Risk of stroke in users of oral contraceptives.
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Cerebrovascular Disorders↗
Biomedical subjects
M Thorogood
Publications and source records attributed to M Thorogood.
Case and control recruitment, and validation of cases for the MICA case-control study in England, Scotland and Wales.
OBJECTIVES: To describe the processes involved in the selection of cases and controls, and the validation of case diagnosis, in a large case-control study on the association between myocardial infarction (MI) and oral contraceptives. DESIGN: Community case-control study in England, Scotland and Wales. SUBJECTS: Cases were women aged 16-44 with a diagnosis of MI. Controls were age and general practice matched women without a diagnosis of MI. RESULTS: The proportion of interviewed cases per number eligible was 19% (95% CI 12-26%) lower in England and Wales than in Scotland. The kappa score for agreement between three cardiologists on diagnostic categories of the potential cases was 0.52 overall ('moderate' agreement). For the 35 cases resubmitted for categorization, the kappa scores for agreement between the first and second classification for the two national committee cardiologists were 0.32 and 0.23 ('fair' agreement). Age matching of controls was better in Scotland than England and Wales, the proportion of the first choice controls being 14% (95% CI 8-19%) higher in Scotland. The mean time to complete a cluster of interviews (one case and four controls) was 36 days in Scotland and 63 days in England and Wales. CONCLUSIONS: Very close age-matching was achieved overall, although the process was more efficient in Scotland than in England and Wales. Some suggestions for improvement in the case validation process are made.
Journal Article↗
Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies.
We combined data from 5 prospective studies to compare the death rates from common diseases of vegetarians with those of nonvegetarians with similar lifestyles. A summary of these results was reported previously; we report here more details of the findings. Data for 76172 men and women were available. Vegetarians were those who did not eat any meat or fish (n = 27808). Death rate ratios at ages 16-89 y were calculated by Poisson regression and all results were adjusted for age, sex, and smoking status. A random-effects model was used to calculate pooled estimates of effect for all studies combined. There were 8330 deaths after a mean of 10.6 y of follow-up. Mortality from ischemic heart disease was 24% lower in vegetarians than in nonvegetarians (death rate ratio: 0.76; 95% CI: 0.62, 0.94; P<0.01). The lower mortality from ischemic heart disease among vegetarians was greater at younger ages and was restricted to those who had followed their current diet for >5 y. Further categorization of diets showed that, in comparison with regular meat eaters, mortality from ischemic heart disease was 20% lower in occasional meat eaters, 34% lower in people who ate fish but not meat, 34% lower in lactoovovegetarians, and 26% lower in vegans. There were no significant differences between vegetarians and nonvegetarians in mortality from cerebrovascular disease, stomach cancer, colorectal cancer, lung cancer, breast cancer, prostate cancer, or all other causes combined.
Adolescent↗
The Oxford Vegetarian Study: an overview.
The Oxford Vegetarian Study is a prospective study of 6000 vegetarians and 5000 nonvegetarian control subjects recruited in the United Kingdom between 1980 and 1984. Cross-sectional analyses of study data showed that vegans had lower total- and LDL-cholesterol concentrations than did meat eaters; vegetarians and fish eaters had intermediate and similar values. Meat and cheese consumption were positively associated, and dietary fiber intake was inversely associated, with total-cholesterol concentration in both men and women. After 12 y of follow-up, all-cause mortality in the whole cohort was roughly half that in the population of England and Wales (standardized mortality ratio, 0.46; 95% CI, 0.42, 0.51). After adjusting for smoking, body mass index, and social class, death rates were lower in non-meat-eaters than in meat eaters for each of the mortality endpoints studied [relative risks and 95% CIs: 0.80 (0. 65, 0.99) for all causes of death, 0.72 (0.47, 1.10) for ischemic heart disease, and 0.61 (0.44, 0.84) for all malignant neoplasms]. Mortality from ischemic heart disease was also positively associated with estimated intakes of total animal fat, saturated animal fat, and dietary cholesterol. Other analyses showed that non-meat-eaters had only half the risk of meat eaters of requiring an emergency appendectomy, and that vegans in Britain may be at risk for iodine deficiency. Thus, the health of vegetarians in this study is generally good and compares favorably with that of the nonvegetarian control subjects. Larger studies are needed to examine rates of specific cancers and other diseases among vegetarians.
