Ruling out coronary heart disease in primary care patients with chest pain: a clinical prediction score

Chest pain is a common complaint that occurs in 1 to 2% of primary care patients [1]. Chest pain raises concerns about the occurrence of a serious condition such as coronary heart disease (CHD) [2], which is present in about 12% of primary care patients with chest pain [1, 3]. Family practitioners should be equipped to rule out an acute CHD related event rapidly. They are used to estimating the probability of CHD in a patient with chest pain on the basis of pain characteristics, patient's age, gender, history and cardiovascular risk factors [4]. Cardiovascular risk factors and chest pain history are associated with CHD, and have been widely studied [4, 5]. However, chest pain characteristics alone are not sufficient to reliably rule out ischemic heart disease [6]. A more complete set of predictors is thus needed for this purpose.

Predictive scores for CHD in emergency settings have been developed [7‐9], and are now implemented [10, 11]. However, these scores are not necessarily useful in the primary care setting [12]. To our knowledge, no ambulatory CHD score has been developed to support primary care physicians in ruling out CHD in patients with chest pain. Such a score might help physicians, reassure patients [13], and spare time and resources from being spent on further investigations. The objective of this study was to develop an ambulatory CHD predictive score, based only on the patient's history and physical examination in the primary care setting, to rule out CHD without further investigations of patients with chest-pain.

Altogether, 672 patients were included in the study. Twenty-seven patients were lost to follow-up at one year. Their CHD status reported at three months was therefore carried forward and these patients were included in the analysis. Excluded patients were those having missing data on baseline cardiovascular risk status (n = 6) or were younger than 16 (n = 5). In the remaining group of 661 patients, an average of 11.2 (SD, ±7.6) patients were recruited in each of the 59 centers. The total practice-year we followed was of 4.8 years including Thursdays, Saturdays and Sundays when practices are closed. This corresponds to an average of 0.7 patients with chest pain for every GP for every working day. The recruitment period was nevertheless not the same between physicians. Eleven physicians stopped recruiting before they were meant to. If we overview the intervals from which patients were recruited for each physicians, inclusion was constant over time. Physicians apparently either stopped recruiting or continued recruiting per protocol. The mean age of patients included in analysis was 55.4 years (SD ±19), and 314 patients (47.5%) were male. Most patients (602, 91.1%) were already known to their family practitioners, and 314 (47.5%) had never experienced the same type of pain before. One hundred and twenty patients (18.2%) had previous evidence of CHD or CVD (revascularization procedures, heart failure, or peripheral arterial disease) and 433 patients (65.5%) were known to have one or more cardiovascular risk factors, 196 were known to have none. The presence of cardio-vascular risk was unknown to the physician for 32 of the 661 patients. Eighty-five patients (12.9%) were diagnosed with CHD, including 75 cases of angina pectoris (11.1%), six cases of unstable angina (0.9%) and four cases of myocardial infarction (0.6%). None of the 196 patients for which it was known that they had no risk factor, and two of the 32 patients with unknown laboratory status were diagnosed with CHD.

We developed a clinical prediction score for ruling out CHD in primary care patients with chest pain. Our CHD score includes eight predictors (age, gender, having at least one CVD risk factor, history of CVD, duration of pain, substernal location of pain, increased pain with exertion, absence of tenderness at palpation), which are all known to be associated with CHD [6], and easily identifiable from history and physical examination. Our score can classify patients in three groups with an increasing prevalence of CHD. Bootstrapping, the recommended tool for this kind of modeling [15], was used to test internal validity. Our ambulatory CHD score is consistent throughout our data, and the predictive power of the model is acceptable. Our ruling-out score classified two thirds of the studied population in the low-risk category with a strong negative predictive value (99.8%). Negative predictive value remained high in the validation cohort (94.8%) with a negative likelihood ratio of 0.31. Our ambulatory CHD score seems adapted for the management of CHDs in primary care. However, this score does not entirely rule out CHD as 5.2% of patients in the low risk group from the validation cohort ended up having CHD within the next six months.

