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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five types of oral antihyperglycemic drugs are currently approved for the treatment of diabetes: biguanides, sulfonylureas, meglitinides, glitazones and alpha-glucosidase inhibitors. We briefly review the cardiovascular effects of the most commonly used antidiabetic drugs in these groups in an attempt to improve knowledge and awareness regarding their influences and potential risks when treating patients with coronary artery disease (CAD). Regarding biguanides, gastrointestinal disturbances such as diarrhea are frequent, and the intestinal absorption of group B vitamins and folate is impaired during chronic therapy. This deficiency may lead to increased plasma homocysteine levels which, in turn, accelerate the progression of vascular disease due to adverse effects on platelets, clotting factors, and endothelium. The existence of a graded association between homocysteine levels and overall mortality in patients with CAD is well established. In addition, metformin may lead to lethal lactic acidosis, especially in patients with clinical conditions that predispose to this complication, such as heart failure or recent myocardial infarction. Sulfonylureas avoid ischemic preconditioning. During myocardial ischemia, they may prevent opening of the ATP-dependent potassium channels, impeding the necessary hyperpolarization that protects the cell by blocking calcium influx. Meglitinides may exert similar effects due to their analogous mechanism of action. During treatment with glitazones, edema has been reported in 5% of patients, and these drugs are contraindicated in diabetics with NYHA class III or IV cardiac status. The long-term effects of alpha-glucosidase inhibitors on morbidity and mortality rates and on diabetic micro- and macrovascular complications is still unknown. Combined sulfonylurea/metformin therapy reveals additive effects on mortality. Four points should be mentioned: (1) the five oral antidiabetic drug groups present proven or potential cardiac hazards; (2) these hazards are not mere 'side effects' but are deeply rooted in the drugs' mechanisms of action; (3) current data indicate that combined glibenclamide/metformin therapy seems to present a special risk and should be avoided in the long-term management of type 2 diabetics with proven CAD, and (4) Non-Insulin Antidiabetic Therapy in Diabetic Cardiac Patients 155 customized antihyperglycemic pharmacological approaches should be investigated for the optimal treatment of diabetic patients with heart disease. New possibilities are represented by incretin mimetic compounds, dipeptidyl peptidase (DPP)-4 inhibitors, inhaled insulin and eventually oral insulin.
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PMID:Non-insulin antidiabetic therapy in cardiac patients: current problems and future prospects. 1823 Sep 61

Chronic volume/pressure overload-induced heart failure augments oxidative stress and activates matrix metalloproteinase which causes endocardial endothelial-myocyte (EM) uncoupling eventually leading to decline in myocardial systolic and diastolic function. The elevated levels of homocysteine (Hcy), hyperhomocysteinemia (HHcy), are associated with decline in cardiac performance. Hcy impairs the EM functions associated with the induction of ventricular hypertrophy leading to cardiac stiffness and diastolic heart failure. Hcy-induced neurological defects are mediated by the NMDA-R (N-methyl-D-aspartate (NMDA) receptor) activation. NMDA-R is expressed in the heart. However, the role of NMDA-R on cardiac function during HHcy is still in its infancy. The blockade of NMDA-R attenuates NMDA-agonist-induced increase in the heart rate. Hcy increases intracellular calcium and activates calpain and calpain-associated mitochondrial (mt) abnormalities have been identified in HHcy. Mitochondrial permeabilization and uncoupling in the pathological setting is fueled by redox stress and calcium mishandling. Recently the role of cyclophilin D, a component of the mitochondrial membrane permeability transition pore, has been identified in cardiac-ischemia. Mechanisms underlying the potentiation between NMDA-R activation and mitochondrial defects leading to cardiac dysfunction during HHcy remain to be elucidated. This review addresses the mitochondrial mechanism by which Hcy contributes to the decline in mechano-electrical function and arrhythmogenesis via agonizing NMDA-R. The putative role of mitochondrial MMP activation, protease stress and mitochondrial permeability transition in cardiac conduction during HHcy is discussed. The review suggests that Hcy increases calcium overload and oxidative stress in the mitochondria and amplifies the activation of mtMMP, causing the opening of mitochondrial permeability transition pore leading to mechano-electrical dysfunction.
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PMID:Mitochondrial MMP activation, dysfunction and arrhythmogenesis in hyperhomocysteinemia. 1839 9

Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of two pathways: remethylation, which requires folic acid and vitamin B12 coenzymes; and transsulfuration, which requires pyridoxal-5'-phosphate, the vitamin B6 coenzyme. Data from a number of laboratories suggest that mild elevations of homocysteine in plasma are a risk factor for occlusive vascular disease. In the Framingham studies, we have shown that plasma homocysteine concentration is inversely related to the intake and plasma levels of folate and vitamin B6 as well as vitamin B12 plasma levels. Almost two-thirds of the prevalence of high homocysteine is attributable to low vitamin status or intake. Elevated homocysteine concentrations in plasma are a risk factor for prevalence of extracranial carotid-artery stenosis > or = 25% in both men and women. Prospectively elevated plasma homocysteine is associated with increased total and cardiovascular mortality, increased incidence of stroke, increased incidence of dementia and Alzheimer's disease, increased incidence of bone fracture, and higher prevalence of chronic heart failure. It was also shown that elevated plasma homocysteine is a risk factor for preeclampsia and maybe neural tube defects (NTD). This multitude of relationships between elevated plasma homocysteine and diseases that afflict the elderly, pregnant women, and the embryo points to the existence ofa common denominator which may be responsible for these diseases. Whether this denominator is homocysteine itself or homocysteine is merely a marker, remains to be determined.
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PMID:Public health significance of elevated homocysteine. 1870 86

In the recent past, hyperhomocysteinemia (HHCY) has been linked to chronic heart failure. Folate and vitamin B12 deficiencies are the common causes of HHCY. The impact of these vitamins on cardiac function and morphology has scarcely been investigated. The aim of this study was to conduct an analysis of the cardiac effect of folate and vitamin B12 deficiency in vivo. Two groups of rats, a control (Co, n = 10) and a vitamin-deficient group (VitDef, n = 10), were fed for 12 weeks with a folate and vitamin B12-free diet or an equicaloric control diet. Plasma and tissue concentrations of HCY, S-adenosyl-homocysteine (SAH), S-adenosyl-methionine (SAM), and brain natriuretic peptide (BNP) were measured. Moreover, echocardiographic and histomorphometric analyses were performed. VitDef animals developed a significant HHCY (Co vs VitDef: 6.8 +/- 2.7 vs 61.1 +/- 12.8 micromol/l, P < 0.001). Fractional shortening, left ventricular dimension at end-diastole and end-systole, posterior wall thickness, perivascular collagen, mast cell number, and BNP tissue levels were comparable in VitDef and Co animals. Interstitial collagen (Co vs VitDef: 6.8 +/- 3.0 vs 4.5 +/- 2.1%, P < 0.05), plasma BNP (Co vs VitDef: 180 +/- 80 vs 70 +/- 60 ng/l, P < 0.05), and tissue HCY (Co vs VitDef: 0.13 +/- 0.07 vs 0.07 +/- 0.04 micromol/g protein, P < 0.05) were lower in VitDef animals. Folate and vitamin B12 deficiency do not affect cardiac function and morphology.
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PMID:The cardiac effects of prolonged vitamin B12 and folate deficiency in rats. 1939 44

