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Background: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD., Methods: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events., Results: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints., Conclusions: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.

Objective:  To estimate the potential magnitude in unselected patients of the benefits and harms of prolonged dual antiplatelet therapy after acute myocardial infarction seen in selected patients with high risk characteristics in trials., Design:  Observational population based cohort study., Setting:  PEGASUS-TIMI-54 trial population and CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records)., Participants:  7238 patients who survived a year or more after acute myocardial infarction., Interventions:  Prolonged dual antiplatelet therapy after acute myocardial infarction., Main Outcome Measures:  Recurrent acute myocardial infarction, stroke, or fatal cardiovascular disease. Fatal, severe, or intracranial bleeding., Results:  1676/7238 (23.1%) patients met trial inclusion and exclusion criteria ("target" population). Compared with the placebo arm in the trial population, in the target population the median age was 12 years higher, there were more women (48.6% v 24.3%), and there was a substantially higher cumulative three year risk of both the primary (benefit) trial endpoint of recurrent acute myocardial infarction, stroke, or fatal cardiovascular disease (18.8% (95% confidence interval 16.3% to 21.8%) v 9.04%) and the primary (harm) endpoint of fatal, severe, or intracranial bleeding (3.0% (2.0% to 4.4%) v 1.26% (TIMI major bleeding)). Application of intention to treat relative risks from the trial (ticagrelor 60 mg daily arm) to CALIBER's target population showed an estimated 101 (95% confidence interval 87 to 117) ischaemic events prevented per 10 000 treated per year and an estimated 75 (50 to 110) excess fatal, severe, or intracranial bleeds caused per 10 000 patients treated per year. Generalisation from CALIBER's target subgroup to all 7238 real world patients who were stable at least one year after acute myocardial infarction showed similar three year risks of ischaemic events (17.2%, 16.0% to 18.5%), with an estimated 92 (86 to 99) events prevented per 10 000 patients treated per year, and similar three year risks of bleeding events (2.3%, 1.8% to 2.9%), with an estimated 58 (45 to 73) events caused per 10 000 patients treated per year., Conclusions:  This novel use of primary-secondary care linked electronic health records allows characterisation of "healthy trial participant" effects and confirms the potential absolute benefits and harms of dual antiplatelet therapy in representative patients a year or more after acute myocardial infarction., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background and Objective: Diagnostic models used in the management of suspected angina provide no explicit information about prognosis. We present a new prognostic model of 10-year coronary mortality in patients presenting for the first time with suspected angina to complement the Diamond-Forrester diagnostic model of disease probability., Methods and Results: A multicentre cohort of 8762 patients with suspected angina was followed up for a median of 10 years during which 233 coronary deaths were observed. Developmental (n=4412) and validation (n=4350) prognostic models based on clinical data available at first presentation showed good performance with close agreement and the final model utilised all 8762 patients to maximise power. The prognostic model showed strong associations with coronary mortality for age, sex, chest pain typicality, smoking status, diabetes, pulse rate, and ECG findings. Model discrimination was good (C statistic 0.83), patients in the highest risk quarter accounting for 173 coronary deaths (10-year risk of death: 8.7%) compared with a total of 60 deaths in the three lower risk quarters. When the model was simplified to incorporate only Diamond-Forrester factors (age, sex and character of symptoms) it underestimated coronary mortality risk, particularly in patients with reversible risk factors., Conclusions: For the first time in patients with suspected angina, a prognostic model is presented based on simple clinical factors available at the initial cardiological assessment. The model discriminated powerfully between patients at high risk and lower risk of coronary death during 10-year follow-up. Clinical utility was reflected in the prognostic value it added to the updated Diamond-Forrester diagnostic model of disease probability., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: The purpose of this analysis was to compare the association between variants at the chromosome 9p21 locus (Ch9p21) and risk of first versus subsequent coronary heart disease (CHD) events through systematic review and meta-analysis., Background: Ch9p21 is a recognized risk factor for a first CHD event. However, its association with risk of subsequent events in patients with established CHD is less clear., Methods: We searched PubMed and EMBASE for prospective studies reporting association of Ch9p21 with incident CHD events and extracted information on cohort type (individuals without prior CHD or individuals with established CHD) and effect estimates for risk of events., Results: We identified 31 cohorts reporting on 193,372 individuals. Among the 16 cohorts of individuals without prior CHD (n = 168,209), there were 15,664 first CHD events. Ch9p21 was associated with a pooled hazard ratio (HR) of a first event of 1.19 (95% confidence interval: 1.17 to 1.22) per risk allele. In individuals with established CHD (n = 25,163), there were 4,436 subsequent events providing >99% and 91% power to detect a per-allele HR of 1.19 or 1.10, respectively. The pooled HR for subsequent events was 1.01 (95% confidence interval: 0.97 to 1.06) per risk allele. There was strong evidence of heterogeneity between the effect estimates for first and subsequent events (p value for heterogeneity = 5.6 × 10(-11)). We found no evidence for biases to account for these findings., Conclusions: Ch9p21 shows differential association with risk of first versus subsequent CHD events. This has implications for genetic risk prediction in patients with established CHD and for mechanistic understanding of how Ch9p21 influences risk of CHD., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether the effect of South Asian ethnicity differs between studies of incidence and prognosis of coronary disease., Design: Systematic literature review and meta-analysis, and cohort analysis from a national acute coronary syndrome (ACS) registry linked to mortality (National Institute of Cardiovascular Outcomes Research/Myocardial Infarction National Audit Project)., Setting: International for the review, and England and Wales for the cohort analysis., Patients: The numbers of South Asians included in the meta-analysis were 111 555 (incidence) and 14 531 (prognosis) of whom 8251 were from the ACS cohort., Main Outcome Measures: Incidence studies: non-fatal myocardial infarction or fatal coronary heart disease; prognostic studies: mortality; HRs for 1-year all-cause death in ACS cohort., Results: South Asians had higher incidence of coronary disease compared with white subjects (HR 1.35 95% CI 1.30 to 1.40) based on meta-analysis of nine studies. Among 10 studies on prognosis, South Asians had better prognosis compared with white subjects (HR 0.78 95% CI 0.74 to 0.82). In the ACS cohort, the impact of diabetes (42.4% of South Asians, 16.9% of white subjects) on 1-year mortality was stronger in South Asians than white subjects (age-adjusted HR 1.83 95% CI 1.59 to 2.11 vs 1.53 95% CI 1.49 to 1.57). However, prognosis was better in South Asians even among diabetics, older people and those living in areas of the highest social deprivation., Conclusions: South Asian ethnicity is associated with higher incidence of coronary disease, but lower mortality once coronary disease is manifest. The dissociation between effects on incidence and prognosis suggests that public health initiatives to reduce inequalities in mortality between South Asian and white populations should focus on primary prevention. This is a CALIBER study with ClinicalTrials.gov Identifier: NCT01163513.

