On the estimation of the effect of weight change on a health outcome using observational data, by utilising the target trial emulation framework.

BACKGROUND/OBJECTIVES: When studying the effect of weight change between two time points on a health outcome using observational data, two main problems arise initially (i) 'when is time zero?' and (ii) 'which confounders should we account for?' From the baseline date or the 1st follow-up (when the weight change can be measured)? Different methods have been previously used in the literature that carry different sources of bias and hence produce different results. METHODS: We utilised the target trial emulation framework and considered weight change as a hypothetical intervention. First, we used a simplified example from a hypothetical randomised trial where no modelling is required. Then we simulated data from an observational study where modelling is needed. We demonstrate the problems of each of these methods and suggest a strategy. INTERVENTIONS: weight loss/gain vs maintenance. RESULTS: The recommended method defines time-zero at enrolment, but adjustment for confounders (or exclusion of individuals based on levels of confounders) should be performed both at enrolment and the 1st follow-up. CONCLUSIONS: The implementation of our suggested method [adjusting for (or excluding based on) confounders measured both at baseline and the 1st follow-up] can help researchers attenuate bias by avoiding some common pitfalls. Other methods that have been widely used in the past to estimate the effect of weight change on a health outcome are more biased. However, two issues remain (i) the exposure is not well-defined as there are different ways of changing weight (however we tried to reduce this problem by excluding individuals who develop a chronic disease); and (ii) immortal time bias, which may be small if the time to first follow up is short.

Obesity during the COVID-19 pandemic: both cause of high risk and potential effect of lockdown? A population-based electronic health record study.

OBJECTIVES: Obesity is a modifiable risk factor for coronavirus disease 2019 (COVID-19)-related mortality. We estimated excess mortality in obesity, both 'direct', through infection, and 'indirect', through changes in health care, and also due to potential increasing obesity during lockdown. STUDY DESIGN: The study design of this study is a retrospective cohort study and causal inference methods. METHODS: In population-based electronic health records for 1,958,638 individuals in England, we estimated 1-year mortality risk ('direct' and 'indirect' effects) for obese individuals, incorporating (i) pre-COVID-19 risk by age, sex and comorbidities, (ii) population infection rate and (iii) relative impact on mortality (relative risk [RR]: 1.2, 1.5, 2.0 and 3.0). Using causal inference models, we estimated impact of change in body mass index (BMI) and physical activity during 3-month lockdown on 1-year incidence for high-risk conditions (cardiovascular diseases, diabetes, chronic obstructive pulmonary disease and chronic kidney disease), accounting for confounders. RESULTS: For severely obese individuals (3.5% at baseline), at 10% population infection rate, we estimated direct impact of 240 and 479 excess deaths in England at RR 1.5 and 2.0, respectively, and indirect effect of 383-767 excess deaths, assuming 40% and 80% will be affected at RR = 1.2. Owing to BMI change during the lockdown, we estimated that 97,755 (5.4%: normal weight to overweight, 5.0%: overweight to obese and 1.3%: obese to severely obese) to 434,104 individuals (15%: normal weight to overweight, 15%: overweight to obese and 6%: obese to severely obese) would be at higher risk for COVID-19 over one year. CONCLUSIONS: Prevention of obesity and promotion of physical activity are at least as important as physical isolation of severely obese individuals during the pandemic.

Incidence and prognosis of angina pectoris in South Asians and Whites: 18 years of follow-up over seven phases in the Whitehall-II prospective cohort study.

BACKGROUND: Whether the higher coronary mortality in South Asians compared with White populations is due to a higher incidence of disease is not known. This study assessed cumulative incidence of chest pain in South Asians and Whites, and prognosis of chest pain. METHODS: Over seven phases of 18-year follow-up of the Whitehall-II study (9,775 civil servants: 9,195 White, 580 South Asian), chest pain was assessed using the Rose questionnaire. Coronary death/non-fatal myocardial infarction was examined comparing those with chest pain to those with no chest pain at baseline. RESULTS: South Asians had higher cumulative frequencies of typical angina by Phase 7 (17.0 versus 11.3%, P < 0.001) and exertional chest pain (15.4 versus 8.5%, P < 0.001) compared with Whites. Typical angina and exertional chest pain at baseline were associated with a worse prognosis compared with those with no chest pain in both groups (typical angina, South Asians: HR, 4.67 and 95% CI, 2.12-0.30; Whites: HR, 3.56 95% CI, 2.59-4.88). Baseline non-exertional chest pain did not confer a worse prognosis. Across all types of pain, prognosis was worse in South Asians. CONCLUSION: South Asians had higher cumulative incidence of angina than Whites. In both, typical angina and exertional chest pain were associated with worse prognosis compared with those with no chest pain.

