Differences in coronary disease severity at time of acute coronary syndrome between Middle East and North America

Patients presenting with acute coronary syndromes (ACS) in the Middle East/Gulf (MEG) region are known to be younger and to have a greater burden of cardiovascular risk factors compared with those in Western countries (1-5). However, severity of coronary artery disease (CAD) in these patients has not been adequately described. Determining the extent of CAD at patients’ first contact with health systems and comparing it across geographic locations with distinct ethnic and racial makeup may shed light onto the contribution of various genetic and environmental risk factors to CAD onset and subsequent progression, which may inform subsequent initiation of preventative therapies at the appropriate time.

Accordingly, we compared CAD severity at the time of first cardiovascular event in two concurrent ACS cohorts treated at two distant hospitals within an international healthcare system (Cleveland Clinic Health System). The MEG site was a 364-bed hospital in the United Arab Emirates (UAE), and the North America (NA) site was a 1,325-bed hospital in Cleveland, OH, USA. Both hospitals serve a diverse patient population and offer comprehensive quaternary cardiac care. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Cleveland Clinic Abu Dhabi Research Ethics Committee (No. MF2437). Need for informed consent was waived given the retrospective nature of the study. All patients admitted with the first ACS [myocardial infarction (MI) or unstable angina] who underwent diagnostic coronary angiography during index admission (January to December 2017) were included. Patients with prior surgical or percutaneous revascularization or ACS hospitalization were excluded. Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score was used as the primary measure of disease severity and was determined through independent review of coronary angiograms by trained investigators at each site, using an online tool (https://syntaxscore.org) (6). Cohen’s weighted kappa (κ) demonstrated moderate to strong inter-rater agreement among a subset of 60 random studies read by both sites (κ=0.69, P<0.001). Data on revascularization strategy for index ACS (surgical, percutaneous or hybrid) and occurrence of adverse cardiac events during hospitalization (cardiovascular and all-cause death, stroke or cardiac arrest) were collected using electronic health records. Continuous variables were presented as means ± standard deviation (or medians and interquartile range where assumption of normality was not met) and compared using t-test. Categorical variables were presented as counts and compared using Chi-squared test. All P values were two-tailed and a value of <0.05 was set for statistical significance. Analyses were performed using Microsoft R Open (Microsoft Corporation, 2020, Microsoft R umbrella package. R package version 4.0.2).

A total of 539 patients with ACS were identified, 158 in MEG and 381 in NA. Patients in MEG were younger (57.3±11.5 vs. 65.0±12.1 years; P<0.001), more likely to be men (82.3% vs. 70.5%; P=0.002), with greater prevalence of diabetes (51.9% vs. 28.9%; P<0.001) and worse glycemic control [glycated hemoglobin (HbA1c) 7.1%±2.1% vs. 6.4%±1.5%; P<0.001], but were less obese [body mass index (BMI) 27.6±4.6 vs. 30.4±6.2 kg/m²; P<0.001]. MEG patients had less dyslipidemia, hypertension, and smoking but similar types of ACS (P=0.25) (Table 1).

Patients in MEG had substantially higher SYNTAX scores than those in NA [23.5±12.3 vs. 13.2±8.6; mean difference 10.3, 95% confidence interval (CI): 8.5–12.1, P<0.001], and higher odds to be in the intermediate- or high-risk groups (SYNTAX score ≥23); 51.3% and 14.2%, respectively [odds ratio (OR) 6.4, 95% CI: 4.2–9.7] (Figure 1). Findings were also consistent across subgroups of sex and ACS subtypes, where SYNTAX scores in MEG and NA were 24.1±12 and 13.5±8.6, respectively, in men (P<0.001), 20.6±13.1 and 12.4±8.7 in women (P<0.001), 24±11.9 and 13.2±8.5 in patients with ST elevation MI (P<0.001), 24±12.1 and 12±7.7 in patients with non-ST elevation MI (P<0.001), and 21±13.4 and 16.2±10.1 in those with unstable angina (P=0.05).

