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)

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. The present study was undertaken to compare the effects of policosanol and ticlopidine in patients with moderately severe intermittent claudication (IC). The study had a 4-week baseline step, followed by a 20-week double-blinded, randomized treatment period. Twenty-eight eligible patients were randomized to policosanol 10 mg or ticlopidine 250 mg tablets twice daily (bid). 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 baseline. Compared with baseline, policosanol significantly increased (p < 0.01) mean values of initial (ICD) and absolute (ACD) claudication distances from 162.1 to 273.2 m and from 255.8 to 401.0 m, respectively. Ticlopidine also raised significantly (p < 0.01) ICD (166.2 to 266.3 m) and ACD (252.9 to 386.4 m). Comparisons between groups did not show significant differences. Policosanol, but not ticlopidine, significantly (p < 0.05), but modestly, increased the ankle/arm pressure ratio. After 10 weeks, policosanol significantly (p < 0.001) lowered low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC) (p < 0.01), and TC/HDL-C and raised (p < 0.05) high-density lipoprotein-cholesterol (HDL-C). At study completion, policosanol lowered (p < 0.001) LDL-C (30.2%), TC (16.9%), and TC/HDL-C (33.9%), increased (p < 0.01) HDL-C (+31.7%), and left triglycerides unchanged. Ticlopidine did not affect the lipid profile variable. Policosanol induced modest, but significant, reductions (p < 0.01) of fibrinogen levels compared with baseline and ticlopidine. Treatments were well tolerated and did not impair safety indicators. Three ticlopidine patients (21.4%) withdrew from the trial, only 1 owing to a serious adverse experience (AE) (unstable angina). Three other ticlopidine patients experienced mild AE (headache, diarrhea, and acidity). It is concluded that policosanol (10 mg bid) can be as effective as ticlopidine (250 mg bid) for improving walking distances of claudicant patients, and it could be advantageous for the global risk of these individuals owing to its cholesterol-lowering effects. This study is, however, just a pilot comparison, so that further studies in larger sample sizes are needed for definitive conclusions of the comparative effects of both drugs on patients with IC.
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PMID:Effects of policosanol and ticlopidine in patients with intermittent claudication: a double-blinded pilot comparative study. 1525 82

Although it is known that LDL-apheresis improves ischemic limb seen in patients with peripheral arterial occlusive disease (PAOD), anti-inflammatory effects are not well known. We studied whether or not serum or plasma levels of high sensitivity C-reactive protein (hsCRP), monocyte chemoatractant protein-1 (MCP-1), or fibrinogen could contribute to favorable effects for ischemic limbs after LDL-apheresis. Twenty-eight patients with PAOD (24 men, 4 women) were enrolled in our study. LDL-apheresis was performed 10 times (treated plasma of 3,000 ml) for 5 weeks. Serum levels of logarithmically transformed values of hsCRP significantly decreased from 3.666 +/- 0.126 to 3.482 +/- 0.139 ng/ml before and after a single session of LDL-apheresis (P < 0.001). Serum levels of MCP-1 decreased from 233 +/- 17.5 to 187 +/- 13.5 pg/ml before and after LDL-apheresis (P < 0.05). Likewise, plasma fibrinogen levels statistically decreased from 196 +/- 9.82 to 159 +/- 9.60 mg/dl (P < 0.001). Overall rates of improvement including foot chillness or numbness, and double folds increase in walking distance were 82.1% 3 months after a completion of LDL-apheresis, while gangrene was only improved 14.3%. Intermittent claudication improved in 53.6%. The favorable actions of LDL-apheresis might include anti-inflammatory effects. To avoid amputation, LDL-apheresis should be applied for patients with PAOD at an early stage of the disease process and may be applicable for patients with atherosclerotic cardiovascular disorders.
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PMID:LDL-apheresis improves peripheral arterial occlusive disease with an implication for anti-inflammatory effects. 1588 Apr 5

