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Primary heart disease in systemic sclerosis (scleroderma): advances in clinical and pathologic features, pathogenesis, and new therapeutic approaches.

Heart disease in SSCL may be primary or secondary. Primary involvement includes pericarditis, myocardial fibrosis, and contraction band necrosis with congestive cardiomyopathy, conduction system fibrosis, intramural coronary artery lesions and, rarely, valvular disease. Symptoms include those of left and right ventricular failure, chest pain, palpitations, syncope, and sudden death. Pathogenesis may be related to functional Raynaud's phenomenon of the heart and/or structural small vessel disease. Therapy at present is symptomatic; however, new therapeutic approaches are warranted.

Coronary Vessels↗

Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction.

BACKGROUND: Patients with acute myocardial infarction who were treated with accelerated tissue plasminogen activator (t-PA) (given over a period of 1 1/2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day mortality that was 15 percent lower than that of patients treated with streptokinase in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study. This was equivalent to an absolute decrease of 1 percent in 30-day mortality. We sought to assess whether the use of t-PA, as compared with streptokinase, is cost effective. METHODS: Our primary, or base-case, analysis of cost effectiveness used data from the GUSTO study and life expectancy projected on the basis of the records of survivors of myocardial infarction in the Duke Cardiovascular Disease Database. In the primary analysis, we assumed that there were no additional treatment costs due to the use of t-PA after the first year and that the comparative survival benefit of t-PA was still evident one year after enrollment. RESULTS: One year after enrollment, patients who received t-PA had both higher costs ($2,845) and a higher survival rate (an increase of 1.1 percent, or 11 per 1000 patients treated) than streptokinase-treated patients. On the basis of the projected life expectancy of each treatment group, the incremental cost-effectiveness ratio--with both future costs and benefits discounted at 5 percent per year--was $32,678 per year of life saved. The use of t-PA was least cost effective in younger patients and most cost effective in older patients. At all ages, the use of t-PA in patients with anterior infarctions yielded more favorable cost-effectiveness values. In our secondary analyses, the cost-effectiveness values were most sensitive to a lowering of the projected long-term survival benefits of t-PA and to moderate or greater increases in the projected medical costs for patients in the t-PA group after the first year. In contrast, our results were not sensitive to even very unfavorable assumptions about the additional costs associated with the higher rate of disabling stroke that was noted in patients treated with t-PA in the GUSTO study. CONCLUSIONS: The cost effectiveness of treatment with accelerated t-PA rather than streptokinase compares favorably with that of other therapies whose added medical benefit for dollars spent is judged by society to be worthwhile.

Adult↗

Codon 54 polymorphism of the fatty acid binding protein (FABP) 2 gene is associated with increased cardiovascular risk in the dyslipidemic diabetic participants of the Veterans Affairs HDL intervention trial (VA-HIT).

The threonine (Thr) for alanine (Ala) codon 54 polymorphism of the fatty acid binding protein (FABP) 2 gene, when compared to the wild type, is associated with dyslipidemia. Since dyslipidemia is common in diabetes and is associated with increased cardiovascular risk, we tested the hypothesis that Thr-54 is associated with increased cardiovascular risk in patients with diabetes. The secondary prevention veterans affairs HDL intervention trial (VA-HIT) was carried out in patients with dyslipidemia. The DNA of trial participants (n=776) was screened for the Thr-54 polymorphism and cardiovascular endpoints were monitored. The polymorphism was detected in 370 (47.7%). For first occurrence of the primary endpoint [myocardial infarction (MI) or coronary heart disease (CHD) death] the hazard ratio (HR) and confidence intervals (Cox proportional hazards model) was 2.5 (1.2, 5.3) p=.02 in diabetic carriers of Thr-54 versus carriers without diabetes or fasting glucose >7 mmol/L. For the expanded endpoint (stroke, MI or CHD death), the corresponding HR was 3.0 (1.4, 5.4) p=.0003 and for the stroke alone the corresponding HR was 3.5 (1.4-8.9) p=.01. The higher cumulative incidence of the expanded endpoint in diabetic participants carrying the FABP2 polymorphism versus non-diabetic carriers was consistently present throughout the 5 years of the study (p=.0002). We conclude that based on the VA-HIT data, the Thr-54 polymorphism of the FABP2 gene is associated with a 2-3.5-fold increase in cardiovascular risk in dyslipidemic men with diabetes compared to their non-diabetic counterparts.

