European Heart Journal (1998) 19, 63–73

Chest pain on questionnaire and prediction of major ischaemic heart disease events in men
F. C. Lampe, P. H. Whincup, S. G. Wannamethee, S. Ebrahim, M. Walker, A. G. Shaper
Cardiovascular Research Unit, Department of Primary Care and Population Sciences, Royal Free Hospital School of Medicine, London, U.K.

Objective To examine the prediction of major ischaemic heart disease events by questionnaire-assessed chest pain and other symptoms. Design Population-based prospective study. Subjects 7735 randomly selected men, aged 40–59 years at entry. Methods Symptoms and history of diagnosed ischaemic heart disease were ascertained by administered questionnaire at baseline. Follow-up was for an average of 14·7 years, for first major ischaemic heart disease event. Results During follow-up, 969 men had a major ischaemic heart disease event. ‘Definite’ angina (chest pain fulfilling all WHO criteria) and ‘possible’ angina (exertional chest pain without all other WHO criteria) were associated with similar ischaemic heart disease outcome, and a single combined angina category was used. In the whole cohort, the relative risks (95% CI) of a major ischaemic heart disease event were 2·03 (1·61, 2·57) for angina only, 2·13 (1·72, 2·63) for possible myocardial infarction only and 4·50 (3·57, 5·66) for angina plus possible myocardial infarction, compared to no chest pain. The relative risk for recall of an ischaemic heart disease diagnosis was 3·98 (3·36, 4·71). Only 33% of men with angina or possible myocardial infarction symptoms recalled a previous ischaemic heart disease diagnosis. In men without recall of an ischaemic heart disease diagnosis (in whom 82% of events during

follow-up occurred), chest pain symptoms remained predictive of major ischaemic heart disease events with relative risks (95% CI) of 1·69 (1·27, 2·24) for angina only, 1·49 (1·12, 1·97) for possible myocardial infarction only and 2·55 (1·44, 4·53) for angina plus possible myocardial infarction. ‘Other chest pain’ increased risk of a major ischaemic heart disease event by 1·19 (1·01, 1·40) compared to no chest pain. Symptoms of breathlessness or calf pain on walking increased ischaemic heart disease risk in men with ‘other chest pain’ and in men without chest pain, but had no further effect on ischaemic heart disease risk in men with symptoms of angina or possible myocardial infarction. Conclusions In defining angina by chest pain questionnaire, the exertional component is the crucial criterion. When using questionnaire-assessed symptoms to determine ischaemic heart disease risk, information on previous ischaemic heart disease diagnoses should be taken into account. The majority of men with angina or possible myocardial infarction symptoms do not have a diagnosis of ischaemic heart disease, but they remain at significantly increased risk of a major ischaemic heart disease event. The value of breathlessness and calf pain on walking in stratifying ischaemic heart disease risk is restricted to men with ‘other chest pain’ or no chest pain. (Eur Heart J 1998; 19: 63–73) Key Words: Chest pain, angina, Rose questionnaire, Ischaemic heart disease, prediction.

Introduction
The WHO (Rose) chest pain questionnaire is used widely in epidemiological studies as a validated and standardized method for defining angina and possible
Revision submitted 26 June 1997, and accepted 10 July 1997. Correspondence: Ms F. Lampe, Cardiovascular Research Unit, Department of Primary Care and Population Sciences, Royal Free Hospital School of Medicine, Rowland Hill Street, London NW3 2PF, U.K. 0195-668X/98/010063+11 $18.00/0 hj970729

myocardial infarction[1,2] and has consistently been shown to be predictive of mortality and major ischaemic heart disease events[3–13]. Despite extensive use of the questionnaire, several aspects merit further study. First, the need for all of the strict criteria used to define angina has been questioned, with evidence that chest pain on exertion (without additional criteria) is a satisfactory definition[9,10]. Second, we have already shown that recall of a doctor diagnosis of ischaemic heart disease is among the strongest predictors of subsequent major ischaemic heart disease events[5,6,12], but the extent to 
1998 The European Society of Cardiology

