Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UE34 (fibrinogen)
 30,244 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral arterial disease has received less attention from epidemiologists than coronary and cerebrovascular disease. Prevalence and incidence data typically show that peripheral arterial disease increases with age, is more common in men than women, and that symptomatic disease is only the tip of the iceberg. Studies concerning the prevalence of peripheral arterial disease rely mainly on the Rose questionnaire, which is used to screen for intermittent claudication, and on the ankle/brachial index, used to detect asymptomatic disease. Although there is a certain parallel between the 2 sets of data, the figures for asymptomatic disease consistently surpass those for clinical disease, and there is a wide variation between frequencies obtained in individual studies. In general, the prevalence of peripheral arterial disease is estimated to be under 2% for men aged less than 50 years, increasing to over 5% in those aged more than 70 years. Women reach these rates almost 10 years after men, although this gender difference decreases with increasing age. Figures for incidence follow a similar trend. The incidence of chronic critical ischaemia is estimated to be between 0.05% and 0.1% of the population. Asymptomatic disease detected with noninvasive tests is 3 to 4 times more frequent than intermittent claudication: its prevalence increases from under 5% for individuals aged less than 50 years to over 20% for individuals aged more than 70 years. The classical risk factors for atherosclerosis also apply to peripheral arterial disease, although their order of importance may be different from that for coronary and carotid disease. Several studies have shown that peripheral arterial disease correlates most strongly with cigarette smoking. Smoking is also the single greatest predictor of the progression of peripheral arterial disease. Other risk factors include hypertension, raised lipid levels (cholesterol and triglycerides for severe disease), diabetes, increased plasma viscosity, fibrinogen and homocysteine levels. Divergent views have been expressed in individual epidemiological studies with regard to the respective contribution of these risk factors to the development and progression of peripheral arterial disease. The natural history of peripheral arterial disease is characterised by a relatively benign local evolution. It can be estimated that, in general, 3 of 4 men presenting with intermittent claudication will never have a serious problem necessitating vascular intervention, and that no more than 5% are ever likely to require a major amputation. However, the underlying atherosclerotic pathology progresses with time: nondiseased arteries become obliterated and disease with an initially unilateral pattern frequently progresses to become bilateral. In addition, the few patients who do progress to critical ischaemia are at a significantly higher risk of amputation. The general prognosis for patients with peripheral arterial disease is particularly negative. There is a high prevalence of coronary heart disease and cerebrovascular disease in such patients, although the exact percentages depend on the patient population selected and on the method used for their evaluation. Coronary heart disease is detected in 40 to 60% of patients through a medical history combined with electrocardiography, while systematic coronary angiography detects coronary heart disease in 90% of those undergoing surgery. Although few patients with peripheral arterial disease have a history of stroke, in studies of surgical patients almost 30% appear to have significant extracranial disease. Patients with peripheral arterial disease have a poor life expectancy: the mortality rate is 3 to 5% per year in those with intermittent claudication and 20% per year in those with critical ischaemia. Coronary heart disease accounts for half of the total mortality, while vascular disease in general accounts for almost two-thirds.
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PMID:[Epidemiology and prognosis of peripheral obliterative arteriopathy]. 984 97

This study aims to estimate the prevalence of Helicobacter pylori in Glasgow, and to provide a systematic analysis of factors associated with this prevalence. The data used are from a random population sample of 793 men and 838 women aged 25-64 years conducted in 1995. The prevalence is estimated to be 66% (95% confidence interval: 63-68%); a level that is more typical of developing countries. Prevalence increases with age and social deprivation (P<0.0001) and is slightly higher in men than women (P = 0.07). After adjustment for age, social class, and sex group, H. pylori prevalence increases with increased cotinine (tobacco consumption) (P = 0.0005), increased number of siblings (P<0.0001), and decreased height (P = 0.03). Prevalence of coronary heart disease, hypertension, diabetes and intermittent claudication, alcohol consumption, fibrinogen, total serum cholesterol, HDL cholesterol, triglycerides, marital status, systolic and diastolic blood pressure had no independent association. The infection seems to be spread more readily in deprived, relatively crowded living conditions in childhood. The independent relationship with smoking suggests a possible second source of spread of infection in later years. The high degree of social deprivation in Glasgow is suggested as a major explanation of the high H. pylori prevalence found there.
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PMID:An investigation into factors associated with Helicobacter pylori infection. 1072 90

