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[Cardiovascular disease after renal transplantation].

Cardiovascular disease is the leading cause of morbidity and mortality following renal transplantation. Because many renal transplant recipients die with functioning grafts, deaths resulting from cardiovascular disease have became an increasingly important cause of graft loss, particularly after the first post-transplantation year. Moreover, a contribution of some cardiovascular risk factors to renal allograft dysfunction has been demonstrated. A number of observational studies suggest that cardiovascular disease is more common in renal transplant patients than in the general population. The excessive risk for cardiovascular disease is related to a high prevalence and accumulation of atherogenic risk factors before and after transplantation. Hypertension, post-transplantation diabetes and hyperlipidemia are well-recognized risk factors for the development of cardiovascular events after renal transplantation and are strongly associated with immunosuppressive therapy. Progressive renal dysfunction may also influence the risk of cardiovascular complications after renal transplantation. The elevated risk may also be caused by non- traditional risk factors such as anaemia, adhesion molecules, hyperhomocysteinemia, microinflammatory state, abnormal coagulation and oxidative stress. To prevent post-transplantation cardiovascular disease it is crucial to define the etiological risk factors. Some risk factors can be modified, and for some of these, there is strong evidence from studies in the general population that intervention improves survival. Given the significant morbidity and mortality of cardiovascular disease in renal transplant recipients, aggressive treatment intervention for potentially modifiable factors are strongly advocated after transplantation. In addition to treatment intervention, risk management should also involve tailoring the immunosuppressive regimen to minimize both direct and indirect cardiovascular risks. In this article we attempted to review and quantify the post-transplant risk factors for cardiovascular disease as well as offer suggestions on optimizing the therapy or treatment strategies to minimize the risk of cardiovascular complications in renal transplant patients. Reduction of cardiovascular morbidity and mortality can improve not only the life expectancy and quality of life of the transplant recipients but also their graft function and survival.

Anemia↗

Erectile dysfunction and cardiovascular disease.

Patients with cardiovascular disease are at increased risk of developing erectile dysfunction (ED). This may be a consequence of atherosclerosis of the penile arteries, a reduced cardiac output, or a side-effect of drugs used to reduce cardiovascular risk factors (particularly beta-blockers, thiazide diuretics and, occasionally, lipid-lowering drugs). ED is a distressing condition, which often diminishes the patient's self-esteem, with the potential for damage to his psychological health and his relationship with his partner and family. When treating ED, the underlying aetiology should be established by careful examination and consideration of medical history and concurrent medication. Until recently, pharmacological treatment options involved intracavernous injections (alprostadil or moxisylyte) or intraurethral alprostadil. These treatments are often inconvenient and not well accepted by the patient. The recent introduction of oral sildenafil promises to revolutionise the treatment of ED. In double-blind, placebo-controlled trials in patients with ED, sildenafil improved erectile function and quality of life and was well tolerated. ED is a clinically important complication of cardiovascular disease and should be asked about and treated accordingly. It is important that effective treatments, including sildenafil, should be available for treating patients with cardiovascular disease and ED.

Coronary Disease↗

How does minor renal dysfunction influence cardiovascular risk and the management of cardiovascular disease?

This review focuses on the association between mild renal insufficiency (stage 2 and 3 of chronic kidney disease) and cardiovascular disease and discusses therapeutic options. Although the association of chronic renal insufficiency and cardiovascular risk was first shown in patients with end-stage renal disease, even minor renal dysfunction is now established as an independent risk for atherosclerotic cardiovascular disease. The association has been established in patients with a high cardiovascular risk but also in the general population. Treatment with angiotensin-converting enzyme inhibitors and statins can reduce cardiovascular morbidity and mortality in patients with renal insufficiency. Coronary revascularization improves the prognosis in patients with minor renal dysfunction, but there is still an underutilization of coronary revascularization procedures in people with renal insufficiency. The use of coronary stenting has now reduced the incidence of restenosis in these patients, and there is hope that the development of new devices will improve the prognosis in patients with renal insufficiency as well. Nevertheless, people with cardiovascular disease and renal insufficiency die significantly more often than people without renal insufficiency independent of prior successful treatment. Further investigations should focus on the causes of and possible preventive interventions for the staggering cardiovascular risk in the ever-increasing number of people with minor renal dysfunction.

