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Background: Social connections may impact the dynamic trajectory of frailty., Methods: Using data from the British Regional Heart Study (BRHS) in the UK (n = 715), and the US Health, Aging and Body Composition (Health ABC) Study (n = 1256), we conducted multinominal regression analyses to examine the association of baseline and change in social engagement and loneliness with progression to pre-frailty and frailty, as well as their association with reversal to pre-frailty and robust status among older adults., Results: A higher level of social engagement at baseline (BRHS: relative risk ratio (RRR) 0.69 [95%CI 0.55-0.85]; Health ABC: 0.56 [0.45-0.70]), as well as increase in social engagement (BRHS: 0.73, [0.59-0.90]; Health ABC: 0.51 [0.41-0.63]), were associated with a lower risk of developing frailty. In BRHS, a higher level of loneliness at baseline (1.42 [1.10-1.83]) and an increase in loneliness (1.50 [1.18-1.90]), increased the risk of developing frailty. For reversal of frailty, higher social engagement at baseline (Health ABC: 1.63 [1.08-2.47]) and an increase in social engagement (BRHS:1.74[1.18-2.50]; Health ABC: 1.79[1.17-.274]) were beneficial., Conclusion: Social connections maybe potentially important and modifiable factors in both preventing and reversing progression of frailty in older adults., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Introduction: cardiovascular disease (CVD) and chronic inflammation are implicated in the development of frailty. Longitudinal analyses of inflammatory markers, biomarkers of cardiac dysfunction and incidence of frailty are limited., Methods: in the British Regional Heart Study, 1,225 robust or pre-frail men aged 71-92 years underwent a baseline examination, with questionnaire-based frailty assessment after 3 years. Frailty definitions were based on the Fried phenotype. Associations between incident frailty and biomarkers of cardiac dysfunction (high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP)) and inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) were examined, by tertile, with the lowest as reference., Results: follow-up data were available for 981 men. Ninety one became frail. Adjusted for age, pre-frailty, prevalent and incident CVD, comorbidity, polypharmacy and socioeconomic status, IL-6 (third tertile OR 2.36, 95% CI 1.07-5.17) and hs-cTnT (third tertile OR 2.24, 95% CI 1.03-4.90) were associated with increased odds of frailty. CRP (third tertile OR 1.83, 95% CI 0.97-4.08) and NT-proBNP (second tertile OR 0.48, 95% CI 0.23-1.01) showed no significant association with incident frailty. The top tertiles of CRP, IL-6, hscTnT and NT-proBNP were strongly associated with mortality prior to follow-up., Conclusion: IL-6 is associated with incident frailty, supporting the prevailing argument that inflammation is involved in the pathogenesis of frailty. Cardiomyocyte injury may be associated with frailty risk. Associations between elevated CRP and frailty cannot be fully discounted; NT-proBNP may have a non-linear relationship with incident frailty. CRP, IL-6, hs-cTnT and NT-proBNP are vulnerable to survivorship bias., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: orthostatic hypotension (OH) that occurs within, or at, 1 minute of standing is associated with higher risk of falls, myocardial infarction, syncope and mortality, compared to OH that occurs after 1 minute of standing. Whether vitamin D deficiency increases the risk of OH is controversial., Methods: this was a cross-sectional analysis of 3,620 older, community-dwelling men. Multinomial, multiple logistic regression models were used to calculate the risk of OH across categories of vitamin D status (deficient [<25 nmol/l], insufficient [≥25-<50 nmol/l] and sufficient [≥50 nmol/l]) and parathyroid hormone quintile., Results: men with vitamin D deficiency were more likely to have OH that occurred within 1 minute of standing in univariate logistic regression (OR 1.88, 95% CI 1.40-2.53) and multinomial, multiple logistic regression (OR 1.51, 95% CI 1.06-2.15), compared to men with sufficient levels of vitamin D. Vitamin D insufficiency was not associated with the risk of OH. Elevated parathyroid hormone was not associated with risk of OH., Conclusion: the absence of an association between vitamin D insufficiency and risk of OH and the presence of an association between vitamin D deficiency and risk of OH suggest that there may be a threshold effect; it is only below a particular level of vitamin D that risk of OH is increased. In this cohort, the threshold was <25 nmol/l. Future work should investigate whether treating vitamin D deficiency can improve postural blood pressure or if preventing vitamin D deficiency reduces the incidence of OH., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke., Methods: Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure., Results: The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke., Conclusions: Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.

Background: increasing numbers of older adults are living with frailty and its adverse consequences. We investigated relationships between diet quality or patterns and incident physical frailty in older British men and whether any associations were influenced by inflammation., Methods: prospective study of 945 men from the British Regional Heart Study aged 70-92 years with no prevalent frailty. Incident frailty was assessed by questionnaire after 3 years of follow-up. Frailty was defined as having at least three of: low grip strength, low physical activity, slow walking speed, unintentional weight loss and feeling of low energy, all based on self-report. The Healthy Diet Indicator (HDI) based on WHO dietary guidelines and the Elderly Dietary Index (EDI) based on a Mediterranean-style dietary intake were computed from questionnaire data and three dietary patterns were identified using principal components analysis: prudent, high fat/low fibre and high sugar., Results: men in the highest EDI category and those who followed a prudent diet were less likely to become frail [top vs bottom category odds ratio (OR) (95% CI) 0.49 (0.30, 0.82) and 0.53 (0.30, 0.92) respectively] after adjustment for potential confounders including BMI and prevalent cardiovascular disease. No significant association was seen for the HDI. By contrast those who had a high fat low fibre diet pattern were more likely to become frail [OR (95% CI) 2.54 (1.46, 4.40)]. These associations were not mediated by C-reactive protein (marker of inflammation)., Conclusions: the findings suggest adherence to a Mediterranean-style diet is associated with reduced risk of developing frailty in older people., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The influence of life-course socioeconomic disadvantage on oral health at older ages is not well-established. We examined the influence of socioeconomic factors in childhood, middle-age and older age on oral health at older ages, and tested conceptual life-course models (sensitive period, accumulation of risk, social mobility) to determine which best described observed associations., Methods: A representative cohort of British men aged 71-92 in 2010-12 included socioeconomic factors in childhood, middle-age and older age. Oral health assessment at 71-92 years (n = 1622) included tooth count, periodontal disease and self-rated oral health (excellent/good, fair/poor) (n = 2147). Life-course models (adjusted for age and town of residence) were compared with a saturated model using Likelihood-ratio tests., Results: Socioeconomic disadvantage in childhood, middle-age and older age was associated with complete tooth loss at 71-92 years-age and town adjusted odds ratios (95% CI) were 1.39 (1.02-1.90), 2.26 (1.70-3.01), 1.83 (1.35-2.49), respectively. Socioeconomic disadvantage in childhood and middle-age was associated with poor self-rated oral health; adjusted odds ratios (95% CI) were 1.48 (1.19-1.85) and 1.45 (1.18-1.78), respectively. A sensitive period for socioeconomic disadvantage in middle-age provided the best model fit for tooth loss, while accumulation of risk model was the strongest for poor self-rated oral health. None of the life-course models were significant for periodontal disease measures., Conclusion: Socioeconomic disadvantage in middle-age has a particularly strong influence on tooth loss in older age. Poor self-rated oral health in older age is influenced by socioeconomic disadvantage across the life-course. Addressing socioeconomic factors in middle and older ages are likely to be important for better oral health in later life.