A national initiative in data science for health: an evaluation of the UK Farr Institute.

OBJECTIVE: To evaluate the extent to which the inter-institutional, inter-disciplinary mobilisation of data and skills in the Farr Institute contributed to establishing the emerging field of data science for health in the UK. DESIGN AND OUTCOME MEASURES: We evaluated evidence of six domains characterising a new field of science:defining central scientific challenges,demonstrating how the central challenges might be solved,creating novel interactions among groups of scientists,training new types of experts,re-organising universities,demonstrating impacts in society.We carried out citation, network and time trend analyses of publications, and a narrative review of infrastructure, methods and tools. SETTING: Four UK centres in London, North England, Scotland and Wales (23 university partners), 2013-2018. RESULTS: 1. The Farr Institute helped define a central scientific challenge publishing a research corpus, demonstrating insights from electronic health record (EHR) and administrative data at each stage of the translational cycle in 593 papers with at least one Farr Institute author affiliation on PubMed. 2. The Farr Institute offered some demonstrations of how these scientific challenges might be solved: it established the first four ISO27001 certified trusted research environments in the UK, and approved more than 1000 research users, published on 102 unique EHR and administrative data sources, although there was no clear evidence of an increase in novel, sustained record linkages. The Farr Institute established open platforms for the EHR phenotyping algorithms and validations (>70 diseases, CALIBER). Sample sizes showed some evidence of increase but remained less than 10% of the UK population in primary care-hospital care linked studies. 3.The Farr Institute created novel interactions among researchers: the co-author publication network expanded from 944 unique co-authors (based on 67 publications in the first 30 months) to 3839 unique co-authors (545 papers in the final 30 months). 4. Training expanded substantially with 3 new masters courses, training >400 people at masters, short-course and leadership level and 48 PhD students. 5. Universities reorganised with 4/5 Centres established 27 new faculty (tenured) positions, 3 new university institutes. 6. Emerging evidence of impacts included: > 3200 citations for the 10 most cited papers and Farr research informed eight practice-changing clinical guidelines and policies relevant to the health of millions of UK citizens. CONCLUSION: The Farr Institute played a major role in establishing and growing the field of data science for health in the UK, with some initial evidence of benefits for health and healthcare. The Farr Institute has now expanded into Health Data Research (HDR) UK but key challenges remain including, how to network such activities internationally.

Long-term excess mortality associated with diabetes following acute myocardial infarction: a population-based cohort study.

BACKGROUND: The long-term excess risk of death associated with diabetes following acute myocardial infarction is unknown. We determined the excess risk of death associated with diabetes among patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) after adjustment for comorbidity, risk factors and cardiovascular treatments. METHODS: Nationwide population-based cohort (STEMI n=281 259 and NSTEMI n=422 661) using data from the UK acute myocardial infarction registry, MINAP, between 1 January 2003 and 30 June 2013. Age, sex, calendar year and country-specific mortality rates for the populace of England and Wales (n=56.9 million) were matched to cases of STEMI and NSTEMI. Flexible parametric survival models were used to calculate excess mortality rate ratios (EMRR) after multivariable adjustment. This study is registered at ClinicalTrials.gov (NCT02591576). RESULTS: Over 1.94 million person-years follow-up including 120 568 (17.1%) patients with diabetes, there were 187 875 (26.7%) deaths. Overall, unadjusted (all cause) mortality was higher among patients with than without diabetes (35.8% vs 25.3%). After adjustment for age, sex and year of acute myocardial infarction, diabetes was associated with a 72% and 67% excess risk of death following STEMI (EMRR 1.72, 95% CI 1.66 to 1.79) and NSTEMI (1.67, 1.63 to 1.71). Diabetes remained significantly associated with substantial excess mortality despite cumulative adjustment for comorbidity (EMRR 1.52, 95% CI 1.46 to 1.58 vs 1.45, 1.42 to 1.49), risk factors (1.50, 1.44 to 1.57 vs 1.33, 1.30 to 1.36) and cardiovascular treatments (1.56, 1.49 to 1.63 vs 1.39, 1.36 to 1.43). CONCLUSIONS: At index acute myocardial infarction, diabetes was common and associated with significant long-term excess mortality, over and above the effects of comorbidities, risk factors and cardiovascular treatments.

