Biomedical subjects

S G Thompson

Publications and source records attributed to S G Thompson.

At least 73 records · Page 4Linked to original sources

PubMed1996

Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities.

BACKGROUND: Disturbances of the fibrinolytic system that lead to decreased removal of fibrin deposits may be important risk factors for coronary thrombosis. There is as yet no consensus on the prognostic value of fibrinolytic parameters, which may be attributed in part to the choice of confounding variables controlled for. METHODS AND RESULTS: The ECAT study is a prospective multicenter study of 3043 patients with angina pectoris followed for 2 years. Baseline measurements included 10 fibrinolytic variables. The results were analyzed in relation to the subsequent incidence of myocardial infarction or sudden coronary death. They are presented before and after adjustment for clusters of confounding variables that are markers of different mechanisms: insulin resistance (body mass index, triglyceride, and HDL cholesterol), inflammation (fibrinogen and C-reactive protein), and endothelial cell damage (von Willebrand factor). An increased incidence of events was associated with higher baseline concentrations of tissue plasminogen activator (TPA) antigen (P = .0002), plasminogen activator inhibitor-1 (PAI-1) activity (P = .02), and PAI-1 antigen (P = .001). The associations of PAI-1 activity and PAI-1 antigen with risk of events disappeared after adjustment for parameters reflecting insulin resistance but were not affected by other adjustments. TPA antigen was affected to a similar extent by adjustment for parameters reflecting insulin resistance. Inflammation, or endothelial cell damage, but the risk association disappeared only after combined adjustments. CONCLUSIONS: The prognostic role of PAI-1 in predicting coronary events is related principally to insulin resistance, whereas that of TPA antigen could be explained only by its relationship with different mechanisms, including insulin resistance, inflammation and endothelial cell damage.

Adult↗

PubMed1996

The relation between treatment benefit and underlying risk in meta-analysis.

In meta-analyses of clinical trials comparing a treated group with a control group it has been common to ask whether the treatment benefit varies according to the underlying risk of the patients in the different trials, with the hope of defining which patients would benefit most and which least from medical interventions. The usual analysis used to investigate this issue, however, which uses the observed proportions of events in the control groups of the trials as a measure of the underlying risk, is flawed and produces seriously misleading results. This arises through a bias due to regression to the mean and will be particularly acute in meta-analyses which include some small trials or in which the variability in the true underlying risks across trials is small. Approaches which previously have been thought to be more appropriate are to substitute the average proportion of events in the control and treated groups as the measure of underlying risk or to plot the proportion of events in the treated group against that in the control group (L'Abbé plot). However, these are still subject to bias in most circumstances. Because of the potentially seriously flawed conclusions that can result from such analyses, they should be replaced either by statistically appropriate (but more complex) approaches or, preferably, by analyses which investigate the dependence of the treatment effect on measured baseline characteristics of the patients in each trial.

Clinical Trials as Topic↗

PubMed1996

Methods for summarizing the risk associations of quantitative variables in epidemiologic studies in a consistent form.

A major problem in reviewing the published results of different epidemiologic studies of the relation between a quantitative variable and the risk of disease is that the results are presented in many different ways. The purpose of this paper is to exemplify methods by which results expressed either as risks (or rates) according to quantlle groups of the quantitative variable or as results derived from a logistic regression analysis can be reexpressed in a uniform manner, as a mean difference in the quantitative variable between the cases of disease and the other subjects in the study. An important assumption of the methods is that the quantitative variable has an approximately normal distribution, and a way of investigating the appropriateness of this assumption is given. The methods can be applied to both prospective and case-control studies and are exemplified by a number of studies of serum albumin concentrations and mortality. In some applications, these methods can be used as a precursor to formal meta-analysis, for example, when differential control of potential confounding factors is not a problem. At the least, the methods can be useful either in quantitatively reviewing published studies before undertaking new research or in putting the results of a new study into the context of previously published ones.

Case-Control Studies↗

PubMed1996

A likelihood approach to meta-analysis with random effects.