Our data show both similarities and differences from the published determinants used to rule out CHD. The American College of Physicians [4] developed guidelines to manage patients in primary care for whom chronic stable angina was suspected. Our scores are in agreement with their recommendations of using age, gender, cardiovascular risk factors, and pain characteristics to estimate the probability of CHD. Like the Framingham risk score [5], our ambulatory CHD score also includes age, gender, and cardiovascular risks as indicators of CHD events. The Framingham risk score does not include a personal history of CVD or characteristics of pain, which are essential to detecting patients with CHD. These characteristics have been included in scores developed in emergency departments [7, 8, 17‐25]. However, the prevalence and etiology of CHD differ considerably between these two settings. CHD is about four times less frequent in patients with chest pain in primary care [1] than in those admitted in emergency departments [26]. Furthermore, the severity of CHD differs between these settings. Over 10% of patients hospitalized with chest pain [26, 27] have a myocardial infarction, whereas we observed a prevalence of only 0.6% in primary care [3]. Factors that may appear to be important or unimportant in samples with relatively few outcome events may be substantially misleading. For example, pain lasting for more than 60 minutes is very atypical for angina but not so unusual for an acute myocardial infarction. Given the very low prevalence of myocardial infarction in this manuscript, factors that may be very important for diagnosing acute myocardial infarction may be substantially undervalued. This could explain why the area under the curve for predicting CHD seems better in our score than for either the TIMI, the PURSUIT or the GRACE scores [28]. This difference illustrates the importance of developing guidelines and scores specifically for the primary care setting instead of a mere use of scores developed for emergency department patients.

The major strength of our study is the development of a clinical tool for family practitioners, using data collected by a research network in primary care [29]. The use of the ambulatory CHD score, based only on the patient's history and physical examination, allows family practitioners to estimate risks of discharging a patient without further examinations.

Our study has some limitations. We would first like to remind physicians that scores derived from logistic regression cannot identify unusual presentations. Consider the example of a young patient who abuses cocaine, and presenting an acute myocardial infarction. This patient would be classified in the low-risk group [30]. Clinical knowledge and experience therefore still remain essential in ruling out CHD in patients with chest pain [31, 32]. Secondly, we used delayed diagnosis instead of referring all patients to a specialist. Logistical resources and patients' unavailability make it very difficult to assure objective confirmation in primary care research. Furthermore, in the derivation cohort, assessors were not blinded to the initial state of exposure when defining cases. However, 28% of the patients have been referred to specialists or to hospitals, and the one-year follow up allows us to reasonably confirm the absence of missed CHD. Furthermore, in cases of doubt, the family practitioner was questioned for further information. In the 10% of records reviewed by experts, only one controversial case was detected and resolved after discussion with the family practitioner. We therefore believe that misclassification is negligible. It should be noted that most patients were known to their primary care physicians, a factor that could have facilitated the diagnostic process. Physicians were therefore not blinded to their patient's condition and could have been more likely to report some signs knowing their patient had cardiac chest pain. Furthermore, we cannot exclude that patients with MI or unstable angina which rapidly became entirely asymptomatic remained undetected. The study is also underpowered to detect any difference in myocardial infarction or unstable angina between the risk groups. Finally, external validation showed the score to be much less sensitive than it was meant to be. Both studies however included different patients. In the Marburg study, young patients were not included (≥35 years vs. ≥16 years), nor were those with posterior chest pain or pain lasting more than one month. The Marburg study therefore excluded patients who were more likely to be at low risk compared to those included in the Lausanne cohort. This method nevertheless shows a better diagnosis ability than recognized laboratory markers such as BNP and NT-proBNP [33] in possible heart failure patients.

In summary, we developed a clinical prediction score to rule out CHD in primary care patients with chest pain. This clinical tool may limit clinical investigation in patients with chest pain in primary care where the presentation and the management are completely different from the emergency departments. However, further analyses of the proposed score should be conducted in various primary care contexts to evaluate its true benefit better and evaluate its implementation.