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Biomedical subjects

A Rumley

Publications and source records attributed to A Rumley.

At least 55 records · Page 3Linked to original sources
PubMed2000

Femoral atherosclerosis in an older British population: prevalence and risk factors.

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.

Age Distribution↗
PubMed2000

Tissue plasminogen activator and leucocyte elastase as predictors of cardiovascular events in subjects with angina pectoris: Edinburgh Artery Study.

AIMS: To evaluate the relationship between haemostatic and rheological factors and cardiovascular outcome in subjects with angina pectoris in the general population. METHODS AND RESULTS: Two hundred and seven men and women aged 55-74 had evidence of angina at baseline. Sixty-seven (32.3%) had a fatal or non-fatal cardiovascular event during follow-up. Median levels of tissue plasminogen activator antigen and leucocyte elastase were higher in the event group compared with the no event group (10.0 ng. ml(-1)vs 7.2 ng. ml(-1);P</=0.001, and 40.3 ng. ml(-1)vs 31.0 ng. ml(-1);P</=0.01, respectively). Whole blood viscosity was also significantly higher in the event group than in the no event group (3.80 mPa.s vs 3.53 mPa.s;P</=0.05). After adjusting for age and sex, unit increases in both tissue plasminogen activator antigen and leucocyte elastase levels were significantly associated with an increased risk of a cardiovascular event. These associations remained after further adjusting for cardiovascular risk factors and baseline myocardial infarction. The relative risks were 2.07 (95% CI, 1.30-3.45;P</=0.01) for tissue plasminogen activator antigen and 1. 95 (95% CI, 1.12-3.50;P</=0.05) for leucocyte elastase. CONCLUSION: Disturbed fibrinolysis and activation of leucocytes may be implicated in the development of thrombotic cardiovascular events in subjects with angina pectoris in the general population.

Aged↗
PubMed2000

Haemostatic factors and risk of varicose veins and chronic venous insufficiency: Edinburgh Vein Study.

Despite much research, the aetiology of venous disease is still poorly understood. Since haemostatic factors are involved in the processes of fibrinolysis and platelet aggregation, it is conceivable that such processes may be implicated in the pathology of varicose veins and chronic venous insufficiency (CVI). The Edinburgh Vein Study examined 1566 men and women aged 18-64 years that were randomly selected from the lists of 12 general practitioners. Each subject completed a questionnaire, underwent a comprehensive clinical examination and had a blood sample taken for the analysis of plasma fibrinogen, tissue plasminogen activator (t-PA) and von Willebrand factor (vWF) antigens. Subjects with trunk varicose veins and those with CVI had higher levels of each haemostatic factor compared with those with no trunk varices and no CVI. Although unit increases in t-PA and vWF were initially associated with a significantly increased risk of CVI in men, and both factors with an elevated risk of trunk varices in women, multiple adjustment for age, smoking status and body mass index reduced the odds ratios to non-significance. However, this does not entirely rule out the possibility of a pathogenic role for haemostatic factors in venous disease, but rather indicates the need for further experimental and epidemiological studies.

Adolescent↗
PubMed2000

Lifestyle and hemostatic risk factors for ischemic heart disease : the Caerphilly Study.

We have recently shown that fibrin D-dimer, tissue plasminogen activator (tPA) antigen, von Willebrand factor antigen, fibrinogen, plasma viscosity, and white cell count are associated with subsequent ischemic heart disease (IHD) in men aged 49 to 65 years in the Caerphilly Study from South Wales. We now report the contribution of major lifestyle factors to plasma levels of these new risk predictors for IHD. Results were available for up to 2188 men. The contribution of factors associated with lifestyle (smoking, alcohol, body mass index, leisure and work activity, social class, and use of prescribed medicines) to variation in plasma levels of 8 hemostatic variables was examined. All results were adjusted for other lifestyle variables, age, and time of day. Most hemostatic variables increased with age and smoking habit. Increasing levels of alcohol consumption were associated with increases in tPA and plasminogen activator inhibitor (PAI-1) activity and with decreases in fibrinogen and white cell count. tPA, PAI-1, fibrinogen (nephelometric), and viscosity were positively associated with body mass index. Increasing levels of leisure activity were inversely associated with D-dimer, von Willebrand factor, nephelometric fibrinogen, and viscosity. Use of prescribed medicines (a marker for chronic illness) was associated with adverse levels of D-dimer, fibrinogen, plasma viscosity, and white cell count. tPA, PAI-1, and plasma viscosity were associated with blood pressure, cholesterol, and triglycerides but not with lipoprotein(a) or homocysteine. We conclude that several lifestyle factors are associated with hemostatic risk predictors for IHD. Lifestyle modifications may reduce IHD risk partly by altering hemostatic function; large intervention studies are required to test this hypothesis.

