Associations between sporting physical activity and cognition in mid and later-life: Evidence from two cohorts.

Evidence has linked sporting leisure time physical activity (sporting-LTPA) to healthy cognition throughout adulthood. This may be due to the physiological effects of physical activity (PA), or to other, psychosocial facets of sport. We examined associations between sporting-LTPA and cognition while adjusting for device-measured PA volume devoid of context, both in midlife (N = 4041) participants from the 1970 British Cohort Study and later-life (N = 957) participants from the British Regional Heart Study. Independent of device-measured PA, we identified positive associations between sporting-LTPA and cognition. Sports with team/partner elements were strongly positively associated with cognition, suggesting LTPA context may be critical to this relationship.

Investigating the importance of the local food environment for fruit and vegetable intake in older men and women in 20 UK towns: a cross-sectional analysis of two national cohorts using novel methods.

BACKGROUND: Local neighbourhood environments can influence dietary behavior. There is limited evidence focused on older people who are likely to have greater dependence on local areas and may suffer functional limitations that amplify any neighbourhood impact. METHODS: Using multi-level ordinal regression analysis we investigated the association between multiple dimensions of neighbourhood food environments (captured by fine-detail, foot-based environmental audits and secondary data) and self-reported frequency of fruit and vegetable intake. The study was a cross-sectional analysis nested within two nationally representative cohorts in the UK: the British Regional Heart Study and the British Women's Heart and Health Study. Main exposures of interest were density of food retail outlets selling fruits and vegetables, the density of fast food outlets and a novel measure of diversity of the food retail environment. RESULTS: A total of 1124 men and 883 women, aged 69 - 92 years, living in 20 British towns were included in the analysis. There was strong evidence of an association between area income deprivation and fruit and vegetable consumption, with study members in the most deprived areas estimated to have 27% (95% CI: 7, 42) lower odds of being in a higher fruit and vegetable consumption category relative to those in the least deprived areas. We found no consistent evidence for an association between fruit and vegetable consumption and a range of other food environment domains, including density of shops selling fruits and vegetables, density of premises selling fast food, the area food retail diversity, area walkability, transport accessibility, or the local food marketing environment. For example, individuals living in areas with greatest fruit and vegetable outlet density had 2% (95% CI: -22, 21) lower odds of being in a higher fruit and vegetable consumption category relative to those in areas with no shops. CONCLUSIONS: Although small effect sizes in environment-diet relationships cannot be discounted, this study suggests that older people are less influenced by physical characteristics of neighbourhood food environments than is suggested in the literature. The association between area income deprivation and diet may be capturing an important social aspect of neighbourhoods that influence food intake in older adults and warrants further research.

Femoral atherosclerosis in an older British population: prevalence and risk factors.

Most estimates of the prevalence of peripheral atherosclerosis have been based on intermittent claudication or lower limb blood flow. The aim of this study was therefore to determine the prevalence of underlying femoral plaque, and to determine its association with other cardiovascular disease and risk factors. Presence of plaque was identified using ultrasound in a random sample of men (n=417) and women (n=367) aged 56-77 years. Coexistent cardiovascular disease, exercise and smoking were determined by questionnaire, blood pressure was recorded, and serum cholesterol and plasma fibrinogen were determined. Of the 784 subjects that were scanned, 502 (64%) demonstrated atherosclerotic plaque. Disease prevalence increased significantly with age (P<0.0001), and was more common in men (67.1 vs. 59.4%, P<0.05). Subjects with femoral plaque had a significantly greater odds of previous ischaemic heart disease (OR 2. 2, 95% CI 1.3, 3.7) and angina (OR 1.7, 95% CI 1.03, 2.7), but not of stroke or leg pain on exercise. Current and ex-smoking, raised serum total cholesterol and plasma fibrinogen levels, but not blood pressure, were associated with an increased risk of femoral plaque, independent of age and sex. Frequent exercise and a high HDL cholesterol were significantly associated with lower risk. In conclusion, therefore, atherosclerotic disease of the femoral artery affects almost two-thirds of the population in late middle age. It is associated with an increased prevalence of ischaemic heart disease and angina, but whether detecting at risk individuals using ultrasound offers advantages over simpler and less expensive risk factor scoring requires evaluation in trials.

A predictive model for failure to control bleeding during acute variceal haemorrhage.

