Mild hyponatremia, hypernatremia and incident cardiovascular disease and mortality in older men: A population-based cohort study.

AIM: To examine the association between serum sodium concentration and incident major cardiovascular disease (CVD) outcomes and total mortality in older men. METHODS AND RESULTS: A prospective study of 3099 men aged 60-79 years without a history of cardiovascular disease followed up for an average 11 years during which there were 528 major CVD events (fatal coronary heart disease [CHD] and non-fatal MI, stroke and CVD death) and 873 total deaths. A U shaped relationship was seen between serum sodium concentration and major CVD events and mortality. Hyponatremia (<136 mEq/L) and low sodium within the normal range (136-138 mEq/L) showed significantly increased risk of major CVD events and total mortality compared to men within the upper normal range (139-143 mEq/L) after adjustment for a wide range of confounders and traditional risk factors [adjusted HRs 1.55 (1.13,2.12) and 1.40 (1.14,1.72) for major CVD events respectively and 1.30 (1.02,1.66) and 1.30 (1.11,1.53) respectively for total mortality]. Hyponatremia was associated with inflammation, NT-proBNP, low muscle mass and alkaline phosphatase; these factors contributed to the increased total mortality associated with hyponatremia but did not explain the increased risk of CVD events associated with hyponatremia or low normal sodium concentration. Hypernatremia (≥145 mEq/L) was associated with significantly increased risk of CVD events and mortality due to CVD causes. CONCLUSION: Mild hyponatremia even within the normal sodium range and hypernatremia are both associated with increased total mortality and major CVD events in older men without CVD which is not explained by known adverse CV risk factors.

Circulating inflammatory and hemostatic biomarkers are associated with risk of myocardial infarction and coronary death, but not angina pectoris, in older men.

AIMS: The extent to which hemostatic and inflammatory biomarkers are related to angina pectoris as compared with myocardial infarction (MI) remains uncertain. We examined the relationship between a wide range of inflammatory and hemostatic biomarkers, including markers of activated coagulation, fibrinolysis and endothelial dysfunction and viscosity, with incident myocardial infarction (MI) or coronary heart disease (CHD) death and incident angina pectoris uncomplicated by MI or CHD death in older men. METHODS: A prospective study of 3217 men aged 60-79 years with no baseline CHD (angina or MI) and who were not on warfarin, followed up for 7 years during which there were 198 MI/CHD death cases and 220 incident uncomplicated angina cases. RESULTS: Inflammatory biomarkers [C-reactive protein (CRP), interleukin-6, fibrinogen], plasma viscosity and hemostatic biomarkers [von Willebrand factor (VWF) and fibrin D-dimer] were associated with a significant increased risk of MI/CHD death but not with uncomplicated angina even after adjustment for age and conventional risk factors. Adjustment for CRP attenuated the relationships between VWF, fibrin D-dimer and plasma viscosity with MI/CHD death. Comparisons of differing associations with risk of MI/CHD deaths and uncomplicated angina were significant for the inflammatory markers (P < 0.05) and marginally significant for fibrin D-dimer (P = 0.05). In contrast, established risk factors including blood pressure and high-density lipoprotein (HDL)-cholesterol were associated with both MI/CHD death and uncomplicated angina. CONCLUSION: Circulating biomarkers of inflammation and hemostasis are associated with incident MI/CHD death but not incident angina uncomplicated by MI or CHD death in older men.

The value of gamma-glutamyltransferase in cardiovascular risk prediction in men without diagnosed cardiovascular disease or diabetes.

AIMS: We have examined the relationship between gamma-glutamyltransferase (GGT) and major coronary heart disease (CHD) and stroke events and cardiovascular mortality in men free of cardiovascular disease (CVD). METHODS: A prospective study of 6997 men aged 40-59 with no history of CVD (CHD or stroke) or diabetes drawn from general practices in 24 British towns and followed up for 24 years. RESULTS: GGT was significantly and positively associated with increased risk of fatal (but not non-fatal CHD events), major stroke events and total CVD mortality after adjustment for established CVD risk factors. Risk of fatal CHD and CVD mortality was only elevated in the top quarter (22IU/L); risk of stroke tended to increase with increasing GGT. The adjusted relative risks (Q4 vs. Q1) were 1.43 (1.09,1.84) for fatal CHD events, 1.56 (1.20,2.04) for stroke incidence and 1.40 (1.16,1.70) for CVD mortality. When stratified by age groups stronger associations were seen between GGT and CVD mortality in the younger men (<55 years) (p=0.01 for interaction). GGT significantly predicted CVD outcomes especially in those at low and medium CHD risk based on Framingham risk score (FRS). CONCLUSION: Elevated GGT is associated with significantly increased risk of stroke, fatal CHD events and CVD mortality independent of established CVD risk factors and may be a useful additional marker for long-term CVD risk.

