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Background—There is increasing interest in the predictive value of C-reactive protein (CRP) and fibrin D-dimer in the prediction of ischemic heart disease (IHD). We assessed their joint and independent associations with IHD in a large combined analysis of 2 population cohorts.Methods and Results—Men aged 49 to 66 years from the general populations of Caerphilly and Speedwell were studied between 1982 and 1988 and re-examined for new IHD events at fixed intervals of ≈105 months (Caerphilly) and 75 months (Speedwell). 3213 men had CRP and D-dimer measured at baseline and 351 (11%) had a new IHD event. Mean levels of CRP and D-dimer were significantly higher among men in whom IHD developed. The relative odds of IHD in men in the top 20% of the distribution of CRP was 2.97 (95% CI, 2.04, 4.32) and for D-dimer was 2.40 (95% CI, 1.69, 3.40); CRP and D-dimer had additive effects on risk of IHD. Multivariate analysis reduced the size of the relative odds, which remained significant for D-dimer.Conclusions—Both inflammatory and thrombogenic markers are important (and potentially additive) predictors of coronary risk.

Objective—To examine the clinical and epidemiological utility of the concepts of metabolic syndrome and insulin resistance syndrome in two prospective cohort studies of white men. Methods—Men aged 45-63 years were screened for evidence of ischaemic heart disease (IHD) between 1979 and 1982 and followed up at regular intervals thereafter. Non-fatal coronary events were validated from hospital records and fatal coronary events from death certificates. Results—Analysis of serum insulin concentrations in non-diabetic individuals measured at entry to the study showed no independent contribution to the prediction of subsequent IHD at 10 year follow up. Blood glucose concentrations, however, showed a small independent contribution in the combined cohort in the upper fifth of the distribution. Three different models of metabolic syndrome among non-diabetic individuals were defined based on tertiles, medians, and clusters. The predictive value of each model was assessed using logistic regression before and after adjustment for conventional and metabolic risk factors. After adjustment the odds were non-significant and close to unity. Conclusions—This study did not detect any complex relation among the five variables defining metabolic syndrome; the excess risk seems to be no greater than can be explained by individual effects of the defining variables in a multiple logistic model. Keywords: metabolic syndrome; insulin resistance; screening; ischaemic heart disease; epidemiology

As part of the Caerphilly and the Speedwell collaborative heart disease studies, associations between outdoor traffic noise level, risk factors for ischemic heart disease, and prevalence and incidence of ischemic heart disease were studied in two samples of 2,512 and 2,348 men, respectively, who were 45-63 y of age. Compared with the lowest noise category [Leq,6-22 h = 51-55 dB(A)], the subjects in the highest noise category [Leq,6-22 = 66-70 dB(A)] showed a slightly worse risk factor profile with respect to 9 identified endogenous risk factors. Logistic regression analysis suggested a marginal increase in risk (relative risk = 1.1) for ischemic heart disease incidence for these men based on risk factors. The prevalence of ischemic heart disease was slightly higher (relative risk = 1.2) in this noise group. The observed incidence of major ischemic heart disease within an observation period of approximately 4 y was slightly lower (relative risk = 0.8) for men in the highest noise group.

As part of two large heart surveys, associations between traffic noise exposure and cardiovascular risk factors were studied. The Caerphilly sample (small town, total sample) consisted of 2512 men aged 45 to 59 years and the Speedwell sample (suburb of a major city, random sample) of 2030 men of same age group. Both studies have a prospective design; cross-sectional results are presented here. Acoustic measurements were carried out in both areas. Among the possible risk factors for ischaemic heart disease studied were blood pressure, blood coagulation, blood lipids and other biochemical factors. Statistically significant noise effects were detected for systolic blood pressure, total cholesterol, HDL cholesterol, total triglycerides, blood viscosity, platelet count and glucose level, although not all of these were consistent with noise being a risk factor for heart disease. In a subsample, the additional influence of work noise as determined by noise dosimetry was studied in 255 men, taking the use of ear protection into account. The associations between traffic noise and risk factors were more pronounced in men who also were exposed to high work noise levels.