BACKGROUND/AIMS: Variceal bleeding is a frequent complication of cirrhosis and is associated with a high risk of early rebleeding. In patients with peptic ulcers, continued bleeding or early rebleeding are risk factors for mortality and can be predicted by statistical models; however, no such models exist for acute variceal bleeding. METHODS: We prospectively evaluated failure to control bleeding in 695 consecutive patients with cirrhosis, admitted for haematemesis and/or melaena. Criteria were defined for failure to control bleeding, which comprised both continued bleeding or early rebleeding within 5 days of admission. There were 2 sequential groups of patients: (i) those with variceal bleeding initially treated with blood transfusion and vasoactive drugs, and if these failed followed by sclerotherapy (n = 385); (ii) those with variceal bleeding treated with injection sclerotherapy at diagnostic endoscopy (n = 144). The third group was those with bleeding from other sources related to portal hypertension (n = 166). RESULTS: Failure to control bleeding was noted in 169 (44%) patients in group 1, 55 (38%) in group 2 and 44 (25%) in group 3. Twenty variables that were evaluable within 6 h of admission, pertaining to severity of bleeding, severity of type of liver disease, mode of admission, and time of diagnostic endoscopy, were entered into a multivariate Cox model. Independent predictors of early rebleeding in group 1 were: active bleeding at endoscopy (irrespective of interval from admission) (p<0.0001), encephalopathy (p = 0.007), platelet count (p = 0.002), history of alcoholism (p = 0.002), presentation with haematemesis (p = 0.02), log urea (p = 0.03) and (shorter) interval to admission (p = 0.007). The variables predictive of 30-day mortality were: early bleeding (p<0.0007), bilirubin (p = 0.0006), encephalopathy (p<0.0001), (shorter) interval to admission (p<0.0001), and log urea (p = 0.004); a model based on these variables was also a good predictor of mortality in the other 2 groups. However, the model derived from group 1 for failure to control variceal bleeding was different in group 2, despite similar patient characteristics and a similar failure rate (following a single injection). This could suggest that sclerotherapy may induce bleeding in some patients independently of the baseline risk for failure to control bleeding. CONCLUSIONS: In cirrhotic patients who present with haematemesis or melaena, active variceal bleeding at diagnostic endoscopy is predictive of failure to control bleeding (continued bleeding or early rebleeding within 5 days of admission), and this failure is predictive of 30-day mortality.

Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: the British Regional Heart Study.

BACKGROUND AND PURPOSE: B-mode ultrasound is a noninvasive method of examining the walls of peripheral arteries and provides measures of the intima-media thickness (IMT) at various sites (common carotid artery, bifurcation, internal carotid artery) and of plaques that may indicate early presymptomatic disease. The reported associations between cardiovascular risk factors, clinical disease, IMT, and plaques are inconsistent. We sought to clarify these relationships in a large, representative sample of men and women living in 2 British towns. METHODS: The study was performed during 1996 in 2 towns (Dewsbury and Maidstone) of the British Regional Heart Study that have an approximately 2-fold difference in coronary heart disease risk. The male participants were drawn from the British Regional Heart Study and were recruited in 1978-1980 and form part of a national cohort study of 7735 men. A random sample of women of similar age to the men (55 to 77 years) was also selected from the age-sex register of the general practices used in the original survey. A wide range of data on social, lifestyle, and physiological factors, cardiovascular disease symptoms, and diagnoses was collected. Measures of right and left common carotid IMT (IMTcca) and bifurcation IMT (IMTbif) were made, and the arteries were examined for plaques 1.5 cm above and below the flow divider. RESULTS: Totals of 425 men and 375 women were surveyed (mean age, 66 years; range, 56 to 77 years). The mean (SD) IMTcca observed were 0. 84 (0.21) and 0.75 (0.16) mm for men and women, respectively. The mean (SD) IMTbif were 1.69 (0.61) and 1.50 (0.77) mm for men and women, respectively. The correlation between IMTcca and IMTbif was similar in men (r=0.36) and women (r=0.38). There were no differences in mean IMTcca or IMTbif between the 2 towns. Carotid plaques were very common, affecting 57% (n=239) of men and 58% (n=211) of women. Severe carotid plaques with flow disturbance were rare, affecting 9 men (2%) and 6 women (1.6%). Plaques increased in prevalence with age, affecting 49% men and 39% of women aged <60 years and 65% and 75% of men and women, respectively, aged >70 years. Plaques were most common among men in Dewsbury (79% affected) and least common among men in Maidstone (34% affected). IMTcca showed a different pattern of association with cardiovascular risk factors from IMTbif and was associated with age, SBP, and FEV1 but not with social, lifestyle, or other physiological risk factors. IMTbif and carotid plaques were associated with smoking, manual social class, and plasma fibrinogen. IMTbif and carotid plaques were associated with symptoms and diagnoses of cardiovascular diseases. IMTbif associations with cardiovascular risk factors and prevalent cardiovascular disease appeared to be explained by the presence of plaques in regression models and in analyses stratified by plaque status. CONCLUSIONS: IMTcca, IMTbif, and plaque are correlated with each other but show differing patterns of association with risk factors and prevalent disease. IMTcca is strongly associated with risk factors for stroke and with prevalent stroke, whereas IMTbif and plaque are more directly associated with ischemic heart disease risk factors and prevalent ischemic heart disease. Our analyses suggest that presence of plaque, rather than the thickness of IMTbif, appears to be the major criterion of high risk of disease, but confirmation of these findings in other populations and in prospective studies is required. The association of fibrinogen with plaque appears to be similar to its association with incident cardiovascular disease. Further work elucidating the composition of plaques using ultrasound imaging would be helpful, and more data, analyzed to distinguish plaque from IMTbif and IMTcca, are required to understand the significance of thicker IMT in the absence of plaque.

