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Biomedical subjects

A D Beswick

Publications and source records attributed to A D Beswick.

17 recordsLinked to original sources

Platelet aggregation in whole blood is a paradoxical predictor of ischaemic stroke: Caerphilly Prospective Study revisited.

The Caerphilly Prospective Study demonstrates a paradoxical association of increased ischaemic stroke risk with decreased whole blood adenosine diphosphate (ADP) induced platelet sensitivity. A reanalysis of this association examines whether other haematological indices and prevalent disease at baseline may explain this finding. There were 1506 men free of clinical cardiovascular disease at baseline, with 85 men manifesting a first ischaemic stroke event over 8.3 years of follow-up in this population-based prospective cohort study. Using two different approaches, the paradoxical findings are confirmed and associations are slightly stronger after accounting for red cell, platelet, and white cell indices. A U-shaped relation of stroke with platelet count is noted. These findings are consistent with the existence of sub-clinical endothelial disease and compensatory mechanisms down-regulating ADP-induced aggregation sensitivity. They support an allostasis model of causality for understanding the paradox. A public health approach to prevention could have measurable impact if intervention strategies can be developed to alter early stages of disease appropriate to such mechanisms of causation.

Adenosine Diphosphate↗

Provision, uptake and cost of cardiac rehabilitation programmes: improving services to under-represented groups.

OBJECTIVES: To estimate UK need for outpatient cardiac rehabilitation, current provision and identification of patient groups not receiving services. To conduct a systematic review of literature on methods to improve uptake and adherence to cardiac rehabilitation. To estimate cost implications of increasing uptake of cardiac rehabilitation. DATA SOURCES: Hospital Episode Statistics (England). Hospital Inpatient Systems (Northern Ireland). Patients Episode Database for Wales. British Association for Cardiac Rehabilitation/British Heart Foundation surveys. Cardiac rehabilitation centres. Patients from general hospitals. Electronic databases. REVIEW METHODS: The study analysed hospital discharge statistics to ascertain the population need for outpatient cardiac rehabilitation in the UK. Surveys of cardiac rehabilitation programmes were conducted to determine UK provision, uptake and audit activity, and to identify local interventions to improve uptake. Data were also examined from a trial estimating eligibility for cardiac rehabilitation and non-attendance. A systematic review of interventions to improve patient uptake, adherence and professional compliance in cardiac rehabilitation was conducted. Estimated costs of improving uptake were identified from national survey, systematic review and sampled cardiac rehabilitation programmes. RESULTS: In England, Wales and Northern Ireland nearly 146,000 patients discharged from hospital with primary diagnosis of acute myocardial infarction, unstable angina or following revascularisation were potentially eligible for cardiac rehabilitation. In England in 2000, 45-67% of these patients were referred, with 27-41% attending outpatient cardiac rehabilitation. If all discharge diagnoses of ischaemic heart disease were considered, nearly 299,000 patients would be potentially eligible and in England rates of attendance and referral would be 22-33% and 13-20% respectively. Rates of referral and attendance were similar in Wales, but somewhat lower in Northern Ireland. It was found that referral and attendance of older people and women at cardiac rehabilitation tended to be low. It was also suggested that patients from ethnic minorities and those with angina or heart failure were less likely to be referred to or join programmes. A wide range of local interventions suggested awareness of the problem of uptake. In an NHS-funded randomised controlled trial, possibly representing more optimal protocol-led care, medical and nursing staff identified 73-81% of patients with acute myocardial infarction as eligible for cardiac rehabilitation. Excluded patients tended to be older with more severe presentation of cardiac disease. Experiences of patients suggested that uptake may be improved by addressing issues of motivation and relevance of rehabilitation to future well-being, co-morbidities, site and time of programme, transport and care for dependents. Systematic review of studies supported the use of letters, pamphlets or home visits to motivate patients and the use of trained lay visitors. Self-management techniques showed some value in promoting adherence to lifestyle changes. Studies examining professional compliance found that professional support for practice nurses may have value in the coordination of postdischarge care. Average costs in 2001 of cardiac rehabilitation to the health service per patient completing a cardiac rehabilitation programme were about GBP350 (staff only) and GBP490 (total). If services were modelled on an intermediate multidisciplinary configuration with three to five key staff, approximately 13% more patients could be treated with the same budget. Depending on staffing configuration an approximate 200-790% budget increase would be required to provide cardiac rehabilitation to all potentially eligible patients. CONCLUSIONS: Provision of outpatient cardiac rehabilitation in the UK is low and little is known about the capacity of cardiac rehabilitation centres to increase this provision. There is an uncoordinated approach to audit data collection and few interventions aimed at improving the situation have been formally evaluated. Motivational communications and trained lay volunteers may improve uptake of cardiac rehabilitation, as may self-management techniques. Experience of low-cost interventions and good practice exists within rehabilitation centres, although cost information frequently is not reported. Increased provision of outpatient cardiac rehabilitation will require extra resources. Further trials are required to compare the cost-effectiveness of comprehensive multidisciplinary rehabilitation with simpler outpatient programmes, also research is needed into economic and patient preference studies of the effects of different methods of using increased funding for cardiac rehabilitation. An evaluation of a range of interventions to promote attendance in all patients and under-represented groups would also be useful. The development of standards is suggested for audit methods and for eligibility criteria, as well as regular and comprehensive data collection to estimate the need for and provision of cardiac rehabilitation. Further areas for intervention could be identified through qualitative studies, and the extension of low-cost interventions and good practice within rehabilitation centres. Regularly updated systematic reviews of relevant literature would also be useful.

