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PubMed1992

Predicting the prevalence of a disease in a cohort at risk.

A non-homogeneous Markov chain model is used to describe the evolution of a progressive chronic disease. Transition probabilities are estimated from data on coronary heart disease in Australia. By varying the transition probabilities, the effects of changes in medical management or in the natural history of the disease are examined. For reducing rates of fatal and non-fatal acute myocardial infarction a multifaceted strategy of primary and secondary prevention and improved acute care is found most effective. Primary prevention reducing the risk of early stages of the disease has the potential to yield the highest proportion of disease-free people. By contrast, intensive medical treatment of acute disease would reduce mortality but increase the total burden of disease in the population.

Adult↗
PubMed2007

Impact of diabetes on five-year outcomes of patients with multivessel coronary artery disease.

BACKGROUND: Diabetes mellitus is a major cause of coronary artery disease. Despite improvement in the management of patients with stable coronary artery disease, diabetes remains a major cause of increased morbidity and mortality. Although coronary artery bypass grafting surgery (CABG) and percutaneous coronary intervention are widely used, no conclusive evidence exists that either treatment modality is better than medical therapy alone for the treatment of stable single- or multivessel coronary disease in patients with diabetes. METHODS: We compared medical therapy, percutaneous coronary intervention, and CABG in 499 diabetic patients (38.5%) and 799 nondiabetic patients (61.5%) with single- or multivessel coronary disease. The composite primary endpoint was cardiac-related death, Q-wave myocardial infarction, or refractory angina requiring revascularization. RESULTS: We treated 1,298 patients with either CABG (n = 524), percutaneous coronary intervention (n = 378), or medical therapy (n = 396). More deaths occurred among patients with diabetes than among patients without diabetes, regardless of which option was used (p < 0.001). When treatment modalities were stratified according to the number of diseased vessels, CABG was shown to be more beneficial for patients with diabetes and multivessel disease than for patients with diabetes and single-vessel disease (p < 0.001). However, when stratified by treatment, patients with diabetes receiving medical therapy had a worse prognosis than patients with diabetes treated with CABG (p = 0.005). CONCLUSIONS: All three therapeutic regimens resulted in high rates of cardiac-related deaths among patients with diabetes compared with patients without diabetes. Moreover, we observed better outcomes among patients with diabetes and multivessel coronary artery disease undergoing CABG regarding the primary endpoint at 5-year follow-up.

Adult↗
PubMed1993

Primary and secondary prevention of myocardial infarction and strokes: an update of randomly allocated, controlled trials.

AIM: To summarize the risk factors associated with coronary heart disease and strokes and to evaluate measures used in the prevention and treatment of these diseases. METHOD: A review of the results of randomly allocated clinical trials of treatment for both primary and secondary prevention of coronary heart disease and strokes. RESULTS: Reductions in elevated blood pressure and cholesterol and cessation of cigarette smoking have clearly been shown to reduce the incidence of coronary heart disease. A reduction in blood pressure has also been shown to reduce the risk of strokes. In addition to other classical risk factors, such as abnormal serum lipids, diabetes and a genetic predisposition, recent studies have shown that elevated levels of fibrinogen and other clotting factors, elevated levels of renin and decreased levels of anti-oxidant vitamins such as E, C and beta-carotene can predict coronary heart disease and strokes. Thrombolytic therapy, aspirin and beta-blockers have been shown to reduce mortality in patients with myocardial infarction, and the latter two agents reduce mortality, re-infarction and strokes with long-term use. Treatment with intravenous magnesium and nitrates has shown promise but larger trials are required to confirm the results. Both aspirin and heparin have proven value in reducing the incidence of myocardial infarction and death in unstable angina. Following an acute myocardial infarction, long-term therapy with aspirin, beta-blockers, lipid-lowering agents and oral anticoagulants has been shown to reduce mortality and re-infarction. In patients with large infarcts associated with a low ejection fraction or heart failure, the use of angiotensin converting enzyme (ACE) inhibitors reduces mortality, hospitalization for heart failure and re-infarction. The use of diuretics to lower blood pressure reduces strokes. In contrast, calcium antagonists do not appear to consistently reduce mortality or prevent vascular events when used for primary or secondary prevention of either myocardial infarction or strokes. CONCLUSIONS: Myocardial infarction and strokes can be prevented by refraining from smoking and maintaining appropriate blood pressure levels and a favourable balance of lipids. Following a myocardial infarction, further drug treatment should include aspirin, thrombolytic therapy (in acute myocardial infarction), beta-blockers, ACE inhibitors (in patients with a low ejection fraction) and perhaps anticoagulants.