The general practice in each town was required to have a social class distribution representative of that town. on the basis of their response to both chest pain and prolonged severe chest pain questions. The criteria for selecting the towns.64 F. the 24 towns were taken from those with populations of 50 000–100 000 (1971 census). The average response rate was 78%. We have examined the prediction of major ischaemic heart disease events by questionnaire-assessed chest pain symptoms in middle-aged men in the British Regional Heart Study. Men were classified into one of three groups: possible myocardial infarction. the extent to which prediction by chest pain symptoms can be enhanced by other questionnaire-assessed symptoms. (iii) Angina only — possible or definite angina. into five mutually exclusive groups: (i) No chest pain — no chest pain of any duration. has been little studied. possible angina. Responses regarding exertional chest pain were inconclusive in 14 cases. 19. Lampe et al. (ii) Other chest pain — non-exertional chest pain or a history of other prolonged severe chest pain. January 1998 . Calf pain on walking was defined as an affirmative response to either question (see Appendix). Possible angina was defined as chest pain brought on by exertion. Twelve further men did not provide information on calf pain. the general practices and the subjects have been reported previously[15]. (v) Angina and possible myocardial infarction — possible or definite angina with a history of possible myocardial infarction. Methods The British Regional Heart Study examined 7735 men aged 40–59 years at entry (1978–80). In brief. (iv) was relieved if the subject did so and (v) was relieved within 10 min. Vol. Men were classified into one of four groups: definite angina. non-exertional chest pain or no chest pain. and prediction by chest pain symptoms assessed in men with and without a pre-existing doctor diagnosis of ischaemic heart disease. lasting for half an hour or more. It is of particular interest to assess the usefulness of questionnaire-assessed symptoms in predicting major ischaemic heart disease events in men who are not already known to their doctors to be suffering from ischaemic heart disease. such as breathlessness and calf pain on walking. Complete and simplified responses to the WHO angina questionnaire have been compared. administered symptom questionnaires (see Appendix) and inquired about cardiovascular diagnoses. which the WHO chest pain questionnaire predicts ischaemic heart disease risk independently of a previous doctor diagnosis of ischaemic heart disease has not been examined. these were classified as non-exertional chest pain. These issues are important both for the use of questionnaires in epidemiological studies and in clinical practice. Calf pain on walking A modified version of the WHO intermittent claudication questionnaire was used[17]. using 14·7 years average followup. Both possible and definite angina could be subdivided according to severity as grade I (chest pain brought on only by walking uphill or hurrying) or grade II (chest pain brought on by walking at an ordinary pace on the level). One man gave no information on chest pain. Chest pain that was not brought on by walking was classified as non-exertional chest pain. (iv) possible myocardial infarction only — a history of possible myocardial infarction without possible or definite angina. without a history of possible myocardial infarction. The two questions were not administered satisfactorily to the 915 men in the first three towns and therefore these men were excluded for this variable. 5 or 8). We have also examined the contribution made by additional symptoms (breathlessness and calf pain on walking) to the prediction of ischaemic heart disease events in men without diagnosed ischaemic heart disease. Classification of symptoms Chest pain Chest pain questions were based on the WHO angina questionnaire[1. but no angina or possible myocardial infarction. (ii) was situated in the central or left anterior chest (site 4. Chest pain status Chest pain status overall was classified for 7733 men. Other prolonged severe chest pain was defined as severe chest pain in a site not consistent with possible myocardial infarction. 5 or 8 on diagram). Research nurses examined each man. Wales and Scotland. Definite angina was defined Eur Heart J. where it is becoming increasingly important to stratify subjects on the basis of their absolute risk of ischaemic heart disease[14].16]. (iii) forced the subject to slow down or stop. Prolonged severe chest pain Questions were based on the WHO severe chest pain question[1. No attempt was made to exclude men with cardiovascular problems. but not fulfilling all of the four additional criteria for definite angina. randomly selected from the age–sex registers of one general practice in each of 24 towns in England. Possible myocardial infarction was defined as ever having had an episode of severe pain in the central or left anterior chest (site 4.16]. according to standard criteria as chest pain or discomfort which: (i) was brought on by exertion. Third. One man gave no information on severe chest pain. C. Information regarding grade of angina was incomplete or contradictory in 16 cases: these were classified as grade I angina. They were chosen to represent the full range of mortality from cardiovascular disease and included all major geographic regions. other prolonged severe chest pain or no prolonged severe chest pain.

512 (84%) had grade I (milder) angina. Prevalence of chest pain Definite angina was present in 367 (4·7%) men. (1·61. Nine men could not be classified. and possible angina in 240 (3·1%). A fatal coronary heart disease event was defined as a death coded to ICD 410–414. adjusted for age. 969 (12·5%) of the 7735 men experienced a major ischaemic heart disease event. adjusted for age. Results Ischaemic heart disease outcome During the period from initial examination to 31 December 1993. Breathlessness was defined as an affirmative response to any of the three questions (see Appendix). Deaths from causes other than ischaemic heart disease were treated as censored observations. were classified as having recall of an ischaemic heart disease diagnosis[19]. Cox proportional hazards models were used to assess the effect of symptoms on time free of a major ischaemic heart disease event. range 13·3 to 16·0) for cardiovascular morbidity and all-cause mortality. January 1998 . A non-fatal myocardial infarction was defined as an event associated with at least two features of: severe prolonged chest pain. cardiac enzyme abnormalities. angina=possible or definite angina. Of the 607 men with questionnaire-assessed angina. with survival for at least 28 days[20]. A single occurrence of pain only was reported by 28 (4·6%) men with angina symptoms. electrocardiographic evidence of myocardial infarction at the time of the event. PMI=possible myocardial infarction. Symptoms of ischaemic heart disease (either angina or a history of Eur Heart J. Vol. (1·72. symptoms and their interactions were fitted using dummy variables with appropriate reference categories. The loglikelihood ratio statistic[21] (LRS) was used to assess statistical significance. Follow-up was achieved for 99% of the original cohort. Age was fitted as a continuous variable. †Relative risks compared to reference category. Information on non-fatal myocardial infarction was obtained from reviews of each subject’s general practice records. Breathlessness A modified version of the MRC respiratory questionnaire was used[18]. The cumulative probability of remaining free of an event during the follow-up period was estimated using the Kaplan–Meier technique. compared to only 30% of those with grade I angina. Eleven men could not be classified. The established ‘tagging’ procedure carried out by the National Health Service Central Registers in Southport (for England and Wales) and Edinburgh (for Scotland) was used for notification of deaths. with date and cause from the death certificate. Recall of ischaemic heart disease diagnosis Men who reported at initial examination having been told by a doctor that they had either angina or a heart attack (including coronary thrombosis or a myocardial infarction). Table 1 shows the prevalence of chest pain status overall. with the first event during follow-up being fatal in 406 men. 19. Results are presented as relative risks with 95% confidence intervals (95% CI). (3·57. 1·40) 2·57) 2·63) 5·66) 2·91) *Reference category. (2·16. Daily or weekly episodes of pain were experienced by the majority (64%) of men with grade II angina. Statistical analysis Event rates per thousand per year were calculated as the number of major ischaemic heart disease events divided by the person-years at risk 1000.Chest pain and prediction of ischaemic heart disease in men 65 Table 1 Major ischaemic heart disease events by chest pain category at baseline: all men n Prevalence (%) Mean age (years) Event rate /1000/year (number of events) RR† age adjusted (95% CI) Chest pain status No chest pain* ‘Other chest pain’ Angina only PMI only Angina and PMI Angina or PMI Total 4787 1849 391 490 216 1097 7733 (61·9) (23·9) (5·1) (6·3) (2·8) (14·2) 50·1 49·5 52·4 51·3 52·9 52·0 50·2 7·5 8·6 17·2 16·9 39·0 20·8 9·5 (485) (213) (82) (103) (86) (271) (969) 1 1·19 2·03 2·13 4·50 2·50 (1·01. The present analysis is concerned with the first major ischaemic heart disease event (non-fatal or fatal myocardial infarction or sudden cardiac death) occurring during the follow-up period. Follow-up The 7735 men initially examined in 1978–80 were followed up until the end of December 1993 (mean 14·7 years. The overall major ischaemic heart disease event rate was 9·5/1000/year.

