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T W Meade

Publications and source records attributed to T W Meade.

At least 145 records · Page 8Linked to original sources
PubMed1986

Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study.

The Northwick Park Heart Study (NPHS) has investigated the thrombotic component of ischaemic heart disease (IHD) by the inclusion of measures of haemostatic function. Among 1511 white men aged between 40 and 64 at the time of recruitment, 109 subsequently experienced first major events of IHD. High levels of factor VII coagulant activity and of plasma fibrinogen were associated with increased risk, especially for events occurring within 5 years of recruitment. These associations seemed to be stronger than for cholesterol, elevations of one standard deviation in factor VII activity, fibrinogen, and cholesterol being associated with increases in the risk of an episode of IHD within 5 years of 62%, 84%, and 43% respectively. Multiple regression analyses indicated independent associations between each of the clotting factor measures and IHD but not between the blood cholesterol level and IHD incidence. The risk of IHD in those with high fibrinogen levels was greater in younger than in older men. Much of the association between smoking and IHD may be mediated through the plasma fibrinogen level. The biochemical disturbance leading to IHD may lie at least as much in the coagulation system as in the metabolism of cholesterol.

Adult↗
PubMed1986

Association between dietary fat intake and plasma factor VII coagulant activity--a predictor of cardiovascular mortality.

Repeated measurements were made in 8 adults of factor VII coagulant activity (VIIc) and fibrinogen concentration (two haemostatic variables associated with cardiovascular mortality), together with factor VII concentration, factor X, prothrombin, and serum cholesterol and triglyceride concentrations, while the usual diet was recorded by precise weighing over 12-14 days. In 6 subjects measurements were continued while low-fat and high-fat diets were taken for a further 2 and 3 weeks respectively. Plasma VIIc was related positively and independently to fat and protein intake, whereas factor VII concentration was associated only with protein consumption. In a second study, consumption of 50% extra energy for one day increased VIIc significantly when taken mainly as fat but not when taken mostly as carbohydrate. The character of the VIIc response to fat intake suggested an association with post-prandial lipaemia. A high fat intake may lead not only to coronary atheroma but also to fibrin deposition and thrombus formation through direct activation of the coagulation system.

Adult↗
PubMed1986

An international and interregional comparison of haemostatic variables in the study of ischaemic heart disease. Report of a working group.

Levels of haemostatic variables that may be involved in thrombogenesis have been compared in groups of men of similar mean age in communities at very low (Gambia), high (England and Czechoslovakia) or very high (Scotland and Finland) risk of ischaemic heart disease (IHD). There was a consistent gradient of higher factor VII levels with higher IHD risk and also suggestive gradients in the case of two other vitamin K dependent factors, factors II and X. Mean platelet counts were lower and mean fibrinolytic activity was greater in Gambian men than in European men. There was a suggestive though not entirely consistent association between mean fibrinogen levels and IHD risk in the groups from IHD-endemic countries. The results as a whole, and particularly those on factor VII, strengthen the case for the increasingly detailed epidemiological as well as laboratory investigation of the role of the haemostatic system in thrombogenesis and IHD.

Adult↗
PubMed1986

An association between the factor VII coagulant activity and thrombin activity induced by surface/cold exposure of normal human plasma.

To test whether factor VII activation correlated with the generation of thrombin activity when plasma was exposed to a glass surface and reduced temperature, an association was sought between the changes in factor VII clotting activity (VIIc) and fibrinopeptide A concentration (an index of thrombin activity) in platelet-poor citrated plasma from 42 healthy adults. The Spearman rank correlation (rs) between responses was 0.82 (P less than 0.001). The VIIc assay response to surface/cold exposure was unaffected when thrombin was suppressed by hirudin. An assay for factor VII activity based upon its activation of tritiated factor X revealed an association between the increase in fibrinopeptide A concentration and reduction in functional factor VII concentration during activation of a subset of 22 plasma samples (rs = -0.62; P = 0.003). This loss of functional factor VII was probably due to conversion of active factor VII to its non-functional end-product by factor Xa. The results suggest that VIIc is an index of flux within the coagulation system and support the hypothesis that a high VIIc is an indicator of a hypercoagulable state.

