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Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests: GSC and KGMM are part of the TRIPOD steering group. GSC is director of the UK EQUATOR Centre. The remaining authors have no additional declarations.

Objective  To ascertain long term cardiovascular outcomes in patients whose chest pain remained undiagnosed six months after first presentation. Design  Cohort study. Setting  UK electronic health record database (CALIBER) linking primary care, secondary care, coronary registry, and death registry information. Participants  172 180 adults aged ≥18 from 223 general practices presenting with a first episode of recorded chest pain, classified from medical records as diagnosed (non-coronary condition or angina) or undiagnosed (cause unattributed) at first consultation between 2002 and 2009 and with no previous record of cardiovascular disease. Main outcome measures  Fatal or non-fatal cardiovascular events over 5.5 years' follow-up. Adjustments were made for age, sex, deprivation, body mass index, smoking status, year of index presentation, and previous records of diabetes or hypertension or previous prescriptions for lipid lowering drugs. Results  At the index presentation, 72.4% of patients (124 688) did not have a cause attributed for their chest pain; 118 687 (95.2%) of these did not receive any type of cardiovascular diagnosis over the next six months. Only a minority of patients in all three groups (non-coronary 2.0% (769 of 39 232); unattributed 11.7% (14 582 of 124 688); angina 31.5% (2606 of 8260)) had a recorded cardiac diagnostic investigation in the first six months after presentation. The long term incidence of cardiovascular events was higher in those whose chest pain remained unattributed after six months (5126 of 109 628; 4.7%) compared with patients with an initial diagnosis of non-coronary pain (1073 of 36 097; 3.0%) (adjusted hazard ratios for 0.5-1 year after presentation: 1.95, 95% confidence interval 1.66 to 2.31; for 1-3 years: 1.35, 1.23 to 1.48); for 3-5.5 years: 1.21, 1.08 to 1.37). Owing to the larger number of patients in the unattributed group, there were more excess myocardial infarctions in the long term in this group (214 more than expected based on the rate in the non-coronary group) than in the angina group (132 more than expected). Patients who had cardiac diagnostic investigations in the first six months had a higher long term risk of cardiovascular events, regardless of the initial chest pain label. Incidence of unattributed chest pain and angina decreased between 2002 (124 per 10 000 person years and 13 per 10 000 person years, respectively) and 2009 (107 per 10 000 person years and 5 per 10 000 person years, respectively), but the incidence of chest pain attributed to a non-coronary cause remained stable (37-40 per 10 000 person years). Risk of cardiovascular events did not change over time. Conclusions  Most patients with first onset chest pain do not have a diagnosis recorded at presentation or in the subsequent six months, including those who undergo cardiac investigations. These patients have an increased risk of cardiovascular events for at least five years. Efforts to better assess and reduce the cardiovascular risk of such patients are warranted., (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.)

