Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to assess the potential role of lipoprotein (a) as a risk factor for cardiovascular disease in diabetes mellitus, plasma concentrations were measured in a large group (n = 500) of non-insulin-dependent (NIDDM, n = 355) and insulin-dependent (IDDM, n = 145) patients. Concentrations of lipoprotein (a) were compared in diabetic patients with (n = 153) or without (347) documented vascular disease (ischaemic heart disease, peripheral vascular disease or macroangiopathy). They were significantly higher (p < 0.05) in patients with ischaemic heart disease (mean [interquartile range] 15.5 (5.0-38.0) vs 9.0 (4.5-26.0) mg/dl) or macroangiopathy (13.0 (5.0-38.0) vs 9.0 (4.0-25.0) mg/dl) compared to patients without manifestations of vascular disease. In addition, stepwise logistic regression analysis identified lipoprotein (a) levels > or = 30 mg/dl as being independently associated with the presence of cardiovascular disease. Lipoprotein (a) was an independent risk factor for ischaemic heart disease and macroangiopathy in this group of IDDM and NIDDM patients.
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PMID:Lipoprotein (a) and vascular disease in diabetic patients. 767 94

Endothelins (ET) are a family of peptides with potent biological properties. Endothelial cells produce exclusively ET-1 while other tissues produce ET-2 and ET-3. The production of ET requires an increase in intracellular Ca2+. This increase can be induced by physical chemicals (i.e. hypoxia) or receptor-operated stimuli (i.e. thrombin, angiotensin II, arginine vasopressin, transforming growth factor beta 1, interleukin-1). Most of ET is released abluminally towards vascular smooth muscle and less luminally. The main vascular effect of ET are vasodilation (transient), profound and sustained vasoconstriction as well as proliferation of vascular smooth muscle. These biological effects are mediated by distinct receptors. Three ET receptors have been cloned, i.e. ETA-, ETB- and ETC-receptors. In vascular tissue ETA-receptors are expressed on vascular smooth muscle and responsible for vasoconstriction. ETB-receptors are expressed on endothelium and linked to nitric oxide and/or prostacyclin release. Activation of these receptors explains the transient vasodilation with intraluminal application of ET. Vascular smooth muscle cells can express ETB-receptors which contribute to ET-induced vasoconstriction particularly at lower concentrations. The role of the recently cloned ETC-receptor in the vasculature is still uncertain. ET production is increased (as judged from circulating plasma levels) in vascular disease and atherosclerosis in particular, in myocardial infarction and heart failure, pulmonary hypertension and renal disease. ET production is increased in arterial hypertension remains controversial. Non-peptidic ET antagonists have been developed which either block ETA- receptors or ETA- and ETB-receptors simultaneously. The advantage of ETA-receptors is that they leave the endothelium-dependent vasodilation to ET (via ETB-receptor) intact. However, ETB-mediated contraction remains unaffected by these antagonists. In contrast ETA-/ETB-antagonists fully prevent ET-induced vasoconstriction, however, they also inhibit the endothelial effects of the peptide. ET antagonists interfere with the effects of ET in isolated vascular tissue (including that obtained from humans) as well as in vivo. In humans, ETA as well as ETA-/ETB-antagonists inhibit endothelin-induced vasoconstriction. Hence in summary ET are a family of potent peptides with profound effects in the vasculature. Several studies suggest a role of ET in cardiovascular disease. The newly developed ET-antagonists are potent and selective tools to delineate the (patho-)physiological roles of ET and may become a new class of cardiovascular drugs.
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PMID:Endothelin and endothelin antagonists: pharmacology and clinical implications. 771 86

The relation between proteinuria and mortality was investigated in 1188 patients with Type 1 diabetes and 3234 patients with Type 2 diabetes, aged 35-55 at baseline and followed up for a mean of 9.4 +/- 3.1 years in the WHO Multinational Study of Vascular Disease in Diabetes. Baseline prevalence of light or heavy proteinuria was the same (25%) in both types of diabetes after adjustment for differences in diabetes duration. Compared with patients with no proteinuria, all cause mortality ratios were 1.5 (95% confidence interval 1.1-2.0) and 2.9 (2.2-3.8) for Type 1 patients with light and heavy proteinuria, respectively, and 1.5 (1.2-1.8) and 2.8 (2.3-3.4) for Type 2 patients, after adjustment for age, duration of diabetes, blood pressure, cholesterol, and smoking. Proteinuria was associated with significantly increased mortality from renal failure, cardiovascular disease, and all other causes of death. In both types of diabetes, the association was strongest for renal deaths, and of similar magnitude for cardiovascular and all other causes of death. In conclusion, proteinuria is a common, important, and rather non-specific risk factor for increased morbidity and mortality in diabetes. The relation of proteinuria to mortality is similar for both types of diabetes. The benefits and risks of proteinuria reduction should be examined in large randomized trials with clinical endpoints.
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PMID:Proteinuria and mortality in diabetes: the WHO Multinational Study of Vascular Disease in Diabetes. 774 62

