Prediction of cardiovascular disease in patients with unattributed chest pain in UK primary care
Problem
Most adults presenting in primary care with chest pain symptoms will not receive a specific diagnosis (“unattributed” chest pain). These patients are more likely to develop cardiovascular disease (CVD) than patients with chest pain attributed to a non-coronary reason. Determining which patients with unattributed chest pain have the greatest risk of CVD would allow for targeted intervention strategies. Current risk prediction algorithms for CVD (e.g. QRISK3) have been developed for the general population but may not be appropriate for this group of patients. The aim was to assess within patients with unattributed chest pain, whether those at greatest risk of CVD can be ascertained.
Approach
We used the CPRD Aurum database containing electronic health records from English general practices linked to admitted patient hospitalisations from the Hospital Episode Statistics database. The study population was patients aged 18 and over with a new primary care record of unattributed chest pain between 2002 and 2018, and no record of CVD up to six months (diagnostic window) afterwards. Outcomes were cardiovascular events starting from end of the diagnostic window.
Flexible parametric survival analyses were used to derive risk factors for future CVD over 10 years. Baseline candidate factors (n=23) were those included in general population cardiovascular risk algorithms, alternative explanations for chest pain, and other comorbidities predictive of CVD. We developed and validated a prediction model, with external validation in a second primary care database (CPRD GOLD) linked to admitted patient hospital data and compared performance to a risk prediction model (QRISK3) developed for use in the general population.
Findings
There were 374,917 patients with unattributed chest pain. Median follow-up was 6.1 years. Incidence of CVD was 19.3 per 1000 person-years. The strongest comorbidity risk factors for CVD included type I diabetes (adjusted hazard ratio 2.41; 95% CI 2.11, 2.76), atrial fibrillation (1.95; 1.85, 2.06), and hypertension (1.55; 1.50, 1.59). Socio-demographic risk factors included older age, male gender, greater deprivation, and Asian ethnicity.
Internal validation of the final model showed high predictive performance with c-statistic of 0.797. Discrimination and calibration performance were good when stratified by gender, neighbourhood deprivation, and geographical region.
In the external validation dataset, the c-statistic was 0.805 and calibration slope close to one. Calibration plots showed good agreement between observed and expected risk at all levels of risk. A reduced model using a subset of key risk factors for CVD gave nearly identical performance. QRISK3 performed less well in this population.
Consequences
Patients presenting to primary care with unattributed chest pain are at increased risk of cardiovascular events, but it is feasible to ascertain those most at risk using routinely recorded information in the primary care record. These patients could then be targeted for preventative measures.