Context: Translational phases of study are important in evaluating whether a prognostic biomarker is likely to have impact on clinical practice but systematic evaluations of such evidence are lacking., Objective: To systematically evaluate the clinical usefulness of the published literature on the association of natriuretic peptides (NP) and prognosis in stable coronary disease., Data Sources: MEDLINE and EMBASE until the end of July 2009, without restrictions., Study Selection: Prospective studies measuring NP in people with stable coronary disease who were followed-up for all cause mortality, coronary or cardiovascular events., Data Extraction: Two independent reviewers categorised studies according to the American Heart Association phase of study, and extracted data according to the study reporting guidelines from the American Heart Association and REMARK., Results: Systematic review of 19 studies found 17 which were phase 2, reporting an association between NP and events, two phase 3 studies, statistically examining the incremental prognostic value of NP, but no studies assessing whether NP predicted risk sufficiently to change management (phase 4), improve clinical outcomes (phase 5) or cost effectiveness (phase 6). No study referred to a statistical analytic protocol. Meta-analysis of 14 studies, reporting 18,841 patients and 1655 outcome events, found an RR for events of 3.28 (95% CI 2.45 to 4.38) comparing top versus bottom third of NP. This effect was 26% lower among the five studies which adjusted for a priori confounders (age, sex, renal function and left ventricular function) and 38% lower when adjusting for publication bias (Egger's p=0.001)., Conclusion: The unbiased strength of association of NP with prognosis in stable coronary disease is unclear, and there is a lack of reports of clinically useful measures of prediction and discrimination or studies relating NP levels to clinical decision making. The available literature is confined to early phases and is of limited clinical usefulness.

Background: Self-reported angina symptoms are collected in epidemiological surveys. We aimed at validating the angina symptoms assessed by the Rose Questionnaire against registry data on coronary heart disease. A further aim was to examine the sex paradox in angina implying that women report more symptoms, whereas men have more coronary events., Design: Angina symptoms of 6601 employees of the City of Helsinki were examined using the postal questionnaire survey data combined with coronary heart disease registries., Methods: The self-reported angina was classified as no symptoms, atypical pain, exertional chest pain, and stable angina symptoms. Reimbursed medications and hospital admissions were available from registries 10 years before the survey. Binomial regression analysis was used., Results: Stable angina symptoms were associated with hospital admissions and reimbursed medications [prevalence ratio (PR), 6.75; 95% confidence interval (CI), 4.56-9.99]. In addition, exertional chest pain (PR, 5.31; 95% CI, 3.45-8.18) was associated with coronary events. All events were more prevalent among men than women (PR, 2.36; 95% CI, 1.72-3.25)., Conclusion: The Rose Questionnaire remains a valid tool to distinguish healthy people from those with coronary heart disease. However, a notable part of those reporting symptoms have no confirmation of coronary heart disease in the registries. The female excess of symptoms and male excess of events may reflect inequality or delay in access to treatment, problems in identification and diagnosis, or more complex issues related to self-reported angina symptoms.

Objectives: To develop a new methodology to systematically compare evidence across diverse risk markers for coronary heart disease and to compare this evidence with guideline recommendations., Design: "Horizontal" systematic review incorporating different sources of evidence., Data Sources: Electronic search of Medline and hand search of guidelines. Study selection Two reviewers independently determined eligibility of studies across three sources of evidence (observational studies, genetic association studies, and randomised controlled trials) related to four risk markers: depression, exercise, C reactive protein, and type 2 diabetes. Data extraction For each risk marker, the largest meta-analyses of observational studies and genetic association studies, and meta-analyses or individual randomised controlled trials were analysed., Results: Meta-analyses of observational studies reported adjusted relative risks of coronary heart disease for depression of 1.9 (95% confidence interval 1.5 to 2.4), for top compared with bottom fourths of exercise 0.7 (0.5 to 1.0), for top compared with bottom thirds of C reactive protein 1.6 (1.5 to 1.7), and for diabetes in women 3.0 (2.4 to 3.7) and in men 2.0 (1.8 to 2.3). Prespecified study limitations were more common for depression and exercise. Meta-analyses of studies that allowed formal Mendelian randomisation were identified for C reactive protein (and did not support a causal effect), and were lacking for exercise, diabetes, and depression. Randomised controlled trials were not available for depression, exercise, or C reactive protein in relation to incidence of coronary heart disease, but trials in patients with diabetes showed some preventive effect of glucose control on risk of coronary heart disease. None of the four randomised controlled trials of treating depression in patients with coronary heart disease reduced the risk of further coronary events. Comparisons of this horizontal evidence review with two guidelines published in 2007 showed inconsistencies, with depression prioritised more in the guidelines than in our review., Conclusions: This horizontal systematic review pinpoints deficiencies and strengths in the evidence for depression, exercise, C reactive protein, and diabetes as unconfounded and unbiased causes of coronary heart disease. This new method could be used to develop a field synopsis and prioritise future development of guidelines and research.

