Goya Wannamethee

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

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

Adiponectin and Coronary Heart Disease A Prospective Study and Meta-Analysis

Background— There is uncertainty about the association between circulating concentrations of adiponectin and coronary heart disease (CHD) risk. We report new data from a prospective study in the context of a meta-analysis of previously published prospective studies. Methods and Results— We measured baseline adiponectin levels in stored serum samples of 589 men with fatal CHD or nonfatal myocardial infarction and in 1231 controls nested within a prospective study of 5661 men (aged 40 to 59 years) recruited during 1978–1980, as well as in paired samples obtained 4 years apart from 221 of these participants. Baseline adiponectin concentrations correlated (P<0.0001) positively with HDL cholesterol (r=0.33) and inversely with C-reactive protein (r=−0.11) and BMI (r=−0.21), and the year-to-year consistency of adiponectin values was comparable to those of blood pressure and total cholesterol levels. No significant difference between median adiponectin levels at baseline was observed between cases and controls (10.2 versus 10.8 &mgr;g/mL; P=0.5), despite the fact that body mass index, HDL, and C-reactive protein were all significant predictors of events in this cohort. The odds ratio for CHD was 0.89 (95% CI, 0.67 to 1.18) in a comparison of men in the top third of adiponectin concentrations compared with those in the bottom third, similar to a meta-analysis (including the present study) of 7 prospective studies involving a total of 1318 CHD cases (odds ratio, 0.84 [95% CI, 0.70 to 1.01]). Conclusions— In contrast to the strong associations previously reported between adiponectin levels and risk of type 2 diabetes, any association with CHD risk is comparatively moderate and requires further investigation.

Physical activity and ischaemic heart disease in middle-aged British men.

OBJECTIVE--To assess the relation between reported physical activity and the risk of heart attacks in middle aged British men. DESIGN--Prospective study of middle-aged men followed for a period of eight years (The British Regional Heart Study). SETTING--One general practice in each of 24 British towns. PARTICIPANTS--7735 men aged 40-59 years at initial examination. END POINT--Heart attacks (non-fatal and fatal). MEASUREMENTS AND MAIN RESULTS--During the follow up period of eight years 488 men suffered at least one major heart attack. A physical activity score used was developed and validated against heart rate and lung function (FEV1) in men without evidence of ischaemic heart disease. Risk of heart attack decreased significantly with increasing physical activity; the groups reporting moderate and moderately vigorous activity experienced less than half the rate seen in inactive men. The benefits of physical activity were seen most consistently in men without preexisting ischaemic heart disease and up to levels of moderately vigorous activity. Vigorously active men had higher rates of heart attack than men with moderate or moderately vigorous activity. The relation between physical activity and the risk of heart attack seemed to be independent of other cardiovascular risk factors. Men with symptomatic ischaemic heart disease showed a reduction in the rate of heart attack at light or moderate levels of physical activity, beyond which the risk of heart attack increased. Men with asymptomatic ischaemic heart disease showed an increasing risk of heart attack with increasing levels of physical activity, but with a progressive decrease in case fatality. Overall, men who engaged in vigorous (sporting) activity of any frequency had significantly lower rates of heart attack than men who reported no sporting activity. However, when all men reporting regular sporting activity at least once a month were excluded from analysis, there remained a strong inverse relation between physical activity and the risk of heart attack in men without pre-existing ischaemic heart disease. CONCLUSION--This study suggests that the overall level of physical activity is an important independent protective factor in ischaemic heart disease and that vigorous (sporting) exercise, although beneficial in its own right, is not essential in order to obtain such an effect.

Physical activity and stroke in British middle aged men.

OBJECTIVES--To assess the relation between physical activity and stroke and to determine the overall benefit of physical activity for all major cardiovascular events. DESIGN--Prospective study of a cohort of men followed up for 9.5 years. SETTING--General practices in 24 towns in England, Wales, and Scotland (British regional heart study). SUBJECTS--7735 men aged 40-59 at screening, selected at random from one general practice in each of 24 towns. MAIN OUTCOME MEASURES--Fatal and non-fatal strokes and heart attacks. RESULTS--128 major strokes (fatal and non-fatal) occurred. Physical activity was inversely associated with risk of stroke independent of coronary risk factors, heavy drinking, and pre-existing ischaemic heart disease or stroke (relative risk 1.0 for inactivity, 0.6 moderate activity, and 0.3 vigorous activity; test for trend p = 0.008). The association remained after excluding men reporting regular sporting (vigorous) activity. However, vigorous physical activity was associated with a marginally significant increased risk of heart attack compared with moderate or moderately vigorous activity in men with no pre-existing ischaemic heart disease or stroke (relative risk 1.6%; 95% confidence interval 0.96 to 2.8). In men with symptomatic ischaemic heart disease or stroke those doing moderately vigorous or vigorous activity had a risk of heart attack slightly higher than that in inactive men (relative risk = 1.6; 0.8 to 3.3). CONCLUSIONS--Moderate physical activity significantly reduces the risk of stroke and heart attacks in men both with and without pre-existing ischaemic heart disease. More vigorous activity did not confer any further protection. Moderate activity, such as frequent walking and recreational activity or weekly sporting activity, should be encouraged without restriction.