Objectives  To investigate the association between alcohol consumption and cardiovascular disease at higher resolution by examining the initial lifetime presentation of 12 cardiac, cerebrovascular, abdominal, or peripheral vascular diseases among five categories of consumption. Design  Population based cohort study of linked electronic health records covering primary care, hospital admissions, and mortality in 1997-2010 (median follow-up six years). Setting  CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records). Participants  1 937 360 adults (51% women), aged ≥30 who were free from cardiovascular disease at baseline. Main outcome measures  12 common symptomatic manifestations of cardiovascular disease, including chronic stable angina, unstable angina, acute myocardial infarction, unheralded coronary heart disease death, heart failure, sudden coronary death/cardiac arrest, transient ischaemic attack, ischaemic stroke, intracerebral and subarachnoid haemorrhage, peripheral arterial disease, and abdominal aortic aneurysm. Results  114 859 individuals received an incident cardiovascular diagnosis during follow-up. Non-drinking was associated with an increased risk of unstable angina (hazard ratio 1.33, 95% confidence interval 1.21 to 1.45), myocardial infarction (1.32, 1.24 to1.41), unheralded coronary death (1.56, 1.38 to 1.76), heart failure (1.24, 1.11 to 1.38), ischaemic stroke (1.12, 1.01 to 1.24), peripheral arterial disease (1.22, 1.13 to 1.32), and abdominal aortic aneurysm (1.32, 1.17 to 1.49) compared with moderate drinking (consumption within contemporaneous UK weekly/daily guidelines of 21/3 and 14/2 units for men and women, respectively). Heavy drinking (exceeding guidelines) conferred an increased risk of presenting with unheralded coronary death (1.21, 1.08 to 1.35), heart failure (1.22, 1.08 to 1.37), cardiac arrest (1.50, 1.26 to 1.77), transient ischaemic attack (1.11, 1.02 to 1.37), ischaemic stroke (1.33, 1.09 to 1.63), intracerebral haemorrhage (1.37, 1.16 to 1.62), and peripheral arterial disease (1.35; 1.23 to 1.48), but a lower risk of myocardial infarction (0.88, 0.79 to 1.00) or stable angina (0.93, 0.86 to 1.00). Conclusions  Heterogeneous associations exist between level of alcohol consumption and the initial presentation of cardiovascular diseases. This has implications for counselling patients, public health communication, and clinical research, suggesting a more nuanced approach to the role of alcohol in prevention of cardiovascular disease is necessary. Registration  clinicaltrails.gov (NCT01864031)., (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.)

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.)

Objective: To assess the between hospital variation in use of guideline recommended treatments and clinical outcomes for acute myocardial infarction in Sweden and the United Kingdom., Design: Population based longitudinal cohort study using nationwide clinical registries., Setting and Participants: Nationwide registry data comprising all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART/RIKS-HIA, n=87; 119,786 patients) and the UK (NICOR/MINAP, n=242; 391,077 patients), 2004-10., Main Outcome Measures: Between hospital variation in 30 day mortality of patients admitted with acute myocardial infarction., Results: Case mix standardised 30 day mortality from acute myocardial infarction was lower in Swedish hospitals (8.4%) than in UK hospitals (9.7%), with less variation between hospitals (interquartile range 2.6% v 3.5%). In both countries, hospital level variation and 30 day mortality were inversely associated with provision of guideline recommended care. Compared with the highest quarter, hospitals in the lowest quarter for use of primary percutaneous coronary intervention had higher volume weighted 30 day mortality for ST elevation myocardial infarction (10.7% v 6.6% in Sweden; 12.7% v 5.8% in the UK). The adjusted odds ratio comparing the highest with the lowest quarters for hospitals' use of primary percutaneous coronary intervention was 0.70 (95% confidence interval 0.62 to 0.79) in Sweden and 0.68 (0.60 to 0.76) in the UK. Differences in risk between hospital quarters of treatment for non-ST elevation myocardial infarction and secondary prevention drugs for all discharged acute myocardial infarction patients were smaller than for reperfusion treatment in both countries., Conclusion: Between hospital variation in 30 day mortality for acute myocardial infarction was greater in the UK than in Sweden. This was associated with, and may be partly accounted for by, the higher practice variation in acute myocardial infarction guideline recommended treatment in the UK hospitals. High quality healthcare across all hospitals, especially in the UK, with better use of guideline recommended treatment, may not only reduce unacceptable practice variation but also deliver improved clinical outcomes for patients with acute myocardial infarction. Clinical trials registration Clinical trials NCT01359033., (© Chung et al 2015.)

