A cardiovascular disease policy model: part 2-preparing for economic evaluation and to assess health inequalities.

OBJECTIVES: This is the second of the two papers introducing a cardiovascular disease (CVD) policy model. The first paper described the structure and statistical underpinning of the state-transition model, demonstrating how life expectancy estimates are generated for individuals defined by ASSIGN risk factors. This second paper describes how the model is prepared to undertake economic evaluation. DESIGN: To generate quality-adjusted life expectancy (QALE), the Scottish Health Survey was used to estimate background morbidity (health utilities) and the impact of CVD events (utility decrements). The SF-6D algorithm generated utilities and decrements were modelled using ordinary least squares (OLS). To generate lifetime hospital costs, the Scottish Heart Health Extended Cohort (SHHEC) was linked to the Scottish morbidity and death records (SMR) to cost each continuous inpatient stay (CIS). OLS and restricted cubic splines estimated annual costs before and after each of the first four events. A Kaplan-Meier sample average (KMSA) estimator was then used to weight expected health-related quality of life and costs by the probability of survival. RESULTS: The policy model predicts the change in QALE and lifetime hospital costs as a result of an intervention(s) modifying risk factors. Cost-effectiveness analysis and a full uncertainty analysis can be undertaken, including probabilistic sensitivity analysis. Notably, the impacts according to socioeconomic deprivation status can be made. CONCLUSIONS: The policy model can conduct cost-effectiveness analysis and decision analysis to inform approaches to primary prevention, including individually targeted and population interventions, and to assess impacts on health inequalities.

A cardiovascular disease policy model that predicts life expectancy taking into account socioeconomic deprivation.

OBJECTIVES: A policy model is a model that can evaluate the effectiveness and cost-effectiveness of interventions and inform policy decisions. In this study, we introduce a cardiovascular disease (CVD) policy model which can be used to model remaining life expectancy including a measure of socioeconomic deprivation as an independent risk factor for CVD. DESIGN: A state transition model was developed using the Scottish Heart Health Extended Cohort (SHHEC) linked to Scottish morbidity and death records. Individuals start in a CVD-free state and can transit to three CVD event states plus a non-CVD death state. Individuals who have a non-fatal first event are then followed up until death. Taking a competing risk approach, the cause-specific hazards of a first event are modelled using parametric survival analysis. Survival following a first non-fatal event is also modelled parametrically. We assessed discrimination, validation and calibration of our model. RESULTS: Our model achieved a good level of discrimination in each component (c-statistics for men (women)-non-fatal coronary heart disease (CHD): 0.70 (0.74), non-fatal cerebrovascular disease (CBVD): 0.73 (0.76), fatal CVD: 0.77 (0.80), fatal non-CVD: 0.74 (0.72), survival after non-fatal CHD: 0.68 (0.67) and survival after non-fatal CBVD: 0.65 (0.66)). In general, our model predictions were comparable with observed event rates for a Scottish randomised statin trial population which has an overlapping follow-up period with SHHEC. After applying a calibration factor, our predictions of life expectancy closely match those published in recent national life tables. CONCLUSIONS: Our model can be used to estimate the impact of primary prevention interventions on life expectancy and can assess the impact of interventions on inequalities.

Effect of social deprivation on mortality and the duration of hospital stay after a stroke.

BACKGROUND: We aim to assess whether social deprivation independently predicts case fatality after a stroke patient has been admitted to hospital, and to assess whether social deprivation affected duration of hospital stay. METHODS: Cohort study in a tertiary teaching hospital included consecutive patients admitted to hospital within 48 h of their stroke between 1988 and 1994. Outcome measures were case fatality at 1 year and length of hospital stay. The socioeconomic category was derived from the postcode sector of residence for the patients (Carstairs index). Cause of death was determined by data linkage to the Registrar General data for Scotland. RESULTS: 2,042 stroke patients were included. A significant age difference existed between the deprivation categories (76.0 +/- 10.9 years in the affluent cohort vs. 71.4 +/- 10.7 years in the deprived cohort). Smoking was more common in the deprived group. ECG findings and neurological score on admission were similar between the groups. No difference existed between groups for length of hospital stay (p = 0.793), and in the proportions remaining alive at 1 year (p = 0.416). When entered into a multivariate Cox regression analysis, the deprivation categories did not predict mortality. Age, sex, Philadelphia Geriatric Center Instrumental Activities of Daily Living (IADL) Scale Score, Orgogozo neurological score on admission, and ECG abnormalities were the significant predictors. CONCLUSIONS: Stroke patients living in more socially deprived areas had their strokes at an earlier age but were not at a greater risk of dying or longer hospital stay once they had been admitted to hospital.

