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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↗

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↗

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↗

The ALLHAT-LLT and ASCOT-LLA trials: are the discrepancies more apparent than real?

During the past decade, numerous landmark trials of statins in secondary and primary prevention and their meta-analyses have demonstrated statistically significant and clinically important reductions in myocardial infarction, stroke, and vascular death (by about one third), as well as total mortality (by about one fifth). In the past year, two trials of statins have been reported among hypertensive subjects enrolled in blood pressure-lowering trials, one in the United States and the other in Europe. The US trial, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial--Lipid Lowering Trial (ALLHAT-LLT), was reported as showing no significant benefit. In contrast, the European trial, the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA), was terminated early based on the unanimous recommendation of the Data and Safety Monitoring Board, due principally to the emergence of a statistically extreme 36% reduction in the primary endpoint of nonfatal myocardial infarction and death from coronary heart disease (P<0.0005). These trial results have been viewed as discrepant, but methodologic issues of inadequate power of ALLHAT due to lower than projected sample size and poor compliance due to an open design render these discrepancies more apparent than real. The ALLHAT-LLT trial should be viewed not as null, but as uninformative, as the 95% confidence limits around the point estimate include the most plausible small to moderate benefit of statins. The totality of evidence on statins continues to strongly support their benefits in a wide range of patients on a large number of cardiovascular disease endpoints.

Antihypertensive Agents↗

Two- to three-year follow-up of patients with single-vessel coronary artery disease randomized to PTCA or medical therapy (results of a VA cooperative study). Veterans Affairs Cooperative Studies Program ACME Investigators. Angioplasty Compared to Medicine.

Despite increasing use of percutaneous transluminal coronary angioplasty (PTCA) to treat stenotic coronary artery disease, there are relatively few prospective studies evaluating its long-term effectiveness. We prospectively randomized 212 stable patients with provocable myocardial ischemia and single-vessel subocclusive coronary disease to receive primary therapy with either PTCA or medical therapy. This report presents the clinical follow-up of these patients at a mean, after randomization, of 2.4 years for interview and 3.0 years for exercise testing. Of the 212 patients originally randomized, 175 received an extended follow-up interview, and 132 underwent exercise testing; 62% of patients in the PTCA group were angina free compared with 47% of patients in the medical group (p <0.05). Furthermore, exercise duration as measured by treadmill testing was prolonged by 1.33 minutes over baseline in the PTCA group, whereas it decreased by 0.28 minutes in the medical group (p <0.04). Although the angina-free time on the treadmill was not different (p=0.50), fewer patients in the medical group developed angina on the treadmill at 3 years than those in the PTCA group (p=0.04). By 36 months, excluding the initial randomized PTCA, use of PTCA and use of coronary artery bypass surgery were not different in the 2 treatment groups. These data indicate that some of the early benefits derived from PTCA in patients with single-vessel coronary artery disease are sustained, making it an attractive therapeutic option for these patients.

Adrenergic beta-Antagonists↗

Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies.

Chronic kidney disease (CKD) is a major public health problem. Conflicting evidence exists among community-based studies as to whether CKD is an independent risk factor for adverse cardiovascular outcomes. After subjects with a baseline history of cardiovascular disease were excluded, data from four publicly available, community-based longitudinal studies were pooled: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Serum creatinine levels were indirectly calibrated across studies. CKD was defined by a GFR between 15 and 60 ml/min per 1.73 m(2). A composite of myocardial infarction, fatal coronary heart disease, stroke, and death was the primary study outcome. Cox proportional hazards models were used to adjust for study, demographic variables, educational status, and other cardiovascular risk factors. The total population included 22,634 subjects; 18.4% of the population was black, and 7.4% had CKD. There were 3262 events. In adjusted analyses, CKD was an independent risk factor for the composite study outcome (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07-1.32), and there was a significant interaction between kidney function and race. Black individuals with CKD had an adjusted HR of 1.76 (95% CI, 1.35-2.31), whereas whites had an adjusted HR of 1.13 (95% CI, 1.02-1.26). CKD is a risk factor for the composite outcome of all-cause mortality and cardiovascular disease in the general population and a more pronounced risk factor in blacks than in whites. It is hypothesized that this effect may be due to more frequent or more severe subclinical vascular disease secondary to hypertension or diabetes in black individuals.

Black People↗

Yoga in cardiac health (a review).

This review studies the efficacy of yoga in the primary and secondary prevention of ischaemic heart disease and post-myocardial infarction patient rehabilitation. Yoga is an unconventional form of physical exercise that has been practised over a long period of time in the Indian sub-continent. It has gained immense popularity as a form of recreational activity all over the world. Its possible contributions to healthy living have been studied and many interesting revelations have been made. Benefits of yoga in the modification of cardiovascular risk factors and in the rehabilitation of the post-myocardial infarction patient are areas of significant importance. It is important to assess the practical significance and the suitability of incorporating yoga into the comprehensive cardiac rehabilitation programme. Majority of the rehabilitation workers believes that incorporating nonconventional forms of physical exercise such as yoga definitely would enhance efficacy and add value. This article attempts to study the history and the science of yoga and evaluate its effects on cardiovascular health.