The relations of body composition and adiposity measures to ill health and physical disability in elderly men.

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.

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

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

Alcohol intake in middle age and risk of cardiovascular disease and mortality: accounting for intake variation over time.

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.

Cardiovascular disease incidence and mortality in older men with diabetes and in men with coronary heart disease.

OBJECTIVE: To examine the relation of diabetes and coronary heart disease (CHD; myocardial infarction (MI) or angina) to the incidence of major CHD and stroke events and total mortality. METHODS: Prospective study of 5934 men aged 52-74 years followed up for 10 years. The men were divided into five groups according to their diabetes and CHD status. RESULTS: During the follow up there were 662 major CHD events, 305 major stroke events, and 1357 deaths from all causes (637 cardiovascular disease (CVD) deaths, 417 CHD deaths). Men with diabetes had significantly increased cardiovascular and total mortality risk compared with non-diabetic men with no CHD but lower risk than men with prior MI only. The adjusted relative risk for CHD deaths was 2.82 (95% confidence interval (CI) 1.85 to 4.28) in men with diabetes only, 2.12 (95% CI 1.53 to 2.93) in men with angina only, 3.91 (95% CI 3.07 to 4.99) in men with MI, and 8.93 (95% CI 6.13 to 12.99) in men with both diabetes and CHD. Case fatality among men with diabetes only was similar to those with prior MI only. CHD and CVD mortality increased with increasing duration of diabetes with risk eventually approaching that of patients with MI without diabetes. CONCLUSION: Men with diabetes only have a CVD risk intermediate between men with angina and men with prior MI. Their absolute risk is high and the prognosis for diabetic patients who develop CHD is extremely poor.

Insulin resistance, haemostatic and inflammatory markers and coronary heart disease risk factors in Type 2 diabetic men with and without coronary heart disease.

AIMS/HYPOTHESIS: We have examined markers of haemostasis and inflammation in men with diabetes, coronary heart disease (CHD) or both, and assessed their associations with insulin resistance in men with Type 2 diabetes. METHODS: The study was carried out in 4066 British men aged 60 to 79 years who were not on warfarin or insulin, of whom there were 426 men with prevalent Type 2 diabetes and 842 with prevalent CHD. RESULTS: Men with Type 2 diabetes were more likely to have multiple risk factors and higher levels of haemostatic and inflammatory markers than men without, irrespective of CHD status. Compared with men with CHD only, men with diabetes only showed increased levels of tissue plasminogen activator antigen, increased plasma and blood viscosity, and increased levels of coagulation factors VII, VIII and IX. They also had dyslipidaemia. In men with diabetes, increased insulin resistance (homeostasis model assessment, HOMA) was associated with increased levels of haemostatic markers and dyslipidaemia. The prevalence of CHD increased significantly with increasing tertiles of HOMA (adjusted odds ratio 1.32 [95% CI: 0.72-2.42] in the second, and 1.70 [95% CI: 0.92-3.44] in the third tertile; p=0.04 for trend). CONCLUSIONS/INTERPRETATION: Increased insulin resistance among men with Type 2 diabetes is associated with increased prevalence of CHD and of activated haemostasis and dyslipidaemia. Reducing insulin resistance in men with diabetes may reduce their tendency to develop thrombosis and hence CHD risk.

North-south gradients in Britain for stroke and CHD: are they explained by the same factors?