Adult↗
PubMed1985

Fibrinogen: a possible link between social class and coronary heart disease.

Mortality from coronary heart disease in civil servants in the lowest grade of employment has been found to be about three times that of men in the highest grade of employment. As part of an investigation of this finding several haemostatic variables were measured in a sample of 29 men in lower grades of employment and 45 men in higher grades. There was a significant difference in plasma fibrinogen concentrations between men in lower grades of employment and those in higher grades (mean 3.39 g/l v 2.95 g/l, respectively; p less than 0.01) but not in other haemostatic variables. Multiple regression analyses showed significant independent associations of fibrinogen concentration with smoking (p less than 0.05) and grade of employment (p less than 0.05). The size of the observed difference between the grades of employment was similar to that between those dying of coronary heart disease or surviving during longitudinal study; it may therefore be an important part of the mechanism underlying social class differences in coronary heart disease. The statistical relation between fibrinogen concentrations and other characteristics that may be concerned in the aetiology of coronary heart disease was examined. A summary measure of job stress was significantly related to fibrinogen concentration (p less than 0.01) and made a substantial contribution to explaining the differences between grades of employment. Behaviour type and a score of physical activity were not significantly related to fibrinogen concentration.

Adult↗
PubMed1985

The effect of physiological levels of fibrinogen on platelet aggregation.

Results from the Northwick Park Heart Study (NPHS) suggest that physiological levels of plasma fibrinogen may influence platelet aggregability. This possibility has been further studied by the addition of purified fibrinogen to the blood of 17 study participants with low plasma fibrinogen levels. The results, which were highly consistent between different individuals, showed that fibrinogen increases aggregability as measured by the ADP ED50, the dose of adenosine diphosphate at which aggregation proceeds at half its maximum velocity. However, an increasing plasma fibrinogen level was associated with decreasing aggregability measured by another parameter, the ADP EMR (estimated maximum response). Although the balance of evidence is that the plasma fibrinogen level enhances aggregability, these conflicting results emphasize the limitation of any simple concept of "platelet aggregability".

Adenosine Diphosphate↗
PubMed1985

Effects of oral contraceptives and obesity on protein C antigen.

In 24 women using oral contraceptives, protein C antigen was higher than in 24 women of the same age and of the same degree of obesity who were not using OC. In the pooled data for all 48 women, there was an increase in protein C of about 1% (of standard) for each 1.0 mm increase in skinfold thickness. Protein C tends to be high rather than low in circumstances predisposing to thrombosis.

Contraceptives, Oral↗
PubMed1985

Epidemiological characteristics of platelet aggregability.

The epidemiological characteristics of platelet aggregability were established in 958 participants in the Northwick Park Heart Study. The main analyses were based on the dose of adenosine diphosphate at which primary aggregation occurred at half its maximum velocity. Aggregability increased with age in both sexes, was greater in whites than blacks (particularly among men), and tended to decrease with the level of habitual alcohol consumption. Aggregability was, however, greater in women than men and in nonsmokers than smokers. There was no relation between aggregability on the one hand and obesity, current or past oral contraceptive use, menopausal state, or blood cholesterol and triglyceride concentrations on the other. Aggregability was somewhat, though not significantly, higher in men with a history of ischaemic heart disease and in those with electrocardiographic evidence of ischaemia than in those without. There was a strong association between the plasma fibrinogen concentration and aggregability. The widely held concept of platelet aggregability and its implications is probably an oversimplification. In the prevention of thrombosis it may be as useful to consider modifying external influences on platelet behaviour, such as plasma fibrinogen concentration or thrombin production, as it is to rely solely on platelet active agents.

