Ethnic Differences in Thrombotic Profiles of Acute Coronary Syndrome Patients and Relationship to Cardiovascular Outcomes: A Comparison of East Asian and White subjects

Background East Asians (EAs), compared to white Caucasians (W), have a lower risk of ischemic heart disease and a higher risk of bleeding with antithrombotic medications. The underlying mechanisms are incompletely understood. Objectives We sought to compare thrombotic profiles of EA and W patients with myocardial infarction (MI) and relate these to cardiovascular outcomes. Methods In a prospective study in the United Kingdom and Korea, blood samples from patients ( n  = 515) with ST- or non-ST-elevation MI (STEMI and NSTEMI) were assessed using the Global Thrombosis Test, measuring thrombotic occlusion (OT) and endogenous fibrinolysis (lysis time [LT]). Patients were followed for 1 year for major adverse cardiovascular events (MACE) and bleeding. Results EA patients showed reduced OT (longer OT) compared to W (646 seconds [470–818] vs. 436 seconds [320–580], p  < 0.001), with similar LT. In STEMI, OT (588 seconds [440–759] vs. 361 seconds [274–462], p  < 0.001) and LT (1,854 seconds [1,389–2,729] vs. 1,338 seconds [1,104–1,788], p  < 0.001) were longer in EA than W. In NSTEMI, OT was longer (OT: 734 seconds [541–866] vs. 580 seconds [474–712], p  < 0.001) and LT shorter (1519 seconds [1,058–2,508] vs. 1,898 seconds [1,614–2,806], p  = 0.004) in EA than W patients. MACE was more frequent in W than EA (6.3 vs. 1.9%, p  = 0.014) and bleeding infrequent. While OT was unrelated, LT was a strong independent predictor of MACE event after adjustment for risk factors (hazard ratio: 3.70, 95% confidence interval: 1.43–9.57, p  = 0.007), predominantly in W patients, and more so in STEMI than NSTEMI patients. Conclusion EA patients exhibit different global thrombotic profiles to W, associated with a lower rate of cardiovascular events.


Supplemental Material Supplementary Definition of Components of the Primary Endpoint
Cardiovascular death was defined as death in the presence of acute coronary syndrome, significant arrhythmia, or refractory congestive heart failure, or death attributed to cardiovascular cause at postmortem.
New myocardial infraction or re-infarction was defined according to the universal definition as the detection of rise and/or fall of troponin T with at least one value >99th percentile of the upper reference limit and with at least one of the following: symptoms of ischemia, new or presumed new significant ST-T changes or new left bundle branch block, development of pathological Q-waves, imaging evidence of new loss of viable myocardium, or new regional wall motion abnormality, identification of intracoronary thrombus at angiography, or stent thrombosis associated with myocardial ischemia detected by angiography. 32Specifically re-infarction following the index pPCI during the same hospitalization (myocardial infarction type 4) was defined as recurrence of symptoms of ischemia and/or new or presumed new electrocardiogram (ECG) changes as defined above distinct from the ECG changes secondary to the index event, together with either (1) an increase in troponin greater than 3 Â 99th percentile upper reference limit and re-elevation by at least 20% from previous baseline following a decrease from the peak value (myocardial infarction type 4a) or (2) angiographic evidence of stent thrombosis as shown by new thrombus, vessel occlusion, or sub-total occlusion (myocardial infarction type 4b).
Stroke was defined as an acute focal brain infarction with one of the following: sudden onset of new focal neurologic deficit, with clinical or imaging evidence of infarction lasting !24 hours and not attributable to a nonischemic cause, or new focal neurologic deficit lasting <24 hours and not attributable to a nonischemic cause but accompanied by neuroimaging evidence of new brain infarction.

Adverse event
All Ethnic Differences in Thrombotic Profile in ACS Suh et al.
Ethnic Differences in Thrombotic Profile inACS Suh et al.TableS3Relationship between adverse cardiovascular events at 1-year follow-up and optimal OT cut-point, by ethnicity, in subgroup of patients not taking aspirin on : ACS, acute coronary syndrome; BARC, Bleeding Academic Research Consortium; CVA, cerebrovascular accident; MACE, major adverse cardiovascular events; N/A, not applicable; PCI, percutaneous coronary intervention; OT, occlusion time, TIA, transient ischemic attack.Ethnic Differences in Thrombotic Profile in ACS Suh et al.TableS4Association between adverse cardiovascular events at 1-year follow-up according to different P2Y 12 inhibitors upon discharge (statistically significant values shown in bold) Abbreviations: ACS, acute coronary syndrome; BARC, Bleeding Academic Research Consortium; CI, confidence interval; CVA, cerebrovascular accident; HR, hazard ratio; ISR, in-stent restenosis; MACE, major adverse cardiovascular events; NA, not applicable; OT, occlusion time; PCI, percutaneous coronary intervention; TIA, transient ischemic attack.Supplementary TableS1Univariate predictors of major adverse cardiovascular events (MACE) (only statistically significant results shown) Abbreviations: CABG, coronary artery bypass grafting; CAD, coronary artery disease; CKD, chronic kidney disease.Note: CKD defined as creatinine >177 μmol/L.Thrombosis and Haemostasis © 2023.The Author(s).AbbreviationsThrombosis and Haemostasis © 2023.The Author(s).Abbreviations: BMI, body mass index; hs-CRP, high sensitivity C-reactive protein; hs-troponin T, high-sensitivity troponin T; INR, international normalized ratio; OT, occlusion time.Abbreviations: aPTT, activated partial thromboplastin time; HbA1c, hemoglobin A1c; hs-CRP, high-sensitivity C-reactive protein; PT, prothrombin time.Thrombosis and Haemostasis © 2023.The Author(s).