Objectives: To investigate whether the use and timing of prescription of β blockers in patients with chronic obstructive pulmonary disease (COPD) having a first myocardial infarction was associated with survival and to identify factors related to their use., Design: Population based cohort study in England., Setting: UK national registry of myocardial infarction (Myocardial Ischaemia National Audit Project (MINAP)) linked to the General Practice Research Database (GPRD), 2003-11., Participants: Patients with COPD with a first myocardial infarction in 1 January 2003 to 31 December 2008 as recorded in MINAP, who had no previous evidence of myocardial infarction in their GPRD or MINAP record. Data were provided by the Cardiovascular Disease Research using Linked Bespoke studies and Electronic Health Records (CALIBER) group at University College London., Main Outcome Measure: Cox proportional hazards ratio for mortality after myocardial infarction in patients with COPD in those prescribed β blockers or not, corrected for covariates including age, sex, smoking status, drugs, comorbidities, type of myocardial infarction, and severity of infarct., Results: Among 1063 patients with COPD, treatment with β blockers started during the hospital admission for myocardial infarction was associated with substantial survival benefits (fully adjusted hazard ratio 0.50, 95% confidence interval 0.36 to 0.69; P<0.001; median follow-up time 2.9 years). Patients already taking a β blocker before their myocardial infarction also had a survival benefit (0.59, 0.44 to 0.79; P<0.001). Similar results were obtained with propensity scores as an alternative method to adjust for differences between those prescribed and not prescribed β blockers. With follow-up started from date of discharge from hospital, the effect size was slightly attenuated but there was a similar protective effect of treatment with β blockers started during hospital admission for myocardial infarction (0.64, 0.44 to 0.94; P=0.02)., Conclusions: The use of β blockers started either at the time of hospital admission for myocardial infarction or before a myocardial infarction is associated with improved survival after myocardial infarction in patients with COPD., Registration: NCT01335672.

Objective: To determine the completeness and diagnostic validity of myocardial infarction recording across four national health record sources in primary care, hospital care, a disease registry, and mortality register., Design: Cohort study., Participants: 21 482 patients with acute myocardial infarction in England between January 2003 and March 2009, identified in four prospectively collected, linked electronic health record sources: Clinical Practice Research Datalink (primary care data), Hospital Episode Statistics (hospital admissions), the disease registry MINAP (Myocardial Ischaemia National Audit Project), and the Office for National Statistics mortality register (cause specific mortality data)., Setting: One country (England) with one health system (the National Health Service)., Main Outcome Measures: Recording of acute myocardial infarction, incidence, all cause mortality within one year of acute myocardial infarction, and diagnostic validity of acute myocardial infarction compared with electrocardiographic and troponin findings in the disease registry (gold standard)., Results: Risk factors and non-cardiovascular coexisting conditions were similar across patients identified in primary care, hospital admission, and registry sources. Immediate all cause mortality was highest among patients with acute myocardial infarction recorded in primary care, which (unlike hospital admission and disease registry sources) included patients who did not reach hospital, but at one year mortality rates in cohorts from each source were similar. 5561 (31.0%) patients with non-fatal acute myocardial infarction were recorded in all three sources and 11 482 (63.9%) in at least two sources. The crude incidence of acute myocardial infarction was underestimated by 25-50% using one source compared with using all three sources. Compared with acute myocardial infarction defined in the disease registry, the positive predictive value of acute myocardial infarction recorded in primary care was 92.2% (95% confidence interval 91.6% to 92.8%) and in hospital admissions was 91.5% (90.8% to 92.1%)., Conclusion: Each data source missed a substantial proportion (25-50%) of myocardial infarction events. Failure to use linked electronic health records from primary care, hospital care, disease registry, and death certificates may lead to biased estimates of the incidence and outcome of myocardial infarction., Trial Registration: NCT01569139 clinicaltrials.gov.