Cardiovascular Diseases↗

Peripheral arterial disease in older adults: management of cardiovascular disease risk factors.

Patients with peripheral arterial disease experience significant functional limitations due to ischemic symptoms (claudication) and are at high risk for cardiovascular disease morbidity and mortality resulting from untreated cardiovascular disease risk factors and aggressive atherosclerosis. Peripheral arterial disease is commonly undiagnosed and cardiovascular disease risk factors are frequently untreated in this population. The increased risk associated with peripheral arterial disease necessitates greater emphasis on detection and management, not only to improve survival but to improve functional capacity and quality of life. This article briefly describes the detection and medical management with emphasis on lifestyle modification for elders with peripheral arterial disease.

Aged↗

Diet and inflammation: a link to metabolic and cardiovascular diseases.

Both epidemiological studies and intervention trials support an important role of diet in reducing the risk of a variety of chronic diseases, including cardiovascular disease, and overall mortality. We discuss available evidence indicating that the generation of a pro-inflammatory milieu might be one mechanism through which unhealthy diets are linked to metabolic and cardiovascular diseases. In practical terms, fully understanding the link between diet and inflammation holds the premise to elucidate the mechanisms by which dietary patterns improve cardiovascular health.

Cardiovascular Diseases↗

[Progress in biochemical and genetic examinations in clinical laboratory of cardiovascular diseases].

For diagnosing cardiovascular emergencies, cardiologists mainly rely on physiological examinations. Biochemical laboratory examinations can facilitate emergency diagnosis and genetic diagnosis can facilitate a fundamental understanding of cardiovascular diseases. Recent progress in biochemical examinations for cardiovascular diseases includes measurement of troponin T, heart type fatty acid-binding protein, and LDL-cholesterol. Recent progress in genetic examinations includes analysis of mitochondrial DNA, obesity-related genes and single nucleotide polymorphisms. A safe and convenient system of collecting, transporting, and storing blood and other biological specimens, and the subsequent purification of genomic DNA from the stored specimens is available. Therefore, busy doctors and staff of clinical laboratory can plan subsequent DNA examinations without causing concern and pain. A recently reported human mutation of heterotrimeric G protein beta 3 subunit produces a gain-of-function G protein signaling abnormality. A common polymorphic base substitution, C825T, in the GNB3 gene is associated with an aberrantly spliced transcript lacking 123 nucleotides. A significant association of the T allele with essential hypertension or obesity has been suggested.

Cardiovascular Diseases↗

Oligonucleotide-based gene therapy for cardiovascular disease: are oligonucleotide therapeutics novel cardiovascular drugs?

Gene therapy is emerging as a potential strategy for the treatment of cardiovascular disease such as restenosis after angioplasty, vascular bypass graft occlusion, transplant coronary vasculopathy, for which no known effective therapy exists. One strategy for combating disease processes has been to target to the transcriptional process. Two approaches have been used to accomplish this. One is the use of antisense that is complimentary to the mRNA of interest. The second approach is the use of ribozymes, a unique class of RNA molecules that not only store information but also process catalytic activity. Ribozymes are known to catalytically cleave specific target RNA leading to degradation, whereas antisense inhibit translation by binding to mRNA sequences on a stoicheometric basis. Theoretically, ribozymes are more effective to inhibit target gene expression. Especially, the application of DNA technology such as antisense strategy to regulate the transcription of disease-related genes in vivo has important therapeutic potential. More recently, transfection of cis-element double stranded (ds) oligodeoxynucleotides (ODN) (= decoy) as a powerful tool in a new class of anti-gene strategies for gene therapy has been reported. Transfection of ds ODN corresponding to cis sequence will result in the attenuation of authentic cis-trans interaction, leading to the removal of trans-factors from the endogenous cis-elements with subsequent modulation of gene expression. This "decoy" strategy is not only a novel strategy for gene therapy as an anti-gene strategy, but also a powerful tool for the study of endogenous gene regulation in vivo as well as in vitro. In this review, we have focused on the future potential of oligonucleotide (antisense, decoy & ribozyme)-based gene therapy for the treatment of cardiovascular disease.