Increasing age and male gender are unavoidable risk factors for peripheral arterial occlusive disease (PAOD). A number of studies have looked at classical risk factors for atherosclerosis, such as diabetes, hypertension, lipid abnormalities, and smoking, as well as some more recently identified associations, such as plasma fibrinogen levels, impaired glucose tolerance, and hyperhomocysteinemia. However, most "risk factors" are really associations. A causal relationship may only reasonably be firmly established if a prospective controlled study shows that removing the risk factor significantly alters the course of the disease, as with smoking. Smoking is probably the strongest risk factor for intermittent claudication (IC), but hyperhomocysteinemia also appears to be strongly associated with the development of PAOD. Moderate alcohol intake and regular physical exercise appear to have a protective effect. A genetic risk factor is suggested but not as yet confirmed. The magnitude of the association varies from odds ratios of 2 to 3 for smoking and diabetes. There is insufficient evidence for hyperhomocysteinemia, but the effect may be even greater. The association with hypertension and lipid abnormalities is surprisingly inconclusive.
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PMID:Predictors of early disease in the lower limbs. 1077 37

Most estimates of the prevalence of peripheral atherosclerosis have been based on intermittent claudication or lower limb blood flow. The aim of this study was therefore to determine the prevalence of underlying femoral plaque, and to determine its association with other cardiovascular disease and risk factors. Presence of plaque was identified using ultrasound in a random sample of men (n=417) and women (n=367) aged 56-77 years. Coexistent cardiovascular disease, exercise and smoking were determined by questionnaire, blood pressure was recorded, and serum cholesterol and plasma fibrinogen were determined. Of the 784 subjects that were scanned, 502 (64%) demonstrated atherosclerotic plaque. Disease prevalence increased significantly with age (P<0.0001), and was more common in men (67.1 vs. 59.4%, P<0.05). Subjects with femoral plaque had a significantly greater odds of previous ischaemic heart disease (OR 2. 2, 95% CI 1.3, 3.7) and angina (OR 1.7, 95% CI 1.03, 2.7), but not of stroke or leg pain on exercise. Current and ex-smoking, raised serum total cholesterol and plasma fibrinogen levels, but not blood pressure, were associated with an increased risk of femoral plaque, independent of age and sex. Frequent exercise and a high HDL cholesterol were significantly associated with lower risk. In conclusion, therefore, atherosclerotic disease of the femoral artery affects almost two-thirds of the population in late middle age. It is associated with an increased prevalence of ischaemic heart disease and angina, but whether detecting at risk individuals using ultrasound offers advantages over simpler and less expensive risk factor scoring requires evaluation in trials.
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PMID:Femoral atherosclerosis in an older British population: prevalence and risk factors. 1099 52

The acute (0.57 microg/kg i.v. in 2 hours) and long-term (0.57 microg/kg i.v. in 2 hours for 5 days over 4 weeks) effects of the PGE1 analogue alprostadil were studied in patients affected with intermittent claudication. Whole Blood Viscosity (WBV), Whole Blood Filterability (WBF), haematocrit (Htc) and fibrinogen plasma concentration, were studied together with P50, 2,3-diphosphoglycerate, and adenosine plasma levels. Moreover, in the long-term study, pain-free (PFWD) and maximal walking distance (MWD) were measured. Single alprostadil infusion induced an improvement in WBV, WBF, and oxygen transport, and an increase in adenosine plasma levels. Long-term alprostadil administration produced a decrease in WBV only, without significant changes in WBF, Htc, fibrinogen, P50, 2,3-diphosphoglycerate, also inducing a significant prolongation of PFWD and MWD. The possibility is suggested that pulse rises in adenosine plasma levels play a role in the effects of chronic alprostadil administration, maybe in a way similar to that observed in the phenomenon of ischaemic preconditioning,
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PMID:Effects of alprostadil on blood rheology and nucleoside metabolism in patients affected with lower limb chronic ischaemia. 1134 34