In a meta-analysis of a set of clinical trials, a crucial but problematic component is providing an estimate and confidence interval for the overall treatment effect theta. Since in the presence of heterogeneity a fixed effect approach yields an artificially narrow confidence interval for theta, the random effects method of DerSimonian and Laird, which incorporates a moment estimator of the between-trial components of variance sigma B2, has been advocated. With the additional distributional assumptions of normality, a confidence interval for theta may be obtained. However, this method does not provide a confidence interval for sigma B2, nor a confidence interval for theta which takes account of the fact that sigma B2 has to be estimated from the data. We show how a likelihood based method can be used to overcome these problems, and use profile likelihoods to construct likelihood based confidence intervals. This approach yields an appropriately widened confidence interval compared with the standard random effects method. Examples of application to a published meta-analysis and a multicentre clinical trial are discussed. It is concluded that likelihood based methods are preferred to the standard method in undertaking random effects meta-analysis when the value of sigma B2 has an important effect on the overall estimated treatment effect.

Antihypertensive Agents↗

PubMed1996

Antithrombin III and fibrinogen as predictors of cardiac events in patients with angina pectoris.

Because measurements of hemostatic factors might aid the prediction of cardiovascular clinical events, we investigated the long-term prognostic importance of selected hemostatic factors in patients with angina pectoris. At recruitment, 209 patients underwent clinical assessment and coronary angiography, and a range of hemostatic factors were measured. During the follow-up period of 9 years, 58 patients (28%) suffered a cardiac event (acute myocardial infarction or death from cardiac causes). The risk of cardiac events was positively related to baseline measurements of fibrinogen (risk ratio per SD [RR] increase 1.29, 95% confidence interval [CI] 0.99 to 1.68, P=.06) and negatively related to antithrombin III activity measurements (RR 0.75, 95% CI 0.59 to 0.95, P=.02). No other hemostatic factor measured was significantly related to the risk of having a cardiac event. Worsening of angina in the few weeks before and ejection fraction evaluation at the initial angiography were both strongly related to the risk of cardiac events. However, the relationships of fibrinogen and antithrombin III measurements to risk remained almost unchanged after adjusting for worsening of angina and ejection fraction. Fibrinogen and antithrombin III may have an important etiologic role in the prognosis of patients with angina pectoris.

Adult↗

PubMed1996

Using a coronary risk score for screening and intervention in general practice. British Family Heart Study.

AIM: To investigate whether a risk score proposed by the British Regional Heart Study (BRHS), derived from data collected in 1978-1980, provides an appropriate basis for current coronary risk factor screening and intervention in general practice. METHODS: The BRHS risk score was applied to 1993 men aged 40-59 years and 1353 women aged 35-59 years, from 13 general practices in England, Wales and Scotland, who had health checks during 1991-1992 in the British Family Heart Study (FHS). Modifications to the BRHS risk score were made in order to identify subjects with a current high risk compared with others of the same age and sex. These were validated on 3272 men and 2229 women recruited from different general practices during 1992-1994 in the FHS. RESULTS: Only 9% of men in the FHS fell into the published top (highest risk) quintile of the BRHS score, versus an expected 20%, and 44% fell into the bottom quintile. Scores were, on average, substantially lower in the FHS men than in the BRHS men, principally because of lower measured cholesterol levels (using a Reflotron) and a lower prevalence of cigarette-smoking. The BRHS scores also tended to increase with age, disproportionately identifying older subjects, and were substantially lower in women than in men. Simple age-related modifications to the risk score were therefore devised to overcome these problems. These modifications performed well in the validation. CONCLUSIONS: The substantial difference in risk scores between the BRHS and FHS men may reflect both a real reduction in risk and changes in calibration and methodology. Current use of the BRHS risk score may therefore mislead doctors and patients in the direction of complacency. In addition, the published BRHS risk score has an age-dependence that is undesirable in terms of guiding the intensity of lifestyle intervention which should be offered to an individual patient. The simple modifications proposed provide a more appropriate basis for coronary risk factor screening and intervention in general practice, and one that can be used both for men and for women.

Adult↗

PubMed1995

Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group.