Aged↗

Description and status of the azithromycin and coronary events study (ACES).

The Azithromycin and Coronary Events Study is a randomized, double-blind, placebo controlled trial of azithromycin among adults with stable coronary artery disease. The study is based on the hypothesis that infection with Chlamydia pneumoniae may be causally associated with cardiovascular disease and therefore that treatment directed against this organism may reduce the risk of subsequent coronary events. Participants randomized to treatment will receive 600 mg of azithromycin orally once a week for 1 year and will be followed a mean of 4 years for the composite primary outcome of coronary heart disease death, nonfatal myocardial infarction, hospitalization for unstable angina, and coronary revascularization. Secondary objectives include those related to a better understanding of the relationship between antibody titer and inflammatory markers with treatment status and outcome; therefore, all participants will have blood specimens obtained at enrollment and a random 25% will have additional specimens collected periodically during follow-up.

Adult↗

Baseline Characteristics of Participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

-Diuretics and ss-blockers have been shown to reduce the risk of cardiovascular morbidity and mortality in people with hypertension in long-term clinical trials. No study has compared newer more costly antihypertensive agents (calcium antagonists, ACE inhibitors, and alpha-adrenergic blockers) with diuretics for reducing the incidence of cardiovascular disease in an ethnically diverse group of middle-aged and elderly hypertensive patients. The study is a randomized, double-blind, active-controlled clinical trial designed to determine whether the incidence of the primary outcome, fatal coronary heart disease or nonfatal myocardial infarction, differs between treatment initiation with a diuretic versus each of 3 other antihypertensive drugs. Men and women aged >/=55 years with at least 1 other cardiovascular disease risk factor were randomly assigned to chlorthalidone (12.5 to 25 mg/d), amlodipine (2.5 to 10 mg/d), lisinopril (10 to 40 mg/d), or doxazosin (2 to 8 mg/d) for planned follow-up of 4 to 8 years. This report describes the baseline characteristics of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants. A total of 42 448 participants were randomized from 625 sites in the United States, Canada, Puerto Rico, and the US Virgin Islands. The mean age was 67 years, with 35% aged >/=70 years. Among those randomized, 36% were black, 19% were Hispanic, and 47% were women. The sample includes a high proportion of people with diabetes (36%), patients with existing cardiovascular disease (47%), and smokers (22%). There were no important differences between the randomized treatment groups at baseline. ALLHAT will add greatly to our understanding of the management of hypertension by providing an answer to the following question: are newer antihypertensive agents similar, superior, or inferior to traditional treatment with diuretics?

Journal Article↗

Thienopyridines or aspirin to prevent stroke and other serious vascular events in patients at high risk of vascular disease? A systematic review of the evidence from randomized trials.

BACKGROUND AND PURPOSE: Aspirin is the most widely studied and prescribed antiplatelet drug for patients at high risk of vascular disease. We aimed to establish how the thienopyridines (ticlopidine and clopidogrel) compare with aspirin in terms of effectiveness and safety. METHODS: We did a systematic review of all unconfounded randomized trials comparing either ticlopidine or clopidogrel with aspirin for patients at high risk of vascular disease. The primary outcome was vascular events (stroke, myocardial infarction, or vascular death). Adverse outcomes were intracranial and extracranial hemorrhage, upper and lower gastrointestinal disturbances, neutropenia, thrombocytopenia, and skin rash. RESULTS: In 4 trials among 22 656 patients (including 9840 presenting with a transient ischemic attack/ischemic stroke), the thienopyridines reduced the odds of a vascular event by 9% (odds ratio 0.91, 95% CI 0.84 to 0. 98; 2P=0.01), preventing 11 (95% CI 2 to 19) events per 1000 patients treated for approximately 2 years. The thienopyridines produced significantly less gastrointestinal hemorrhage and upper gastrointestinal upset (indigestion/nausea/vomiting) than did aspirin. Both thienopyridines increased the odds of skin rash and of diarrhea (ticlopidine by approximately 2-fold and clopidogrel by approximately one third). Only ticlopidine increased the odds of neutropenia. CONCLUSIONS: The thienopyridines appear modestly more effective than aspirin in preventing serious vascular events in high-risk patients. Clopidogrel appears to be safer than ticlopidine and as safe as aspirin, making it an appropriate, but more expensive, alternative antiplatelet drug for patients unable to tolerate aspirin. However, there is insufficient information to determine which particular types of patients would benefit most, and which least, from clopidogrel instead of aspirin.