Angina symptoms and ischaemic heart disease outcome During follow-up.4 0. with both groups being clearly distinct from non-exertional chest pain (Fig. Angina only and possible myocardial infarction only were each associated with approximately a twofold increase in risk. but only 216 (20%) of these had both angina and possible myocardial infarction. C. but this difference was not statistically significant (age adjusted relative risk (95% CI): 1·33 (0·90. possible myocardial infarction) were found in 1097 (14·2%) men.67). P =0. These men were at extremely high risk of a new major ischaemic heart disease event during follow-up. ‘angina’ refers to definite and possible angina combined i. the major ischaemic heart disease event rates for definite and possible angina were 25·4/1000/year and 22·2/1000/year respectively.66 F.e.2 0. compared to a rate of 22·7/1000/year for grade I Eur Heart J. 1. only 69 had a history of prolonged severe chest pain in an inappropriate site for possible myocardial infarction.3 0. daily or weekly episodes of pain (34·5% and 36·1%. Chest pain status and ischaemic heart disease outcome The influence of chest pain status at baseline on major ischaemic heart disease events is shown in Table 1. compared to 9·3% of men with non-exertional pain). to any exertional chest pain. Recall of an ischaemic heart disease diagnosis and chest pain symptoms A doctor diagnosis of ischaemic heart disease (angina or myocardial infarction) was recalled by 424 (5·5%) men. Of the 1849 men with ‘other chest pain’. The event free survival experience of the two groups over the follow-up period was very similar. with an event rate of 39·1/1000/year. Grade II (severe) angina was associated with a major ischaemic heart disease event rate of 32·5/1000/ year.7 0.0 No chest pain 0. ‘Other chest pain’ marginally but significantly increased risk of a major ischaemic heart disease event compared to no chest pain. Neither frequency of chest pain.9 Non-exertional pain 0. Lampe et al.1 Possible angina Definite angina 0 2 4 6 8 Years of follow up 10 12 14 16 Figure 1 Proportion free of a major ischaemic heart disease event by WHO angina status. 1·95) LRS chi-squared (1)=1·94. compared to 15·7% of men with non-exertional pain) and a history of possible myocardial infarction (37·3% and 32·9%. 1·47) (LRS chisquared (1)=0·18. Vol. and the age-adjusted relative risk (95% CI) of definite compared to possible angina was 1·07 (0·78. but the presence of both symptoms together increased risk considerably. January 1998 angina.8 Cumulative proportion event free 0.5 0. In the remainder of this paper. nor how recently pain had occurred significantly influenced risk of a major ischaemic heart disease event in men with angina during the follow-up period. P =0·16). compared to a rate of 8·2/1000/year for men who did not recall an ischaemic heart disease diagnosis (age-adjusted relative .6 0. The groups were also similar at baseline with regard to the proportion with grade II angina (16·3% and 14·6% for definite and possible respectively). 1). the remainder having non-exertional chest pain. The presence of either angina or possible myocardial infarction at baseline was associated with an age-adjusted relative risk of 2·5 compared with no chest pain. 19.

