Abstract
The research described in this thesis focuses on the potential value of early cardiac biomarkers in the diagnosis of acute coronary syndrome (ACS) in the primary care setting, with special attention for point-of-care tests. The design and results of a large diagnostic study on the value of a bedside test
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for heart-type fatty acid-binding protein (H-FABP) in the diagnosis of ACS in primary care are presented. In 298 consecutive patients suspected of ACS by the GP the H-FABP bedside test (Cardiodetect, cutoff 7 ng/ml) was performed within 24 hours after symptom onset. ACS was present in 66 patients (22%). The overall PPV of H-FABP was 65% (95%CI 50-78) and the NPV was 84% (95%CI 80-88), sensitivity was 43% (95%CI 31-57) and specificity 94% (95%CI 89-97). Adding H-FABP to a diagnostic model of signs and symptoms led to an increase in the area under the receiver operating curve (AUC) from 0.66 (95%CI 0.58-0.73) to 0.75 (95%CI 0.68-0.82). Thus, the H-FABP bedside test did provide additional diagnostic certainty in combination with clinical findings. However, the test cannot be used to safely exclude ACS. We recommend use of the test to confirm ACS in patients who were otherwise not referred to hospital by the GP, since the test can be used as an extra precaution not to miss ACS. Median patient delay (defined as the time from onset of symptoms until call for help) was 132 minutes (interquartiel range (IQR) 44 to 360 minutes). Median doctor delay (defined as time from call for help until GP consultation) was 33 (IQR 20 to 55) minutes in men and 45 (IQR 26 to 72) minutes in women (p=0.01). Women reported radiation of chest pain more often than men (68% versus 57%). Thus, in patients suspected of ACS in primary care doctor delay was longer in women than in men, while presenting symptoms of ACS were similar, or even more typical, in women. GPs were asked to estimate the probability (0% to 100%) of the presence of ACS. Comparing the area under the receiver operating curve of the GP estimate and the clinical decision rule (CDR) revealed that the GP more adequately classified patients as ACS or no ACS than the CDR (AUC 0.75 (95%CI 0.68 ; 0.82) and 0.66 (95%CI 0.58 ; 0.73)) respectively. In a classification table for three predefined categories, that is, low, intermediate and high risk (20%), there was a 51% concordance between the risk estimation of the GP and the decision rule. We performed a meta-analysis of 16 diagnostic studies (3709 patients). In the included studies, the prevalence of ACS ranged from 13 to 74%, male gender ranged from 49 to 84%, median age ranged from 64 to 76 years. The summary estimate, calculated using the bivariate random effects approach, was 84% (95% confidence interval (CI) 76-90%) for sensitivity and 84% (95%CI 76-89%) for specificity. Concluding, H-FABP did not fulfil the requirements needed for a safe and early diagnosis of ACS when it was tested as a stand-alone test.
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