Aspirin↗

[The peculiarities of cardial arrhythmias in patients with type 2 diabetes].

The aim of the study was to clarify the pathogenetic mechanisms of arrhythmias in patients with diabetes mellitus type 2 (DM 2), and the role of diabetic factors in their onset. A comparative analysis of arrhythmias was performed in 212 cardiological patients, 114 of whom had DM 2, and 98 did not. The character of concomitant pathology was similar: the patients had primary arterial hypertension, coronary heart disease, and no myocardial infarction background. The study found that the frequency of more severe and prognostically unfavorable arrhythmias was higher in the DM 2 subgroup; these arrhythmias were associated with the compensation of carbohydrate metabolism according to the level of glycated hemoglobin (HbA(1c), immunoreactive insulin (IRI), and C-peptide. Severe metabolism decompensation (HbA(1c) > 8.5%) was more often associated with ventricular arrhythmias and low IRI and C-peptide levels, whereas relatively low (< 7.0%) HbA(1c) level was associated with supraventricular arrhythmias and elevation of IRI and C-peptide levels. Arrhythmias in DM 2 were also associated with left ventricular geometric anomalies, revealed by means of electrocardiography.

Arrhythmias, Cardiac↗

[X-ray computed tomographic diagnosis of primary cardiac malignant lymphoma in AIDS].

Primary lymphomas rarely affect the heart. The myocardial disease is usually latent and the diagnosis is based on post mortem observations. The cardiac symptoms do not reveal the disease and symptomatology is not specific. Our observation shows the complementarity of non invasive techniques, for a better screening of cardiac tumoral forms. Although echocardiography is the main examination, CT scan provides a detection of infiltrative forms and of extracardiac extension. Concurrently, MRI remains the method of choice to display beginning infiltrative forms, revealed by pericardial effusion in AIDS disease.

Aged↗

[Cardiopathy in systemic sclerosis].

Cardiac involvement is quite frequent in systemic sclerosis (SSc). From a pathophysiologic point of view, one must differentiate a primary scleroderma heart disease due to pericardial and/or myocardial and/or small coronary intramyocardial vessel involvement from heart disease secondary to either pulmonary interstitial or vascular involvement (pulmonal cor) or to kidney disease (hypertensive myocardial disease). A significant difference emerges when the prevalence of clinically and standard ECG detected cardiac involvement in SSc patients is compared with that registered at autopsy. In the last years, however, Holter ECG, echocardiography, perfusional scintigraphy and ventriculography have reduced such gap, a preclinical scleroderma heart disease being detected by such techniques in quite a high percentage of SSc patients. Asymptomatic SSc patients may be found to present small pericardial effusions and/or either fixed (fibrosis) or reversible (vascular disease) or both types thallium defects or a defective cardiac functional reserve. Both clinically evident scleroderma heart disease and ventricular arrhythmias have a poor prognostic significance. Therefore, a complete cardiological work-up must be periodically carried out in SSc patients. Scleroderma heart disease has long been considered a condition difficult to treat. The detection of diastolic abnormalities and of diastolic failure in SSc patients make us able to understand the therapeutic failure of inotropic agents. Recently, captopril has been shown to improve cardiac function in SSc. It might act either on vascular disease or on fibrosis by affecting the remodelling process of the myocardial wall.

