Mary Walker

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

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 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.

Childhood size is more strongly related than size at birth to glucose and insulin levels in 10–11-year-old children

Summary In adults low birthweight and thinness at birth are associated with increased risk of glucose intolerance and non-insulin-dependent diabetes mellitus. We have examined the relations between size at birth (birthweight, thinness at birth) and levels of plasma glucose and serum insulin in children, and compared them with the effects of childhood size. We performed a school-based survey of 10–11-year-old British children (response rate 64 %) with measurements made after an overnight fast. One group of children (n = 591) was studied fasting while the other (n = 547) was studied 30 min after a standard oral glucose load (1.75 g/kg). Serum insulin was measured by a highly specific ELISA method. Birthweight was assessed by maternal recall and thinness at birth using birth records. Neither fasting nor post-load glucose levels showed any consistent relationship with birthweight or ponderal index at birth. After adjustment for childhood height and ponderal index, both fasting and post-load insulin levels fell with increasing birthweight. For each kg increase in birthweight, fasting insulin fell by 16.9 % (95 % confidence limits 7.1–25.8 %, p = 0.001) and post-load insulin by 11.6 % (95 % confidence limits 3.5–19.1 %, p = 0.007). However, the proportional change in insulin level for a 1 SD increase in childhood ponderal index was much greater than that for birthweight (27.2 % and − 8.8 %, respectively, for fasting insulin). We conclude that low birthweight is not related to glucose intolerance at 10–11 years, but may be related to the early development of insulin resistance. However, in contemporary children obesity is a stronger determinant of insulin level and insulin resistance than size at birth. [Diabetologia (1997) 40: 319–326]

Validity of a self-reported history of doctor-diagnosed angina.

The objective of this study was to assess the validity of a self-reported history of doctor-diagnosed angina in population-based studies in men. Subjects were 5789 men from the British Regional Heart Study who reported being without an angina diagnosis at entry (1978-1980) and were alive at the end of 1992, aged 52 to 75 years. In 1992, subjects were asked in a self-administered questionnaire if they recalled ever having had a doctor diagnosis of angina. Self-report of diagnosed angina was compared with general practice (GP) record of angina obtained from reviews of medical records from study entry to the end of 1992. Men were followed for a further 3 years from 1992 for major ischemic heart disease events. The prevalence of diagnosed angina in 1992 was 10.1% according to self-reported history and 8.9% according to GP record review. There was substantial agreement between the two sources of information: 80% of men with a GP record of angina reported their diagnosis, and 70% of men who reported an angina diagnosis had confirmation of this from the record review. When all ischemic heart disease (angina or myocardial infarction) was considered, agreement was higher. Genuine angina was likely in many of the 177 men who had self-reported angina not confirmed by the GP record review: 78 had an ischemic heart disease history (myocardial infarction or coronary revascularization) identified by the review, and 31 had a GP record of angina after 1992. Angina symptoms, nitrate use, cardiological investigation, and surgical intervention for angina compared between agreement groups showed a very consistent pattern. All these indicators of angina were most common in men with both self-report and GP record of angina, least common in men with neither self-report nor GP record of angina, but had a substantially higher prevalence in men with self-reported angina only than in those with GP-recorded angina only. After 3 years follow-up from 1992, 9.5% of men with both self-report and GP record of angina, and 11.3% of men with self-reported angina only had experienced a new major ischemic heart disease event; compared to 5.7% of men with a GP record of angina only and 2.7% of those without angina by either criteria. This pattern of risk remained similar after adjustment for age and previous myocardial infarction. These results suggest that self-reported history of a doctor diagnosis of angina is a valid measure of diagnosed angina in population-based studies in men.

Serum total homocysteine and coronary heart disease: prospective study in middle aged men

OBJECTIVES To examine the prospective relation between total homocysteine and major coronary heart disease events. DESIGN A nested case–control study carried out within the British regional heart study, a prospective investigation of cardiovascular disease in men aged 40–59 years at entry. Serum total homocysteine concentrations were analysed retrospectively and blindly in baseline samples from 386 cases who had a myocardial infarct during 12.8 years of follow up and from 454 controls, frequency matched by age and town. RESULTS Geometric mean serum total homocysteine was slightly higher in cases (14.2 μmol/l) than in controls (13.5 μmol/l), a proportional difference of 5.5% (95% confidence interval (CI) −0.02% to 10.8%, p = 0.06). Age adjusted risk of myocardial infarction increased weakly with log total homocysteine concentration; a 1 SD increase in log total homocysteine (equivalent to a 47% increase in total homo cysteine) was associated with an increase in odds of myocardial infarction of 1.15 (95% CI 1.00 to 1.32; p = 0.05). The relation was particularly marked in the top fifth of the total homocysteine distribution (values >16.5 μmol/l), which had an odds ratio of 1.77 (95% CI 1.28 to 2.42) compared with lower levels. Adjustment for other risk factors had little effect on these findings. Total homocysteine concentrations more than 16.5 μmol/l accounted for 13% of the attributable risk of myocardial infarction in this study population. Serum total homocysteine among control subjects varied between towns and was correlated with town standardised mortality ratios for coronary heart disease (r = 0.43, p = 0.08). CONCLUSIONS Serum total homocysteine is prospectively related to increased coronary risk and may also be related to geographical variation in coronary risk within Britain. These results strengthen the case for trials of total homocysteine reduction with folate.

Identification and management of stroke risk in older people: a national survey of current practice in primary care.