Peripheral artery disease is associated with altered blood rheologic properties, including increased viscosity and decreased red blood cell (RBC) deformability. Pentoxifylline and cilostazol are available therapies for intermittent claudication. Improvement of blood viscosity and erythrocyte deformability have been cited as potential mechanisms of action for pentoxifylline. Cilostazol is a new drug with antiplatelet and vasodilating activity, but the mechanism by which it promotes an improvement in walking is not known. This study was performed to evaluate and compare the hemorheologic effects of pentoxifylline and cilostazol on viscosity, fibrinogen levels, and erythrocyte deformability when administered to adults with moderate to severe claudication. A double-blind, controlled study was conducted and included 59 patients (46 male, 13 female; mean age 65 yr) randomized to pentoxifylline 400 mg orally thrice daily (n=20), cilostazol 100 mg orally twice daily (n=19), or placebo (n=20); all subjects were observed for 24 weeks. Walking ability was assessed before, during, and at the conclusion of treatment by standard constant speed, variable grade treadmill testing. Erythrocyte deformability was measured by passage of washed RBCs, 10% hematocrit in phosphate buffered saline (PBS), through a polycarbonate membrane with 4.7 to 5.0 microm pores. Whole blood and plasma viscosity were measured using a cone/plate viscometer at variable shear rates (from 4.5 to 450 sec(-1)). Erythrocyte sedimentation rate was measured by a modified Westergren technique. Fibrinogen was assayed by a commercial reference laboratory. Plasma viscosities did not change significantly in any treatment group. Within-group comparisons demonstrated a significant (p<0.01) drop in whole blood viscosity (week 24 compared with week 0) for cilostazol-treated subjects (at shear rates of 45, 90, 225, and 450 sec(-1)), but these changes were not significantly different from those in the placebo group. There were no significant changes in whole blood viscosity for subjects treated with pentoxifylline or placebo. There were no significant changes in erythrocyte deformability, fibrinogen, or erythrocyte sedimentation rate. A trend toward improved walking distances was noted for both pentoxifylline and cilostazol in comparison with placebo. This trend was not correlated with changes in any underlying rheologic parameter. Ex vivo rheologic characteristics of blood from patients with intermittent claudication are not significantly affected by long-term administration of pentoxifylline or cilostazol. Pentoxifylline did not modulate viscosity or red cell deformability, a finding at variance with its putative mechanism of action. Pentoxifylline cannot be differentiated from cilostazol based on specific hemorheologic effects evaluated in this study. Different mechanisms of action for these medications should be considered.
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PMID:Failure of pentoxifylline or cilostazol to improve blood and plasma viscosity, fibrinogen, and erythrocyte deformability in claudication. 1236 57

