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Adenosine and cardioprotection in the diseased heart.

Biological and mechanical stressors such as ischemia, hypoxia, cellular ATP depletion, Ca2+ overload, free radicals, pressure and volume overload, catecholamines, cytokines, and renin-angiotensin may independently cause reversible and/or irreversible cardiac dysfunction. As a defense against these forms of stress, several endogenous self-protective mechanisms are exerted to avoid cellular injury. Adenosine, a degradative substance of ATP, may act as an endogenous cardioprotective substance in pathophysiological conditions of the heart, such as myocardial ischemia and chronic heart failure. For example, when brief periods of myocardial ischemia precede sustained ischemia, infarct size is markedly limited, a phenomenon known as ischemic preconditioning. We found that ischemic preconditioning activates the enzyme responsible for adenosine release, ie, ecto-5'-nucleotidase. Furthermore, the inhibitor of ecto-5'-nucleotidase reduced the infarct size-limiting effect of ischemic preconditioning, which establishes the cause-effect relationship between activation of ecto-5'-nucleotidase and the infarct size-limiting effect. We also found that protein kinase C is responsible for the activation of ecto-5'-nucleotidase. Protein kinase C phosphorylated the serine and threonine residues of ecto-5'-nucleotidase. Therefore, we suggest that adenosine produced via ecto-5'-nucleotidase gives cardioprotection against ischemia and reperfusion injury. Also, we found that plasma adenosine levels are increased in patients with chronic heart failure. Ecto-5'-nucleotidase activity increased in the blood and the myocardium in patients with chronic heart failure, which may explain the increases in adenosine levels in the plasma and the myocardium. In addition, we found that further elevation of plasma adenosine levels due to either dipyridamole or dilazep reduces the severity of chronic heart failure. Thus, we suggest that endogenous adenosine is also beneficial in chronic heart failure. We propose potential mechanisms for cardioprotection attributable to adenosine in pathophysiological states in heart diseases. The establishment of adenosine therapy may be useful for the treatment of either ischemic heart diseases or chronic heart failure.

5'-Nucleotidase↗

Relationship of the platelet glycoprotein PlA and fibrinogen T/G+1689 polymorphisms with peripheral arterial disease and ischaemic heart disease.

INTRODUCTION: Genetic variation in plasma fibrinogen and the platelet receptor GP IIIa locus has been independently associated with increased risks of ischaemic heart disease, but there have been few reports on the relationship with peripheral arterial disease. This study determined the risk of peripheral arterial disease and ischaemic heart disease associated with polymorphisms of fibrinogen T/G(+1689) and platelet glycoprotein Pl(A) genes and the effects of cigarette smoking and fibrinogen. MATERIALS AND METHODS: In the 5-year follow-up phase of the Edinburgh Artery Study, 939 subjects (60-79 years) had DNA extracted from a venous blood sample. One hundred sixteen subjects were identified as having angina, 87 a myocardial infarction, 104 had intermittent claudication and 663 subjects comprised a healthy group. RESULTS: Distribution of the fibrinogen genotype was similar across the disease and healthy groups. Logistic regression analyses found no significant association between fibrinogen genotype and ischaemic heart disease and peripheral arterial disease. A lower percentage of claudicants had the Pl(A2) allele (8.3% vs. 15.2%, p=0.025). After adjustment for age and sex, the risk of IC associated with the Pl(A2) was half that of the homozygous Pl(A1) genotype (OR 0.49, 95% CI 0.25, 0.88; p<==0.05). Adjustment for lifetime smoking and fibrinogen levels increased the odds slightly to nonsignificance. CONCLUSIONS: The Pl(A2) genotype was associated with a decreased risk of developing IC. There was no significant relationship between fibrinogen T/G(+1689) genotype and ischaemic and peripheral heart disease in this older population.

Aged↗

[Costs of coronary heart diseases over the remaining life time in coronary heart disease cases--an analysis of the current status of coronary heart disease cases in Germany from the social perspective].