Several studies have suggested that men with raised plasma triglycerides (TGs) in combination with adverse levels of other lipids may be at special risk of subsequent ischemic heart disease (IHD). We examined the independent and combined effects of plasma lipids at 10 years of follow-up. We measured fasting TGs, total cholesterol (TC), and high density lipoprotein cholesterol (HDLC) in 4362 men (aged 45 to 63 years) from 2 study populations and reexamined them at intervals during a 10-year follow-up. Major IHD events (death from IHD, clinical myocardial infarction, or ECG-defined myocardial infarction) were recorded. Five hundred thirty-three major IHD events occurred. All 3 lipids were strongly and independently predictive of IHD after 10 years of follow-up. Subjects were then divided into 27 groups (ie, 3 3 ) by the tertiles of TGs, TC, and HDLC. The number of events observed in each group was compared with that predicted by a logistic regression model, which included terms for the 3 lipids (without interactions) and potential confounding variables. The incidence of IHD was 22.6% in the group with the lipid risk factor combination with the highest expected risk (high TGs, high TC, and low HDLC) and 4.7% in the group with the lowest expected risk ( P

BACKGROUND The relative importance of HDL2 and HDL3 cholesterol as risk factors for ischemic heart disease (IHD) is still uncertain. Their associations with the incidence of IHD in the Caerphilly and Speedwell prospective studies are described. METHODS AND RESULTS The two studies have a common core protocol and are based on a total of 4860 middle-aged men from the general population. The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell: 251 major IHD events had occurred. Lipid levels were measured on fasting samples. Different laboratories were used by the two studies. Each laboratory used ultracentrifugation to separate HDL2 and HDL3. Both subfractions were inversely associated with risk of IHD. Standardized relative odds of developing major IHD were 0.95 (95% confidence interval [CI], 0.80 to 1.14) for HDL2 cholesterol and 0.83 (95% CI, 0.68 to 1.00) for HDL3 cholesterol in Caerphilly and 0.76 (95% CI, 0.57 to 1.01) for HDL2 and 0.64 (95% CI, 0.49 to 0.83) for HDL3 in Speedwell. The association with incident IHD appeared to be stronger for HDL3 in both areas. No linear combination of the two subfractions was a better predictor of IHD than total HDL cholesterol alone. CONCLUSIONS In British men, both HDL2 and HDL3 cholesterol are inversely associated with the incidence of IHD. However, the prediction of the risk of IHD from total HDL cholesterol alone could not be improved upon by measurement of the two HDL subfractions. The relative value of the two HDL subfractions as predictors of risk is still unresolved. The uncertainty may be due, at least in part, to problems associated with their measurement.

OBJECTIVE--To examine the associations between air temperature and risk factors for ischaemic heart disease. METHOD--Data on risk factors are available from up to 2036 men in the Caerphilly Prospective Heart Disease Study. Daily temperatures were obtained from the Meteorological Office. Relations between these were examined by regression. RESULTS--The coldest month of the year has a mean temperature that is 16 degrees C lower than that in the warmest month. A fall in temperature of this magnitude is associated with higher blood pressures (by 3-5 mm Hg) and a lower concentration of high density lipoprotein cholesterol (by 0.08 mmol/l). The most important effects however, seem to be on the haemostatic system. Fibrinogen is 0.34 g/l higher in the coldest month than in the warmest (p < 0.001) and alpha 2 macroglobulin, a protein that inhibits fibrinolysis, is also raised. Platelet count is increased by 30% of a standard deviation and the sensitivity of platelets in whole blood to adenosine diphosphate is increased by cold. CONCLUSIONS--These effects on haemostasis, together with the effect on blood pressure, could explain a large part of the increase in ischaemic heart disease in the winter but are unlikely to explain much of the difference in mortality within different areas of England and Wales.