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. The present study was undertaken to compare the effects of policosanol and lovastatin on patients with moderately severe intermittent claudication. The study had a 4-week baseline step, followed by a 20-week double blinded, randomized treatment period. Twenty-eight patients who met study entry criteria were randomized to policosanol 10 mg or lovastatin 20 mg tablets once daily. Walking distances in a treadmill (constant speed 3.2 km/hr, slope 10 degrees, temperature 25 degrees C) were assessed before and after 20 weeks of treatment. Both groups were similar at randomization. Compared with baseline, policosanol increased significantly (p < 0.01) the initial claudication distance (ICD) from 160.39 +/- 15.82 m to 211.31 +/- 21.48 m (+33.7%) and the absolute claudication distance (ACD) (p < 0.001) from 236.39 +/- 25.44 m to 288.09 +/- 28.47 m (+24.3%); meanwhile both variables remained unchanged after lovastatin therapy. Changes in ICD and ACD were significantly larger in the policosanol than in the lovastatin group (p < 0.01). Policosanol, but not lovastatin, significantly increased (p < 0.05) the ankle/arm index, although between-group differences were not significant. The frequency of patients reporting improvement on quality of life domains was greater in the policosanol than in the lovastatin group. Policosanol significantly (p < 0.001) lowered total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) by 17.5% and 31.0%, respectively, and meanwhile increased (p < 0.01) high-density lipoprotein-cholesterol (HDL-C) levels by 31.5%. Lovastatin reduced (p < 0.01) TC (18.0%), LDL-C (22.6%), and (p < 0.05) triglycerides (9.8%). In addition, policosanol, but not lovastatin, moderately, but significantly, reduced (p < 0.05) fibrinogen levels, so that final values and percent changes in both groups were different (p < 0.01). Treatments were well tolerated. Only 1 lovastatin patient withdrew from the study because of a nonfatal myocardial infarction. Five lovastatin patients, but none from the policosanol group, experienced 6 adverse events (AE) (p < 0.01). The present results indicate that policosanol, but not lovastatin, is a suitable alternative to manage patients with intermittent claudication because of pleiotropic properties beyond its cholesterol-lowering effects.
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PMID:Effects of policosanol and lovastatin in patients with intermittent claudication: a double-blind comparative pilot study. 1259 93

Peripheral artery disease (PAD) and intermittent claudication are common in men aged over 55 years. Once the diagnosis has been made, very few patients suffer from a deterioration of the disease. Those that do deteriorate tend to do so due to thrombosis of an affected artery. It is apparent that the disruption in the vessel wall accounts for some of the cause of the thrombosis but blood constituents also play a role. We hypothesized that levels of soluble P-selectin (sP-sel, a marker of platelet activation), von Willebrand factor (vWf, an index of endothelial damage/dysfunction), tissue factor (TF, a coagulation protein involved in the 'extrinsic' coagulation pathway) and fibrinogen would be abnormally elevated in relation to disease severity and correlated with each other, and related to ethnicity, in a multiethnic population of patients with PAD. To test this hypothesis, we studied 234 patients (80% white, 7% Indo-Asian, 13% Afro-Caribbean) with confirmed PAD [ankle brachial pressure index (ABPI)< or =0.8] and 50 healthy controls. All of the indices studied were increased in patients over controls (p<0.05). None of the indices of the hypercoagulable state were significantly different between the three ethnic groups studied. Patients with ischaemic rest pain were shown to have higher levels of plasma fibrinogen (p<0.001) although none of the other prothrombotic markers were increased in this group. Furthermore, fibrinogen was higher in cases whose ABPI was below the median (<0.52) when compared to those less severely affected, with an inverse correlation between fibrinogen and ABPI (Spearman, r=-0.178, p=0.009). In conclusion, we found a prothrombotic state in patients with PAD with increased levels of markers of endothelial damage/dysfunction, platelet activation and thrombosis, which may contribute to the pathogenesis of this condition. However, disease severity was only related to plasma fibrinogen levels.
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PMID:Thrombogenesis and endothelial damage/dysfunction in peripheral artery disease. Relationship to ethnicity and disease severity. 1469 67