Adrenergic beta-Antagonists↗
PubMed2002

Is there a clinically significant gender bias in post-myocardial infarction pharmacological management in the older (>60) population of a primary care practice?

BACKGROUND: Differences in the management of coronary artery disease between men and women have been reported in the literature. There are few studies of potential inequalities of treatment that arise from a primary care context. This study investigated the existence of such inequalities in the medical management of post myocardial infarction in older patients. METHODS: A comprehensive chart audit was conducted of 142 men and 81 women in an academic primary care practice. Variables were extracted on demographic variables, cardiovascular risk factors, medical and non-medical management of myocardial infarction. RESULTS: Women were older than men. The groups were comparable in terms of cardiac risk factors. A statistically significant difference (14.6%: 95% CI 0.048-28.7 p = 0.047) was found between men and women for the prescription of lipid lowering medications. 25.3% (p = 0.0005, CI 11.45, 39.65) more men than women had undergone angiography, and 14.4 % (p = 0.029, CI 2.2, 26.6) more men than women had undergone coronary artery bypass graft surgery. CONCLUSION: Women are less likely than men to receive lipid-lowering medication which may indicate less aggressive secondary prevention in the primary care setting.

Age Distribution↗
PubMed2005

The Coronary Artery Revascularisation in Diabetes (CARDia) trial: background, aims, and design.

BACKGROUND: Patients with diabetes have an increased incidence and severity of ischemic heart disease, which leads to an increased requirement for coronary revascularization. Comparative information regarding mode of revascularization--coronary artery bypass graft surgery surgery (CABG) or percutaneous coronary intervention (PCI)--is limited, mainly confined to a subanalysis of the Bypass Angioplasty Revascularization (BARI) trial, suggesting a mortality benefit of CABG over PCI. No prospective trial has specifically compared these modes of revascularization in patients with diabetes. OBJECTIVE: The Coronary Artery Revascularisation in Diabetes (CARDia) trial is designed to address the hypothesis that optimal PCI is not inferior to modern CABG as a revascularization strategy for diabetics with multivessel or complex single-vessel coronary disease. The primary end point is a composite of death, nonfatal myocardial infarction, and cerebrovascular accident at 1 year. METHOD: A total of 600 patients with diabetes are to be randomized to either PCI or CABG, with few protocol restrictions on operative techniques or use of new technology. This gives a power of 80% to detect non-inferiority of PCI assuming that the PCI 1-year event rate is 9%. A cardiac surgeon and a cardiologist must agree that a patient is suitable for revascularization by either technique prior to recruitment into the study. Twenty-one centers in the United Kingdom and Ireland are recruiting patients. Data on cost effectiveness, quality of life, and neurocognitive function are being collected. Long-term (3-5 year) follow-up data will also be collected.

Angioplasty, Balloon, Coronary↗
PubMed1999

Technetium-99m sestamibi single-photon emission tomography detects subclinical myocardial perfusion abnormalities in patients with systemic lupus erythematosus.

In patients with systemic lupus erythematosus, involvement of the cardiovascular system is the third leading cause of death. However, although autopsy studies have demonstrated a high incidence of abnormalities in both the myocardium and coronary vessels, clinical manifestations have been reported in only a small percentage of cases. The aim of this study was to evaluate myocardial perfusion in asymptomatic lupus patients using technetium-99m sestamibi single-photon emission tomography (SPET). Twenty-eight patients without overt cardiac involvement and risk factors were studied with 99mTc-sestamibi SPET at rest and after dipyridamole infusion. Perfusion abnormalities were detected in 18 cases: six had persistent defects, three had reversible defects, seven had both persistent and reversible defects, and two showed rest defects which normalized on dipyridamole images ("reverse redistribution pattern"). Coronary angiography was performed in eight patients with positive 99mTc-sestamibi SPET, and showed normal epicardial vessels in all the cases. These results indicate that 99mTc-sestamibi SPET reveals a high prevalence (18 out of 28 patients in this study, i.e. 64%) of myocardial perfusion abnormalities in asymptomatic lupus patients, probably due to the primary immunological damage of this autoimmune disease. In conclusion, rest/dipyridamole 99mTc-sestamibi SPET can be a useful non-invasive method to identify subclinical myocardial involvement in systemic lupus erythematosus, and patients potentially at risk of later cardiac events.