UNLABELLED: Cardiovascular diseases are the major cause of death not only in Germany. Coronary heart diseases result in substantial disability and loss of productivity and contribute to escalating costs of health care. OBJECTIVE: It was our objective to estimate the costs of CHD for the German population from the perspective of the society. The characteristic of this approach is the calculating of costs until the approximated end of life. METHODS: In the study, all health care costs concerning CHD in Germany were allocated to age, sex, health care sector and primary diagnosis on the basis of comprehensive data on morbidity, mortality, direct and indirect costs. For the estimate of indirect costs the human capital approach was taken. Considered as cases were all patients hospitalized in the reference year (1996). The costs of this cohort in 1996 and up to their protected end of life were estimated. It was taken into account that, in comparison to the general population, life expectancy of cases with risk factors or CHD would have been reduced. In calculating indirect costs, gender and age specific unemployment rates were considered. All future costs were discounted by 4% from the reference year onward. RESULTS: Direct costs are approximately 39 billion DM discounted at 4%, indirect costs total 73 billion DM. The average cost per case (including morbidity and mortality) until the approximated end of life is nearly 125,000 DM. CONCLUSION: In our cost analysis, the indirect costs are higher than the direct costs. For the future, it will be important to estimate the costs of prevalent cases until the end of life and to compare the influence of different interventions on these parameters and on the whole budget of the social security system.

Adolescent↗

Assessing the relationship between dental disease and coronary heart disease in elderly U.S. veterans.

Several recent studies have shown a link between dental disease and coronary heart disease. The authors studied 320 U.S. veterans in a convenience sample to assess the relationship between oral health and systemic diseases among older people. They present cross-sectional data confirming that a statistically significant association exists between a diagnosis of coronary heart disease and certain oral health parameters, such as the number of missing teeth, plaque benzoyl-DL-arginine-naphthylamide test scores, salivary levels of Streptococcus sanguis and complaints of xerostomia. The oral parameters in these subjects were independent of and more strongly associated with coronary heart disease than were recognized risk factors, such as serum cholesterol levels, body mass index, diabetes and smoking status. However, because of the convenience sample studied, these findings cannot be generalized to other populations.

Aged↗

Occupational life tables for cerebrovascular disease and ischemic heart disease in Japan compared with England and Wales.

Life tables have been calculated for cerebrovascular disease and ischemic heart disease in various occupational groups in Japan, and England and Wales. For cerebrovascular disease there are large occupational differences in both countries, and the experience of the lowest-ranking Japanese group (administrators and managers) is better than that of the highest-ranking group in England and Wales (miners). For ischemic heart disease the occupational variations within each country are less, and all Japanese groups fare better than any groups in England and Wales. Within each country mortality from cerebrovascular disease in different occupations has many positive and significant correlation coefficients with rates for stillbirth, and mortality from infections, cancers, etc. However, mortality from ischemic heart disease shows relatively less correlation coefficients with other diseases.

Actuarial Analysis↗

Association of metabolic syndrome with exercise capacity and heart rate recovery in patients with coronary heart disease in the heart and soul study.

It is not known whether the metabolic syndrome is associated with poor exercise capacity among patients who have established coronary heart disease. We evaluated the association of the metabolic syndrome with treadmill exercise capacity and heart rate recovery among patients who had coronary heart disease. We measured treadmill exercise capacity (METs) and heart rate recovery (beats per minute) in 943 subjects who had known coronary heart disease. Of these, 377 (40%) had the metabolic syndrome as defined by criteria of the National Cholesterol Education Program. Participants who had the metabolic syndrome were more likely to have poor exercise capacity (METs <5, 33% vs 18%, p <0.0001) and poor heart rate recovery (<or=16 beats/min, 34% vs 21%, p <0.0001) than those who did not have the metabolic syndrome. In ordinal logistic regression analyses, the metabolic syndrome was associated with decreased exercise capacity (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.7 to 2.8, p <0.0001) and decreased heart rate recovery (OR 1.8, 95% CI 1.4 to 2.3, p <0.0001). These associations remained strong after adjusting for potential confounding variables (OR 1.6, 95% CI 1.2 to 2.1, p = 0.003 for decreased exercise capacity; OR 1.4, 95% CI 1.1 to 1.9, p = 0.02 for decreased heart rate recovery). The metabolic syndrome is independently associated with poor exercise capacity and poor heart rate recovery in patients who have established coronary heart disease. Decreased exercise capacity may contribute to the adverse outcomes associated with the metabolic syndrome.

Aged↗

Interactions between diabetes and family history of coronary heart disease and other risk factors for coronary heart disease among adults with diabetes in Utah.