High plasma homocysteine levels are a known risk factor in heart failure and sudden cardiac death. The G proteins, G(s) (stimulatory) and G(i) (inhibitory), are involved in calcium regulation; overexpression has pathological consequences. The aims of this study were to examine the differential expression of G(s) G protein and G(i) in the hearts of hyperhomocysteinemic (Hhcy) mice, and to determine if homocysteine (Hcy) acts as an agonist in cell culture to mediate the change in G protein isoforms. To create Hhcy, heterozygous cystathionine-beta-synthase (CBS) knockout (KO) mice were used. Mice were sacrificed, hearts were excised, cardiac tissue homogenates were prepared, and Western blots were performed. The results suggested that G(s) G protein was downregulated in cardiac tissue of heterozygous CBS KO mice to 46% that of control hearts. However, the intracellular G(i) G protein content remained the same in heterozygous CBS KO mice. Transformed cardiomyocyte HL-1 cells were treated with varying concentrations of homocysteine. The results suggested no detectable differential G(s) and G(i) expression. This suggested that Hcy did not act as an agonist in vitro to alter G protein content, but that Hcy produced some other in vivo effects to incur these results.
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PMID:Differential expression of Gs in a murine model of homocysteinemic heart failure. 1943 74

Four decades of research on the link between hyperhomocysteinemia and cardiovascular disease has led to a crossroads. Several negative studies on the role of homocysteine-lowering B-vitamin therapy in reducing the risk of atherothrombotic cardiovascular disease have dampened enthusiasm for this important field of research. In this review, we assess the present state of homocysteine research and suggest potential avenues that would help to clarify the purported link between the plasma homocysteine level and cardiovascular risk. We address several questions raised by the findings of various basic, epidemiological and clinical studies and attempt to construct a framework that we believe will allow us to address the fundamental unresolved issues in this controversial area, specifically focusing on the risk of coronary vascular disease and cardiac failure. This review should allow researchers to deconstruct this complex field into separate areas that, when addressed adequately, may lead to findings that elucidate the overall link between hyperhomocysteinemia and cardiovascular disease and allow the design of appropriate clinical trials.
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PMID:Quo vadis: whither homocysteine research? 1948 90

Elevated level of homocysteine (Hcy) called hyperhomocysteinemia (HHcy) is one of the major risk factors for chronic heart failure. Although the role of Hcy in cardiac remodeling is documented, the regulatory mechanism involved therein is still nebulous. MicroRNAs (miRNAs) and dicer have been implicated in regulation of cardiovascular diseases. Dicer is the only known enzyme involved in miRNA maturation. We investigated the involvement of dicer and miRNA in Hcy-induced cardiac remodeling. HL-1 cardiomyocytes were cultured in different doses of Hcy. Total RNA was isolated and RT-PCR and real-time PCR was performed for dicer, MMP-2,-9, TIMP-1,-3, and NOX-4. MiRNA microarray was used for analyzing the differential expression of miRNAs. Individual miRNA assay was also done. Western blotting was used to assess the MMP-9 expression in HHcy cardiomyocytes. The RT-PCR results suggest that dicer expression is enhanced in HHcy cardiomyocytes suggesting its involvement in cardiac remodeling caused due to high dose of Hcy. On the other hand, high dose of Hcy increased NOX-4 expression, a marker for oxidative stress. Additionally, HHcy cardiomyocytes showed elevated levels of MMP-2,-9 and TIMP-1,-3, and reduced expression of TIMP-4, suggesting cardiac remodeling due to oxidative stress. The miRNA microarray assay revealed differential expression of 11 miRNAs and among them miR-188 show dramatic downregulation. These findings suggest that dicer and miRNAs especially miR-188 are involved in Hcy-induced cardiac remodeling.
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PMID:MicroRNAs are involved in homocysteine-induced cardiac remodeling. 1966 42

