Family Practice Advance Access originally published online on February 3, 2006
Family Practice 2006 23(2):167-174; doi:10.1093/fampra/cmi124
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Chest pain in general practice: incidence, comorbidity and mortality
a Centro Español de Investigación Farmacoepidemiológica (CEIFE), Madrid, Spain, b AstraZeneca R&D, Mölndal, Sweden, c Department of General Practice and Primary Care, King's College, London, UK.
Correspondence to Ana Ruigómez, Centro Español de Investigación Farmacoepidemiológica (CEIFE), Madrid, Spain; Email: aruigomez{at}ceife.es
Received 4 July 2005; Accepted 28 December 2005.
Ruigómez A, Rodríguez LAG, Wallander M-A, Johansson S, Jones R. Chest pain in general practice: incidence, comorbidity and mortality. Family Practice 2006; 23: 167–174.
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Abstract |
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Background. Chest pain is a common symptom that presents the primary care physician with a complex diagnostic and therapeutic challenge.
Aims. To evaluate the natural history and management of patients diagnosed with chest pain of unspecified type or origin in primary care.
Design. Population-based case–control study.
Methods. The study included 13 740 patients with a first diagnosis of unspecified chest pain and 20 000 age- and sex-matched controls identified from the UK General Practice Research Database. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression. Risk estimates were adjusted for age, sex and number of physician visits.
Results. The incidence of a new diagnosis of chest pain was 15.5 per 1000 person-years and increased with age, particularly in men. The risk of a chest pain diagnosis was greatest in patients with prior diagnoses of coronary heart disease (OR: 7.1; 95% CI: 6.1–8.2) and gastroesophageal reflux disease (OR: 2.0; 95% CI: 1.7–2.3). In the year after diagnosis, chest pain patients were more likely than controls to be newly diagnosed with coronary heart disease (OR: 14.9; 95% CI: 12.7–17.4) and heart failure (OR: 4.7; 95% CI: 3.6–6.1). A new diagnosis of chest pain was associated with an increased risk of death in the following year (RR: 2.3; 95% CI: 1.9–2.8).
Conclusions. Some causes of chest pain are underdiagnosed in primary care. This is of particular consequence for the minority of chest pain patients with cardiac disease.
Keywords. Chest pain, automated database, population-based sudy, primary care, incidence.
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Introduction |
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Chest pain is a commonly occurring symptom affecting between 20 and 40% of the general population during their lifetime.1–4 Approximately 1.5% of the general population consult a primary care physician each year because of chest pain symptoms.5 In the UK, a presenting complaint of chest pain makes up 1% of all primary care consultations.6 Furthermore, more than 5% of visits to emergency departments, and up to 40% of emergency admissions, are due to chest pain.7–9
Chest pain can be triggered by a range of different illnesses, including cardiac, gastrointestinal, musculoskeletal, psychological, malignant and pulmonary diseases.1,2 While life-threatening cardiac disease is of the greatest immediate concern to both patient and physician, cardiac disease is estimated to account for only a minority (8–18%) of all cases of chest pain.5,10,11 Chest pain patients in whom no underlying cause is diagnosed still remain anxious that they may have a potentially life-threatening disease,12 and experience impaired health-related quality of life as a result.13 The primary care physician is, therefore, faced with a complex diagnostic and therapeutic challenge. While forced to consider optimal utilization of health care resources, it is important that other potential causes of chest pain are considered, and that a correct diagnosis is provided to enable appropriate management of patients.
There is a shortage of information regarding the natural history, clinical course and management of chest pain in primary care. In order to gain further epidemiological insights into this symptom, the General Practice Research Database (GPRD) was used to compare demographics, health care use, comorbidity and mortality in patients with and without chest pain of unspecified type or origin in UK primary care.