Objective: To measure the association between use of proton pump inhibitors and a range of harmful outcomes in patients using clopidogrel and aspirin., Design: Observational cohort study and self controlled case series., Setting: United Kingdom General Practice Research Database with linked data from the Myocardial Ischaemia National Audit Project (MINAP) and the Office for National Statistics (the cardiovascular disease research using linked bespoke studies and electronic records (CALIBER) collaboration), Population: 24,471 patients receiving clopidogrel and aspirin., Main Outcome Measures: The primary outcome was death or incident myocardial infarction. Secondary outcomes were death, incident myocardial infarction, vascular death, and non-vascular death. Comparisons were made between proton pump inhibitor use and non-use., Results: Of the 24,471 patients prescribed clopidogrel and aspirin, 12,439 (50%) were also prescribed a proton pump inhibitor at some time during the study. Death or incident myocardial infarction occurred in 1419 (11%) patients while they were receiving a proton pump inhibitor compared with 1341 (8%) who were not receiving a proton pump inhibitor. In multivariate analysis, the hazard ratio for the association between proton pump inhibitor use and death or incident myocardial infarction was 1.37 (95% confidence interval 1.27 to 1.48). Comparable results were seen for secondary outcomes and with other 2C19 inhibitors and with non-2C19 inhibitors. With the self controlled case series design to remove the effect of differences between people, there was no association between proton pump inhibitor use and myocardial infarction, with a rate ratio of 0.75 (0.55 to 1.01). Similarly, with the self controlled case series there was no association with myocardial infarction for other 2C19 inhibitors/non-inhibitors., Conclusion: The lack of a specific association and the discrepancy between findings of the analyses between and within people suggests that the interaction between proton pump inhibitors and clopidogrel is clinically unimportant.

Objective: To determine the effectiveness and cost effectiveness of using information from circulating biomarkers to inform the prioritisation process of patients with stable angina awaiting coronary artery bypass graft surgery., Design: Decision analytical model comparing four prioritisation strategies without biomarkers (no formal prioritisation, two urgency scores, and a risk score) and three strategies based on a risk score using biomarkers: a routinely assessed biomarker (estimated glomerular filtration rate), a novel biomarker (C reactive protein), or both. The order in which to perform coronary artery bypass grafting in a cohort of patients was determined by each prioritisation strategy, and mean lifetime costs and quality adjusted life years (QALYs) were compared., Data Sources: Swedish Coronary Angiography and Angioplasty Registry (9935 patients with stable angina awaiting coronary artery bypass grafting and then followed up for cardiovascular events after the procedure for 3.8 years), and meta-analyses of prognostic effects (relative risks) of biomarkers., Results: The observed risk of cardiovascular events while on the waiting list for coronary artery bypass grafting was 3 per 10,000 patients per day within the first 90 days (184 events in 9935 patients). Using a cost effectiveness threshold of pound20,000- pound30,000 (euro22,000-euro33,000; $32,000-$48,000) per additional QALY, a prioritisation strategy using a risk score with estimated glomerular filtration rate was the most cost effective strategy (cost per additional QALY was < pound410 compared with the Ontario urgency score). The impact on population health of implementing this strategy was 800 QALYs per 100,000 patients at an additional cost of pound 245,000 to the National Health Service. The prioritisation strategy using a risk score with C reactive protein was associated with lower QALYs and higher costs compared with a risk score using estimated glomerular filtration rate., Conclusion: Evaluating the cost effectiveness of prognostic biomarkers is important even when effects at an individual level are small. Formal prioritisation of patients awaiting coronary artery bypass grafting using a routinely assessed biomarker (estimated glomerular filtration rate) along with simple, routinely collected clinical information was cost effective. Prioritisation strategies based on the prognostic information conferred by C reactive protein, which is not currently measured in this context, or a combination of C reactive protein and estimated glomerular filtration rate, is unlikely to be cost effective. The widespread practice of using only implicit or informal means of clinically ordering the waiting list may be harmful and should be replaced with formal prioritisation approaches.

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.