(1·12. Eur Heart J. 4·71)). calf pain on walking and chest pain in men without diagnosed ischaemic heart disease Table 4 shows the associations of breathlessness and calf pain on walking with chest pain status in men without recall of an ischaemic heart disease diagnosis. In men with an ischaemic heart disease diagnosis (n=424). with about half reporting breathlessness and about a third reporting calf pain.Chest pain and prediction of ischaemic heart disease in men 67 Table 2 Association between chest pain category and recall of ischaemic heart disease diagnosis: all men Recall of diagnosis of IHD (angina or MI) n Chest pain status No chest pain ‘Other chest pain’ Angina only PMI only Angina and PMI Total (%) n 4782 1847 390 489 216 7724* 26 37 79 118 164 (0·5) (2·0) (20·3) (24·1) (75·9) diagnosed ischaemic heart disease reported chest pain. 1·28) 1·57) 1·82) 2·12) 1·82) 4756 1810 311 371 52 734 7300 7·4 8·4 13·5 11·2 20·1 12·7 8·2 (474) (205) (53) (54) (12) (119) (798) 1 1·19 1·69 1·49 2·55 1·64 (1·01. 19. and men who had both angina and possible myocardial infarction were at markedly higher risk than those with one symptom alone. symptoms of angina or possible myocardial infarction were associated with an ageadjusted relative risk of 1·64 compared to no chest pain. but numbers in the reference group were very small as the vast majority of men with Table 3 Major ischaemic heart disease events by chest pain category at baseline in men with and without recall of an ischaemic heart disease diagnosis With IHD diagnosis n Event rate /1000/year (number of events) RR† age adjusted (95% CI) n Without IHD diagnosis Event rate /1000/year (number of events) RR† age adjusted (95% CI) Chest pain status No chest pain* ‘Other chest pain’ Angina only PMI only Angina and PMI Angina or PMI Total 26 37 79 118 164 361 424 40·9 20·7 34·0 38·9 46·0 40·9 39·1 (11) (8) (28) (49) (74) (151) (170) 1 0·51 0·78 0·95 1·13 0·99 (0·21. PMI=possible myocardial infarction. Breathlessness. In men who did not recall an ischaemic heart disease diagnosis (n=7302). (1·27. Vol. Breathlessness and calf pain were less common in men who had possible myocardial infarction only — this group having similar rates of these symptoms to men with ‘other chest pain’. (0·39. 37 (10·2%) had grade II angina and this increased risk by 1·36 times that for grade I. Men with questionnaire-assessed angina were particularly likely to have these additional symptoms. the presence of angina symptoms or a history of possible myocardial infarction did not appear to greatly influence risk of a new event. ‘Angina or possible myocardial infarction’ was used as a single group in order to have sufficient numbers for analysis. (0·53. 1·40) 2·24) 1·97) 4·53) 2·01) *Reference category. (1·44. January 1998 . (0·60. Of the 363 men who had questionnaire-assessed angina in this group. angina=possible or definite angina. Both breathlessness and calf pain were much more likely to be reported by men who had chest pain. (0·50. Breathlessness in addition to chest pain: effect on outcome in men without diagnosed ischaemic heart disease The influence of breathlessness with chest pain on major ischaemic heart disease events and total mortality was examined in men without recall of an ischaemic heart disease diagnosis (Table 5). †Relative risks compared to reference category. The effect of breathlessness on major ischaemic heart disease *Two men had missing data for chest pain status and 9 men had missing data for ischaemic heart disease recall. angina=possible or definite angina. PMI=possible myocardial infarction. Chest pain symptoms in men with and without diagnosed ischaemic heart disease: effect on outcome The influence of questionnaire-assessed chest pain symptoms on major ischaemic heart disease events was examined separately in men with and without recall of an ischaemic heart disease diagnosis (Table 3). There was a very strong association between chest pain symptoms and recall of a doctor diagnosis of ischaemic heart disease (Table 2). Again. although overall only 33% of men with questionnaireassessed angina or possible myocardial infarction symptoms reported having an ischaemic heart disease diagnosis. (1·34. risk (95% CI): 3·98 (3·36. adjusted for age. relative risks were similar for angina only and possible myocardial infarction only.

the additional presence of breathlessness did not increase risk of a major ischaemic heart disease event (test for interaction between chest pain status and breathlessness: LRS chisquared (2)=6·59. Calf pain on walking in addition to chest pain: effect on outcome in men without diagnosed ischaemic heart disease The effect of calf pain with chest pain on major ischaemic heart disease events in men without an ischaemic heart disease diagnosis showed a similar pattern to that seen for breathlessness (Table 5). Breathlessness in the absence of chest pain was associated with an age-adjusted relative risk of 1·36. men with ‘other chest pain’ and breathlessness had an event rate similar to that of men with symptoms of angina or possible myocardial infarction. Eur Heart J. P =0·028). Breathlessness and calf pain on walking increased ischaemic heart disease risk only in those without symptoms of ischaemic heart disease. but caused only a marginal non-significant increase in men with angina or possible myocardial infarction. in middle-aged British men. this present paper has extended the follow-up period and shown that men who had standard WHO (Rose) angina had a similar long-term outcome to those who had chest pain on exertion which did not fulfil all remaining criteria for angina. Again. definite and possible WHO (Rose) angina were associated with similar ischaemic heart disease outcome over a long follow-up period. in men with angina or possible myocardial infarction. Similarly. P =0·037). January 1998 Discussion This paper has examined prediction of major ischaemic heart disease events by the use of an administered questionnaire for the assessment of chest pain symptoms. who were at very high risk of a new major ischaemic heart disease event. These findings emphasize that the exertional component of chest pain is the crucial feature in the definition of angina by . but did not increase the risk in those with angina or possible myocardial infarction (test for interaction LRS chi-squared (2)=7·14. Calf pain increased total mortality risk in men with no chest pain and ‘other chest pain’. Vol. However. PMI=possible myocardial infarction. This finding is supported by a follow-up study in men and women aged 65 and over which found the 3-year coronary heart disease mortality associated with exertional chest pain to be at least as high as that associated with standard WHO angina[10]. †Eight hundred and eighty-one men without an ischaemic heart disease diagnosis had missing or unusable data for calf pain or had missing data for chest pain status. which was mainly due to an increase in non-cardiovascular deaths. in those with ‘other chest pain’. a significant increased risk remained in men with questionnaire-assessed angina and/or possible myocardial infarction who did not have a previous diagnosis of ischaemic heart disease. The effect of calf pain on total mortality was weaker than that of breathlessness. breathlessness had a marked effect on total mortality. angina=possible or definite angina. Table 4 Association of chest pain category with breathlessness and calf pain on walking: men without recall of an ischaemic heart disease diagnosis n Breathlessness n (%) n Calf pain on walking n (%) Chest pain status No chest pain ‘Other’ chest pain Angina only PMI only Angina and PMI Total 4751 1808 310 371 52 7292* 502 349 141 83 35 1110 (10·6) (19·3) (45·5) (22·4) (67·3) (15·2) 4193 1568 285 328 47 6421† 302 221 70 51 20 664 (7·2) (14·1) (24·6) (15·5) (42·6) (10·3) *Ten men without an ischaemic heart disease diagnosis had missing data for breathlessness or chest pain status. Lampe et al. C. A large part of the risk associated with questionnaire-assessed chest pain symptoms in the cohort of men as a whole was attributable to men with a pre-existing ischaemic heart disease diagnosis. among those without diagnosed ischaemic heart disease. breathlessness increased the risk by a factor of 1·55. lower ischaemic heart disease event rates were seen only in those who had neither calf pain nor angina or possible myocardial infarction symptoms. events differed according to category of chest pain. 19. However. We have shown that. In addition. In all three chest pain groups.68 F. It can also be seen that. Calf pain increased the risk of a major ischaemic heart disease event by 1·63 and 1·79 in those with no chest pain and ‘other chest pain’ respectively. a Norwegian follow-up study reported the ‘site of pain’ criteria used in WHO angina to be of no value in predicting mortality[8]. Definite and possible angina on questionnaire A previous report from the British Regional Heart Study (BRHS) compared definite and possible questionnaire-assessed angina over 7·5 years of followup[9].

