Biomedical subjects

G D Lowe

Publications and source records attributed to G D Lowe.

At least 91 records · Page 5Linked to original sources

PubMed1997

Prediction of postoperative venous thrombosis using haemostasis tests.

The prediction of patients who are at sufficiently high risk of postoperative deep venous thrombosis to indicate perioperative antithrombotic prophylaxis has traditionally used only clinical risk factors. The associations of preoperative and/or postoperative haemostatic tests with postoperative deep venous thrombosis are reviewed. In general, the results support the biological concept of a preoperative and postoperative prothrombotic tendency in patients who develop deep venous thrombosis. Increased levels of coagulation activation markers and decreased assays of fibrinolytic potential show consistent relationships to postoperative deep venous thrombosis. At present, however, the clinical utility of such tests is unproven; so that at present they cannot be advocated for routine preoperative or postoperative screening.

Biomarkers↗

PubMed1997

Treatment of venous thrombo-embolism.

Clinically suspected deep vein thrombosis (DVT) or pulmonary thromboembolism (PE) should be initially treated with heparin, and an objective diagnosis obtained. In pregnancy, heparin is usually continued until delivery, following which warfarin is substituted. In the absence of pregnancy, warfarin is substituted and usually continued for 3 months after a first thrombo-embolic event. Low molecular weight heparins are increasingly preferred to unfractionated heparin in non-pregnant patients with acute DVT, because of efficacy when given by daily subcutaneous injection without routine monitoring of coagulation assays, greater efficacy, and lower risks of major bleeding and of mortality. Unfractionated heparin requires monitoring by the APTT (target ratio 1.5-2.5), and warfarin requires monitoring by the International Normalized Ratio (INR) of the prothrombin time (target ratio 2.0-3.0). Graduated elastic compression stockings reduce post-thrombotic leg symptoms after DVT. Secondary prevention is important in future high risk situations.

Anticoagulants↗

PubMed1997

Acute exercise and markers of endothelial injury in peripheral arterial disease.

OBJECTIVES: To determine the acute effects of exercise on plasma levels of markers of endothelial damage in patients with symptomatic peripheral arterial occlusive disease (PAOD). DESIGN: Prospective observational study of patients with angiographically proven PAOD undergoing treadmill exercise testing prior to surgical or radiological intervention. MATERIALS AND METHODS: Ante-cubital venous blood sampling was performed in 20 patients with symptomatic PAOD prior to, and 2 min after, treadmill exercise testing. Samples were then assayed for von Willebrand factor (vWf), tissue-type plasminogen activator (tPa), and plasminogen activator inhibitor (PAI) levels. RESULTS: Despite a significant fall in median ankle-brachial pressure indices from 0.96 pre-exercise to 0.59 post-exercise on the right, and from 0.92 to 0.40 on the left (both p < 0.005), there were no significant changes in plasma levels of vWf, tPa, or PAI following claudication-inducing exercise. CONCLUSIONS: Claudication-inducing exercise does not produce acute alterations in plasma markers of endothelial damage, and the results of this study do not support the belief that claudication-inducing exercise in PAOD is damaging to vascular endothelium.

Aged↗

PubMed1997

Haemostatic and rheological factors as predictors of restenosis following percutaneous transluminal angioplasty.

OBJECTIVES: To determine whether pre-angioplasty levels of haemostatic and rheological factors predicted restenosis of the dilated arterial segment following percutaneous transluminal angioplasty. DESIGN AND SETTING: Prospective study, Two regional hospital centres for angioplasty in Edinburgh and Glasgow, Scotland, UK. METHOD: Haemostatic and rheological factors were measured in 102 subjects with atherosclerotic disease of the lower limbs, immediately prior to percutaneous transluminal angioplasty. Subjects were followed up after 2-3 years for restenosis of the original angioplasty site using duplex scanning. RESULTS: Baseline clinical characteristics were similar between subjects who restenosed (n = 27) and those with no restenosis (n = 39), except that occluded lesions were more likely to restenose than stenoses (p < or = 0.05). There was no significant difference in age- and sex-adjusted mean levels of whole blood viscosity, plasma viscosity, haematocrit, von Willebrand factor, fibrin D-dimer or plasminogen activator inhibitor-1 activity between the stenosed and no restenosis groups (p > 0.1), but mean plasma fibrinogen was lower in the restenosed group (3.31 g/l vs. 3.75 g/l; p < or = 0.05). These results persisted after multivariate adjustment for smoking habit and type of lesion dilated. CONCLUSIONS: This study provides no evidence that raised, pre-angioplasty levels of haemostatic and rheological factors predict restenosis following percutaneous transluminal angioplasty of the arteries of the lower limbs.