Cardiovascular Diseases↗

Possible explanations for the tooth loss and cardiovascular disease relationship.

Several studies have shown relationships between periodontal disease and cardiovascular disease (CVD). A few studies have also shown that tooth loss may be associated with increased risk of coronary heart disease and stroke. We have reviewed the relevant literature to assess possible explanations for the reported associations between tooth loss and CVD. In particular, we considered whether the reported association between tooth loss and CVD could be explained by antecedent periodontal disease, antecedent caries, the extraction process, dietary changes following tooth loss, or confounding or bias from other sources. Since access to care and attitudes to health care may influence the decision to extract teeth, as well as cardiovascular disease risk, one needs to be cautious about confounding from behaviorally related factors. Available evidence suggests that further studies are needed to rule out that confounding is a possible explanation for the tooth loss and CVD relationship, that prior periodontal disease may not completely explain the tooth loss-CVD relationship, and that the role of diet needs to be further explored

Attitude to Health↗

Free radicals and antioxidants in cardiovascular diseases.

It has been demonstrated that redox homeostasis is important in the pathophysiology of several human diseases, including cardiovascular diseases. In this respect, genetic polymorphism, nutritional and environmental factors, age, lifestyle and physical activity may account for variable antioxidant defenses, which may be more or less effective at counteracting oxidative damage. Since accumulating oxidative damage may be associated with several pathologic conditions, including different cardiovascular diseases, prevention of oxidative stress appears to be a promising approach to improve such diseases. Exercise training, diets rich in antioxidants and a good control of blood glucose and lipid levels help to strengthen the physiologic antioxidant defense system, perhaps coupled to drugs capable of increasing the nitric oxide bioavailability and decreasing superoxide production. Within the next few years other therapeutic approaches will be available, such as gene therapy, which will prove to be even more effective but devoid of several important systemic side effects.

Antioxidants↗

Stem cells and cellular therapy: potential treatment for cardiovascular diseases.

This paper reviews the current status of cloning and stem cell research and its application to treating various diseases, particularly cardiovascular disease. Recently new techniques have been developed to isolate embryonic stem cells from preimplantation embryos. These cells are undifferentiated and are therefore able to develop into the cells of whichever organ it is in contact with. These cells would be especially beneficial for the treatment of ischemia and various other cardiovascular diseases. There are a variety of various issues that need to be discussed before this technology can be applied safely, including government regulations to ensure the clinical safety and effectiveness of the procedures, as well as the prevention of improper handling or the use of contaminated tissues.

Cardiovascular Diseases↗

Hyperhomocysteinemia and end-stage renal disease: determinants and association with cardiovascular disease in Tunisian patients.

The study reports on plasma total homocysteine (tHcy) levels in Tunisian patients with chronic renal failure (CRF) and those treated with hemodialysis (HD) and renal transplant (RT). The aims of the study were to identify the determinants of tHcy concentration and to test the association between hyperhomocysteinemia and atherothrombotic disease in end-stage renal disease (ESRD). A total of 35 CRF patients on conservative treatment, 50 HD patients, and 30 RT recipients, and 31 age- and sex-matched healthy subjects were included. Plasma tHcy was assessed by a fluorescent-polarizing immunoassay method. Multivariate analysis was applied to identify the main determinants of tHcy concentration and to assess the relationship between hyperhomocysteinemia and cardiovascular disease. Plasma mean tHcy concentration was significantly increased (p < 0.001) in CRF patients (mean +/- SD) (28.9 +/- 9.8 micromol/l), in HD patients (29.4 +/- 11.1 micromol/l), and in RT (19.3 +/- 6.3 micromol/l) patients compared to controls (11.9 +/- 4.1 micromol/l). Multivariate analysis using GLM ANOVA modeling demonstrated that tHcy was significantly higher in males (p = 0.02), and was related to age (p = 0.008), albumin (p = 0.005), vitamin B12 (p = 0.002), folate (p = 0.00001), and creatinine clearance (p = 0.0008). However, tHcy was not associated with C-reactive protein and did not significantly differ between CRF, HD, or RT patients. The upper quartile of tHcy concentration was significantly associated with atherothrombotic cardiovascular disease (unadjusted odds ratio (OR) = 3.09; 95% CI, 1.11-8.61; p = 0.01). This association remained significant after adjusting for sex, age, hypertension, and smoking (multi-adjusted OR = 4.78; 95% CI, 1.92-11.9; p = 0.0008). The mean tHcy concentration was 2 to 3 times higher in ESRD patients than in subjects with normal renal function. This increase could be related to glomerular filtration rate reduction and functional B vitamins deficiency, but was not associated with inflammation. The upper quartile of tHcy concentrations confers 4.78-fold increased independent risk for atherothrombotic events in ESRD patients.