Nitric oxide derived from the vascular endothelium and other cells of the cardiovascular system has important roles in physiological regulation of blood flow and may have pathophysiological functions in cardiovascular disease. Nitric oxide can be synthesised from L-arginine by any of three isoforms of nitric oxide synthase (NOS), and its interaction with prostacyclin, its proposed mechanisms of action and cytotoxicity are briefly reviewed in the context of cardiovascular function. Although nitric oxide can hyperpolarize vascular smooth muscle, activation of the endothelium can induce hyperpolarization and vasodilatation by other means. Nitric oxide has important roles in the physiological regulation of local blood flow and blood pressure, especially during exercise and in response to shear stresses and other local factors in arterioles. Nitric oxide is also involved in neurogenic control of the microcirculation through autonomic efferent nerves and it contributes to vasodilatation and inflammation associated with activation of sensory nerves. In pathological circumstances, excess nitric oxide produced by inducible NOS compromises circulatory function in septic shock, during transplant rejection, and during myocardial ischaemia and reperfusion injury. Immunosuppressant drugs like cyclosporin A inhibit the expression of NOS through complex intracellular intermediates. Disturbances in the activity of constitutive and inducible NOS in the artery wall accompany the development of atherosclerosis, vasospasm and thrombosis, and may contribute to some forms of hypertension and diabetic vascular disease. Reversing the nitric oxide defect with therapeutic agents including angiotensin-converting enzyme inhibitors offers promise in protecting against some manifestations of vascular disease.
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PMID:Nitric oxide in cardiovascular disorders. 777 76

The decline in cardiovascular disease has been a major public health success. The relationship between key risk factors such as blood cholesterol levels, smoking, high blood pressure and clinical disease are universally accepted. The approaches to the prevention of cardiovascular disease are changing to a greater emphasis on the prevention of elevated risk factors by better understanding of the relationship between lifestyle and host susceptibility (genetic attributes) and the risk factor changes with age. The development of new methods to measure vascular disease non-invasively in vivo changes the approaches to evaluation of both risk and definition of endpoints in analytical studies and clinical trials. It is possible now to increase the rate of decline in coronary heart disease.
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PMID:Future in lipid and lipoprotein research: from preventing clinical disease to preventing elevated risk factors. 780 21

Insulin is frequently considered to be a risk factor for atherosclerosis (or for coronary and vascular disease). Furthermore, hyperinsulinaemia is claimed to be the primary cause underlying the other features which make up the insulin resistance syndrome. However, if proof of these assertions is based only on prospective studies, its value is limited. Only two studies, both carried out, surprisingly, in policemen, have shown convincingly that insulin was a coronary risk factor. In one of the studies, the Paris Prospective Study, the insulin-coronary disease correlation was shown to subside with increasing duration of follow-up. The other prospective studies have failed to evidence a correlation between insulinaemia and cardiovascular events, even with univariate analysis. One study even showed a negative correlation between insulinaemia and coronary complications. In view of the fact that insulinaemia has been shown repeatedly to be associated with classic cardiovascular risk factors--systolic hypertension, decrease in HDL cholesterol, increase in triglycerides, and abdominal obesity--it is highly surprising that univariate analysis has not been able to show the same correlation between insulin and cardiovascular complications. In fact, the combination of elevated insulinaemia and classic risk factors may result in protection against the deleterious effects of these factors. Another possibility would be that insulinaemia is associated with unknown protective factors. Both hypotheses would account for the existence of a correlation between insulin and current cardiovascular disease, as well as the absence of correlation between insulin and later onset of cardiovascular disease.
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PMID:[Why is insulin tied to the prevalence of cardiovascular diseases without being a risk factor for their incidence?]. 782 81

Carvedilol is a nonselective beta-adrenoceptor blocking vasodilator drug that may be a promising new agent in the management of cardiovascular disease. The rationale for the development of agents of this type is that the alpha-blocking component may overcome the direct vasoconstrictor consequence of beta 2-blockade, whilst the beta-blocker component may inhibit the reflex tachycardia that occurs following alpha-blockade. In clinical trials published to date, carvedilol has been demonstrated to be effective as an antihypertensive agent as monotherapy and also as additional therapy in those patients whose blood pressure cannot be controlled on other standard agents. It is also effective in the management of angina. Carvedilol has beneficial haemodynamic effects in patients with congestive heart failure. beta-Blocker vasodilator drugs of this type may be particularly useful in this condition as the vasodilator component of the drug may overcome the initial negative inotropy of the beta-blocker. In addition, carvedilol possess potentially useful pharmacological actions. In particular, the drug has antimitogenic and free radical scavenging effects that may make it a useful therapy in the long term management of atherosclerotic vascular disease. Its metabolic profile is also favourable, presumably on the basis of its alpha-blocking properties. Thus, beta 2-mediated adverse effects on peripheral vascular tone, glycaemic control and lipid status appear to be offset by the alpha-blocking property of the drug. Carvedilol thus far appears to be well tolerated, with postural dizziness the major adverse effect, especially in the elderly. As with nonselective beta-blockers, carvedilol is contraindicated in patients with asthma.
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PMID:A risk-benefit assessment of carvedilol in the treatment of cardiovascular disorders. 794 2

