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Computerised record linkage systems have great potential for enhancing or even replacing traditional methods of adverse event reporting based on active patient follow-up, both in clinical trials and in epidemiological studies. However, these methods must be evaluated. The West of Scotland Coronary Prevention Study (WOSCOPS) is a randomised double-blind clinical trial of pravastatin versus placebo in the primary prevention of coronary heart disease, with coronary heart disease death plus nonfatal myocardial infarction as its primary end point. Adverse event reporting is based on active patient follow-up at routine trial visits. In parallel with this approach, we have obtained computer records of all deaths, incident cancers, and hospitalisations for our subjects by linking their names, dates of birth, and postcodes of their home addresses with a Scottish national database operated by the Scottish Record Linkage system. The results of this comparative study, based on follow-up of the 6595 men ages 45-64 randomised in WOSCOPS, demonstrate minor flaws in both systems, show that follow-up based on computerised linkage alone can be as effective as reporting based on direct contact with the patients, and show that a system based on both approaches provides a direct cross-validation of the two approaches to adverse event reporting while minimising the frequency of unreported events. Preliminary results are reported for a prospective epidemiological study of 80,184 men, ages 45-64 years, who were screened for coronary heart disease risk factors as part of WOSCOPS. This study is based solely on computerised linkage reporting of events on these subjects. This provides an indication of the number of events in various categories that will be available for analysis in future reports. The associations between death rates and standard risk factors such as age, blood pressure, total cholesterol level, and smoking status mirror those reported in other studies.
The findings of recent clinical trials have led to renewed interest in the role of oral anticoagulant therapy in patients with coronary artery disease. However, there are currently two major limitations to the routine use of oral anticoagulant therapy. The first is the need for laboratory monitoring and dose adjustment. This limitation may be overcome if fixed low doses of warfarin (e.g. 1 mg/day), which have antithrombotic effects, are shown by clinical trials to be effective and safe. A second limitation to oral anticoagulant therapy is uncertainty about its effectiveness and safety compared to aspirin, or in combination with aspirin. The current pathophysiologic knowledge and recent clinical trial data provide support for further clinical trials evaluating combined warfarin and aspirin treatment in the long-term care of patients with coronary artery disease, and in the primary prevention of myocardial infarction.
Aspirin, nonsteroidal antiinflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors are widely used in patients with rheumatoid arthritis. Aspirin has the largest and most persuasive body of randomized trial evidence to support its use in secondary prevention for cardiovascular disease (CVD) and primary prevention for myocardial infarction. There is, however, a possible deleterious interaction between aspirin and NSAIDs on CVD that requires further research. Aspirin, NSAIDs, and to a lesser extent COX-2 inhibitors are associated with increased gastrointestinal side effects and bleeding, alone and in combination. The more widespread and appropriate use of aspirin in patients with rheumatoid arthritis will avoid many premature deaths in secondary prevention for CVD and first myocardial infarctions in primary prevention.
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BACKGROUND: Whether the absence of coronary artery calcium, or conversely the presence of high volumes of coronary artery calcium, may alter assessment of coronary heart disease risk based on traditional risk factors is uncertain. We sought to identify a potential threshold of coronary artery calcium for clinical use and examine the predictive power of coronary artery calcium in individuals categorized using conventional coronary heart disease risk assessment. METHODS: The study included 10,746 men and women (36.3%) with a mean age of 53.8+/-9.9 years who were either physician- or self-referred for electron beam tomography scanning to a preventive medical clinic. Coronary heart disease risk factors were elicited by use of a questionnaire. RESULTS: During a mean follow-up of 3.5 years, 81 primary events (coronary heart disease death or nonfatal myocardial infarction) occurred. Among individuals with a coronary artery calcium score of zero, the primary event rate was very low (0.4 events per 1000 person-years of observation). When participants were stratified by self-reported coronary heart disease risk factors (0-2, or 3-4), a coronary artery calcium score >or=100 was associated with substantially increased risk of coronary heart disease events within each level of stratification. In a subgroup of participants with available clinical data, similar results were found when participants were categorized by Framingham risk scores. CONCLUSIONS: Coronary artery calcium score can identify individuals at increased risk for coronary heart disease events who otherwise would be considered low-risk based on clinical assessment. A coronary artery calcium score of zero is associated with very low risk for coronary heart disease in the short to intermediate term ( approximately 3.5 years) regardless of the number of risk factors present.