Factors related to early mortality after transjugular intrahepatic portosystemic shunt for failed endoscopic therapy in acute variceal bleeding.

BACKGROUND: Uncontrolled variceal haemorrhage is the main indication for transjugular intrahepatic portosystemic shunt. However, mortality is 50% for this high-risk group. We have evaluated clinical and laboratory variables prior to transjugular intrahepatic portosystemic shunt in order to establish predictors of mortality, validated prospectively. METHOD: Over a 4-year period, 367 patients were admitted with variceal bleeding. In 54 patients endoscopic therapy for acute variceal bleeding failed and they had emergency transjugular intrahepatic portosystemic shunt. Failure of therapy was defined as continued bleeding after 2 endoscopy sessions (n=39) or vasoconstrictor-resistant bleeding from gastric/ectopic varices (n=15). Thirty-three variables were analysed from data available immediately prior to transjugular intrahepatic portosystemic shunt. RESULTS: Twenty-six patients died within 6 weeks. In a multivariate analysis, 6 factors had independent prognostic value: moderate/severe ascites, requirement for ventilation, white cell blood count (WBC), platelet count (PLT), partial thromboplastin time with kaolin (PTTK) and creatinine. A prognostic index (PI) score was derived, in which presence of moderate/severe ascites, or need for ventilation, scored 1: PI=1.54 (Ascites)+1.27 (Ventilation)+1.38 Ln (WBC)+2.48 ln (PTTK)+1.55 Ln (Creat)-1.05 Ln (PLT). Using this equation, 42% (n=10) of deaths occurred in the fifth quintile (PI > or = 18.52), where the mortality was 100%. The score was prospectively validated in a further 31 patients, giving 100% positive predictive value. Eleven further patients died, including all seven with a PI >18.5. No survivors had a PI >18.3. CONCLUSION: Despite immediate control of bleeding by transjugular intrahepatic portosystemic shunt, patients with uncontrolled variceal haemorrhage have a high mortality, particularly when associated with markers of advanced liver disease, sepsis and multi-organ failure. The use of transjugular intrahepatic portosystemic shunt is probably not justified in this subgroup. Our prognostic index can help identify such patients, and, if validated elsewhere, will help in deciding when to use transjugular intrahepatic portosystemic shunt.

Blood pressure and cancer in middle-aged British men.

