A G Shaper

Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men

Moderate hyperhomocysteinaemia is common in the general population and has been linked with cardiovascular disease. However, there are no data from prospective, population-based studies. We examined the association between serum total homocysteine (tHcy) concentration and stroke in a nested case-control study within the British Regional Heart Study cohort. Between 1978 and 1980 serum was saved from 5661 men, aged 40-59 years, randomly selected from the population of one general practice in each of 18 towns in the UK. During follow-up to December, 1991, there were 141 incident cases of stroke among men with no history of stroke at screening. Serum tHcy was measured in 107 cases and 118 control men (matched for age-group and town, without a history of stroke at screening, who did not develop a stroke or myocardial infarction during follow-up). tHcy concentrations were significantly higher in cases than controls (geometric mean 13.7 [95% CI 12.7-14.8] vs 11.9 [11.3-12.6] mumol/L; p = 0.004). There was a graded increase in the relative risk of stroke in the second, third, and fourth quarters of the tHcy distribution (odds ratios 1.3, 1.9, 2.8; trend p = 0.005) relative to the first. Adjustment for age-group, town, social class, body-mass index, hypertensive status, cigarette smoking, forced expiratory volume, packed-cell volume, alcohol intake, diabetes, high-density-lipoprotein cholesterol, and serum creatinine did not attenuate the association. These findings suggest that tHcy is a strong and independent risk factor for stroke.

Prospective study of risk factors for development of non-insulin dependent diabetes in middle aged British men.

Abstract Objective: To determine the risk factors for non-insulin dependent diabetes in a cohort representative of middle aged British men. Design: Prospective study. Subjects and setting: 7735 men aged 40-59, drawn from one group practice in each of 24 towns in Britain. Known and probable cases of diabetes at screening (n=158) were excluded. Main outcome measures: Non-insulin dependent diabetes (doctor diagnosed) over a mean follow up period of 12.8 years. Results: There were 194 new cases of non-insulin dependent diabetes. Body mass index was the dominant risk factor for diabetes, with an age adjusted relative risk (upper fifth to lower fifth) of 11.6; 95% confidence interval 5.4 to 16.8. Men engaged in moderate levels of physical activity had a substantially reduced risk of diabetes, relative to the physically inactive men, after adjustment for age and body mass index (0.4; 0.2 to 0.7), an association which persisted in full multivariate analysis. A non-linear relation between alcohol intake and diabetes was observed, with the lowest risk among moderate drinkers (16-42 units/week) relative to the baseline group of occasional drinkers (0.6; 0.4 to 1.0). Additional significant predictors of diabetes in multivariate analysis included serum triglyceride concentration, high density lipoprotein cholesterol concentration (inverse association), heart rate, uric acid concentration, and prevalent coronary heart disease. Conclusion: These findings emphasise the interrelations between risk factors for non-insulin dependent diabetes and coronary heart disease and the potential value of an integrated approach to the prevention of these conditions based on the prevention of obesity and the promotion of physical activity. Key messages Key messages This study shows a strong, graded association between body mass index and risk of diabetes in middle aged men, with no evidence of a threshold effect The risk of diabetes is reduced by more than 50% among men who take moderately vigorous exercise Cardiovascular disease risk factors that are linked with insulin resistance, such as hypertriglyceridaemia and hyperuricaemia, predict non-insulin dependent diabetes These findings support an integrated approach to the prevention of non-insulin dependent diabetes and cardiovascular disease based on the prevention of obesity and the promotion of physical activity

Prospective Study of Serum γ-Glutamyltransferase and Risk of NIDDM

OBJECTIVE Serum γ-glutamyltransferase (GGT) levels are raised inobese individuals, and a particularly strong association with central obesity has been described. We hypothesized that elevated GGT levels are a marker for visceral fat, and specifically for hepatic steatosis (fatty liver), and that hepatic steatosis leads to hepatic insulin resistance. To test this hypothesis, we examined the association between GGT levels and risk of NIDDM. RESEARCH DESIGN AND METHODS We carried out a prospective cohort study of incident cases of doctor-diagnosed NIDDM in a group of 7,458 nondiabetic men (aged 40–59 years) followed for a mean of 12.8 years (range 11.5–13.0). The men were randomly selected from general practice lists in 24 British towns. Cases of NIDDM were ascertained by repeated postal questionnaires to the men and by regular systematic review of primary care records. RESULTS A total of 194 men developed NIDDM during follow-up. Mean serum GGT at baseline (geometric mean [95% Cl]) was significantly higher in the NIDDM patients than in the rest of the cohort (20.9 [19.3–22.6] vs. 15.3 U/l [15.0–15.6], P < 0.0001). There was a smooth, graded increase in the age-adjusted risk of NIDDM with increasing GGT levels, with a relative risk in the top fifth of the distribution of 6.8 (3.5–12.9) relative to the bottom fifth (trend P < 0.0001). This association was independent of serum glucose and BMI and of other predictors of NIDDM with which GGT is associated, including alcohol intake and physical activity level (adjusted upper to lower fifth relative risk: 4.8 [2.0–11.8], trend P < 0.0001]). CONCLUSIONS These findings suggest that a raised serum GGT levelis an independent risk factor for NIDDM. Serum GGT level may be a simple andreliable marker of visceral and hepatic fat and, by inference, of hepatic insulin resistance.