The trajectories of physical activity (PA) from midlife into old age and their associations with established and novel cardiovascular disease (CVD) risk factors in later life remain unclear. This study examined associations between 20-year nonoccupational PA trajectories and a range of CVD biomarkers at ages 60-79 years. We used data from a sample of 3,331 men (mean baseline age = 50.2 ± 5.8 years) recruited in 1978-1980, with follow-up after 12, 16, and 20 years, reporting habitual nonoccupational PA at each wave. At the 20-year follow-up, surviving men attended a physical examination and provided a fasting blood sample. Group-based trajectory modeling was used to identify trajectories. Adjusted regression analyses examined the association between trajectory-group membership and several cardiometabolic, cardiac, and inflammatory markers at follow-up. Three distinct 20-year trajectories were identified: low/decreasing (21.3%), light/stable (51.8%), and moderate/increasing (27.0%). Compared with the low/decreasing group, membership in the light/stable and moderate/increasing trajectory groups was associated with a more favorable cardiometabolic profile and lower levels of inflammation and endothelial dysfunction. Although following a moderate-increasing PA trajectory was most favorable, more modest but sustained doses of PA into old age may be sufficient to lower CVD risk.

Background: kidney function declines in older adults and physical activity levels are low. We investigated whether higher levels of physical activity and lower levels of sedentary behaviour were associated with lower odds of low kidney function in older men., Methods: cross-sectional study of 1,352 men from the British Regional Heart Study, mean (standard deviation) age 78.5 (4.6) year. Physical activity and sedentary behaviour were measured using Actigraph GT3X accelerometers. Kidney function was measured by estimated Glomerular filtration rate (eGFR) using the chronic kidney disease-EPI creatinine-cystatin equation. Associations between physical (in)activity and kidney function were investigated using regression models., Results: higher levels of physical activity and lower levels of sedentary behaviour were associated with reduced odds ratios (ORs) for lower eGFR (<45 versus ≥45 ml/min per 1.73 m2) after adjustment for covariates. Each additional 1,000 steps, 30 min of light physical activity and 10 min of moderate/vigorous physical activity per day were associated with a lower odds (95% confidence interval (CI)) of a low eGFR; OR 0.81 (0.73, 0.91), OR 0.87 (0.78, 0.97) and OR 0.84 (0.76, 0.92), respectively. Each additional 30 min of sedentary behaviour per day was associated with a higher odds of a low eGFR (1.16 95% CI 1.06, 1.27). Associations between moderate/vigorous physical activity and lower kidney function persisted after adjustment for light physical activity or sedentary behaviour., Conclusion: physical activity is associated with kidney function in older men and could be of public health importance in this group who are at increased risk of poor kidney function and low physical activity. More evidence is needed on whether the association is causal., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Background Previous studies demonstrated that lower outdoor temperatures increase the levels of established cardiovascular disease risk factors, such as blood pressure and lipids. Whether or not low temperatures increase novel cardiovascular disease risk factors levels is not well studied. The aim was to investigate associations of outdoor temperature with a comprehensive range of established and novel cardiovascular disease risk factors in two large Northern European studies of older adults, in whom cardiovascular disease risk is increased. Design and methods Data came from the British Regional Heart Study (4252 men aged 60-79 years) and the Prospective Study of Pravastatin in the Elderly at Risk (5804 men and women aged 70-82 years). Associations between outdoor temperature and cardiovascular disease risk factors were quantified in each study and then pooled using a random effects model. Results With a 5℃ lower mean temperature, total cholesterol was 0.04 mmol/l (95% confidence interval (CI) 0.02-0.07) higher, low density lipoprotein cholesterol was 0.02 mmol/l (95% CI 0.01-0.05) higher and SBP was 1.12 mm Hg (95% CI 0.60-1.64) higher. Among novel cardiovascular disease risk factors, C-reactive protein was 3.3% (95% CI 1.0-5.6%) higher, interleukin-6 was 2.7% (95% CI 1.1-4.3%) higher, and vitamin D was 11.2% (95% CI 1.0-20.4%) lower. Conclusions Lower outdoor temperature was associated with adverse effects on cholesterol, blood pressure, circulating inflammatory markers, and vitamin D in two older populations. Public health approaches to protect the elderly against low temperatures could help in reducing the levels of several cardiovascular disease risk factors.