Angioplasty, Balloon↗

PubMed1997

Moderate weight reduction improves red cell aggregation and factor VII activity in overweight subjects.

OBJECTIVE: To investigate the effect of a dietary intervention to reduce body weight on red cell aggregation (RCA), factor VII activity, plasminogen activator inhibitor (PAI) activity, tissue plasminogen activator (t-PA) antigen, fibrinogen, whole blood and plasma viscosity, haematocrit and lipids. DESIGN: Open single stranded study of dietary intervention for weight loss in a volunteer sample. SUBJECTS: Forty-five subjects whose BMI exceeded 26 kg/m2 were recruited and received dietetic advice designed to reduce body weight by 0.5 kg per week. MEASUREMENTS: Body weight and waist and hip circumferences, dietary intake by seven day weighed inventory, RCA, factor VII activity, PAI activity, t-PA antigen, fibrinogen, whole blood and plasma viscosity, haematocrit and lipids. RESULTS: After 12 weeks of dietary intervention there were reductions in body weight and BMI by 5.9 (s.d. 3.3) kg and 1.9 (s.d. 1.0) kg/m2 respectively in males, and 4.1 (s.d. 2.9) kg and 1.6 (s.d. 1.1) kg/m2 in females (P < 0.0001). Factor VII activity (P = 0.0043), RCA (P = 0.01) and t-PA antigen (P = 0.016) were reduced in females after weight reduction but no differences were found in PAI activity, whole blood, plasma viscosity or haematocrit. The changes in factor VII activity and RCA were appropriate for the changes in BMI on the basis of the relationships of the risk factors with BMI in a cross sectional survey of a representative Scottish population. Plasma total cholesterol was reduced (P = 0.016) but HDL cholesterol and triglycerides remained unchanged. There were significant associations between the reductions in factor VII activity and BMI (r = 0.395, P = 0.013) and between the reductions in RCA and waist to hip ratio (r = 0.350, P = 0.04). No relationship was seen between changes in serum cholesterol and changes in factor VII activity or RCA. CONCLUSIONS: Modest weight loss, of 5% body weight, with conventional dietary intervention reduces two established risk factors for ischaemic heart disease (factor VII activity and RCA) which are generally elevated in those with increased body weight.

Adult↗

PubMed1997

Epidemiology of coagulation factors, inhibitors and activation markers: the Third Glasgow MONICA Survey. I. Illustrative reference ranges by age, sex and hormone use.

Adult↗

PubMed1997

Epidemiology of coagulation factors, inhibitors and activation markers: The Third Glasgow MONICA Survey. II. Relationships to cardiovascular risk factors and prevalent cardiovascular disease.

Coagulation factor activity (fibrinogen, VII, VIII and IX), coagulation inhibitor activity (antithrombin, protein C, protein S), and coagulation activation markers (prothrombin fragment F1, 2; thrombin-antithrombin complexes) were measured in 746 men and 816 women aged 25-74 years, randomly sampled from the north Glasgow population in the Third MONICA Survey. After age-adjustment, significant associations with cardiovascular risk factors were observed. Serum cholesterol and triglyceride were associated with increases in factors VII and IX, as well as antithrombin, protein C and protein S; and with increased fibrinogen and factor VIII in women. Apart from factor VIII (related to blood pressure in men, but not in women), similar associations were observed for blood pressure and body mass index. Smoking status and/or smoking markers were related to fibrinogen, factor IX, antithrombin and protein S. Alcohol intake was related to protein S, and inversely to fibrinogen and antithrombin in men. Low social class was associated with fibrinogen, factor VIII, factor IX, and with antithrombin, protein S, and low protein C in men. Serum vitamin C was associated inversely with coagulation factors and coagulation inhibitors. The only associations of activation markers were with low serum vitamin C, and with alcohol consumption and low social class in men. Prevalent cardiovascular disease was associated only with fibrinogen. These associations of coagulation factors and inhibitors with cardiovascular risk factors are plausibly relevant to thrombotic risk in cardiovascular disease. In general, 'worse' values of risk factors are associated with increased plasma levels of both coagulation factors and inhibitors, without significant increase in coagulation activation markers. However, the association of lower serum vitamin C with increased coagulation activation markers is of potential therapeutic interest.