Objective—To assess the roles of plasma triglyceride and high density lipoprotein (HDL) cholesterol concentrations in predicting ischaemic heart disease. Design—Two prospective cohort studies with common core protocols. Setting and participants—Both cohorts are 100% samples of middle aged men. In Caerphilly the 2512 men were living within a defined area. In Speedwell the 2348 men were registered with local general practitioners. Main outcome measures—Fasting blood samples were taken at initial examination and plasma lipid concentrations were measured. Major ischaemic heart disease events were assessed from hospital notes, death certificates, and electrocardiograms. Results—At first follow up, after an average of 5·1 years in Caerphilly and 3·2 years in Speedwell, 251 major ischaemic heart disease events had occurred. Men with triglyceride concentrations in the top 20% of the distribution had a relative odds value for ischaemic heart disease of 2·3 (95% confidence interval (95% CI) 1·3 to 4·1) compared with men in the bottom 20%, after adjusting for both plasma total and HDL cholesterol, and non-lipid risk factors. Men in the lowest 20% of the distribution of HDL cholesterol concentration had a relative odds value of 1·7 (95% CI 1·0 to 2·8) compared with the top 20%, after adjustment was made for total cholesterol and triglyceride concentrations, and non-lipid risk factors. These relations were not caused by β blockers, which were being taken by 5% of the men. Conclusions—Plasma triglyceride concentration predicts major ischaemic events after allowance is made for total and HDL cholesterol concentrations and other risk factors. In these populations, triglyceride is a more important predictor than total cholesterol concentration.

BACKGROUND Recent studies have suggested that hemostatic factors and white blood cell count are predictive of ischemic heart disease (IHD). The relations of fibrinogen, viscosity, and white blood cell count to the incidence of IHD in the Caerphilly and Speedwell prospective studies are described. METHODS AND RESULTS The two studies have a common core protocol and are based on a combined cohort of 4,860 middle-aged men from the general population. The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell; 251 major IHD events had occurred. Age-adjusted relative odds of IHD for men in the top 20% of the distribution compared with the bottom 20% were 4.1 (95% confidence interval, 2.6-6.5) for fibrinogen, 4.5 (95% confidence interval, 2.8-7.4) for viscosity, and 3.2 (95% confidence interval, 2.0-4.9) for white blood cell count. Associations with IHD were similar in men who had never smoked, exsmokers, and current smokers, and the results suggest that at least part of the effect of smoking on IHD is mediated through fibrinogen, viscosity, and white blood cell count. Multivariate analysis shows that white blood cell count is an independent risk factor for IHD as is either fibrinogen or viscosity, or possibly both. Jointly, these three variables significantly improve the fit of a logistic regression model containing all the main conventional risk factors. Further, a model including age, smoking habits, fibrinogen, viscosity, and white blood cell count predicts IHD as well as one in which the three hemostatic/rheological variables are replaced by total cholesterol, diastolic pressure, and body mass index. CONCLUSION Jointly, fibrinogen, viscosity, and white blood cell count are important risk factors for IHD.

A survey of titres of diphtheria and tetanus antitoxins and of antibodies to polioviruses in the sera of 291 schoolchildren aged 15, 11, and 7 years showed that high immunisation rates can evoke protective concentrations of tetanus antitoxin in 98% of children and protective levels of the antibodies to diphtheria and all three types of poliomyelitis in 85% of children. Reinforcing immunisation at school entry appeared to be necessary to maintain adequate titres of diphtheria antitoxin in children up to 15 years of age, not essential to maintain adequate titres of tetanus antitoxin, and to have little effect on the titres of antibodies to poliomyelitis.

Certain features of the relationship between 11 measurements of weekly temperature and the number of deaths from ischaemic heart disease (IHD) within age groups in Greater London between 1970 and 1974 are described. Firstly, the correlation coefficients between age-specific deaths from IHD and each of the temperature variables are of a similar order. Secondly, in contrast, the linear regression coefficients between deaths and temperature are more variable and depend upon the particular measurement of temperature chosen. Thirdly, the proportional changes in the number of deaths with the temperature variables are similar within specific age groups; consequently it is suggested that deaths from IHD and temperature may be directly related.

Data from two community studies on men from South Wales and the west of England suggest that the effects of smoking on the haemostatic system remain for many years after giving up. Long term correlations between several variables, including plasma fibrinogen and white cell count, and the length of time after giving up were seen in ex-smokers. Dose response relations were apparent in current smokers in terms of the white cell count and two haematological variables, the packed and mean cell volumes. These long term correlations probably reflect the toxicity of other agents in tobacco smoke besides nicotine and carbon monoxide, which act only in the short term. Identification of these agents may further our understanding of the mechanism by which cigarette smoking is associated with atherosclerotic disease.

