[When should a clinical trial be prematurely discontinued?].
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Biomedical subjects
Publications and source records attributed to L Wilhelmsen.
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The authors considered whether the difference in body fat distribution between men and women, measured as waist:hip ratio, might explain part of the sex difference in coronary heart disease incidence in prospective population studies of 1,462 women and 792 men. In these studies, conducted in Sweden, men were found to have about four times higher odds for coronary heart disease than women during a 12-year follow-up period (men, 1967 to 1979; women, 1968-1969 to 1980-1981). Controlling for differences in blood pressure, serum cholesterol, smoking, and body mass index only marginally altered the magnitude of the male-female difference. When waist:hip ratio, which predicted coronary heart disease rates in both sexes, was also considered, the sex difference in coronary heart disease risk was significantly reduced and virtually disappeared (odds ratios = 1.0-1.1; nonsignificant). The findings suggest that body fat distribution or a factor highly correlated with waist:hip ratio (genetic, hormonal, or behavioral) may help to explain the sex differences in coronary heart disease.
A clustering of metabolic disturbances has been indicated in hypertension. The distribution of such factors was assessed among hypertensives and normotensives in a general population sample of 644 men aged 67 years. Fasting serum insulin, glucose and triglyceride levels were measured. In this study hypertension was defined as DBP > or = 95 mmHg or present use of antihypertensives. Impaired glucose tolerance (IGT) or diabetes mellitus, hyperinsulinaemia (> or = 20 mU l-1) and hypertriglyceridaemia (> or = 2.3 mmol l-1) were defined as metabolic disturbances. When all these disturbances were present simultaneously a complete 'metabolic syndrome' was considered to be present. Hypertension was found in 185 (29%) men, IGT in 15%, diabetes mellitus in 11%, hyperinsulinaemia in 18% and hypertriglyceridaemia in 19%. Among hypertensives, 11 (6%) men had a 'metabolic syndrome', compared to 12 (3%) men in the normotensive group (P = 0.039). At least one metabolic disturbance was present in 109 (59%) of the hypertensive men, and in 173 (38%) of the normotensive men (P < 0.001). The prevalence rates of metabolic disturbances did not differ significantly between lean (BMI < 26 kg m-2) and obese (BMI > or = 26 kg m-2) hypertensives. Only hypertriglyceridaemia was more frequent in obese than in lean hypertensives (20% vs. 37%, P = 0.015). The 'metabolic syndrome' was found in 6% of all hypertensives, which was twice as common as in the normotensive population. The 'metabolic syndrome' was uncommon in both lean and obese hypertensives (5% vs. 7%, NS). These findings indicate that hypertension and metabolic disturbances may have a common underlying cause, at least in some individuals.
We examined the effect of light smoking in relation to incidence of coronary heart disease (CHD) in a general population sample consisting of 6879 men aged 47-55 years and free of previous myocardial infarction (MI) at baseline. After a follow-up of mean duration 11.8 years, 11.0% of men smoking 1-4 cigarettes daily (n = 228) had suffered a major CHD event, compared to 3.7% of non-smokers (n = 2049) [adjusted odds ratio 2.8 (1.7-4.7)]. No further increase in risk was observed in men who smoked more. There was an increasing risk of death from cancer with the number of cigarettes smoked per day. Mortality was increased in all categories of cigarette smokers, particularly among the very heavy smokers, who had a mortality risk of 22% compared to 6% among nonsmokers [adjusted odds ratio 4.4 (2.7-7.1)]. Data from an examination 4 years later considered only those men who stated that their smoking habits were identical on both occasions (n = 3981). Among these subjects the incidence of CHD after a mean period of 7.1 years was 10.6% in men smoking 1-4 cigarettes per day, compared to 2.6% in nonsmokers [adjusted O.R. 4.6 (2.1-10.1)]. No dose-response effect was observed. Even very light cigarette smoking considerably increases the risk of CHD in middle-aged men.