Two concepts from pathologic descriptions of myocardial hypertrophy in trained individuals merit consideration: (1) The heart of the trained athlete can be twice the normal size, but histologic structure remains intact, and (2) the weight of the trained heart does not usually surpass the limit of 500 g, defined as the critical heart weight. Even though this threshold cannot be accepted dogmatically, the concept of an upper limit for physiologic cardiac remodeling is nevertheless relevant to the clinical question of distinguishing extreme expressions of athlete's heart from primary pathologic conditions. This morphologic distinction depends on whether the magnitude of cardiac remodeling in athletes exceeds that expected as a result of athletic conditioning alone. There has also been a great interest in understanding the impact that types of athletic conditioning and gender have on defining the upper limits to which such physiologic hypertrophy may extend.
The influence of multivessel coronary artery disease on the outcome of reperfusion therapy for myocardial infarction has not been fully characterized. Direct coronary angioplasty without antecedent thrombolytic therapy was performed during evolving myocardial infarction in 285 patients with multivessel coronary artery disease at 5.2 +/- 4.2 h after the onset of chest pain. Two vessel disease was present in 163 patients (57%) and three vessel disease in 122 (43%). An anterior infarct was present in 123 patients (43%), cardiogenic shock in 33 (12%) and age greater than or equal to 70 years in 59 (21%). Angioplasty of the infarct-related vessel was successful in 256 patients (90%), including 92% with two vessel and 88% with three vessel disease (p = NS). Emergency bypass surgery was needed in six patients (2%). In-hospital death occurred in 33 patients (12%), including 13 with two vessel and 20 with three vessel disease (p less than 0.05). The mortality rate was only 4% in the subgroup of 101 patients who met entry criteria for thrombolytic trials. The in-hospital mortality rate was 45% in patients in shock and 7% in patients not in shock (p less than 0.01). Logistic regression analysis identified shock and age greater than or equal to 70 years as independently associated with in-hospital death. In 135 patients who underwent predischarge left ventriculography, global ejection fraction increased from 50% to 57% (p less than 0.001) and regional wall motion in the infarct zone improved in 59% of patients. Follow-up data were available in 251 patients (99%) at a mean of 35 +/- 19 months.(ABSTRACT TRUNCATED AT 250 WORDS)
CONTEXT: Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. OBJECTIVE: To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. DESIGN: Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. INTERVENTIONS: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. CONCLUSIONS: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
The purpose of this paper is to review the history of the clinico-pathologic investigations performed at the University of Padua on an old morbid entity ("parchment heart"), which, in the 1960s, led to the clinical description of the disease, in the 1980s to the revival of the scientific interest, and in the mid 1990s to the understanding of the genetic background. All the steps of the progressive knowledge are reviewed: necropsy of young people who died suddenly, in vivo diagnosis by ECG, echocardiography, angiocardiography, endomyocardial biopsy, nuclear magnetic resonance, and diagnostic criteria. Familial occurrence with autosomic dominant transmission and various penetrance was documented. Gene defects were recently mapped both to chromosome 14q23-q24 and 1q42-q43, thus providing evidence for genetic heterogeneity. The pathologic substrates of arrhythmogenic right ventricular cardiomyopathy pointed to an acquired progressive myocardial atrophy with fibro-fatty replacement of dying myocytes. Nowadays the disease is definitively regarded as a primary myocardial disorder and it has been included in the revised WHO classification of cardiomyopathies.
Antihemostatic drugs are widely used in the treatment and prevention of ischemic heart disease. Fibrinolytic agents are prescribed in the early phase of acute myocardial infarction, to reduce its size and improve survival. Their use in unstable angina is still controversial. Anticoagulants have substantial benefit in myocardial infarction, unstable angina and primary prevention of coronary disease. Finally, antiplatelet agents are used in stable and unstable angina, myocardial infarction and high risk patients.
BACKGROUND: Although effects of statins on cardiovascular outcomes are well established in men, fewer data exist for women. Furthermore, the effects of statins plus hormone replacement therapy (HRT) on cardiovascular outcomes are uncertain. METHODS AND RESULTS: We examined statin use, cardiovascular events, and total mortality in the Heart and Estrogen/progestin Replacement Study (HERS), a randomized clinical trial of estrogen plus progestin versus placebo in postmenopausal women with heart disease (n=2763). A nonrandomized comparison of statin users and nonusers revealed lower rates of the primary outcome, nonfatal myocardial infarction or coronary heart disease death (relative hazard [RH]=0.79, 95% confidence intervals [CI] 0.63 to 0.99, P=0.04), and total mortality (RH=0.67, 95% CI 0.51 to 0.87, P=0.003). Rates of venous thromboembolic events were also lower among statin users (RH=0.45, 95% CI 0.23 to 0.88, P=0.02). HRT resulted in a significant increase in early risk for primary events in women who did not use statins (RH=1.75, 95% CI 1.02 to 3.03, P=0.04) but not in statin users (RH=1.34, 95% CI 0.63 to 2.86, P=0.45). Adjustment for postrandomization statin use showed no effect of HRT on risk for the primary outcome (RH=0.96, 95% CI 0.77 to 1.29; P=0.72). CONCLUSIONS: In HERS, statin use was associated with lower rates of cardiovascular events, venous thromboembolic events, and total mortality. These data provide strong support for statin use in eligible women with coronary disease.