BACKGROUND: Increased levels of certain hemostatic factors may play a part in the development of acute coronary syndromes and may be associated with an increased risk of coronary events in patients with angina pectoris. METHODS: We conducted a prospective multicenter study of 3043 patients with angina pectoris who underwent coronary angiography and were followed for two years. Base-line measurements included the concentrations of selected hemostatic factors indicative of a thrombophilic state or endothelial injury. The results were analyzed in relation to the subsequent incidence of myocardial infarction or sudden coronary death. RESULTS: After adjustment for the extent of coronary artery disease and other risk factors, an increased incidence of myocardial infarction or sudden death was associated with higher base-line concentrations of fibrinogen (mean +/- SD, 3.28 +/- 0.74 g per liter in patients who subsequently had coronary events, as compared with 3.00 +/- 0.71 g per liter in those who did not; P = 0.01), von Willebrand factor antigen (138 +/- 49 percent vs. 125 +/- 49 percent, P = 0.05), and tissue plasminogen activator (t-PA) antigen (11.9 +/- 4.7 ng per milliliter vs. 10.0 +/- 4.2 ng per milliliter, P = 0.02). The concentration of C-reactive protein was also directly correlated with the incidence of coronary events (P = 0.05), except when we adjusted for the fibrinogen concentration. In patients with high serum cholesterol levels, the risk of coronary events rose with increasing levels of fibrinogen and C-reactive protein, but the risk remained low even given high serum cholesterol levels in the presence of low fibrinogen concentrations. CONCLUSIONS: In patients with angina pectoris, the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent acute coronary syndromes. In addition, low fibrinogen concentrations characterize patients at low risk for coronary events despite increased serum cholesterol levels. Our data are consistent with a pathogenetic role of impaired fibrinolysis, endothelial-cell injury, and inflammatory activity in the progression of coronary artery disease.

Adult↗

PubMed1995

Dietary change after smoking cessation: a prospective study.

A population sample of 375 men and women cigarette smokers were recruited to take part in a prospective study of smoking cessation to test the hypothesis that stopping smoking is associated with an increased consumption of the essential fatty acid linoleic acid, which explains the concomitant reduction in risk of coronary heart disease. Diet was assessed using a 10 d weighed record in 301 smokers at baseline, 153 at 4-month follow-up, of whom twenty-six had quit smoking, and 122 at 1-year follow-up, of whom twenty had quit. Compared with continuing smokers, those who had quit at the 4-month follow-up (mean 10 and 13 weeks for men and women respectively) had statistically significant increases in body weight (5%), energy intake (13%), total dietary fat (24%), all specific types of dietary fat (26% polyunsaturated fat, 26% linoleic acid, 30% eicosapentaenoic acid, 23% monounsaturated fat and 22% saturated fat) and vitamin E intake (19%). The foods which appeared to contribute to increases in energy and fat intakes at the 4-month follow-up were vegetable oils and polyunsaturated margarines, processed meats and meat pies. By follow-up at 1 year (mean time since quitting 31 and 41 weeks for men and women respectively) there were no detectable differences in energy and total fat intakes. However, intakes of eicosapentaenoic acid and pteroylglutamate (folate) were statistically significantly higher in the quitters compared with the continuing smokers (37% for eicosapentaenoic acid and 16% for folate). We conclude that the short-term increase in dietary intake of linoleic acid, which is not sustained by 1 year, cannot explain the reduction in risk of coronary disease following smoking cessation.

Adult↗

PubMed1995

Dose-response relationships of serum lipid measurements with the extent of coronary stenosis. Strong, independent, and comprehensive. ECAT Angina Pectoris Study Group.

Serum lipids, lipoproteins, and more recently apolipoproteins and lipoprotein(a) [Lp(a)] have been shown to be independent risk factors for coronary vessel disease and its prognosis. However, the relationships between serum lipid levels and the extent of coronary artery disease (CAD) have not been consistently shown. Twenty-five hundred male and female patients with suspected angina pectoris were recruited from 18 European medical centers. The independent relations of total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apo A-I and B, and Lp(a) with the presence and extent of CAD, as assessed by coronary angiography, were investigated. All of the lipid measures showed strong relations P < .0001) with the presence of CAD, defined by the existence of at least one > or = 50% coronary vessel stenosis. Total cholesterol, LDL cholesterol, apo B, triglycerides, and Lp(a) were substantially higher and HDL cholesterol and apo A-I lower in patients with CAD. The odds ratio of CAD, in the high-risk tertile of each lipid's distribution compared with the low-risk tertile, was in the range 1.5 to 2.3. Each of total cholesterol (or LDL cholesterol or apo B), HDL cholesterol (or apo A), and Lp(a) had an independent effect in predicting the presence of CAD. In addition, all lipids showed a strong association (P = .0006 for triglycerides, P < .0001 otherwise) with the extent of CAD as defined by the number of stenosed coronary vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗

PubMed1995

Haemostasis factors in angina pectoris; relation to gender, age and acute-phase reaction. Results of the ECAT Angina Pectoris Study Group.

The ECAT Angina Pectoris Study is a European multicentre study with the aim of investigating the pathogenetic and predictive role of haemostatic factors in the progression of coronary heart disease. It is the largest study performed up to now with regard to both the number of patients with angina pectoris (n = 3043) and the number of haemostasis assays (n = 23) included. The present paper presents baseline cross-sectional data with particular reference to the relationship of haemostatic factors with each other and with the coronary risk factors age, gender and acute-phase reaction (1). Two clusters of haemostatic factors could be distinguished in which each variable was correlated (P < 0.001) to every other variable: (a) Eight fibrinolysis assays including t-PA, PAI-1 and euglobulin clot lysis time (ECLT), for which PAI-1 appeared to be the dominating factor; (b) antithrombin III, protein C, alpha 2-antiplasmin and plasminogen, the interdependence of which has no obvious explanation. (2). Twelve out of the 23 haemostasis assays were associated (P < or = 0.01) with age. Except for alpha 2-antiplasmin, these relationships indicated an increased tendency to thrombosis with increasing age. (3). Gender differences found in 14 haemostasis parameters do not indicate a consistent difference in the tendency to thrombosis between men and women. Eight haemostasis parameters were on average higher in female than in male patients in the age group over 50 years. (4). C-reactive protein, an acute-phase reactant, was positively correlated (P < 0.001) with fibrinogen, factor VIIIc, von Willebrand factor, the fibrinolysis assays t-PA, PAI-1, ECLT and plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗

PubMed1995

Comparing non-nested regression models.

A method for comparing the fits of two non-nested models, based on a suggestion of Davidson and MacKinnon (1981), is developed in the context of linear and nonlinear regression with normal errors. Each model is regarded as a special case of an artificial "supermodel" and is obtained by restricting the value of a mixing parameter gamma to 0 or 1. To enable estimation and hypothesis testing for gamma, an approximate supermodel is used in which the fitted values from the individual models appear in place of the original parametrization. In the case of nested linear models, the proposed test essentially reproduces the standard F test. The calculations required are for the most part straight-forward (basically, linear regression through the origin). The test is extended to cover situations in which serious bias in the maximum likelihood estimate of gamma occurs, simple approximate bounds for the bias being given. Two real datasets are used illustratively throughout.

Biometry↗

PubMed1995

Readiness for lifestyle advice: self-assessments of coronary risk prior to screening in the British family heart study. Family Heart Study Group.

BACKGROUND: Where health professionals and patients hold similar views of a problem, health outcomes may be better. AIM: The aims of this paper were to document how attenders at primary care cardiovascular screening clinics perceived their risks of coronary heart disease prior to screening; the degree of similarity between perceived level of risk and an epidemiologically derived risk score; and the relative importance assigned to individual risk factors by subjects compared with those assigned by the risk score. METHOD: These issues were investigated in 3725 middle aged men and women who accepted an invitation to attend health screening as part of the British family heart study. RESULTS: Overall, there was a tendency for subjects to be optimistic (37%) rather than pessimistic (21%) when judging their risk of coronary heart disease. Nevertheless, there were strong significant associations between perceived risk and the levels of individual risk factors, particularly personal and family medical history and body mass index. There was also a strong association with the overall risk score though a large minority (31%) held views of their risk of coronary heart disease that were quite different from those based upon the epidemiologically derived index of risk. Respondents accorded greater importance to smoking and parental death from coronary heart disease and less importance to cholesterol level and blood pressure than did the risk score. CONCLUSION: Possible explanations for the observed disagreement are over-optimism or the relative importance given to individual risk factors. The relationships between patients' perceptions of risk and the epidemiological indices likely to be espoused by health professionals are important in understanding the difficulties in communication that might arise in offering lifestyle advice after screening for cardiovascular risk.