Aims/hypothesis: We determined the degree to which metabolic syndrome components, inflammation and health behaviours account for the social gradient in CHD., Methods: A total of 5312 men, initially aged 39 to 63 years, were followed for 13.1 years for incident coronary death or non-fatal myocardial infarction according to socioeconomic position (employment grade). The contribution of explanatory factors to socioeconomic differences in CHD was assessed by the reduction in hazard ratios computed using Cox models. The effects of measurement error were taken into account., Results: Coronary events were more common in lower employment grades than in higher, with a hazard ratio (relative index of inequality) of 2.2 (95% CI 1.3-3.7), after adjustment for age and ethnic group. Behavioural risk factors (mainly smoking and diet) explained a third of the socioeconomic gradient in CHD incidence. Components of the metabolic syndrome and inflammatory markers predicted CHD incidence and also explained a third of the gradient. Combined, these two groups of predictors, i.e. behavioural and biological, accounted for over half of the socioeconomic gradient in incident CHD. Adding body height as a marker of the effects of early life increased this figure to about 60%., Conclusions/interpretation: A major question has been how someone's socioeconomic position can lead to increased risk of CHD. Socioeconomic differences in components of the metabolic syndrome (and inflammatory markers) provide part of the answer. This was, to an important degree, independent of the contribution of health behaviours to the socioeconomic differentials in CHD.

Aims: To determine the biological and behavioural factors linking work stress with coronary heart disease (CHD)., Methods and Results: A total of 10 308 London-based male and female civil servants aged 35-55 at phase 1 (1985-88) of the Whitehall II study were studied. Exposures included work stress (assessed at phases 1 and 2), and outcomes included behavioural risk factors (phase 3), the metabolic syndrome (phase 3), heart rate variability, morning rise in cortisol (phase 7), and incident CHD (phases 2-7) on the basis of CHD death, non-fatal myocardial infarction, or definite angina. Chronic work stress was associated with CHD and this association was stronger among participants aged under 50 (RR 1.68, 95% CI 1.17-2.42). There were similar associations between work stress and low physical activity, poor diet, the metabolic syndrome, its components, and lower heart rate variability. Cross-sectionally, work stress was associated with a higher morning rise in cortisol. Around 32% of the effect of work stress on CHD was attributable to its effect on health behaviours and the metabolic syndrome., Conclusion: Work stress may be an important determinant of CHD among working-age populations, which is mediated through indirect effects on health behaviours and direct effects on neuroendocrine stress pathways.

Objective: To determine whether cardiothoracic ratio (CTR), within the range conventionally considered normal, predicted prognosis in patients undergoing coronary angiography., Design: Cohort study with a median of 7-years follow-up., Setting: Consecutive patients undergoing coronary angiography at Barts and The London National Health Service (NHS) Trust., Subjects: 1005 patients with CTRs measured by chest radiography, and who subsequently underwent coronary angiography. Of these patients, 7.3% had a CTR > or =0.5 and were excluded from the analyses., Outcomes: All-cause mortality and coronary event (non-fatal myocardial infarction or coronary death). Adjustments were made for age, left ventricular dysfunction, ACE inhibitor treatment, body mass index, number of diseased coronary vessels and past coronary artery bypass graft., Results: The risk of death was increased among patients with a CTR in the upper part of the normal range. In total, 94 (18.9%) of those with a CTR below the median of 0.42 died compared with 120 (27.8%) of those with a CTR between 0.42 and 0.49 (log rank test p<0.001). After adjusting for potential confounders, this increased risk remained (adjusted HR 1.45, 95% CI 1.03 to 2.05). CTR, at values below 0.5, was linearly related to the risk of coronary event (test for trend p = 0.024)., Conclusion: In patients undergoing coronary angiography, CTR between 0.42 and 0.49 was associated with higher mortality than in patients with smaller hearts. There was evidence of a continuous increase in risk with higher CTR. These findings, along with those in healthy populations, question the conventional textbook cut-off point of > or =0.5 being an abnormal CTR.

