Timing and Dose of Statin Therapy Define Its Impact on Inflammatory and Endothelial Responses During Myocardial Infarction

Objective-Clinical trials of statins during myocardial infarction (MI) have differed in their therapeutic regimes and generated conflicting results. This study evaluated the role of the timing and potency of statin therapy on its potential mechanisms of benefit during MI. Methods and Results-ST-elevation MI patients (n = 125) were allocated into 5 groups: no statin; 20, 40, or 80 mg/day simvastatin starting at admission; or 80 mg/day simvastatin 48 hours after admission. After 7 days, all patients switched their treatment to 20 mg/day simvastatin for an additional 3 weeks and then underwent flow-mediated dilation in the brachial artery. As of the second day, C-reactive protein (CRP) differed between non-statin users (12.0 +/- 4.1 mg/L) and patients treated with 20 (8.5 +/- 4.0 mg/L), 40 (3.8 +/- 2.5 mg/L), and 80 mg/day (1.4 +/- 1.5 mg/L), and the daily differences remained significant until the seventh day (P < 0.0001). The higher the statin dose, the lower the elevation of interleukin-2 and tumor necrosis factor-alpha, the greater the reduction of 8-isoprostane and low-density lipoprotein(-), and the greater the increase in nitrate/nitrite levels during the first 5 days (P < 0.001). Later initiation of statin was less effective than its early introduction in relation to attenuation of CRP, interleukin-2, tumor necrosis factor-alpha, 8-isoprostane, and low-density lipoprotein(-), as well as in increase in nitrate/nitrite levels (P < 0.0001). At the 30th day, there was no longer a difference in lipid profile or CRP between groups; the flow-mediated dilation, however, was proportional to the initial statin dose and was higher for those who started the treatment early (P = 0.001). Conclusion-This study demonstrates that the timing and potency of statin treatment during MI are key elements for their main mechanisms of benefit.

Outcome with calcium channel antagonists after myocardial infarction: A community-based study

Objectives. We sought to estimate the risk of death and recurrent myocardial infarction associated with the use of calcium antagonists after myocardial infarction in a population-based cohort study. Background. Calcium antagonists are commonly prescribed after myocardial infarction, but their long-term effects are not well established. Methods. Patients 25 to 69 years old with a suspected myocardial infarction were identified and followed up through a community-based register of myocardial infarction and cardiac death (part of the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease [MONICA] Project in Newcastle, Australia). Data were collected by review of medical records, in-hospital interview and review of death certificates. Results. From 1989 to 1993, 3,982 patients with a nonfatal suspected myocardial infarction were enrolled in the study. At hospital discharge, 1,001 patients were treated with beta-adrenergic blocking agents, 923 with calcium antagonists, 711 with both beta-blockers and calcium antagonists and 1,346 with neither drug. Compared with patients given beta-blockers, patients given calcium antagonists were more likely to suffer myocardial infarction or cardiac death (adjusted relative risk [RR] 1.4, 95% confidence interval [CI] 1.0 to 1.9), cardiac death (RR 1.6, 95% CI 1.0 to 2.7) and death from all causes (RR 1.7, 95% CI 1.1 to 2.6). Compared with patients given neither beta-blockers nor calcium antagonists, patients given calcium antagonists were not at increased risk of myocardial infarction or cardiac death (RR 1.0, 95% CI 0.8 to 1.3), cardiac death (RR 0.9, 95% CI 0.6 to 1.2) or death from all causes (RR 1.0, 95% CI 0.7 to 1.3). No excess in risk of myocardial infarction or cardiac death was observed among patients taking verapamil (RR 0.9, 95% CI 0.6 to 1.6), diltiazem (RR 1.1, 95% CI 0.8 to 1.4) or nifedipine (RR 1.3, 95% CI 0.7 to 2.2) compared,vith patients taking neither calcium antagonists nor beta-blockers. Conclusions. These results are consistent with randomized trial data showing benefit from beta blockers after myocardial infarction and no effect on the risk of recurrent myocardial infarction and death with the use of calcium antagonists. Comparisons between beta-blockers and calcium antagonists favor beta blockers because of the beneficial effects of beta-blockers and not because of adverse effects of calcium antagonists. (C) 1998 by the American College of Cardiology.

