Risk factors for stroke in middle aged British men.

OBJECTIVE--To determine the risk factors for stroke in a cohort representative of middle aged British men. DESIGN--Prospective study of a cohort of men followed up for eight years. SETTING--General practices in 24 towns in England, Wales, and Scotland (the British regional heart study). SUBJECTS--7735 men aged 40-59 at screening, selected at random from one general practice in each town. MAIN OUTCOME MEASURE--Fatal and non-fatal strokes. RESULTS--110 of the men had at least one stroke; there were four times as many non-fatal as fatal strokes. The relative risk of stroke was 12.1 in men who had high blood pressure (systolic blood pressure greater than or equal to 160 mm Hg) and were current smokers compared with normotensive, non-smoking men. Diastolic blood pressure yielded no additional information, and former cigarette smokers had the same risk as men who had never smoked. Heavy alcohol intake was associated with a relative risk of stroke of 3.8 in men without previously diagnosed cardiovascular disease. Men with pre-existing ischaemic heart disease had an increased risk of stroke, but only when left ventricular hypertrophy on electrocardiography was also present. CONCLUSIONS--Systolic blood pressure, cigarette smoking, and left ventricular hypertrophy on electrocardiography in men with pre-existing ischaemic heart disease were found to be the major risk factors for stroke in middle aged British men. Heavy alcohol intake seemed to increase the risk of stroke in men without previously diagnosed cardiovascular disease. A large proportion of strokes should be preventable by controlling blood pressure and stopping smoking.     

Risk factors for early death in non-insulin dependent diabetes and men with known glucose tolerance status.

OBJECTIVE--To identify risk factors for all cause mortality according to glucose tolerance status. DESIGN--Cohort study with an average 15.6 years'' follow up. SETTING--Paris, France. SUBJECTS--7166 working men aged 44-55 in 1968-72 in the Paris prospective study cohort, with non-insulin dependent diabetes or known result of two hour 75 g oral glucose tolerance test. MAIN OUTCOME MEASURES--Risk factors for death from all causes. RESULTS--128 men were known to be diabetic, 180 had diabetes diagnosed, and 697 had impaired glucose tolerance diagnosed. Compared with normoglycaemic men the relative risks of death in these groups were 2.0 (95% confidence interval 1.4 to 3.0), 2.7 (2.0 to 3.6), and 1.6 (1.3 to 2.0) respectively. Obesity, smoking, high blood pressure, and high non-esterified fatty acid concentration were risk factors for death in all subjects and were unaffected by glucose tolerance. The risks for fasting and two hour insulin concentrations and mean corpuscular volume were two times higher in known diabetic men than in men not known to be diabetic. Central obesity was significant only in men not known to be diabetic (1.6 (1.4 to 1.9)). In known diabetic men a two hour glucose concentration higher than 11.1 mmol/l carried a relative risk of death of 3.8 (1.4 to 9.4). CONCLUSIONS--Diabetic men have similar risk factors for early mortality to other men but are at higher risk from hyperinsulinaemia, hyperglycaemia, and high mean corpuscular volume.     

Risk factors for developing non-insulin dependent diabetes: a 10 year follow up of men in Uppsala.

OBJECTIVE--To analyse anthropometric and metabolic characteristics as risk factors for development of non-insulin dependent diabetes mellitus in middle aged normoglycaemic men. DESIGN--Prospective population study based on data collected in a health survey and follow up 10 years later. SETTING--Uppsala, a middle sized city in Sweden. SUBJECTS--2322 men aged 47-53, of whom 1860 attended the follow up 7-14 years later, at which time they were aged 56-64. MAIN OUTCOME MEASURES--Incidence of non-insulin dependent diabetes. RESULTS--In a multivariate logistic regression analysis, variations of 1 SD from the mean of the group that remained euglycaemic were used to calculate odds ratios and 95% confidence intervals. Blood glucose concentration 60 minutes after the start of an intravenous glucose tolerance test (odds ratio = 5.93, 95% confidence interval 3.05 to 11.5), fasting serum insulin concentration (2.12, 1.54 to 2.93), acute insulin increment at an intravenous glucose tolerance test (1.71, 1.21 to 2.43), body mass index (1.41, 1.01 to 1.97), and systolic blood pressure (1.23, 0.97 to 1.56) were independent predictors of diabetes. In addition, the use of antihypertensive drugs at follow up (selective or unselective beta blocking agents, thiazides, or hydralazine) was an independent risk factor (1.70, 1.11 to 2.60). CONCLUSIONS--Metabolic and anthropometric characteristics associated with or reflecting insulin resistance as well as a poor acute insulin response to glucose challenge were important predictors of future diabetes in middle aged men. Antihypertensive drugs were found to constitute a further, iatrogenic risk factor.     

Physical activity and stroke in British middle aged men.

