ANÁLISIS METALOGRÁFICO 1 ALEACIÓN DE ANTENA ORIGINAL

The endpoints for analysis in this thesis are non-fatal MI (symptomatic and silent); fatal CHD; and angina pectoris (chronic stable or unstable). Full details o f the ascertainment, case definition and validation are given elsewhere but are summarised here^^"^.

iy .3 .1 Ascertainment of potential cases

The sources o f data to ascertain potential CHD cases were questionnaires, ECG’s at Phases 1, 3 and 5; sickness absence records; and death certificates.

Questionnaire

At each study phase, positive responses to any o f the following questionnaire items indicated a potential case. The relevant questions are included in Appendix 1.2.

1. Symptoms: Rose angina, or prolonged chest pain, which the doctor indicated was angina or MI or unspecified^^^. The Rose questionnaire angina was assessed using standard criteria, i.e. pain located over the sternum or in both left chest and arm, that comes on with exertion, causes the person to stop and goes away in 10 minutes or less.

2. Diagnosis investigation or treatment: (Phases 4 and 5 only)

a. “Has a doctor ever told you that you have angina/heart attack?”

b. “Have you ever had any of the following: An exercise ECG (treadmill test). Angioplasty o f coronary arteries (balloon treatment for angina). Coronary artery bypass graft (CABG). An admission to hospital with chest pain, angina or heart attack”.

c. “Have you had heart trouble suspected confirmed by your GP or hospital doctor?”, with a self-reported diagnosis o f angina or ML

The name and institutional address of GP or hospital consultant were obtained for clinical record validation.

3. General questions: on longstanding illness (coded as angina or MI), prescribed medication within last fourteen days (coded as nitrates) and hospital admissions during the last 12 months (coded as angina, MI, angiography, angioplasty or CABG).

Studv electrocardiograms

12 lead resting ECGs were performed at Phases 1, 3 and 5 using a Seimans Mingorec 4 ECG machine. The digitised images were transferred electronically to Professor Macfarlane’s laboratory in the Department o f Medical Cardiology, University o f Glasgow, where Minnesota codes (MC) were assigned by computer^^^ The presence o f any o f the following Minnesota codes on the computer coding was taken as evidence o f ischaemia: diagnostic Q waves (MC: all 1-1, 1-2-1 to 1-2-5, and 1-2-7); equivocal Q waves (MC: 1- 2-8 and all 1-3); ST segment depression (MC: 4-1 to 4-3); T wave inversion (MC: 5-1 to 5- 3); or left bundle branch block (MC: 7-1-1). All computer abnormals, and a sample of computer normals, were reviewed by an experienced manual Minnesota coder to confirm the computer code and to exclude technically poor readings. The ECG’s were classified by a combination o f computer and manual coding. Manual M C’s were assigned if there was a computer code for ischaemia.

A lower prevalence o f ECG abnormalities was noted at Phase 3 compared to Phase 1. The overall prevalence o f ischaemic abnormalities at Phase 1 was 6.1% in men and 7.0% in women, and 5.1% and 4.3% respectively at Phase 3, despite the population being on average five years older. Validation studies have shown that changes in manual coder between Phase 1 and 3 led to a lower proportion o f computer abnormals being confirmed at Phase 3.

Mortalitv records

10293 members o f the study population (99.8% o f the total) were flagged at the National Health Service (NHS) central registry at Southport, using NHS number as a unique

coding of the causes listed in parts I and II of the death certificate. Deaths with an ICD-9 code o f 410 to 414 were considered potential cases. Mortality follow-up was censored at the end of 1999, by which time there had been 355 deaths.

Sickness absence records

9564 participants (93%) gave consent at Phase 1 for follow-up based on their sickness absence records and 96% o f these (9179) were linked to their record. For two thirds of Civil Service departments, the reasons for absence were included. Records with cause of absence were available from 1988 until 1995. Participants with cardiovascular disease as a reason for absence were considered potential cases.

IV.3.2 Validation of events

Clinical record data were sought to validate all the potential CHD cases, from GP’s and hospitals. Written permission to examine such data had been obtained as part o f the questionnaire. For all CHD deaths, hospital, GP and post-mortem records were sought. Where possible investigation results were recorded but if these were not available, a diagnosis stated in the records, so-called clinical record validation, was used. A single trained coder coded the accumulated evidence and events were placed into following categories :-

Death (based on Simon^^*) Definite required death certificate plus post-mortem reports; probable required death certificate plus evidence in clinical notes; and possible required death certificate or clinical notes only. Study data did not contribute to the death classification.

MI (based on MONICA criteria) Definite required a definite ECG or hospital records with two out o f three o f [-symptoms, ischaemic ECG and enzyme changes; probable required clinical record validation ; possible required self-reported MI on study questionnaire, with or without abnormal study ECG or clinical test result.

Angina Definite angina required the combination of typical symptoms and an abnormal test result; probable was assigned in the absence o f a test but with clinical record validation; possible angina was defined by self-report only with no test or clinical record

corroboration. In the analyses in this thesis, Rose questionnaire angina alone was not included in the possible category.

All events were dated, where possible, from medical records. Where an event could not be dated but was known to have occurred between two phases, e.g. silent MI on study ECGs, a date midway between the attendances at the two phases was assigned. The events were hierarchical so that a participant contributed only one event, the most severe, to analyses. Mortality follow-up was censored at the end o f 1999. Non-fatal follow-up was censored at the date of last attendance at screening or questionnaire completion. For participants who had not attended screening and had no sickness absence records, mortality follow-up was censored at the median date o f the phase after their last attendance e.g. for a participant who had not attended since Phase 1, mortality follow-up was censored at the median of Phase 2 screening dates. Since the interval between Phase 1 and Phase 3 varied, follow-up from Phase 3 baseline is not an accurate measure o f time since Phase 1. To allow analysis o f long-term effects from Phase 1, the follow-up period from Phase 1 was subdivided into the first six years o f follow-up and subsequently.

Analyses in this thesis will use an amalgamated endpoint of CHD events including the definite, probable and possible categories o f CHD deaths, MI and angina but excluding those with only Rose angina. The amalgamated group was separated into two groups of endpoint for some analyses: CHD death/non-fatal MI and angina. Cases in the self­ reported/possible category were identified for other analyses. CHD events were analysed from either the Phase 1 or the Phase 3 baseline. Participants with validated events before Phase 1 were excluded from analyses from the Phase 1 baseline, as were those with events before Phase 3 from analyses from the Phase 3 baseline. Table IV.2 shows follow-up and CHD events from the Phase 1 and Phase 3 baselines and Table IV.3 details the number and different types o f events included.