Rapid-access chest pain clinics and the traditional cardiology out-patient clinic.

BACKGROUND: The National Service Framework for coronary heart disease recommends rapid-access chest pain clinics (RACPCs) for cardiological assessment of new-onset chest pain within 2 weeks of referral. AIM: To measure the extent to which an RACPC successfully substituted for an out-patient cardiology clinic (OPCC) at a general hospital, in assessing new-onset chest pain referrals. METHODS: Prospective measurement of attendance and waiting times for consecutive patients at the RACPC and OPCC, and multivariate analysis of factors associated with referral for angiography. RESULTS: From September 2002 to August 2004, 1382 patients with chest pain attended the RACPC, and 228 patients, the OPCC. All RACPC patients were seen within 24 h of referral, except those referred on Friday afternoons, or the day before national holidays. The mean +/- SD waiting time for OPCC appointments was 97 +/- 43 days. Of 208 OPCC patients, 30 (14%) fulfilled the RACPC referral criterion of recent onset chest pain (<4 weeks duration) vs. 926/1382 (67%) RACPC patients. Thus the RACPC substituted for the OPCC in 926/956 (97%) new chest pain referrals. Patients from the OPCC were 3.82 (95%CI 1.85-7.90) more likely to be referred for a coronary angiogram. compared to those attending the RACPC. DISCUSSION: The RACPC has provided efficient and effective substitution for the OPCC in the assessment of new chest pain referrals according to pre-defined referral criteria. Broadening the referral criterion of the RACPC to patients with chest pain of >4 weeks duration would result in more referrals.

Prolonged dual antiplatelet therapy in stable coronary disease: comparative observational study of benefits and harms in unselected versus trial populations.

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.

Geographic variation in the treatment of non-ST-segment myocardial infarction in the English National Health Service: a cohort study.

OBJECTIVES: To investigate geographic variation in guideline-indicated treatments for non-ST-elevation myocardial infarction (NSTEMI) in the English National Health Service (NHS). DESIGN: Cohort study using registry data from the Myocardial Ischaemia National Audit Project. SETTING: All Clinical Commissioning Groups (CCGs) (n=211) in the English NHS. PARTICIPANTS: 357 228 patients with NSTEMI between 1 January 2003 and 30 June 2013. MAIN OUTCOME MEASURE: Proportion of eligible NSTEMI who received all eligible guideline-indicated treatments (optimal care) according to the date of guideline publication. RESULTS: The proportion of NSTEMI who received optimal care was low (48 257/357 228; 13.5%) and varied between CCGs (median 12.8%, IQR 0.7-18.1%). The greatest geographic variation was for aldosterone antagonists (16.7%, 0.0-40.0%) and least for use of an ECG (96.7%, 92.5-98.7%). The highest rates of care were for acute aspirin (median 92.8%, IQR 88.6-97.1%), and aspirin (90.1%, 85.1-93.3%) and statins (86.4%, 82.3-91.2%) at hospital discharge. The lowest rates were for smoking cessation advice (median 11.6%, IQR 8.7-16.6%), dietary advice (32.4%, 23.9-41.7%) and the prescription of P2Y12 inhibitors (39.7%, 32.4-46.9%). After adjustment for case mix, nearly all (99.6%) of the variation was due to between-hospital differences (median 64.7%, IQR 57.4-70.0%; between-hospital variance: 1.92, 95% CI 1.51 to 2.44; interclass correlation 0.996, 95% CI 0.976 to 0.999). CONCLUSIONS: Across the English NHS, the optimal use of guideline-indicated treatments for NSTEMI was low. Variation in the use of specific treatments for NSTEMI was mostly explained by between-hospital differences in care. Performance-based commissioning may increase the use of NSTEMI treatments and, therefore, reduce premature cardiovascular deaths. TRIAL REGISTRATION NUMBER: NCT02436187.

