Prognosis of angina with and without a diagnosis: 11 year follow up in the Whitehall II prospective cohort study

Participants

We invited all non-industrial civil servants aged 35-55 years working in the London offices of 20 departments to participate in this study. The final cohort consisted of 10 308 participants (3413 women) with an overall response rate of 73%.11 We obtained written informed consent from participants to examine clinical records. Participants completed questionnaires at five phases of data collection between 1985 and 1999 (fig A on bmj.com). At phase 5, 7830 participants completed a questionnaire (76% response rate from phase 1). At each phase we used the seven item Rose angina questionnaire to define angina independent of contact with medical care.12

Diagnosis of angina by a doctor

We obtained evidence of a diagnosis of angina from questionnaire items on diagnosis (four items), investigation (two items), and treatment (two items) (see bmj.com). We examined general practitioner and hospital records for details of diagnoses and abnormal test results among participants reporting positively on any of these eight questionnaire items. We also sought clinical records where the civil service gave a reason for sickness absence as angina or myocardial infarction or when the spell of absence exceeded 21 days.

Abnormal test results

Regardless of contact with medical care, we investigated each participant with a resting 12 lead electrocardiogram at phases 1, 3, and 5. We defined abnormal results as Q waves (Minnesota codes 1-1 to 1-3), ST depression (4-1 to 4-4), inverted T waves (5-1 to 5-3), or left bundle branch block (7-1).13 Additionally, among participants who had sought medical care, we defined abnormal test results as the presence of one or more diseased vessels at coronary angiography or ≥ 1 mm ST depression on exercise electrocardiogram or a reversible defect on stress imaging.

Outcomes: classification of angina and recurrent reports

We classified angina according to evidence of diagnosis by a doctor and the presence of an abnormal test result (table 1). We made chronological listings of each item of epidemiological and clinical record data. We coded pairwise combinations of evidence from two columns in the table in a hierarchy starting from a clinical record of diagnosis of angina plus an abnormal coronary angiogram at the top (first row) down to angina identified by the Rose angina questionnaire (“Rose angina”) plus a normal study electrocardiogram at the bottom (last row). Two independent coders assigned dated codes for each report of angina. In the rare event of disagreement a third coder adjudicated. We defined a report of angina at each date that new evidence became available, but we allocated only one code, the highest, within any 28 day period. For participants reporting Rose angina at follow up but not at the previous phase, we used the mid-point date as the date of the report.

Outcomes: mortality, non-fatal myocardial infarction and physical functioning

Almost all (99.9%) participants were flagged at the NHS Central Registry, which notified us of dates of death. We defined non-fatal myocardial infarction by following the MONICA criteria of typical symptoms, enzyme abnormalities, and electrocardiographic changes.14 We assessed physical functioning at phase 5 in 6839 participants by using the 10 item scale of the SF-36 health survey.15 16 This scale asks: “Does your health now limit you in these [10 different] activities?” The activities range from running, through climbing stairs, to bathing and dressing. The scale ranges from 0 (worst) to 100 (best) and has previously been validated against risk factors, severity of angina, and time on an exercise electrocardiogram.16 17

Statistical analysis

We compared participants with four categories of angina, defined by the presence or absence of a diagnosis by a doctor or an abnormal test result, with participants who did not have angina or a myocardial infarction throughout follow up. All analyses concern incident angina among people without previous myocardial infarction. We excluded from all analyses 102 participants with angina or myocardial infarction (n = 224 reports) before phase 1 and 15 participants not flagged at the Central Registry. By 31 December 1999, 344 deaths had occurred among the remaining 10 191 participants (2.9 per 1000 person years). To examine the prognosis of participants after their first report of angina, we calculated the risk (probability) of specified events occurring in the next five years from their rate of occurrence. We calculated person years of survival by using the date of phase 1 and the dates of angina events and death or censoring at the end of 1999. We described the relation between types of angina and subsequent mortality with hazard ratios and 95% confidence intervals, calculated by using time dependent Cox's proportional hazards models that allowed for transitions during the follow up period, but only to a more severe category of angina. Thus the numbers of participants in the categories of angina in tables 1 and 4 differ. We defined impaired SF-36 physical functioning as below the lowest sex specific quartile (< 86 for men and < 71 for women) and used logistic regression to determine odds ratios of impaired physical functioning.