By neglecting deprivation, cardiovascular risk scoring will exacerbate social gradients in disease.

OBJECTIVE: To examine whether the efficiency and equity of cardiovascular risk scores that identify patients at high risk for preventive interventions are compromised by omitting social deprivation, which contributes to risk. DESIGN: Cohort study. SETTING: The SHHEC (Scottish heart health extended cohort) study of random sample risk factor surveys across 25 districts of Scotland in 1984-87 and North Glasgow in 1989, 1992, and 1995. PARTICIPANTS: 6419 men and 6618 women aged 30-74, free of cardiovascular disease at baseline, followed up with permission for mortality and morbidity to March 1997. Participants were allocated to population fifths of the Scottish index of multiple deprivation (SIMD) and their observed coronary risk was compared with that expected from the Framingham score for all coronary heart disease. RESULTS: The Framingham score overestimated risk overall and in each SIMD fifth. It seriously underestimated the variation in risk with deprivation. The relative risk of observed 10 year coronary risk (sexes combined) analysed across population fifths had a steep gradient, from least to most deprived, of 1.00, 1.81, 1.98, 2.22, and 2.57. Expected risk, calculated from baseline risk factor values and the Framingham score, had one quarter of that gradient, with relative risks of 1.00, 1.17, 1.19, 1.28, and 1.36. CONCLUSION: Cardiovascular risk estimated by the Framingham and related scores is misleading in guiding treatment decisions among people at different levels of social deprivation. Such scores foster relative undertreatment of the socially deprived, exacerbating the social gradients in disease, which national policies seek to minimise. Debate and action are needed to correct this anomaly.

Pre-hospital coronary care and coronary fatality in the Belfast and Glasgow MONICA populations.

BACKGROUND: The aim of this study was to describe and compare coronary event case fatality and care pathways in two defined populations with access to different models of pre-hospital care provision. METHODS: Secondary analysis of MONItoring of Trends and Determinants in CArdiovascular Disease (MONICA) population coronary event registers (1988, 1989, 1990, 1992 and 1993). RESULTS: Case fatality at 28 days following an acute coronary event was 6.5% greater in the Glasgow MONICA Project (GMP) population (46.7%) than in the Belfast MONICA Project (BMP) population (40.2%). Pre-hospital case fatality was 33.9% in the GMP population and 28.3% in the BMP population. These differences could not be fully explained by mobile coronary care unit (MCCU) responses in the BMP area. Initial care was provided in hospital for 28.3% of the BMP events and only 7.7% of the GMP events. Additional data collected by the Belfast and Glasgow MONICA investigators support a large difference between the median delay to main medical care in the BMP events (120 min) and the median delay to ward admission in the GMP area (220 min) at this time. CONCLUSIONS: Our findings suggest that the delay between coronary event onset and access to specialist coronary care was the most likely critical difference, irrespective of hospital-based MCCU provision in the BMP area. An established 'culture of early intervention' in Belfast may have been an important factor. As a large proportion of coronary event fatalities continue to occur outside hospital, there is a need to strengthen the evidence base underpinning the provision of appropriate skilled care and treatment at the earliest possible opportunity.

Trends and social factors in blood pressure control in Scottish MONICA surveys 1986-1995: the rule of halves revisited.

Time trends and social factors in detection, treatment and control of hypertension in the community were examined in four independent Scottish MONICA cross-sectional surveys in 1986, 1989, 1992 and 1995. Residents aged 25-64 years were recruited randomly from general practice lists in north Glasgow, Scotland with stratification by sex and 10-year age groups. A total of 1262 participated in the first survey, 1397 in the second, 1516 in the third and 1836 in the fourth. Differences and trends in proportions of hypertension undetected, detected but untreated, treated but uncontrolled and controlled across the four surveys were tested by chi(2), and the associations of the poor control of hypertension with social factors were estimated by multivariate logistic regression model to derive odds ratios. Using the cut point of >/=160/95 mmHg, proportion of hypertension undetected across the four surveys was 56.3, 44.6, 32.0 and 38.2%, and of treated controlled hypertension was 15.2, 26.4, 32.0 and 32.8% (both trends P<0.001). Multivariate analysis showed that poor control of hypertension was not related to social deprivation, but significantly related to being male, young, of low body mass index and heavy alcohol drinking. Undetected hypertension was significantly related to full-time employment, and untreated hypertension to high social class and possibly education level. These findings suggest that in this part of Scotland the management of hypertension has improved, so the 'rule of halves' no longer applies. Control of blood pressure is not positively associated with social deprivation, but people at a high risk of poor control of hypertension should be targeted.

Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project.

AIMS: The SCORE project was initiated to develop a risk scoring system for use in the clinical management of cardiovascular risk in European clinical practice. METHODS AND RESULTS: The project assembled a pool of datasets from 12 European cohort studies, mainly carried out in general population settings. There were 20,5178 persons (88,080 women and 11,7098 men) representing 2.7 million person years of follow-up. There were 7934 cardiovascular deaths, of which 5652 were deaths from coronary heart disease. Ten-year risk of fatal cardiovascular disease was calculated using a Weibull model in which age was used as a measure of exposure time to risk rather than as a risk factor. Separate estimation equations were calculated for coronary heart disease and for non-coronary cardiovascular disease. These were calculated for high-risk and low-risk regions of Europe. Two parallel estimation models were developed, one based on total cholesterol and the other on total cholesterol/HDL cholesterol ratio. The risk estimations are displayed graphically in simple risk charts. Predictive value of the risk charts was examined by applying them to persons aged 45-64; areas under ROC curves ranged from 0.71 to 0.84. CONCLUSIONS: The SCORE risk estimation system offers direct estimation of total fatal cardiovascular risk in a format suited to the constraints of clinical practice.

Measurement of passive smoking in adults: self-reported questionnaire or serum cotinine?

BACKGROUND: Low to moderate agreement between self-reported exposure to environmental tobacco smoke (ETS) and serum cotinine levels in non-smokers questions the accuracy of the measurement of ETS exposure. We examined the relationship of serum cotinine to different self-reported ETS questionnaires in a large community-based study. METHODS: Subjects were derived from four Scottish MONICA surveys. Agreement between self-reported ETS (yes/no) and serum cotinine levels (> 0, 0) in non-smokers was tested by K, and the difference in cotinine levels among self-reported ETS exposure by ANOVA and the relationship by linear regression. RESULTS: None of the values for K was > 0.24 for any ETS questionnaire. In non-smokers with serum cotinine > 0, cotinine levels increased with increasing ETS exposures. In the first and second surveys with the questionnaire of ETS exposure in the last 3 days, standardised coefficients were 0.28-0.39, while in the third and fourth surveys with the questionnaire of a total exposure to ETS at work, at home and in other places the standardised coefficients were 0.19-0.36, with the questionnaire of ETS daily exposure hours, 0.23-0.36. The relationship between self-reported ETS and cotinine levels varied with the questionnaires, and with the time of day of the blood sample collection. In current smokers, cotinine levels were significantly related to both the number of cigarettes smoked daily (the coefficients were 0.13-0.41) and time elapsed since the last cigarette (-0.24 to -0.40). CONCLUSION: The findings raise the question of whether it is ideal to take only serum cotinine as an index of ETS exposure in adults, because of time delays between ETS exposure and blood collection, and suggest the combined use of appropriately worded self-reported questionnaires and cotinine levels to estimate ETS exposure.

Serological markers of Chlamydia pneumoniae infection in men and women and subsequent coronary events; the Scottish Heart Health Study Cohort.

AIMS: To investigate the relationship between serum markers of Chlamydia pneumoniae infection and subsequent coronary events. METHODS AND RESULTS: In a nested case-control study, based on the Scottish Heart Health Study cohort, we estimated IgG, IgA and IgM antibodies to C. pneumoniae, and circulating immune complexes containing C. pneumoniae antigen in baseline serum samples from 217 cases experiencing a subsequent coronary event during follow-up (mean 7.5 years) and from their matched controls. In men, the proportion of specimens positive for IgG, IgA and IgM antibodies showed no case-control differences (80% vs 80%, 57% vs 53% and 3% vs 3%, respectively). The odds ratio for a coronary event was 1.00 (95% confidence interval 0.59-1.69) for the presence of IgG antibodies to C. pneumoniae; 1.21 (0.76-1.92) for IgA and 0.75 (0.17-3.35) for IgM. Similar results were seen in women. The proportion of specimens with circulating immune complexes with C. pneumoniae antigen also showed no case-control differences (12% vs 12%, both sexes combined) with an odds ratio of 1.00 (0.57-1.76). CONCLUSION: Prior infection with C. pneumoniae, as estimated by these markers, does not appear to be a risk factor for subsequent coronary heart disease.