Adult↗

PubMed1994

Why sources of heterogeneity in meta-analysis should be investigated.

Although meta-analysis is now well established as a method of reviewing evidence, an uncritical use of the technique can be very misleading. One common problem is the failure to investigate appropriately the sources of heterogeneity, in particular the clinical differences between the studies included. This paper distinguishes between the concepts of clinical and statistical heterogeneity and exemplifies the importance of investigating heterogeneity by using published meta-analyses of epidemiological studies of serum cholesterol concentration and clinical trials of its reduction. Although not without some dangers of speculative conclusions, prompted by overzealous inspection of the data to hand, a sensible investigation of sources of heterogeneity should increase both the scientific and the clinical relevance of the results of meta-analyses.

Adult↗

PubMed1994

By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease?

OBJECTIVE: To estimate by how much and how quickly a given reduction in serum cholesterol concentration will reduce the risk of ischaemic heart disease. DESIGN: Data on the incidence of ischaemic heart disease and serum cholesterol concentration were analysed from 10 prospective (cohort) studies, three international studies in different communities, and 28 randomised controlled trials (with mortality data analysed according to allocated treatment to ensure the avoidance of bias). MAIN OUTCOME MEASURE: Decrease in incidence of ischaemic heart disease or mortality for a 0.6 mmol/l (about 10%) decrease in serum cholesterol concentration. RESULTS: For men results from the cohort studies showed that a decrease of serum cholesterol concentration of 0.6 mmol/l (about 10%) was associated with a decrease in incidence of ischaemic heart disease of 54% at age 40 years, 39% at age 50, 27% at 60, 20% at 70, and 19% at 80. The combined estimate from the three international studies (for ages 55-64 years) was 38% (95% confidence interval 33% to 42%), somewhat greater than the cohort study estimate of 27%. The reductions in incidence of ischaemic heart disease in the randomised trials (for ages 55-64 years) were 7% (0 to 14%) in the first two years, 22% (15% to 28%) from 2.1-5 years, and 25% (15% to 35%) after five years, the last estimate being close to the estimate of 27% for the long term reduction from the cohort studies. The data for women are limited but indicate a similar effect. CONCLUSIONS: The results from the cohort studies, international comparisons, and clinical trials are remarkably consistent. The cohort studies, based on half a million men and 18,000 ischaemic heart disease events, estimate that a long term reduction in serum cholesterol concentration of 0.6 mmol/l (10%), which can be achieved by moderate dietary change, lowers the risk of ischaemic heart disease by 50% at age 40, falling to 20% at age 70. The randomised trials, based on 45,000 men and 4000 ischaemic heart disease events show that the full effect of the reduction in risk is achieved by five years.

Adult↗

PubMed1994

Assessing possible hazards of reducing serum cholesterol.

OBJECTIVE: To assess whether low serum cholesterol concentration increases mortality from any cause. DESIGN: Systematic review of published data on mortality from causes other than ischaemic heart disease derived from the 10 largest cohort studies, two international studies, and 28 randomised trials, supplemented by unpublished data on causes of death obtained when necessary. MAIN OUTCOME MEASURES: Excess cause specific mortality associated with low or lowered serum cholesterol concentration. RESULTS: The only cause of death attributable to low serum cholesterol concentration was haemorrhagic stroke. The excess risk was associated only with concentrations below about 5 mmol/l (relative risk 1.9, 95% confidence interval 1.4 to 2.5), affecting about 6% of people in Western populations. For noncirculatory causes of death there was a pronounced difference between cohort studies of employed men, likely to be healthy at recruitment, and cohort studies of subjects in community settings, necessarily including some with existing disease. The employed cohorts showed no excess mortality. The community cohorts showed associations between low cholesterol concentration and lung cancer, haemopoietic cancers, suicide, chronic bronchitis, and chronic liver and bowel disease; these were most satisfactorily explained by early disease or by factors that cause the disease lowering serum cholesterol concentration (depression causes suicide and lowers cholesterol concentration, for example). In the randomised trials nine deaths (from a total of 687 deaths not due to ischaemic heart disease in treated subjects) were attributed to known adverse effects of the specific treatments, but otherwise there was no evidence of an increased mortality from any cause arising from reduction in cholesterol concentration. CONCLUSIONS: There is no evidence that low or reduced serum cholesterol concentration increases mortality from any cause other than haemorrhagic stroke. This risk affects only those people with a very low concentration and even in these will be outweighed by the benefits from the low risk of ischaemic heart disease.