BACKGROUND: This paper examines the relationship between blood pressure and cancer mortality. METHODS: A prospective study of 7735 middle-aged men drawn at random from one general practice in each of 24 British towns. RESULTS: During a mean follow-up period of 12.75 years there were 351 deaths from cancers. The relationship between blood pressure and cancer differed with respect to follow-up period. In the first 5 years of follow-up, a significant inverse relationship was seen between systolic (SBP) and diastolic blood pressure (DBP) and cancer mortality even after adjustment for age, smoking, social class, physical activity, alcohol intake, body mass index, diabetes, pre-existing ischaemic heart disease, use of antihypertensive drugs, cholesterol, heart rate and serum albumin. In the subsequent follow-up period (5.1-12.75 years) a significant positive association was seen between SBP (but not DBP) and risk of cancer mortality, even after adjustment for the other risk factors. Men in the top fifth of SBP ( > or = 161 mmHg) showed over a 50% increase in risk of cancer mortality compared to men in the bottom quintile (RR = 1.56 95% CI 95% CI: 1.04-2.38). This positive relationship between SBP and cancer was seen only in current cigarette smokers. Use of antihypertensive drugs was not associated with cancer mortality. CONCLUSION: The association of elevated SBP with increased risk of cancer mortality seen only in current smokers warrants the search for factors which affect SBP, interact with smoking and are potentially carcinogenic.

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.

Gamma-glutamyltransferase: determinants and association with mortality from ischemic heart disease and all causes.

The association of serum levels of gamma-glutamyltransferase (GGT) with cardiovascular disease risk factors, and with mortality from all causes, cardiovascular disease, and non-cardiovascular diseases, has been examined in a prospective study of 7,613 middle-aged British men followed for 11.5 years. GGT levels were strongly associated with all-cause mortality, largely due to a significant increase in deaths from ischemic heart disease and other non-cardiovascular disease causes, i.e., non-cancer deaths, in the top quintile of the GGT distribution. No association was seen with cancer mortality. However, GGT was significantly (positively) associated with alcohol intake, body mass index, smoking, preexisting ischemic heart disease, diabetes mellitus, antihypertensive medication, systolic and diastolic blood pressure, total and high density lipoprotein cholesterol, heart rate, and blood glucose, and negatively associated with physical activity and lung function (forced expiratory volume in 1 second (FEV1)). After adjustment for these personal characteristics and biologic variables, elevated GGT (highest quintile > or = 24 unit/liter vs. the rest) was still associated with a significant increase in mortality from all causes (relative risk (RR) = 1.22, 95% confidence interval (CI) 1.01-1.42; n = 818 deaths) and from ischemic heart disease (RR = 1.42, 95% CI 1.12-1.80; n = 332 deaths). The increase in other non-cardiovascular disease causes was of marginal significance (RR = 1.45, 95% CI 0.95-2.20; n = 127 deaths). When examined separately by the presence or absence of preexisting ischemic heart disease, the increased risk of ischemic heart disease mortality was more marked in those with evidence of ischemic heart disease at screening, particularly in those with previous myocardial infarction (RR = 1.67, 95% CI 1.03-2.69; n = 84 deaths). The increased risk of other non-cardiovascular disease deaths was only seen in men without preexisting ischemic heart disease, largely due to an excess of hepatic cirrhosis. In summary, many factors other than alcohol intake are associated with increased levels of GGT, in particular body mass index, diabetes mellitus, and serum total cholesterol. The finding of increased risk of ischemic heart disease mortality seen in men with preexisting ischemic heart disease is related to the severity of the underlying myocardial damage. The biologic significance of raised GGT in men with preexisting ischemic heart disease merits further study.

Marital status, change in marital status, and mortality in middle-aged British men.

The effects of marital status and change in marital status on mortality among middle-aged British men were examined in a prospective cohort study, the British Regional Heart Study. This is a nationally representative cohort of men selected at random from general medical practices in 24 towns in England, Wales, and Scotland. It comprises 7,735 men aged 40-59 recruited in 1978-1980 and followed up for 11.5 years. Marital status and a wide range of biologic and lifestyle variables were measured at screening, and changes in marital status were assessed after 5 years. Single (never-married) men had an increased risk of cardiovascular disease mortality (relative risk (RR) = 1.5, 95% confidence interval (CI) 1.0-2.2) and noncancer, noncardiovascular mortality (RR = 1.8, 95% CI 1.1-3.3) after adjustment for potentially confounding variables: age, social class, smoking, recall of ischemic heart disease, recall of diabetes mellitus, use of antihypertensive drugs, body mass index, physical activity, alcohol intake, employment status, systolic blood pressure, blood cholesterol, and forced expiratory volume in 1 second. Divorced/separated men were not at increased risk of mortality, and widowed men were only at increased risk of other non-cardiovascular disease mortality (RR = 2.4, 95% CI 1.1-5.3). There was no effect of marital status on cancer mortality. Men who divorced during the follow-up period were at increased risk of both cardiovascular disease mortality (RR = 1.9, 95% CI 0.9-3.9) and other non-cardiovascular disease mortality (RR = 4.0, 95% CI 1.5-10.6), but men who became widowed during this time were not at increased risk. The excess mortality among single and recently divorced men was not explained by poor health or by exposure to a wide range of risk factors. It is unlikely that selection bias, chance, or artifact is responsible for the general relation between marital status and mortality. Variable and incomplete control for confounding by socioeconomic status and risk factors for common diseases may explain some of the inconsistencies observed between studies and between different categories of unmarried men (i.e., never-married, widowed, and divorced). It is possible that the social support offered by marriage exerts a protective effect for some men.

