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Y Stirling

Publications and source records attributed to Y Stirling.

At least 37 records · Page 2Linked to original sources
PubMed1989

Fat consumption and factor VII coagulant activity in middle-aged men. An association between a dietary and thrombogenic coronary risk factor.

Diet was measured by 5-day weighed inventory to search for an association between fat intake in the general population and factor VII coagulant activity (VIIc), a strong predictor of coronary heart disease. Of 275 men aged 40-59 years registered with a medical practice, 203 (74%) participated and 170 (62%) provided a satisfactory record. After allowance for the increase in fat intake with body size, a statistically significant and positive association was found between dietary fat and VIIc (r = 0.18; P less than 0.05). The correlation coefficient was increased to 0.24 when adjusted for the effect of day-to-day variability in individual fat intake, thereby providing an improved estimate of the true strength of association. The mean difference in VIIc of 12% of standard between men in the highest and lowest quarters of the distribution of fat intake was similar to that reported between men experiencing coronary heart disease and those remaining free. The results support previous experimental fat-feeding studies and suggest that a high fat diet has adverse consequences for blood coagulability and coronary thrombosis.

Adult↗
PubMed1989

Protocol for the evaluation of automated blood coagulation instruments (coagulometers) for determination of the international normalised ratio.

Results of prothrombin time tests for the control of oral anticoagulant therapy, when using automated blood coagulation instruments (coagulometers), may not be the same as those obtained when using manual methods, and variation in coagulometer performance may affect clinical interpretation of data. The haematology advisory committee of the Institute of Medical Laboratory Sciences has recommended that coagulometers should be used for determination of prothrombin times only if it can be demonstrated that the results are valid when compared with those of a standardised manual method. A protocol for the evaluation of coagulometers, and details of the procedures, are given in this report, the main emphasis of which is on the assessment of instruments for determination of the International Normalised Ratio. Guidelines are also provided for the general use of machines of this type and for the assessment of safety. The principles of the protocol are applicable to other automated tests of blood coagulation.

Autoanalysis↗
PubMed1988

Dietary and other characteristics relevant for coronary heart disease in men of Indian, West Indian and European descent in London.

The origins of the high standardized mortality ratio (SMR) for coronary heart disease (CHD) among Indians in Britain, and the low SMR for West Indian immigrants, have been explored by a community survey in London. Serum lipoproteins, plasma glucose, haemostatic factors and other putative risk characteristics were measured in 75 Indian, 64 European and 24 West Indian men aged 45-54 years. These represented 81% of men registered with a general practice and resident within a defined area. In 51 men, diet was assessed by 5-day weighed inventory. Plasma phospholipid fatty acids (PFA) were measured in 18 Indians and 19 Europeans with dietary records. The relatively high HDL and HDL2-cholesterol concentrations, low LDL-cholesterol concentration, reduced fat intake, increased ratio of dietary polyunsaturated/saturated fat, relatively frequent use of alcohol, and lack of obesity in West Indians accorded with their low SMR from CHD. By contrast, only the relatively low HDL and HDL2-cholesterol concentrations, infrequency of alcohol consumption, and lower proportion of PFA as n-3 fatty acids of marine origin afforded explanations for the high SMR of Indians. Hyperglycaemia appeared similarly prevalent in Indians and West Indians, but less common in Europeans. Of the haemostatic factors, West Indians had a relatively low VIIc (not statistically significant), while Indians had an increased platelet count and reduced platelet volume. Improved understanding of these ethnic differences in CHD mortality may depend upon elucidation of the contrasts in HDL-cholesterol concentration.

Blood Coagulation Tests↗
PubMed1988

Randomized controlled trial of low dose warfarin in the primary prevention of ischaemic heart disease in men at high risk: design and pilot study.

We report the pilot stage of a double-blind randomized controlled trial of low dose warfarin in the primary prevention of ischaemic heart disease (IHD) in men at high risk. The first objective was to see if levels of factor VII coagulant activity, VIIc, could be reduced without undue difficulty from a mean level of about 115% to about 70% (the level in patients on conventional warfarin doses being about 30%). This was accomplished with a mean daily dose of 4.6 mg warfarin. The international normalized ratio (INR) corresponding to a VIIc value of 70% was about 1.5. The second objective was to assess the risk of bleeding associated with the intended level of anticoagulation. There was no significant excess in the number of actively treated men ever reporting nose bleeds, possible haematuria, rectal bleeding or bruising, although there may have been an increase in the frequency of rectal bleeding in men who did report this symptom. The third objective was to establish the willingness of patients to take part in a trial of this kind. Of those invited to the initial screening examination, 72% attended. Of those invited to enter the treatment phase of the trial, 71% did so. Compliance with trial treatment was at a very high level. The rate of withdrawal from randomized treatment was within acceptable limits, at about 15% over a three- or four-year period. The scientific case for a full trial is strong and the pilot trial shows that it could be accomplished.