Percutaneous transluminal coronary angioplasty was performed as primary therapy in 215 consecutive patients (aged 56 +/- 11 years, 75% male) with acute myocardial infarction and single vessel coronary artery disease. Wide patency of the infarct-related artery was restored in 212 patients (99%). Complications consisted of one urgent coronary bypass operation (0.5%); there were no procedural deaths. A recurrent ischemic event before discharge occurred in eight patients (4%). The in-hospital mortality rate was 1%; five of six patients presenting with cardiogenic shock were alive at discharge. In 126 patients in whom predischarge angiography was performed, the ejection fraction improved from 55 +/- 12% to 61 +/- 12% (p less than 0.005) and increased by greater than or equal to 5% units in 66 patients (52%). Regional wall motion improved in 60 patients (48%). By multivariate analysis, a depressed initial ejection fraction, a limited increase in serum creatine kinase, young age and sustained patency of the infarct-related artery were found to be independent predictors of improvement in left ventricular function. Follow-up data were available in 214 patients (99.5%) at a mean interval of 35 months. The actuarial 3 year cardiac survival rate was 92%. By multivariate analysis, only the baseline ejection fraction correlated with long-term cardiac survival. Nine patients (4%) sustained a late nonfatal myocardial infarction, and 11 patients (5%) underwent subsequent coronary bypass surgery. At late follow-up study, 149 (77%) of 194 patients alive were free of angina. In summary, in patients with acute myocardial infarction and single vessel disease, coronary angioplasty without prior thrombolytic therapy can be performed with a high success rate and few procedural complications. After direct angioplasty, regional wall motion and global ejection fraction improve in 50% of patients, especially in those with depressed initial left ventricular function. This approach results in an excellent early and late event-free survival.
AIMS: Although recognized as an important feature of atherosclerotic coronary disease, little is known about the frequency and prognostic importance of distal embolization during primary angioplasty for acute myocardial infarction. METHODS AND RESULTS: As part of a randomized trial of thrombolysis vs primary angioplasty, 178 patients with acute myocardial infarction were treated with primary angioplasty. In these patients the occurrence of distal embolization after angioplasty was assessed. Embolization was defined as a distal filling defect with an abrupt 'cutoff' in one of the peripheral coronary artery branches of the infarct-related vessel, distal to the site of angioplasty. We analysed myocardial blush grade, ST-T segment elevation resolution, enzymatic infarct size and left ventricular ejection fraction in patients with and without distal embolization. Clinical information was collected for a mean of 5 years. Distal embolization was present in 27 patients (15.2%). Mean age and gender were not different from patients without distal embolization. Angiographic success (thrombolyis in myocardial infarction flow grade 3 and residual stenosis <50%) after primary angioplasty was less frequently observed in patients with distal embolization (70% vs 90%, P<0.01). Myocardial blush and ST-T segment elevation resolution after angioplasty were reduced when distal embolization was present. Patients with distal embolization had a larger enzymatic infarct size (mean cumulative lactate dehydrogenase measured over 72 h, 1612 vs 847, P<0.05) and a lower left ventricle ejection fraction at discharge (42% vs 51%, P<0.01). Long-term mortality was higher in patients with distal embolization (44% vs 9%, P<0.001). CONCLUSION: Distal embolization in patients treated with primary angioplasty is visible on the coronary angiogram in 15.2% of patients. It is related to reduced myocardial reperfusion, more extensive myocardial damage and a poor prognosis. Additional pharmacological interventions and/ or mechanical devices should be studied to prevent and/or treat distal embolization.
Myocardial infarction and stroke are the major cause of death in developed countries and are the clinical manifestation of atherosclerosis and hypertension. Both the environmental factors and genetic predisposition have an influence on the pathogenesis of these diseases. Despite we know lots of environmental risk factors and we made important advances in the prevention and treatment of mentioned diseases, our knowledge about the pathogenic linkage between genetic predisposition and cardiovascular diseases is still very little. Activation of the renin-angiotensin system has been proposed as a very important step in the pathogenesis of hypertension and atherosclerosis. In spite of vasoconstrictor activity, angiotensin II can stimulate migration and proliferation of vascular smooth muscle cells, macrophage-foam cells formation, adhesion and aggregation of platelets and fibrinolytic system inhibition. Angiotensin convertin enzyme inhibitors reduce the development of the atherosclerotic process after vascular injury and in hyperlipidemic animals. Blockade of renin-angiotensin system seems to be also effective in secondary prevention of myocardial infarction in men. In sum, the genetic variations inside the renin-angiotensin system which may affect the function of its components might have an influence on genetic predisposition to cardiovascular diseases. The paper deals with the current state of knowledge on association between polymorphic variations in renin gene, angiotensinogen gene, angiotensin converting enzyme gene and AT1 receptor gene and primary hypertension, ischaemic heart disease and myocardial infarction.