Adrenocortical, autonomic, and inflammatory causes of the metabolic syndrome: nested case-control study.

BACKGROUND: The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, are uncertain. We hypothesize that disturbances in neuroendocrine and cardiac autonomic activity (CAA) contribute to development of MS. We examine reversibility and the power of psychosocial and behavioral factors to explain the neuroendocrine adaptations that accompany MS. METHODS AND RESULTS: This was a double-blind case-control study of working men aged 45 to 63 years drawn from the Whitehall II cohort. MS cases (n=30) were compared with healthy controls (n=153). Cortisol secretion, sensitivity, and 24-hour cortisol metabolite and catecholamine output were measured over 2 days. CAA was obtained from power spectral analysis of heart rate variability (HRV) recordings. Twenty-four-hour cortisol metabolite and normetanephrine (3-methoxynorepinephrine) outputs were higher among cases than controls (+ 0.49, +0.45 SD, respectively). HRV and total power were lower among cases (both -0.72 SD). Serum interleukin-6, plasma C-reactive protein, and viscosity were higher among cases (+0.89, +0.51, and +0.72 SD). Lower HRV was associated with higher normetanephrine output (r=-0.19; P=0.03). Among former cases (MS 5 years previously, n=23), cortisol output, heart rate, and interleukin-6 were at the level of controls. Psychosocial factors accounted for 37% of the link between MS and normetanephrine output, and 7% to 19% for CAA. Health-related behaviors accounted for 5% to 18% of neuroendocrine differences. CONCLUSIONS: Neuroendocrine stress axes are activated in MS. There is relative cardiac sympathetic predominance. The neuroendocrine changes may be reversible. This case-control study provides the first evidence that chronic stress may be a cause of MS. Confirmatory prospective studies are required.

Mortality and missed opportunities along the pathway of care for ST-elevation myocardial infarction: a national cohort study.

AIMS: To examine the association between cumulative missed opportunities for care (CMOC) and mortality in patients with ST-elevation myocardial infarction (STEMI). METHODS: A cohort study of 112,286 STEMI patients discharged from hospital alive between January 2007 and December 2010, using data from the Myocardial Ischaemia National Audit Project (MINAP). A CMOC score was calculated for each patient and included: pre-hospital ECG, acute use of aspirin, timely reperfusion, prescription at hospital discharge of aspirin, thienopyridine inhibitor, ACE-inhibitor (or equivalent), HMG-CoA reductase inhibitor and ß-blocker, and referral for cardiac rehabilitation. Mixed-effects logistic regression models evaluated the effect of CMOC on risk-adjusted 30-day and 1-year mortality (RAMR). RESULTS: 44.5% of patients were ineligible for ≥1 care component. Of patients eligible for all nine components, 50.6% missed ≥1 opportunity. Pre-hospital ECG and timely reperfusion were most frequently missed, predicting further missed care at discharge (pre-hospital ECG incident rate ratio [95% CI]: 1.64 [1.58-1.70]; timely reperfusion 9.94 [9.51-10.40]). Patients ineligible for care had higher RAMR than those eligible for care (30-days: 1.7% vs. 1.1%; 1-year: 8.6% vs. 5.2%), whilst those with no missed care had lower mortality than patients with ≥4 CMOC (30-days: 0.5% vs. 5.4%, adjusted OR (aOR) per CMOC group 1.22, 95% CI: 1.05-1.42; 1-year: 3.2% vs. 22.8%, aOR 1.23, 1.13-1.34). CONCLUSIONS: Opportunities for care in STEMI are commonly missed and significantly associated with early and later mortality. Thus, outcomes after STEMI may be improved by greater attention to missed opportunities to eligible care.

Discussion of "Combining Health Data Uses to Ignite Health System Learning".