Cigarette smoking is probably the most important risk factor for the development of peripheral arterial disease, but it may be less important in the aetiology of ischaemic heart disease. The objectives of this study were to determine whether any other cardiovascular risk factors showed a significant interaction with cigarette smoking which would explain the greater association between smoking and peripheral atherosclerosis. One thousand five hundred and ninety-two subjects aged 55-74 years were selected randomly from the age-sex registers of 10 general practices in Edinburgh, Scotland. The presence of peripheral arterial disease was determined by the World Health Organisation questionnaire on intermittent claudication, the ankle brachial pressure index and a reactive hyperaemia test. Heart disease was identified by the patients' recall of a doctor diagnosis of angina or myocardial infarction. There were 131 subjects with peripheral arterial disease but no ischaemic heart disease, and 169 with heart disease without peripheral disease. Significantly more smokers occurred in the peripheral than the heart disease group (P <0.01), and in current smokers the age and sex adjusted odds ratio were highly significant for peripheral arterial disease (odds ratio 5.09, 95% confidence interval 2.97-8.72, P<0.001), but not for heart disease (odds ratio 1.72, 95% confidence interval 0.98-2.33, P>0.05). Subjects with lower limb disease also had higher systolic pressures (P<0.001), serum high density lipoprotein cholesterol (P<0.01) and plasma fibrinogen (P<0.05). On logistic regression, adjusting for a range of individual risk factors had no significant impact on the effect of smoking. Plasma fibrinogen produced the biggest reduction in odds ratio (4.23, 95% confidence interval 2.44-7.35, in current smokers with peripheral arterial disease). Therefore the stronger association between smoking and peripheral arterial disease than ischaemic heart disease does not appear to be influenced by the other risk factors examined here, and must be explained by some other mechanism.
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PMID:The relationship between cigarette smoking and cardiovascular risk factors in peripheral arterial disease compared with ischaemic heart disease. The Edinburgh Artery Study. 1603 87

The influence of optimal medical treatment (OMT) with or without additional percutaneous transluminal angioplasty (PTA) on vascular inflammation in peripheral arterial occlusive disease (PAD) patients was investigated. Patients with intermittent claudication (IC) and angiographically verified PAD were randomized to OMT (n = 28) or OMT + PTA (n = 28) and followed for 12 months. Ankle-brachial index (ABI), treadmill walking distances (WD), visual analogue scale (VAS), and blood sampling for the determination of selected soluble biomarkers were undertaken at baseline and after 3 and 12 months. After both 3 and 12 months, ABI, WD and VAS were highly significantly improved in favour of OMT + PTA (p < 0.05 for all). Significant improvements were recorded in both groups in serum lipids (p < 0.01 for all), except for triglycerides, and in the inflammatory markers P-selectin, interleukin-6, interleukin-10, monocyte chemoattractant protein-1 and fibrinogen (p < 0.05 for all). There were, however, no differences in the changes from baseline between the groups in any variable. Intervention with OMT alone or in combination with PTA did not differ with regard to the effects on serum lipids and markers of inflammation in our population of PAD patients. The combined treatment was, however, better for the treadmill walking distance.
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PMID:Beneficial effects of 1-year optimal medical treatment with and without additional PTA on inflammatory markers of atherosclerosis in patients with PAD. Results from the Oslo Balloon Angioplasty versus Conservative Treatment (OBACT) study. 1804 63

Intermittent claudication is the primary symptom of peripheral arterial disease, affecting between 1 and 3 million Americans. Symptomatic improvement can be achieved by endovascular revascularization, but such procedures are invasive, expensive, and may be associated with procedural adverse events. Medical treatment options, including claudication medications and supervised exercise training, are also known to be effective, albeit also with associated limitations. The CLEVER (Claudication: Exercise Vs. Endoluminal Revascularization) study, funded by the Heart, Lung, and Blood Institute of the National Institutes of Health, is a prospective, multicenter, randomized, controlled clinical trial evaluating the relative efficacy, safety, and health economic impact of four treatment strategies for people with aortoiliac peripheral arterial disease and claudication. The treatment arms are: (1) optimal medical care (claudication pharmacotherapy); (2) primary stent placement; (3) supervised exercise rehabilitation; and (4) combined stenting with supervised exercise rehabilitation. The CLEVER study is a 5-year randomized, controlled clinical trial to be conducted at approximately 25 centers in the United States that will monitor 252 patients and their responses to treatment during an 18-month follow-up period. The primary end point is change in maximum walking duration on a graded treadmill test. Secondary end points include the change at 18 months in maximum walking duration from baseline, comparisons of free-living daily activity levels assessed by pedometer, health-related quality of life, and cost-effectiveness. Other analyses include the effect of these treatment strategies on anthropomorphic and physiologic variables, including body mass index, waist circumference, blood pressure, pulse pressure, and resting pulse as well as biochemical markers of cardiovascular health, including fasting lipids, fibrinogen, C-reactive protein, and hemoglobin A 1c values.
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PMID:The Claudication: Exercise Vs. Endoluminal Revascularization (CLEVER) study: rationale and methods. 1844 Jan 81