2·21) (1·26. Eur Heart J. 1·76) (1·14. 2·08) (1·65. angina=possible or definite angina. 2·80) (1·17. BR=breathlessness. CAP=calf pain on walking. 2·43) (0·78. 2·54) (0·53. 1·66) Angina or PMI Chest pain and calf pain No chest pain no BR* BR no BR* BR no BR* BR 4249 502 1459 349 474 259 7·0 10·6 7·5 12·4 12·9 12·1 (407) (67) (149) (55) (79) (39) 1 1·36 1 1·55 1 0·84 9·5 19·0 7·7 18·3 12·2 22·9 (561) (124) (158) (84) (79) (76) 1 1·71 1 2·15 1 1·61 ‘Other chest pain’ Angina or PMI no CAP* CAP no CAP* CAP no CAP* CAP 3891 302 1347 221 519 141 7·1 12·5 7·6 14·6 12·8 12·2 (370) (47) (137) (41) (84) (21) 1 1·63 1 1·79 1 0·85 10·1 19·4 8·5 16·7 14·9 19·9 (539) (75) (159) (49) (103) (36) 1 1·71 1 1·77 1 1·14 Chest pain and prediction of ischaemic heart disease in men *Reference category.Table 5 Effect of breathlessness and calf pain on walking with chest pain on major ischaemic heart disease events and total mortality: men without recall of an ischaemic heart disease diagnosis Major IHD events n Event rate /1000/year (number of events) RR† age adjusted (95% CI) Death rate /1000/year (number of deaths) Total mortality RR† age adjusted (93% CI) Chest pain and breathlessness No chest pain (1·05. 1·38) ‘Other chest pain’ (1·41. PMI=possible myocardial infarction. 19. January 1998 69 . adjusted for age. 2·18) (1·28. Vol. 2·12) (0·57. 1·23) (1·21. 2·20) (1·34. †Relative risk compared to reference category.