Background and Objective: hearing impairment is common in older adults and has been implicated in the risk of disability and mortality. We examined the association between hearing impairment and risk of incident disability and all-cause mortality., Design and Setting: prospective cohort of community-dwelling older men aged 63-85 followed up for disability over 2 years and for all-cause mortality for 10 years in the British Regional Heart Study., Methods: data were collected on self-reported hearing impairment including hearing aid use, and disability assessed as mobility limitations (problems walking/taking stairs), difficulties with activities of daily living (ADL) and instrumental ADL (IADL). Mortality data were obtained from the National Health Service register., Results: among 3,981 men, 1,074 (27%) reported hearing impairment. Compared with men with no hearing impairment, men who could hear and used a hearing aid, and men who could not hear despite a hearing aid had increased risks of IADL difficulties (age-adjusted OR 1.86, 95% CI 1.29-2.70; OR 2.74, 95% CI 1.53-4.93, respectively). The associations remained after further adjustment for covariates including social class, lifestyle factors, co-morbidities and social engagement. Associations of hearing impairment with incident mobility limitations, incident ADL difficulties and all-cause mortality were attenuated on adjustment for covariates., Conclusion: this study suggests that hearing problems in later life could increase the risk of having difficulties performing IADLs, which include more complex everyday tasks such as shopping and light housework. However, further studies are needed to determine the associations observed including the underlying pathways., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Background: Hearing and vision problems are common in older adults. We investigated the association of self-reported sensory impairment with lifestyle factors, chronic conditions, physical functioning, quality of life and social interaction., Methods: A population-based cross-sectional study of participants of the British Regional Heart Study aged 63-85 years., Results: A total of 3981 men (82% response rate) provided data. Twenty-seven per cent (n = 1074) reported hearing impairment including being able to hear with aid (n = 482), being unable to hear (no aid) (n = 424) and being unable to hear despite aid (n = 168). Three per cent (n = 124) reported vision impairment. Not being able to hear, irrespective of use of hearing aid, was associated with poor quality of life, poor social interaction and poor physical functioning. Men who could not hear despite hearing aid were more likely to report coronary heart disease (CHD) [age-adjusted odds ratios (ORs) 1.89 (95% confidence interval 1.36-2.63)]. Vision impairment was associated with symptoms of CHD including breathlessness [OR 2.06 (1.38-3.06)] and chest pain [OR 1.58 (1.07-2.35)]. Vision impairment was also associated with poor quality of life, poor social interaction and poor physical functioning., Conclusions: Sensory impairment is associated with poor physical functioning, poor health and poor social interaction in older men. Further research is warranted on pathways underlying these associations., (© The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Prior studies suggested a role for the arginine vasopressin (AVP) system in the pathogenesis of diabetes. Prospective studies on the association between copeptin (the C-terminal fragment of AVP hormone) and incident diabetes are limited., Objective: We have examined the association between plasma copeptin and the risk of incident diabetes in older men., Design: The British Regional Heart Study was a prospective study with an average of 13 years follow-up., Setting: General practices in the United Kingdom were studied., Participants: Participants were 3226 men aged 60 to 79 years with no prevalent diabetes., Outcome: We measured 253 patients with incident diabetes., Results: Copeptin was positively and significantly associated with renal dysfunction, insulin resistance (homeostasis model assessment of insulin resistance), metabolic risk factors (waist circumference, blood pressure, triglycerides, and liver function), C-reactive protein, tissue plasminogen activator, and von Willebrand factor (endothelial dysfunction) but not with plasma glucose. The risk of incident diabetes was significantly elevated only in men in the top fifth of the copeptin distribution (>6.79 pmol/L), and this risk persisted after adjustment for several diabetes risk factors including metabolic risk factors and C-reactive protein (adjusted hazard ratio in the top fifth vs the rest = 1.78 [95% confidence interval, 1.34-2.37]). Risk was markedly attenuated although it remained significant after further adjustment for homeostasis model assessment of insulin resistance and plasma glucose (adjusted hazard ratio = 1.47 [1.11-1.97]). The increased risk was seen even when the analysis was restricted to men with no chronic kidney disease or to men with no impaired fasting glucose (<6.1 mmol/L)., Conclusion: Copeptin is associated with a significantly increased risk of diabetes in older men. The association is partly mediated through lower insulin sensitivity. The findings suggest a potential role of the AVP system in diabetes.

Aims: Socioeconomic position has been linked to incident heart failure (HF), but the underlying mechanisms are unclear. We examined the association of socioeconomic measures with incident HF in older adults and examined possible underlying pathways., Methods and Results: A socially representative cohort of men aged 60-79 years in 1998-2000 from 24 British towns was followed-up for 10 years for incident HF. Adult socioeconomic position was based on a cumulative score, including occupation, education, housing tenure, pension, and amenities. Childhood socioeconomic measures included father's occupational social class and household amenities. Prevalent myocardial infarction and HF cases were excluded. Among 3836 men, 229 incident cases of HF occurred over 10 years. Heart failure risk increased with an increasing score of adverse adult socioeconomic measures (P for trend = < 0.0001). Compared with men with a score of 0, the hazard ratio for men with a score of ≥ 4 was 2.19 (95% confidence interval, CI, 1.34-3.55), which was attenuated to 1.87 (95% CI 1.12-3.11) after adjusting for systolic blood pressure, body mass index, smoking, HDL-cholesterol, diabetes, and lung function. Adjustment for left ventricular hypertrophy, atrial fibrillation, heart rate, and renal function made little difference. Further adjustment for C-reactive protein, von Willebrand Factor, N-terminal pro-brain natriuretic peptide, and plasma vitamin C also made little difference to the hazard ratio [1.89 (95% CI 1.10-3.24)]. Heart failure risk did not vary by childhood socioeconomic measures., Conclusion: Heart failure risk in older men was greater in the most deprived socioeconomic groups, which was only partly explained by established risk factors for HF. Novel risk factors contribute little to the associated risk.

Objective: It has been suggested that elevated levels of C-reactive protein (CRP) might interfere with leptin signalling and contribute to leptin resistance. Our aim was to assess whether plasma levels of CRP influence leptin resistance in humans, and our hypothesis was that CRP levels would modify the cross-sectional relationships between leptin and measures of adiposity., Design and Methods: W assessed four measures of adiposity: BMI, waist circumference, fat mass and body fat (%) in 2113 British Regional Heart Study (BRHS) men (mean (s.d.) age 69 (5) years), with replication in 760 (age 69 (6) years) European Male Ageing Study (EMAS) subjects., Results: IN BRHS subjects, leptin correlated with CRP (SPEARMAN'S R=0.22, P0.0001). Leptin and crp correlated with all four measures of adiposity (R VALUE RANGE: 0.22-0.57, all P<0.0001). Age-adjusted mean levels for adiposity measures increased in relation to leptin levels, but CRP level did not consistently influence the β-coefficients of the regression lines in a CRP-stratified analysis. In BRHS subjects, the BMI vs leptin relationship demonstrated a weak statistical interaction with CRP (P=0.04). We observed no similar interaction in EMAS subjects and no significant interactions with other measures of adiposity in BRHS or EMAS cohorts., Conclusion: We have shown that plasma CRP has little influence on the relationship between measures of adiposity and serum leptin levels in these middle-aged and elderly male European cohorts. This study provides epidemiological evidence against CRP having a significant role in causing leptin resistance.

Objective: We examined patterns in medication use for secondary prevention of cerebrovascular disease in older British men from 1999 to 2005, and investigated socio-demographic and disease-related influences on medication use., Methods: Percentage use of antiplatelet drugs, blood pressure-lowering drugs and statins use was calculated in men, aged 65-87 years in 2005, who had been diagnosed with stroke or transient ischaemic attack (TIA) from a population-based cohort based in one general practice in each of 24 British towns., Results: In 1999, most men with cerebrovascular disease received antiplatelet drugs (67%). However, a few received blood pressure-lowering drugs (50%) and statins (13%). By 2005, the use of all drug types had increased; at least half of the patients received each type of drug. However, only one-third of patients received all three medication types and combined blood pressure treatment was limited. Older age, a diagnosis of TIA rather than stroke and absence of co-existing coronary heart disease were associated with lower rates of use of specific medication categories., Conclusion: Despite improvements in secondary prevention medication use, there is scope for achieving the full potential of these medications, particularly by increasing combination blood pressure treatment and statin use and ensuring that older patients receive the benefits of prevention.