Adult↗
PubMed2003

Treatment of chronic peripheral arterial disease.

Peripheral arterial disease (PAD) is a common but under-recognized problem. Intermittent claudication is the most frequent symptom of PAD, although the diagnosis of PAD is often overlooked until the patient is presented with limb-threatening ischemia. Importantly, PAD is a marker of generalized atherosclerosis and is closely associated with coronary and cerebrovascular disease. The primary causes of death in patients with PAD are myocardial infarction and stroke. Reducing risk factors is an integral and aggressive part of the treatment regimen. The recognition and diagnosis of PAD, combined with its appropriate medical management, may well reduce the overall risk of cardiovascular morbidity. When diagnosed early, both exercise and pharmacotherapy can ameliorate symptoms of claudication. augment functional performance, and improve quality of life. This review focuses on the general medical management and specific therapeutic options. Because PAD is a manifestation of generalized atherosclerosis, the principal issue in medical management of PAD is a treatment plan that modifies known risk factors for atherosclerosis and its atherothrombotic complications. All patients with PAD should be receiving antiplatelet therapy to prevent ischemic events and ACE inhibitors should be used if appropriate. Medical treatment for patients with claudication includes exercise in rehabilitation and drug therapy. It is also recognized that selected patients with claudication symptoms may benefit from catheter-based interventions, and most PAD patients with critical leg ischemia require revascularization procedures. Although many therapies for claudication have been thoroughly investigated, research continues on new treatments. In contrast, more prospective, randomized trials are needed to evaluate various therapies for treating patients with PAD.

Arterial Occlusive Diseases↗
PubMed1993

The Nordic Diltiazem Study (NORDIL). A prospective intervention trial of calcium antagonist therapy in hypertension.

NORDIL--the Nordic diltiazem intervention study was started in September 1992. This trial is a prospective randomized open blinded-endpoint (PROBE) multicenter, parallel-group study conducted in Norway and Sweden. The study is designed to evaluate the potential preventive effects of diltiazem compared with conventional antihypertensive drug treatment. Primary endpoints are cardiovascular mortality defined as fatal acute myocardial infarction, fatal acute cerebrovascular disease (stroke), sudden death and other fatal cardiovascular disease as well as cardiovascular morbidity defined as myocardial infarction and cerebrovascular disease (stroke). Secondary endpoints are total mortality, the development or deterioration of ischaemic heart disease, congestive heart failure, atrial fibrillation, transient ischaemic attacks, diabetes mellitus and renal insufficiency. Male and female patients, aged 50-69, with primary hypertension are randomly allocated to therapy starting with either diltiazem (180-360 mg daily) or conventional treatment (diuretics or beta-adrenergic blockers). Add-on therapy in the conventional treatment group excludes all types of calcium antagonists. The goal of treatment will be a target diastolic blood pressure of < or = 90 mmHg or a 10% diastolic blood pressure reduction. The NORDIL study will allow the detection of a 20% difference in cardiovascular mortality between the two groups with a power of 80% at the 5% significance level (two-sided test). A total of 12,000 patients will be recruited from about 480 primary Health Care Centers or hospital based Hypertension Units. Patients will be treated for an average period of 5 years.

Aged↗
PubMed1977

Prevalence of angina pectoris and myocardial infarction in a general population sample of Swedish men.

A primary preventive trial against cardiovascular diseases has been in progress since 1970 in Göteborg, Sweden. The study population comprises all men in the city born in 1915-22 and 1924-25, a total of about 30 000 men. One third of this population constitutes the intervention group. The prevalence of angina pectoris and myocardial infarction among men aged 47-53 years has been studied in this group. The cases were identified by means of a postal questionnaire, direct interview at screening examination and by clinical examination. A validation of the postal questionnaire technique gave a sensitivity of 74% and a specificity of 94%. The minimum prevalence of angina pectoris amounted to 4.3% and the prevalence of myocardial infarction to 1.6%. In the angina series, 22% had suffered a myocardial infarction that preceded angina pectoris in 9%.

Angina Pectoris↗
PubMed1990

Serum-manganese-superoxide dismutase: normal values and increased levels in patients with acute myocardial infarction and several malignant diseases determined by an enzyme-linked immunosorbent assay using a monoclonal antibody.