Objective: To determine whether resting and exercise electrocardiograms (ECGs) provide prognostic value that is incremental to that obtained from the clinical history in ambulatory patients with suspected angina attending chest pain clinics., Design: Multicentre cohort study., Setting: Rapid access chest pain clinics of six hospitals in England., Participants: 8176 consecutive patients with suspected angina and no previous diagnosis of coronary artery disease, all of whom had a resting ECG recorded. 4848 patients with a summary exercise ECG result recorded (positive, negative, equivocal for ischaemia) comprised the summary ECG subset of whom 1422 with more detailed exercise ECG data recorded comprised the detailed ECG subset., Main Outcome Measure: Composite of death due to coronary heart disease or non-fatal acute coronary syndrome during median follow-up of 2.46 years., Results: Receiver operating characteristics curves for the basic clinical assessment model alone and with the results of resting ECGs were superimposed with little difference in the C statistic. With the exercise ECGs the C statistic in the summary ECG subset increased from 0.70 (95% confidence interval 0.68 to 0.73) to 0.74 (0.71 to 0.76) and in the detailed ECG subset from 0.74 (0.70 to 0.79) to 0.78 (0.74 to 0.82). However, risk stratified cumulative probabilities of the primary end point at one year and six years for all three prognostic indices (clinical assessment only; clinical assessment plus resting ECG; clinical assessment plus resting ECG plus exercise ECG) showed only small differences at all time points and at all levels of risk., Conclusion: In ambulatory patients with suspected angina, basic clinical assessment encompasses nearly all the prognostic value of resting ECGs and most of the prognostic value of exercise ECGs. The limited incremental value of these widely applied tests emphasises the need for more effective methods of risk stratification in this group of patients.

Objectives: To determine whether coronary angiography for suspected stable angina pectoris is underused in older patients, women, south Asian patients, and those from socioeconomically deprived areas, and, if it is, whether this is associated with higher coronary event rates., Design: Multicentre cohort with five year follow-up., Setting: Six ambulatory care clinics in England., Participants: 1375 consecutive patients in whom coronary angiography was individually rated as appropriate with the Rand consensus method., Main Outcome Measures: Receipt of angiography (420 procedures); coronary mortality and acute coronary syndrome events., Results: In a multivariable analysis, angiography was less likely to be performed in patients aged over 64 compared with those aged under 50 (hazard ratio 0.60, 95% confidence interval 0.38 to 0.96), women compared with men (0.42, 0.35 to 0.50), south Asians compared with white people (0.48, 0.34 to 0.67), and patients in the most deprived fifth compared with the other four fifths (0.66, 0.40 to 1.08). Not undergoing angiography when it was deemed appropriate was associated with higher rates of coronary event., Conclusions: At an early stage after presentation with suspected angina, coronary angiography is underused in older people, women, south Asians, and people from deprived areas. Not receiving appropriate angiography was associated with a higher risk of coronary events in all groups. Interventions based on clinical guidance that supports individualised management decisions might improve access and outcomes.

Objective: To assess whether revascularisation that is considered to be clinically appropriate is also cost effective., Design: Prospective observational study comparing cost effectiveness of coronary artery bypass grafting, percutaneous coronary intervention, or medical management within groups of patients rated as appropriate for revascularisation., Setting: Three tertiary care centres in London., Participants: Consecutive, unselected patients rated as clinically appropriate (using a nine member Delphi panel) to receive coronary artery bypass grafting only (n=815); percutaneous coronary intervention only (n=385); or both revascularisation procedures (n=520)., Main Outcome Measure: Cost per quality adjusted life year gained over six year follow-up, calculated with a National Health Service cost perspective and discounted at 3.5%/year., Results: Coronary artery bypass grafting cost 22,000 pounds sterling (33,000 euros; $43,000) per quality adjusted life year gained compared with percutaneous coronary intervention among patients appropriate for coronary artery bypass grafting only (59% probability of being cost effective at a cost effectiveness threshold of 30,000 pounds sterling per quality adjusted life year) and 19,000 pounds sterling per quality adjusted life year gained compared with medical management among those appropriate for both types of revascularisation (probability of being cost effective 63%). In none of the three appropriateness groups was percutaneous coronary intervention cost effective at a threshold of 30,000 pounds sterling per quality adjusted life year. Among patients rated appropriate for percutaneous coronary intervention only, the cost per quality adjusted life year gained for percutaneous coronary intervention compared with medical management was 47,000, pounds sterling exceeding usual cost effectiveness thresholds; in these patients, medical management was most likely to be cost effective (probability 54%)., Conclusions: Among patients judged clinically appropriate for coronary revascularisation, coronary artery bypass grafting seemed cost effective but percutaneous coronary intervention did not. Cost effectiveness analysis based on observational data suggests that the clinical benefit of percutaneous coronary intervention may not be sufficient to justify its cost.