Environmental tobacco smoke and lung function in employees who never smoked: the Scottish MONICA study.

OBJECTIVES: To investigate the relation between lung function in employees and exposure to environmental tobacco smoke (ETS) at work and elsewhere. METHODS: Never smokers in employment (301) were identified from the fourth Scottish MONICA survey. They completed a self administered health record, which included details of exposure to ETS, and attended a survey clinic for physical and lung function measurements, and for venepuncture for estimation of serum cotinine. Differences in lung function in groups exposed to ETS were tested by analysis of variance (ANOVA), the exposure-response relation by a linear regression model, and a case-control analysis undertaken with a logistic regression model. RESULTS: Both men and women showed effects on forced expiratory volume in the first second (FEV(1)) and forced vital capacity (FVC) from exposure to ETS-higher exposure going with poorer lung function. This was found at work, and in total exposure estimated from ETS at work, at home, and at other places. Linear regression showed an exposure-response relation, significant for ETS at work, total exposure, and exposure time/day, but not at home or elsewhere. Compared with those not exposed to ETS at work, those who were exposed a lot had a 254 ml (95% confidence interval (95% CI) 84 to 420) reduction in FEV(1), and a 273 ml (60 to 480) reduction in FVC after adjusting for confounders. Although lung function was not significantly associated with serum cotinine in all the data, a significant inverse relation between cotinine concentration and FVC occurred in men who had had blood collected in the morning. Case-control analysis also showed a significant exposure-response relation between ETS, mainly at work, and lung function. A higher exposure measured both by self report and serum cotinine went with lower lung function. CONCLUSION: The exposure-response relation shows a reduction in pulmonary function of workers associated with passive smoking, mainly at work. These findings endorse current policies of strictly limiting smoking in shared areas, particularly working environments.

Helicobacter pylori infection reduces systemic availability of dietary vitamin C.

OBJECTIVE: Helicobacter pylori infection is recognized to lower the concentration of vitamin C in gastric juice. The objective of this study was to assess the effect of the infection on the systemic availability of dietary vitamin C. METHODS: The study involved 1,106 men and women aged 25-74 randomly recruited from the population of north Glasgow. Their H. pylori status, dietary vitamin C intake calculated from a food frequency questionnaire and plasma vitamin C concentration were measured. Correction was made for potential confounding factors such as age, sex, smoking and social status. RESULTS: The mean plasma vitamin C concentration in those who were H. pylori-positive was only 65% of that in those classified negative. Although partly explained by differences in age, sex, social class, smoking and vitamin C intake, the systemic reduction was observed across almost all sub-groups after stratification. Correction for all these factors still gave a plasma vitamin C level for H. pylori positives which was only 80% of that for negatives (P < 0.0001). CONCLUSIONS: H. pylori substantially impairs the bio-availability of vitamin C. This, together with the reduced vitamin C intake of H. pylori-positive subjects, markedly reduces the plasma vitamin C level of infected subjects. The reduced circulating levels of vitamin C in H. pylori-infected subjects may contribute to the aetiology of gastric cancer, as well as other diseases associated with anti-oxidant deficiency.

Association of dietary antioxidants and waist circumference with pulmonary function and airway obstruction.

Dietary antioxidants, waist circumference, and pulmonary function were measured in the Fourth Scottish MONICA cross-sectional survey of 865 men and 971 women aged 25-64 years. Waist circumference was inversely related to forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), even after adjustment for age, height, weight, working status, energy intake, and smoking variables in a multiple linear regression model (men: beta = -0.017 for FEV1 l/cm, p < 0.01 and beta = -0.008 for FVC, p = 0.04; women: beta = -0.009 for FEV1, p < 0.01 and beta = -0.007 for FVC, p = 0.01). After additional adjustment for waist circumference, estimated vitamin C and beta-carotene intakes were positively associated with lung function in men (vitamin C: beta = 0.102 for FEV1 l/mg/day, p = 0.03; beta-carotene: beta = 0.073 for FVC l/g/day, p = 0.02). Retinol and vitamin E were not significantly related to lung function for either sex. A case-control study of airway obstruction showed that waist circumference was significantly associated, while vitamin C could be protective. The study suggests that adequate intake of antioxidants and avoidance of increasing girth could help to preserve lung function.

Plasma vitamin C and food choice in the third Glasgow MONICA population survey.