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Methods |
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Data source
Data for this study were extracted from the GPRD. The GPRD is a large longitudinal primary care database and contains information entered by about 1500 primary care physicians covering a population of
3 million individuals representative of the UK general population.14,15 Each individual in the GPRD is registered with a single GP. The physicians hold the complete medical records of all individuals registered with them, including demographics, diagnosis (using OXMIS and READ codes), prescriptions and referrals. This information is anonymized and sent to the Medicines and Health care products Regulatory Agency (MHRA) for data management and use in research projects. A number of studies have validated the accuracy and completeness of the GPRD.16,17
Study population
To identify patients with a new diagnosis of chest pain of unspecified type or origin in 1996, we first identified a study source population of all individuals aged 2–79 in 1996, who had been registered with the physician for at least 2 years and who had at least one entry in the GPRD in the previous 3 years (Fig. 1). Follow-up for each individual in the source population started on 1 January 1996. We excluded individuals who, before the start of the follow-up, had a prior history of cancer, a history of chest pain in the previous 2 years, or who were pregnant during 1996. Follow-up ended at the first occurrence of one of the following: diagnosis of unspecified chest pain, cancer, pregnancy, date of last data collection, death or 31 December 1996, whichever came first. Only codes for chest pain that did not specify the type or location of this symptom were included (i.e. only patients who presented with chest pain where a specific diagnostic label was not applied) (Fig. 1). The index date of the 13 740 cases with unspecified chest pain was the date of first diagnosis of chest pain. We identified an age- and sex-matched control group without a chest pain diagnosis from the same source population using the same eligibility criteria, assigning a random date during 1996 for use as the index date (n = 20 000). Individuals in the control group had to be free of a chest pain diagnosis in the 2 years prior to the index date. To estimate mortality, individuals in the two groups (chest pain and controls free of chest pain) were followed-up from index date until death, date of last data collection or March 2002. We ascertained the cause of death registered by the physician by manually reviewing the computer patient profiles of all deaths that occurred within the first year of follow-up. Mortality data from the GPRD have been analysed in several recent peer-reviewed publications.18–20
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Data collection
Demographic data and information on risk factors [smoking status, body mass index (BMI) and alcohol intake] were collected from computer records, as well as information on the number of consultations, admissions and referrals in the 12 months before the index date, and morbidity in the 12 months before and 12 months after the index date.
We assessed current use of certain prescription medications associated with potential causes of chest pain [non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, nitrates, paracetamol, proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, antidepressants and anxiolytics]. Current use was defined as a prescription lasting until the index date or ending in the previous 3 months, and was compared with non-use (no prescription recorded before the index date).
To estimate the morbidity in the two groups (chest pain and controls free of chest pain), the following diagnoses were collected from the GPRD for each patient during the 12 months before and the 12 months after the index date: gastrointestinal (GERD, dyspepsia, peptic ulcer disease, irritable bowel syndrome, gall bladder disease and hiatus hernia), psychological (stress, sleep disorders, anxiety and depression), cardiac (coronary heart disease and heart failure), respiratory (asthma and COPD) and musculoskeletal complaints (including trauma/injury).
Statistical analysis
Incidence rates of unspecified chest pain were calculated for both sexes in eight 10-year age groups as the ratio of the number of chest pain patients to the total number of patient-years within that group. We performed a nested case–control analysis using all patients with unspecified chest pain as cases and the comparison cohort free of chest pain as controls. We used unconditional logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with chest pain. All risk estimates were adjusted for the matching factors (age and sex), and for the number of visits to the physician in the previous year.
To assess the number of deaths in each study group, patients alive at end of the study period (March 2002) were regarded as censored at that date. A few practices had their last information recorded in the GPRD at an earlier date. For patients belonging to these practices, follow-up was censored at the date of last data collection. We used Cox proportional hazards regression to estimate the relative risk of dying in the chest pain group compared with the control group. Within the chest pain group, we also estimated the 1-year mortality risk in patients with prior cardiovascular morbidity compared with those free of cardiovascular disease in the year prior. We similarly assessed the risk of death in patients with prior non-cardiovascular morbidity (GI, psychological, respiratory, musculoskeletal) compared with patients without such non-cardiovascular morbidity in the year prior. Information on the cause of death was extracted from computerized files, and was grouped into four categories as follows: ischaemic heart disease, other cardiac (non-ischaemic) and cerebrovascular disease, cancer, and other general causes (non-cardiovascular) and unknown cause.
