P H Whincup

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

ASSOCIATION BETWEEN SERUM ALBUMIN AND MORTALITY FROM CARDIOVASCULAR DISEASE, CANCER, AND OTHER CAUSES

In a prospective study of 7735 middle-aged British men (British Regional Heart Study) 660 died during an average follow-up period of 9.2 years. There was a marked increase in mortality rate with decreasing serum albumin concentrations that persisted even after adjustment for age, social class, town of residence, cigarette smoking, serum total cholesterol, systolic blood pressure, serum total calcium, and forced expiratory volume in 1 s. When serum albumin concentration was less than 40 g/l, the mortality rate was 23/1000 per year compared with 4/1000 per year for a concentration equal to or above 48 g/l. A similar pattern was observed for cardiovascular, cancer, and other deaths. The associations persisted for cardiovascular disease and cancer even when deaths within the first five years of follow-up were excluded. These results must be interpreted with caution since there was no prior hypothesis concerning serum albumin. However, the strength of the association between serum albumin and mortality seems to be comparable with that for cigarette smoking.

Prospective relations between Helicobacter pylori infection, coronary heart disease, and stroke in middle aged men.

OBJECTIVE: To determine whether Helicobacter pylori, a chronic bacterial infection often acquired in childhood, is associated with increased risk of coronary heart disease and stroke later in life. DESIGN: Nested case-control study. SETTING: Prospective study of cardiovascular disease in men aged 40-59 years at entry (1978-1980) in 24 British towns. SUBJECTS: 135 cases of myocardial infarction and 137 cases of stroke occurring before December 1991; 136 controls were identified, frequency matched to cases by town and age group. METHODS: Serum samples stored at entry were analysed by an enzyme linked immunosorbent assay for the presence of H pylori specific IgG antibodies. RESULTS: 95 of the myocardial infarction cases (70%) and 93 (68%) of the stroke cases were seropositive for H pylori compared with 78 (57%) of the controls (odds ratio for myocardial infarction 1.77, 95% confidence interval (CI) 1.06 to 2.95, P = 0.03; odds ratio for stroke 1.57, 95% CI 0.95 to 2.60, P = 0.07). Helicobacter pylori infection was associated with manual social class, residence in Northern England or Scotland, cigarette smoking, higher systolic pressure and blood glucose, and a lower height-standardised forced expiratory volume in one second. Adjustment for these factors attenuated the relation between H pylori and myocardial infarction (odds ratio = 1.31, 95% CI 0.70 to 2.43, P = 0.40) and effectively abolished the relation with stroke (odds ratio = 0.96, 0.46 to 2.02, P = 0.92). The relation between helicobacter infection and fatal myocardial infarction was slightly stronger (odds ratio 2.41, 95% CI 1.13 to 5.12) but was also markedly attenuated after adjustment (1.56, 95% CI 0.68 to 3.61). CONCLUSION: In this prospective study the association between Helicobacter pylori infection and increased risk of myocardial infarction and stroke was substantially confounded by the relation between this infection, adult social class, and major cardiovascular risk factors.

Comparison of the associations of body mass index and measures of central adiposity and fat mass with coronary heart disease, diabetes, and all-cause mortality: a study using data from 4 UK cohorts

BACKGROUND Measures of regional adiposity have been proposed as alternatives to the measurement of body mass index (BMI) for identifying persons at risk of future disease. OBJECTIVE The objective was to compare the magnitudes of association of BMI and alternative measurements of adiposity with coronary heart disease, diabetes, and cardiovascular disease risk factors and all-cause mortality. DESIGN Data from 4 cohorts of adults [3937 women from the British Womens Heart and Health Study (BWHHS); 2367 and 1950 men from phases 1 and 3, respectively, of the Caerphilly Prospective Study (CaPS); 403 men and women from the Boyd Orr Study; and 789 men and women from the Maidstone-Dewsbury Study] were analyzed. RESULTS The magnitudes of associations of BMI with incident coronary heart disease and cardiovascular disease risk factors were similar to those with measurements of central adiposity [waist circumference (WC), waist-hip ratio (WHR), or waist-height ratio (WHtR)] and more direct measurements of fat mass (bioimpedance/skinfold thickness). In CaPS (men only), there was no strong evidence of differences in the strengths of association with incident diabetes between BMI, WC, WHR, and WHtR (P for heterogeneity > 0.49 for all). In the BWHHS (women only), there was statistical evidence that WC [hazard ratio (HR): 2.35; 95% CI: 2.03, 2.73] and WHtR (HR: 2.29; 95% CI: 1.98, 2.66) were more strongly associated with diabetes than with BMI (HR: 1.80; 95% CI: 1.59, 2.04) (P for heterogeneity < 0.02 for both). Central adiposity measurements were positively associated with all-cause mortality, as was BMI, but only when those with a BMI (in kg/m(2)) <22.5 were removed from the analyses. CONCLUSION No strong evidence supports replacing BMI in clinical or public health practice with other adiposity measures.