Diabetes Mellitus↗

Doxazosin and congestive heart failure.

Doxazosin remains a commonly used antihypertensive medication, although its use has been tainted by recent findings from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT was a large, simple trial, designed in a fashion to closely mimic clinical practice as it occurs in high-risk hypertensive patients aged 55 years or older. Its goals were to determine whether the incidence of the primary outcome--a composite of fatal coronary heart disease and nonfatal myocardial infarction--differed between treatment with a diuretic (chlorthalidone) (12.5-25.0 mg/day) and treatment with each of three other types of antihypertensive drugs-a calcium-channel blocker (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), and a peripheral alpha-adrenergic blocker (doxazosin) (2-8 mg/day). Doxazosin was recently withdrawn from this trial after an interim analysis showed the secondary end point of combined cardiovascular disease to be 25% greater in patients on doxazosin than in those assigned to treatment with chlorthalidone. This finding was largely driven by congestive heart failure. The practicing clinician should not abandon doxazosin completely because of the ALLHAT findings, although these findings are indisputably important. These results represent an interim analysis and their application to clinical practice needs to occur carefully. A valued member of our therapeutic armamentarium need not be laid entirely to rest; rather, doxazosin should now be viewed as a secondary or tertiary antihypertensive therapy pending a more complete review of the ALLHAT data.

Adrenergic alpha-Antagonists↗

[Thormboembolisms and heart ruptures in myocardial infarct].

An analysis of the incidence of thromboembolism and heart ruptures with reference to different causative factors was conducted on the basis of 585 patients dying of myocardial infarction during the recent 30 years (autopsy data) and 1417 patients with myocardial infarction (298 mortality cases among them) hospitalized during the recent 10 years. A reduction of the incidence of thromboembolism and an increase of the incidence of heart ruptures in the recent years were revealed. Thromboembolism and heart ruptures play an important role among the causes of mortality in myocardial infarction. The development of thromboembolism in myocardial infarction is favoured by the macro-focal nature of the heart lesion, repeated necroses of the myocardium, localization of infarction in the posterior and posteriolateral zones, old age of the patients (over 60), presence of diabetes mellitus and acute cardiac aneurysm. Thromboembolism occurs with the same incidence rate within the initial 7 days, and later during the acute phase. Thrombi are most often found in the cardiac cavities, pulmonary, renal and splenic vessels, in the cerebral, mesenteric and other vessels. Heart ruptures are favoured by the macro-focal nature of the cardiac lesion, localization of the infarction in the anterior and anteriolateral zones, old age (over 60), presence of acute cardiac aneurysm. Most frequently the ruptures are observed in primary myocardial infarction within the initial 5--7 days of the disease. The use of anticoagulants in myocardial infarction decreases the incidence of thromboembolic complications and heart ruptures.

Aged↗

Risk reduction strategies in coronary artery disease.

The growing knowledge of the basic science of the atherosclerotic plaque, the identification of modifiable risk factors, and the development of the effective medical therapies have provided the physician with powerful tools to alter the course of atherosclerotic disease in the post myocardial infarction patient. Lipids have emerged as a primary target for modification in addition to attention to traditional lifestyle modification such as smoking cessation, diet, and exercise. This article reviews lipid management as well as therapy and goals. Traditional and some "new" risk factors are also addressed. The risk of subsequent events in the post myocardial infarction patient can be dramatically altered, thus the patient who follows suggested guidelines can expect to have improved quality and quantity of life after an infarction.

Cholesterol, HDL↗

Treatment of peripheral arterial disease.

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis strongly associated with cardiovascular (CV) morbidity and mortality. Approximately 12% of the US adult population is affected. Despite its prevalence, the disease has received little attention from clinicians. The primary causes of death in patients with PAD are myocardial infarction and stroke; thus, current treatment strategies for symptomatic PAD include aggressive modification of risk factors for CV disease such as cessation of smoking, treatment of hypertension and diabetes, and normalization of low-density lipoprotein cholesterol levels. All patients with PAD should be receiving antiplatelet therapy to prevent ischemic events. Medical treatment for patients with claudication includes exercise rehabilitation and drug therapy. 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.

Arteriosclerosis↗

[Epidemiology of sudden cardiac death in Spain].