Arrhythmias and mortality after myocardial infarction in diabetic patients - Relationship to diabetes treatment

OBJECTIVE- To assess the relationship between clinical course after acute myocardial infarction (AMI) and diabetes treatment. RESEARCH DESIGN AND METHODS- Retrospective analysis of data from all patients aged 25-64 years admitted to hospitals in Perth, Australia, between 1985 and 1993 with AMI diagnosed according to the International Classification of Diseases (9th revision) criteria was conducted. Short- (28-day) and long-term survival and complications in diabetic and nondiabetic patients were compared. For diabetic patients, 28-day survival, dysrhythmias, heart block, and pulmonary edema were treated as outcomes, and factors related to each were assessed using multiple logistic regression. Diabetes treatment was added to the model to assess its significance. Long-term survival was compared by means of a Cox proportional hazards model. RESULTS- Of 5,715 patients, 745 (12.9%) were diabetic. Mortality at 28 days was 12.0 and 28.1% for nondiabetic and diabetic patients, respectively (P < 0.001); there were no significant drug effects in the diabetic group. Ventricular fibrillation in diabetic patients taking glibenclamide (11.8%) was similar to that of nondiabetic patients (11.0%) but was lower than that for those patients taking either gliclazide (18.0%; 0.1 > P > 0.05) or insulin (22.8%; P < 0.05). There were no other treatment-related differences in acute complications. Long-term survival in diabetic patients was reduced in those taking digitalis and/or diuretics but type of diabetes treatment at discharge had no significant association with outcome. CONCLUSlONS- These results do not suggest that ischemic heart disease should influence the choice of diabetes treatment regimen in general or of sulfonylurea drug in particular.

Do simple prudent health behaviours protect men from myocardial infarction?

Background We tested whether behaviours such as discarding obvious fat on meat, cessation of smoking, avoidance of passive smoking, habitual use of reduced fat milk, prudent consumption of alcohol and regular but moderate physical exercise are associated with a reduction of cardiovascular risk. Methods This was a population-based case-control study done in Perth, Western Australia. The cases (n = 336) were men aged 27-64 years with a first-ever acute myocardial infarction (AMI) during the period 1992-1993, and who survived at least 28 days. The controls (n = 735) were participants in a population-based survey of cardiovascular risk factors conducted during May-November 1994. Both groups completed the same questionnaire and the data were analysed with multiple logistic regression using backward elimination technique. Results Among men aged 27-64 years simple measures such as participation in non-vigorous exercise (odds ratio [OR] = 0.5, 95% CI : 0.4-0.7), and avoidance of added salt (OR = 0.6, 95% CI : 0.4-0.9) are associated with significant and Important protection from AMI. Conclusion After 25 years of falling mortality in Australia, lifestyles can still be significantly improved to reduce heart disease even further.

Effect of combined supplementation with vitamin E and alpha-lipoic acid on myocardial performance during in vivo ischaemia-reperfusion

Reactive oxygen species (ROS) contribute significantly to myocardial ischaemia-reperfusion (I-R) injury. Recently the combination of the antioxidants vitamin E (VE) and alpha-lipoic acid (alpha-LA) has been reported to improve cardiac performance and reduce myocardial lipid peroxidation during in vitro I-R. The purpose of these experiments was to investigate the effects of VE and alpha-LA supplementation on cardiac performance, incidence of dysrhythmias and biochemical alterations during an in vivo myocardial I-R insult. Female Sprague-Dawley rats (4-months old) were assigned to one of the two dietary treatments: (1) control diet (CON) or (2) VE and alpha-LA supplementation (ANTIOXID). The CON diet was prepared to meet AIN-93M standards, which contains 75 IU VE kg(-1) diet. The ANTIOXID diet contained 10 000 IU VE kg(-1) diet and 1.65 g alpha-LA kg(-1) diet. After the 14-week feeding period, significant differences (P < 0.05) existed in mean myocardial VE levels between dietary groups. Animals in each experimental group were subjected to an in vivo I-R protocol which included 25 min of left anterior coronary artery occlusion followed by 10 min of reperfusion. No group differences (P > 0.05) existed in cardiac performance (e.g. peak arterial pressure or ventricular work) or the incidence of ventricular dysrhythmias during the I-R protocol. Following I-R, two markers of lipid peroxidation were lower (P < 0.05) in the ANTIOXID animals compared with CON. These data indicate that dietary supplementation of the antioxidants, VE and alpha-LA do not influence cardiac performance or the incidence of dysrhythmias but do decrease lipid peroxidation during in viva I-R in young adult rats.