Elevated plasma concentrations of the sulphur-containing amino acid homocysteine (Hcy) is associated with increased risk of atherosclerosis and arterial thrombosis. The mechanism by which Hcy exerts these effects has yet to be fully elucidated, although a variety of possible mechanisms have been proposed, including endothelial dysfunction or haemostatic abnormalities. However, the influence of Hcy on platelets, cells central to the atherothrombotic process, has never been addressed directly in patient studies. Here, the influence of mild hyperhomocysteinaemia (hHcy) on platelet function was explored in patients with peripheral occlusive arterial disease as evidence by intermittent claudication. Claudicants (n = 39) were assigned to one of two subgroups depending on their plasma Hcy concentrations. hHcy claudicants had plasma Hcy concentrations of 18.9 +/- 1.0 microM (n = 24), compared to 11.3 +/- 0.5 microM for normohomocysteinemic (nHcy) claudicants (n = 15) and 12.6 +/- 0.7 microM for age-matched controls (n=15). Platelet function was evaluated ex vivo in both groups and compared to age-matched controls. Platelet activation and sensitivity to nitric oxide-mediated inhibition was assessed by platelet fibrinogen binding and P-selectin expression. At low concentrations of adenosine diphosphate (ADP; 0.1 microM) and thrombin (0.02 U/ml), platelets from hHcy claudicants were more reactive than those from age-matched controls, but not nHcy claudicants. Agonist-induced P-selectin expression was significantly raised in hHcy claudicants compared to all other groups. Interestingly no differences were observed between nHcy claudicants and age-matched controls, indicating that claudication per se did not affect platelet function. Since platelet activity in vivo is determined by the exposure to both agonists and antagonists, we subsequently tested the sensitivity of platelets to inhibition by nitric oxide (NO), using the same platelet markers. Platelets from hHcy claudicants were significantly less sensitive to GSNO (1-100 microM)-mediated inhibition than all other groups. GSNO (1microM) induced 42.6 +/- 10 and 39 +/- 11.5% inhibition of ADP-induced fibrinogen binding for the nHcy claudicants and age-matched controls, respectively. However, in hHcy claudicants only 16.4 +/- 9.7% inhibition was observed, significantly less than the other groups (P < 0.01). Again no differences between nHCy claudicants and controls were observed. These results suggest the presence of claudication alone does not influence platelet function but if complicated with mild hyperhomocysteinemia, the sensitivity to agonists is increased, and more importantly, their sensitivity to inhibition is greatly reduced. The overall effect would be an increased propensity for platelet activation. The presence of even mildly elevated plasma Hcy could dramatically increase thrombotic risk.
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PMID:Altered platelet reactivity in peripheral vascular disease complicated with elevated plasma homocysteine levels. 1518 48

The US FDA has approved two drugs for the management of intermittent claudication: pentoxifylline and cilostazol. The mechanism of action that provides symptom relief with pentoxifylline is poorly understood but is thought to involve red blood cell deformability as well as a reduction in fibrinogen concentration, platelet adhesiveness and whole blood viscosity. The recommended dose of pentoxifylline is 400 mg three times daily with meals. Cilostazol is a potent, reversible, phosphodiesterase III inhibitor. The inhibition of phosphodiesterase allows for the increased availability of cyclic adenosine monophosphate (cAMP). cAMP mediates many agonist-induced platelet inhibitory, vasodilatory and vascular antiproliferative responses. Cilostazol, at a dose of 100 mg twice daily, is recommended to be taken 30 minutes before or 2 hours after breakfast and dinner. In addition to pentoxifylline and cilostazol, clinical trials indicate many other drugs may relieve the symptoms of intermittent claudication. Ginkgo biloba, available as an over-the-counter extract, provides symptom relief comparable to pentoxifylline. Two European agents, naftidrofuryl and buflomedil, also have efficacy that is reported to be similar to pentoxifylline. Policosanol is a mixture of fatty alcohols derived from honeybee wax which, according to very limited data, reduces symptoms of claudication. Amino acids, certain peptides and prostaglandins may have a therapeutic role. Finally, novel approaches including angiogenesis mediated by growth factors, are currently under investigation.
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PMID:Drug treatment of intermittent claudication. 1525 27


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