Objective: To determine whether rapid access chest pain clinics are clinically effective by comparison of coronary event rates in patients diagnosed with angina with rates in patients diagnosed with non-cardiac chest pain and the general population., Design: Multicentre cohort study of consecutive patients with chest pain attending the rapid access chest pain clinics (RACPCs) of six hospitals in England., Participants: 8762 patients diagnosed with either non-cardiac chest pain (n = 6396) or incident angina without prior myocardial infarction (n = 2366) at first cardiological assessment, followed up for a median of 2.57 (interquartile range 1.96-4.15) years., Main Outcome Measures: Primary end point--death due to coronary heart disease (International Classification of Diseases (ICD)10 I20-I25) or acute coronary syndrome (non-fatal myocardial infarction (ICD10 I21-I23), hospital admission with unstable angina (I24.0, I24.8, I24.9)). Secondary end points--all-cause mortality (ICD I20), cardiovascular death (ICD10 I00-I99), or non-fatal myocardial infarction or non-fatal stroke (I60-I69)., Results: The cumulative probability of the primary end point in patients diagnosed with angina was 16.52% (95% confidence interval (CI) 14.88% to 18.32%) after 3 years compared with 2.73% (95% CI 2.29% to 3.25%) in patients with non-cardiac chest pain. Coronary standardised mortality ratios for men and women with angina aged <65 years were 3.52 (95% CI 1.98 to 5.07) and 4.39 (95% CI 1.14 to 7.64). Of the 599 patients who had the primary end point, 194 (32.4%) had been diagnosed with non-cardiac chest pain. These patients were younger, less likely to have typical symptoms, more likely to be south Asian and more likely to have a normal resting electrocardiogram than patients with angina who had the primary end point., Conclusion: RACPCs are successful in identifying patients with incident angina who are at high coronary risk, but there is a need to reduce misdiagnosis and improve outcomes in patients diagnosed with non-cardiac chest pain who accounted for nearly one third of cardiac events during follow-up.

Aims: With negative treatment trials, the role of depression as an aetiological or prognostic factor in coronary heart disease (CHD) remains controversial. We quantified the effect of depression on CHD, assessing the extent of confounding by coronary risk factors and disease severity., Methods and Results: Meta-analysis of cohort studies measuring depression with follow-up for fatal CHD/incident myocardial infarction (aetiological) or all-cause mortality/fatal CHD (prognostic). We searched MEDLINE and Science Citation Index until December 2003. In 21 aetiological studies, the pooled relative risk of future CHD associated with depression was 1.81 (95% CI 1.53-2.15). Adjusted results were included for 11 studies, with adjustment reducing the crude effect marginally from 2.08 (1.69-2.55) to 1.90 (1.49-2.42). In 34 prognostic studies, the pooled relative risk was 1.80 (1.50-2.15). Results adjusted for left ventricular function result were available in only eight studies; and this attenuated the relative risk from 2.18 to 1.53 (1.11-2.10), a 48% reduction. Both aetiological and prognostic studies without adjusted results had lower unadjusted effect sizes than studies from which adjusted results were included (P<0.01)., Conclusion: Depression has yet to be established as an independent risk factor for CHD because of incomplete and biased availability of adjustment for conventional risk factors and severity of coronary disease.

Background: PubMed is the most widely used method for searches of the medical literature, but fails to identify many relevant articles. Electronic citation tracking offers an alternative search method., Methods: Articles investigating the role of depression in the aetiology and prognosis of coronary heart disease were sought through two methods: a) PubMed, and b) citation tracking where Science Citation Index was searched for all articles which cited ("forward citation tracking") or were cited by ("backward citation tracking") any of the articles in an index review. The number and quality of eligible articles identified by the two methods were compared., Results: 50 articles that were not already included in the index review met our inclusion criteria; 11 were identified through Science Citation Index alone, 8 through PubMed alone, and 31 through both methods. Articles identified by Science Citation Index alone were published in higher impact factor journals, were larger and were less likely to show a positive association., Conclusion: Science Citation Index identified more eligible articles than PubMed, and these differed qualitatively. Failing to use citation tracking in a systematic review of observational studies may result in bias.

Background: Laboratory and clinical studies suggest that the autonomic nervous system responds to chronic behavioral and psychosocial stressors with adverse metabolic consequences and that this may explain the relation between low social position and high coronary risk. We sought to test this hypothesis in a healthy occupational cohort., Methods and Results: This study comprised 2197 male civil servants 45 to 68 years of age in the Whitehall II study who were undergoing standardized assessments of social position (employment grade) and the psychosocial, behavioral, and metabolic risk factors for coronary disease previously found to be associated with low social position. Five-minute recordings of heart rate variability (HRV) were used to assess cardiac parasympathetic function (SD of N-N intervals and high-frequency power [0.15 to 0.40 Hz]) and the influence of sympathetic and parasympathetic function (low-frequency power [0.04 to 0.15 Hz]). Low employment grade was associated with low HRV (age-adjusted trend for each modality, P< or =0.02). Adverse behavioral factors (smoking, exercise, alcohol, and diet) and psychosocial factors (job control) showed age-adjusted associations with low HRV (P<0.03). The age-adjusted mean low-frequency power was 319 ms2 among those participants in the bottom tertile of job control compared with 379 ms2 in the other participants (P=0.004). HRV showed strong (P<0.001) linear associations with components of the metabolic syndrome (waist circumference, systolic blood pressure, HDL cholesterol, triglycerides, and fasting and 2-hour postload glucose). The social gradient in prevalence of metabolic syndrome was explained statistically by adjustment for low-frequency power, behavioral factors, and job control., Conclusions: Chronically impaired autonomic function may link social position to different components of coronary risk in the general population.

Objectives: Although sick, some people take no time off work, a phenomenon called "sickness presenteeism." This study examined the association between sickness presenteeism and incidence of serious coronary events., Methods: The analyses were based on a cohort of 5071 male British civil servants without previous myocardial infarction. Baseline screening included measurements of health status and coronary risk factors. Absence records were assessed for the 3 years subsequent to baseline screening. The outcome of interest was incident nonfatal myocardial infarction or fatal coronary heart disease (mean length of follow-up=9.1 years)., Results: Seventeen percent of unhealthy employees took no absence during the 3-year follow-up. Their incidence of serious coronary events was twice as high as that of the unhealthy employees with moderate levels of sickness absenteeism (after adjustment for conventional risk factors, hazard ratio 1.97, 95% confidence interval=1.02, 3.83)., Conclusions: Employers and employees should be aware of the potential harmful effects caused by sickness presenteeism.