An enzyme-linked immunosorbent assay (ELISA) has been developed for human manganese-superoxide dismutase (Mn-SOD), using a specific monoclonal antibody raised against the purified enzyme. The Mn-SOD molecule comprises four identical sub-units and this permitted the development of a symmetrical assay, using the same monoclonal antibody as both capture and detector. The assay offers a specific, sensitive and convenient means of measuring immunoreactive Mn-SOD in human sera. Under optimum conditions, the sensitivity of the assay permits the detection of 2-200 ng of purified Mn-SOD from human liver. The mean serum Mn-SOD levels of normal healthy males and females were 99.8 +/- 24.8 (mean +/- SD) and 88.8 +/- 20.8 (mean +/- SD), respectively. A high level of the enzyme was found in the sera of patients with acute myocardial infarction as well as malignant diseases such as acute myeloid leukemia, primary hepatoma and gastric cancer. This is the first report of an ELISA using a monoclonal antibody specific for a distinct epitope of Mn-SOD.

Adult↗
PubMed1976

Thromboembolic disease in renal allograft recipients. What is its clinical significance?

Detailed analysis of the clinical data and autopsy material of 100 consecutive renal transplant recipients revealed significant thromboembolic disease in 25 patients and a total of 41 complications. In six of them, thromboembolism was associated with sepsis. Nine patients died (20% of total number of deaths) due to a primary thromboembolic event. The incidence of pulmonary embolism was 14%; myocardial infarction, 3%; cerebrovascular disease, 4%; renal artery thrombosis, 2%; renal vein thrombosis, 3%; thrombophlebitis/deep vein thrombosis, 13%; and miscellaneous, 2%. The incidence of thromboembolism was higher in patients older than 40 years of age (P = .02) and during the earlier months after transplantation. We summarize the general incidence and mortality related to thromboembolism and discuss the factors predisposing the graft recipient to thromboembolic disease. Prevention and therapy of this complication should decrease the morbidity and mortality in graft recipients and enhance the success of renal transplantation.

Adolescent↗
PubMed1976

[Manifestations of cardiac decompensation in myocardial infarct].

A study of the causes of mortality among myocardial infarction patients and of the peculiarities of the manifestations of cardiac decompensation was conducted by way of mathematical prognosing and with the aid of the "Mmirp-1" computer, and permitted to conclude on the necessity of distinguishing between the primary circulatory insufficiency in the acute period, and relapsing circulatory disorders. The prognosis in myocardial infarction permits indirect appraisal of the reserve capacities of the diseased heart. The results of the conducted study indicate that the primary circulatory disorders are 6 times as frequent as the relapsing ones and that half of the patients with signs of circulatory failure dies within the first day of the disease. The long-term prognosis is equally unfavourable for the patients with circulatory insufficiency signs in the acute period: by the end of the 2nd year only 4 of every 10 patients with primary circulatory disorders survive, and 1--2 of every 10 patients with signs of relapsing circulatory disorders, which should be taken into consideration when developing the methods of complex therapy.

Acute Disease↗
PubMed2005

Determinants of coronary events in patients with stable angina: results from the impact of nicorandil in angina study.

BACKGROUND: IONA was a randomized trial of nicorandil (20 mg twice daily) versus placebo in 5126 patients with stable angina of effort. We present the characteristics as measured at baseline that were found to be associated with increased risk of major outcomes. METHODS: The primary end point of the study was coronary heart disease death, nonfatal myocardial infarction (MI), or unplanned hospitalization for cardiac chest pain. The secondary outcome excluded the softer outcome of unplanned hospitalization for chest pain. Potential prognostic factors included nicorandil treatment, sex, smoking, severity of angina (Canadian Cardiovascular Society [CCS] grading), previous MI, coronary artery bypass graft/percutaneous transluminal coronary angioplasty (CABG/PTCA), left ventricular dysfunction, left ventricular hypertrophy (LVH) on electrocardiography (ECG), histories of diabetes or hypertension, baseline cardiovascular drugs, age, blood pressures, heart rate, height, weight, and body mass index. RESULTS: A total of 5047 patients had complete baseline information. There were 724 primary outcomes and 240 secondary outcomes. The strongest determinants of the hard secondary end point were CCS score (hazards ratio [HR] 2.25, 95% confidence intervals [CI] 1.50-3.38) for grades III and IV versus grade I, age (HR 1.23, 95% CI 1.13-1.33) for 5-year risk, and previous MI (HR 2.05, 95% CI 1.48-2.85). The results for the primary outcome were similar, with stronger associations with LVH on ECG and smoking, and a weaker association with age. CONCLUSIONS: We present models of risk factors for coronary outcomes in a population with angina of effort. The strongest risk factors were the CCS score and previous MI.