Adult↗

PubMed1997

Blood viscosity and risk of cardiovascular events: the Edinburgh Artery Study.

We examined the relationships of whole blood viscosity and its major determinants to incident cardiovascular events (ischaemic heart disease and stroke) in a prospective study of a random population sample of 1592 men and women aged 55-74 years (the Edinburgh Artery Study). 272 fatal and non-fatal cardiovascular events occurred during 5 years of follow-up (cumulative incidence 17.1%). Age and sex adjusted mean levels of blood viscosity (3.70 v 3.55 mPa.s), haematocrit (46.2 v 45.7%), haematocrit-corrected blood viscosity (3.57 v 3.48 mPa.s), plasma viscosity (1.35 v 1.33 mPa.s) and fibrinogen (2.88 v 2.67 g/l) were significantly higher in subjects who experienced events than in subjects who did not. The relationships of these rheological variables to cardiovascular events were at least as strong as those of conventional risk factors (smoking habit, diastolic blood pressure, and low-density lipoprotein cholesterol). After adjustment for these conventional risk factors, the associations of blood viscosity and haematocrit remained significant for stroke, but not for total events; whereas the associations of plasma viscosity and fibrinogen remained significant for total events and for stroke. These findings suggest that increased blood viscosity may be one plausible biological mechanism through which increases in haematocrit and fibrinogen may promote ischaemic heart disease and stroke. Randomized controlled trials of viscosity reduction in the prevention of cardiovascular events (e.g. by lowering high levels of haematocrit or plasma fibrinogen) are suggested.

Aged↗

PubMed1997

Helicobacter pylori infection and coronary heart disease in the North Glasgow MONICA population.

AIM: Recent evidence suggests that Helicobacter pylori infection is associated with coronary heart disease. We investigated whether H. Pylori infection is related to prevalent coronary heart disease, in a random sample of 1428 men and women aged 25-74 years. METHODS AND RESULTS: Coronary heart disease was assessed by questionnaire and electrocardiography (ECG). Standard risk factors for coronary heart disease, fibrinogen concentration and serum concentrations of H. pylori-specific IgG antibody were measured. H. pylori seropositivity increased with age (P < or = 0.001) and was significantly more prevalent in men than women. H. pylori infection was associated with current smoking and a higher systolic blood pressure in men but not in women. There was no significant increase in the odds ratio in those seropositive for H. pylori with regard to any manifestation of coronary heart disease, after adjustment for age, standard cardiovascular risk factors and social class. Likewise, age-adjusted plasma fibrinogen was no higher in seropositives. CONCLUSION: Seropositivity to H. pylori is associated with a trend towards a greater prevalence of coronary heart disease. However, that association is likely to be spurious and can be adequately explained by the much stronger association of H. pylori infection with age and social class, both of which are linked with coronary heart disease.

Adult↗

PubMed1997

Hemostatic factors as predictors of ischemic heart disease and stroke in the Edinburgh Artery Study.

Plasma fibrinogen is a consistent predictor of ischemic heart disease (IHD) in prospective studies, but there are fewer data relating other hemostatic variables to IHD and also to stroke. We therefore studied the relationships of plasma fibrinogen, von Willebrand factor antigen, tissue plasminogen activator (TPA) antigen, factor VII, and fibrin D-dimer to incidence of IHD and stroke and determined whether any associations could be explained by conventional risk factors and baseline heart disease. In the Edinburgh Artery study, 1592 men and women aged 55 to 74 years, randomly sampled from the general population, were followed prospectively over 5 years to detect fatal and nonfatal IHD and stroke events. During the 5 years, 268 new vascular events were identified. Baseline plasma fibrinogen was independently related to risk of stroke in multivariate analysis that adjusted for cigarette smoking, LDL-cholesterol, systolic blood pressure, and preexisting IHD (relative risk [RR] 1.52, 95% confidence interval [CI] 1.17, 1.98). TPA antigen, and fibrin D-dimer were also independently associated with risk of stroke (RR 1.69,95% CI 1.22,2.35 and RR 1.96, 95% CI 1.12,3.41, respectively). Significant relationships were found between TPA antigen and myocardial infarction (P < or = .05). In older men and women, increased coagulation activity and disturbed fibrinolysis are predictors of future vascular events (both IHD and stroke).

Aged↗

PubMed1997

Randomized controlled trial of antioxidants in intermittent claudication.