Objective: To determine whether access to cardiac procedures and drugs contributes to social and ethnic differences in coronary heart disease in a population setting., Design: Prospective study with follow up over 15 years. Civil service employment grade was used as a measure of individual socioeconomic position. Need for cardiac care was determined by the presence of angina, myocardial infarction, and coronary risk factors., Setting: 20 civil service departments originally located in London., Participants: 10,308 civil servants (3414 women; 560 South Asian) aged 35-55 years at baseline in 1985-8., Main Outcome Measures: Use of exercise electrocardiography, coronary angiography, and coronary revascularisation procedures and secondary prevention drugs., Results: Inverse social gradients existed in incident coronary morbidity and mortality. South Asian participants also had higher rates than white participants. After adjustment for clinical need, social position showed no association with the use of cardiac procedures or secondary prevention drugs. For example, men in the low versus high employment grade had an age adjusted odds ratio for angiography of 1.87 (95% confidence interval 1.32 to 2.64), which decreased to 1.27 (0.83 to 1.94) on adjustment for clinical need. South Asians tended to be more likely to have cardiac procedures and to be taking more secondary prevention drugs than white participants, even after adjustment for clinical need., Conclusion: This population based study, which shows the widely observed social and ethnic patterning of coronary heart disease, found no evidence that low social position or South Asian ethnicity was associated with lower use of cardiac procedures or drugs, independently of clinical need. Differences in medical care are unlikely to contribute to social or ethnic differences in coronary heart disease in this cohort.

Background: Coronary heart disease is more common among some ethnic minority groups (particularly people from the Indian sub-continent living in Europe and North America) and in socially deprived populations. Hospital studies in the United Kingdom (UK) suggest that these groups have less access to treatment for coronary heart disease. Studies from primary care have found reduced access to angiography for lower social class groups, but there are no studies on the ethnicity of primary care populations in relation to angiography., Aims: To determine the influence of ethnicity and social deprivation in primary care on access to coronary angiography., Design of Study: Ecological study measuring general practices' ethnicity, socioeconomic status, and nitrate prescribing rates with angiography rates., Setting: General practices (n = 143) in East London, UK., Method: Ecological study measuring the proportion of general practice populations with South Asian ethnicity and high social deprivation score (Carstairs). Nitrate prescriptions and admissions for myocardial infarction per 1000 population per year were used as measures of need. Distance from the tertiary centre was used as a measure of supply. The outcome measure was coronary angiography procedures data (n = 869) collected in the context of the appropriateness of coronary revascularisation study., Results: Practices with a higher proportion of South Asian patients had higher rates of angiography after adjustment for age, distance, deprivation, nitrate prescribing and myocardial infarction admissions (regression coefficient B = 0.02, 95% confidence interval [CI] = 0.01 to 0.03, P<0.001). There was no association between deprivation and angiography (regression coefficient B = -0.41, 95% CI = -0.13 to 0.05, P = 0.393)., Conclusion: General practices with a higher proportion of South Asian patients had higher rates of angiography, challenging the widely held belief that access may be inequitable. Deprivation shows no relationship with angiography in this study.

Social position and psychosocial factors are associated with coronary disease, but the underlying pathophysiologic mechanisms remain unclear. In a sample of 283 nonsmokers, we found that social position was inversely associated with interleukin-6 and C-reactive protein and that participants with mild depression had impaired endothelial function.

The application of Bayesian hierarchical models to measure spatial effects in time to event data has not been widely reported. This case study aims to estimate the effect of area of residence on waiting times to coronary artery bypass graft (CABG) and to assess the role of important individual specific covariates (age, sex and disease severity). The data involved all patients with definite coronary artery disease who were referred to one cardiothoracic unit from five contiguous health authorities covering 488 electoral wards (areas). Time to event was the waiting time in months from angiography (diagnosis) to CABG (event). A number of discrete time survival models were fitted to the data. A discrete baseline hazard was estimated by fitting waiting time non-parametrically into the models. Ward was fitted as a spatial effect using a Gaussian Markov random field prior. Individual specific covariates considered were age, sex and number of diseased vessels. The recently proposed DIC criteria was used for comparing models. Results showed a marked spatial effect on time to bypass surgery after including age, sex and disease severity in the model. Notably this spatial effect was not apparent when these covariates were not included in the model. The observed small area spatial variation in time to CABG warrants further investigation., (Copyright 2003 John Wiley & Sons, Ltd.)

The extent to which the associations between psychosocial factors and coronary heart disease (CHD) are causal has seldom been the subject of systematic enquiry. We are updating our previous systematic review up to 2001. The objective of this study is to assess the relative strength of the epidemiological evidence for causal links between psychosocial factors and CHD incidence among healthy populations, and prognosis among CHD patients. Our methods were to systematically review prospective cohort studies identified through the Science Citation index, which met pre-specified quality criteria. We found that the proportion of etiologic studies reporting a strong or moderate association was: 6/18 for Type A behavior and hostility, 15/22 for depression, 4/8 for anxiety, 10/13 for psychosocial work characteristics and 6/9 for social support. For prognostic studies the proportions were: 2/15 for type A behavior and hostility, 18/34 for depression, 8/18 for anxiety, 2/4 for psychosocial work characteristics and 14/21 for social support. Positive studies were more likely to be cited by other papers than negative studies. We concluded that, based on prospective epidemiological data, there was evidence for an association between depression, social support and psychosocial work characteristics and CHD aetiology and prognosis. Evidence for an effect of anxiety or type A behavior was less consistent. Methods to address bias in the reporting of psychosocial data are required.