Cholesterol↗
Risk of myocardial infarction in young female smokers.
OBJECTIVES: To determine the extent of risk of myocardial infarction from cigarette smoking in young women, and to examine the relation of smoking with other putative risk factors. DESIGN: Community based case control study. SETTING: England, Scotland, and Wales. PATIENTS: Women (n = 448) between 16 and 44 years old with a diagnosis of incident myocardial infarction between 1 October 1993 and 16 October 1995. Controls (n = 1728) were age and general practice matched women without a diagnosis of myocardial infarction. OUTCOMES MEASURES: Odds ratios for risk of myocardial infarction associated with smoking and other risk factors. RESULTS: Odds ratios for myocardial infarction in smokers versus non-smokers showed a strong dose response, from 2.47 (95% confidence interval (CI) 1.12 to 5.45) in smokers of 1-5 cigarettes per day to 74.6 (95% CI 33.0 to 169) in smokers of >/= 40 cigarettes per day. There was no interaction of smoking with use of oral contraceptives, but there were additive risks with other clinical risk factors such as hypertension and diabetes. It is estimated that if all women aged 16-44 years were able to stop smoking, 400 cases of myocardial infarction per annum (of whom 112 would die) would be prevented. CONCLUSIONS: In young women the risk of myocardial infarction from smoking was considerable, and heavy smokers with other risk factors were especially at risk.
Adolescent↗
Mortality in people taking selegiline: observational study.
OBJECTIVE: To evaluate mortality among patients with Parkinson's disease receiving different treatment. DESIGN: Cohort study based on computerised medical records. SETTING: UK General Practice Research Database. SUBJECTS: 12 621 patients aged between 35 and 90 years who had received a prescription for an antiparkinsonian drug, whether or not a diagnosis of Parkinson's disease had been recorded. Patients prescribed an antipsychotic drug before or at the same time as their first antiparkinsonian drug or before age 35 were excluded to avoid including drug-induced Parkinsonism. MAIN OUTCOME MEASURE: Death from any cause. RESULTS: 1720 deaths occurred during 14 000 person-years of observation. There was a non-significant 11% (95% confidence interval 0% to 23%) increase in the risk of death associated with taking selegiline either alone or in combination with levodopa. The death rate was higher among younger patients (aged under 80 years) and those with a recorded diagnosis of Parkinson's disease taking selegiline alone. CONCLUSIONS: The results are compatible with a small excess mortality in people taking selegiline and suggest a larger excess in patients under 80 years of age and those with a confirmed diagnosis of Parkinson's disease taking selegiline without levodopa.
Adult↗
Search for evidence of effective health promotion. Quantitative outcome evaluation with qualitative process evaluation is best.
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Evidence-Based Medicine↗
Thromboembolic stroke in young women. A European case-control study on oral contraceptives. Transnational Research Group on Oral Contraceptives and the Health of Young Women.
A matched case-control study was performed between 1993 and 1996 in 16 centers in the United Kingdom, Germany, France, Switzerland, and Austria. The objective was to determine the influence of oral contraceptives (OC), particularly those containing modern progestins, on the risk for ischemic stroke in women aged 16-44 years. A total of 220 women who had had an incident ischemic stroke and were compared with 775 control subjects who were unaffected by stroke. At least one hospital and one community control subject per patient was matched and interviewed with the corresponding patient for 5-year age band and for area of residence. Crude odds ratios (95% confidence intervals [CI]) for ischemic stroke were as follows. For current use of any OC versus no use 2.3 (1.7-3.2), the adjusted odds ratio (OR) 3.6 (2.4-5.4). The OC associated risk was higher for first generation than for second or third generation OC. The risk estimates for patients versus community control subjects were always lower than for hospital control subjects. No major regional difference of the risk estimates was found. Compared with nonusers of OC without hypertension, women with hypertension who used OC had an almost 10-fold increased risk. However, OC users who had had a blood pressure check before OC prescription had a lower risk than did those without such a check. Smoking > 10 cigarettes/day is associated with higher risk of stroke, particularly for OC users. No significant effect was found for duration of OC use. We conclude that although there is a small relative risk of occlusive stroke for healthy women currently using OC, the attributable risk is very small because the incidence in this age group is very low. The small increase in risk of OC use may be further reduced by preventive efforts for cardiovascular risk factors, particularly hypertension and smoking.