Epidemiological evidence suggests that antioxidants protect against the development of atherosclerosis. To determine the effectiveness of antioxidant therapy in patients with lower limb atherosclerosis, a randomized placebo-controlled trial was performed in 120 men and women with intermittent claudication and an ankle/brachial pressure index (ABPI) < or = 0.9. The study was analysed on an intention-to-treat basis. After 2 years, there were no significant differences between antioxidant and placebo groups in plasma cholesterol, lipoproteins, haemostatic or rheological factors. However, after 6 months, low density lipoprotein cholesterol was significantly lower in those taking antioxidant (108.0 mg/dl compared with 120.1 mg/dl, p < 0.05). There were no differences in the ABPI or walking distance, although both groups improved slightly with time. The incidence of cardiovascular events and death was nonsignificantly lower in the antioxidant compared with the placebo group: event rates per year were 5.5% (95% CI 2.4-8.6) in the first year and 9.6% (95% CI 6.8-12.4) in the second year for those on antioxidants; and 7.7% (95% CI 5.1-10.3) and 13.3% (95% CI 8.9-17.7) respectively for those on placebo. Significantly fewer serious adverse events occurred in the antioxidant than the placebo group: 21.8% (95% CI 16.2-27.4) compared with 40.0% (95% CI 33.9-46.1). This study therefore suggests that although antioxidants may prevent cardiovascular events in patients with peripheral atherosclerosis, they do not improve lower limb function.

Aged↗

PubMed1997

Prediction of postoperative deep-vein thrombosis.

Prediction of patients at sufficiently high risk of postoperative deep vein thrombosis (DVT) to indicate perioperative antithrombotic prophylaxis usually employs only clinical risk factors. Studies of preoperative and/or postoperative haemostatic tests in the prediction of postoperative DVT are reviewed. In general, the results support the biological concept of a preoperative and postoperative prothrombotic tendency in patients who develop DVT. However, the clinical utility of such tests is unproven; so at present they cannot be advocated for routine preoperative or postoperative screening.

Biomarkers↗

PubMed1997

Fibrinogen, fibrin turnover, endothelial products and vascular surgery.

BACKGROUND: Raised plasma fibrinogen levels and markers of fibrin turnover or endothelial disturbance are associated with cardiovascular disease. METHODS: This is a critical review of the English language literature relating to fibrinogen, fibrin degradation products and endothelial products in peripheral arterial disease and revascularization surgery. RESULTS AND CONCLUSION: Altered levels of plasma fibrinogen and endothelial products are associated with atherosclerosis and some studies have shown an association with poor outcome following revascularization surgery. Randomized clinical trials of therapies that modify thrombotic pathways in patients undergoing surgery for peripheral arterial occlusive disease are therefore required.

Arteriosclerosis↗

PubMed1997

Relationship between factor VIII replacement therapy and joint damage in severe haemophilia.

Most of the physical, psychosocial and financial disability in severe haemophilia A is caused by the effects of recurrent haemarthroses and of chronic arthritis. Recent evidence suggests that this morbidity is related to insufficient factor VIII replacement therapy, not only quantitative (annual dose) but also qualitative (need for regular long-term prophylaxis). The recent development of recombinant factor VIII may increase the acceptability of prophylaxis to parents and patients, and hence reduce morbid outcomes.

Arthritis↗

PubMed1996

Fibrin D-dimer and beta-thromboglobulin as markers of thrombogenesis and platelet activation in atrial fibrillation. Effects of introducing ultra-low-dose warfarin and aspirin.

BACKGROUND: Previous studies have demonstrated increased markers of thrombogenesis in patients with atrial fibrillation (AF), suggesting the presence of a hypercoagulable or prothrombotic state. The objective of this study was to determine the effects of introducing ultra-low-dose warfarin (1 mg), conventional warfarin, and aspirin. (300 mg) therapy on thrombogenesis and platelet activation in AF. METHODS AND RESULTS: We measured sequential changes in plasma fibrin D-dimer (an index of thrombogenesis) and beta-thromboglobulin (beta-TG, a measure of platelet activation) in 51 patients with chronic AF before and at 2 and 6 weeks after randomization to either 1 mg warfarin or 300 mg aspirin (phase 1). Then all patients were started on conventional warfarin therapy (phase 2) with samples taken 2 and 6 weeks later. Pretreatment results were compared with those from 26 healthy control subjects in sinus rhythm. Baseline (pretreatment) beta-TG and D-dimer levels in patients with AF were elevated compared with those of control subjects (P < .001). In phase 1, there were no significant changes in median levels of fibrin D-dimer or beta-TG, despite warfarin 1 mg or aspirin 300 mg. With standard warfarin therapy (phase 2), there was a reduction in median beta-TG at 6 weeks (P = .025) and a sequential reduction in median D-dimer levels at 2 (P = .001) and 6 (P < .001) weeks compared with baseline levels. CONCLUSIONS: Patients with AF have increased intravascular thrombogenesis and platelet activation compared with patients in sinus rhythm. Introduction of ultra-low-dose warfarin (1 mg) or aspirin 300 mg does not significantly alter these markers, although conventional warfarin therapy reduces beta-TG and fibrin D-dimer levels. This is consistent with the beneficial effect of full-dose warfarin in preventing stroke and thromboembolism in AF and suggests that ultra-low-dose warfarin and aspirin may not exert similar beneficial effects.