Mortality from ischaemic heart disease remains high in the United Kingdom, and the present report describes the prevalence of the various epidemiological manifestations of the disease in two recent community studies with a common core protocol, each containing samples of over 2000 men, carried out in South Wales (Caerphilly) and the West of England (Speedwell, Bristol). The prevalence of electrocardiographic evidence of ischaemia was similar in the two communities--8.7% of men aged 45-49 years rising to 18.6% in men aged 55-59 years in the samples from South Wales, and 8.0% and 17.2% respectively in the Bristol population. The overall prevalence of angina was 7.7% in Caerphilly and 7.8% in Speedwell in men aged 45-59 years, but symptoms of severe chest pain were more commonly reported in South Wales than in Speedwell (10.1% compared with 6.3%). The data, however, suggested that the overall prevalence of ischaemic heart disease was very similar in the two areas. The prevalence of ischaemic heart disease was compared with that found in other population studies carried out in the United Kingdom and was higher than that found when employed men only were studied. There were substantial differences in mortality between the two areas; possible reasons for this are differences in community or medical services, smoking habit, or unemployment rates.

In epidemiological studies the diagnosis of a past history of myocardial infarction is made from the answer to a single question: "Have you ever had a severe pain across the front of your chest lasting for half an hour or more?" Two additional questions, which form an optional part of the London School of Hygiene and Tropical Medicine chest pain questionnaire, were used in two large community studies, with other information to determine the likely accuracy of the diagnosis ("Did you see a doctor about this pain?" If so, "What did he say it was?") The prevalence of possible myocardial infarction from the use of the single question was significantly higher among men from South Wales than among men from Speedwell, Bristol (10.1% and 6.9% respectively); in contrast, positive responses to the additional questions reduced the prevalence in the two populations to 5.8% and 4.9% respectively. These latter figures are very similar to those of self-reported coronary thrombosis in the two populations. Among subjects with positive responses to the additional questions the prevalence of ECG ischaemia was about 50%; in contrast, the prevalence of ECG ischaemia among those positive only to the severe chest pain question was very similar to that among those with no history of chest pain (12%). Preliminary mortality data show a similar classification of level of risk. These findings indicate that the false positive error rate for possible myocardial infarction could be significantly reduced by the use of two additional questions which form an optional part of the London School of Hygiene chest pain questionnaire but are rarely used. However, the present findings relate to populations with uniform levels of adequately accessible medical care; comparisons between populations with different levels of medical care will require cautious interpretation.

Baker I A (Bristol and Weston Health Authority, 10 Marlborough St Bristol BS1 3NP, UK), Sweetnam P M, Yarnell J W G, Bainton 0 and Elwood P C Haemostatic and other risk factors for ischaemic heart disease and social class: evidence from the Caerphilly and Speedwell studies. International Journal ot Epidemiology1988,17: 759-765. There are marked associations between social class and mortality from ischaemic heart disease (IHD). Using data from the Caerphilly and Speedwell Collaborative Heart Disease Studies the relationships between a number of known risk factors for IHD and social class are explored. The overall conclusions are that lipids and obesity are unlikely to play any part in explaining sodal differences in ischaemic heart disease. Blood pressure, particularly stystolic pressure, could be involved but the two data sets are inconsistent and associations are only shown in Speedwell. There are marked differences in the haemostatic related variables in the various social classes and the pattern of these is similar in Caerphilly and Speedwell. It is possible therefore that the class pattern of IHD is generated, in part at least by differences in haemostatic mechanisms. These differences in haemostatic function are almost entirely due to the large social class differences in smoking habit It is possible therefore that the class differences in IHD result from differences in smoking habit

A total population survey of serum lipoprotein concentrations was undertaken in an urban community in Port-of-Spain, Trinidad, and the results compared with rural survey on the same island and a study of healthy adults in Bristol, England. Lipoproteins were separated with identical techniques and lipid determinations made in a common laboratory. In Trinidad, response rates for men and women were 93 and 88% respectively in the urban survey, and 89% in the smaller rural study. Mean concentration of HDL cholesterol was significantly lower and LDL cholesterol significantly higher in urban men than rural men. No urban-rural differences were found in women. In urban men under 55 years, HDL and LDL cholesterol concentrations were similar in Port-of-Spain and Bristol while VLDL triglyceride was relatively high in Trinidad. Distinct ethnic differences in lipoprotein concentrations were found in Trinidad. Indian men and women tended to have a low HDL cholesterol relative to other ethnic groups, while African men and women were characterized by relatively low concentrations of LDL cholesterol and VLDL triglyceride. The reduction in HDL cholesterol of Indian men appeared to be due mainly to a relatively low HDL3 concentration. The results are consistent with reported regional, sex and ethnic differences in CHD incidence in Trinidad, and accord with statistics which show cardiovascular disease to have emerged as the major cause of death in this community.