Serum bilirubin and risk of ischemic heart disease in middle-aged British men.

The possibility that low concentrations of serum bilirubin may be associated with increased risk of ischemic heart disease has been examined in a prospective study of 7685 middle-aged British men. During 11.5 years there were 737 major ischemic heart disease (IHD) events. A U-shaped relationship was observed between serum bilirubin and risk of IHD. Low bilirubin was associated with several cardiovascular risk factors, in particular smoking, low concentrations of high-density lipoprotein cholesterol, low forced expiratory volume in 1 s, and low serum albumin. The U-shaped relationship persisted even after adjusting for several risk factors. Compared with men in the lowest fifth of the distribution (bilirubin < 7 mumol/L), those in the middle range (8-9 mumol/L) showed a 30% reduction in relative risk [RR = 0.68 (95% confidence intervals 0.51-0.89)] in IHD, whereas men in the top fifth (> 12 mumol/L) showed similar risk to the lowest fifth [RR = 0.99 (95% confidence intervals 0.73-1.34)], which persisted after exclusion of men with bilirubin > 17 mumol/L. The significance of this U-shaped relationship is unclear, but it could be interpreted as support for the role of endogenous antioxidants in the etiology of IHD.

Factors determining case fatality in myocardial infarction "who dies in a heart attack"?

OBJECTIVE: To examine the determinants of case fatality in the first major ischaemic heart disease event (heart attack) after screening. METHODS: Prospective study of 7735 middle aged men drawn from general practices in 24 British towns. RESULTS: During 11.5 years follow up there were 743 major ischaemic heart disease events of which 302 (40.6%) were fatal within 28 days of onset. Previous definite myocardial infarction or stroke and age at time of event were most strongly associated with case fatality. In men with no previous myocardial infarction or stroke, after adjustment for a range of risk factors, antihypertensive treatment (odds ratio (OR) = 1.97, P < 0.05), arrhythmia (OR = 1.93, P = 0.06), increased heart rate (OR = 2.03, P = 0.06), and diabetes (OR = 2.61, P = 0.07) were associated with increased case fatality. High levels of physical activity (OR = 0.53, P < 0.05) and moderate drinking (16-42 units/week) (OR = 0.61, P < 0.05) were associated with lower case fatality, although moderate drinking was not associated with a lower incidence of major ischaemic heart disease events. Current smoking, serum total cholesterol, and systolic blood pressure were not significantly associated with case fatality. In men with previous myocardial infarction or stroke, arrhythmia and to a lesser degree antihypertensive treatment, moderate or heavy drinking, and diabetes were associated with higher case fatality. CONCLUSION: These findings suggest that physical activity may be an important modifiable factor influencing the incidence of ischaemic heart disease and the chance of survival in men without a previous heart attack or stroke. Arrhythmia, increased heart rate, diabetes, and treatment for hypertension are also areas of concern.

Weight change and risk of heart attack in middle-aged British men.

