A total of ACS 10,043 visits from 9,118 patients were included in this study. Figures 1.B-D present race/sex characteristics of the study participants.
Sex/Race Differences in Symptom Presentation
Males had a higher prevalence of chest pain (47.53%) than females (43.67%) (Table 1). Caucasian ACS patients had the highest prevalence of chest pain (47.13%) and dyspnea (41.45%), followed by African Americans (42.11% and 31.86%) and Asians with 37.54% and 31.72% (Table 2). The prevalence of dyspnea was similar for both sexes (females: 39.29%; males: 39.49%). We observed significant group differences in the prevalence of several symptoms (Tables 1 and 2). Females had a higher prevalence of abdominal pain (6.45%) and nausea (5.96%) than men (abdominal pain: 3.78%; p<0.0001; z-statistics: 122.96 and nausea: 3.58%; p<0.0001; z-statistics: 60.15). We also conducted a series of marginal structural models to determine associations between sex/race (predictors) and the two primary symptoms (chest pain and dyspnea) as outcomes while controlling for the effect of confounding variables. When predicting symptoms with race, the model was adjusted for age and sex. When predicting symptoms with sex, the model was adjusted for age and race. The causal odds ratios and associated 95% confidence intervals (CIs) for all pairwise comparisons are summarized in Supplementary Table 3. We found that Caucasians were more likely to report chest pain (odds ratio: 1.53; p < 0.0001; 95% CI: 1.43 - 1.63) and dyspnea (odds ratio: 1.44; p < 0.0001; 95% CI: 1.35 - 1.54), whereas African Americans were less likely to report these symptoms (chest pain: 0.64, p < 0.0001; 95% CI: 0.55 - 0.75; dyspnea: 0.65, 95% CI: 0.56 - 0.76). In terms of the average number of symptoms per visit from 12 examined symptoms, Caucasians had a significantly higher number of average symptoms per visit than Asians (p = 0.0009; t-statistics: 3.1; Cohen’s d = 0.180) and African Americans (p < 0.0001; t-statistics: 3.9; Cohen’s d = 0.115).
Troponin Measurement & Pharmacological Treatment
Initial troponin levels were ordered within 24 hours after admission for 4,384 ED visits. The time to the first troponin order was shorter in male ACS patients than in female patients (p-value = 0.0167). However, the difference did not reach the Bonferroni-adjusted level of significance of p = 0.00357 for 14 comparisons across sexes, races, and tests. Antiplatelet administration, including glycoprotein IIb/IIIa antagonists, was the most common treatment within 24 hours post-admission, experienced in 6,699 ED visits (66.70% of total ED visits). This was followed by anticoagulation (56.90%), beta-blockers (42.17%), opiates (25.38%), ACE inhibitors (18.32%), calcium channel blockers (15.98%), and anti-ischemic/antianginal agents (0.11%). For most patients, the initial medication was administered within the first five hours. However, there were individuals who received their medications after 10 hours (see the outliers in Figures 2.B and 2.C). The remaining 1,774 patient visits did not receive pharmacological interventions within the first 24 hours. Figure 2.A illustrates the sex and race proportion of ACS patients who did not receive any medications within 24 hours. Compared to males, females were more likely to receive no medication (p-value = 0.033; z-statistics = 1.84; Cohen’s d = 0.037). However, the difference was only marginally significant. The proportion of visits receiving no treatment within the first 24 hours was higher in Caucasians (Figure 2.A) than African Americans (p-value < 0.0001; z-statistics = 4.25; Cohen’s d = 0.123) and Asians (p-value < 0.0001; z-statistics = 3.73; Cohen’s d = 0.216 ). Sex and race differences in the post-admission treatment timing were also observed. Female patients experienced a longer door-to-treatment time within the first 24 hours than male patients (Figure 2.B) (p-value <0.0001; z-statistics = 6.18; Cohen’s d = 0.142). Caucasian patients experienced a shorter time than African American patients (p < 0.0001, z-statistics = -4.39; Cohen’s d = -0.14).
Sex/race Differences in EHR Data Missingness
Vital signs, creatinine, blood urea nitrogen, and glucose levels were used to examine sex/race differences associated with the EHR data missingness among ACS patients (Supplementary Figure 1). Caucasian ACS patients had the highest mean feature missingness (2.02) compared to Asians (mean feature missingness = 0.83; p-value < 0.0001; t-statistics = 7.92; Cohen’s d = 0.46), and African Americans (mean feature missingness = 1.54; p-value < 0.0001; t-statistics = 6.42; Cohen’s d = 0.19). African Americans had a higher number of feature missingness than Asians (p-value < 0.0001; t-statistics = 5.15; Cohen’s d = 0.32). We did not observe a significant difference in data missingness between males and females.
Four clusters were identified in our study population (Figure 3), each corresponding to ACS patients with common clinical features (vital signs and lab measures) and symptom presentations. A total of 6,408 ED visits were included in the cluster analysis. ED visits that did not have all required vital signs and lab measures were excluded. A total of 6,127 visits were assigned to one of the four non-noise clusters. The largest cluster encompassed 3,125 ED visits, accounting for 51% of ED visits in the analysis. The clusters largely grouped around ACS symptom presentations, with clusters roughly corresponding to chest pain in all patients and no dyspnea (cluster 0 with 1,104 visits), no dominant symptom and almost no chest pain and dyspnea (cluster 1, the largest cluster with 3,125 visits), chest pain and dyspnea in nearly all patients (cluster 2 with 1,390 visits), dyspnea in all patients and almost no chest pain (cluster 3 with 506 visits). The prevalence of male patients was 62.6% in cluster 0, 59.4% in cluster 1, 59.9% in cluster 2, and 52.0% in cluster 3. The prevalence of female patients was 37.4% in cluster 0, 40.6% in cluster 1, 40.1% in cluster 2, and 48.0% in cluster 3. Using logistic regression, we identified several significant associations between patient demographics and clusters. Age was negatively associated with cluster 0 (p <1e-20) and positively associated with cluster 3 (p <1e-20). The prevalence of Caucasians was negatively associated with cluster 1 (p<6e-4). We identified significant differences in door-to-treatment time across the clusters (Figure 4.B), with clusters 0 (all chest pain and no dyspnea) and 2 (nearly all chest pain and dyspnea) having the shortest mean time-to-treatment than the two other groups with lower chest pain prevalence (Supplementary Table 4). The proportion of visits receiving no pharmacological treatment also varied across the four clusters (Figure 4.A). Cluster 1 (no dominant symptom, almost no chest pain and dyspnea) had the largest proportion of visits receiving no pharmacological administration within 24 hours post-admission and cluster 0 (chest pain in all patients and no dyspnea) had the smallest proportion of visits with no pharmacological administration within 24 hours after ED admission (Supplementary Table 5). Cluster 2 (chest pain and dyspnea) experienced a significantly shorter time to troponin order with 24 hours than cluster 0 (p <0.0001; z-statistics = -4.96; Cohen’s d = -0.27), cluster 1 (p <0.0001; z-statistics = -6.72; Cohen’s d = -0.32), and cluster 3 (p <0.0001, z-statistics = -3.82, Cohen’s d = -0.27).