BACKGROUND AND PURPOSE: The geographic variation in CHD and stroke within Great Britain is well known. We aimed to quantify these variations and to determine the contribution of established risk factors. METHODS: This prospective study consisted of 7735 men 40 to 59 years of age in 24 British towns who were followed up for 20 years from screening in 1978 to 1980. We compared age-adjusted incidences of major stroke and CHD events in southern England and the rest of Britain before and after adjustment for established cardiovascular risk factors. RESULTS: At least 1 episode of stroke occurred in 467 men (3.54 per 1000 person-years, age standardized) and of CHD in 1299 men (10.05 per 1000 person-years). Event rates varied between towns, from 2.00 to 5.45 per 1000 person-years for stroke and from 6.16 to 12.21 per 1000 person-years for CHD. Incidence for both diseases was highest in Scottish towns and lowest in southern English towns ("north-south gradient"). The hazard ratio for stroke in the rest of Britain compared with southern England was 1.44 (95% confidence interval [CI], 1.16 to 1.78); for CHD, it was 1.32 (95% CI, 1.14 to 1.53). After adjustment for baseline systolic blood pressure, smoking status, physical activity, social class, and height, the hazard ratio was 1.24 (95% CI, 1.00 to 1.54) for stroke and 1.17 (95% CI, 1.02 to 1.35) for CHD. CONCLUSIONS: Similar north-south gradients were observed for major stroke and major CHD events. The magnitude of these gradients was considerably diminished when individual risk variables were taken into account.

Pipe and cigar smoking and major cardiovascular events, cancer incidence and all-cause mortality in middle-aged British men.

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.

Alcohol consumption and the incidence of type II diabetes.

BACKGROUND: This study examines the relation between alcohol and type II diabetes and the possible mediating effects of HDL-cholesterol and serum insulin. METHODS: Prospective study of 5221 men aged 40-59 years with no history of coronary heart disease, diabetes, or stroke drawn from general practices in 18 British towns. RESULTS: During the mean follow up of 16.8 years there were 198 incident cases of type II diabetes. Occasional drinkers were the reference group. A non-linear relation was seen between alcohol intake and age adjusted risk of diabetes, with risk lowest in light and moderate drinkers and highest in heavy drinkers (quadratic trend p=0.03). Further adjustment for body mass index decreased risk in heavy drinkers. After additional adjustment for physical activity, smoking, and (undiagnosed) pre-existing coronary heart disease, only moderate drinkers showed significantly lower risk than occasional drinkers (RR=0.66 95% CI 0.44 to 0.99). Alcohol intake was inversely associated with serum insulin and positively associated with HDL-cholesterol. Adjustment for these factors reduced the "protective" effect in moderate drinkers (adjusted RR=0.73 95% CI 0.48 to 1.10) but the quadratic trend remained significant (p=0.02). CONCLUSION: There is a non-linear relation between alcohol intake and the risk of type II diabetes. Serum insulin and HDL-cholesterol explained a small amount (20%) of the reduction in risk of type II diabetes associated with moderate drinking. The adverse effect of heavy drinking seemed to be partially mediated through its effect on body weight.

Non-attendance at re-examination 20 years after screening in the British Regional Heart Study.

BACKGROUND: Maintenance of high participation rates in longitudinal studies is critical to their validity because of the possibility of bias associated with non-participation, which may differ between studies. This paper examines factors associated with participation status over time, by comparing the characteristics of non-attenders and attenders at a 20 year follow-up examination in a cardiovascular cohort study with an initial participation rate of 78 percent. METHODS: A baseline examination was carried out between 1978 and 1980 and subjects have been followed up through regular reviews of general practice records, postal questionnaires, and a clinical re-examination of survivors in 1998-2000. Data obtained by questionnaire in 1996 (Q96) and at baseline examination have been used to compare the characteristics of these recent non-attenders and attenders who remain in the cohort for further follow-up. RESULTS: The non-attendance rate of available survivors at re-examination was 23 per cent (n = 1313). Rates of non-attendance were highest in Scotland and lowest in Southern England. Non-attenders were older than attenders, more likely to smoke, and reported more disabling conditions and greater use of multiple medications at Q96, but recalled similar rates of diagnosed coronary heart disease. Marked differences in social factors were identified. Total mortality rates within 1 year of re-examination were over three times higher amongst non-attenders than attenders. CONCLUSIONS: Non-attendance is related to health status, risk factor status and social circumstances and may affect some estimates of disease prevalence, but does not appearto have a major impact on the estimated prevalence of coronary heart disease. Information collected on non-attenders in longitudinal studies helps to estimate, adjust and minimize these effects.

Taking up regular drinking in middle age: effect on major coronary heart disease events and mortality.