Aged↗
PubMed2000

Plasma fibrinogen, haemostatic factors and prediction of peripheral arterial disease in the Edinburgh Artery Study.

The role of fibrinogen and other haemostatic factors in prediction of peripheral arterial disease (PAD) has not been established. We examined the associations of plasma fibrinogen, von Willebrand Factor (vWF), tissue plasminogen activator (t-PA) antigen, fibrin D-dimer, and factor VII with the development and clinical progression of PAD. In the Edinburgh Artery Study, 1592 men and women, aged between 55 and 74 years, were followed prospectively over 5 years to detect the onset of PAD, and the deterioration of established PAD. At baseline, 418 individuals had evidence of PAD and 60 (14.4%) subsequently deteriorated. 1080 subjects had no baseline disease, but 59 (5.5%) developed PAD during follow-up. Median levels of fibrinogen and vWF were higher in the group developing disease compared with the group which did not (2.78 g/l versus 2.57 g/l, P< or =0.01; 116 IU/dl versus 104 IU/dl, P< or =0.05; respectively). After adjusting for age and sex, fibrinogen (P< or =0.01) and vWF (P< or =0.05) were significantly associated with the risk of developing PAD. The association between fibrinogen and development of disease remained after adjusting for cardiovascular risk factors and baseline ischaemic heart disease (relative risk, 1.35, 95% confidence interval, 1.05, 1.73; P< or =0.05). None of the haemostatic factors were significantly associated with progression of PAD. In conclusion, plasma fibrinogen levels are related to the future onset of PAD, providing further evidence of a possible role of elevated fibrinogen in the development of atherosclerotic disease.

Aged↗
PubMed2000

Thrombotic variables and risk of idiopathic venous thromboembolism in women aged 45-64 years. Relationships to hormone replacement therapy.

Hormone replacement therapy (HRT) has been shown to increase the relative risk of idiopathic venous thromboembolism (VTE) about threefold in several observational studies and one randomised controlled trial. Whether or not this relative risk is higher in women with underlying thrombophilia phenotypes, such as activated protein C (APC) resistance, is unknown. We therefore restudied the participants in a case-control study of the relationship between the use of HRT and the occurrence of idiopathic VTE in women aged 45-64 years. After protocol exclusions, 66 of the cases in the original study and 163 of the controls were studied. Twenty haematological variables relevant to risk of VTE were analysed, including thrombotic states defined from the literature. The relative risk of VTE showed significant associations with APC resistance (OR 4.06; 95% CI 1.62, 10.21); low antithrombin (3.33; 1.15, 9.65) or protein C (2.93; 1.06, 8.14); and high coagulation factor IX (2.34; 1.26, 4.35), or fibrin D-dimer (3.84; 1.99, 7.42). HRT use increased the risk of VTE in women without any of these thrombotic states (OR 4.09; 95% CI 1.26, 13.30). A similar effect of HRT use on the relative risk of VTE was also found in women with prothrombotic states. Thus for example, the combination of HRT use and APC resistance increased the risk of VTE about 13-fold compared with women of similar age without either APC resistance or HRT use (OR 13.27; 95% CI 4.30, 40.97). We conclude that the combination of HRT use and thrombophilias (especially if multiple) increases the relative risk of VTE substantially; hence women known to have thrombophilias (especially if multiple) should be counselled about this increased risk prior to prescription of HRT. However, HRT increases the risk of VTE about fourfold even in women without any thrombotic abnormalities: possible causes are discussed.

Activated Protein C Resistance↗
PubMed2000

Blood rheology, cardiovascular risk factors, and cardiovascular disease: the West of Scotland Coronary Prevention Study.