Objective: To evaluate the effect of opt-in compared with opt-out recruitment strategies on response rate and selection bias., Design: Double blind randomised controlled trial., Setting: Two general practices in England., Participants: 510 patients with angina., Intervention: Patients were randomly allocated to an opt-in (asked to actively signal willingness to participate in research) or opt-out (contacted repeatedly unless they signalled unwillingness to participate) approach for recruitment to an observational prognostic study of patients with angina., Main Outcome Measures: Recruitment rate and clinical characteristics of patients., Results: The recruitment rate, defined by clinic attendance, was 38% (96/252) in the opt-in arm and 50% (128/258) in the opt-out arm (P = 0.014). Once an appointment had been made, non-attendance at the clinic was similar (20% opt-in arm v 17% opt-out arm; P = 0.86). Patients in the opt-in arm had fewer risk factors (44% v 60%; P = 0.053), less treatment for angina (69% v 82%; P = 0.010), and less functional impairment (9% v 20%; P = 0.023) than patients in the opt-out arm., Conclusions: The opt-in approach to participant recruitment, increasingly required by ethics committees, resulted in lower response rates and a biased sample. We propose that the opt-out approach should be the default recruitment strategy for studies with low risk to participants.

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.

Objective: To investigate the prognosis of angina among people with and without diagnosis by a doctor and an abnormal cardiovascular test result., Design: Prospective cohort study with a median follow up of 11 years., Setting: 20 civil service departments originally located in London., Participants: 10 308 civil servants aged 35-55 years at baseline., Main Outcome Measures: Recurrent reports of angina; quality of life (SF-36 physical functioning); non-fatal myocardial infarction; death from any cause (n = 344)., Results: 1158 (11.4%) participants developed angina, and 813 (70%) had no evidence of diagnosis by a doctor at the time of the initial report. Participants without a diagnosis had an increased risk of impaired physical functioning (age and sex adjusted odds ratio of 2.36 (95% confidence interval 1.91 to 2.90)) compared with those who had neither angina nor myocardial infarction throughout follow up. Among reported cases of angina without a diagnosis, the 15.5% with an abnormality on a study electrocardiogram had an increased risk of death (hazard ratio 2.37 (1.16 to 4.87)). These effects were similar in magnitude to those in participants with a diagnosis of angina., Conclusion: Undiagnosed angina was common and had an adverse impact on prognosis comparable to that of diagnosed angina, particularly among people with electrocardiographic abnormalities. Efforts to improve prognosis among people with angina should take account of this submerged clinical iceberg.

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.

Objective: To measure within-person change in scores on the short form general health survey (SF-36) by age, sex, employment grade, and disease status., Design: Longitudinal study with a mean of 36 months (range 23-59 months) follow up, with screening examination and questionnaire to detect physical and psychiatric morbidity., Setting: 20 civil service departments originally located in London., Participants: 5070 male and 2197 female office based civil servants aged 39-63 years., Main Outcome Measures: Change in the eight scales of the SF-36 (adjusted for baseline score and length of follow up) and effect sizes (adjusted change standard deviation of differences)., Results: Within-person declines (worsening health) with age were greater than estimated by cross sectional data alone. General mental health showed greater declines among younger participants (P for linear trend < 0.001). Employment grade was inversely related to change; lower grades had greater deteriorations than higher grades (P < 0.001 for each scale in men; P < 0.05 for each scale in women except general health perceptions and role limitations due to physical problems). The greatest declines were seen among participants with disease at baseline, with the effects of physical and psychiatric morbidity being additive. Effect sizes ranged from 0.20 to 0.65 in participants with both physical and psychiatric morbidity., Conclusions: Health functioning, as measured by the SF-36, changed in hypothesised directions with age, employment grade, and disease status. These changes occurred within a short follow up period, in an occupational, high functioning cohort which has not been the subject of intervention, suggesting that the SF-36 is sensitive to changes in health in general populations.

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.