Aged↗
PubMed1998

High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor.

BACKGROUND: In patients with established ischemic heart disease, prospective cohort studies have indicated that plasminogen activator inhibitor (PAI-1), the inhibitor of the fibrinolytic system, may predict cardiovascular events. So far, there have been no primary prospective studies of PAI-1. METHODS AND RESULTS: The aim of the present study was to test whether plasma levels of PAI-1, tissue-type plasminogen activator (tPA), von Willebrand factor (vWF), and thrombomodulin (TM) could predict the occurrence of a first acute myocardial infarction (AMI) in a population with high prevalence of coronary heart disease by use of a prospective nested case-control design. Mass concentrations of PAI-1 and tPA were significantly higher for the 78 subjects who developed a first AMI compared with the 156 references matched for age, sex, and sampling time; for tPA, this increase was independent of smoking habits, body mass index, hypertension, diabetes, cholesterol, and apolipoprotein A-I. The ratio of quartile 4 to 1 for tPA was 5.9 for a patient to develop a first AMI. The association between tPA and AMI was seen in both men and women. Increased levels of vWF were associated with AMI in a univariate analysis. High levels of TM were associated with AMI in women but not in men. CONCLUSIONS: The plasma levels of PAI-1, tPA, and vWF are associated with subsequent development of a first AMI; for PAI-1 and tPA, this relation was found in both men and women. For tPA but not for PAI-1 and vWF, this association is independent of established risk factors.

Adult↗
PubMed2005

Apoptotic myocardial cell death in the setting of arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary heart muscle disease characterized by progressive atrophy of the right ventricular myocardium accompanied by fibro-fatty replacement. We examined whether the loss of myocardial cells in the setting of ARVC could result from cell death by apoptosis as demonstrated by the detection of DNA fragmentation and the expression of apoptosis regulatory proteins (e.g. CPP-32, Bcl-2, and Bax). METHODS: Specimens obtained from the right ventricular myocardium of 11 patients with ARVC (ARVC group) and 10 age-matched normal individuals (control group) were analysed. To identify individual cells undergoing apoptosis, paraffin sections were examined with the TdT-mediated dUTP-biotin nick end labelling method (TUNEL) and the rabbit polyclonal anti-single stranded DNA method (ssDNA). The apoptotic index was calculated as the percentage of nuclei staining positive by the TUNEL or ssDNA method. We also used immunohistochemical techniques to examine the levels of CPP-32, Bcl-2, and Bax expression. RESULTS: Apoptosis was detected in the ARVC group with a mean apoptotic index of 5.7 +/- 4.5% (ssDNA) and 23.8 +/- 7.5% (TUNEL), but not in the control group (p < 0.01). CPP-32 expression and Bax overexpression were observed in the ARVC group. However, Bcl-2 expression was not seen in either group. CONCLUSIONS: Apoptotic myocardial cell death occurs in the setting of ARVC and may contribute to the loss of myocardial cells.

Adult↗
PubMed1981

Spectrum of congestive heart failure late after aortic valve or mitral replacement: differentiation of valvular versus myocardial cause by radionuclide ventriculogram-ejection fraction.

Heart failure (CHF) appearing late after aortic (AV) or mitral valve (MV) replacement (R) may be due to mechanical factors such as prosthetic or native dysfunction, or due to myocardial disease. We studied 41 patients who developed CHF late (6 weeks to 11 years) after AVR or MVR with gated blood pool scan (RNV) to analyze the spectrum of ejection fraction (EF) and its clinical correlates. Of the 17 patients who developed CHF after AVR, 10 had RNV EF greater than 0.5 (all of whom had severe valve or prosthetic dysfunction as the primary cause of CHF) and seven had EF less than 0.5 (five with severe myocardial disease and two with prosthetic dysfunction). Of the 24 with CHF after MVR, 13 had RNV EF greater than 0.5. In contrast to post-AVR patients, only 8 of the 13 patients had mechanical causes of CHF (seven prosthetic dysfunction and one constrictive pericarditis). Of the 11 patients after MVR with EF less than 0.5, nine had severe myocardial disease and two had prosthetic dysfunction. Thus (1) reduced EF in patients and CHF-after AVR or MVR suggests myocardial disease as the basis for CHF, and (2) normal EF implies a mechanical cause of CHF after AVR but may be associated with either myocardial or mechanical factors after MVR.

Adult↗