The West of Scotland Coronary Prevention Study (WOSCOPS) showed that pravastatin reduced the risk of coronary heart disease (CHD) events in 6,595 middle-aged hypercholesterolaemic men aged 45-64 years without prior myocardial infarction followed for an average of 4.9 years. We hypothesised prospectively (a) that baseline levels of haemorheological variables were related to baseline and incident CHD and to mortality; and (b) that reduction in lipoproteins by pravastatin would lower plasma and blood viscosity, a potential contributory mechanism to CHD events. We therefore studied plasma and blood viscosity, fibrinogen, haematocrit, and blood cell counts at baseline and 1 year. At baseline, plasma and blood viscosity were related to risk factors, CHD measures, and claudication. On univariate analysis, baseline levels of all rheological variables (except platelet count) were related to incident CHD; CHD mortality; and total mortality. On multivariate analysis including baseline CHD and risk factors, plasma and blood viscosity, haematocrit and white cell count each remained significantly associated with incident CHD; while fibrinogen remained an independent predictor of mortality (all p < 0.03). After one year, lipoprotein reduction by pravastatin was associated with significant reductions (about one quarter of a standard deviation) in plasma viscosity (mean difference 0.02 mPa.s, p <0.001) and in blood viscosity (mean difference 0.06 mPa.s, p<0.001), but was not associated with significant changes in other rheological variables. We therefore suggest that pravastatin therapy, which reduces elevated lipoproteins in hypercholesterolaemic men, may lower risks of CHD and mortality partly by lowering plasma and blood viscosity. Further studies are required to test this hypothesis.

Anticholesteremic Agents↗
PubMed1999

Associations of blood rheology and interleukin-6 with cardiovascular risk factors and prevalent cardiovascular disease.

Haemorheological variables (whole-blood, plasma and relative blood viscosity, haematocrit, red cell aggregation, white cell count and fibrinogen) were measured in 753 men and 821 women aged 25-74 years, and related to cardiovascular risk factors and prevalent cardiovascular disease (CVD). Men had higher levels than women of blood viscosity, haematocrit, corrected viscosity and relative viscosity. Post-menopausal women had higher levels than pre-menopausal women of blood viscosity, haematocrit, corrected blood viscosity, plasma viscosity and fibrinogen: each of these differences was completely or partly abolished by use of hormone replacement therapy. Serum total cholesterol, triglycerides, diastolic blood pressure, body mass index and smoking markers showed positive associations with most rheological variables, whereas HDL-cholesterol, plasma vitamin C and social class showed inverse associations. Rheological variables were associated with prevalent CVD after age-adjustment. However, after multiple risk factor adjustment only plasma viscosity and red cell aggregation showed significant (P<0.04) associations in both men and women (comparing top to bottom quarters). Plasma interleukin-6 (measured in a 25% subsample of 196 men and 221 women) correlated significantly with age, fibrinogen, white cell count, plasma and blood viscosity, current smoking, and (in men) with low serum vitamin C levels; but not with other major risk factors or with prevalent cardiovascular disease.

Adult↗
PubMed1999

The role of haematological factors in diabetic peripheral arterial disease: the Edinburgh artery study.

The relationship between haematological factors and peripheral arterial disease (PAD) among diabetics has not been widely examined. 1592 men and women aged 55-74 years were selected from the general population. They underwent an assessment for PAD and a glucose tolerance test. 288 subjects (18.7%) were identified as having diabetes or impaired glucose tolerance (IGT). Among the diabetes/IGT group, median levels of fibrinogen, von Willebrand factor (VWF), tissue plasminogen activator (t-PA), fibrin D-dimer and plasma viscosity were higher in subjects with PAD than those without PAD (P </= 0.05). The prevalence of PAD was higher in those with diabetes/IGT (20.6%) compared to those with normal glucose tolerance (12.5%) (odds ratio 1.64; 95% CI 1.17, 2.31). After separate adjustment for fibrinogen, VWF, t-PA, fibrin D-dimer, leucocyte elastase, plasma viscosity and haematocrit, those with diabetes/IGT no longer had a significantly higher risk of PAD compared to those with a normal glucose tolerance test. Simultaneous adjustment for the first four of these haematological factors reduced the risk of PAD among subjects with diabetes/IGT to 1.11 (95% CI 0.76, 1.63). Increased levels of haemostatic factors may partly explain the higher prevalence of PAD in diabetic/IGT subjects compared to normal glucose-tolerant subjects. Future randomized controlled trials involving the indirect lowering of levels of haematological factors should help to explain whether the associations reported here are of causal significance.

Aged↗
PubMed1999

Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease: Edinburgh Artery Study.

