2-year mortality rate of 6.9%. Consecutive arrhythmias (ventricular pairs and runs of ventricular premature beats) and left-ventricular dysfunction alone were associated with a low mortality of 4.0% and 3.6%, respectively. However, the combination of both defined a high-risk group characterized by a 2-year mortality rate of 16.7%. Additionally, the risk of dying was dependent on the frequency of consecutive arrhythmias: 22.2% of the patients with greater than 10 ventricular pairs per day died during the follow-up period in contrast to 9.9% of those with only 1-10 ventricular pairs per day. Thus, only the combination of electrical and mechanical risk factors, and especially the frequency of consecutive VPB, is helpful in identifying a subgroup of postMI patients with poor clinical outcome. An intervention study should restrict itself to this risk population only.

Arrhythmias, Cardiac↗