The current practice of stroke prevention was assessed among UK general practitioners (GPs) using a postal questionnaire. A random sample of 583 GPs (response rate 60%) in practice throughout the UK was examined. Main outcomes were the reported practice in the identification of stroke risk, management of hypertension, and use of other interventions (particularly aspirin treatment) to reduce the risk of stroke. Most respondents (451, 77%) reported that they specifically identified patients at high risk of stroke. However, of these only 301 (67%) used more than one major risk factor to do this and less than one-third used either age or pre-existing cardiovascular disease as an indicator. Thresholds for drug treatment of hypertension increased markedly with patient age with only 68%, 23% and 9% of respondents reporting treating elevated systolic, diastolic and isolated systolic pressures respectively, in accord with the British Hypertension Society (BHS) guidelines for patients aged 70–79 years. Thresholds for blood pressure (BP) treatment in older patients did not differ by region but were higher among respondents who had been in general practice for more than 10 years. The value of aspirin in preventing stroke in patients with pre-existing cardiovascular disease was recognized by almost all (560, 96%) respondents. The results suggest that there is scope for increasing the benefits of stroke prevention in primary care, by focusing on the management of patients at high absolute risk, in whom the greatest treatment benefits are likely to be obtained.

Resting Electrocardiogram and Risk of Coronary Heart Disease in Middle-Aged British Men:

Objective: To examine the relation between resting electrocardiographic (ECG) abnormalities and risk of coronary heart disease (CHD). Design and setting: This was a prospective study of 7735 middle-aged men aged 40–59 years at entry (British Regional Heart Study). At baseline assessment each man completed a modified World Health Organization (WHO) (Rose) chest-pain questionnaire, gave details of his medical history and had a three-lead orthogonal electrocardiogram recorded. ‘Symptomatic CHD’ refers to a history of anginal chest pain and/or a prolonged episode of central chest pain on WHO questionnaire and/or recall of a doctor diagnosis of CHD (angina or myocardial infarction). Main outcome measures: These were the first major CHD events, i.e. fatal CHD and non-fatal myocardial infarction, occurring during 9.5 years of follow-up. Results: Of 611 first major CHD events during follow-up, 243 (40%) were fatal. After adjustment for age, other ECG abnormalities and symptomatic CHD, the ECG abnormalities most strongly associated with risk of a major CHD event were definite myocardial infarction (relative risk 2.5; 95% confidence interval 1.8–7.5) and definite myocardial ischaemia (1.9; 1.1–2.9). Other ECG abnormalities independently associated with a statistically significant increase in risk were left ventricular hypertrophy (2.2; 1.5–3.3), left axis deviation (1.3; 1.1–1.6) and ectopic beats, particularly if these were ventricular (1.6; 1.1–2.4). Three ECG abnormalities associated with a marked increase in CHD case-fatality rate were pre-existing myocardial infarction (67%), major conduction defect (71%) and arrhythmia (67%); the rate in men with none of these abnormalities was 32%. The relative risks associated with each ECG abnormality were similar in men with and without symptomatic CHD. The increase in risk in the presence of symptomatic CHD (2.4-fold) and ECG evidence of definite myocardial infarction (2.5-fold) was similar; the presence of both factors increased risk more than six-fold. The most serious ECG abnormalities — definite myocardial infarction and ischaemia — were useful predictors of future major CHD events only in men with symptomatic CHD. Conclusion: The prognostic importance of major ECG abnormalities is strongly influenced by the presence of symptomatic CHD. In men with symptomatic CHD the resting electrocardiogram may help to define a group at high risk who may benefit from intervention. However, it has little or no value as a screening tool in middle-aged men without symptomatic CHD.

Blood pressure in British children: associations with adult blood pressure and cardiovascular mortality

Blood pressure was measured in 4186 children aged 5 to 7 years in 9 British towns. 3 towns had high, 3 had intermediate, and 3 had low adult blood pressure levels observed in an earlier study of middle-aged men. Significant differences between the towns were found for the childrens mean systolic blood pressure (range 96.7 to 102.4 mm Hg) and diastolic pressure (range 55.9 to 60.3 mm Hg). The pattern of systolic blood pressure differences in children was similar to that observed in the study of middle-aged men (r = 0.65). The town mean systolic pressures in children show an association with standardised mortality ratios for cardiovascular disease in adults. The pattern of geographical differences in blood pressure observed in British adult men may have its origins early in life.

Sporting Activity and Hyperglycemia in Middle-Aged Men

OBJECTIVE To assess the relationship between self-reported frequency of participation in sporting activity and the prevalence of hyperglycemia (nonfasting glucose level > or = 7.8 mM) in middle-aged men. RESEARCH DESIGN AND METHODS We used a cross-sectional study of 7617 British middle-aged men, drawn from 24 general practices in England, Wales, and Scotland, who were participants in the British Regional Heart Study. The response rate was 78%. Patients with diabetes (physician-diagnosed) were excluded from our analysis. Frequency of participation in sporting activity was determined by the respondents and reported as none (61%), occasionally (12%), or frequently (27%). RESULTS The age-adjusted prevalence odds ratio for hyperglycemia was 0.86 (95% confidence interval, 0.6–1.2) in those reporting occasional, and 0.62 (95% confidence interval, 0.4–0.85) in those reporting frequent sporting activity, compared with those reporting none. This effect of frequent sporting activity on the prevalence of hyperglycemia was independent of body mass index, occupational status, smoking status, systolic blood pressure, use of antihypertensive therapy, and time of sampling. CONCLUSIONS Frequent sporting activity in middle-aged men is associated with a reduced prevalence of hyperglycemia and may reduce the risk of NIDDM.