Pentoxifylline is a methylxanthine derivative that has been used for several decades in the symptomatic management of intermittent claudication. For reasons that remain fairly obscure, this drug benefits blood rheology in a number of complementary ways: decreasing blood and plasma viscosity, lowering plasma fibrinogen while promoting fibrinolysis, and improving blood filterability by enhancing erythrocyte distensibility and lessening neutrophil activation. Anti-inflammatory effects on neutrophils and macrophage/monocytes-some of them attributable to pentoxifylline metabolites-appear to play a mediating role in this regard. Although clinical trials with pentoxifylline have often been too small in size to reach statistically significant findings regarding impacts on hard end points, a review of the existing literature suggests that pentoxifylline may have potential for slowing the progression of atherosclerosis, stabilising plaque, reducing risk for vascular events, improving the outcome of vascular events, dampening the systemic inflammatory response following cardiopulmonary bypass, providing symptomatic benefit in angina and intermittent claudication, enhancing cerebral blood flow in patients with cerebrovascular disease while slowing progression of vascular dementia, improving prognosis in congestive heart failure, and aiding diabetes control. This safe and usually well-tolerated drug works in ways quite distinct from other drugs more commonly used for cardiovascular protection, and hence may confer complementary benefit when used in conjunction with them. Major clinical trials of adequate statistical power are now needed to confirm the scope of benefits that pentoxifylline can confer; studies evaluating hard end points in acute coronary syndrome, stroke/transient ischaemic attack and systolic heart failure might be particularly valuable.
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PMID:Pentoxifylline for vascular health: a brief review of the literature. 2687 Mar 89

The formation of monocyte-platelet aggregates and neutrophil-platelet aggregates (MPA and NPA, respectively) is influenced by inflammation, but also might contribute to an exacerbation of inflammatory responses in atherosclerotic plaque. The purpose of this study was to analyze MPA and NPA proportions in regard to different stages of peripheral arterial disease (PAD). Forty-five patients with intermittent claudication (IC) (3 groups: Rutherford (R)-1, R-2, and R-3; each n = 15), 20 patients with critical limb ischemia (CLI) (Rutherford 5 (40%) and 6 (60%)), and 20 healthy controls were studied. Analyses of monocyte (Mon) subpopulations (CD14++CD16- (classical) Mon1, CD14++CD16+ (intermediate) Mon2, CD14+CD16++ (non-classical) Mon3), MPA, and NPA was performed from whole blood by flow cytometry. Controls showed an increased proportion of the Mon1 subpopulation (p < 0.001), whereas CLI patients showed a significant increase of the Mon2 subpopulation compared to controls, R-1, or R-2 patients (p < 0.0001). For the Mon3 subpopulation, CLI and R-3 patients showed an increased proportion (p < 0.05). MPA formation with the proinflammatory Mon2 and Mon3 subpopulations was increased in CLI patients (both p < 0.01). Similarly, NPA was significantly increased in CLI patients (p < 0.05). Serological markers of inflammation and procoagulation (fibrinogen [r = 0.459, p < 0.001], soluble triggering receptor expressed on myeloid cells (sTREM-1) [r = 0.237, p < 0.05] and P-Selectin [r = 0.225, p < 0.05]) correlated directly with MPA formation on the Mon2 subpopulation. We found an association of inflammatory and procoagulatory markers with increased formation of MPA on the Mon2 subpopulation. Since R-3 patients also had significantly increased MPA, one can speculate that the inflammatory burden might promote an aggravation of the disease.
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PMID:Leukocyte-platelet aggregates-a phenotypic characterization of different stages of peripheral arterial disease. 2735 29

These case reports aim to show that hyperfibrinogenemia is a risk factor for the progression and prognosis of peripheral arterial disease (PAD), in patients with and without diabetes mellitus type 2. We present a patient with PAD who has type 2 diabetes mellitus, who has previously been repeatedly treated for lower limb ischemia with multiple vascular surgeries performed. A few weeks before admission the patient developed critical lower limb ischemia, which was treated with an iliaco-popliteal and femorofemoral bypass. The patient had elevated serum fibrinogen values. In the current admission, renewed left limb ischemia was diagnosed, and surgically evaluated with a recommendation for amputation of the left limb as a surgical recommendation. Our second patient had a stable intermittent claudication, dyslipidemia and hyperfibrinogenemia. He was successfully treated for those risk factors. Regular monitoring of the patient showed improved claudication distance and quality of life Our case reports, supported by a literature review, demonstrate that hyperfibrinogenemia is a possible risk factor for progression and the prognosis of PAD.
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PMID:Hyperfibrinogenemia in Peripheral Arterial Disease: Coexistent and Independent Risk Factor (A Report of Two Cases and Review of Literature). 3086 71


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