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Results |
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Using the GPRD, we identified 13 740 patients with new-onset chest pain of unspecified type or location in UK general practice in 1996. The annual incidence rate for an unspecified chest pain diagnosis in primary care corresponded to 15.5 per 1000 person-years. The incidence of an unspecified chest pain diagnosis increased with age, particularly in men (Fig. 2). In the 20–29 year age group, the incidence rate for unspecified chest pain per 1000 person-years was 10.0 for men, compared with 9.9 for women. In the 70–79 year age group, however, the incidence rate had more than doubled to 32.2 for men and 25.8 for women.
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In comparison with an age- and sex-matched sample of 20 000 patients without an unspecified chest pain diagnosis, patients with a new unspecified chest pain diagnosed were marginally more likely to be current smokers (OR: 1.2; 95% CI: 1.2–1.3). Alcohol intake and BMI were not significantly associated with an unspecified chest pain diagnosis (data not shown). In the 12 months before diagnosis, patients with unspecified chest pain were more likely to have consulted their physician three times or more (OR: 1.7; 95% CI: 1.6–1.8) or to have been referred to a specialist or hospitalized (OR: 1.3; 95% CI: 1.2–1.4). The concurrent prescription of medications for a number of potential causes of chest pain was more prevalent in patients with a new unspecified chest pain diagnosis than in the control group. After adjustment for ischaemic heart disease, health care utilization and each of the other prescriptions studied, current use of PPIs (OR: 1.4; 95% CI: 1.2–1.6), H2-receptor antagonists (OR: 1.4; 95% CI: 1.2–1.6), anxiolytics (OR: 1.4; 95% CI: 1.2–1.6), NSAIDs (OR: 1.2; 95% CI: 1.1–1.3), paracetamol (OR: 1.5; 95% CI: 1.4–1.7) and nitrates (OR: 1.5; 95% CI: 1.3–1.7) was more common among patients with an unspecified chest pain diagnosis than among the controls.
In the 12 months before an unspecified chest pain diagnosis, a number of diagnoses were more common in the chest pain group than the control group (Table 1). The most common prior diagnoses were musculoskeletal (24.1% in the chest pain group versus 16.2% in the control group), followed by gastrointestinal (11.9 versus 5.2%), psychological (11.7 versus 6.2%) and cardiac (8.2 versus 1.1%). After adjustment for age, sex and number of primary care consultations, the risk of an unspecified chest pain diagnosis was greatest in patients with a prior coronary heart disease diagnosis (OR: 7.1; 95% CI: 6.1–8.2), followed by those with a prior diagnosis of GERD (OR: 2.0; 95% CI: 1.7–2.3). An increased likelihood of presenting with a new unspecified chest pain diagnosis was also observed among patients with a prior diagnosis of heart failure (OR: 1.9; 95% CI: 1.5–2.4), dyspepsia (OR: 1.8; 95% CI: 1.6–2.0), hiatus hernia (OR: 1.8; 95% CI: 1.2–2.5) and COPD (OR: 1.7; 95% CI: 1.4–2.1).Small but significant associations were also seen between a new unspecified chest pain diagnosis and a prior diagnosis of sleep disorders, asthma or musculoskeletal disorders. No associations were observed between unspecified chest pain and a prior diagnosis of peptic ulcer disease, gall bladder disease, psychological stress or depression.