Loss of employment and mortality

Abstract Objective: To assess effect of unemployment and early retirement on mortality in a group of middle aged British men. Design: Prospective cohort study (British Regional Heart Study). Five years after initial screening, information on employment experience was obtained with a postal questionnaire. Setting: One general practice in each of 24 towns in Britain. Subjects: 6191 men aged 40-59 who had been continuously employed for at least five years before initial screening in 1978-80: 1779 experienced some unemployment or retired during the five years after screening, and 4412 remained continuously employed. Main outcome measure: Mortality during 5.5 years after postal questionnaire. Results: Men who experienced unemployment in the five years after initial screening were twice as likely to die during the following 5.5 years as men who remained continuously employed (relative risk 2.13 (95% confidence interval 1.71 to 2.65). After adjustment for socioeconomic variables (town and social class), health related behaviour (smoking, alcohol consumption, and body weight), and health indicators (recall of doctor diagnoses) that had been assessed at initial screening the relative risk was slightly reduced, to 1.95 (1.57 to 2.43). Even men who retired early for reasons other than illness and who appeared to be relatively advantaged and healthy had a significantly increased risk of mortality compared with men who remained continuously employed (relative risk 1.87 (1.35 to 2.60)). The increased risk of mortality from cancer was similar to that of mortality from cardiovascular disease (adjusted relative risk 2.07 and 2.13 respectively). Conclusions: In this group of stably employed middle aged men loss of employment was associated with an increased risk of mortality even after adjustment for background variables, suggesting a causal effect. The effect was non-specific, however, with the increased mortality involving both cancer and cardiovascular disease.

Physical activity and ischaemic heart disease in middle-aged British men.

OBJECTIVE--To assess the relation between reported physical activity and the risk of heart attacks in middle aged British men. DESIGN--Prospective study of middle-aged men followed for a period of eight years (The British Regional Heart Study). SETTING--One general practice in each of 24 British towns. PARTICIPANTS--7735 men aged 40-59 years at initial examination. END POINT--Heart attacks (non-fatal and fatal). MEASUREMENTS AND MAIN RESULTS--During the follow up period of eight years 488 men suffered at least one major heart attack. A physical activity score used was developed and validated against heart rate and lung function (FEV1) in men without evidence of ischaemic heart disease. Risk of heart attack decreased significantly with increasing physical activity; the groups reporting moderate and moderately vigorous activity experienced less than half the rate seen in inactive men. The benefits of physical activity were seen most consistently in men without preexisting ischaemic heart disease and up to levels of moderately vigorous activity. Vigorously active men had higher rates of heart attack than men with moderate or moderately vigorous activity. The relation between physical activity and the risk of heart attack seemed to be independent of other cardiovascular risk factors. Men with symptomatic ischaemic heart disease showed a reduction in the rate of heart attack at light or moderate levels of physical activity, beyond which the risk of heart attack increased. Men with asymptomatic ischaemic heart disease showed an increasing risk of heart attack with increasing levels of physical activity, but with a progressive decrease in case fatality. Overall, men who engaged in vigorous (sporting) activity of any frequency had significantly lower rates of heart attack than men who reported no sporting activity. However, when all men reporting regular sporting activity at least once a month were excluded from analysis, there remained a strong inverse relation between physical activity and the risk of heart attack in men without pre-existing ischaemic heart disease. CONCLUSION--This study suggests that the overall level of physical activity is an important independent protective factor in ischaemic heart disease and that vigorous (sporting) exercise, although beneficial in its own right, is not essential in order to obtain such an effect.

Body weight: implications for the prevention of coronary heart disease, stroke, and diabetes mellitus in a cohort study of middle aged men

Abstract Objective:To determine the body mass index associated with the lowest morbidity and mortality. Design:Prospective study of a male cohort. Setting:One general practice in each of 24 British towns. Subjects:7735 men aged 40-59 years at screening. Main outcome measures:All cause death rate, heart attacks, and stroke (fatal and non-fatal) and development of diabetes, or any of these outcomes (combined end point) over an average follow up of 14.8 years. Results:There were 1271 deaths from all causes, 974 heart attacks, 290 strokes, and 245 new cases of diabetes mellitus. All cause mortality was increased only in men with a body mass index (kg/m2) <20 and in men with an index ≥30. However, risk of cardiovascular death, heart attack, and diabetes increased progressively from an index of <20 even after age, smoking, social class, alcohol consumption, and physical activity were adjusted for. For the combined end point the lowest risks were seen for an index of 20.0-23.9. In never smokers and former smokers, deaths from any cause rose progressively from an index of 20.0-21.9 and for the combined end point, from 20.0-23.9. Age adjusted levels of a wide range of cardiovascular risk factors rose or fell progressively from an index <20. Conclusion:A healthy body mass index in these middle aged British men seems to be about 22. Key messages The body mass index associated with the lowest mortality and the lowest incidence of coronary heart disease, stroke, and diabetes mellitus is not known In this study of middle aged men the risk of cardiovascular mortality, heart attack, and diabetes increased progressively from a body mass index <20 For a combined end point (heart attack, stroke, diabetes, or death from any cause) the lowest risk was in the range 20-24 Levels of a wide range of cardiovascular risk factors increased progressively from an index of <20 A healthy body mass index in middle aged men seems to be around 22

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.