OBJECTIVES--To assess the relation between physical activity and stroke and to determine the overall benefit of physical activity for all major cardiovascular events. DESIGN--Prospective study of a cohort of men followed up for 9.5 years. SETTING--General practices in 24 towns in England, Wales, and Scotland (British regional heart study). SUBJECTS--7735 men aged 40-59 at screening, selected at random from one general practice in each of 24 towns. MAIN OUTCOME MEASURES--Fatal and non-fatal strokes and heart attacks. RESULTS--128 major strokes (fatal and non-fatal) occurred. Physical activity was inversely associated with risk of stroke independent of coronary risk factors, heavy drinking, and pre-existing ischaemic heart disease or stroke (relative risk 1.0 for inactivity, 0.6 moderate activity, and 0.3 vigorous activity; test for trend p = 0.008). The association remained after excluding men reporting regular sporting (vigorous) activity. However, vigorous physical activity was associated with a marginally significant increased risk of heart attack compared with moderate or moderately vigorous activity in men with no pre-existing ischaemic heart disease or stroke (relative risk 1.6%; 95% confidence interval 0.96 to 2.8). In men with symptomatic ischaemic heart disease or stroke those doing moderately vigorous or vigorous activity had a risk of heart attack slightly higher than that in inactive men (relative risk = 1.6; 0.8 to 3.3). CONCLUSIONS--Moderate physical activity significantly reduces the risk of stroke and heart attacks in men both with and without pre-existing ischaemic heart disease. More vigorous activity did not confer any further protection. Moderate activity, such as frequent walking and recreational activity or weekly sporting activity, should be encouraged without restriction.     

Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50-60 years.

OBJECTIVE: To establish whether the relation between size at birth and non-insulin dependent diabetes is mediated through impaired beta cell function or insulin resistance. DESIGN: Cohort study. SETTING: Uppsala, Sweden. SUBJECTS: 1333 men whose birth records were traced from a cohort of 2322 men born during 1920-4 and resident in Uppsala in 1970. MAIN OUTCOME MEASURES: Intravenous glucose tolerance test at age 50 years and non-insulin dependent diabetes at age 60 years. RESULTS: There was a weak inverse correlation (r=-0.07, P=0.03) between ponderal index at birth and 60 minute insulin concentrations in the intravenous glucose tolerance test at age 50 years. This association was stronger (r=-0.19, P=0.001) in the highest third of the distribution of body mass index than in the other two thirds (P=0.01 for the interaction between ponderal index and the body mass index). Prevalence of diabetes at age 60 years was 8% in men whose birth weight was less than 3250 g compared with 5% in men with birth weight 3250 g or more (P=0.08; 95% confidence interval for difference -0.3% to 6.8%). There was a stronger association between diabetes and ponderal index: prevalence of diabetes was 12% in the lowest fifth of ponderal index compared with 4% in the other four fifths (P=0.001; 3.0% to 12.6%). CONCLUSION: These results confirm that reduced fetal growth is associated with increased risk of diabetes and suggest a specific association with thinness at birth. This relation seems to be mediated through insulin resistance rather than through impaired beta cell function and to depend on an interaction with obesity in adult life.     

Alcohol and ischaemic heart disease in middle aged British men.

The relation between alcohol intake and ischaemic heart disease was examined in a large scale prospective study of middle aged men drawn from general practices in 24 British towns. After an average follow up of 6.2 years 335 of the 7729 men had experienced a myocardial infarction (fatal or non-fatal) or sudden cardiac death. No significant relation was found between reported alcohol intake and the incidence of such events. Though the group of light daily drinkers had the lowest incidence of ischaemic heart disease events, it also contained the lowest proportion of current smokers, had the lowest mean blood pressure, had the lowest mean body mass index, and contained the lowest proportion of manual workers. These characteristics are more likely to account for the apparent protective effect of alcohol against ischaemic heart disease than a direct effect of alcohol. Compared with the effects of established risk factors alcohol seems to be quite unimportant in the development of ischaemic heart disease.     

Risk factors for premature death in middle aged men

The causes of premature death and the associated risk factors were analysed in a cohort of 7935 middle aged men participating in a preventive population programme in Malmö. They were screened when aged 46-48 and then followed up for 3½-8 years. Two hundred and eighteen died, of whom 181 (83%) underwent necropsy. Three major causes of death were established: cancer in 61 (28%), deaths related to consumption of alcohol in 55 (25%), and coronary heart disease in 50 (23%).Distinctly different patterns of risk factors were found to be associated with each of the three main causes of premature death. In death due to coronary heart disease smoking (p=0·0062), serum cholesterol concentration (p=0·00014), serum triglyceride concentration (p=0·00013), systolic blood pressure (p=0·000012), and diastolic blood pressure (p=0·0021) were the strongest single determinants but diastolic blood pressure ceased to be a predictive factor in a multivariate analysis whereas all the other variables could be combined in a highly predictive logistic model. In death related to consumption of alcohol equal or even stronger associations were found for serum γ glutamyltransferase activity (p<0·0001), points scored in a questionnaire screening for alcoholism (p<0·0001), and, inversely, serum cholesterol (p=0·0046) and serum creatinine (p<0·0001) concentrations both when applied independently and when combined in a logistic model. In death due to cancer significant associations were found for serum urate concentration (p=0·023) and, inversely, serum cholesterol concentration (p=0·056-0·031).Malignant diseases and diseases related to consumption of alcohol were at least as prominent as cardiovascular disorders in causing premature death in the cohort of men studied. All three types of conditions are potentially avoidable and seem to be associated with significant and distinctive patterns of risk factors. These patterns should be used, as blood pressure and serum lipid concentrations already are, to predict the risk of premature death and indicate preventive measures.     