Biomarkers↗

Undiagnosed dysglycaemia and inflammation in cardiovascular disease.

BACKGROUND: Cardiovascular (CV) disease is associated with increased levels of glucose, but the prevalence of dysglycaemia in CV diseases is not fully known. The study examined the prevalence of unknown dysglycaemia and its association with inflammation in Caucasian patients with ischaemic vascular complications, i.e. coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral artery disease (PAD). MATERIALS AND METHODS: This case-controlled study involved 149 patients (mean age 68 years) hospitalized for CAD, PAD or CVD and 59 control-subjects (CTR) free from CV-disease. The prevalence of dysglycaemia according to WHO/ADA criteria (impaired fasting glycaemia, impaired glucose tolerance or diabetes mellitus) was assessed by a 75-g oral glucose tolerance test. Inflammatory parameters were analyzed in fasting samples. RESULTS: Dysglycaemia was found in 49%, 55% and 57% of patients with CAD, CVD and PAD, respectively; all were significantly higher than among the controls (29%). The odds ratio (95% CI) for being dysglycaemic were 1.7 (1.04-2.77), 1.9 (1.19-3.06) and 2.0 (1.25-3.19) for CAD, CVD and PAD, respectively. Inflammatory markers (the total leucocyte count, soluble tumour necrosis factor-receptor type I, C-reactive protein) were elevated in patient groups and tended to increase with increasing blood glucose levels in all groups. The levels of the anti-inflammatory cytokine transforming growth factor-beta1 and insulin-like growth factor binding protein 3 were lowered in patients with CAD and, in patients with PAD, the former was inversely related to the levels of the blood glucose. CONCLUSIONS: Undiagnosed dysglycaemia was common in patients with ischaemic CV manifestations regardless of vascular bed involved. Inflammation was associated in a dosage-related manner to glucose levels.

Adult↗

Tobacco use and cardiovascular disease: a knowledge, attitude and practice study in rural Kerala.

BACKGROUND: Tobacco consumption, either in smokeless form or as smoking, is reported to be responsible for major non-communicable diseases, namely, cardiovascular diseases, chronic obstructive pulmonary diseases and cancers. Whatsoever control strategy is being used, the community participation is of utmost importance, which will depend largely on the level of the knowledge in the community. AIM: To assess the knowledge and attitude of a rural community towards the harmful effects of tobacco use. SETTING AND DESIGN: Venganoor Gram Panchayat of Thiruvananthapuram district of Kerala; cross-sectional study. MATERIALS AND METHODS: Interview schedule was used to collect the information on pre-designed and pre-tested proforma. The information recorded, included the demographic characteristics and socio-economic characteristics. The awareness regarding tobacco use and the attitude towards its non-usage was done, by putting forward, open and closed-ended questions. STATISTICAL ANALYSIS: Percentages and proportions; t-test; chi-square test. RESULTS: The present study included 302 (64.7%) females and 165 (35.3%) males. Among the males, 44 (38.5%) were ever smokers. Though 451 (96.6%) of the subjects knew that tobacco use is harmful for health, only 101 (22.5%) of the subjects knew that it causes cardiovascular diseases. Electronic and print media were the common source of such knowledge being reported by 265 (58.7%) and 202 (44.7%) subjects, respectively. CONCLUSIONS: The subjects were aware about the harmful effects of tobacco use. However, more efforts are needed to make them aware about the role of tobacco smoking and chewing, in causing cardiac problems.

Adolescent↗

Cardiovascular diseases in women.

Cardiovascular disease is the leading cause of death in women. Approaches to diagnosis and management of cardiovascular disease in women often differ from those in men. In some instances, these differences are justified by clinical trial and epidemiologic data.