AIMS: The aim was to determine whether the effect of smoking on the development of peripheral or coronary artery disease might be mediated by other cardiovascular risk factors, including dietary antioxidant vitamin intake, serum low and high density lipoproteins, blood pressure, plasma fibrinogen, blood viscosity and markers of endothelial disturbance and fibrin turnover. METHODS AND RESULTS: 1592 men and women aged 55-74 years were selected at random from 11 general practices in Edinburgh, Scotland and followed-up for 5 years. The incidences of peripheral arterial disease and coronary artery disease were 5.1% and 11.1%, respectively. Both conditions were more common in moderate and heavy smokers than in never smokers: cigarette smoking was a stronger risk factor for peripheral arterial disease than for coronary artery disease. Smoking was associated with reduced dietary antioxidant vitamin intake, serum high density lipoprotein cholesterol and diastolic blood pressure and with increased alcohol intake, serum triglycerides, blood viscosity, plasma fibrinogen, and markers of endothelial disturbance (tissue plasminogen activator and von Willebrand factor antigens). Simultaneous adjustment for these risk factors reduced the relative risk of peripheral arterial disease only slightly, from 3.94 (95% CI 2.04, 7.62) to 2.72 (95% CI 1.13, 6.53) in heavy smokers and from 1.87 (95% CI 0.91, 3.85) to 1.70 (95% CI 0.72, 3.99) in moderate smokers. Similar adjustment also had little effect on the risk of coronary artery disease associated with smoking. CONCLUSION: The combined effect of smoking on the cardiovascular risk factors studied may explain part of its influence on peripheral and coronary arterial disease, but the majority of the effect appears to be due to other mechanisms.

Aged↗
PubMed1999

Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: the British Regional Heart Study.

BACKGROUND AND PURPOSE: B-mode ultrasound is a noninvasive method of examining the walls of peripheral arteries and provides measures of the intima-media thickness (IMT) at various sites (common carotid artery, bifurcation, internal carotid artery) and of plaques that may indicate early presymptomatic disease. The reported associations between cardiovascular risk factors, clinical disease, IMT, and plaques are inconsistent. We sought to clarify these relationships in a large, representative sample of men and women living in 2 British towns. METHODS: The study was performed during 1996 in 2 towns (Dewsbury and Maidstone) of the British Regional Heart Study that have an approximately 2-fold difference in coronary heart disease risk. The male participants were drawn from the British Regional Heart Study and were recruited in 1978-1980 and form part of a national cohort study of 7735 men. A random sample of women of similar age to the men (55 to 77 years) was also selected from the age-sex register of the general practices used in the original survey. A wide range of data on social, lifestyle, and physiological factors, cardiovascular disease symptoms, and diagnoses was collected. Measures of right and left common carotid IMT (IMTcca) and bifurcation IMT (IMTbif) were made, and the arteries were examined for plaques 1.5 cm above and below the flow divider. RESULTS: Totals of 425 men and 375 women were surveyed (mean age, 66 years; range, 56 to 77 years). The mean (SD) IMTcca observed were 0. 84 (0.21) and 0.75 (0.16) mm for men and women, respectively. The mean (SD) IMTbif were 1.69 (0.61) and 1.50 (0.77) mm for men and women, respectively. The correlation between IMTcca and IMTbif was similar in men (r=0.36) and women (r=0.38). There were no differences in mean IMTcca or IMTbif between the 2 towns. Carotid plaques were very common, affecting 57% (n=239) of men and 58% (n=211) of women. Severe carotid plaques with flow disturbance were rare, affecting 9 men (2%) and 6 women (1.6%). Plaques increased in prevalence with age, affecting 49% men and 39% of women aged <60 years and 65% and 75% of men and women, respectively, aged >70 years. Plaques were most common among men in Dewsbury (79% affected) and least common among men in Maidstone (34% affected). IMTcca showed a different pattern of association with cardiovascular risk factors from IMTbif and was associated with age, SBP, and FEV1 but not with social, lifestyle, or other physiological risk factors. IMTbif and carotid plaques were associated with smoking, manual social class, and plasma fibrinogen. IMTbif and carotid plaques were associated with symptoms and diagnoses of cardiovascular diseases. IMTbif associations with cardiovascular risk factors and prevalent cardiovascular disease appeared to be explained by the presence of plaques in regression models and in analyses stratified by plaque status. CONCLUSIONS: IMTcca, IMTbif, and plaque are correlated with each other but show differing patterns of association with risk factors and prevalent disease. IMTcca is strongly associated with risk factors for stroke and with prevalent stroke, whereas IMTbif and plaque are more directly associated with ischemic heart disease risk factors and prevalent ischemic heart disease. Our analyses suggest that presence of plaque, rather than the thickness of IMTbif, appears to be the major criterion of high risk of disease, but confirmation of these findings in other populations and in prospective studies is required. The association of fibrinogen with plaque appears to be similar to its association with incident cardiovascular disease. Further work elucidating the composition of plaques using ultrasound imaging would be helpful, and more data, analyzed to distinguish plaque from IMTbif and IMTcca, are required to understand the significance of thicker IMT in the absence of plaque.