OBJECTIVE: To assess the relation between myocardial viability, coronary flow reserve, and recovery of myocardial contractility after stenting for acute myocardial infarction. DESIGN: Consecutive sample prospective study. SETTING: University hospital. PATIENTS: 41 patients with single vessel disease and successful primary stenting for a first acute myocardial infarction. INTERVENTIONS: (201)Tl single photon emission computed tomography, contrast ventriculography, and intracoronary Doppler performed 7 (1) days after primary stenting. MAIN OUTCOME MEASURES: Regional contractility recovery assessed by contrast ventriculography at 6 (1) months' follow up. RESULTS: On univariate analysis, contractility recovery was correlated to prereperfusion anterograde and collateral flow grades (r = 0.41, p = 0.03 and r = 0.55, p = 0.0004), viability index (r = 0.55, p = 0.04), peak creatine kinase concentrations (r = -0.55, p = 0.0005), left ventricular ejection fraction (r = 0.45, p = 0.005), end diastolic pressure (r = -0.62, p < 0.0001), end systolic volume index (r = -0.47, p = 0.01), and the extent of hypokinetic area (r = -0.48, p = 0.003), but not the coronary flow reserve. On multivariate analysis, independent predictors of late contractility recovery were prereperfusion anterograde and collateral flow grades and viability index. Relative coronary flow reserve, reflecting the culprit vessel's microvascular function, was correlated only to the extent of the infarct risk area (r = -0.45, p = 0.003). CONCLUSIONS: Independent predictors of contractility recovery between the seventh day and the sixth month after successful stenting for acute myocardial infarction are prereperfusion anterograde and collateral flows and myocardial viability. The culprit vessel's microvascular dysfunction is independent of myocardial viability and contractility and correlated to the extent of "jeopardised microvasculature".
BACKGROUND: Current guidelines broadly recommend comprehensive cardiac rehabilitation (CR), although evidence for this is still limited. It is not known whether evidence from before 1995 is still valid. STUDY DESIGN: The DANish Cardiac ReHABilitation (DANREHAB) trial was designed as a centrally randomized clinical trial to clarify whether hospital-based comprehensive CR is superior to usual care for patients with congestive heart failure, ischemic heart disease, or high risk for ischemic heart disease. A combined primary outcome measure included total mortality, myocardial infarction, or readmissions due to heart disease based on linkage to public registries. The CR was an individually tailored, multidisciplinary program (6 weeks of intensive CR and 12 months of follow-up) including patient education, exercise training, dietary counseling, smoking cessation, psychosocial support, risk factor management, and clinical assessment. STUDY POPULATION: Of 5060 discharged patients, 1614 (32%) were eligible for the trial and 770 patients were randomized (47% of those eligible). Participants were younger (P < .001) and had less comorbidity than nonparticipants (P < .03). CONCLUSION: Our trial shows that a large-scale, centrally randomized clinical trial on comprehensive CR can be conducted among a broadly defined patient group, but reaching the stipulated number of 1800 patients was difficult. Although the study included relatively many women and older people, elderly patients and patients with high comorbidity were underrepresented, which may influence the external validity.
OBJECTIVES: Construct a predictive model for early mortality in coronary reoperations (RECABG). METHODS: Five hundred and forty one RECABG (1987-1998) were studied by univariate and multivariate analysis. Stepwise selective procedure (p<0.05) was used to identify a subset of variables with prognostic value for early mortality. This subset was used to calculate a prognostic score 'S' and a predicted probability 'P' for early mortality, P=1/1+e(-S). Sensitivity analysis was used for evaluation. RESULTS: The best predictive variables for early mortality were diabetes, vascular-, lung-disease, a myocardial infarction between the primary and the RECABG, acute- and emergency operation and the operative period. The prognostic accuracy (receiver operating characteristics curve (ROC) area) was 80%. Observed probabilities compare well with the predicted probabilities, and patients were classified in low risk (5%), intermediate risk (15%), high risk (30%) and very high risk (40%). A predicted probability of > or =0.40 was used as cut-off point for the prognostic test. The specificity of this test was 97%, sensitivity 33%, predictive value of a positive test 63% and 90% for a negative test. CONCLUSIONS: The results show that individual patients presented for RECABG, can be stratified according to their early mortality risk. This information can be used to inform the patient, and also to discus the opportunity of the RECABG.