Adolescent↗
Stroke and steroid hormonal contraception.
The rate of stroke in young women has been falling for some years. The data presented here suggest that the relative risk associated with oral contraceptive use also is falling. This is probably due to a combination of younger age at use of oral contraceptives, lower steroid dose of preparations, and more systematic screening of potential users; particularly with respect to blood pressure. The risk associated with oral contraceptive use is greater for occlusive stroke but increases with age in hemorrhagic stroke. Risk of occlusive stroke increases with increasing doses of estrogen. The evidence for a risk related to type or dose of progestogen is less consistent, but there is no support for an increase in risk associated with use of desogestrel or gestodene.
Age Factors↗
Low body mass index in non-meat eaters: the possible roles of animal fat, dietary fibre and alcohol.
OBJECTIVE: To examine the associations of diet and other lifestyle factors with body mass index (BMI) using data from the Oxford Vegetarian Study. SUBJECTS: 1914 male and 3378 female non-smokers aged 20-89 y at recruitment to the study. MEASUREMENTS: All subjects completed a diet/lifestyle questionnaire at recruitment giving details of their usual diet and other characteristics including height and weight, smoking and drinking habits, amount of exercise, occupation and reproductive history. Answers to the food frequency questionnaire were used to classify subjects as either meat eaters or non-meat eaters, and to estimate intakes of animal fat and dietary fibre. Subjects were further classified according to their alcohol consumption, exercise level, social class, past smoking habits and parity. RESULTS: Mean BMI was lower in non-meat eaters than in meat eaters in all age groups for both men and women. Overall age-adjusted mean BMIs in kg/m2 were 23.18 and 22.05 for male meat eaters and non-meat eaters respectively (P < 0.0001) and 22.32 and 21.32 for female meat eaters and non-meat eaters respectively (P < 0.0001). In addition to meat consumption, dietary fibre intake, animal fat intake, social class and past smoking were all independently associated with BMI in both men and women; alcohol consumption was independently associated with BMI in men, and parity was independently associated with BMI in women. After adjusting for these factors, the differences in mean BMI between meat eaters and non-meat eaters were reduced by 36% in men and 31% in women. CONCLUSIONS: Non-meat eaters are thinner than meat eaters. This may be partly due to a higher intake of dietary fibre, a lower intake of animal fat, and only in men a lower intake of alcohol.
Adult↗
Mortality in vegetarians and non-vegetarians: a collaborative analysis of 8300 deaths among 76,000 men and women in five prospective studies.
OBJECTIVE: To compare the mortality rates of vegetarians and non-vegetarians. DESIGN: Collaborative analysis using original data from five prospective studies. Death rate ratios for vegetarians compared to non-vegetarians were calculated for ischaemic heart disease, cerebrovascular disease, cancers of the stomach, large bowel, lung, breast and prostate, and for all causes of death. All results were adjusted for age, sex and smoking. A random effects model was used to calculate pooled estimates of effect for all studies combined. SETTING: USA, UK and Germany. SUBJECTS: 76,172 men and women aged 16-89 years at recruitment. Vegetarians were those who did not eat any meat or fish (n = 27,808). Non-vegetarians were from a similar background to the vegetarians within each study. RESULTS: After a mean of 10.6 years of follow-up there were 8330 deaths before the age of 90 years, including 2264 deaths from ischaemic heart disease. In comparison with non-vegetarians, vegetarians had a 24% reduction in mortality from ischaemic heart disease (death rate ratio 0.76, 95% CI 0.62-0.94). The reduction in mortality among vegetarians varied significantly with age at death: rate ratios for vegetarians compared to non-vegetarians were 0.55 (95% CI 0.35-0.85), 0.69 (95% CI 0.53-0.90) and 0.92 (95% CI 0.73-1.16) for deaths from ischaemic heart disease at ages <65, 65-79 and 80-89 years, respectively. When the non-vegetarians were divided into regular meat eaters (who ate meat at least once a week) and semi-vegetarians (who ate fish only or ate meat less than once a week), the ischaemic heart disease death rate ratios compared to regular meat eaters were 0.78 (95% CI 0.68-0.89) in semi-vegetarians and 0.66 (95% CI 0.53-0.83) in vegetarians (test for trend P< 0.001). There were no significant differences between vegetarians and non-vegetarians in mortality from the other causes of death examined. CONCLUSION: Vegetarians have a lower risk of dying from ischaemic heart disease than non-vegetarians.