Sudden cardiac death is a remarkable public health problem though its incidence in Spain is lower than in other industrialised countries. Approximately 12% of all natural deaths occur suddenly, and 88% of them are of cardiac origin. This is the form of death in more than 50% of coronary heart disease patients. Moreover, it is the first symptom in 19-26% of cases. This close relationship with coronary heart disease results in cardiovascular risk factors being also risk factors for sudden death. Several factors, such as physical activity or certain drugs may act as sudden death triggers. The more effective strategy addressed to sudden cardiac death prevention includes identification high-risk subgroups of patients (i.e. patients with previous coronary heart disease, heart failure, out-of-hospital sudden death survivors and patients who developed a ventricular fibrillation or tachycardia after a myocardial infarction) and development of efficacious therapeutic interventions. Given that most sudden death are related to coronary heart disease, those primary preventive measures directed to reduce the coronary heart disease incidence rates will also prevent sudden cardiac deaths in population. Finally, community programs directed to reduce the time to reach cardiac emergencies by trained personnel, and to train general population in cardio-respiratory reanimation have shown to be efficacious owing to the fact that most sudden cardiac deaths occur out of hospitals.

Adult↗

[Myocardial disease in diabetes mellitus].

Diabetes mellitus is associated with excessive cardiovascular morbidity and mortality. Patients with diabetes mellitus suffer premature and severe atherosclerosis, and the relative impact is greater in women than in men. Clinical, experimental and pathological studies support the existence of a specific cardiomyopathy associated with diabetes mellitus. The cardiomyopathy plays an essential role in the pathogenesis of primary myocardial involvement, resulting in ventricular dysfunction, diminished cardiac pump performance and eventually overt heart failure. The authors discuss coronary heart disease and diabetic cardiomyopathy and indicate relevant treatment regimens.

Cardiomyopathies↗

[Cardiovascular risk factors in persons aged 40-42 years in the county of Hedmark 1988-94].

We present the results from three surveys conducted in 1988, 1991 and 1994 in Hedmark comparing risk factors for cardiovascular disease among men and women age 40-42 years. The data are compared with the results for persons in the same age group from the counties Vestfold, Rogaland and Nordland, and examined in the same periods. In 1991 the average levels of total cholesterol and infarction risk score were the same in Hedmark and the three other counties, but in 1994 Hedmark compared less favourably. While the mean levels of total cholesterol showed minimal difference between rural and urban municipalities in Hedmark, triglycerides and systolic blood pressure were higher in the rural areas. Adjustment of the results in Hedmark for lower attendance rate among unmarried, divorced and widowed persons in 1991 and 1994 than in 1988 does not affect other risk factors than smoking. We discuss possible explanations of the less favourable results and the implications for primary prevention of cardiovascular diseases.

Adult↗

How effective are rapid access chest pain clinics? Prognosis of incident angina and non-cardiac chest pain in 8762 consecutive patients.

OBJECTIVE: To determine whether rapid access chest pain clinics are clinically effective by comparison of coronary event rates in patients diagnosed with angina with rates in patients diagnosed with non-cardiac chest pain and the general population. DESIGN: Multicentre cohort study of consecutive patients with chest pain attending the rapid access chest pain clinics (RACPCs) of six hospitals in England. PARTICIPANTS: 8762 patients diagnosed with either non-cardiac chest pain (n = 6396) or incident angina without prior myocardial infarction (n = 2366) at first cardiological assessment, followed up for a median of 2.57 (interquartile range 1.96-4.15) years. MAIN OUTCOME MEASURES: Primary end point--death due to coronary heart disease (International Classification of Diseases (ICD)10 I20-I25) or acute coronary syndrome (non-fatal myocardial infarction (ICD10 I21-I23), hospital admission with unstable angina (I24.0, I24.8, I24.9)). Secondary end points--all-cause mortality (ICD I20), cardiovascular death (ICD10 I00-I99), or non-fatal myocardial infarction or non-fatal stroke (I60-I69). RESULTS: The cumulative probability of the primary end point in patients diagnosed with angina was 16.52% (95% confidence interval (CI) 14.88% to 18.32%) after 3 years compared with 2.73% (95% CI 2.29% to 3.25%) in patients with non-cardiac chest pain. Coronary standardised mortality ratios for men and women with angina aged <65 years were 3.52 (95% CI 1.98 to 5.07) and 4.39 (95% CI 1.14 to 7.64). Of the 599 patients who had the primary end point, 194 (32.4%) had been diagnosed with non-cardiac chest pain. These patients were younger, less likely to have typical symptoms, more likely to be south Asian and more likely to have a normal resting electrocardiogram than patients with angina who had the primary end point. CONCLUSION: RACPCs are successful in identifying patients with incident angina who are at high coronary risk, but there is a need to reduce misdiagnosis and improve outcomes in patients diagnosed with non-cardiac chest pain who accounted for nearly one third of cardiac events during follow-up.

Angina Pectoris↗