it is likely that these. Some studies have included subjects with possible angina in the ‘other chest pain’ group. irrespective of their response to the chest pain questionnaire. where their considerably worse prognosis is likely to be diluted by large numbers with non-exertional chest pain[4. The observation that angina grade has a discriminating effect on ischaemic heart disease outcome.11]. both angina and a history of possible myocardial infarction on questionnaire were predictive of major ischaemic heart disease events.11] and clinical[22] studies. January 1998 Implications for use of the WHO (Rose) questionnaire in epidemiological studies The similarity of ‘possible’ and ‘definite’ angina in terms of ischaemic heart disease outcome suggest that a shortened chest pain questionnaire could be used to define angina in epidemiological studies. but we have previously reported that this association may be restricted to men without any evidence of ischaemic heart disease[18]. In men who did not recall a doctor diagnosis of ischaemic heart disease.34]. Vol. although subjective. questionnaire. in this study it did not increase risk when questionnaire-assessed ischaemic heart disease symptoms were present. Breathlessness and calf pain in addition to chest pain. the presence of angina and possible myocardial infarction together identified a small group at exceptionally high risk of an adverse ischaemic heart disease outcome. Clinical studies have also suggested the prognosis of ‘atypical chest pain’ to be relatively benign[23]. although calf pain on walking is a predictor of ischaemic heart disease events in men without any evidence of ischaemic heart disease[17. Although breathlessness or calf pain had no further effect on ischaemic heart disease outcome in the presence of angina or possible myocardial infarction symptoms. Retaining both questions relating to angina grade allows for stratification on the basis of exercise tolerance.30–32] have been shown previously. Breathlessness may precede angina as an important early indicator of unrecognized ischaemic heart disease[29]. It is possible that variations in factors such as effective anti-anginal drug treatment and physical activity limit the value of angina symptoms as a marker of prognosis in those with established ischaemic heart disease. and of calf pain with cardiovascular deaths and stroke[17. has been reported in epidemiological[4.11]. This would consist of questions 1.30–32]. although weak and non-significant in the present study. when it is often not satisfactorily completed. although the excess risk associated with these symptoms was considerably lower than that seen in the whole population. and there is some support for this possibility from clinical studies[24]. both angina alone and possible myocardial infarction alone were associated with about a threefold increase in ischaemic heart disease mortality during a 10-year follow-up period. Several studies have found that men who have WHO (Rose) angina but are not considered to have angina by a simultaneous clinical assessment are at similar risk of coronary heart disease death to those that are clinically judged to have angina[25–27]. In both the Whitehall Study and the BRHS. presumably in part due to an increased likelihood of genuine cardiac pain. This paper shows that breathlessness provided improved prediction of ischaemic heart disease risk only in men with ‘other chest pain’ or no chest pain but not in men with questionnaire-assessed symptoms of ischaemic heart disease. is likely to be a powerful indicator of the presence of severe ischaemic heart disease[5]. Lampe et al. A . in men without diagnosed ischaemic heart disease Breathlessness has been shown to be a strong predictor of major ischaemic heart disease events[28]. We have suggested previously that recall of an ischaemic heart disease diagnosis. although the power to assess this in our study was very limited. but this study suggests that once the disease has developed to a symptomatic stage. they did cause an increase in total mortality: for breathlessness this effect was pronounced.7. Chest pain and risk prediction The patterns of risk associated with angina and possible myocardial infarction in this population sample of middle-aged British men are consistent with those seen in other studies[4. C. Once indications of ischaemic heart disease are present. 19.8. 5 and 6 in the chest pain questionnaire for angina given in the Appendix. infrequent or less severe symptoms). There was some indication that questionnaire-assessed angina or possible myocardial infarction were not predictive of ischaemic heart disease events in this subgroup. rather than markers of peripheral vascular disease. This simplification of the WHO chest pain questionnaire would be of particular benefit if the questionnaire is used in a self-administered form. are the dominating factor in defining risk of a major event. the additional presence of breathlessness does not increase risk of a major ischaemic heart disease event.70 F. Similarly. Symptom prediction and pre-existing ischaemic heart disease diagnosis Those who recalled a doctor diagnosis of ischaemic heart disease at entry were at very high risk of a new event. Men with questionnaireassessed ischaemic heart disease symptoms but without a diagnosis of ischaemic heart disease are likely to consist not only of those who have not presented to their GP Eur Heart J. The associations of breathlessness with non-cardiovascular disease mortality[33. In the Whitehall study of middleaged male civil servants. but also those who have sought medical help but whose symptoms were considered not to be diagnostic of ischaemic heart disease.11]. Chest pain which is not consistent with angina or possible myocardial infarction has previously been shown to be associated with a small increase in ischaemic heart disease risk[4. with chest pain (for example because of new. and a test for interaction between chest pain symptoms and a previous ischaemic heart disease diagnosis was not significant.7.