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In the 12 months after diagnosis, patients with unspecified chest pain were more likely than controls to be newly diagnosed with a range of cardiac, gastrointestinal, respiratory, psychological and musculoskeletal diseases (Table 2). After adjustment for age, sex and number of primary consultations, the odds of a diagnosis of heart failure or coronary heart disease were 4.7 and 14.9 times greater, respectively, in patients who had received an unspecified chest pain diagnosis in the prior 12 months than in controls (95% CI: 3.6–6.1 and 12.7–17.4, respectively). Similarly, compared with controls, the odds of a diagnosis of GERD, hiatus hernia or peptic ulcer disease were increased at least 3-fold in patients with a prior unspecified chest pain diagnosis. The odds of a diagnosis of other gastrointestinal diseases, as well as psychological, respiratory and musculoskeletal diseases, were also increased in patients with a prior unspecified chest pain diagnosis compared with controls, but to a lesser extent. When analysing the corresponding associations by age, patients with unspecified chest pain aged 30–59 years were at greatest increased risk of receiving a new diagnosis of gastrointestinal or cardiovascular disease compared with the control cohort.
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The mortality rate was increased among patients with unspecified chest pain. During a mean follow-up period of 4 years (SD 1.2 years), 842 of 13 740 patients died in the unspecified chest pain cohort, compared with 710 of 20 000 patients in the comparison control cohort. Patients with unspecified chest pain had a significantly lower survival rate than patients without unspecified chest pain (Fig. 3). The risk of mortality over the average 4-year follow-up was similar in both cohorts once adjusted for age, sex, health care use and prior ischaemic heart disease (RR: 1.1; 95% CI: 1.0–1.3). There was an excess risk of death concentrated in the first year of follow-up, when the risk of death in patients with unspecified chest pain was more than double that in controls (adjusted RR: 2.3; CI: 1.9–2.9) (Table 3). This increased mortality was mainly due to ischaemic heart disease (Table 4).
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In the first year of follow-up, there were two deaths among patients with unspecified chest pain younger than 30 years (n = 1934) and none in the comparison cohort (n = 2832). Although the relative risk of death among chest pain patients in the first year of follow-up was higher in the 30–59 year age group (RR: 3.7; 95% CI: 2.1–6.6) than in the 60–79 year age group (RR: 2.6; 95% CI: 2.1–3.2), this difference was not statistically significant. Among chest pain patients, those with prior cardiovascular morbidity had a higher 1-year mortality risk than those free of cardiovascular morbidity (RR: 1.4; 95% CI: 1.2–1.8). In contrast, chest pain patients with prior non-cardiovascular morbidity (GI, psychological, respiratory, musculoskeletal) did not have a higher 1-year mortality risk (RR: 1.0; 95% CI: 0.8–1.4) than those free of non-cardiovascular morbidity.
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Discussion |
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The incidence of diagnosis of chest pain of unspecified type or location in UK general practice in 1996 was 15.5 per 1000 person-years and increased steadily with age in both males and females. The overall incidence rate found in this study was similar to that reported in a recent large study of primary care patients in Sweden, in which the rate was 19.6 per 1000 patient-years.5 As in the Swedish study, our investigation showed that men were more likely to be diagnosed with chest pain than women. A study of primary care consultations in England and Wales conducted in 1991–92 did not report on the incidence rate of chest pain in patients for whom a specific diagnosis could not be made. It did, however, observe a lower prevalence rate (defined as number of patients consulting at least once) in this patient group, which was 10.7 per 1000 patient-years.6
Population-based surveys show that chest pain is a common symptom, affecting at least a fifth of the population in a given year,1,2,4 which is considerably higher than the incidence we report. While this may, in part, reflect the chronicity of chest pain, low consultation rates are likely to make the major contribution to this difference. In a population-based self-report survey, over half of individuals with chest pain did not consult a physician about this symptom, rising to over three-quarters of those without a history of cardiac disease.2 As our study was based on physician diagnosis in primary care rather than on patient-reported symptoms, chest pain incidence will inevitably have been under-ascertained. The increasing incidence of chest pain diagnosis with age that we report confirms previous findings.3 This trend is likely to reflect the increasing risk of cardiac disease with age, as it is generally reversed when chest pain patients with a history of ischaemic heart disease and angina are excluded from analysis.1,2
Our study reported 3% mortality rate in patients with unspecified chest pain in the first year after diagnosis, compared with <1% in the control group during the first year. Similar mortality rates have been demonstrated in studies of chest pain patients following discharge from hospital.21,22 Following adjustment for age, sex, prior history of ischaemic heart disease and visits to the GP in the year before chest pain diagnosis, the relative risk of death was 2.3 times higher in patients with unspecified chest pain than in the control group. The 1-year mortality rate was greatest in patients with an unspecified chest pain diagnosis who were older than 30 years, primarily as a result of deaths from ischaemic heart disease.
