Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis is a chronic inflammatory disease which may cause obstructions of the coronary, cerebral and peripheral arteries. It is typically multifactorial, most often dependent on risk factors such as hypercholesterolemia, diabetes, smoking, hypertension, sedentarism, and obesity. It is the single main cause of death in most developed countries due to myocardial infarction, angina, sudden death, and heart failure. Several epidemiological studies suggest that moderate alcohol intake, especially red wine, decrease cardiac mortality due to atherosclerosis. The alcohol effect is described by a J curve, suggesting that moderate drinkers may benefit while abstainers and heavy drinkers are at higher risk. Experimental studies indicate that most beneficial effects of drinking are attributable to flavonoids that are present in red wine, purple grape juice and several fruits and vegetables. The mechanisms include antiplatelet actions, increases in high-density lipoprotein, antioxidation, reduced endothelin-1 production, and increased endothelial nitric oxide synthase expression which causes augmented nitric oxide production by endothelial cells. These findings lead to the concept that moderate red wine drinking, in the absence of contraindications, may be beneficial to patients who are at risk of atherosclerotic cardiovascular events. Moreover, a diet based on fruits and vegetables containing flavonoids may be even more beneficial.
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PMID:Wine, alcohol and atherosclerosis: clinical evidences and mechanisms. 1533 93

There is abundant evidence that the endothelium plays a crucial role in the maintenance of vascular tone and structure. One of the major endothelium-derived vasoactive mediators is nitric oxide (NO). Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase. ADMA inhibits vascular NO production in concentrations found in pathophysiological conditions; ADMA also causes local vasoconstriction when it is infused intraarterially. Thus, elevated ADMA levels may explain the "L-arginine paradox," i.e., the observation that supplementation with exogenous L-arginine improves NO-mediated vascular functions in vivo, although its baseline plasma concentration is about 25-fold higher than the Michaelis-Menten constant K(m) of the isolated, purified endothelial NO synthase in vitro. The biochemical and physiological pathways related to ADMA are well understood: Dimethylarginines are the result of degradation of methylated proteins; the methyl group is derived from S-adenosylmethionine. Both ADMA and its regioisomer, symmetric dimethylarginine, are eliminated from the body by renal excretion, whereas only ADMA is metabolized via hydrolytic degradation to citrulline and dimethylamine by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). DDAH activity and/or expression may therefore contribute to the pathogenesis of endothelial dysfunction in various diseases. Plasma ADMA levels are increased in humans with hypercholesterolemia, atherosclerosis, hypertension, chronic renal failure, and chronic heart failure. Increased ADMA levels are associated with reduced NO synthesis as assessed by impaired endothelium-dependent vasodilation. In several prospective and cross-sectional studies, ADMA evolved as a marker of cardiovascular risk. With increasing knowledge of the role of ADMA in the pathogenesis of cardiovascular disease, ADMA is becoming a goal for pharmacotherapeutic interventions. Among other potential strategies that are currently being tested, administration of L-arginine has been shown to improve endothelium-dependent vascular functions in subjects with high ADMA levels. Finally, ADMA has gained clinical importance recently because several studies have shown that ADMA is an independent cardiovascular risk factor.
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PMID:Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the "L-arginine paradox" and acts as a novel cardiovascular risk factor. 1546 97

Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase (NOS). Elevated ADMA plasma levels have been reported in connection with diseases associated with an impaired endothelial L-arginine-NO pathway and endothelial dysfunction, such as atherosclerosis, hypercholesterolemia, chronic heart failure, diabetes mellitus, and hypertension. NO production by NOS is decreased due to elevated ADMA levels. In fact, there is increasing interest in determination of ADMA levels in samples of various origins. The aim of this work was to develop a precise and easy immunoassay in contrast to the existing methods, such as HPLC, liquid chromatography-mass spectrometry (LC-MS) and gas chromatography (GC)-MS. We determined cross-reactivity in our immunoassay of 1.2% for symmetric dimethylarginine and <0.02% for L-arginine. The limit of quantitation was 0.05 micromol/l. We found good correlation of the values measured when we compared our assay with LC-tandem MS (n = 29; r = 0.984; p < 0.0001). We determined ADMA levels in human serum and plasma, mouse and rat plasma, and cell culture supernatant. For human plasma we found a mean of 0.65 micromol/l in healthy subjects. In the plasma of mice and rats we found mean concentrations of 1.05 and 1.09 micromol/l, respectively.
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PMID:Determination of asymmetric dimethylarginine (ADMA) using a novel ELISA assay. 1557 99