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Combining Health Data Uses to Ignite Health System Learning" written by John D. Ainsworth and Iain E. Buchan [1]. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the paper of Ainsworth and Buchan. In subsequent issues the discussion can continue through letters to the editor. With these comments on the paper "Combining Health Data Uses to Ignite Health System Learning", written by John D. Ainsworth and Iain E. Buchan [1], the journal seeks to stimulate a broad discussion on new ways for combining data sources for the reuse of health data in order to identify new opportunities for health system learning. An international group of experts has been invited by the editor of Methods to comment on this paper. Each of the invited commentaries forms one section of this paper.

Differences in biological risk factors for cardiovascular disease between three ethnic groups in the Whitehall II study.

This study compares risk factors for cardiovascular disease in civil servants of three ethnic groups screened as part of the Whitehall II cohort study. Previously identified risk factors for cardiovascular disease in 360 Afro-Caribbean and 577 South Asian subjects are compared with the 8973 white Caucasian subjects. Controlling for socio-economic status is more precise than in most previous studies of cardiovascular differences between ethnic groups. After controlling for socio-economic confounding factors, age and sex, South Asian subjects were found to have increased prevalence of hypertension (defined as either having systolic pressure of > 160, diastolic pressure of > 95 or being on antihypertensives) OR 2.3 (95% CI 1.6-3.3), diabetes OR 4.2 (95%, CI 3.0-5.8) and a high risk lipid profile, although total cholesterol was lower than in the white population. Afro-Caribbean subjects had more hypertension OR 4.0 (95% CI 2.8-5.7) and diabetes OR 2.8 (95% CI 1.7-4.6), but this was accompanied by a favourable lipid profile with low cholesterol and high HDL. Afro-Caribbean alcohol and smoking habits were low-risk. Socio-economic status was found to be an important confounding factor for ethnic differences in biochemical risk factors for cardiovascular disease. However, adjusting for socioeconomic class only attenuates observed differences; it does not abolish them.

Magnitude and consequences of error in coronary angiography interpretation (the ACRE study).

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.

Seasonal variation in cause-specific mortality: are there high-risk groups? 25-year follow-up of civil servants from the first Whitehall study.

OBJECTIVES: To determine the seasonal effect on all-cause and cause-specific mortality and to identify high-risk groups. METHODS: A 25-year follow-up of 19,019 male civil servants aged 40-69 years. RESULTS: All-cause mortality was seasonal (ratio of highest mortality rate during winter versus lowest rate during summer 1.22, 95% CI : 1.1-1.3), largely due to the seasonal nature of ischaemic heart disease. Participants at high risk based on age, employment grade, blood pressure, cholesterol, forced expiratory volume, smoking and diabetes did not have higher seasonal mortality, although participants with ischaemic heart disease at baseline did have a higher seasonality effect (1.38, 95% CI : 1.2-1.6) than those without (1.18, 95% CI : 1.1-1.3) (P = 0.03). CONCLUSIONS: Seasonal mortality differences were greater among those with prevalent ischaemic heart disease and at older ages, but were not greater in individuals of lower socioeconomic status or with a high multivariate risk score. Since seasonal differences showed no evidence of declining over time, elucidating their causes and preventive strategies remains a public health challenge.

Human angiotensin I-converting enzyme gene and endurance performance.

Human physical performance is strongly influenced by genetic factors. A variation in the structure of the human angiotensin I-converting enzyme (ACE) gene has been reported in which the insertion (I) variant is associated with lower ACE levels than the deletion (D) gene. We have previously reported that the I variant was associated with improved endurance performance in high-altitude mountaineers and British Army recruits. We now examine this genotype distribution in 91 British Olympic-standard runners (79 Caucasians). DNA was extracted from the buccal cells contained in 10 ml of saline mouthwash donated by the subjects, and the I and D variants of the ACE gene were identified by PCR amplification of the polymorphic region. There was an increasing frequency of the I allele with distance run [0.35, 0.53, and 0.62 for /=5,000 m (n = 34), respectively; P = 0.009 for linear trend]. Among 404 Olympic-standard athletes from 19 other mixed sporting disciplines (in which endurance performance was not necessarily a key factor), the I allele did not differ significantly from that found in control subjects: 0.50 vs. 0.49 (P = 0.526). These results support a positive association of the I allele with elite endurance performance.

Relative contribution of early life and adult socioeconomic factors to adult morbidity in the Whitehall II study.

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.