Cardiomyopathies↗

Brain cardioembolism. Issues in diagnosis and management.

The diagnosis of cardioembolism is always based on circumstantial evidence. Echocardiography has a limited useful yield and should be reserved for young patients or older patients with clinical heart disease. Primary prophylaxis with anticoagulants appears to be reasonable for patients with acute anterior wall myocardial infarction, rheumatic valvular disease, or dilated cardiomyopathy and, possibly, for those with chronic nonvalvular atrial fibrillation. Secondary prophylaxis (after an initial embolism) is reasonable for the same conditions and, possibly, for mitral valve prolapse. Acute anticoagulation therapy is warranted when a large infarct is excluded by computed tomography 24 hours after a cerebral embolism.

Anticoagulants↗

What ALLHAT tells us about treating high-risk patients with hypertension and hyperlipidemia.

Hypertension and hyperlipidemia are potent cardiovascular risk factors. Treatment can lower blood pressure and reduce events, but the optimal drug for initial hypertension treatment and the benefits of long-term cholesterol reduction on clinical outcomes in understudied hypertensive subpopulations were unknown. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a long-term randomized, multicenter study undertaken to address these questions. In the hypertension component, 42,448 patients with mild-moderate hypertension and 1 or more other coronary risk factors were randomized to initial therapy with chlorthalidone, or to a newer antihypertensive agent--doxazosin (alpha blocker), amlodipine (calcium blocker), or lisinopril (angiotensin-converting enzyme inhibitor). The primary combined endpoint was coronary heart disease mortality or nonfatal myocardial infarction, with secondary endpoints including combinations of mortality, cardiac, and vascular complications. By interim analysis, doxazosin was shown inferior to diuretics in preventing secondary endpoints, resulting in early termination of this arm. There were no differences in primary endpoint frequency in chlorthalidone-amlodipine and chlorthalidone-lisinopril comparisons, but both amlodipine and lisinopril therapy resulted in more secondary events. In the lipid-lowering trial, 10,355 patients enrolled in the hypertensive trial with low-density-lipoprotein levels 100 to 189 mg/dL were randomized to pravastatin or usual care. There was no overall difference in the primary endpoint (total mortality) or most secondary endpoints, with statin therapy reducing stroke and coronary events modestly but nonsignificantly. Subgroup comparisons showed equivalent treatment effects in all groups except blacks, who had greater reduction in total coronary events but more strokes with pravastatin therapy and more strokes with lisinopril treatment.

Antihypertensive Agents↗

Relation of early saphenous vein graft failure to outcomes following coronary artery bypass surgery.

Up to 20% of saphenous vein grafts (SVGs) fail within 2 years of coronary artery bypass grafting (CABG). The long-term effects of early SVG failure on major clinical events remain undefined in contemporary patient populations. We sought to examine the relation between early SVG failure and long-term outcomes after CABG. Using the Duke Cardiovascular Databank, we examined baseline clinical and angiographic characteristics and clinical outcomes among patients who underwent catheterization 1 to 18 months after their first CABG from 1986 to 2004. Patients were classified on the basis of their worst SVG stenosis as having no (<25%), noncritical (25% to 74%), critical (75% to 99%), or occlusive (100%) SVG disease. Our primary outcome measure was the composite of death, myocardial infarction, or repeat revascularization after catheterization. Of 1,243 patients included in the analysis, 27.9% had no, 11.9% had noncritical, 20.8% had critical, and 39.3% had occlusive SVG disease. At 10 years, the corresponding adjusted composite event rates were 41.2%, 56.2%, 81.2%, and 67.1%, respectively (p <0.0001). Most events occurred immediately after catheterization in patients with critical and occlusive SVG disease and were primarily repeat revascularization. On multivariate analysis, critical, nonocclusive SVG disease was the strongest predictor of the composite outcome (hazard ratio 2.36, 95% confidence interval 2.00 to 2.79, p <0.0001). In conclusion, in contemporary clinical practice, early SVG failure is associated with worse long-term outcomes after CABG.