11. Prineas RJ. Six year mortality related to cardiorespiratory symptoms and environmental risk factors in a sample of the Norwegian population. Overall. [6] Shaper AG. the absolute risk of ischaemic heart disease in men identified and their potential benefit from intervention. 71 of ischaemic heart disease. The predictive power of the chest pain questionnaire may be limited to those without diagnosed ischaemic heart disease. risk factors and death from coronary heart disease. [2] Rose GA. Enquiry about symptoms of breathlessness and calf pain on walking can help in identifying those men with atypical pain that are at increased risk References [1] Rose GA. Phillips AN. Should a self-administered chest pain questionnaire be used to identify men with angina or possible myocardial infarction who have not yet been identified by their doctor? This depends on the screening yield. as this substantially affects the level of risk associated with questionnaire-assessed angina or possible myocardial infarction symptoms. However. The chest pain questionnaire should be used in conjunction with information on pre-existing ischaemic heart disease diagnoses. men reporting a doctor diagnosis of ischaemic heart disease have an absolute risk of major ischaemic heart disease events of 3·9% per annum. breathlessness or calf pain. [8] Zeiner-Henrikson T. 24: 553–67. the exertional nature of the chest pain is the crucial factor which should be emphasized above the specific site of pain. the presence of both exertional chest pain and possible myocardial infarction. Hamilton PJS. Risk factors for ischaemic heart disease: the prospective phase of the British Regional Heart Study. the majority of men with symptoms of angina or possible myocardial infarction on questionnaire did not recall a doctor diagnosis of ischaemic heart disease. Clinical implications The results show clearly that recall of a doctor diagnosis of ischaemic heart disease is a more powerful predictor of ischaemic heart disease risk than any combination of chest pain symptoms. the patient’s response to the pain or the timing of disappearance of the pain on resting. in the subgroup with sustained LDL cholesterol levels of 4·0 mmol or more. they are still likely to derive considerable absolute benefit from risk factor modification. For men without a history of diagnosed ischaemic heart disease (in whom 82% of all ischaemic heart disease events during followup occurred). J Epidemiol Comm Health 1985. It is clear that in diagnosing angina. J Chron Dis 1976.35. Both groups would stand to benefit from risk factor modification and aspirin treatment. Myocardial ischaemia. McCartney P. Self-administration of a questionnaire on chest pain and intermittent claudication. much greater yields of men at similar levels of risk could be obtained by using multiple risk factor scoring systems[12.36]. Risk factors for ischaemic heart disease. allow the definition of a high risk group with a major ischaemic heart disease event rate of about 2·0% per year. 19: 2–7. Pocock SJ. Our results suggest that screening middle-aged men without a diagnosis of ischaemic heart disease would yield 1·2% with either grade II angina or angina with possible myocardial infarction and a further 3·8% with grade I angina. inclusion of ‘possible’ angina increased the prevalence of questionnaire-assessed angina by 65% (from 4·7% to 7·8%) and the overall prevalence estimate of ischaemic heart disease (including ECG abnormalities) by 7% (from 23·1% to 24·7%). Macfarlane PW. Reid DD. 1: 105–9. [3] Rose G. from lipid lowering treatment[39]. Eur Heart J. [7] Zeiner-Henriksen T.37]. January 1998 . the characteristics of chest pain can play an important part in quantifying the absolute level of ischaemic heart disease risk. particularly. Lancet 1977. Reid DD. Although the absolute ischaemic heart disease risk in these men remains considerably lower than that in men with a doctor diagnosis of ischaemic heart disease. breathlessness or calf pain do not help further in the stratification of risk in this group. the second a rate of 1·3% per annum. [5] Shaper AG.13]. Fiona Lampe is supported by the Department of Health. Keen H. The British Regional Heart Study is a British Heart Foundation Research Group and receives support from the Department of Health. Shaper AG. 19.Chest pain and prediction of ischaemic heart disease in men missing response for one or more questions precludes a classification of angina according to the standard criteria. Whitehead TP. the inclusion of ‘possible’ cases considerably increases prevalence[10. Gillum RF. Bull Wld Hlth Org 1962. 27: 645–58. J Chron Dis 1971. The longterm prognosis of atypical chest pain (non-exertional chest pain or severe chest pain in an inappropriate site) is relatively good. The first group would have an absolute ischaemic heart disease event rate of 2·0% per annum. Cardiovascular Survey Methods (2nd edn) WHO Geneva 1982. Cardiovascular disease symptoms in Norway — a study of prevalence and a mortality follow-up. Identifying men at high risk In this study. from aspirin[38] and. Blackburn H. 39: 197–209. In this study. In the absence of these additional symptoms. Br J Prev Soc Med 1977. Angina prevalence may well have been underestimated by earlier studies reporting only ‘definite’ angina[4. McCartney P. a process which is also increasingly important in defining the likely benefits from treatment[14]. which also help to define a prevention strategy. Walker M. Macfarlane PW. Using the WHO (Rose) angina questionnaire in cardiovascular epidemiology. [4] Rose G. 31: 42–8. This suggests that a combination of risk factors and symptoms may be more helpful than symptoms alone in identifying men without a doctor diagnosis who are at high absolute risk of future ischaemic heart disease events. [9] Cook DG. Health Trends 1987. More limiting exertional chest pain and. 29: 15–33. The diagnosis of ischaemic heart pain and intermittent claudication in field surveys. Jarrett RJ. 18: 607–13. although this requires further examination in other studies. Int J Epid 1989. Vol. men with atypical chest pain are at similar overall risk of a major ischaemic heart disease event to men with no chest pain.