Age Distribution↗
PubMed1999

Factor VIII, von Willebrand factor and the risk of major ischaemic heart disease in the Caerphilly Heart Study.

The relationships of three measurements of the factor VIII/von Willebrand factor (VWF) complex (factor VIII activity, FVIIIc (one-stage assay); VWF antigen, VWF Ag (ELISA); and VWF activity, VWF act, measured by a recently-developed ELISA) to major ischaemic heart disease (IHD) events were studied in 1997 men aged 49-65 years, in the second phase of the Caerphilly Heart Study. These variables were related using logistic regression analysis to myocardial infarction or IHD death, which occurred in 129 men during an average follow-up period of 61 months. All three measurements were highly correlated (r = 0.63-0.77), and each was significantly associated with incident major IHD on univariate analyses (relative odds in highest fifth compared to lowest fifth, 1.68-1.90; P = 0.028-0.006) and on multivariate analyses adjusting for major IHD risk factors and for baseline IHD. Neither FVIIIc nor VWF act was significantly related to incident IHD following adjustment for VWF Ag. We therefore suggest that the associations between these three measurements of the factor VIII/VWF complex and incident IHD might have at least three explanations: VWF Ag is a marker of arterial endothelial disturbance; VWF act promotes platelet adhesion/aggregation and hence the platelet component of arterial thrombosis; and FVIIIc promotes fibrin formation and hence the fibrin component of arterial thrombosis.

Enzyme-Linked Immunosorbent Assay↗
PubMed1999

Fibrinogen, factor VII and PAI-1 genotypes and the risk of coronary and peripheral atherosclerosis: Edinburgh Artery Study.

There are now many epidemiological studies that have shown a relationship between haemostatic factors and subsequent risk of both coronary and peripheral arterial disease. However, there is less information on the association between genetic variation in these factors and the risks of coronary and peripheral arterial disease. As part of the five-year follow-up of the Edinburgh Artery Study, polymorphisms of the fibrinogen (-455G/A), factor VII (R/Q353) and PAI-1 (HindIII) genes were measured in men and women aged 60-79 years, together with their plasma levels. Using widely accepted criteria, 88 subjects were identified as having peripheral arterial disease (PAD), 195 having coronary artery disease (CAD) and 423 subjects comprised a "healthy" group. The -455AA genotype of the fibrinogen gene was found to be more frequent among those subjects with PAD. This genotype also showed the highest plasma fibrinogen levels in both disease groups and in the healthy group. Using logistic regression, after adjustment for age, sex, smoking and plasma level, the -455AA genotype was associated with over twice the risk of PAD compared with the -455GG genotype, the odds ratio reaching marginal significance (p < or = 0.10). Combining those with genotype -455AA with the heterozygotes in order to increase the power of the study resulted in a more significant multiple-adjusted risk of PAD (p < or = 0.05). These data provide evidence that a polymorphism of the P fibrinogen gene is associated with an increased risk of peripheral atherosclerosis.

Aged↗
PubMed1999

Activated protein C resistance and the FV:R506Q mutation in a random population sample--associations with cardiovascular risk factors and coagulation variables.

Activated protein C (APC) resistance, defined as a low APC ratio, is associated with the factor V mutation R506Q (factor V Leiden). APC ratio may also be influenced by other clinical and coagulation variables, which we studied in 460 men and 495 women aged 25-74 years, from a random population sample (Glasgow MONICA Survey). APC ratio correlated positively with APTT; and inversely with factor VIIIc, factor IXc, antithrombin activity, prothrombin F1+2 fragment, and thrombin-antithrombin complexes; but not with other coagulation variables. APC ratio decreased with age, but APTT did not. APC ratio and APTT were significantly lower in women versus men, and were significantly lower in users of oral contraceptives or hormone replacement therapy. The FV:R506Q mutation (prevalence 2.5%) was associated with lower APC ratio and protein C and S activities and with higher factor VIIIc levels; but not with increases in F1+2 fragment or thrombin-antithrombin complexes. APC ratio correlated inversely with total cholesterol and diastolic blood pressure; and in women with triglycerides, systolic blood pressure, and body mass index. Obesity was associated with a significantly lower APC ratio. In contrast, smoking markers correlated positively with APC ratio in men. These associations of APC ratio may be relevant to the increased risks of venous thrombosis with age, female sex, oestrogen use, obesity and high factor VIIIc levels. The association of APC resistance with elevated plasma levels of coagulation markers suggests that this phenotype represents an in vivo hypercoagulable state.

Activated Protein C Resistance↗