Cost-Benefit Analysis↗

Platelet aggregation and incident ischaemic heart disease in the Caerphilly cohort.

BACKGROUND: Platelets are involved in myocardial infarction but evidence of prediction of infarction by measures of platelet function are sparce. METHODS: Platelet aggregation to thrombin and to ADP in platelet rich plasma was recorded for 2176 men aged 49-65 years in the Caerphilly cohort study. RESULTS: Results from 364 men were excluded, 80 of whom had not fasted before venepuncture; most of the others were excluded because antiplatelet medication had been taken shortly before the platelet tests. During the five years following the platelet tests 113 ischaemic heart disease (IHD) events which fulfilled the World Health Organisation criteria were identified--42 fatal and 71 non-fatal. No measure of platelet aggregation was found to be significantly predictive of incident IHD. The possibility that platelet function is predictive for only a limited time after it is characterised, and that prediction falls off with time, was tested. When IHD events are grouped by their time of occurrence after aggregation had been measured, the test results show a gradient suggestive of prediction of early IHD events. Thus, 24% of the men who had an event within 500 days of the test had had a high secondary response to ADP while only 12% of those whose IHD event had been 1000 or more days after the test had shown a high platelet response at baseline. The trend in these proportions is not significant. CONCLUSIONS: Platelet aggregation to thrombin and ADP in platelet rich plasma was recorded in the Caerphilly cohort study. No measure of aggregation was found to be predictive of IHD.

Adenosine Diphosphate↗

Fibrinogen, viscosity and the 10-year incidence of ischaemic heart disease.

AIMS: To use the ten year follow-up of the Caerphilly and Speedwell studies to assess the contributions of fibrinogen and viscosity to the prediction of risk of ischaemic heart disease. METHODS AND RESULTS: Caerphilly and Speedwell are prospective studies based on representative samples of middle-aged males. Ischaemic heart disease morbidity and mortality were defined using hospital notes, repeat electro-cardiographs and death certificates. There were 603 incident events among the 4860 men. Age-adjusted relative odds of ischaemic heart disease increased to 3.3 and 3.4 in the 20% of men with the highest levels of fibrinogen and viscosity, respectively. After standardizing for the major cardiovascular risk factors, these relative odds were 2.2 (95% confidence interval 1.6 to 3.1) for fibrinogen and 2.3 (95% confidence interval 1.7 to 3.2) for viscosity. When fibrinogen and viscosity were entered jointly, both remained significant (P < 0.01) predictors. Incidence of ischaemic heart disease increased with increasing fibrinogen at every level of viscosity, and vice versa. Interactions with lipids were also examined. There was no support for the suggestion that risk is independent of cholesterol level when fibrinogen is low. CONCLUSIONS: Fibrinogen and viscosity are powerful, long term and independent predictors of the risk of ischaemic heart disease.

Age Distribution↗

Attitudes and ischaemic heart disease in the Caerphilly Study: the Health Attitude Inventory.