Adolescent↗
Oral contraceptives and thrombosis.
The debate on whether the so-called third-generation progestogens (desogestrel, gestodene, and norgestimate) are associated with a higher risk of venous thrombosis than the older, so-called second-generation progestogens (principally levonorgestrel and norethindrone) continues. Much of the debate focuses on finding alternative explanations for the observed relationship. Alternative explanations include a prescribing bias, in which women at greater risk of venous thromboembolism were preferentially prescribed newer preparations; a failure by researchers to adjust adequately for residual confounding by age; and a failure by researchers to allow adequately for confounding by the duration of use of oral contraceptives. None of these explanations have been accepted without dispute, and the debate will clearly continue. A possible biologic explanation for the observed relationship of higher thrombosis risk with use of third-generation preparations has been put forward by Rosing et al. from Maastricht, who developed a new way of measuring activated protein C (APC) resistance. They found that users of third-generation preparations have higher acquired APC resistance than users of second-generation products. This finding requires confirmation.
Activated Protein C Resistance↗
The influence of oral contraceptives on the risk of multiple sclerosis.
OBJECTIVE: To examine the risk of multiple sclerosis in users of combined oral contraceptives. DESIGN: Cohort study conducted between 1968 and 1996 using diagnostic data supplied by general practitioners SETTING: General practices throughout the United Kingdom. POPULATION: Royal College of General Practitioners' Oral Contraception Study cohort of initially 46,000 women recruited during the late 1960s. METHODS: Directly standardised incidence rates of multiple sclerosis were calculated for current, former and never-users of oral contraceptives using first ever cases of multiple sclerosis reported by the general practitioners. The standardisation variables were age, parity, social class and smoking history. Five-year survival rates in the different contraceptive groups were calculated using standard life table techniques. RESULTS: One hundred and fourteen first ever cases of multiple sclerosis had been reported by November 1996 during 564,000 woman-years of observation. The incidence rate in both current and former users was not materially different to that in never-users. Although based on limited evidence there was no suggestion that the five-year survival was affected by a woman's use of combined oral contraceptives. CONCLUSIONS: These findings do not suggest a greatly elevated risk of multiple sclerosis during, or after, use of combined oral contraceptives.
Adult↗
Cost-effectiveness of a primary care based physical activity intervention in 45-74 year old men and women: a randomised controlled trial.
OBJECTIVE: To assess the cost-effectiveness of a primary care based intervention aimed at increasing levels of physical activity in inactive people aged 45-74. METHODS: A total of 714 inactive people aged 45-74, taken from two west London general practices, were randomised into two groups. Intervention subjects were invited to a consultation with an exercise development officer, and offered a personalised 10 week programme to increase their level of regular physical activity, combining leisure centre and home based activities. Control subjects were sent information on local leisure centres. All subjects were followed up at eight months. RESULTS: There was a net 10.6% (95% confidence interval 4.5 to 16.9%) reduction in the proportion of people classified as sedentary in the intervention group compared with the control group, eight months after the intervention. The intervention group also reported an increase in the mean number of episodes of physical activity per week, as compared with the control group (an additional 1.52 episodes (95% confidence interval 1.14 to 1.95)). The cost of moving a person out of the sedentary group was shown to be less than 650 Pounds. The cost of moving someone to the now commonly recommended level was estimated at almost 2500 Pounds. CONCLUSIONS: Moderate physical activity can be successfully encouraged in previously sedentary men and women aged 45-74 through a primary care based intervention. The process of recruitment was the most important variable cost. A high uptake rate would maximise cost-effectiveness, and sensitivity analysis suggests that unit costs could be halved with a more effective recruitment strategy.
Age Factors↗
Case-control study of oral contraceptives and risk of thromboembolic stroke: results from International Study on Oral Contraceptives and Health of Young Women.