Impact of socioeconomic status on coronary mortality in people with symptoms, electrocardiographic abnormalities, both or neither: the original Whitehall study 25 year follow up.

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.

Is retirement good or bad for mental and physical health functioning? Whitehall II longitudinal study of civil servants.

BACKGROUND: To determine whether retirement at age 60 is associated with improvement or deterioration in mental and physical health, when analysed by occupational grade and gender. METHODS: Longitudinal study of civil servants aged 54 to 59 years at baseline, comparing changes in SF-36 health functioning in retired (n=392) and working (n=618) participants at follow up. Data were collected from self completed questionnaires. RESULTS: Mental health functioning deteriorated among those who continued to work, but improved among the retired. However, improvements in mental health were restricted to those in higher employment grades. Physical functioning declined in both working and retired civil servants. CONCLUSION: The study found that retirement at age 60 had no effects on physical health functioning and, if anything, was associated with an improvement in mental health, particularly among high socioeconomic status groups.

Behavioural and biological correlates of physical functioning in middle aged office workers: the UK whitehall II study.

STUDY OBJECTIVES: (1) To identify behavioural and biological correlates of poor physical functioning and (2) to determine whether such associations are independent of disease. DESIGN: Potential correlates were obtained from questionnaires and screening visits at baseline and five year follow up. Physical functioning was measured at follow up using the 10 item scale from the short-form 36 health survey. SETTING: London offices at baseline. PARTICIPANTS: 10,308 civil servants (6895 men and 3413 women), with a median age (range) of 49 years (39-63) at follow up. MAIN RESULTS: Multiple logistic regression showed that cigarette smoking, physical activity, body mass index (BMI), triglycerides, fibrinogen, and insulin were independently associated with poor physical functioning for men. For women, physical activity, eating habits, body mass index, fibrinogen, and insulin were independently associated with poor physical functioning. For example, among men, current smokers who had smoked more than 20 pack years were 1.89 (95% CI 1.35 to 2.67) times as likely to have poor physical functioning as never smokers. Men with BMI of 30 kg/m2 or more were 1.71 (95% CI 1.13 to 2.59) times as likely to have poor physical functioning as those with BMI < 20 kg/m2. The corresponding odds ratio for women was 2.66 (95% CI 1.80 to 3.93). With the exceptions of fibrinogen and insulin, associations remained on exclusion of subjects with physical disease. CONCLUSIONS: Risk factors established for physical diseases are associated with poor physical functioning in a population of working age. These associations may be independent of current disease.

Are risk factors for atherothrombotic disease associated with back pain sickness absence? The Whitehall II Study.

STUDY OBJECTIVE: To explore the previously stated hypothesis that risk factors for atherothrombotic disease are associated with back pain. DESIGN: Prospective (mean of four years of follow up) and retrospective analyses using two main outcome measures: (a) short (< or = 7 days) and long (> 7 days) spells of sickness absence because of back pain reported separately in men and women; (b) consistency of effect across the resulting four duration of spell and sex cells. SETTING: 14 civil service departments in London. PARTICIPANTS: 3506 male and 1380 female white office-based civil servants, aged 35-55 years at baseline. MAIN RESULTS: In age adjusted models, low apo AI was associated with back pain across all four duration-sex cells and smoking was associated across three cells. Six factors were associated with back pain in two cells: low exercise and high BMI, waist-hip ratio, triglycerides, insulin and Lp(a). On full adjustment (for age, BMI, employment grade and back pain at baseline), each of these factors retained a statistically significant effect in at least one duration-sex cell. Triglycerides were associated with short and long spells of sickness absence because of back pain in men in fully adjusted models with rate ratios (95% confidence intervals) of 1.53 (1.1, 2.1) and 1.75 (1.0, 3.2) respectively. There was little or no evidence of association in age adjusted models with: fibrinogen, glucose tolerance, total cholesterol, apoB, hypertension, factor VII, von Willebrand factor, electrocardiographic evidence of coronary heart disease and reported angina. CONCLUSIONS: In this population of office workers, only modest support was found for an atherothrombotic component to back pain sickness absence. However, the young age of participants at baseline and the lack of distinction between different types of back pain are likely to bias the findings toward null. Further research is required to ascertain whether a population sub-group of atherothrombotic back pain can be identified.