STUDY OBJECTIVE: To determine the contribution of different foods to the estimated intakes of vitamin C among those differing in plasma vitamin C levels, and thereby inform dietary strategies for correcting possible deficiency. DESIGN: Cross sectional random population survey. SETTING: North Glasgow, Scotland, 1992. PARTICIPANTS: 632 men and 635 women, aged 25 to 74 years, not taking vitamin supplements, who participated in the third MONICA study (population survey monitoring trends and determinants of cardiovascular disease). MEASUREMENTS AND MAIN RESULTS: Dietary and sociodemographic information was collected using a food frequency and lifestyle questionnaire. Plasma vitamin C was measured in non-fasted venous blood samples and subjects categorised by cut points of 11.4 and 22.7 micromol/l as being of low, marginal or optimal vitamin C status. Food sources of dietary vitamin C were identified for subjects in these categories. Plasma vitamin C concentrations were compared among groups classified according to intake of key foods. More men (26%) than women (14%) were in the low category for vitamin C status; as were a higher percentage of smokers and of those in the older age groups. Intake of vitamin C from potatoes and chips (fried potatoes) was uniform across categories; while the determinants of optimal versus low status were the intakes of citrus fruit, non-citrus fruit and fruit juice. Optimal status was achieved by a combined frequency of fruit, vegetables and/or fruit juice of three times a day or more except in older male smokers where a frequency greater than this was required even to reach a marginal plasma vitamin C level. CONCLUSION: Fruit, vegetables and/or fruit juice three or more times a day increases plasma vitamin C concentrations above the threshold for risk of deficiency.

Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations.

BACKGROUND: From the mid-1980s to mid-1990s, the WHO MONICA Project monitored coronary events and classic risk factors for coronary heart disease (CHD) in 38 populations from 21 countries. We assessed the extent to which changes in these risk factors explain the variation in the trends in coronary-event rates across the populations. METHODS: In men and women aged 35-64 years, non-fatal myocardial infarction and coronary deaths were registered continuously to assess trends in rates of coronary events. We carried out population surveys to estimate trends in risk factors. Trends in event rates were regressed on trends in risk score and in individual risk factors. FINDINGS: Smoking rates decreased in most male populations but trends were mixed in women; mean blood pressures and cholesterol concentrations decreased, bodymass index increased, and overall risk scores and coronary-event rates decreased. The model of trends in 10-year coronary-event rates against risk scores and single risk factors showed a poor fit, but this was improved with a 4-year time lag for coronary events. The explanatory power of the analyses was limited by imprecision of the estimates and homogeneity of trends in the study populations. INTERPRETATION: Changes in the classic risk factors seem to partly explain the variation in population trends in CHD. Residual variance is attributable to difficulties in measurement and analysis, including time lag, and to factors that were not included, such as medical interventions. The results support prevention policies based on the classic risk factors but suggest potential for prevention beyond these.

Estimation of contribution of changes in coronary care to improving survival, event rates, and coronary heart disease mortality across the WHO MONICA Project populations.

BACKGROUND: The revolution in coronary care in the mid-1980s to mid-1990s corresponded with monitoring of coronary heart disease (CHD) in 31 populations of the WHO MONICA Project. We studied the impact of this revolution on coronary endpoints. METHODS: Case fatality, coronary-event rates, and CHD mortality were monitored in men and women aged 35-64 years in two separate 3-4-year periods. In each period, we recorded percentage use of eight treatments: coronary-artery reperfusion before, thrombolytics during, and beta-blockers, antiplatelet drugs, and angiotensin-converting-enzyme (ACE) inhibitors before and during non-fatal myocardial infarction. Values were averaged to produce treatment scores. We correlated changes across populations, and regressed changes in coronary endpoints on changes in treatment scores. FINDINGS: Treatment changes correlated positively with each other but inversely with change in coronary endpoints. By regression, for the common average treatment change of 20, case fatality fell by 19% (95% CI 12-26) in men and 16% (5-27) in women; coronary-event rates fell by 25% (16-35) and 23% (7-39); and CHD mortality rates fell by 42% (31-53) and 34% (17-50). The regression model explained an estimated 61% and 41% of variance for men and women in trends for case fatality, 52% and 30% for coronary-event rates, and 72% and 56% for CHD mortality. INTERPRETATION: Changes in coronary care and secondary prevention were strongly linked with declining coronary endpoints. Scores and benefits followed a geographical east-to-west gradient. The apparent effects of the treatment might be exaggerated by other changes in economically successful populations, so their specificity needs further assessment.