Risk Factors for Sudden Cardiac Death in Middle-Aged British Men

BACKGROUND Risk factors specific to sudden cardiac death (SCD), ie, death within 1 hour after onset of symptoms, have been poorly identified, although recent findings from the present study incriminate heavy drinking and elevated heart rate. This paper examines the relations between a wide range of established and potential risk factors for ischemic heart disease (IHD) and SCD to identify independent risk factors for SCD and factors that might particularly or specifically relate to SCD. METHODS AND RESULTS We present a prospective study of a cohort that was drawn from general practices in 24 British towns of 7735 middle-aged men who were followed up for 8 years. During 8 years of follow-up, the men experienced 488 major IHD events (nonfatal and fatal), of which 117 (24%) were classified as SCD. Age, preexisting IHD, arrhythmia, systolic blood pressure, blood cholesterol, elevated heart rate (> or = 90 beats per minute), physical activity (all, P < .05), and, to a lesser extent, smoking (P = .06), HDL cholesterol (P < .07), and elevated hematocrit (> or = 46%, P < .09) emerged as independent risk factors for SCD after adjustment for a wide range of factors. Diabetes was not found to be associated with SCD, and forced expiratory volume in 1 second, body mass index, white blood cell count, and antihypertensive drugs were not associated with risk of SCD after adjustment. When examined in relation to non-sudden IHD deaths and nonfatal myocardial infarction, elevated heart rate, heavy drinking, and arrhythmia emerged as factors that appear to be specific or particular to SCD. These three factors and age and blood cholesterol were associated with an increased risk of SCD in men both with and without preexisting IHD. Physical activity, systolic blood pressure, and current smoking were associated with SCD only in men without preexisting IHD. HDL cholesterol and hematocrit were strong predictors of SCD only in men with preexisting IHD. CONCLUSIONS Three risk factors appear to be specific or particular to the risk of SCD, and these and other risk factors operate differently in patients with versus those without preexisting IHD. These findings have implications for the causes and prevention of SCD.

Alcohol and sudden cardiac death

Objective—To assess the relation between alcohol intake and sudden cardiac death—ie, death within one hour of the onset of symptoms. Design—Prospective study of a cohort of men followed up for eight years. Setting—General practices in 24 towns in England, Wales, and Scotland. Subjects—7735 men aged 40–59 at screening who were selected at randon from one general practice in each of 24 towns. Main outcome measure—All deaths from ischaemic heart disease with particular reference to those that were sudden (death within one hour of the onset of symptoms). Results—During the follow up period of eight years there were 217 deaths from ischaemic heart disease of which 117 (54%) were classified as sudden. Although heavy drinkers (more than six drinks daily) did not show a high incidence rate of fatal heart attack, they showed the highest incidence rate of sudden cardiac death. This was seen in both manual and non-manual workers and was most clearly seen in older (50–59) men. Death from ischaemic heart disease was more likely to be sudden in heavy drinkers than in other drinking groups; this phenomenon was seen irrespective of the presence or degree of pre-existing ischaemic heart disease. The positive association between heavy drinking and the incidence of sudden death was most apparent in men without pre-existing ischaemic heart disease, with heavy drinkers showing an increase of >60% compared with occasional or light drinkers. After adjustment for age, social class, and smoking, heavy drinkers free of pre-existing ischaemic heart disease had a marginally significantly higher incidence rates of sudden death than other drinkers combined (relative risk 2·00, 95% confidence interval 0·98 to 4·8). Additional adjustment for systolic blood pressure reduced the risk to 1·7. Conclusions—This study suggests that heavy drinking is associated with an increased risk of sudden death. Studies that do not take pre-existing ischaemic heart disease into account are likely to underestimate the adverse effects of heavy drinking on the incidence of sudden death because the effects are not as evident in men with pre-existing ischaemic heart disease.

Heart rate, ischaemic heart disease, and sudden cardiac death in middle-aged British men.