A prior diagnosis of cardiac disease was more likely in patients with unspecified chest pain than in controls. Patients newly diagnosed with unspecified chest pain were also much more likely to receive a subsequent cardiac diagnosis. However, although an unspecified chest pain diagnosis was most highly associated with a prior cardiac disease diagnosis in our study, overall, only a minority of patients with unspecified chest pain had cardiac disease diagnosed (less than 1 in 10 in the preceding 12 months). This reflects observations from other studies that, of ambulatory patients presenting with chest pain, only 11–34% are found to have a cardiac cause.23
The major non-cardiac diagnoses associated with unspecified chest pain were gastrointestinal, most notably GERD. The association between GERD and chest pain is currently the subject of much interest.24 GERD is consistently reported as a risk factor for chest pain in cross-sectional surveys of the general population1,2,4 and we previously observed an increased risk of chest pain in a cohort of newly diagnosed GERD patients in primary care.25 In the current primary care study, we found that almost 4% of patients with unspecified chest pain were diagnosed with GERD in the 12 months before chest pain diagnosis and that a similar number had a GERD diagnosis in the following year. However, GERD appeared to be under-represented as a potential cause of chest pain in our study. In previous population-based surveys, GERD was recorded in more than a third of individuals without prior cardiac disease,2,4 and GERD was diagnosed in up to 60% of patients with non-cardiac chest pain in tertiary care.26,27 This suggests that GERD may be under-recognized as a cause of chest pain in UK primary care, as well as being under-recognized as a potential diagnosis. An association between GERD and chest pain is suggested by several small studies reporting improvement of chest pain symptoms upon anti-reflux therapy in up to 95% of GERD patients.26,28,29 This link with GERD may account for the associations of chest pain diagnosis with a prior diagnosis of dyspepsia or hiatus hernia observed in the current study. A recent decision analysis concluded that, in chest pain patients lacking a cardiac abnormality, empirical treatment with high dose acid suppressive therapy can provide a readily available and potentially cost-saving diagnostic tool.26,30,31
Our study sheds light on the relative importance of different potential causes of chest pain in UK primary care patients. It should be noted, however, that the GPRD does not definitively link these diagnoses to chest pain; thus, while many chest pain patients did not receive any diagnosis to explain their symptoms, other patients may have received more than one potentially relevant diagnosis during the study period. The pattern of diagnosis and symptom recording is also likely to vary between physicians. In addition, it may be influenced by variations over time and by the patients' age, sex and comorbidities. Nevertheless, we feel that the large population base investigated in our study, together with evidence from other studies, suggests a real association between chest pain and GERD in addition to that between chest pain and cardiac disease.
In conclusion, chest pain is a frequent cause of consultation in UK primary care, with almost 2% of the population consulting a primary care physician with new-onset chest pain in a given year. Cardiovascular mortality was increased in the year following the initial unspecified chest pain diagnosis, although fewer than one in 10 patients had a history of cardiac disease. This suggests that the absence of a history of cardiac disease cannot be relied upon to exclude cardiac causes of chest pain. Other potentially treatable causes of chest pain such as GERD may have been under-diagnosed, highlighting the need to identify those patients whose symptoms are a consequence of musculoskeletal, gastrointestinal, psychological and respiratory disease. The new information presented in this paper emphasizes the importance of attempting to reach a firm diagnosis in primary care patients with an initial diagnosis of ‘ non-specific chest pain’, because a substantial minority will go on to develop significant cardiac disease.
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Acknowledgments |
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The authors are grateful to Drs Anja Becher and Chris Winchester for editorial advice and comments on a previous version of the manuscript. This study was supported by a research grant from AstraZeneca.
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References |
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