Aged↗

PubMed1996

ABC of atrial fibrillation. Antithrombotic treatment for atrial fibrillation.

Antithrombotic prophylaxis with long term warfarin or aspirin reduces thromboembolic risk in atrial fibrillation. Identification, risk assessment, and regular review of all patients with atrial fibrillation should be routine in general and hospital practice. Risk stratification is easily performed on clinical grounds--echocardiography may refine it.

Anticoagulants↗

PubMed1996

Determination of contact phase activation by the measurement of the activity of supernatant and membrane surface-adsorbed factor XII (FXII): its relevance as a useful parameter for the in vitro assessment of haemodialysis membranes.

We investigated hemodialysis membrane biocompatibility with respect to contact phase activation by determination of FXII-like activity (FXIIA) on the membrane surface and in the supernatant phase, during plasma contact with various hemodialysis membranes using an in vitro incubation test cell. The results were compared to the influence of these membranes on the activation of purified FXII. A time course for the generation of activated FXII using purified FXII solution at physiologic concentrations on two similar negatively charged polymers was performed. The membranes assessed were regenerated cellulose (Cuprophan; Akzo Faser AG, Germany), modified cellulosic (Hemophan; Akzo Faser AG), acrylonitrile-sodium methallyl copolymer-based membrane AN69S (Hospal, France), and SPAN, a new polyacrylonitrile-based copolymer (akzo Nobel AG). The plasma FXIIA at the membranes surface was significantly different between the membranes, while the supernatant phase FXIIA exhibited no significant differences. In contrast, activation of purified FXII in a plasma-free system with respect to supernatant activity indicated significant differences between the materials. A similar finding for the membrane-bound factor XIIA was also observed when purified factor XII was used. The membrane-bound FXIIA values observed in the plasma system containing heparin were significantly greater than in citrated plasma. This demonstrated the strong influence of heparin and the interaction of other plasma components to the membrane surface on the activation of contact phase of coagulation.

Adsorption↗

PubMed1996

Fibrinogen and fibrin D-dimer levels in paroxysmal atrial fibrillation: evidence for intermediate elevated levels of intravascular thrombogenesis.

Because abnormalities in hemostatic factors may in part account for the risk of stroke and thromboembolism in atrial fibrillation, we measured plasma fibrinogen and fibrin D-dimer levels in 33 patients (18 men and 15 women, mean age 60.8 +/- 1.4 years [mean +/- SEM]) with paroxysmal atrial fibrillation (PAF) and 12 patients (3 men and 9 women, mean age 51.0 +/- 4.2 years) with paroxysmal supraventricular tachycardia (PSVT). Levels of these markers were compared to levels in (1) patients with chronic atrial fibrillation; (2) hospital controls (age-matched [age +/- 5 years] and sex-matched patients in sinus rhythm with coronary artery disease and normal left ventricular function); and (3) healthy population controls in sinus rhythm. Patients with PAF had intermediate levels of median plasma fibrinogen and fibrin D-dimer when compared to patients with chronic atrial fibrillation and controls in sinus rhythm (both p < 0.001). There was no relation with atrial size or ventricular function on echocardiography. Patients with PSVT had plasma fibrinogen and fibrin D-dimer levels that were similar to the median levels of the population controls, suggesting that there was no excess in thrombogenesis. These findings are consistent with the hypothesis that atrial fibrillation is related to the increases in plasma fibrinogen and fibrin D-dimer levels. Patients with PAF have intermediate levels of these markers, a finding that is consistent with the intermediate risk of thromboembolism in such patients.

Aged↗