Accidents↗

PubMed1993

Variability over time of haemostatic and other cardiovascular risk factors in patients suffering from angina pectoris. ECAT Angina Pectoris Study Group.

The variability of haemostatic factor measurements in patients presenting with angina pectoris is investigated. In all, 219 middle aged patients (almost all men) provided repeat measurements 2.5 years apart on a battery of haemostatic and haematological tests and other cardiovascular risk factors. Correlations between repeat measurements were lower than might be expected in a healthy population, reflecting a relatively large degree of variability within individuals over time. The highest correlations observed for haemostatic factors were for von Willebrand factor related antigen (r = 0.48) and fibrinogen (r = 0.45). The correlations were generally lower amongst patients who had undergone coronary surgery or angioplasty between the two measurements. We conclude that the underlying relationship of fibrinogen to coronary risk must be much greater than is generally appreciated, since even single measurements are found to be important predictors of risk, despite only moderate stability over time. The very low correlations for beta-thromboglobulin (r = 0.10) and platelet factor 4 (r = 0.03) which were observed in this study casts doubt on their potential usefulness as predictors of long-term cardiovascular risk.

Adult↗

PubMed1993

Prothrombin activation fragment 1 + 2 and thrombin antithrombin III complexes in patients with angina pectoris: relation to the presence and severity of coronary atherosclerosis.

Plasma levels of the prothrombin activation fragment 1 + 2 (F 1 + 2) and of thrombin antithrombin III complexes (TAT) were determined in 225 patients with angina pectoris undergoing coronary angiography. Oral anticoagulant therapy was associated with a marked reduction in mean F1 + 2 (0.63 vs 1.62 nmol/l, p < 0.0001) and TAT levels (1.65 vs 2.23 micrograms/l, p < 0.0001). Omitting patients on oral anticoagulants, TAT values showed a positive association with patients' age (r = 0.18; p = 0.01) and were slightly higher in patients with a history of myocardial infarction than in those without (2.47 vs 2.11 micrograms/l; p = 0.06). Both F1 + 2 and TAT levels were increased in patients with angiographically verified coronary atherosclerosis as compared to patients with angina and angiographically normal coronaries (F1 + 2: 1.76 vs 1.36 nmol/l, TAT: 2.35 vs 2.00 micrograms/l; p-values after adjusting for age, sex and past history of myocardial infarction 0.06 and 0.11 respectively). However, no graded relationship between F1 + 2 or TAT values and severity of atherosclerosis was observed. This study provides suggestive evidence that a procoagulant state exists in patients with angina pectoris and coronary atherosclerosis. Its relevance in predicting coronary ischaemic events needs to be studied prospectively.

Adult↗

PubMed1993

Cigarette smoking, polyunsaturated fats, and coronary heart disease.

The relation between smoking habit and diet was investigated in 910 men and women. Diet was assessed by a self-administered food frequency questionnaire. After adjustment for age, sex, and occupational group, smokers had a substantially higher saturated fat (SFA) intake and much lower polyunsaturated fat (PUFA), principally due to a lower linoleic acid (LA) intake, resulting in a lower P:S ratio compared with never smokers, and these dietary differences remained after adjustment for alcohol consumption, BMI, and energy intake. Smokers also had different food choices obtaining more PUFA from saturated fat products such as dairy foods, lard, and ordinary margarine, and less from concentrated sources such as PUFA margarines and vegetable oils than nonsmokers. The food choices of cigarette smokers leading to a higher SFA and lower PUFA intakes may partly explain their increased risk of coronary heart disease.

Adult↗