Background: The independent influence of childhood social circumstances on health in later life remains uncertain. We examined the extent to which childhood socio-economic circumstances are related to the risk of coronary heart disease (CHD) in older British men, taking account of adult social class and behavioural risk factors., Methods: A socio-economically representative sample of 5552 British men (52-74 years) with retrospective assessment of childhood socio-economic circumstances (father's occupation and childhood household amenities) who were followed up for CHD (fatal and non-fatal) for 12 years., Results: Men whose childhood social class was manual had an increased hazard ratio (HR) 1.34 (95% CI 1.11-1.63)-this effect was diminished when adjusted for adult social class and adult behavioural risk factors (cigarette smoking, alcohol, physical activity and body weight) (HR 1.19; 95% CI 0.97-1.46). Men whose family did not own a car in their childhood were at increased CHD risk even after adjustments for adult social class and behaviours (HR 1.35, 95% CI 1.04-1.75). Men with combined exposure to both childhood and adult manual social class had the highest risk of CHD (HR 1.51; 95% CI 1.19-1.91); this was substantially reduced by adjustment for adult behavioural risk factors (adjusted HR 1.28; 95% CI 0.99-1.65)., Conclusions: Less affluent socio-economic conditions in childhood may have a modest persisting influence on risk of CHD in later life.

Aims: To assess the extent to which inflammatory, procoagulant, and endothelial biomarkers modify the relationship between diminished renal function and cardiovascular mortality., Methods and Results: Prospective study of 4029 men aged 60-79 years followed up for a mean period of 6 years, during which 304 cardiovascular deaths occurred. Predicted estimated glomerular filtration rate (eGFR) was used as a measure of renal function. Reduced eGFR was associated with increased prevalence of established cardiovascular risk factors [cardiovascular disease, diabetes, hypertension, left ventricular (LV) hypertrophy, and dyslipidaemia] and higher levels of inflammatory markers [interleukin 6 (IL-6), C-reactive protein], endothelial markers [von Willebrand factor (vWF) and tissue plasminogen activator], activated coagulation markers (fibrin D-dimer), and blood viscosity. Cardiovascular mortality risk increased with decreasing levels of eGFR, particularly among men with eGFR <60 mL/min per 1.73 m(2) even after adjustment for established risk factors (adjusted RR 1.49, 95% CI 1.10, 2.03; <60 vs. > or =70 mL/min per 1.73 m(2)). The association was attenuated after further adjustment for vWF, D-dimer, and IL-6 (adjusted RR 1.34, 95% CI 0.98-1.82)., Conclusion: Mild-to-moderate renal insufficiency is associated with significantly increased cardiovascular mortality in elderly men, which is partly explained by the increased prevalence of established risk factors, markers of coagulation, endothelium, and inflammation.

Although body build is related to disability and mortality in older people, the independent contributions of adiposity and lean mass are not fully defined. The authors examined the relations of body composition (fat mass index, fat-free mass index) and adiposity (body mass index, waist circumference) to ill health and physical disability in a cross-sectional study of 4,252 British men aged 60-79 years in 1998-2000. Increased body mass index, waist circumference, and fat mass index were associated with increased prevalence of cardiovascular disease, overall ill health, and disability. Adjusted odds ratios of cardiovascular disease (top vs. bottom fifth) were 1.58 (95% confidence interval (CI): 1.23, 2.03) for fat mass index, 1.45 (95% CI: 1.14, 1.86) for body mass index, and 1.27 (95% CI: 0.99, 1.62) for waist circumference. For overall "poor/fair" health, the corresponding odds ratios were 1.71 (95% CI: 1.33, 2.21), 1.49 (95% CI: 1.17, 1.90), and 1.64 (95% CI: 1.28, 2.09) and, for mobility limitation, they were 1.56 (95% CI: 1.17, 2.06), 1.96 (95% CI: 1.48, 2.56), and 1.88 (95% CI: 1.42, 2.49). A high fat-free mass index was associated with only a decreased prevalence of respiratory problems and cancer (odds ratios=0.45 (95% CI: 0.33, 0.62) and 0.62 (95% CI: 0.42, 0.94), respectively). Body fatness, not fat-free mass, is associated with cardiovascular disease and disability in older men. Simple measures of overweight, such as body mass index and waist circumference, are good indicators of the likelihood of morbidity in older men. Prevention of weight gain with increasing age is likely to reduce morbidity and disability among older men.

Aims: To examine the associations between cigarette smoking, pipe/cigar smoking, and years since quitting smoking, and inflammatory and haemostatic markers., Methods and Results: A study in 2920 men aged 60-79 with no history of myocardial infarction, angina, stroke, or diabetes, and who were not on warfarin, from general practices in 24 British towns. After adjustment for other major cardiovascular risk factors, compared with never smokers, current cigarette smokers showed significantly higher levels of C-reactive protein (2.53 vs. 1.35 mg/L), white cell count (7.92 vs. 6.42 x 10(9)/L), and fibrinogen (3.51 vs. 3.13 g/L). They also showed higher levels of haematocrit, blood and plasma viscosity, tissue plasminogen activator antigen, and fibrin D-dimer, and lower levels of albumin. Primary pipe/cigar smokers showed levels similar to never smokers. Ex-cigarette smokers and secondary pipe/cigar smokers showed intermediate levels although secondary pipe/cigar smokers showed higher odds of having elevated white cell count and fibrinogen than ex-cigarette smokers. Most inflammatory and haemostatic levels improved within 5 years of smoking cessation but took over 20 years to revert to levels of never smokers., Conclusion: These findings suggest that activation of inflammation and haemostasis may be potential mechanisms by which cigarette and pipe/cigar smoking increase cardiovascular risk.

Aims: To examine the effect that within-person variation has on the estimated risk associations between cigarette smoking, physical inactivity, and increased body mass index (BMI) and the development of cardiovascular disease (CVD) in middle-aged British men., Methods and Results: In total, 6452 men aged 40-59 with no prior evidence of CVD were followed for major CVD events (fatal/non-fatal myocardial infarction or stroke) and all-cause mortality over 20 years; lifestyle characteristics were ascertained at regular points throughout the study. A major CVD event within the first 20 years was observed in 1194 men (18.5%). Use of baseline assessments of cigarette smoking and physical activity in analyses resulted in underestimation of the associations between average cumulative exposure to these factors and major CVD risk. After correction for within-person variation, major CVD rates were over four times higher for heavy smokers (> or =40 cigarettes/day) compared with never smokers and three times higher for physically inactive men compared with moderately active men. Major CVD risk increased by 6% for each 1 kg/m(2) increase in usual BMI. If all men had experienced the risk levels of the men who had never regularly smoked cigarettes, were moderately active, and had a BMI of < or =25 kg/m(2) (6% of the population), 66% of the observed major CVD events would have been prevented or postponed (63% before adjustment for within-person variation). Adjustment for a range of other risk factors had little effect on the results. Similar results were obtained for all-cause mortality., Conclusion: Failure to take account of within-person variation can lead to underestimation of the importance of lifestyle characteristics in determining CVD risk. Primary prevention through lifestyle modification has a great preventive potential.