Figure 1 Syntax scores for patients with the first ACS presentation in MEG and NA locations. Each star represents the city location for each of the study locations; Abu Dhabi in MEG (map on the left) and Cleveland in NA (map on the right). ACS, acute coronary syndrome; MEG, Middle East/Gulf; NA, North America; SYNTAX, Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery.

Moreover, patients in MEG were more likely to receive surgical or hybrid revascularization (41.8% vs. 25.7%; OR 2.1, 95% CI: 1.4–3.1) but less likely to receive percutaneous coronary interventions (46.2% vs. 73.2%; OR 0.3, 95% CI: 0.2–0.5) compared with NA. Unadjusted rates of in-hospital events were similar in both groups, including stroke (0.7% vs. 1.1%; P=0.47), cardiac arrest (1.3% vs. 1.5%; P=0.15), cardiovascular death (1.9% vs. 1.6%; P=0.79) and all-cause mortality (2.5% vs. 2.4%; P=0.91).

In this cross-sectional analysis of patients presenting with the first ACS in MEG and NA, those in MEG had more severe CAD despite being almost 8 years younger. Higher prevalence and poorer control of diabetes are likely the main drivers of the aggressive CAD phenotype in MEG. This observation is in line with prior data showing that poor glycemic control is a major driver of worse CAD phenotype, even with lower prevalence of other cardiovascular risk factors (7). The role of additional genetic and environmental factors remains uncertain and warrants further investigation. Lower levels of education, limited access to care, higher levels of health illiteracy in MEG may also contribute to the poorer control of cardiovascular risk factors, especially diabetes, and hence more advanced CAD (8). It is also critical to determine whether patients in MEG present with more complex CAD at the time of their first clinical CAD event due to an earlier onset of atherosclerosis or a more rapidly progressive disease phenotype compared with those in NA. This distinction could potentially provide valuable insight into why patients in lower-income countries experience higher mortality rates despite a lower prevalence of conventional CAD risk factors (9).

The primary limitation of the current study is whether its findings can be generalized to the broader patient population in the MEG and NA. However, both study sites are major referral centers that offer quaternary care to a highly diverse patient demographic, drawing not only from the local area surrounding these medical centers, but also from a wide range of neighboring regions. This broad geographic representation supports wider generalizability of our findings. A second limitation is the potential bias in the estimation of SYNTAX scores, with scores being systematically overestimated by investigators at one site. To address this concern, we evaluated inter-rater agreement in SYNTAX score estimation and found moderately good agreement between sites, suggesting investigators were reasonably consistent in their estimates of SYNTAX scores, and that the observed difference is driven primarily by patient demographics rather than systemic bias in scoring. Lastly, data on pre-ACS use of cardioprotective medications, including statins, antiplatelet and antihypertensive medications, are not available. Such data may shed light onto differences in intensity of risk factor modification between the locations, and future efforts to correlate use of these classes of medication with CAD severity at time of ACS presentation.

Our findings have potential clinical implications for the management of ACS patients in the MEG region. Given the higher likelihood of these patients to present with extensive CAD and consequently undergo surgical revascularization during the index ACS event, prudence is warranted with the use of a second anti-platelet medication prior to the definition of coronary anatomy. This approach may help avoid unnecessary delays in surgical revascularization in the setting of dual anti-platelet therapy. Adequately powered future studies are needed to address the implications of CAD severity at time of ACS on initial treatment strategies and subsequently longer-term clinical outcomes. Furthermore, these data underscore the need for greater awareness about the surging cardiovascular risk throughout the MEG region. These data warrant a call to action to improve early access to preventative therapies, particularly those needed to address cardio-metabolic risk, to offset the impact of obesity epidemic in MEG (8,10).

In conclusion, patients in the MEG region present with more severe CAD at the time of their first ACS, despite being significantly younger than patients in NA. There is an urgent need for further research to investigate the genetic, environmental, and metabolic factors that may contribute to the accelerated progression of CAD in MEG populations. Such studies are crucial to developing targeted interventions to mitigate this emerging public health concern.

Acknowledgments

None.

Footnote

Peer Review File: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-53/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-53/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Cleveland Clinic Abu Dhabi Research Ethics Committee (No. MF2437). Need for informed consent was waived given the retrospective nature of the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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