We used a unique data base containing medical family history information from representative Utah families to investigate interactions between diabetes and family history of coronary heart disease and other risk factors for coronary heart disease. We compared nonrelated individuals reported to have had diabetes mellitus diagnosed over the age of 19 (948) with 2150 nondiabetic individuals. Among both men and women, diabetes and family history of early coronary heart disease magnified the risk for coronary heart disease, so that in diabetic individuals with a positive family history of coronary heart disease, about 74% of the coronary heart disease could be attributed to interaction. Relative to nondiabetics without a family history of early coronary heart disease, nondiabetics with family history had a relative risk of 4.5 (2.3-8.7), diabetics without a family history had a relative risk of 2.8 (1.6-4.9), and diabetics with a family history had a relative risk of 21.3 (9.1-50.0). Smoking also interacted with diabetes; among smoking diabetics, 47% of early heart disease may be attributable to interaction between smoking and diabetes. Smoking entailed the highest risk for diabetic women. Hypertension and diabetes appeared to act additively, with little interaction. Among women, family history of diabetes was a risk factor for coronary heart disease with a relative risk of 2.5 (1.0-6.4), whereas for men the relative risk was estimated to be 0.4 (0.2-1.1).

Adult↗

Antithrombotic therapy in patients with valvular heart disease and prosthetic heart valves.

Indications and the type of antithrombotic therapy for the prevention of thromboembolism in patients with valvular heart disease, mechanical prosthetic heart valves and bioprosthetic heart valves are discussed. The evidence for these clinical recommendations is described and graded into five levels. The indications for anticoagulation in patients with valvular heart disease are chronic or paroxysmal atrial fibrillation, sinus rhythm with a very large left atrium, severe left ventricular dysfunction or presence of heart failure or a history of previous thromboembolism. Anticoagulant therapy is administered to prolong the prothrombin time to 1.5 to 2.0 times control, using rabbit brain thromboplastin (standardized international normalized ratio = 3.0 to 4.5). Risk factors for thromboembolism in patients with prosthetic heart valves are discussed. Because intracardiac thrombus formation may start during and continues early after operation, restarting heparin therapy 6 hours after operation and continuing it for the duration of the hospitalization is advised. For mechanical prosthetic heart valves, oral anticoagulation as outlined plus dipyridamole is advised indefinitely. Platelet inhibitor therapy alone is insufficient. For bioprosthetic heart valves, heparin is followed by oral anticoagulation as outlined for 3 months after mitral or aortic valve replacement and indefinitely after mitral valve replacement if there is atrial fibrillation or a very large left atrium; aspirin may be recommended indefinitely after aortic valve replacement. Antithrombotic therapy is also considered for four special situations: noncardiac surgery, prosthetic valve endocarditis, anticoagulation after a thromboembolic event, and antithrombotic therapy during pregnancy.

Anticoagulants↗

Is there a link between periodontal disease and coronary heart disease?

OBJECTIVE: To provide a critical review of the studies completed to date that have investigated a link between coronary heart disease and dental health. DESIGN: Retrospective analysis. SETTING: Mainly hospital-based patients or subjects involved in longitudinal health care studies. MAIN OUTCOME MEASURES: The incidence of coronary heart disease and its relationship to dental health and other recognised risk factors. RESULTS: Evidence suggests that dental health, in particular periodontal disease, may be a significant risk factor for coronary heart disease and further coronary events. Possible biological mechanisms that link the two diseases are appraised. CONCLUSIONS: There does appear to be increasing evidence that a relationship exists between dental health and coronary heart disease, especially in males aged 40-50 years. The presence of a hyperinflammatory monocyte phenotype may provide a common biological mechanism that links the two diseases.

Adult↗

Prevalence of cardiac arrhythmias during and after pregnancy in women with Chagas' disease without apparent heart disease.

OBJECTIVE: To evaluate cardiac arrhythmias during and after pregnancy in women with Chagas' disease without apparent heart disease using dynamic electrocardiography. METHODS: Twenty pregnant women with Chagas' disease without apparent heart disease aged 19 to 42 years (26.96 +/- 3.6) and a control group of 20 non-chagasic pregnant patients aged 16 to 34 years (22.5 +/- 4.8). The patients were submitted to passive hemagglutination and indirect immunofluorescence for the detection of Trypanosoma cruzi evaluation, and electrocardiography, echocardiography and 24-h dynamic electrocardiography. RESULTS: Supraventricular premature depolarizations were observed in 18 (90%) patients and ventricular premature depolarization in 11 (55%) patients of both groups during pregnancy. After delivery, supraventricular premature depolarizations were present in 13 (60%) chagasic patients and in 16 (89.4%) control patients (P</=0.05). Ventricular premature depolarization were observed in 9 (45%) chagasic patients and 11 (57.8%) control patients. CONCLUSION: The prevalence of ventricular premature depolarization was similar for the chagasic and control groups during and after pregnancy. The incidence of supraventricular premature depolarizations was similar in the two groups during pregnancy, while after delivery a predominance was observed in the control group compared to the chagasic group.

Adolescent↗