Specific antibodies against lysosomal membranes were prepared by using techniques previously described (Louvard, D., H. Reggio, and G. Warren, 1982, J. Cell Biol., 92:92-107) for obtaining organelle-specific antibodies. The purified antibodies stained an acidic vacuolar compartment as shown by double-labeling experiments with acridine orange and indirect immunofluorescence. Characterization of the antibodies by immunoreplica methods revealed one major protein of approximately 100,000 mol wt. The antibodies cross-reacted with purified H+,K+ ATPase from pig gastric mucosa, the enzyme responsible for HCl secretion, but not with ATPases transporting other ions. They may therefore recognize a component of the proton pump involved in the acidification of lysosomes. As was expected, secondary lysosomes contained immunoreactive antigen, as determined by the fine-structural localization of reaction product for peroxidase or immunogold probes in several cell types. The antigen was also found in vacuoles containing phagocytosed bacteria in macrophages so it is present in at least some of the compartments of an endocytic pathway. In liver, the antigen was present in small amounts on the plasma membrane and in large amounts in some coated vesicles (near the sinusoidal surface of hepatocytes), putative endosomes, two cisternae on the cis side of the Golgi complex, adjacent vesicles and vacuoles, and pericanalicular dense bodies. In summary, the antigen seems to be present in those compartments that have recently been demonstrated to be acidified by an ATP-driven pump.

A three year longitudinal study of psychotropic drug prescribing in one inner city general practice showed that there was a greater use of such drugs among women and elderly men and women. Repeat prescriptions without consultation accounted for 44% of prescriptions written. We think that any attempt to reduce the volume of prescriptions for psychotropic drugs should take into account the prescribing habits and attitudes of doctors as well as the problems and needs of patients.

We report on the pattern of use of benoxaprofen (Opren) in a single group practice for a period which included the complete clinical life of the drug. One hundred and seventy-two patients of the 6495 practice patients had been prescribed benoxaprofen, but 55% had only a small exposure (less than 20 g). Recorded adverse reactions, of which none was serious, appeared in 25 patients. Most were taking benoxaprofen for osteoarthritis (53%) or non-specific musculoskeletal pain (39.9%). The issue of a prescription was not recorded in 19.6% of cases and 88% were on additional drugs. Greater precision in record-keeping is required to avoid problems similar to the experience with benoxaprofen.

In a weighted random sample of the specially enumerated population of a South Wales industrial town, examined by cholecystography for gallstones, the overall prevalence rates were 6.2 per cent for men 45 to 69 years of age and 12.1 per cent for women of the same ages. Contrary to our expectation there was no marked increase in prevalence with age in either sex. Symptoms of dyspepsia said to be suggestive of gallstones were found with approximately equal frequency in those with and without gallbladder disease.

Summary— Previous workers have debated the value of maximal perineal stimulation (MPS) in the treatment of urinary incontinence in women. In order to assess the efficacy of this simple technique a prospective study was undertaken on 107 consecutive incontinent women. They included those with stress, urge and mixed patterns of leakage. Patients were placed at random into treatment and control groups. All underwent clinical assessment, urodynamic study and a single session of pelvic floor re-education with measurement of pelvic contraction and cystoscopy. Those in the treatment group were given MPS using monophasic square wave pulses while under anaesthesia. Independent follow-up assessment was performed 6 and 12 weeks after treatment. Of the 107 patients 94 completed the trial. Forty-five were treated and 49 acted as controls. Analysis of age, parity, duration and severity of incontinence showed that randomisation had produced comparable results between the treated and the control groups. Sixty per cent of the treatment group and 66% of the control group had significant symptomatic improvement. Pelvic floor function was re-assessed, using a perineometer, and found to be more efficient, having increased equally in both groups. Both groups of women improved irrespective of the pattern of incontinence. This suggests that MPS does not contribute to the management and that a single physiotherapy session with skilful counselling can produce beneficial results in women with all types of urinary incontinence.