Serum urate and the risk of major coronary heart disease events.

OBJECTIVE: To examine the relation between serum urate and the risk of major coronary heart disease events. DESIGN: A prospective study of a male cohort. SETTING: One general practice in each of 24 British towns. SUBJECTS: 7688 men aged 40-59 years at screening. MAIN OUTCOME MEASURES: Fatal and non-fatal coronary heart disease events. RESULTS: There were 1085 major coronary heart disease events during the average follow up period of 16.8 years. Serum urate was significantly associated with a wide range of cardiovascular risk factors including body mass index, alcohol intake, antihypertensive treatment, pre-existing coronary heart disease, serum triglycerides, cholesterol, and diastolic blood pressure. There was a significant positive association between serum urate and risk of coronary heart disease after adjustment for lifestyle factors and disease indicators. This relation was attenuated to non-significance upon additional adjustment for diastolic blood pressure and serum total cholesterol: cholesterol appeared to be the critical factor in attenuating this relation. When the association between serum urate and risk of coronary heart disease was examined by presence and grade of pre-existing coronary heart disease, a positive association was seen only in men with previous definite myocardial infarction, even after full adjustment (P = 0.07). CONCLUSIONS: The relation between serum urate and the risk of coronary heart disease depends heavily upon the presence of pre-existing myocardial infarction and widespread underlying atherosclerosis as well as the clustering of risk factors. Thus serum urate is not a truly independent risk factor for coronary heart disease. Raised serum urate appears to be an integral part of the cluster of risk factors associated with the insulin resistance syndrome that include obesity, raised serum triglycerides, and serum cholesterol.

Early influences on blood pressure: a study of children aged 5-7 years.

OBJECTIVE--To examine factors that influence blood pressure in children. DESIGN--Cross sectional study of children aged 5.0-7.0 years who had blood pressure measurements and for whom parental questionnaires were completed. SETTING--School based survey. SUBJECTS--3591 Children aged 5.0-7.5 years selected by stratified random sampling of primary schools in nine British towns (response rate 72%); 3591 were examined and their parental questionnaires were completed. Data were complete for birth rank in 3559, maternal age in 3542, maternal history of hypertension in 3524, and paternal history in 2633. RESULTS--Birth weight was inversely related to mean systolic blood pressure but only when standardised for current weight (weight standardised regression coefficient -1.83 mm Hg/kg (95% confidence interval -1.31 to -2.35). Mean diastolic pressure was similarly related to birth weight. Maternal age, birth rank, and a parental history of hypertension were all related to blood pressure. After standardisation for current weight a 10 year increase in maternal age was associated with a 1.0 mm Hg (0.4 to 1.6) rise in systolic pressure; first born children had systolic blood pressure on average 2.53 mm Hg (0.81 to 4.25) higher than those whose birth rank was greater than or equal to 4; and a maternal history of hypertension was associated with a systolic pressure on average 0.96 mm Hg (0.41 to 1.51) higher than in those with no such history. The effects described were largely independent of one another and of age and social class. The relation for birth rank was, however, closely related to that for family size. CONCLUSIONS--Influences acting in early life may be important determinants of blood pressure in the first decade. The relation between birth weight and blood pressure may reflect the rate of weight gain in infancy. The reasons for the relation with birth rank and maternal age are unknown; if confirmed they imply that delayed motherhood and smaller family size may be associated with higher blood pressure in offspring.

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.