OBJECTIVE--To examine the relation between resting heart rate and new major ischaemic heart disease events in middle aged men with and without pre-existing ischaemic heart disease. DESIGN--Prospective study of a cohort of men with eight years follow up for cardiovascular morbidity and mortality for all men. SETTING--General practices in 24 British towns (the British Regional Heart study). SUBJECTS--7735 men aged 40-59 years drawn at random from the age-sex registers of one general practice in each town. MAIN OUTCOME MEASURES--Major ischaemic heart disease events such as sudden cardiac death, other deaths attributed to ischaemic heart disease, and non-fatal myocardial infarction. RESULTS--During the follow up period of eight years, 488 men had a major ischaemic heart disease event (217 fatal and 271 non-fatal). Of these, 117 were classified as sudden cardiac death (death within one hour of the start of symptoms). The relation between heart rate and risk of all major ischaemic heart disease events, ischaemic heart disease deaths, and sudden cardiac death was examined separately in men with and without pre-existing ischaemic heart disease. In men with no evidence of ischaemic heart disease, there was a strong positive association between resting heart rate and age adjusted rates of all major ischaemic heart disease events (fatal and non-fatal), ischaemic heart disease deaths, and sudden cardiac death. This association remained significant even after adjustment for age, systolic blood pressure, blood cholesterol, smoking, social class, heavy drinking, and physical activity, with particularly high risk in those with heart rate > or = 90 beats/min. The increased risk seen in those with increased heart rate was largely due to a significantly increased risk of sudden cardiac death, which was five times higher than in those with heart rate < 60 beats/min. The effect of heart rate on sudden cardiac death was present irrespective of blood pressure or smoking state. In men with pre-existing ischaemic heart disease a positive association was seen between raised heart rate and risk of all major ischaemic heart disease events, ischaemic heart disease death, and sudden cardiac death, but the effect was less noticeable than in men without pre-existing ischaemic heart disease. CONCLUSION--In this study of middle aged British men increased heart rate > or = 90 beats/min) is a risk factor for fatal ischaemic heart disease events but particularly for sudden cardiac death. The effect is not dependent on the presence of other established coronary risk factors and is most clearly seen in men free of pre-existing ischaemic heart disease at initial examination.

Leptin and coronary heart disease: prospective study and systematic review.

OBJECTIVES This study sought to better determine the link between leptin and coronary heart disease (CHD). BACKGROUND Circulating leptin is considered a risk factor for CHD but larger studies are needed. METHODS Leptin levels were measured in 550 men with fatal CHD or nonfatal myocardial infarction and in 1,184 controls nested within a prospective study of 5,661 British men and set in context with a meta-analysis. RESULTS Baseline leptin correlated with body mass index (BMI), blood pressure, total cholesterol, triglyceride, and inflammatory markers; correlations persisted after BMI adjustment. The within-person consistency of leptin values over 4 years (correlation coefficient: 0.79; 95% confidence interval [CI]: 0.73 to 0.83) was higher than those of some established cardiovascular risk factors. In a comparison of individuals in the top third with those in the bottom third of baseline leptin, the age- and town-adjusted odds ratio for CHD was 1.25 (95% CI: 0.96 to 1.62), decreasing to 0.98 (95% CI: 0.72 to 1.34) after adjustment for BMI. A systematic review identified 7 prospective reports with heterogeneous findings (I(2) = 60%, 13% to 82%). The combined adjusted risk ratio across all studies was 1.44 (95% CI: 0.95 to 2.16) in a comparison of extreme thirds of leptin levels. The inconsistency between studies was partially explained by sample size, with combined estimates from studies involving >100 CHD cases (1.28, 95% CI: 0.80 to 2.04) being somewhat weaker than those from smaller studies (1.81, 95% CI: 0.76 to 4.31). CONCLUSIONS Previous studies appear to have overestimated associations of leptin and CHD risk. Our results suggest a moderate association that is largely dependent on BMI.

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

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

Observer bias in blood pressure studies

Observer variation in blood pressure measurement following training with standard techniques has been investigated in a study of 7735 middle-aged men. The initial training produced consistent results between observers, but there were progressive deteriorations in the ensuing months. Subsequent re-training led to marked though inconsistent reductions in variation, but within 1 or 2 months, observers reverted back to an individual level of bias. The magnitude of observer variation is in line with the few other published accounts, and is sufficient to have important implications for group comparisons, clinical trials, and the clinical care of individual patients. Four methods of reducing observer variation are considered: regular re-training, self-measurement and ambulatory monitoring, automatic sphygmomanometers, and adjustment in the analysis. The adjustment procedure used in the British Regional Heart Study is described. Regular and frequent re-training with monitoring of performance, or the use of automatic machines are presently considered the two most practical methods of reducing observer variation.