Moderate alcohol consumption is associated with a decreased risk of cardiovascular disease. However, the impact of variation in alcohol intake over time on estimated risk relations has not been adequately addressed. In this study, 6,544 middle-aged British men without previous cardiovascular disease were followed for cardiovascular events and all-cause mortality over 20 years from 1978/1980 to 1998/2000. Alcohol intake was ascertained at regular points throughout the study. A total of 922 men had a major coronary event within 20 years, 352 men had a stroke, and 1,552 men died of all causes. Baseline alcohol intake displayed U-shaped relations with cardiovascular disease and all-cause mortality, with light drinkers having the lowest risks and nondrinkers and heavy drinkers having similarly high risks. However, the nature of these relations changed after adjustment for intake variation; risks associated with nondrinking were lowered, and risks associated with moderate and heavy drinking increased. Regular heavy drinkers had a 74% higher risk of a major coronary event, a 133% higher risk of stroke, and a 127% higher risk of all-cause mortality than did occasional drinkers (these estimates were 8%, 54%, and 44% before adjustment for intake variation). The findings suggest that considerable caution may be needed before any recommendations regarding acceptable limits of alcohol consumption are made.

Background: Pipe and cigar smoking are still regarded by many as less hazardous to health than cigarette smoking., Methods: Prospective study of 7735 men aged 40-59 years drawn from general practices in 24 British towns with mean follow-up of 21.8 years. The outcome measures include major coronary heart disease (CHD) and stroke events, cancer incidence, and deaths from all causes., Results: There were 1133 major CHD events and 440 stroke events, 919 new cancers and 1994 deaths from all causes in the 7121 men with no diagnosed CHD, stroke, diabetes, or cancer at screening. Compared with never smokers, pipe/cigar smokers (primary and secondary combined) showed significantly higher risk of major CHD events (relative risk [RR] = 1.69, 95% CI: 1.32, 2.14) and stroke events (RR = 1.62, 95% CI: 1.08, 2.41) and of cardiovascular, non-cardiovascular, and total mortality (RR = 1.49, 95% CI: 1.13, 1.96, RR = 1.40, 95% CI: 1.08, 1.83 and RR = 1.44, 95% CI: 1.19, 1.74, respectively), after adjustment for lifestyle and biological characteristics. They also showed a significantly higher incidence of smoking-related cancers (RR = 2.67, 95% CI: 1.70, 4.26), largely due to lung cancer (RR = 4.35, 95% CI: 2.05, 8.94). Overall, the effects in pipe/cigar smokers were intermediate between never-smokers and light cigarette smokers, although risks for lung cancer were similar to light cigarette smokers., Conclusion: Pipe and cigar smoking, whether primary or secondary, carries significant risk of smoking-related ill health.

Aim: To examine the relative contributions of early life and adult life factors to risk of cardiovascular disease (CVD) in middle-aged men using migration within Great Britain (GB)., Methods: Prospective study of 7,735 men (40-59 years) drawn from one group practice in each of 24 British towns. Zones of birth and/or examination: South of England and rest of GB (Midlands and Wales, North of England, and Scotland)., Results: There were 1,392 coronary heart disease (CHD) events and 1154 cardiovascular deaths during 21.8 years mean follow-up. Regardless of birth zone, men examined in the South showed lower risk of CHD events and CVD mortality than those examined in the rest of GB. Migrants from South to rest of GB showed a small increase in cardiovascular risk. Men born and examined in the rest of GB showed the highest adjusted risk of CHD events (RR = 1.15, 95% CI: 0.96-1.38) and CVD mortality (RR = 1.28, 95% CI: 1.04-1.57). Men born in the rest of GB who moved to the South showed adjusted risks of CHD events and CVD mortality similar to those born and examined in the South. Zone of examination was more strongly associated with CHD events and CVD mortality than zone of birth (RR = 1.23 versus 0.95 for CHD; RR = 1.26 versus 1.04 for CVD mortality). Smokers, irrespective of zone of birth or examination, showed higher risk than non-smokers., Conclusion: Factors in adult life appear to be dominant in determining cardiovascular risk in middle and older age although this does not exclude early life effects on cardiovascular risk.

Objectives: This paper examines the influence of cigarette smoking and ill health on the relationship between weight change, body weight and subsequent mortality to determine whether weight loss and leanness in middle to older age is deleterious to health., Methods: Men aged 40-59 years at screening drawn from one general practice in each of 24 British towns, who completed a questionnaire 5 years after screening (Q5) and provided full information on changes in weight and smoking status (n = 7065) were then followed up for an average of 13.8 years., Results: In all men a shallow U-shaped relationship was seen between body mass index (BMI) at Q5 and all-cause mortality rates. Weight loss and substantial weight gain (> or =10%) were associated with increased mortality rates compared to the stable weight group. The increased risk associated with weight loss was seen in long- term non-smokers (n = 4101) and recent ex-smokers (n = 722) but not in current smokers (n = 2242) after adjustment for a wide range of potential confounders. However, the increased risk was markedly attenuated after exclusion of those with ill health (relative risk [RR] = 1.16, 95% CI : 0.84-1.59 and RR = 0.79, 95% CI : 0.29-2.20 for long-term non-smokers and recent ex-smokers, respectively). Moderate weight gain (4-10%) was associated with lower risk of mortality than observed in those with stable weight but only in recent ex-smokers and in current smokers, not in long-term non-smokers. A positive association was seen between BMI at Q5 and all-cause mortality in non-smokers and this was strengthened by exclusion of men with weight loss., Conclusion: The increased risk of mortality associated with weight loss or low body weight in middle-aged and older men appears to be a direct consequence of ill health leading to weight loss and leanness. In healthy non-smoking men weight loss and leanness are not associated with increased mortality and moderate weight gain (4-10%) was neither deleterious nor beneficial.

Variability of angina symptoms over a 5-year period was examined in a prospective study, in which 7,109 British middle-aged men completed two chest pain questionnaires, Q1 (1978-1980) and Q5 (1983-1985), and were classified as having no chest pain, nonexertional chest pain, or angina (Q) (exertional chest pain) on each occasion. Within persons, there was considerable variability in response to the chest pain questions at Q1 and Q5. Angina (Q) persistence showed marked associations with previous myocardial infarction, diagnosed angina, electrocardiogram ischemia, and subsequent major ischemic heart disease events from Q5 onward. Compared with men without angina (Q), the age-adjusted hazard ratios were 1.5 (95% confidence interval (CI): 1.1, 2.2) for angina (Q) at Q1 only, 2.6 (95% CI: 2.1, 3.2) for angina (Q) at Q5 only, and 3.4 (95% CI: 2.8, 4.3) for angina (Q) on both occasions. For men without diagnosed ischemic heart disease, for whom apparent remission of angina (Q) was particularly frequent, a similar pattern of association was found between angina (Q) persistence and subsequent major events. In middle-aged men, exertional chest pain is a strong indicator of major coronary risk but frequently appears transient in the longer term. Persistently reported symptoms are associated with severe disease and a poor prognosis.