Recurrent angina and non-fatal myocardial infarction

At the time of the first report of angina, 718/970 (74%) participants had no evidence of a diagnosis of angina by a doctor (table 2). Of these, 470 (65%) reported angina again during follow up and remained without a diagnosis. Among participants with an abnormal test result, the absolute risk of non-fatal myocardial infarction was similar in those without a diagnosis by a doctor (15%) and those with a diagnosis (16%).

Impaired physical functioning

Participants with angina had an increased risk of impaired physical functioning at phase 5 (mean follow up seven years) compared with participants who did not have angina or myocardial infarction throughout follow up (table 3). The age and sex adjusted odds ratio was similar in participants without a diagnosis by a doctor (2.36 (95% confidence interval 1.91 to 2.90)) and those with a diagnosis (3.19 (2.25 to 4.53)). Separate analyses showed that the prospective impact of angina on functional impairment was the same in women and men (table A on bmj.com). Angina diagnosed within the seven years before functional assessment had a similar impact on functional impairment to angina diagnosed earlier (table B on bmj.com). As the median year of phase 5 was 1998, this approximates to diagnoses before or after 1991.

Survival

Mortality was increased in people with undiagnosed angina and an abnormal test result, compared with participants with neither angina nor myocardial infarction (table 4). Abnormal study electrocardiograms occurred in 268/1733 (15.5%) reported cases of undiagnosed angina (table 1). The age and sex adjusted hazard ratio for mortality in this group was 2.37 (1.16 to 4.87, P = 0.02). Among participants with a diagnosis by a doctor, we found some evidence for adverse survival in those with an abnormal test result (hazard ratio 1.83 (0.95 to 3.52, P = 0.07)).

Angina without a diagnosis

No previous prospective studies during the 1990s have estimated the frequency and prognosis of angina without diagnosis by a doctor. Primary care consultations for angina rose between 1981 and 1991,1 during a period of declining incidence of myocardial infarction. Most patients with symptoms of acute myocardial infarction seek medical care and obtain a diagnosis from a doctor–the submerged clinical iceberg is small. Our study shows that this is not true for angina. Our findings indicate that primary care disease registers, required by national policy,2 are underestimating the burden of angina in the general population. Consistent with a previous study,18 employment grade did not influence the probability of having a diagnosis (data not shown).

Several reasons exist for a lack of diagnosis. A person with angina may not seek medical care. Little is known about factors predicting uptake of medical care and the negotiation of a diagnosis.7 Once medical care has been sought, the doctor may miss or not record the diagnosis–a group that this study was not able to identify. If this were an important reason for the lack of diagnosis then the adverse prognosis suggests a need for improvements in the diagnostic ability of clinicians.

Prognosis of angina

A strength of our study lies in the repeated assessments of angina status made over prolonged follow up. An estimated 60% of the undiagnosed group reported angina again but remained without a diagnosis over five years of follow up. The British regional heart study found that Rose angina reported on two occasions was associated with a greater risk of fatal and non-fatal myocardial infarction than was angina reported on only one occasion.6 Recurrent reports of angina may represent severe disease or ongoing ischaemia, as Rose proposed.19

As physical exercise is a common precipitant of angina, impairments in physical activities of everyday living constitute a major dimension of prognosis of angina. The presence of angina at baseline was associated with worse physical functioning at follow up, as assessed by a generic measure of health related quality of life. Importantly, this effect was similar in people with and without a diagnosis from a doctor and among both women and men.

We investigated all participants with resting electrocardiography and found adverse survival in people with angina without a diagnosis from a doctor in the presence of an abnormal resting electrocardiogram. Importantly, this effect was similar in magnitude (doubling of mortality) in those people with diagnosed angina who had an abnormal test result. Although many general practices have facilities for electrocardiography, the prognostic importance of common abnormalities is underappreciated.8

Impact of medical care and policy implications

Secondary prevention and revascularisation improve outcomes in angina, but only in people with a diagnosis. Underuse of investigation and treatment, widespread in the United States and the United Kingdom,20 21 may have an adverse effect on outcomes.22 We found no evidence that the impact of diagnosed angina on long term functional impairment improved over time. Guidelines in the United States and the United Kingdom recommend that all people with angina should undergo resting electrocardiography in order to identify high risk groups for further investigation and treatment.2 4 The cost effectiveness of systematic case finding (with questionnaire) and risk assessment (with electrocardiography) of people with angina in the general population awaits investigation.

Conclusion

Among people with angina, a submerged clinical iceberg is associated with adverse prognosis across a range of outcomes. Reducing the population burden of angina requires consideration of people who have yet to be given a diagnosis.