In surveys of 4860 middle-aged men in Caerphilly (South Wales) and Speedwell (Bristol) alcohol consumption has been related to high density lipoprotein (HDL) cholesterol and its major subfractions, HDL2 and HDL3, measured in a single fasting blood sample. The results confirm that high density lipoprotein cholesterol concentration increases as the amount of alcohol regularly consumed increases. The relationship appears to be linear and is independent of age, smoking habit, body mass index, low density lipoprotein cholesterol and plasma total triglyceride. This rise in HDL cholesterol is not mediated through either HDL2 cholesterol or HDL3 cholesterol alone. Both subclasses increase significantly and by similar amounts with increasing alcohol intake.

A longitudinal study has been set up to examine the incidence of ischaemic heart disease and its associations with serum lipoproteins including high density lipoprotein cholesterol and its subfractions, certain haemostatic factors, and other "risk' factors. We report here on our pilot study findings. Cross-sectional data were available on 283 men and 68 women aged 45 to 64 representing 85% of the available population randomly selected from the lists of 16 general practitioners. Reproducibility of the measurements of total serum cholesterol, triglyceride, and low density lipoprotein cholesterol was acceptable. The reproducibility of some of the other serum lipid fractions, for example high density lipoprotein cholesterol, was less good, in part because of the small range of the values found for these components. Univariate associations of physical and behavioural characteristics and serum lipoproteins of men and women, with and without ischaemic heart disease, disclosed small and statistically nonsignificant differences except for levels of blood pressure. In particular, there was no significant difference in mean levels of serum high density lipoprotein cholesterol between men with ischaemic heart disease (0.91 mmol/l) and men without it (0.94 mmol/l). In examining our data for the determinants of serum high density lipoprotein cholesterol using a linear multiple regression model, sex, serum high density lipoprotein cholesterol, and very low density lipoprotein triglyceride were the major factors, each individually explaining about 7% of the variance of serum high density lipoprotein cholesterol levels. In addition, alcohol intake and obesity each explained a further 2% of the variance. The experience of the pilot study has led to modifications in the collection of blood samples and the subsequent estimation of lipid fractions.

Approximately 200 children aged 8, 12 and 16 years with poliovirus neutralising antibody titres of less than 1/45 to at least one type were given a single dose of oral or inactivated polio vaccine. Almost all children given IPV responded with high levels of neutralising antibody to all 3 types. The response to the oral vaccine was less dramatic. The relationship between pre-existing antibody and the further response and the implications for susceptibility to reinfection will be discussed.

Cardiovascular surveys were conducted in areas with different water supplies. In two areas with hard water 243 men were seen and in three areas with soft water 357 men were seen. There was no evidence of an important difference between the two areas in blood pressure, serum cholesterol, blood sugar, or packed cell volume. A variety of measurements were made on an E.C.G. The P-R interval was significantly longer in the men in the hard water area, and a 40-complex trace showed ventricular extrasystoles in a significantly higher proportion of these men than in those in the soft water area.

The effect of azathioprine in patients with active Crohn's disease has been evaluated in a double-blind cross-over trial. Fifteen patients were treated with both azathioprine and placebo: only two improved while on azathioprine, six got worse, and in seven there was no change. The drug seemed to be the cause of deterioration in two of the patients. Although the drug may be of some value in a few patients, it should be used with caution and only when other measures have failed.

Fifty-one female patients, incontinent of urine, were asked to compared two different combinations of pants and pads used in the ambulatory management of their incontinence. They were offered the Kanga pant with a Kanga pad and the Sandra pant with a Bambi pad. Each patient tried both pants and pads and thus comparisons could be made on a within-patient basis. Both systems kept a similar proportion of patients dry during the day and night. In terms of comfort, however, the Kanga pant was quite clearly preferred to the Sandra. The Bambi pad was rated more highly than the Kanga pad, although the difference between the two pads was not so pronounced as that between pants.