Based upon community myocardial infarction (MI) records in five Swedish cities, geographical variation and time trends in the attack rate of fatal and non-fatal MI have been evaluated. During the study period 1975-1982, a total of 7699 events were registered among men and 1823 events among women. The mean annual mortality was highest in the north, and a declining gradient in mortality was observed from the northern to the southern part of the country. The out-of-hospital death rate was highest in the north, while no difference in in-hospital mortality was observed. However, the geographical variation in the morbidity of MI was less consistent. Changes over time generally followed the same pattern in all cities. The attack rate of fatal and non-fatal MI tended to decline among women and men aged 60-64 years. The pattern was less consistent among younger men. Among women aged 50-59 years the mortality remained unchanged, but the attack rate of non-fatal MI increased in all cities. This increase was not explained by inclusion of less severe infarctions. A considerable proportion, about 85%, were recorded as primary events, emphasizing the possible role of primary prevention in obtaining a decrease in the incidence of the disease. The results of this study support previous findings of an important regional difference in the mortality of MI in Sweden. However, the magnitude of the regional variation in the incidence of coronary heart disease might be overestimated if only the mortality pattern is studied.
BACKGROUND AND PURPOSE: Stroke risk factors have been shown to change with time in several places; simultaneously, stroke incidence rates have increased in some and decreased in other places. In Göteborg, Sweden, cardiovascular epidemiological research has included stroke registration since 1971. From these data on stroke, incidence and fatality rates from a 17-year period are given. METHODS: During the period 1971-1987 all cases of stroke occurring in people aged 15-65 years in the city of Göteborg were uniformly recorded, with an estimated case detection rate of 90% or more. RESULTS: Age-adjusted incidence rates of first-ever stroke by sex did not change during the period. Age-specific rates and rates for individual types of stroke (subarachnoid hemorrhage, intracerebral hemorrhage, and cerebral infarction-unspecified stroke combined) were also largely unchanged. A slight increase in the incidence rate of intracerebral hemorrhage may be due to better detection after computed tomography came into use in 1976. Stroke fatality rates declined through the whole period in both sexes and all age groups, markedly so for intracerebral hemorrhage and subarachnoid hemorrhage. CONCLUSIONS: This conforms with vital statistics for Göteborg and for Sweden of declining stroke mortality during the period. The decline in stroke fatality rates may be related to decreases in smoking habits and blood pressure together with an increase in the percentage of people on antihypertensive treatment among middle-aged men, and to some extent even middle-aged women, reported from the same population. Why stroke incidence rates did not decline concomitantly is unexplained.
Despite the great therapeutic advances, the control of hypertension in populations is far below the achievable level, even in populations with highly developed health care. By the end of the 1980's, in selected European centres, 18-34% of cases of hypertension were undetected, and among those previously known, 22-38% were untreated. The cooperative WHO/WHL Hypertension Management Audit Project aimed at assessing some of the impediments to better control of hypertension. The concepts and attitudes of 2,215 physicians were surveyed. In various centres and at various patient ages, 25-45% of physicians would not start drug treatment below 100 mm Hg. When inquiring into the perceived reasons why hypertension had not been detected earlier, among other reasons, physicians tended to incriminate their workload, while patients often felt that there was a lack of interest on the doctor's part to take a blood pressure reading. In general, patient satisfaction seemed suboptimal. Physician's sources of information were varied; neither WHO, nor ISH or WHL seemed to play an important role in informing the physicians.
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Self-perceived psychological stress as a risk factor for coronary artery disease (CAD) was evaluated in a general population study comprising 6,935 men aged 47 to 55 years at baseline without previous myocardial infarction. In 1970 to 1973, the men answered a question about psychological stress defined as a feeling of tension, irritability or anxiety, or as having sleeping difficulties as a result of conditions at work or at home. Psychological stress was graded as follows: (1) never experienced stress; (2) greater than or equal to 1 period of stress; (3) greater than or equal to 1 period of stress during the last 5 years; (4) several periods of stress during the last 5 years; and (5 to 6) permanent stress during the last year or the last 5 years. After a mean follow-up of 11.8 years, 6% of the men with the lowest 4 stress ratings (n = 5,865) had either developed a nonfatal myocardial infarction or died from CAD, with no increase in risk from grade 1 to 4. The corresponding figure among the men with the highest 2 stress ratings (n = 1,070) was 10%; the odds ratio was 1.5 (95% confidence interval 1.2-1.9) after controlling for age and other risk factors. Similar, independent associations were seen with stroke, and with death from cardiovascular disease and from all causes, but not with death from cancer. With respect to CAD, no decrease in the effect of stress at baseline could be seen over time. No relation between life events and self-perceived psychological stress was found in another sample of 732 fifty-year-old men.