Adenosine Diphosphate↗
PubMed1985

Assay of factor VII activity by two techniques: evidence for increased conversion of VII to alpha VIIa in hyperlipidaemia, with possible implications for ischaemic heart disease.

Factor VII was assayed in healthy adults and pregnant women by a coagulation method (VIIc) and a procedure (VIIt) based upon activation of factor X. Although VIIc and VIIt were highly correlated (r 0.8) they apparently measured different aspects of VII activity. This difference was related to plasma lipid concentrations. Plasma VIIc showed independent positive associations in vivo with VIIt, cholesterol and triglyceride concentrations, but was unaffected by in vitro adjustment of plasma lipoprotein concentrations. The difference between assays might be due to differing reactivities of VII. The VIIc assay measures VII in its in vivo proportions as the single-chain protein and fully active double-chain form (alpha VIIa). In VIIt, all VII is converted to alpha VIIa before measurement. Thus an increase in VIIc but not VIIt with increasing lipid concentrations reflects an increased proportion of VII as alpha VIIa, possibly secondary to activation of the contact system. This effect may explain at least part of the increased VIIc and normal VIIt in pregnancy, and the increased VIIc of hyperlipidaemias in general. The relative values of VIIc and VIIt are proposed as a measure of flux within the coagulation system, and as a measure of coagulability in hyperlipidaemia and other states.

Adult↗
PubMed1985

Blood pressure and the menstrual cycle.

A retrospective analysis of data from 207 non-pregnant premenopausal women showed that the mean level of systolic blood pressure varied with the stage of the menstrual cycle, being higher on days 17-26, the part of the luteal phase during which the peak of progestogen levels develops, than during the luteal phase as a whole, and significantly higher than the mean for all other days of the cycle. The mean levels were 125.4 mmHg (SE 1.76) for days 17-26, 122.5 (SE 1.25) for days 15-28 and 120.1 (SE 1.07) for days 1-16, 27 and 28. This finding supported the hypothesis that endogenous progestogen might have a hypertensive effect, as does exogenous progestogen. However, a second study designed to confirm this finding failed to do so, showing no cyclical change in the level of blood pressure. The subjects in the first study may have been subject to greater psychological stress when the measurements were made than were those in the second, a possibility supported by the large difference in pressure between the two studies. The discrepancy between the two sets of results could be explained if the effect possibly associated with progestogen levels in the retrospective study was due not to a hypertensive action per se but to a progestogen-related increased reaction to stress.

Adolescent↗
PubMed1985

Coronary artery disease and haemostatic variables in heterozygous familial hypercholesterolaemia.

Haemostatic variables were measured in 61 patients with heterozygous familial hypercholesterolaemia, 32 of whom had evidence of coronary heart disease. Age adjusted mean concentrations of plasma fibrinogen and factor VIII were significantly higher in these patients than in the 29 patients without coronary heart disease, but there were no significant differences in serum lipid concentrations between the two groups. Comparisons in 30 patients taking and not taking lipid lowering drugs showed lower values for low density lipoprotein cholesterol, high density lipoprotein cholesterol and antithrombin III, and a higher high density lipoprotein ratio while receiving treatment. The results suggest that hypercoagulability may play a role in the pathogenesis of coronary heart disease in patients with familial hypercholesterolaemia.

Adult↗
PubMed1985

The value of preventive medicine. Screening in adults.

Controversy over cervical cytology prompted the setting of guidelines for the provision of a screening service. These are discussed in terms of the relationship between blood pressure and cerebrovascular disease and the relationship between the blood cholesterol level and ischaemic heart disease. In the first case, concern mainly centres on the level of blood pressure at which treatment should be started and the effectiveness of treatment. In the second case, a currently active controversy is whether intervention by dietary methods should be directed towards the whole community or only towards those at particularly high risk. The economic issues are illustrated by reference to a detailed theoretical study of the cost-effectiveness of four options for the prevention of ischaemic heart disease, based on action starting in childhood.

Adult↗