AIM: To examine effects of taking up regular drinking by middle aged non-drinkers and occasional drinkers on major coronary heart disease events and total mortality. METHODS: A prospective study of 7735 men from general practices in 24 British towns screened in 1978-80 at age 40-59 years (Q1). Five years after screening, 7157 men then aged 45-64 completed postal questionnaires (Q5) on changes in alcohol intake. RESULTS: In 6503 men without diagnosed coronary heart disease, there were 874 major coronary heart disease events and 1613 total deaths during 16.8 years of follow up after Q5. With stable occasional drinkers as baseline, men who continued to drink regularly had a significantly lower risk of major coronary heart disease events, coronary heart disease mortality, and overall cardiovascular mortality, but a slightly increased risk of non-cardiovascular mortality. New regular drinkers (89% light), even after adjustment for their many advantageous characteristics, showed a lower risk of major coronary heart disease events than stable occasional drinkers (relative risk (RR) = 0.70; 95% confidence interval (CI) 0.48 to 1.03; p = 0.07). New drinkers showed no reduction in coronary heart disease or cardiovascular mortality and experienced an increase in risk of non-cardiovascular mortality (RR = 1.40; 95% CI 0.99 to 1.97; p = 0.06). In 654 men with diagnosed coronary heart disease, new drinkers experienced no mortality benefit compared with stable occasional drinkers. CONCLUSIONS: Middle aged new regular drinkers experienced lower risk of major coronary heart disease events than stable occasional drinkers or non-drinkers, but had increased risk of non-cardiovascular mortality and total mortality. These findings provide little support for encouraging older men who do not drink or who only drink occasionally to take up regular drinking, whether or not they have coronary heart disease.

Physical activity and risk of cancer in middle-aged men.

A prospective study was carried out to examine the relationship between physical activity and incidence of cancers in 7588 men aged 40-59 years with full data on physical activity and without cancer at screening. Physical activity at screening was classified as none/occasional, light, moderate, moderately-vigorous or vigorous. Cancer incidence data were obtained from death certificates, the national Cancer Registration Scheme and self-reporting on follow-up questionnaires of doctor-diagnosed cancer. Cancer (excluding skin cancers) developed in 969 men during mean follow-up of 18.8 years. After adjustment for age, smoking, body mass index, alcohol intake and social class, the risk of total cancers was significantly reduced only in men reporting moderately-vigorous or vigorous activity; no benefit seen at lesser levels. Sporting activity was essential to achieve significant benefit and was associated with a significant dose-response reduction in risk of prostate cancer and upper digestive and stomach cancer. Sporting (vigorous) activity was associated with a significant increase in bladder cancer. No association was seen with colo-rectal cancer. Non-sporting recreational activity showed no association with cancer. Physical activity in middle-aged men is associated with reduced risk of total cancers, prostate cancer, upper digestive and stomach cancer. Moderately-vigorous or vigorous levels involving sporting activities are required to achieve such benefit.

Is the prevalence of coronary heart disease falling in British men?

OBJECTIVE: To assess whether long term trends over time in acute coronary heart disease (CHD) event rates have influenced the burden of prevalent CHD in British men. DESIGN: Longitudinal cohort study. PARTICIPANTS: 7735 men, aged 40-59 at entry (1978-80), selected from 24 British towns. METHODS: The prevalences of current angina symptoms and history of diagnosed CHD were ascertained by questionnaire in 1978-80, 1983-85, 1992, and 1996. New major CHD events (fatal and non-fatal) were ascertained throughout the study from National Health Service central registers and general practice record reviews. Age adjusted trends in CHD prevalence were compared with trends in major CHD event rates. RESULTS: From 1978-1996 there was a clear decline in the prevalence of current angina symptoms: the age adjusted annual percentage change in odds was -1.8% (95% confidence interval (CI) -2.8% to -0.8%). However, there was no evidence of a trend in the prevalence of history of diagnosed CHD (annual change in odds 0.1%, 95% CI -1.0% to 1.2%). Over the same period, the CHD mortality rate fell substantially (annual change -4.1%, 95% CI -6.5% to -1.6%); rates of non-fatal myocardial infarction, all major CHD events, and first major CHD event fell by -1.7% (95% CI -3.9% to 0.5%), -2.5% (95% CI -4.1% to -0.8%), and -2.4% (95% CI% -4.3 to -0.4%), respectively. CONCLUSIONS: These results suggest that middle aged British men are less likely to experience symptoms of angina than in previous decades but are just as likely to have a history of diagnosed CHD. Despite falling rates of new major events and falling symptom prevalence, the need for secondary prevention among middle aged men with established CHD is as great as ever.