Aged↗

The influence of admission glucose on epicardial and microvascular flow after primary angioplasty.

BACKGROUND: Patients with elevated admission glucose levels may be at increased risk of death after myocardial infarction, independent of other baseline risk factors and more severe coronary artery disease. However, data regarding admission glucose and epicardial and microvascular flow after primary angioplasty is limited. METHODS: Angioplasty was performed in 308 ST-segment elevated myocardial infarction patients. Patients were divided into 3 groups on the basis of admission glucose level: group 1, < 7.8 mmol/L; group 2, (7.8 - 11.0) mmol/L; and group 3, >or= 11.0 mmol/L. RESULTS: Compared with group 1, patients in group 2 and group 3 were more often female and older. Triglycerides (TG) in group 3 were significantly higher than group 1. At angiography, they more frequently had 2-vessel or 3-vessel disease. In the infarct-related artery, there was no relationship between hyperglycemia and thrombolysis in myocardial infarction (TIMI) 3 flow after percutaneous coronary intervention (PCI) (89.7%, 86.0% and 86.3%, P = NS). However, corrected TIMI frame count (CTFC) in group 2 and group 3 were more than group 1. TIMI myocardial perfusion grade (TMPG) 0 - 1 grade among patients with hyperglycemia after PCI were more frequent (30.9% and 29.0% vs 17.3%, P < 0.05). There was less frequent complete ST - segment resolution (STR) and early T wave inversion among patients with hyperglycemia after PCI. CONCLUSION: Elevated admission glucose levels in ST - segment elevation myocardial infarction patients treated with primary PCI are independently associated with impaired microvascular flow. Abnormal microvascular flow may contribute at least in part to the poor outcomes observed in patients with elevated admission glucose.

Adult↗

Serum cholesterol and long-term prognosis in middle-aged men with myocardial infarction and angina pectoris. A 16-year follow-up of the Primary Prevention Study in Göteborg, Sweden.

OBJECTIVE: To compare the role of serum cholesterol in the long-term prognosis of men with a history of myocardial infarction, in men with clinical angina without myocardial infarction, and men without clinical coronary disease. METHODS: In the second screening of the Primary Prevention Study in Göteborg which comprised 7100 men aged 51 to 59 years at baseline in 1974-1977, 314 men with clinical angina but no myocardial infarction at baseline were identified and 195 men who had survived a myocardial infarction for 0 to 19 years (median 3 years). RESULTS: Of the men without clinical coronary disease at baseline and cholesterol at or below 5.2 mmol.l-1, 2.7 per 1000 observation years died from coronary disease compared to 8.5 per 1000 of the men with serum cholesterol of 7.2 mmol.l-1 or more. Corresponding figures for men with angina was 5.5 and 31.0 per 1000 observation years, and for men with prior myocardial infarction 19.8 and 58.3, respectively, per 1000. After adjustment for age, smoking, systolic blood pressure, body mass index and diabetes the risk of coronary death in men with serum cholesterol above 7.2 mmol.l-1 compared to below 5.2 mmol.l-1 was 2.42 (1.66-3.51) in healthy men, 4.82 (1.44-16.09) in men with angina, 2.70 (0.95-7.67) in survivors of myocardial infarction, and 4.07 (1.86-8.91) in the combined group of men with either angina or prior infarction. The strongest effect was seen during the first half of the follow-up, with an adjusted relative risk for high in relation to low serum cholesterol of 8.08 (1.95-33.55) in men with preexisting coronary disease. Non-coronary deaths varied little by serum cholesterol or coronary disease status at baseline. After 16 years, 76% of the healthy men with low cholesterol and 65% of healthy men with cholesterol above 7.2 mmol.l-1 were still alive. Of the men with prior myocardial infarction, 50% in the group with low cholesterol were alive after 16 years, as compared to 21% of those with high cholesterol. CONCLUSION: The long-term absolute risk of death in men with coronary disease and elevated serum cholesterol is very high. Implementation of lipid-lowering strategies shown to be efficacious is important in this high-risk group.