Overweight and obesity and the burden of disease and disability in elderly men

OBJECTIVE: To examine the prevalence of disease burden and disability associated with overweight and obesity in men aged 60–79 y and to assess whether the current WHO weight guidelines are appropriate in the elderly.DESIGN: Cross-sectional survey 20 y after enrolment.SETTING: General practices in 24 British towns.PARTICIPANTS: In total, 4232 men aged 60–79 y (77% of survivors) with measured weight and height.MAIN OUTCOME MEASURES: Cardiovascular (CV) risk factors, prevalence of diabetes, cardiovascular disease, cancer, disability and regular medication.RESULTS: In total, 17% of the men were obese (body mass index (BMI) ≥30 kg/m2) and a further 52% were overweight (BMI 25–29.9 kg/m2). Prevalence of hypertension, low HDL-cholesterol, high triglycerides and insulin resistance and the prevalence of most disease outcomes increased with increasing degrees of overweight/obesity. Men in the normal weight range (18.5–24.9 kg/m2) had the lowest prevalence of ill health. Compared with normal weight men, obese men showed a two-fold risk of major CVD (odds ratio (OR)=1.96, 95% CI 1.44–2.67) and locomotor disability (OR=2.26, 95% CI 1.66, 3.09) and were nearly three times as likely to have diabetes, CV interventions or to be on CV medication. Over 60% of the prevalence of high insulin resistance was attributable to overweight and obesity as was over a third of diabetes and hypertension, a quarter of locomotor disability and a fifth of major CVD.CONCLUSION: In elderly men, overweight and obesity are associated with a significantly increased burden of disease, in particular CV-related disorders and disability. The current guidelines for overweight and obesity appear to be appropriate in elderly men.

Alcohol and adiposity: effects of quantity and type of drink and time relation with meals

BACKGROUND:It has been suggested that the effects of alcohol on body weight and fat distribution may be influenced by the quantity and type of drink and may differ according to whether the alcohol is consumed with meals or not.OBJECTIVE:We have examined the cross-sectional association between alcohol intake, patterns of drinking and adiposity (body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC) and percentage body fat (%BF)).METHODS:We studied 3327 men aged 60–79 y with no history of myocardial infarction, stroke or diabetes drawn from general practices in 24 British towns.RESULTS:BMI, WHR, WC and %BF increased significantly with increasing alcohol intake even after adjustment for potential confounders (all P<0.0001), although the effects were stronger for WC and WHR (measures of central adiposity). Men who consumed ≥21 units/week showed higher levels of central adiposity (WHR, WC) and general adiposity (BMI, %BF) than nondrinkers and lighter drinkers, irrespective of the predominant type of drink consumed (wine, beer, spirits or mixed). The positive association was most clearly seen in beer and spirit drinkers; positive but weaker associations were seen for wine. Among drinkers, a positive association was seen between alcohol intake and the adiposity variables irrespective of whether the alcohol was drunk with or separately from meals.CONCLUSION:Higher alcohol consumption (≥21 units/week) is positively associated with general and to a greater extent with central adiposity, irrespective of the type of drink and whether the alcohol is drunk with meals or not.

ABO blood group and ischaemic heart disease in British men.

OBJECTIVE--To establish whether ABO blood group is related to ischaemic heart disease on an individual and geographic basis in Britain. DESIGN--Prospective study of 7662 men with known ABO blood group selected from age-sex registers in general practices in 24 British towns. MEASUREMENTS--ABO blood group, standard cardiovascular risk factors, social class, and presence or absence of ischaemic heart disease determined at entry to study. END POINTS--Eight year follow up of fatal and nonfatal ischaemic heart disease events achieved for 99% of study population. RESULTS--Towns with a higher prevalence of blood group O had higher incidences of ischaemic heart disease. In individual subjects, however, the incidence of ischaemic heart disease was higher in those with group A than in those with other blood groups (relative risk 1.21, 95% confidence limits 1.01 to 1.46). Total serum cholesterol concentration was slightly higher in subjects of blood group A. No other cardiovascular risk factor (including social class) was related to blood group. CONCLUSIONS--Blood group A is related to the incidence of ischaemic heart disease in individual subjects. Geographic differences in the distribution of ABO blood groups do not explain geographic variation in rates of ischaemic heart disease in Britain. The findings do not support the view that ABO blood group and social class are related.