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The prevalence, characteristics and significance of ventricular arrhythmias detected by ambulatory electrocardiography were evaluated in 1,498 patients who were randomized to encainide, flecainide or placebo in the Cardiac Arrhythmia Suppression Trial. The mean ventricular premature complex (VPC) frequency at baseline was 133 +/- 257 VPCs/hour. Nonsustained ventricular tachycardia (VT) (rate greater than or equal to 120 beats/min) was present in 22% of patients. Accelerated idioventricular rhythm (rate less than 120 beats/min) occurred in 22% of subjects. There were 63 deaths/resuscitated cardiac arrests in the active treatment (encainide/flecainide) group and 26 in the placebo group. In the treatment group mortality increased with increasing VPC frequency, (p = 0.006), whereas in the placebo group such a relation was not present. Mortality/resuscitated cardiac arrest increased in patients with greater than or equal to 2 VT episodes than in those with less than or equal to 1 episode in the active treatment group (p = 0.04). There was no significant association between VT and mortality/resuscitated cardiac arrest in the placebo group. The presence of accelerated idioventricular rhythm was not associated with increased mortality/resuscitated cardiac arrest in either the active treatment or placebo groups. However, mortality was lower in patients with accelerated idioventricular rhythm rates less than 100 beats/min than in those with rates greater than or equal to 100 beats/min (p = 0.05). Thus, in the Cardiac Arrhythmia Suppression Trial the previously described association between mortality/resuscitated cardiac arrest and ventricular arrhythmias (VPC and VT) were only observed in the active treatment group. In addition, based on the results obtained in this highly selected population, it is suggested that the definition of accelerated idioventricular rhythm should be a rate less than 100 beats/min, and at a rate greater than or equal to 100 beats/min it should be categorized as VT.
Identification of incident myocardial infarction (MI) cases in a defined population using hospital discharge data and mortality data in combination has been suggested. This method of case identification was compared to that of use of MI community registers set up in accordance with principles adopted in a World Health Organization collaborative programme. The comparison comprised data for four Swedish cities over a number of years. On average 81% of incident hospital-treated cases below 65 years of age identified through MI community registers were found by the retrospective use of the method based on hospital discharge data and mortality data. Of hospital-treated cases identified by the latter method, 83% were also found by the MI community registers. For cases fulfilling the diagnostic criteria employed by the MI community registers this proportion would be higher, probably 87%-92%. Several reasons for cases being missed by either method were suggested by the results. According to the findings of this study, the case identification of the method based on hospital discharge data and mortality data seems to be somewhat less efficient compared to use of MI community registers. This may be of importance in descriptive epidemiological studies, but is of less significance in analytical studies. The relative efficiency of the former method could be improved by a more reliable system for the recording of hospital discharges. If supplemented by a validation procedure, it could yield sufficiently accurate data for many epidemiological applications at a fairly low cost.
In the Gothenburg Primary Prevention Study the incidence of coronary heart disease (CHD) in 103 bus and tram drivers was compared with that of 6596 men in other occupation groups. The follow-up extended through a mean of 11.8 years. Bus and tram drivers had an incidence of CHD of 18.4% compared with 6.4% among the other men in the study; odds ratio (OR) 3.3 (95% confidence interval (CI) 2.0-5.5). The only other group with an increase in risk of similar magnitude were taxi drivers; OR 3.1 (1.6-6.2). No significant differences were noted as to smoking habits, serum cholesterol or blood pressure between bus and tram drivers and the other men. The bus and tram drivers tended to be more physically active during leisure time, but had a significantly higher body mass index than other men. In a multivariate logistic regression analysis with CHD as the dependent variable and age, serum cholesterol, blood pressure, smoking, body mass index, diabetes, marital state, family history of CHD, alcohol abuse, socioeconomic status, leisure time physical activity, physical activity at work, psychological stress and bus and tram driving as independent variables the OR for bus and tram driving was only slightly reduced to 3.0 (1.8-5.2). In this population, being a bus or tram driver was an independent predictor of CHD of considerable magnitude. The increased risk of taxi drivers was not significant in multivariate analysis.
The effect of coffee consumption on the incidence of coronary heart disease (CHD) was studied prospectively in a population sample of 6765 men aged 51-59 years at baseline during the period 1974-1977, and free of myocardial infarction (MI) prior to the screening. During a 7.1-year follow-up there were 230 non-fatal myocardial infarctions. 169 coronary deaths and 478 deaths from all causes. Among men who were smokers at baseline there was no relationship between either non-fatal MI or death from CHD, and coffee consumption. Among non-smokers, a weak but far from significant trend towards an increasing incidence of CHD in heavy consumers of coffee was observed. There was an inverse relationship between mortality from all causes and coffee consumption.
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