Angina Pectoris↗

[Right ventricular dysplasia and sudden death in young people].

In this study two autoptic cases of right ventricular dysplasia, observed in young and asymptomatic subjects who died suddenly are reported. In these patients, the "primary" myocardial atrophy involved the right ventricle, the right atrium and the conduction system: the sinoatrial node and the internodal pathways (in both cases) and the hisian bifurcation (only in the second case). The primary ventricular dysplasia was always associated with "secondary" transmural hyperplasia of the sub-epicardial fat tissue except for the anterior wall of the pulmonary infundibulum. According to the findings observed, we think that: 1) in all cases of right ventricular dysplasia a careful examination of the conduction system must be performed due to the fact that the lethal arrhythmias can be not only "hyperkinetic" but also "hypokinetic" arrhythmias; 2) right ventricular dysplasia is a dysplastic-congenital disease and transmural fatty hyperplasia depends both on "primary" myocardial atrophy and on the presence of sub-epicardial fat tissue; the latter is related to the age of the patient.

Adult↗

Benefits of physical activity in the prevention of cardiovascular diseases.

Today it is undisputed that physical exercise and sports activity have beneficial effects in the prevention of cardiovascular diseases. Heberden, who in 1772 brilliantly described the clinical manifestations of angina pectoris, anticipated the benefits of physical exercise when he asked whether "chopping wood for 30 min every day would not be a remedy." These beneficial effects have been demonstrated in primary and in secondary prevention after a heart attack or coronary event. Physical rehabilitation enables patients to recuperate quickly, and provides optimal conditions for their reintegration into professional, social, and family life after a temporary incapacity. Since the days of Heberden, physical exercise and rehabilitation of the cardiac patient have acquired great importance in the fight against the risk factors for atherosclerosis, owing to their practical importance and to the many research problems they provoke. The European Society of Cardiology, the French Society of Cardiology, the European Federations, and the French Federation of Cardiology have unanimously recognized the theoretical and practical importance of this issue, and each of these organizations has formed a working group, undertaken clinical research, or assisted cardiac patients with counseling. The Fifth World Congress, held at Bordeaux in 1992, has confirmed the importance of the topics in cardiology that are discussed here. The aim of this general review is to analyze the benefits obtained from physical activity on cardiovascular function, and, in the light of the most recent and important studies, to discuss the effects of physical exercise in the primary and secondary prevention of cardiovascular diseases, particularly of coronary atherosclerosis.

Carbohydrate Metabolism↗

Similar decline in post-myocardial infarction mortality among subjects with and without diabetes.

BACKGROUND: Data from the 1970s and 1980s suggest that the rate of mortality from coronary disease for patients with diabetes has changed less than that for patients without diabetes. We evaluated trends in post-myocardial infarction mortality and morbidity in patients with and without diabetes over a 7-year period from 1990 through 1997, when substantial changes occurred in the management of coronary disease. METHODS: All patients discharged with the primary diagnosis of acute myocardial infarction (MI) from any Veterans Affairs Medical Center in the country between October 1990 and September 1997 were identified. Demographic, comorbid conditions, inpatient, outpatient, mortality, and readmission data were extracted. Mortality, trends in mortality over time, revascularization, readmissions, and length of hospital stay for MI were compared for the group with diabetes and the group without diabetes. Independent predictors of survival using a Cox regression model were examined. RESULTS: We identified 67,889 patients with MI, of whom 17,756 (26%) had diabetes. At 60 days post-MI, there was a 29% higher mortality rate in the group with diabetes (5.2% versus 4.0%, P < 0.001), which increased to 35% at 1 year (16.1% versus 11.9%, P < 0.001). Diabetes was independently associated with increased overall mortality. Age-adjusted 1-year post-MI mortality from 1991 to 1998 had a significant downward trend (4.9% decrease in odds of mortality per year, P < 0.001) regardless of diabetes status. CONCLUSIONS: Patients with diabetes showed a trend toward declining 1-year post-MI mortality rate that was not significantly different from that seen in patients without diabetes. Further work needs to be done to narrow the gap between the two groups.

Aged↗