BACKGROUND: Both weight gain and weight loss have been associated with increased risk of cardiovascular disease mortality in recent studies from the US. This finding has led to concern and uncertainty about appropriate advice for overweight and obese subjects. METHODS: In a prospective study of cardiovascular disease, the relationship between weight change over a 5-year period and subsequent risk of a heart attack during a further 6.5 year follow-up was examined in 7100 middle-aged British men. RESULTS: Over half of the men remained stable (< 4% change in bodyweight) and served as the reference group; 31% gained weight and 13% lost weight. The 6445 men free from a history of coronary heart disease experienced 318 heart attacks, fatal and non-fatal, during the 6.5 years. Men who gained 4-10% bodyweight had the lowest rate of heart attack, although this was not significantly different from the stable group. The men who lost weight had an increased risk of heart attack, which after adjustment (for age, recall of doctor-diagnosed hypertension and diabetes and other coronary risk factors i.e. serum total cholesterol, blood pressure, social class, initial body mass index (BMI) and lung function (FEV1), and smoking status at screening and 5 years later), was of a similar level of risk to the stable group. The men who gained > 10% bodyweight had a significantly increased risk of a heart attack after the above adjustment (P < 0.05). When the effect of weight change was examined according to initial BMI, those men with a BMI < 25 kg/m2 who lost weight had a marginally increased relative risk of heart attack after full adjustment (P = 0.06), while men who were overweight (BMI 25-27.9 kg/m2) or obese (BMI > or = 28 kg/m2) showed no benefit from weight loss. A small amount of weight gain (4-10%) in the overweight or obese men was associated with decreased risk, whereas considerable weight gain (> 10%) was associated with increased risk, both findings reaching statistical significance in the overweight men (P < 0.05 and P < 0.001 respectively). CONCLUSIONS: Considerable weight gain (> 10%) in middle-aged men is associated with increased risk of a heart attack, but weight loss does not appear to reduce risk even in the overweight or obese.

Low serum total cholesterol concentrations and mortality in middle aged British men.

OBJECTIVE: To examine the relation between low serum total cholesterol concentrations and causes of mortality. DESIGN: Cohort study of men followed up for an average of 14.8 years (range 13.5-16.0 years). SETTING: One general practice in each of 24 British towns. SUBJECTS: 7735 men aged 40-59 at screening selected at random from the 24 general practices. MAIN OUTCOME MEASURES: Deaths from all causes, cardiovascular causes, cancer, and non-cardiovascular, non-cancer causes. RESULTS: During the mean follow up period of 14.8 years there were 1257 deaths from all causes, 640 cardiovascular deaths, 433 cancer deaths, and 184 deaths from other causes. Low serum cholesterol concentrations (< 4.8 mmol/l), present in 5% (n = 410) of the men, were associated with the highest mortality from all causes, largely due to a significant increase in cancer deaths (age adjusted relative risk 1.6 (95% confidence interval 1.1 to 2.3); < 4.8 v 4.8-5.9 mmol/l) and in other non-cardiovascular deaths (age adjusted relative risk 1.9 (1.1 to 3.1)). Low serum cholesterol concentration was associated with an increased prevalence of several diseases and indicators of ill health and with lifestyle characteristics such as smoking and heavy drinking. After adjustment for these factors in the multivariate analysis the increased risk for cancer was attenuated (relative risk 1.4 (0.9 to 2.0) and the inverse association with other non-cardiovascular, non-cancer causes was no longer significant (relative risk 1.5 (0.9 to 2.6); < 4.8 v 4.8-5.9 mmol/l). The excess risks of cancer and of other non-cardiovascular deaths were most pronounced in the first five years and became attenuated and non-significant with longer follow up. By contrast, the positive association between serum total cholesterol concentration and cardiovascular mortality was seen even after more than 10 years of follow up. CONCLUSION: The association between comparatively low serum total cholesterol concentrations and excess mortality seemed to be due to preclinical cancer and other non-cardiovascular diseases. This suggests that public health programmes encouraging lower average concentrations of serum total cholesterol are unlikely to be associated with increased cancer or other non-cardiovascular mortality.

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.

The association between heart rate and blood pressure, blood lipids and other cardiovascular risk factors.