Risk factors for development of incipient and overt diabetic nephropathy in patients with non-insulin dependent diabetes mellitus: prospective,observational study.

OBJECTIVE: To evaluate putative risk factors for the development of incipient diabetic nephropathy (persistent microalbuminuria) and overt diabetic nephropathy (persistent macroalbuminuria) in patients with non-insulin dependent diabetes. DESIGN: Prospective, observational study of a cohort of white, non-insulin dependent diabetic patients followed for a median period of 5.8 years. SETTING: Outpatient clinic in tertiary referral centre. SUBJECTS: 191 patients aged under 66 years with non-insulin dependent diabetes and normoalbuminuria (urinary albumin excretion rate < 30 mg/24 h) who attended the clinic during 1987. MAIN OUTCOME MEASURES: Incipient and overt diabetic nephropathy. RESULTS: Fifteen patients were lost to follow up. Thirty six of the 176 remaining developed persistent microalbuminuria (30-299 mg/24 h in two out of three consecutive 24 hour urine collections) and five developed persistent macroalbuminuria (> or = mg/24 h in two out of three consecutive collections) during follow up. The five year cumulative incidence of incipient diabetic nephropathy was 23% (95% confidence interval 17% to 30%). Cox''s multiple stepwise regression analysis revealed the following risk factors for the development of incipient or overt diabetic nephropathy: increased baseline log urinary albumin excretion rate (relative risk 11.1 (3.4 to 35.9); P < 0.0001); male sex (2.6 (1.2 to 5.4); P < 0.02); presence of retinopathy (2.4 (1.3 to 4.7); P < 0.01); increased serum cholesterol concentration (1.4 (1.1 to 1.7); P < 0.01); haemoglobin A1c concentration (1.2 (1.0 to 1.4); P < 0.05); and age (1.07 (1.02 to 1.12); P < 0.01). Known duration of diabetes, body mass index, arterial blood pressure, serum creatinine concentration, pre-existing coronary heart disease, and history of smoking were not risk factors. CONCLUSION: Several potentially modifiable risk factors predict the development of incipient and overt diabetic nephropathy in normoalbuminuric patients with non-insulin dependent diabetes.     

Type A behaviour and ischaemic heart disease in middle aged British men.

The Bortner questionnaire, which measures aspects of type A (coronary prone) behaviour was completed by 5936 men aged 40-59 selected at random from one general practice in each of 19 British towns. The presence of ischaemic heart disease was determined at initial examination and the men were followed up for an average of 6.2 years for morbidity and mortality from myocardial infarction and for sudden cardiac death. Non-manual workers had significantly higher scores (more type A) than manual workers and the score decreased (less type A) with increasing age. After adjustment for social class and age men with higher scores had higher prevalences of ischaemic heart disease less marked for electrocardiographic evidence and more marked for response to a chest pain questionnaire (angina or possible myocardial infarction). A man''s recall of a doctor''s diagnosis of ischaemic heart disease, however, did not relate to his Bortner score. There was no significant relation between the Bortner score and the attack rate or incidence of major ischaemic heart disease events. In this study type A behaviour, as measured by the Bortner questionnaire, did not predict major ischaemic heart disease events in British middle aged men.     

Body weight and mortality in middle aged British men: impact of smoking.

OBJECTIVE--To assess the relation between body mass index and mortality in middle aged British men. DESIGN--Men who were recruited for the British Regional Heart Study were followed up for a mean of nine years. SETTING--General practices in 24 British towns. SUBJECTS--7735 Men aged 40-59 years selected from the age-sex registers of one group practice in each of the 24 towns. MAIN OUTCOME MEASURE--Mortality from cardiovascular and non-cardiovascular causes. RESULTS--660 Of the men died. There was a U-shaped relation between body mass index and total mortality. Very lean men (less than 20 kg/m2) had by far the highest mortality followed by lean men (20-22 kg/m2) and obese men (greater than or equal to 28 kg/m2). The high mortality in lean and very lean men was due largely to non-cardiovascular causes, particularly lung cancer and respiratory disease, which are associated with cigarette smoking. In obese men deaths were more likely to be due to cardiovascular causes. There was a strong inverse association between body weight and cigarette smoking. When the pattern of mortality was examined by age, smoking habits, and pre-existing smoking related disease both very lean men and obese men consistently had an increased mortality. The U-shaped relation was most prominent in men in the oldest age group (55-59). Current smokers had a higher mortality than former smokers at virtually all values of body mass index. An increased mortality in lean men was seen only in current smokers and in men with smoking related disease. Among men who had never smoked, lean men had the lowest total mortality, thereafter mortality increased with increasing body mass index (p less than 0.01). CONCLUSIONS--This study provides strong evidence of the impact of cigarette smoking on body weight and mortality and strongly suggests that the benefits of giving up smoking are far greater than the problems associated with the increase in weight that may occur.