Aged↗
PubMed1987

Effects of changes in smoking and other characteristics on clotting factors and the risk of ischaemic heart disease.

The Northwick Park Heart Study (NPHS) has demonstrated associations of high levels of factor VII coagulant activity (VIIc) and of plasma fibrinogen concentration with the risk of subsequent ischaemic heart disease (IHD). In cross-sectional data from the 2023 white men in NPHS, lifetime duration of smoking was a determinant of initial plasma fibrinogen levels. Fibrinogen levels had apparently begun to fall soon after smoking was discontinued but it was over 5 years before they had returned to levels found in life-long non-smokers. In prospective data, smoking cessation and the adoption or resumption of smoking were associated with a decrease or an increase, respectively, of about 0.15 g/l in plasma fibrinogen. These changes would lower or raise the risk of IHD by about 20%. A switch from cigarettes to cigars was associated with a large increase in fibrinogen. A substantial part of the relation between smoking and IHD appears to be mediated through the fibrinogen concentration. Following changes in body mass, VIIc rose in those who had given up smoking and fell in those who resumed.

Age Factors↗
PubMed1987

Role of genetic variation at the fibrinogen locus in determination of plasma fibrinogen concentrations.

Three restriction fragment length polymorphisms (RFLPs) of the fibrinogen genes were used in 91 individuals to investigate the role of genetic variation at this locus in the determination of plasma fibrinogen. The strongest association was with a polymorphism detected with the beta-fibrinogen probe and the enzyme BclI. The probe detects two alleles, designated B1 and B2. The individuals with the genotype B1B1 had a mean fibrinogen of 2.74 g/l; those with B2B2 had a mean fibrinogen of 3.69 g/l (a level previously associated with a strongly increased risk of ischaemic heart disease); and those heterozygous for the two alleles, with the genotype B1B2, had a mean of 2.98 g/l. Genetic variation at the fibrinogen gene locus accounted for 15% of the total phenotypic variance in fibrinogen.

Female↗
PubMed1987

Value and application of automation in laboratory diagnosis of haemostatic disorders.

There is a bewildering variety of instrumentation available for automation of coagulation procedures. The advantages and draw-backs of the most widely-used types are discussed to help the prospective purchaser to decide the most suitable instrument for his needs. Operator satisfaction is of considerable importance. Anticoagulated plasmas give shorter clotting times on many instruments as compared with the manual method which may necessitate an extrapolation curve or change of therapeutic range. An instrument, carefully selected, can increase the throughput of samples and improve the overall accuracy and precision of results.

Automation↗
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

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↗
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

Antithrombin III "Northwick Park": a variant antithrombin with normal affinity for heparin but reduced heparin cofactor activity.

Further studies have been carried out in a previously reported family with congenital antithrombin III (AT III) deficiency due to an abnormal variant of AT III (AT III Northwick Park). The variant has been identified in five members of the family, three of whom had a history of venous thrombosis. Inheritance followed an autosomal dominant pattern. The affected family members have reduced levels of antithrombin heparin cofactor (41-67%) and progressive antithrombin activity (44-62%) but normal levels of immunoreactive AT III (91-162%). Two dimensional immunoelectrophoresis (2 DIE) of AT III in the absence of heparin revealed an abnormal fast-moving peak in addition to the normal peak but 2 DIE in the presence of heparin appeared normal. Further studies confirmed that the abnormal AT III binds completely to heparin but has no heparin cofactor or progressive antithrombin activity. These results would be consistent with a mutation affecting the binding site for thrombin.

Adolescent↗
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

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↗
PubMed1984

Haemostasis in normal pregnancy.

A study has been undertaken in 72 women to provide systematic information on the changes that occur in a wide range of haemostatic variables during and after pregnancy. Factors VII, VIII:C, VIIIR:Ag, X, fibrinogen and alpha 1-antitrypsin, rose markedly throughout pregnancy. Factors II and V and alpha 2 macroglobulin all rose early on but then decreased steadily. Antithrombin III:C and Ag fell slightly. There was a marked decrease in fibrinolytic activity from 11-15 weeks onwards. Levels of fibrin degradation products rose from 21-25 weeks onwards. The rise in coagulation factors that occurs could be due to increased synthesis or increased activation by thrombin, or to both. The findings are consistent with a mild degree of local intravascular coagulation from early on in pregnancy in some women.

Antigens↗