Objective: To describe the long-term outcome of different forms of symptomatic and asymptomatic ischaemic heart disease in middle-aged men., Methods: 7735 men aged 40-59, randomly selected from 24 general practices in Britain were classified into one of seven ischaemic heart disease groups according to a questionnaire and electrocardiogram (ECG): I=diagnosed myocardial infarction; II=unrecognized myocardial infarction; III= diagnosed angina; IV=angina symptoms; V=possible myocardial infarction symptoms; VI=ECG ischaemia or possible myocardial infarction; VII=no evidence of ischaemic heart disease. The association of disease group with a range of fatal and non-fatal outcomes during 15 years of follow-up was assessed., Results: At baseline 25% of men had evidence of ischaemic heart disease (groups I-VI). Risks of major ischaemic heart disease events, total and cardiovascular mortality, stroke, and major cardiovascular events tended to increase strongly from group VII to I. Diagnosed myocardial infarction was associated with a much poorer prognosis than all other groups (including unrecognized infarction) for all cardiovascular outcomes other than stroke. The relative risk associated with ischaemic heart disease at baseline declined dramatically over time. However, men with myocardial infarction who survived event-free for 10 years continued to experience a high excess risk in the subsequent 5 years, in contrast to event-free survivors of angina and other ischaemic heart disease. Adjusted to an average age of 50, the percentage of men surviving for 15 years free of a new major cardiovascular event was 44 for diagnosed myocardial infarction, 52 for unrecognized myocardial infarction, 66 for diagnosed angina, 68 for angina symptoms, 73 for possible myocardial infarction symptoms, 73 for ECG ischaemia, and 79 for no ischaemic heart disease. Comparison of outcome between prevalent and incident myocardial infarction illustrated the improved prognosis of men surviving the initial years after their event., Conclusions: Differing manifestations of prevalent ischaemic heart disease are associated with widely differing outcome, and the majority of middle-aged men in the community who have evidence of ischaemic heart disease short of myocardial infarction survive for 15 years without heart attack or stroke. The excess risk associated with myocardial infarction appears more persistent than that associated with angina and other ischaemic heart disease, remaining high even after 10 years of event-free survival.

Background: Increasing life expectancy has brought public health concern about the increase in prevalence of disability in old age. Reducing the prevalence of disability in older age requires the identification of preventable or modifiable risk factors earlier in life. We have examined the relationship between lifestyle and other potential risk factors in men aged 40-59 years at screening and locomotor disability 12-14 years later to assess whether any of these factors have direct and independent roles in influencing disability in later life., Methods: In 1978-1980, a longitudinal study of cardiovascular disease was initiated in 7735 men aged 40-59 years drawn from one general practice in each of 24 British towns. The present study concerns 5717 men, 88% of the surviving men who were available to follow-up (i.e. were registered with a GP and had an address) and who satisfactorily completed the disability section of a follow-up postal questionnaire in 1992 (Q92). The main endpoint from the questionnaire was locomotor disability based on self-reported inability in any one or more of the following: to get outdoors, walk 400 m, climb stairs, maintain balance, bend down, or straighten up., Results: In the 5717 men (mean age 63 years) who provided information on disability status, 25.0% reported locomotor disability and the majority of these men recalled a doctor-diagnosed disease of which cardiovascular disease was most strongly associated with locomotor disability. Lifestyle factors at screening (smoking, physical inactivity, obesity and heavy drinking) and manual social class were strongly and independently associated with increased odds of locomotor disability 12-14 years later. By contrast, baseline blood pressure and serum total cholesterol showed little relationship with locomotor disability. Among men with diagnosed major cardiovascular disease (stroke, myocardial infarction, angina or aortic aneurysm) those with locomotor disability showed significantly higher adverse lifestyle factors at screening than those who were able. Similarly, adverse lifestyle factors were also seen more frequently among disabled men with respiratory disease and among disabled men with other non-cardiovascular conditions than among their able counterparts., Conclusions: Smoking, obesity, physical inactivity and heavy drinking in middle age are strong predictors of locomotor disability in later life independent of the presence of diagnosed disease. Leading a healthy lifestyle improves survival and reduces the incidence of disease. It also reduces the risk of locomotor disability and increases the odds of being disability-free even in the event of developing major cardiovascular disease.

In most prospective studies involving older subjects, weight loss is associated with increased mortality. The authors examined the characteristics and health status of middle-aged men from 24 towns (the British Regional Heart Study), who reported that they had lost weight intentionally or unintentionally as they aged. Questionnaires were completed at screening (1978-1980), 5 years later, and in 1992 and 1996. This paper concerns the 4,713 men who reported their weight in 1992 and 1996 and their perceived weight change over this period. Weight loss was reported by 847 men (18%), of whom 39% stated that it was intentional. Compared with intentional weight loss, unintentional weight loss was associated with lower social class, more smoking, less obesity, and less physical activity and with the highest rates of "poor health,"long-standing disability, cancer, and respiratory diseases. The rates of recalled heart attack, stroke, diabetes, and cardiovascular hospitalization were higher than among men whose weight was stable. Men who lost weight intentionally had been more obese than those who lost weight unintentionally and had high rates of obesity-related conditions. Thus, both intentional and unintentional weight loss may follow the development of disease. These findings probably account for the lack of benefit and the increased mortality associated with weight loss observed in most large-scale prospective studies.

Background: There is considerable evidence that insulin resistance with compensatory hyperinsulinaemia is an early and modifiable defect in the pathogenesis of non-insulin dependent diabetes (NIDDM). Current data, however, are largely based on studies that have used insulin assays which cross-react with proinsulin and other insulin precursors. Using a specific assay, we have addressed the hypothesis that an elevation of serum true insulin concentration, reflecting insulin resistance, is an early event in the pathogenesis of NIDDM., Methods: We have used a prospective cohort study design in which a group of 5550 non-diabetic men aged 40-59 years, from 18 British towns, have been followed for incident cases of physician-diagnosed NIDDM for an average of period of 14.8 years (range 13.5-15 years). We have estimated the incidence of physician-diagnosed NIDDM by quintile of non-fasting serum true insulin concentration at entry into the study., Results: There were 168 cases of clinically diagnosed NIDDM among the group of 5550 men during follow-up. Mean serum insulin at entry (geometric mean and 95% range, adjusted for time of sampling) was significantly higher in men who subsequently developed NIDDM than in the rest of the cohort, 19.5 mU/l (4.3-88.2) versus 12.2 mU/l (2.7-54.0), P < 0.0001. There was a highly significant linear trend of increasing risk of NIDDM by quintile of serum insulin which was not attenuated substantially after adjustment for age and body mass index (BMI) and additional lifestyle and biological factors associated with serum insulin and risk of NIDDM. However, in men with non-fasting serum glucose > or =6.1 mmol/l at baseline (80th percentile, n = 1125, 82 cases), the risk of NIDDM, adjusted for age and BMI, was higher in the first quintile of serum insulin than in all other quintiles., Conclusion: These findings are consistent with the hypothesis that the majority of cases of adult onset NIDDM in this population are characterized by the early development of insulin resistance with compensatory true hyperinsulinaemia.