The association of epilepsy with risk of acute myocardial infarction (AMI) remains uncertain, and its association with myocardial infarction prognosis has not been evaluated. In this study, we performed a population-based case-control study that included 1799 cases with first AMI and 2339 controls, frequency matched by age, sex and hospital catchment area. A history of epilepsy was identified using the Swedish hospital discharge registry. Information on lifestyle and biomarkers was determined from questionnaires and standardized clinic examinations. The cohort of cases was followed for 8 years to evaluate the relationship between epilepsy and post AMI prognosis. A diagnosis of epilepsy was associated with higher risk of incident AMI, with an odds ratio (OR) of 4.92 [95% confidence interval (CI) 2.34-10.31] after adjustment for age, gender, hospital catchment area, and education. There was a graded positive relation between number of hospitalizations for epilepsy and risk of AMI. Adjustment for smoking and levels of tissue plasminogen activator (tPA)/plasminogen activator inhibitor 1 (PAI-1) complex, von Willebrand factor and homocysteine weakened, and adjustment for high-density lipoprotein (HDL) and fibrinogen strengthened, the relationship between epilepsy and AMI. The OR for epilepsy was 4.83 (95% CI 1.62-14.43) when age, gender, hospital catchment area, education and established, clinically relevant AMI risk factors, i.e. diabetes mellitus, smoking, hypertension, physical activity, obesity, high-density lipoprotein, total cholesterol and alcohol consumption were simultaneously controlled for. Epilepsy was also associated with AMI prognosis. Multivariable adjusted hazard ratios for total and cardiac mortality and for a combined outcome of cardiac death and non-fatal reinfarction, heart failure and stroke during follow up, were 1.95 (0.70-5.43), 3.49 (1.05-11.65) and 2.39 (1.16-4.90), respectively. We conclude that epilepsy might be a risk and an adverse prognostic factor for AMI. Smoking and increase in the level of homocysteine, tPA/PAI-1 complex and von Willebrand factor are candidate mechanisms linking epilepsy to increased AMI risk. Physicians should be aware of the potential cardiovascular implications of epilepsy.
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PMID:Increased risk and worse prognosis of myocardial infarction in patients with prior hospitalization for epilepsy--the Stockholm Heart Epidemiology Program. 1971 32

Several studies and recent patents have demonstrated that hyperhomocysteinemia (HHCY) is an independent risk factor for congestive heart failure (CHF); it is also correlated to the severity of the disease. In literature there are some data about effects of HHCY on myocardial structure and function in animal models. These studies indicate a direct effect of HCY in promoting reactive myocardial fibrosis and systolic dysfunction, promoting miocardial redox state, endothelial and mithocondryal dysfunction, negative inotropic effect. According to some authors the HHCY is a potential ethiological factor for heart failure while according to others it is just an epiphenomenon without direct effects on myocardium. Nevertheless the literature studies show the relevant involvement of HHCY in CHF and the strong relations between HHCY plasma levels and the severity and prognosis of the disease. Regarding the potential mechanistic role of HHCY in CHF, all of these studies do not provide any mechanistic insights because of their epidemiological nature. Future studies need to explore the exact pathomechanisms of HHCY in CHF.
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PMID:[Homocysteine: a casual link with heart failure?]. 1991 Aug 94

Part 2 highlights the use of food products, bioactive additives, micronutrients, and phytotherapyforprevention of diseases. Many studies demonstrated positive effect of omega-3 PUFA, stanols, sterols, and esterified pargarines, soluble cellulose, controlled alcohol consumption, tea, Mg-enriched dietetic factors, folic acid combined with vitamins B6 and B12 on subjects with the initially enhanced homocysteine level. Garlic is known to reduce blood lipids, hawthorn may be useful at early stages of cardiac insufficiency, ginkgo biloba in arterial and cerebral disorders, horse chestnut for the treatment of peripheral vascular pathology. Results of controlled studies indicate that the use of many foods for prevention of different diseases is currently based on recommendations of individual doctors and needs to be substantiated by evidence-based practice. Physicians treating and educating patients must be well aware of alternative and supplemental therapeutic modalities with the use of foodstuffs, bioactive additives, micronutrients, and phytotherapy.
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PMID:[Alternative medicine. Past, present, future. Part 2]. 2013 88


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