In maintenance hemodialysis (MHD) patients, associations between demographic, clinical and laboratory values and mortality, including cardiovascular death, are significantly different and, in some cases, in the opposite direction of those derived from the general population. This phenomenon, termed 'reverse epidemiology', is not limited to MHD patients but is also observed in populations that encompass an estimated 20 million Americans including those with an advanced age, heart failure, malignancies, and AIDS. A significant portion of this reversal may be due to the overwhelming effect of the malnutrition-inflammation complex syndrome (MICS). Since two thirds of MHD patients die within 5 years of initiation of dialysis treatment, traditional cardiovascular risk factors such as obesity, hypercholesterolemia and hypertension cannot exert a long-term deleterious impact, and instead, their short-term beneficial effects on MICS provides a survival advantage. In order to improve survival and quality of life in MHD patients, extrapolated ideal norms derived from the general population should be substituted with novel norms obtained from outcome-oriented epidemiologic analyses while accounting for the differential effect of MICS in different case-mix subgroups.
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PMID:Reverse epidemiology: a spurious hypothesis or a hardcore reality? 1562 38

The role of oxidation injury as an important factor in the pathophysiology of cardiomyopathy (CMP) has recently gained increasing interest. Semiquantitative analysis for isoprostane, 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)), and oxidised low-density lipoprotein (ox-LDL) of coronary vascular tissue samples derived from CMP patients revealed an increased extent and intensity of uptake as compared to the respective controls. To evaluate oxidative stress in vivo, we examined plasma, serum, salivary, and urinary 8-epi-PGF(2alpha) in patients with dilated CMP (n=20) and ischemic CMP (n=20) with decreased left ventricular ejection fraction (LVEF). Patients with coronary heart disease (CHD) (n=20) and 20 healthy, age-matched, and sex-matched controls were investigated in parallel. 8-Epi-PGF(2alpha) levels were correlated with the functional severity of heart failure [New York Heart Association (NYHA) classification] and LVEF. 8-Epi-PGF(2alpha) levels were matched according to risk factors (smoking and hypercholesterolemia) and were significantly higher in patients with CMP as compared to healthy controls and patients with CHD in all investigated compartments. A positive correlation between NYHA stages and 8-epi-PGF(2alpha), as well as a negative correlation to LVEF, could be demonstrated in a subgroup analysis. These findings reflect the enhanced oxidation injury in patients with CMP and, to a lesser extent, in CHD as compared to healthy controls, thus highly indicating the relevance of oxidative stress for the pathogenesis and progression of cardiovascular disease.
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PMID:Enhanced oxidative stress in coronary heart disease and chronic heart failure as indicated by an increased 8-epi-PGF(2alpha). 1570 62

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.
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PMID:Clinical aspects of reactive oxygen and nitrogen species. 1577 17

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes mellitus, chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species (ROS), such as the superoxide radical, and the subsequent decrease in vascular bioavailability of nitric oxide (NO). Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include the NAD(P)H oxidase, the xanthine oxidase, and mitochondrial superoxide-producing enzymes. Superoxide produced by the NADPH oxidase may react with NO released by endothelial nitric oxide synthase (eNOS), thereby generating peroxynitrite. Peroxynitrite in turn has been shown to uncouple eNOS, thereby switching an antiatherosclerotic NO-producing enzyme to an enzyme that may initiate or even accelerate the atherosclerotic process by producing superoxide. Increased oxidative stress in the vasculature, however, is not restricted to the endothelium and has also been demonstrated to occur within the smooth muscle cell layer in the setting of hypercholesterolemia, diabetes mellitus, hypertension, congestive heart failure, and nitrate tolerance. Increased superoxide production by the endothelial and/or smooth muscle cells has important consequences with respect to signaling by the soluble guanylyl cyclase (sGC) and the cGMP-dependent protein kinase I (cGK-I), the activity and expression of which has been shown to be regulated in a redox-sensitive fashion. The present review summarizes current concepts concerning eNOS uncoupling and also focuses on the consequences for downstream signaling with respect to activity and expression of the sGC and cGK-I in various diseases.
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PMID:Vascular consequences of endothelial nitric oxide synthase uncoupling for the activity and expression of the soluble guanylyl cyclase and the cGMP-dependent protein kinase. 1587 5