Prior calcium channel blockade and short-term survival following acute myocardial infarction

There is concern over the safety of calcium channel blockers (CCBs) in acute coronary disease. We sought to determine if patients taking calcium channel blockers (CCBs) at the time of admission with acute myocardial infarction (AMI) had a higher case-fatality compared with those taking beta-blockers or neither medication. Clinical and drug treatment variables at the time of hospital admission predictive of survival at 28 days were examined in a community-based registry of patients aged under 65 years admitted to hospital for suspected AMI in Perth, Australia, between 1984 and 1993. Among 7766 patients, 1291 (16.6%) were taking a CCB and 1259 (16.2%) a betablocker alone at hospital admission. Patients taking CCBs had a worse clinical profile than those taking a beta-blocker alone or neither drug (control group), and a higher unadjusted 28-day mortality (17.6% versus 9.3% and 11.1% respectively, both P < 0.001). There was no significant heterogeneity with respect to mortality between nifedipine, diltiazem, or verapamil when used alone, or with a beta-blocker. After adjustment for factors predictive of death at 28 days, patients taking a CCB were found not to have an excess chance of death compared with the control group (odds ratio [OR] 1.06, 95% confidence interval [CI]; 0.87, 1.30), whereas those taking a beta-blocker alone had a lower odds of death (OR 0.75, 95% CI; 0.59, 0.94). These results indicate that established calcium channel blockade is not associated with an excess risk of death following AMI once other differences between patients are taken into account, but neither does it have the survival advantage seen with prior beta-blocker therapy.

Current smoking and the risk of non-fatal myocardial infarction in the WHO MONICA Project populations

Background: Cohort studies have shown that smoking has a substantial influence on coronary heart disease mortality in young people. Population based data on non-fatal events have been sparse, however. Objective: To study the impact of smoking on the risk of non-fatal acute myocardial infarction (MI) in young middle age people. Methods: From 1985 to 1994 all non-fatal MI events in the age group 35 - 64 were registered in men and women in the WHO MONICA ( multinational monitoring of trends and determinants in cardiovascular disease) project populations ( 18 762 events in men and 4047 in women from 32 populations from 21 countries). In the same populations and age groups 65 741 men and 66 717 women participated in the surveys of risk factors ( overall response rate 72%). The relative risk of non-fatal MI for current smokers was compared with non-smokers, by sex and five year age group. Results: The prevalence of smoking in people aged 35 - 39 years who experienced non-fatal MI events was 81% in men and 77% in women. It declined with increasing age to 45% in men aged 60 - 64 years and 36% in women, respectively. In the 35 - 39 years age group the relative risk of non-fatal MI for smokers was 4.9 (95% confidence interval (CI) 3.9 to 6.1) in men and 5.3 ( 95% CI 3.2 to 8.7) in women, and the population attributable fractions were 65% and 55%, respectively. Conclusions: During the study period more than half of the non-fatal MIs occurring in young middle age people can be attributed to smoking.

Prognostic Significance of Myocardial Fibrosis Quantification by Histopathology and Magnetic Resonance Imaging in Patients With Severe Aortic Valve Disease

Objectives We sought to determine whether the quantitative assessment of myocardial fibrosis (MF), either by histopathology or by contrast-enhanced magnetic resonance imaging (ce-MRI), could help predict long-term survival after aortic valve replacement. Background Severe aortic valve disease is characterized by progressive accumulation of interstitial MF. Methods Fifty-four patients scheduled to undergo aortic valve replacement were examined by ce-MRI. Delayed-enhanced images were used for the quantitative assessment of MF. In addition, interstitial MF was quantified by histological analysis of myocardial samples obtained during open-heart surgery and stained with picrosirius red. The ce-MRI study was repeated 27 +/- 22 months after surgery to assess left ventricular functional improvement, and all patients were followed for 52 +/- 17 months to evaluate long-term survival. Results There was a good correlation between the amount of MF measured by histopathology and by ce-MRI (r = 0.69, p < 0.001). In addition, the amount of MF demonstrated a significant inverse correlation with the degree of left ventricular functional improvement after surgery (r = -0.42, p = 0.04 for histopathology; r = -0.47, p = 0.02 for ce-MRI). Kaplan-Meier analyses revealed that higher degrees of MF accumulation were associated with worse long-term survival (chi-square = 6.32, p = 0.01 for histopathology; chi-square = 5.85, p = 0.02 for ce-MRI). On multivariate Cox regression analyses, patient age and the amount of MF were found to be independent predictors of all-cause mortality. Conclusions The amount of MF, either by histopathology or by ce-MRI, is associated with the degree of left ventricular functional improvement and all-cause mortality late after aortic valve replacement in patients with severe aortic valve disease. (J Am Coll Cardiol 2010; 56: 278-87) (c) 2010 by the American College of Cardiology Foundation