An inverse relation between adult height and risk of coronary heart disease (CHD) has been reported in many studies, but the association between adult height and stroke remains uncertain. The authors examined the relation between adult height and risk of stroke and CHD in a prospective study of 7,735 men drawn from general medical practices in 24 towns in England, Wales, and Scotland. The men were followed up for an average of 16.8 years (range, 15.5-18.0 years) between 1978 and 1995. During this period, there were 351 major stroke events (63 fatal, 288 nonfatal) and 1,093 major CHD events (465 fatal, 628 nonfatal). The mean height of the men was 173.3 cm. Total stroke risk was increased only in the men who fell into the lowest quintile of the height distribution (<167.7 cm), with little difference being seen between the other groups. When data were examined separately for fatal and nonfatal events, no relation was seen with nonfatal stroke. An apparent inverse association was seen with fatal stroke, even after adjustment for a wide range of confounding variables, but the number of deaths was small and the trend was not statistically significant (p = 0.17). By contrast, a significant inverse relation was seen between height and risk of major CHD events: Risk decreased progressively with increasing height, even after full adjustment (highest quintile vs. lowest: relative risk (RR) = 0.74, 95% confidence interval (CI) 0.59-0.91; test for trend: p < 0.001). A stronger inverse association was seen with nonfatal CHD events (RR = 0.64, 95% CI 0.49-0.84) than with fatal CHD events (RR = 0.82, 95% CI 0.60-1.11). This study confirms the finding of an inverse association between height and CHD. The inverse association seen for fatal stroke but not nonfatal stroke suggests that height may be related to specific subtypes of stroke. There are different patterns of association between height and stroke and height and CHD. If the apparent association between short stature and increased risk of fatal stroke is confirmed in other prospective studies, this would suggest that different mechanisms underlie the effects of height on stroke and CHD.

Background: To assess the association between the CD4 count and clinical diseases in a cohort of Thai patients., Methods: In all, 1902 patients who presented with human immunodeficiency virus (HIV) infection at the Chulalongkorn University Hospital in Bangkok were investigated., Results: At the time of presentation 295 (15.5%) patients had acquired immunodeficiency syndrome (AIDS) and there was a highly significant tendency for lower CD4 counts in this group (median 67/mm3) than in patients free of AIDS (median 369/mm3). A total of 757 patients had data available on follow-up and were free of AIDS at the first visit. During a median follow-up of 0.9 years, 110 developed AIDS or AIDS-related death (12.2/100 person years). Subjects with CD4 count < 200/mm3 at initial visit showed over a ninefold increase in risk of developing AIDS compared to subjects with levels > or = 500/mm3 (relative risk [RR] = 9.1; 95% CI: 5.4-16.0). The rate/100 person years was 47.1 compared with 6.0 in subjects with levels > or = 500/mm3. After adjusting for initial CD4 count, homosexual men showed over a twofold increase in risk of developing AIDS compared to heterosexuals (RR = 2.4; 95% CI: 1.6-4.4) and intravenous drug users (IVDU) showed nearly a twofold increase (RR = 1.8; 95% CI: 0.9-3.9). The increased risk in homosexual men persisted even after further adjustment for clinical stage (RR = 2.2; 95% CI: 1.3-3.7) but the increased risk in IVDU was attenuated (RR = 1.5; 95% CI: 0.7-3.2) although it remained increased albeit non-significantly. Men tended to progress faster to AIDS than women but the difference was not significant. However, the faster progression in homosexual men was seen even when compared to heterosexual men only., Conclusion: The rate of progression of AIDS according to CD4 count group at baseline in this Thai cohort is broadly comparable with Western cohorts. It appears that heterosexuals in Thailand show slower progression to AIDS than homosexual men.

Objective: To examine the prediction of major ischaemic heart disease events by questionnaire-assessed chest pain and other symptoms., Design: Population-based prospective study., Subjects: 7735 randomly selected men, aged 40-59 years at entry., Methods: Symptoms and history of diagnosed ischaemic heart disease were ascertained by administered questionnaire at baseline. Follow-up was for an average of 14.7 years, for first major ischaemic heart disease event., Results: During follow-up, 969 men had a major ischaemic heart disease event. 'Definite' angina (chest pain fulfilling all WHO criteria) and 'possible' angina (exertional chest pain without all other WHO criteria) were associated with similar ischaemic heart disease outcome, and a single combined angina category was used. In the whole cohort, the relative risks (95% CI) of a major ischaemic heart disease event were 2.03 (1.61, 2.57) for angina only, 2.13 (1.72, 2.63) for possible myocardial infarction only and 4.50 (3.57, 5.66) for angina plus possible myocardial infarction, compared to no chest pain. The relative risk for recall of an ischaemic heart disease diagnosis was 3.98 (3.36, 4.71). Only 33% of men with angina or possible myocardial infarction symptoms recalled a previous ischaemic heart disease diagnosis. In men without recall of an ischaemic heart disease diagnosis (in whom 82% of events during follow-up occurred), chest pain symptoms remained predictive of major ischaemic heart disease events with relative risks (95% CI) of 1.69 (1.27, 2.24) for angina only, 1.49 (1.12, 1.97) for possible myocardial infarction only and 2.55 (1.44, 4.53) for angina plus possible myocardial infarction. 'Other chest pain' increased risk of a major ischaemic heart disease event by 1.19 (1.01, 1.40) compared to no chest pain. Symptoms of breathlessness or calf pain on walking increased ischaemic heart disease risk in men with 'other chest pain' and in men without chest pain, but had no further effect on ischaemic heart disease risk in men with symptoms of angina or possible myocardial infarction., Conclusions: In defining angina by chest pain questionnaire, the exertional component is the crucial criterion. When using questionnaire-assessed symptoms to determine ischaemic heart disease risk, information on previous ischaemic heart disease diagnoses should be taken into account. The majority of men with angina or possible myocardial infarction symptoms do not have a diagnosis of ischaemic heart disease, but they remain at significantly increased risk of a major ischaemic heart disease event. The value of breathlessness and calf pain on walking in stratifying ischaemic heart disease risk is restricted to men with 'other chest pain' or no chest pain.