Hypercholesterolemia is a major risk factor in the development of cardiovascular disease and HMG-CoA reductase inhibitors (i.e. statins) were originally designed to reduce serum cholesterol levels and thus reduce this risk factor. However, it has become increasingly apparent that the effects of statins extend well beyond their lipid lowering actions, and these pleiotropic effects have a major role in protecting the myocardium against ischemic injury. There have been a large number of clinical studies demonstrating the safety and efficacy of statins in reducing total mortality as well as many other secondary endpoint markers in patients with cardiovascular disease. In addition, statins appear to benefit patients with a variety of clinical conditions such as acute coronary syndromes and severe heart failure. Recent experimental studies demonstrated that stains can rapidly (i.e. within hours) upregulate endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production. These landmark studies of statins and eNOS function set the foundation for the investigation of the protective effects of statins. Many experimental studies investigating the effects of statins on eNOS and cardiac injury in the setting of ischemia and reperfusion have been performed in an attempt to determine the extent of the protection as well as the mechanism of the protection. This review article will focus on our current understanding of statin-mediated protection of the myocardium against ischemia-reperfusion injury and infarction.
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PMID:Statin mediated protection of the ischemic myocardium. 1592 59

The objective of this study was to prospectively determine the incidence of venous thrombosis (VT) in the upper limbs in patients with peripherally inserted central catheters (PICC). We prospectively investigated the incidence of VT in the upper limbs of 26 patients who had PICC inserted. The inclusion criteria were all patients who had a PICC inserted, whilst the exclusion criterion was the inability to perform a venogram (allergies, previous contrast medium reaction and inability of gaining venous access). Both valved and non-valved catheters were evaluated. Prior to removal of the PICC, an upper limb venogram was performed. The number of segments involved with VT were determined. The duration of central venous catheterization was classified as; less than 6 days, between 6 days and 14 days and more than 14 days. VT was confirmed in 38.5% (10/26) of the patients. The majority 85.7% (12/14) were complete occlusive thrombi and the majority of VT only involved one segment. There was no statistical correlation between the site of insertion of the PICC and the location of VT. Neither was there any observed correlation between the occurrence of VT with the patient's history of hypertension, hypercholesterolaemia, coronary artery disease, diabetes mellitus, cardiac insufficiency, smoking or cancer. There was also no statistical correlation with the size of the catheter. In conclusion, PICCs are associated with a significant risk of upper extremity deep vein thrombosis (UEVT).
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PMID:Incidence of upper limb venous thrombosis associated with peripherally inserted central catheters (PICC). 1596 40

This was a retrospective cohort study to assess the effect of hypertension (HTN) among Qatari and Asian patients admitted to the Hamad General Hospital in Qatar with heart failure (HF) and to identify risk factors that contribute to the development of HF in HTN patients in the State of Qatar. A total of 20,856 patients were treated during the 10-year period; 8446 were Qataris and 60% were male. Among the total Qatari patients admitted with HF (n=2342), 52.4% had HTN. The incidence of HTN was slightly higher in males than in females (50.4 vs. 49.6%; p<0.001). Significantly more HTN patients had diabetes mellitus (DM) (p<0.001) and hypercholesterolemia (p<0.001). There was also a significant difference between Qatari and Asian HTN patients in respect of their age (p<0.001) and gender (p<0.001). Qatari hypertensive patients were more likely to have DM (p<0.001). HTN and DM were the most common risk factors for HF.
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PMID:Is hypertension a predictor for heart failure? A cross cultural comparison over a 10-year period. 1604 5


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