BACKGROUND: The Health Attitude Inventory (HAI) is developed to assess attitudes, beliefs and values towards coronary-related behaviour in epidemiological studies. It comprises a 76-item self-administered questionnaire which can be completed in under 10 minutes by most adults. METHODS: The HAI was administered to 2100 men aged 50-64 years along with measures of ischaemic heart disease risk factors, including the following coronary-related behaviours: smoking, exercise, type A behaviour and the consumption of fried food, dairy produce, wholemeal bread and vegetables. RESULTS: Cross-sectional analyses using linear regression showed attitudes, beliefs and values to explain between 8% and 27% of the variance in the dietary coronary-related behaviour. For exercise 13% of the variance was explained, and for type A behaviour 18%. Similar analysis for smoking using logistic regression (non-smoker versus current smoker) showed a predictive concordance of 95%. CONCLUSIONS: The HAI has demonstrated the assessment of attitudes, beliefs and values in an epidemiological setting to show associations with a range of coronary risk behaviours. This finding has potential public health as well as aetiological application in that influential attitudes, values and beliefs can be identified to aid increasing healthy as well as reducing risky coronary-related behaviour.

Attitude to Health↗

Cigarette smoking sensitizes and desensitizes impedance-measured ADP-induced platelet aggregation in whole blood.

The effect of smoking on platelet aggregation appears to produce conflicting results, with some studies indicating an enhancement and others a decrease of aggregation. This epidemiological study of 120 male smokers, a subset of the Caerphilly Heart Disease Study, examined the relationship of two dimensions of smoking (time proximity of last cigarette before venepuncture and serum nicotine concentration) with threshold dose of adenosine diphosphate (ADP) necessary to induce platelet aggregation in whole blood. Means (range) of ADP threshold dose and nicotine concentration were 1.66 (0.5-2.5, censored) microM and 12.2 (0-35.2) ng/ml. Men smoking within 30 min of venepuncture demonstrated lower ADP threshold doses (-0.48 microM lower [95% C.I.: -0.95, -0.02])--reflecting increased sensitivity. Men with higher nicotine concentration had higher ADP threshold doses (Regression Coefficient: +0.032 microM per ng/ml [95% C.I.: 0.003, 0.062])--reflecting decreased sensitivity. Men smoking 30 min or more before venepuncture who also had high nicotine concentration (25-30 ng/ml) demonstrated the highest ADP threshold doses compared to never smokers and to men smoking the previous day (approximately 2.20 vs 1.86 and 1.81 microM). Relations involving nicotine concentration do not necessarily reflect a pharmacological effect although the potential for a short term nicotine mediated tolerance effect cannot be dismissed. These observations support an hypothesis suggesting a temporal sequence of platelet sensitization and desensitization during smoking.

Adenosine Diphosphate↗

Inter-relationships between haemostatic tests and the effects of some dietary determinants in the Caerphilly cohort of older men.

Inter-relationships between fibrinogen, platelets and other haemostatic factors were examined in 1030 men aged 55-99 years. Fasting blood was taken and used for cell counts, platelet counts and platelet parameters, aggregation of platelets to ADP by a whole blood method and a filter test of platelet activation. Plasma fibrinogen, von Willebrand factor, factor VII and plasma viscosity were measured by standard methods. A stressed bleeding time was conducted on the forearm of the arm not used for venepuncture. Variability within the laboratory and short-term intra-subject variation were examined and found to be acceptably small. The effect of age on the tests was modest, except for von Willebrand factor which increased by about 50% of a SD for every 10 years of age. Cholesterol and triglyceride levels had small effects on the platelet tests and a large effect on factor VII. A number of dietary and life-style determinants were examined: smokers had increased levels of fibrinogen, viscosity and white cell count and reduced bleeding times. Alcohol drinkers showed reduced platelet activity and have lower levels of fibrinogen, von Willebrand factor and white cell count. Men who took fish oil capsules had substantially increased bleeding times and lower levels of von Willebrand factor and men who took capsules containing an extract of garlic showed reduced platelet retention in the filter test.

Aged↗

Endogenous sex hormones and ischemic heart disease in men. The Caerphilly prospective study.