Cardiovascular Diseases↗

Molecular analysis of cardiovascular disease: some delay due to gene-environment interactions.

The absence of a clear relation between genotype and phenotype has complicated molecular analyses of the susceptibility to common diseases such as cardiovascular disease. Gene-gene and gene-environment interactions may have biased genetic association studies on cardiovascular disease. In the general population, susceptibility to cardiovascular disease is probably the result of many loci with frequently occurring alleles that have relatively small effects. We hypothesize that addition of mortality analyses to genetic association studies may provide important information on the clinical relevance of molecular findings. We propose to use a parent-offspring model for this purpose: the parents contribute large follow-up and the index cases (offspring) are eliminated from the analyses to remove selection on cardiovascular disease. In particular, indirect estimation of mortality risk has high statistical power and may establish the role of common genetic variation with small effects on cardiovascular disease in the general population. Moreover, the effect of a candidate gene on excess mortality illustrates the quality of such a gene or protein as a novel target for intervention. The results of genetic association studies may have been of little clinical relevance for cardiovascular disease, but we conclude that the methodology still has possibilities for improvements and we propose to use analyses of mortality in a parent-offspring model.

Cardiovascular Diseases↗

Molecular diagnostics for cardiovascular disease.

The etiology of cardiovascular diseases is known to be multi-factorial. Some forms of cardiovascular disease are influenced by unclear genetic factors but are predominantly affected by factors such as diet, obesity, cigarette smoking, diabetes mellitus and dyslipidaemia. Some are caused by specific gene defects, with environmental factors playing a precipitating role. Others result from complex gene-gene or gene-environment interactions. Advances in knowledge of the molecular genetics of lipidaemic and vascular disorders have identified gene aberrations that are associated with cardiovascular disease. Techniques in molecular biology have been applied for rapid and reliable detection of specific gene defects to provide unequivocal diagnosis beneficial for appropriate drug therapy and genetic counseling. Pre-symptomatic diagnosis is possible and carriers can be advised on effective preventive measures. However, prior to the provision of a molecular diagnostic service, all gene alterations associated with cardiovascular disease have to be identified and their prevalence established in a population. The number of mutations in so many causative genes is enormous. While more cost-effective laboratory methodologies will be developed in the future, it is also anticipated that more mutations with direct or indirect effects on cardiovascular disease will be discovered in different populations.

Cardiovascular Diseases↗

Evidence for increased cardiovascular disease risk in patients with chronic kidney disease.

PURPOSE OF REVIEW: Chronic kidney disease is becoming recognized as an important risk factor for cardiovascular disease. Recent publications on cardiovascular disease risk in chronic kidney disease, cardiovascular disease risk factors in chronic kidney disease and clinical trials for cardiovascular disease risk reduction in chronic kidney disease are summarized. RECENT FINDINGS: An American Heart Association statement published in 2003 recommended that patients with chronic kidney disease be considered as members of the 'highest risk group' for subsequent cardiovascular disease events. In the past year, several large prospective studies have reported that cardiovascular disease risk is independently associated with chronic kidney disease markers, e.g. elevated serum creatinine, low estimated glomerular filtration rate and microalbuminuria. The populations studied have included community samples of middle-aged and older adults, subjects with myocardial infarction, those undergoing coronary angiography, and transplant patients. There is a very strong crude association between a low glomerular filtration rate and cardiovascular disease and mortality. Much of the association is explained by traditional cardiovascular disease risk factors, but an independent risk remains. Studies have documented a disturbing underutilization of preventive treatments for cardiovascular disease among patients with chronic kidney disease. Studies of non-traditional cardiovascular disease risk factors are reviewed. The utility of targeting these for cardiovascular disease risk reduction needs to be proved. A summary of large ongoing clinical trials intended to reduce cardiovascular disease risk in chronic kidney disease is presented. SUMMARY: Increasing data support the importance of chronic kidney disease as a predictor of cardiovascular disease risk. However, treatments designed to lower cardiovascular disease risk are used less often in patients with chronic kidney disease than in patients without chronic kidney disease. There is a need for increased application and testing of cardiovascular disease prevention treatments in chronic kidney disease.

Aging↗