Objectives: To compare rates of revascularisation in south Asian and white patients undergoing coronary angiography in relation to the appropriateness of revascularisation and clinical outcome., Design: Prospective cohort study of patients with two and a half years' follow up; appropriateness of revascularisation rated by nine experts with no knowledge of ethnicity of patient., Setting: Tertiary cardiac centre in London with referral from five contiguous health authorities., Participants: Consecutive patients (502 south Asian, 2974 white) undergoing coronary angiography in the appropriateness of coronary revascularisation study (ACRE)., Main Outcome Measures: Coronary revascularisation, non-fatal myocardial infarction, mortality., Results: There was no difference between south Asian and white patients in the proportions deemed appropriate for revascularisation (72% (361) v 68% (2022)) or in the proportions for whom the physician's intended management was revascularisation (39% (196) v 41% (1218)). Among patients appropriate for revascularisation, age adjusted rates of coronary angioplasty (hazard ratio 0.69, 95% confidence interval 0.47 to 1.00, P=0.058) and coronary artery bypass grafting (0.74, 0.58 to 0.91, P=0.007) were lower in south Asian than in white patients. These differences were smaller but still present after adjustment for socioeconomic status and after restriction of analysis to those patients for whom the intended management was revascularisation. There were no differences in mortality and non-fatal myocardial infarction between south Asian and white patients (1.07, 0.78 to 1.47)., Conclusion: Among patients deemed appropriate for coronary artery bypass grafting, south Asian patients are less likely than white patients to receive it. This difference is not explained by physician bias.

Background: Psychosocial factors are associated with the etiology and prognosis of coronary heart disease (CHD) in White populations; however, previous studies have not examined the distribution of psychosocial factors in ethnic groups with coronary rates higher (South Asian) and lower (Afro-Caribbean) than those of Whites., Study Objective: To determine whether ethnic differences in psychosocial risk factors parallel those in CHD mortality., Design: Cross-sectional survey., Setting: 20 civil service departments in London., Participants: 8973 White, 577 South Asian, and 360 Afro-Caribbean office-based civil servants, aged 35-55 years., Outcome Measures: Minor psychiatric morbidity (General Health Questionnaire), social supports (marital status, social networks, negative aspects of support, confiding/emotional support, social support at work), psychosocial work characteristics (job control, effort-reward imbalance), hostility levels and presence of Type A personality., Results: South Asians, compared to Whites, had more depression, higher negative supports, less social support at work, less job control, more effort-reward imbalance and higher levels of hostility, when adjusting for age and sex. Afro-Caribbeans, compared to Whites, had lower minor psychiatric morbidity and lower Type A scores. The remaining psychosocial factors showed either no ethnic differences in distribution, or differences contrary to those predicted from coronary event rates. Adjustment for employment grade made little difference to these associations., Conclusion: Among South Asians, the majority of whom were Indian, the distribution of psychosocial factors was consistent with ethnic differences in coronary rates; the pattern for Afro-Caribbeans was less consistent. Further research is required to test the extent to which psychosocial factors predict coronary events within ethnic groups and to characterize better psychosocial measures.

Objective: To determine whether ratings of coronary angiography appropriateness derived by an expert panel on hypothetical patients are associated with actual angiographic findings, mortality, and subsequent revascularisation in the ACRE (appropriateness of coronary revascularisation) study., Design: Population based, prospective study. The ACRE expert panel rated hypothetical clinical indications as inappropriate, uncertain, or appropriate before recruitment of a cohort of real patients., Setting: Royal Hospitals Trust, London, UK., Participants: 3631 consecutive patients undergoing coronary angiography (no exclusion criteria)., Main Outcome Measures: Angiographic findings, mortality (n = 226 deaths), and revascularisation (n = 1556 procedures) over 2.5 years of follow up., Results: The indications for coronary angiography were rated appropriate in 2253 (62%) patients. 166 (5%) coronary angiograms were performed for indications rated inappropriate, largely for asymptomatic or atypical chest pain presentations. The remaining 1212 (33%) angiograms were rated uncertain, of which 47% were in patients with mild angina and no exercise ECG or in patients with unstable angina controlled by inpatient management. Three vessel disease was more likely among appropriate cases and normal coronaries were more likely among inappropriate cases (p < 0.001). Mortality and revascularisation rates were highest among patients with an appropriate indication, intermediate in those with an uncertain indication, and lowest in the inappropriate group (log rank p = 0.018 and p < 0.0001, respectively)., Conclusion: The ACRE ratings of appropriateness for angiography predicted angiographic findings, mortality, and revascularisation rates. These findings support the clinical usefulness of expert panel methods in defining criteria for performing coronary angiography.