Numerous case-control studies have suggested that elevated levels of endogenous estrogen and low levels of testosterone are associated with ischemic heart disease (IHD) in men. These findings were tested in the Caerphilly study of 2,512 men from the general population who were aged 45-59 years at baseline and were followed for 5 years. Some 153 men experienced a new episode of IHD (fatal and nonfatal) during the period of follow-up. Baseline values of estradiol were marginally higher in subjects who developed IHD than in those who did not, but the difference was not statistically significant. Plasma values of testosterone were similar in the two groups. Among quintiles of the distribution of the hormone values, the incidence of IHD was similar in the case of estradiol; there was also no clear trend in the case of testosterone. These findings provide no support for the suggestion that plasma estradiol or testosterone are primary risk factors for IHD, although the associations between plasma testosterone and other probable risk markers (triglycerides, insulin, body mass index, and high density lipoprotein cholesterol) indicate the possibility that testosterone may play an indirect role in the pathogenesis of IHD.

Cohort Studies↗

Alcohol and platelet aggregation: the Caerphilly Prospective Heart Disease Study.

Intakes of alcohol and saturated fatty acids were determined through a dietary questionnaire from 1600 men (aged 49-66 y) in the Caerphilly Prospective Heart Disease Study. Platelet aggregation induced by thrombin adenosine disphosphate (ADP), and collagen was studied in subjects who had fasted and had not recently taken drugs affecting platelets. In subjects who drank alcohol, the odds ratio of a high response to aggregation was significantly reduced (primary ADP, P less than 0.05; secondary ADP, P less than 0.001; collagen, P less than 0.02). The significance was enhanced by adjusting for smoking and by including only the subjects with a high intake of saturated fatty acids or a low intake of polyunsaturated fatty acids. By contrast, the responsiveness to thrombin was slightly increased at all levels of alcohol consumption. We therefore suggest that part of the effects of alcohol on coronary heart disease may be mediated by a dose-dependent effect on certain platelet functions, modulated by the intake of dietary fat.

Adenosine Diphosphate↗

Long-term diet modification and platelet activity.

Platelet activity was assessed in a sub-sample of 56 participants in the MRC Diet and Reinfarction Trial (DART). Men whose diets contained a high ratio of polyunsaturated to saturated fatty acids (a P:S ratio of greater than 0.5) showed reduced secondary platelet aggregation to adenosine diphosphate (ADP) in platelet-rich plasma (PRP), and diminished platelet aggregation to ADP in whole blood. A trend of reduced secondary platelet aggregation to ADP with increasing dietary eicosapentaenoic acid was noted, but this was not statistically significant. The results of this study and the MRC Diet and Reinfarction Trial suggest a mediatory role for platelet activity in the relationship between diet and ischaemic heart disease.

Adult↗

Ischemic heart disease and platelet aggregation. The Caerphilly Collaborative Heart Disease Study.

The Caerphilly Collaborative Heart Disease Study is based on a large cohort of men (2,398) aged 49-66 years at the time of study. Platelet aggregation induced by collagen, thrombin, and ADP was measured in fasting blood samples and was related to prevalent angina, past myocardial infarction, and electrocardiographic evidence of ischemic heart disease. A number of subjects had taken aspirin, other nonsteroidal anti-inflammatory drugs, or other drugs affecting platelet aggregation 7 days before blood sample collection; after the exclusion of these subjects, data were available for 1,811 men. No relations were demonstrated with angina, but significant relations were shown between past myocardial infarctions and electrocardiographic evidence of ischemia and ADP-induced aggregation (both primary and secondary) and between electrocardiographic evidence of ischemia and thrombin-induced aggregation. The strongest relation indicated more than a twofold increase in the odds of a past myocardial infarction in subjects of the highest fifth of ADP-induced primary platelet aggregation compared with the lowest fifth. No significant relations were detected with collagen-induced aggregation. Accounting for a number of possible confounding factors had a relatively small impact on the relations between platelet aggregation and ischemic heart disease. Other evidence, including the well-established effect of aspirin on reducing the incidence of ischemic heart disease, indicates that the relations we describe are unlikely to be simply an effect of IHD on platelets.

Aged↗

The association of platelet and red cell count with platelet impedance changes in whole blood and light-scattering changes in platelet rich plasma: evidence from the Caerphilly Collaborative Heart Disease Study.