Social class differences in ischaemic heart disease in British men.

To examine why ischaemic heart disease (IHD) mortality rates in Britain are higher in manual than in non-manual workers 7735 middle-aged men in the British Regional Heart Study were followed up for 6 years, during which time 336 men experienced a major IHD event (fatal or non-fatal myocardial infarction or sudden cardiac death). The prevalence rates of IHD at screening, were higher in manual workers. Also, the attack rate of major IHD events during follow-up was 44% higher in manual workers. Marked differences in cigarette smoking contributed substantially to the increased risk of IHD in manual workers, who also had higher levels of blood pressure, were more obese, and took much less physical activity in leisure time. Adjustment for differences in these risk factors narrowed the gap between manual and non-manual workers in attack rates of IHD. Since the risk of IHD in Great Britain is high in all social classes, there would seem to be little justification for any overall policy for prevention of IHD to focus on social class. However, anti-smoking strategies might well take into account the social class differences described.

Risk factors for ischaemic heart disease: the prospective phase of the British Regional Heart Study.

Risk factors for major ischaemic heart disease (acute myocardial infarction or sudden death) have been investigated in a prospective study of 7735 men aged 40-59 years drawn from general practices in 24 British towns. After a mean follow-up of 4.2 years, there have been 202 cases of major ischaemic heart disease. Univariate estimates of the risk of ischaemic heart disease show that serum total cholesterol, HDL-cholesterol and triglyceride concentrations, systolic and diastolic blood pressures, cigarette smoking, and body mass index are all associated with increased risk of ischaemic heart disease. Evidence of ischaemic heart disease at initial examination is also strongly associated with increased risk of subsequent ischaemic heart disease. All these factors were then considered simultaneously using multiple logistic models. Definite myocardial infarction on electrocardiogram and recall of a doctor diagnosis of ischaemic heart disease remained predictive of subsequent major ischaemic heart disease, after allowance for all other risk factors. Serum total cholesterol, blood pressure, and cigarette smoking each remained as highly significant independent risk factors whereas overweight, above average levels of HDL-cholesterol and serum triglyceride were not predictive of risk after allowance for the above factors. Men with and without pre-existing ischaemic heart disease were examined separately in the same way (using multiple logistic models). The strength of association between the principal risk factors and subsequent major ischaemic heart disease was reduced in the men with pre-existing ischaemic heart disease, only age and serum total cholesterol remaining highly significant. Overall the levels of the major risk factors commonly encountered in British men have a marked effect on the risk of ischaemic heart disease. Modification of these risk factors in the general population constitutes an important national priority.

Risk Factors for Sudden Cardiac Death in Middle-Aged British Men

BACKGROUND Risk factors specific to sudden cardiac death (SCD), ie, death within 1 hour after onset of symptoms, have been poorly identified, although recent findings from the present study incriminate heavy drinking and elevated heart rate. This paper examines the relations between a wide range of established and potential risk factors for ischemic heart disease (IHD) and SCD to identify independent risk factors for SCD and factors that might particularly or specifically relate to SCD. METHODS AND RESULTS We present a prospective study of a cohort that was drawn from general practices in 24 British towns of 7735 middle-aged men who were followed up for 8 years. During 8 years of follow-up, the men experienced 488 major IHD events (nonfatal and fatal), of which 117 (24%) were classified as SCD. Age, preexisting IHD, arrhythmia, systolic blood pressure, blood cholesterol, elevated heart rate (> or = 90 beats per minute), physical activity (all, P < .05), and, to a lesser extent, smoking (P = .06), HDL cholesterol (P < .07), and elevated hematocrit (> or = 46%, P < .09) emerged as independent risk factors for SCD after adjustment for a wide range of factors. Diabetes was not found to be associated with SCD, and forced expiratory volume in 1 second, body mass index, white blood cell count, and antihypertensive drugs were not associated with risk of SCD after adjustment. When examined in relation to non-sudden IHD deaths and nonfatal myocardial infarction, elevated heart rate, heavy drinking, and arrhythmia emerged as factors that appear to be specific or particular to SCD. These three factors and age and blood cholesterol were associated with an increased risk of SCD in men both with and without preexisting IHD. Physical activity, systolic blood pressure, and current smoking were associated with SCD only in men without preexisting IHD. HDL cholesterol and hematocrit were strong predictors of SCD only in men with preexisting IHD. CONCLUSIONS Three risk factors appear to be specific or particular to the risk of SCD, and these and other risk factors operate differently in patients with versus those without preexisting IHD. These findings have implications for the causes and prevention of SCD.