Study Objective: To determine the relative contribution of adult compared with early life socioeconomic status as predictors of morbidity attributable to coronary heart disease (CHD), chronic bronchitis and depression in the Whitehall II study of British civil servants., Design: Prospective observational study with mean 5.3 years (range 3.7-7.6) follow up., Setting: 20 civil service departments originally located in London., Participants: 6895 male and 3413 female office-based civil servants aged 35-55 years at baseline., Outcome Measures: New cases at follow up of CHD, chronic bronchitis and depression defined using validated questionnaires., Main Results: Employment grade was inversely associated with CHD, chronic bronchitis and depression in men (odds ratio per unit decrease in grade 1.30, 1.44 and 1.20 respectively). Employment grade was strongly related to father's social class. Chronic bronchitis, in women, and depression, in men, were more common among those with fathers of higher social class. When mutual adjustment was made for father's social class, grade at entry to the civil service and current grade, the strongest effects on adult morbidity were found for current grade. Among participants in whom neither parent had died < or =70 years of age the inverse association with adult SES was maintained., Conclusions: Adult socioeconomic status was a more important predictor of morbidity attributable to coronary disease, chronic bronchitis and depression than measures of social status earlier in life. In this population, the importance of social circumstances early in life may be in the way they influence employment and social position and thus exposures in adult life.

Background: Ratings by an expert panel of the appropriateness of treatments may offer better guidance for clinical practice than the variable decisions of individual clinicians, yet there have been no prospective studies of clinical outcomes. We compared the clinical outcomes of patients treated medically after angiography with those of patients who underwent revascularization, within groups defined by ratings of the degree of appropriateness of revascularization in varying clinical circumstances., Methods: This was a prospective study of consecutive patients undergoing coronary angiography at three London hospitals. Before patients were recruited, a nine-member expert panel rated the appropriateness of percutaneous transluminal coronary angioplasty (PTCA) and coronary-artery bypass grafting (CABG) on a nine-point scale (with 1 denoting highly inappropriate and 9 denoting highly appropriate) for specific clinical indications. These ratings were then applied to a population of patients with coronary artery disease. However, the patients were treated without regard to the ratings. A total of 2552 patients were followed for a median of 30 months after angiography., Results: Of 908 patients with indications for which PTCA was rated appropriate (score, 7 to 9), 34 percent were treated medically; these patients were more likely to have angina at follow-up than those who underwent PTCA (odds ratio, 1.97; 95 percent confidence interval, 1.29 to 3.00). Of 1353 patients with indications for which CABG was considered appropriate, 26 percent were treated medically; they were more likely than those who underwent CABG to die or have a nonfatal myocardial infarction--the composite primary outcome (hazard ratio, 4.08; 95 percent confidence interval, 2.82 to 5.93)--and to have angina (odds ratio, 3.03; 95 percent confidence interval, 2.08 to 4.42). Furthermore, there was a graded relation between rating and outcome over the entire scale of appropriateness (P for linear trend=0.002)., Conclusions: On the basis of the ratings of the expert panel, we identified substantial underuse of coronary revascularization among patients who were considered appropriate candidates for these procedures. Underuse was associated with adverse clinical outcomes.

Objectives: To determine the impact of socioeconomic status (SES) on coronary heart disease (CHD) mortality in people with and without prevalent CHD at baseline., Design: Cohort study with 25 year follow up; prevalent CHD was defined by Q, ST or T wave electrocardiographic (ECG) abnormalities or symptoms (defined by the Rose chest pain questionnaire and self reported doctor diagnosis) or both. SES was defined by four civil service employment grades., Setting: London., Participants: 17 907 male civil servants aged 40-69 years., Main Outcome Measures: CHD mortality (n=2695 deaths)., Results: The lowest versus highest employment grade was associated with increased CHD mortality (age adjusted hazard ratio 1.56 (95% CI 1.2, 2.1)), prevalence of symptoms and, among symptomatic participants only, the prevalence of Q, ST or T abnormalities. Thirty one per cent of CHD deaths occurred in participants with prevalent CHD at baseline. Among participants without Q, ST or T abnormality employment grade was associated with CHD mortality; the hazard ratios (lowest v highest grade) adjusted for age, systolic and diastolic blood pressure were 1.72 (95% CI 1.4, 2.1) for asymptomatic and 1.52 (95% CI 1.1, 2.1) for symptomatic participants; among participants with Q, ST or T abnormality the corresponding hazard ratios were 1.46 (95% CI 0.7, 2.9) and 1.14 (95% CI 0.6, 2.0) respectively., Conclusions: SES was inversely associated with CHD mortality in civil servants with and without prevalent CHD at baseline. Further distinguishing the relative contribution of SES to the initiation and progression of CHD requires repeated measures studies of pre-clinical and clinical measures of CHD.

In the routine reporting of coronary angiograms, there are no contemporary estimates of the magnitude and consequences of interobserver variability. We therefore measured the agreement beyond chance between (1) the number of narrowed arteries on an angiographic report extracted from case notes and independent assessments by 2 cardiologists, and (2) actual patient management over an 18-month follow-up period and each cardiologist's hypothetical management proposal based on abstracted clinical details. Two hundred nine angiograms were randomly selected from 4,121 patients in a prospective study (Appropriateness of Coronary Revascularisation [ACRE study]). The number of narrowed arteries was defined using Coronary Artery Surgery Study (CASS) criteria. For the number of narrowed arteries, cardiologists A and B agreed with the angiographic report in 126 patients (60%, weighted kappa = 0.64) and 124 patients (59%, weighted kappa = 0.63), respectively. In a subset of 92 patients (44%) there was unanimous agreement on the number of narrowed arteries (both cardiologists agreed with the angiographic report). Comparing actual management (34 percutaneous transluminal coronary angioplasty and 39 coronary artery bypass grafting procedures on follow-up) with each of the cardiologist's management recommendations showed agreement in 150 patients (72%, kappa = 0.46) and 154 patients (74%, kappa = 0.48) for cardiologists A and B, respectively. These agreements on management improved (p = 0.05) for cardiologist B (but not A) when analysis was confined to the subset of 92 patients, showing agreement in 73 patients (79%, kappa = 0.60). Thus, in routine clinical practice, the agreement beyond chance in interpretation of the number of narrowed arteries was good. Disagreements on subsequent patient management arose as a result of, and independent of, errors in angiographic interpretation.