Objective: It has been suggested that mortality differences between groups in society may be greater than are indicated by social class based on occupation. We have examined the relationship between social class and mortality using home and car ownership as additional indices of socioeconomic status within social class., Design: A prospective study of a cohort of men representative of the social class distribution of middle-aged men in Great Britain., Setting: One general practice in each of 24 towns in England, Wales and Scotland., Subjects: Five years after the initial screening of 7735 men aged 40-59 years, 7262 men (94% of the original cohort) provided information on housing tenure and car ownership by completing a postal questionnaire., Main Outcome Measure: Deaths from all causes, cardiovascular, cancer and other non-cardiovascular causes during an average follow-up of 9.8 years (range 8.5-11.0 years) after the postal questionnaire., Results: During the follow-up period there were 946 deaths from all causes among the 7262 men. The lowest mortality rates for all causes, cardiovascular, cancer and other non-cardiovascular causes were seen in non-manual social classes I and II. Manual social classes III and IV+V showed a significant 40% increase in risk of death compared to social classes I+II, even after adjustment for a wide range of risk factors (relative risk [RR] = 1.4, 95% confidence interval [CI]: 1.2-1.7 and RR = 1.4, 95% CI: 1.1-1.7 respectively). Within all social class groups, those owning both home and car showed lower rates than those who owned neither, even after adjustment for a wide range of risk factors and employment status. Compared with social classes I+II owning both home and car, all those not owning home and/or car, in each social group, showed a significant approximately twofold increase in risk of death. Adjusted RR for non-manual I+II = 2.1 (95% CI: 1.5-2.9), non-manual III RR = 2.0 (95% CI: 1.3-2.9), manual III RR = 1.8 (95% CI: 1.4-2.4) and manual IV+V RR = 1.8 (95% CI: 1.3-2.5). Similar relationships were seen in all major geographical regions of Great Britain., Conclusion: Mortality differences within society are greater than indicated by social class based on occupation alone. Irrespective of social class, men with greater material assets have lower rates of mortality from all causes than men less well endowed, independent of a wide range of lifestyle and biological factors. These findings suggest that mortality differences within our society are closely related to relative wealth.

Background: To determine the risk of all cause mortality and the incidence of major coronary heart disease (CHD) events in lifelong teetotallers and in ex-drinkers compared with occasional and regular drinkers., Methods: A prospective study of middle-aged men drawn at random from one general practice in each of 24 British towns. Five years after the screening of 7735 men aged 40-59 years, 7167 provided further information on postal questionnaire enabling separation of non-drinkers into lifelong teetotallers and ex-drinkers., Results: During the follow-up period of 9.8 years after the postal questionnaire there were 929 deaths from all causes and 490 major CHD events. Ex-drinkers exhibited increased cardiovascular and non-cardiovascular mortality; lifelong teetotallers showed the lowest cardiovascular mortality but a significantly increased non-cardiovascular mortality. After adjustment for confounding factors and pre-existing disease, the two non-drinking groups did not differ significantly in all cause mortality from occasional and regular drinkers (light, moderate or heavy) but lifelong teetotallers still showed a significant increase in non-cardiovascular mortality. Adjustment considerably attenuated the risk of both cardiovascular and non-cardiovascular mortality in the ex-drinkers. In men without a diagnosis of CHD, lifelong teetotallers and ex-drinkers showed similar increased relative risk (RR) of heart attacks, with regular drinkers (combined) having a significantly decreased risk compared to occasional drinkers (RR = 0.78, 95% confidence interval [CI] : 0.64-0.96) and non-drinkers (RR = 0.69, 95% CI : 0.52-0.91). This decreased risk was small in absolute terms at around 2-3 major CHD events/1000 person-years., Conclusions: Lifelong teetotallers and ex-drinkers showed a significantly increased RR of major CHD events compared with regular drinkers, although this risk is small in absolute terms. Lifelong teetotallers have a low risk of overall cardiovascular mortality and an increased risk of non-cardiovascular mortality. Non-drinkers constitute an unsuitable reference group in alcohol-related studies; occasional or even light drinkers may be more appropriate. Overall, there is no convincing evidence that light or moderate drinking has a protective effect on total or cardiovascular mortality in these middle-aged British men.

The relation between serum potassium level and all-cause mortality was examined in a prospective study of 7,636 middle-aged British men followed for 11.5 years (1978-1991). Men being treated for hypertension had a significantly lower mean (+/- standard error) potassium level than men not in treatment (4.24 +/- 0.03 mmol/liter vs. 4.32 +/- 0.01 mmol/liter; p < 0.01). During the follow-up period of 11.5 years, after exclusion of the 374 men under antihypertensive treatment, there were 771 deaths from all causes in the remaining 7,262 men. A low potassium level (< 3.7 mmol/liter) was not associated with increased mortality. Elevated potassium levels > or = 5.2 mmol/liter were associated with a significant increase in mortality, particularly noncardiovascular deaths, even after adjustment for potentially confounding factors. However, serum potassium was strongly related to smoking, and the increased risk of mortality associated with elevated potassium was seen only among current smokers. In current smokers with raised potassium levels (> or = 5.2 mmol/liter) compared with smokers with levels under 5.2 mmol/liter, the relative risks of mortality were 1.7 (95% confidence interval (CI) 1.2-2.5) for deaths from all causes, 1.8 (95% CI 1.0-3.2) for all cancer deaths, and 2.5 (95% CI 1.1-5.6) for lung cancer deaths. In the 374 men receiving regular antihypertensive treatment, a low potassium level was not associated with excess mortality; those with raised potassium levels had excess risks for both cardiovascular and noncardiovascular deaths. The findings suggest that either raised potassium levels in association with smoking have an influence on the risk of death from noncardiovascular disease, particularly lung cancer, or a raised serum potassium level is a marker for some other risk factor associated with smoking. The prognostic and therapeutic implications of these observations warrant further exploration.

Earlier studies have not resolved the question of whether elevated circulating insulin levels are independently related to the development of coronary heart disease. Previous studies have not used a specific insulin assay and in all but a minority of studies that have addressed this issue it has not been possible to adjust for possible confounding due to high density lipoprotein (HDL) cholesterol. The authors examined the relation between serum insulin concentration and major coronary disease events (fatal and non-fatal myocardial infarction) in the British Regional Heart Study. The data are based on 5,550 men (aged 40-59 years) in 18 towns whose baseline, non-fasting serum samples were analyzed for insulin using a specific enzyme-linked immunoadsorbent assay (ELISA) method. Known diabetics were excluded. At 11.5 years of follow-up, 521 major coronary disease events had occurred, 261 fatal and 260 non-fatal. A nonlinear relation between serum insulin and coronary disease events was observed with an almost twofold increased relative risk in the 10th decile of the serum insulin distribution (> or = 33.8 mU/liter) relative to the 1st to the 9th deciles combined (age-adjusted relative risk (RR) = 1.9, 95% confidence interval (CI) 1.6-2.4). There was some attenuation of this association on cumulative adjustment for a wide range of biologic and life-style coronary disease risk factors, including HDL cholesterol, though it remained significant in the fully adjusted proportional hazards model (RR = 1.6, 95% CI 1.1-2.3). Similar associations between insulin and coronary disease events were seen in men with and without evidence of coronary disease at screening and in men with baseline serum glucose below the 80th percentile. These data are consistent with the hypothesis that a high level of serum insulin (hyperinsulinemia) is atherogenic, with a threshold effect. However, the markedly nonlinear form of the association and the attenuation in multivariate analysis strongly suggest that elevated insulin levels may only be a marker for common etiologic factors in the development of both coronary disease and non-insulin-dependent diabetes mellitus.