BACKGROUND: Several studies have shown that an elevated heart rate is associated with an increased risk of ischaemic heart disease. The aim of this study was to examine the relationship between heart rate, blood pressure, blood lipids and other cardiovascular risk factors in middle-aged men. METHODS: A total of 7735 men, aged 40-59 years at screening, were selected at random from one of the general practices in each of the 24 towns participating in the cross-sectional (screening) phase of the British Regional Heart Study. Blood pressure and levels of blood lipids (serum total cholesterol, high-density-lipoprotein (HDL) cholesterol and triglycerides) and blood glucose were measured. RESULTS: All men with pre-existing evidence of ischaemic heart disease and those on regular antihypertensive treatment were excluded from the analysis. In the remaining 5597 men, heart rate showed a strong positive correlation with cigarette smoking and body-mass index and decreased significantly at higher levels of physical activity and FEV1 (forced expiratory volume in 1 s). These associations remained significant after adjustment for each other. Age, alcohol intake and social class were not independently associated with heart rate. There was a significant positive association between heart rate and systolic and diastolic blood pressures, levels of blood cholesterol, triglycerides and blood glucose and a significant inverse association between heart rate and HDL-cholesterol levels, even after adjusting for the above confounding factors. After further adjustment for each of the other physiological variables, heart rate remained independently associated with diastolic and systolic blood pressures and levels of triglycerides and blood glucose. The relationship between heart rate and levels of total cholesterol and HDL cholesterol appeared to be secondary to its association with triglyceride levels. The association between body-mass index and heart rate diminished after further adjustments for systolic blood pressure, suggesting that the primary effect of body weight is on blood pressure rather than on heart rate. CONCLUSION: Our findings indicate that elevated heart rate is associated with hypertension and with an atherogenic lipoprotein profile and support the suggestion that disturbance of the autonomic nervous system may underlie these associations.

Serum sodium concentration and risk of stroke in middle-aged males.

BACKGROUND AND METHODS: Clinical disturbances of the circulating sodium concentration are both a cause and a consequence of cerebrovascular disease. We examined the relationship between serum sodium level and risk of stroke and major ischaemic heart disease in a prospective study of 7690 middle-aged males drawn from general practices in 24 British towns followed over a 9.5-year period. RESULTS: The mean serum sodium level was 141.5 mmol/l and 375 males on antihypertensive treatment were excluded from the analyses. A significant inverse trend was seen between serum sodium and risk of stroke up to 144 mmol/l; above this the risk of stroke was increased. Those with levels of 143-144 mmol/l showed over a 70% reduction in risk of stroke compared with those with levels of < or = 140 mmol/l. The inverse relationship between sodium and stroke up to 144 mmol/l was seen in males with and without pre-existing ischaemic heart disease or stroke, in normotensives and untreated hypertensives, and in non-smokers and current smokers. A weak but significant inverse association was seen between serum sodium and diastolic but not systolic blood pressure. The association between serum sodium level and stroke remained significant after adjustment for diastolic blood pressure and other factors associated with stroke: age, smoking, social class, body mass index, physical activity, heavy drinking, presence of diabetes, blood glucose and pre-existing ischaemic heart disease. No association was seen between serum sodium level and risk of ischaemic heart disease after adjustment for other risk factors. All-cause and non-cardiovascular mortality were significantly increased at serum sodium levels of < or = 138 mmol/l, probably due to an association between lung cancer and hyponatraemia. CONCLUSION: These findings suggest that sodium concentration may be related to risk of stroke even at levels of sodium usually regarded as normal.

Haematocrit: relationships with blood lipids, blood pressure and other cardiovascular risk factors.

The relationship between haematocrit and cardiovascular risk factors, particularly blood pressure and blood lipids, has been examined in detail in a large prospective study of 7735 middle-aged men drawn from general practices in 24 British towns. The analyses are restricted to the 5494 men free of any evidence of ischaemic heart disease at screening. Smoking, body mass index, physical activity, alcohol intake and lung function (FEV1) were factors strongly associated with haematocrit levels independent of each other. Age showed a significant but small independent association with haematocrit. Non-manual workers had slightly higher haematocrit levels than manual workers; this difference increased considerably and became significant after adjustment for the other risk factors. Diabetics showed significantly lower levels of haematocrit than non-diabetics. In the univariate analysis, haematocrit was significantly associated with total serum protein (r = 0.18), cholesterol (r = 0.16), triglyceride (r = 0.15), diastolic blood pressure (r = 0.17) and heart rate (r = 0.14); all at p < 0.0001. A weaker but significant association was seen with systolic blood pressure (r = 0.09, p < 0.001). These relationships remained significant even after adjustment for age, smoking, body mass index, physical activity, alcohol intake, lung function, presence of diabetes, social class and for each of the other biological variables; the relationship with systolic blood pressure was considerably weakened. No association was seen with blood glucose and HDL-cholesterol. This study has shown significant associations between several lifestyle characteristics and the haematocrit and supports the findings of a significant relationship between the haematocrit and blood lipids and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)