OBJECTIVE: To determine the influence of oral contraceptives (particularly those containing modern progestins) on the risk for ischaemic stroke in women aged 16-44 years. DESIGN: Matched case-control study. SETTING: 16 Centres in the United Kingdom, Germany, France, Switzerland, and Austria. SUBJECTS: Cases were 220 women aged 16-44 who had an incident ischaemic stroke. Controls were 775 women (at least one hospital and one community control per case) unaffected by stroke who were matched with the corresponding case for 5 year age band and for hospital or community setting. Information on exposure and confounding variables were collected in a face to face interview. MAIN OUTCOME MEASURES: Odds ratios derived with stratified analysis and unconditional logistic regression to adjust for potential confounding. RESULTS: Adjusted odds ratios (95% confidence intervals) for ischaemic stroke (unmatched analysis) were 4.4 (2.0 to 9.9), 3.4 (2.1 to 5.5), and 3.9 (2.3 to 6.6) for current use of first, second, and third generation oral contraceptives, respectively. The risk ratio for third versus second generation was 1.1 (0.7 to 2.0) and was similar in the United Kingdom and other European countries. The risk estimates were lower if blood pressure was checked before prescription. CONCLUSION: Although there is a small relative risk of occlusive stroke for women of reproductive age who currently use oral contraceptives, the attributable risk is very small because the incidence in this age range is very low. There is no difference between the risk of oral contraceptives of the third and second generation; only first generation oral contraceptives seem to be associated with a higher risk. This small increase in risk may be further reduced by efforts to control cardiovascular risk factors, particularly high blood pressure.
Adolescent↗
A randomised controlled trial of feedback to general practitioners of their prophylactic aspirin prescribing.
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Adult↗
Myocardial infarction and oral contraceptives, a retrospective case control study in England and Scotland ('MICA' Study).
Recent studies have shown that modern (third generation), oral contraceptives (OC) are associated with an increased incidence of venous thromboembolic disease compared to older (second generation), OC. It is not known, however, whether this association is also true for arterial thrombosis, in particular myocardial infarction. In fact, it has been suggested that third generation OC may even be protective against myocardial infarction (MI), compared to second generation OC. The protocol for a multicentre case-control study, involving the whole of England and Scotland, is described. Cases will be female patients aged 16-44 years, who suffered an MI between 1.10.93 and 1.10.95. Controls will be drawn from the community, using the GP list, to which the case belonged. Odds ratios will be calculated primarily to compare current users of third generation OC with current users of second generation OC.
Journal Article↗
Dietary determinants of ischaemic heart disease in health conscious individuals.
OBJECTIVE: To investigate dietary determinants of ischaemic heart disease (IHD) in health conscious individuals to explain the reduced risk in vegetarians, and to examine the relation between IHD and body mass index (BMI) within the normal range. DESIGN: Prospective observation of vegetarians, semi-vegetarians, and meat eaters for whom baseline dietary data, reported weight and height information, social class, and smoking habits were recorded. SUBJECTS: 10,802 men and women in the UK aged between 16 and 79, mean duration of follow up 13.3 years. MAIN OUTCOME MEASURES: Death rate rations for IHD and total mortality in relation to dietary and other characteristics recorded at recruitment (reference category death rate = 100). RESULTS: IHD mortality was less than half that expected from the experience reported for all of England and Wales. An increase in mortality for IHD was observed with increasing intakes of total and saturated animal fat and dietary cholesterol-death rate ratios in the third tertile compared with the first tertile: 329, 95% confidence interval (CI) 150 to 721; 277, 95% CI 125 to 613; 353, 95% CI 157 to 796, respectively. No protective effects were observed for dietary fibre, fish or alcohol. Within the study, death rate ratios were increased among those in the upper half of the normal BMI range (22.5 to < 25) and those who were overweight (BMI > or = 25) compared with those with BMI 20 to < 22.5. CONCLUSIONS: In these relatively health conscious individuals the deleterious effects of saturated animal fat and dietary cholesterol appear to be more important in the aetiology of IHD than the protective effect of dietary fibre. Reduced intakes of saturated animal fat and cholesterol may explain the lower rates of IHD among vegetarians compared with meat eaters. Increasing BMI within the normal range is associated with increased risk of IHD. The results have important public health implications.
Adolescent↗