Diabetes is associated with increased morbidity and mortality from cardiovascular disease in the absence of the major risk factors--cigarette smoking, hypertension and serum cholesterol concentration. When these risk factors are present, the attributable risk to each factor alone and to the combination of risk factors is higher in diabetic than in nondiabetic subjects. Thus, stringent measures to correct risk factors for cardiovascular disease have been advocated in diabetic patients. In addition to hypercholesterolaemia, other lipid and lipoprotein abnormalities collectively referred to as diabetic dyslipidaemia probably contribute to vascular risk. Hypertriglyceridaemia, often associated with low high-density-lipoprotein cholesterol, is common in NIDDM patients and is associated with insulin resistance. Recent information in diabetic patients, pointing to the association of hypertriglyceridaemia with accumulation of remnant particles and alterations in low-density-lipoprotein subfractions, helps to explain the strong relationship between hypertriglyceridaemia and vascular risk in these individuals. Although there are as yet no intervention trials with lipid-lowering diets or drugs in diabetic patients to judge the impact on vascular disease, national and international bodies have furnished guidelines for the identification and treatment of lipid disorders in diabetes in the hope of reducing the huge toll of vascular disease in these patients.
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PMID:Diabetic dyslipidaemia: treatment implications. 798 8

Diabetes is associated with increased morbidity and mortality from cardiovascular disease in the absence of the major risk factors: cigarette smoking, hypertension, and serum cholesterol concentration. When these risk factors are present, the attributable risk to each factor alone and to the combination of risk factors is higher in diabetics than in nondiabetics. Thus, stringent measures to correct risk factors for cardiovascular disease have been advocated in diabetic patients. In addition to hypercholesterolemia, other lipid and lipoprotein abnormalities collectively referred to as diabetic dyslipidemia are likely to contribute to vascular risk. Hypertriglyceridemia often associated with low high-density lipoprotein cholesterol is common in non-insulin-dependent diabetes mellitus patients and is associated with insulin resistance. Recent information in diabetic patients pointing to the association of hypertriglyceridemia with accumulation of remnant particles and alterations in low-density lipoprotein subfractions helps to explain the strong relationship between hypertriglyceridemia and vascular risk in these individuals. Although there are as yet no intervention trials with lipid-lowering diets or drugs in diabetic patients to judge the impact on vascular disease, national and international bodies have furnished guidelines for the identification and treatment of lipid disorders in diabetes in the hope of reducing the huge toll of vascular disease in these patients.
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PMID:Diabetic dyslipidemia. 801 62

Microalbuminuria and its association with vascular disease has previously been reported in nondiabetic individuals. The aims of this study were to determine whether there is a cross-sectional relationship between urinary albumin excretion rate and cardiovascular disease in nondiabetic subjects and to investigate hereditary predisposition to microalbuminuria by studying offspring of the main study population. Europid patients, aged 40-70 years, were randomly selected from a large inner-city general practice; there was a 62.6% attendance rate, and a study population of 959 remained after exclusions. Blood pressure, ankle systolic pressure, height, and weight were measured. Albumin excretion rate was calculated from overnight and morning urine collections. Venous blood was taken for lipids, fibrinogen, and factor VII; and resting electrocardiograms were carried out. Offspring (aged 15-40 years) of those found to be microalbuminuric were invited to attend for the same tests, and controls were selected by age and sex matching the parents. There was no association between parents' albumin excretion rate with that of their offspring, and there were no significant differences in albumin excretion rate between offspring subjects and their controls. There were no statistically significant associations of prevalent coronary heart disease (CHD) with albumin excretion rate or microalbuminuria in either sex [CHD in women: odds ratio (OR) 1.85; 95% confidence interval (CI) 0.19,9.0] [CHD in men: OR 2.13; 95% CI (0.64, 6.59)]. In women, there were significant associations between albumin excretion rate and peripheral vascular disease (positive) and fibrinogen (negative). Because established risk factors may not be as strongly associated with CHD in cross-sectional studies, we intend to follow this group prospectively.
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PMID:Associations of urinary albumin excretion rate with vascular disease in europid nondiabetic subjects. 808 57


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