Aim: To examine the association of radiographic measures of heart size with mortality from coronary heart disease., Methods and Results: One thousand, one hundred and ninety-one male civil servants aged 40-69 years were followed-up for mortality over 25 years in relation to cardiothoracic ratio and relative heart volume. A high cardiothoracic ratio and relative heart volume predicted coronary (n = 196 deaths) and all-cause mortality, but not respiratory or malignant mortality. After adjustment for age, systolic and diastolic blood pressure, the highest (> or = 0.47) compared to the lowest quintile of the cardiothoracic ratio (< 0.40) was associated with a rate ratio of 1.84 (95% CI 1.14-2.97) for the effect on coronary heart disease mortality. Further adjustment for heart rate, smoking, cholesterol, angina and ECG ischaemia had little effect, reducing the rate ratio to 1.65 (95% CI 1.01-2.70). Similar rate ratios were observed for relative heart volume., Conclusions: Cardiothoracic ratio within the range considered 'normal' in clinical practice predicted coronary heart disease mortality independent of established coronary heart disease risk factors. The relative heart volume, which uses measurements from the lateral as well as the posteroanterior chest X-ray, did not predict coronary heart disease any better than the cardiothoracic ratio. The extent to which left ventricular mass and systolic dysfunction-- pathophysiological correlates of the cardiothoracic ratio and relative heart volume--are independent risk factors for coronary heart disease should be further investigated.

The discharge summary from hospital to community physician contributes importantly to patient management, but deficiencies in its preparation are well documented. We sought to determine the preferences of general practitioners for standard dictated or computer-generated discharge summaries for patients with acute coronary syndromes. The majority (68.5%) of GPs preferred the computerized summary and particularly liked its comprehensive content, concise style, ease of access to relevant information, clarity and ease of reading. Most (66.9%) thought the computer-generated summary provided the clearer management plan and 70.8% recommended its use for other specialities. In addition, its speed of generation enables GPs to receive a summary within seven days of patient discharge.

Background: The first Whitehall Study showed an inverse social gradient in mortality from coronary heart disease (CHD) among British civil servants--namely, that there were higher rates in men of lower employment grade. About a quarter of this gradient could be attributed to coronary risk factors. We analysed 5-year CHD incidence rates from the Whitehall II study to assess the contribution to the social gradient of psychosocial work environment, social support, coronary risk factors, and physical height., Methods: Data were collected in the first three phases of examination of men and women in the Whitehall II study. 7372 people were contacted on all three occasions. Mean length of follow-up was 5.3 years. Characteristics from the baseline, phase 1, questionnaire, and examination were related to newly reported CHD in people without CHD at baseline. Three self-reported CHD outcomes were examined: angina and chest pain from the Rose questionnaire, and doctor-diagnosed ischaemia. The contribution of different factors to the socioeconomic differences in incident CHD was assessed by adjustment of odds ratios., Findings: Compared with men in the highest grade (administrators), men in the lowest grade (clerical and office-support staff) had an age-adjusted odds ratio of developing any new CHD of 1.50. The largest difference was for doctor-diagnosed ischaemia (odds ratio for the lowest compared with the highest grade 2.27). For women, the odds ratio in the lowest grade was 1.47 for any CHD. Of factors examined, the largest contribution to the socioeconomic gradient in CHD frequency was from low control at work. Height and standard coronary risk factors made smaller contributions. Adjustment for all these factors reduced the odds ratios for newly reported CHD in the lowest grade from 1.5 to 0.95 in men, and from 1.47 to 1.07 in women., Interpretation: Much of the inverse social gradient in CHD incidence can be attributed to differences in psychosocial work environment. Additional contributions were made by coronary risk factors--mainly smoking--and from factors that act early in life, as represented by physical height.

Objective: To determine the association between adverse psychosocial characteristics at work and risk of coronary heart disease among male and female civil servants., Design: Prospective cohort study (Whitehall II study). At the baseline examination (1985-8) and twice during follow up a self report questionnaire provided information on psychosocial factors of the work environment and coronary heart disease. Independent assessments of the work environment were obtained from personnel managers at baseline. Mean length of follow up was 5.3 years., Setting: London based office staff in 20 civil service departments., Subjects: 10,308 civil servants aged 35-55 were examined-6895 men (67%) and 3413 women (33%)., Main Outcome Measures: New cases of angina (Rose questionnaire), severe pain across the chest, diagnosed ischaemic heart disease, and any coronary event., Results: Men and women with low job control, either self reported or independently assessed, had a higher risk of newly reported coronary heart disease during follow up. Job control assessed on two occasions three years apart, although intercorrelated, had cumulative effects on newly reported disease. Subjects with low job control on both occasions had an odds ratio for any subsequent coronary event of 1.93 (95% confidence interval 1.34 to 2.77) compared with subjects with high job control at both occasions. This association could not be explained by employment grade, negative affectivity, or classic coronary risk factors. Job demands and social support at work were not related to the risk of coronary heart disease., Conclusions: Low control in the work environment is associated with an increased risk of future coronary heart disease among men and women employed in government offices. The cumulative effect of low job control assessed on two occasions indicates that giving employees more variety in tasks and a stronger say in decisions about work may decrease the risk of coronary heart disease.