[25] Blackwelder WC. 82: 1925–31. Clark EC. Elwood PC. Rose G. [23] Wilcox RG. Phillips AN. Circulation 1978. Prevalence of coronary heart disease in Scotland: Scottish Heart Health Study. Rose G. N Engl J Med 1992. Wannamethee G. Cohen NM. [39] Shepherd J. [12] Shaper AG. Markowe HLJ. British Regional Heart Study: cardiovascular risk factors in middle-aged men in 24 towns. 19. 59: 201–6. Prevention of coronary heart disease in clinical practice — Recommendations of the Task Force of the European Society of Cardiology. Br Heart J 1984. [11] Bulpit CJ. 38: 195–201. European Atherosclerosis Society and European Society of Hypertension. [13] Shaper AG. Sigfusson N. Graham I. [29] Cook DG. N Engl J Med 1995. Siegelaub AB. Margolis JR. Thorgeirsson G. A scoring system to identify men at high risk of a heart attack. Br Heart J 1988. Gordon T. lung function and the risk of heart attack. Br Heart J 1990. Walker M. [27] Sigurrdsson E. [34] Kaplan GA. 64: 295–8. Circulation 1979. Shaper AG. London: Chapman and Hall 1995. [16] Shaper AG. Eur Heart J 1994. Int J Epidemiol 1990. Comparison of methods for diagnosing angina pectoris: The Honolulu Heart Study. [37] Reeder BA. and stroke by prolonged antiplatelet therapy in various categories of patients. Langer RD. 121: 555–62. J Clin Epidemiol 1988. Pocock SJ.72 F. C. Kagan A. [32] Criqui MH. Ostfeld AM. Poole Wilson P. [19] Shaper AG. Respiratory symptoms and pulmonary function as predictors of 10-year mortality from respiratory disease. risk factors and cardiovascular outcome in middleaged British men. Guralnik JM. [26] Friedman LM. 29: 683–96. [14] Pyo ¨ ra ¨ la ¨ K. Phillips AN. [17] Shaper AG. Walker M. J Chron Dis 1985. Cook DG. Predicting death from coronary heart disease using a questionnaire. Am J Cardiol 1989. 282: 431–433. 333: 1301–7. Friedman GD. Sigvaldason H. Walker M. BMJ 1986. Assessment of angina pectoris after myocardial infarction: comparison of ‘Rose questionnaire’ with physician judgment in the Beta-Blocker Heart Attack Trial. [24] Harris PJ. Pocock SJ. Eur Heart J 1988. [21] Collett D. Circulation 1990. Intermittent claudication. Prognosis of patients with ‘‘chest pain? cause’’ BMJ 1981. Agnarsson U. Wale CJ. Proposal for the multinational monitoring of trends and determinants in cardiovascular disease (MONICA) project and protocol. Calf pain on walking. Demirovic J. [33] Ebi-Kryston KL. Walker M. Modelling survival date in medical research. Macfarlane PW. Circulation 1990. [36] Smith WCS. Baker IA. Crombie IK. West of Scotland Coronary Prevention Study Group. Identifying men at high risk of heart attacks: strategy for use in general practice. 60: 1259–69. 81: 437–46. 19: 37–9. Int J Epid 1981. go to next section 2 Where did you get this severe pain? (Show chart) 3 Did you see a doctor because of this pain? CHEST PAIN 1 Do you ever have any pain or discomfort in your chest? If NO. ed. KL et al. Self-reports predictive of mortality from ischaemic heart disease: a nine-year follow-up of the Human Population Laboratory Cohort. Yarnell JW. 41: 251–60. Roland JM. Wallace RB. Br Heart J 1994. Rosati RA. angina pectoris and coronary artery disease. [38] Collaborative overview of randomised trials of antiplatelet therapy-I: Prevention of death. Hennekens CH. Elwood P. Prevention of coronary heart disease with pravastatin in men with hypercholesterolaemia. Sociodemographic variation in the prevalence of cardiovascular disease in Saskatchewan: results from the Saskatchewan Heart Health Survey. cardiovascular disease and all causes in the Whitehall study. Ford I et al. Sweetnam P. 57: 64–70. 12: 271–7. World Health Organisation. Eur Heart J. 63: 921–24. Curb D. Breathlessness. 51: 606–11. Pocock SJ. Fronek A et al. Br Heart J 1984. Rhoads GG. Long-term prognosis of different forms of coronary heart disease: The Reykjavik Study. Survival in medically treated coronary artery disease. Geneva: Cardiovascular Diseases Unit. Shipley M. 51: 595–605. Harrell FE Jr. go next section 2 When did you last get the pain Within 1 month 1–5 months ago 6–12 months ago Over 1 year ago Occasionally 3 How often do you get it Daily Weekly Monthly Once only Occasionally 4 Where do you get this pain or discomfort? (Show chart) (Y/N) (Y/N) 1 2 3 4 5 1 2 3 4 5 . In: Fowkes FGR. BMJ 1981. Ebi-Kryston KL. Macfarlane PW. 24: 58–68. 10: 211–15. 308: 81–106. Walker M. Health Trends 1987. [20] World Health Organisation. Prevalence of ischaemic heart disease in middle-aged British men. 15: 1300–31. Lee. [22] McNeer JF. Prevalence of ischaemic heart disease: the Caerphilly and Speedwell surveys. Antiplatelet Trialists’ Collaboration. Shaper AG. 72: 128–32. Breathlessness. Cobbe SM. Peripheral vascular disease: consequence for survival and association with risk factors in the Speedwell prospective heart disease study. 9: 1215–22. [10] LaCroix AZ. Cook DG. 326: 381–6. Wood D. Byington RP and The Beta Blocker Heart Attack Trial Research Group. myocardial infarction. Lampe et al. 1983. 19: 899–904. Am J Epid 1985. Recall of diagnosis by men with ischaemic heart disease. Lee KJ. [28] Klatsky AL. January 1998 [31] Davey Smith G. heart disease risk factors and mortality: The Whitehall Study. Hampton JR. London: Springer. Sweetnam PM. 293: 474–9. Medical history questions predictive of myocardial infarction: results from the Kaiser-Permanente Epidemiologic Study of Myocardial Infarction. Vol. Thomson AG. Kenicer MB. Shipley MJ. Int J Epid 1995. Can J Cardiol 1996. [30] Bainton D. Appendix: Symptom questionnaires SEVERE CHEST PAIN 1 Have you ever had a severe pain in your chest lasting for half an hour or more? (Y/N) If NO. The role of exercise testing in the evaluation of patients with ischaemic heart disease. 283: 179–86. BMJ 1994. Behar VS. [18] Cook DG. Epidemiology of peripheral vascular disease. DeBacker G. J Chron Dis 1976. Horlick L. 1991: 127–35. [35] Bainton D. Tunstall-Pedoe H. Walker M. Chest pain and coronary heart disease mortality among older men and women in three communities. Mortality over a period of 10 years in patients with peripheral arterial disease. Kotler PL. Baker I. [15] Shaper AG. Liu L.

19.Chest pain and prediction of ischaemic heart disease in men 73 5 When you walk at an ordinary pace on the level. what do you do? Stop 1 Slow down 2 Continue at same 3 pace 8 Does the pain or discomfort in your chest go away if you stand still? (Y/N) 9 How long does it take to go away? 10 minutes or less 1 More than 10 2 minutes BREATHLESSNESS 1 Do you get short of breath walking with people your own age on level ground? (Y/N) 2 On walking up hills or stairs. do you get more breathless than people your own age? (Y/N) 3 Do you ever have to stop walking because of breathlessness? (Y/N) Right 1 Left 2 3 4 5 6 2 7 8 9 6 CALF PAIN 1 Do you ever get pain in your calf muscles on walking at an ordinary pace. does this (Y/N) produce the pain? 7 When you get any pain or discomfort in your chest on walking. January 1998 . does this produce the pain? (Y/N) 6 When you walk uphill or hurry. on the level? (Y/N) 2 Do you get pain in your calf muscles when you walk uphill or hurry? (Y/N) Eur Heart J. Vol.