This epidemiological study was undertaken to explore possible relationships among various haematological indices, prevalent ischaemic heart disease and platelet "function" as measured by two rather different methods. ADP-induced platelet impedance changes in whole blood were strongly associated with prevalent ischaemic heart disease in a general population of 49-66 year men at increased risk. Adenosine diphosphate (ADP) induced platelet aggregation in platelet rich plasma (PRP) at a constant platelet count and also the whole blood platelet count and red cell (RBC) count were strongly and independently related to ADP-induced platelet impedance changes. Both platelet count and platelet aggregation in PRP assessed by changes in optical density were directly related to increasing platelet "sensitivity" as measured by impedance changes in whole blood but RBC count was inversely related. Positive independent relationships between platelet impedance changes and plasma viscosity and fibrinogen were markedly attenuated when platelet count was taken into account, but this finding does not discount a role for these factors in platelet aggregation. No relationship was noted between white blood cell (WBC) count and platelet impedance changes; however, a significant inverse relationship was noted with platelet aggregation in PRP. These findings indicate that laboratory-based experimental findings can be observed in population based studies, and that these haematological factors may be important indicators of ischaemic disease in the population.

Adenosine Diphosphate↗

Type A behaviour and pressor response in a representative sample of middle-aged men.

The hypothesis that type A behaviour is associated with greater pressor response to stress was tested in a representative sample of 114 men aged 30-65 yr. Jenkins Activity Survey, Framingham and Bortner type A scores were related to blood pressure and heart rate under rest, serial reaction time, mental arithmetic, and noise conditions. Type A scores were modestly intercorrelated (r = 0.59 to r = 0.67). Type A scores were inversely related to age and resting systolic pressure and were independent of smoking history, social class, marital status, and task performance parameters. Type A scores were not related to pressor or heart rate response to stress under any of the stress conditions. These findings do not support the importance of physiological response as an explanation of the association between type A and heart disease.

Adult↗

Sex hormones, insulin, lipids, and prevalent ischemic heart disease.

The relations between estradiol, testosterone, insulin, lipids, and prevalent ischemic heart disease were examined using the cross-sectional data from the Caerphilly Heart Disease Study, a cohort of 2,512 men (aged 45-59 years) surveyed between 1978 and 1982. Endogenous levels of estradiol were associated directly with high density lipoprotein (HDL) cholesterol (r = 0.106, p less than 0.001), but this relation was removed after adjustment for testosterone and insulin levels. Estradiol was not associated with prevalent ischemic heart disease. Endogenous levels of testosterone were associated directly with HDL cholesterol (r = 0.148, p less than 0.001) and inversely with triglyceride (r = -0.217, p less than 0.001). Persons with prevalent ischemic heart disease had significantly lower testosterone levels than persons without ischemic heart disease (mean levels 20.9 vs. 22.0 nmol/liter, p less than 0.01). These relations were confounded by associations with insulin. The associations between testosterone and the lipids persist after adjusting for body mass index, age, and insulin. The association between testosterone and prevalent ischemic heart disease was reduced after adjusting for insulin and/or triglyceride levels. The results suggest that insulin and testosterone may have an interdependent regulatory effect on lipid metabolism. The effect of testosterone on ischemic heart disease appears to be primarily mediated through its association with insulin. Future work on sex hormones and ischemic heart disease will need to account for the effects of insulin.

Blood Pressure↗

Whole blood impedance platelet aggregometry and ischemic heart disease. The Caerphilly Collaborative Heart Disease Study.

The Caerphilly Collaborative Heart Disease Study is based on a large cohort of men who were ages 49 to 64 years at the time of the study. We report the results for platelet aggregation measured in whole blood from a subsample of 308 men. The index of sensitivity used was the minimum concentration of adenosine diphosphate that produced a defined degree of impedance change in the Chronolog 560 aggregometer. There was a marked association between aggregation and prevalent ischemic heart disease (IHD). The odds ratios and 95% confidence intervals (CI) for prevalent IHD in men with the most sensitive platelets compared with those with the least sensitive platelets were 3.6 (95% Cl: 1.1 to 12.2) for angina; 7.3 (95% Cl: 2.0 to 24.3) for previous myocardial infarction (MI); and 2.7 (95% Cl: 1.0 to 7.6) for electrocardiogram evidence of ischemia. The confidence limits for these odds ratios are large because of the small sample size, but the estimates of odds ratio are relatively large compared to similar relationships between the traditional risk factors of serum cholesterol, blood pressure, smoking, and prevalent IHD (1.5 to 2.5). A number of factors that might confound the relationships between platelets and IHD were examined, but the associations remained statistically significant when these were taken into account.

Adenosine Diphosphate↗