Research AppraisalSystematic Review

Sex Differences Among Young Patients With ST-Segment-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis

Journal of the American Heart AssociationPugliesi, Giordano Maria, Onyeji, Paul, Verolino, Giuseppe et al.19 May 2026DOI

Clinical Snapshot

90CEBM
Evidence: ModerateSystematic Review

PICO Framework

P — PopulationYoung patients aged ≤45 years with ST-segment-elevation myocardial infarction
I — InterventionFemale sex
C — ComparatorMale sex
O — OutcomesIn-hospital and 1-year all-cause mortality, extent of coronary artery disease

Bottom Line

This large meta-analysis of over 738,000 young STEMI patients reveals a concerning paradox: despite having less extensive coronary artery disease, young women face significantly higher mortality rates than men both in-hospital (56% increased risk) and at one year (78% increased risk). The findings challenge assumptions about cardiovascular risk in young women and highlight potential gaps in recognition, treatment, or biological responses to STEMI. However, the unadjusted nature of these analyses limits clinical interpretation, as important confounders like comorbidities, treatment delays, and baseline characteristics weren't accounted for. Australian clinicians should maintain heightened vigilance for young women presenting with chest pain and ensure rapid, guideline-concordant STEMI management regardless of sex. The results underscore the need for sex-specific research in cardiovascular medicine and may inform future risk stratification tools, though adjusted analyses are essential before definitive practice changes.

Evidence: Moderate

Key Findings

  • P Value: Not explicitly reported but confidence intervals exclude null

  • Effect Size: In-hospital mortality RR 1.56, 1-year mortality RR 1.78

  • Primary Outcome: In-hospital and 1-year all-cause mortality

  • Nnt Or Sensitivity: Women 56% more likely to die in-hospital, 78% more likely to die at 1-year despite less extensive CAD

  • Confidence Interval: In-hospital: 95% CI 1.40-1.74; 1-year: 95% CI 1.50-2.12

Clinical Application

Findings applicable to current practice but require integration with risk stratification tools and consideration of confounding factors Relevant to Australian STEMI networks and aligns with National Heart Foundation guidelines emphasising sex-specific cardiovascular risk assessment. May inform PBS criteria for intensive monitoring and TGA-approved therapies in young women post-STEMI Young patients (≤45 years) presenting with STEMI in Australian emergency departments and cardiac centres

Abstract

BACKGROUND: Female sex is associated with lower incidence of myocardial infarction, especially at younger ages. However, sex differences in mortality and coronary artery disease patterns among young patients with ST-segment-elevation myocardial infarction are not well established. This study evaluated sex differences in in-hospital and 1-year all-cause death and in the extent of coronary artery disease in patients aged ≤45 years with ST-segment-elevation myocardial infarction. METHODS: A systematic review (December 9, 2025) was conducted using PubMed, Cochrane, Embase, major cardiology conference proceedings, and ClinicalTrials.gov. Studies comparing sexes for outcomes were included. Non-English publications, abstracts without full text, and studies published before 2010 were excluded. A random-effects meta-analysis was performed, with results presented as relative risks (RR) and 95% CIs. Heterogeneity was assessed using τ and I2, risk of bias using the Risk of Bias in Nonrandomized Studies of Interventions tool. The study was registered on the International Prospective Register of Systematic Reviews. RESULTS: Eleven studies including 738 029 patients with ST-segment-elevation myocardial infarction (22% women) were analyzed. Female sex was associated with higher unadjusted in-hospital (RR, 1.56 [95% CI, 1.40-1.74]; τ=0.04; I2=0%) and 1-year mortality rate (RR, 1.78 [95% CI, 1.50-2.12]; τ=0.00; I2=0%). Women more frequently had single-vessel disease (73% versus 60%; RR, 1.13 [95% CI, 1.03-1.23]; τ=0.07; I2=67%), while men had 2-vessel (23% versus 18%; RR, 0.76 [95% CI, 0.68-0.85]; τ=0.00; I2=0%;) and 3-vessel disease (16% versus 9%; RR, 0.49 [95% CI, 0.27-0.86]; τ=0.41; I2=33%). CONCLUSIONS: In young patients with ST-segment-elevation myocardial infarction, female sex is associated with higher unadjusted in-hospital and 1-year death despite less extensive CAD. Further studies adjusting for comorbidities and standardizing CAD definitions are needed.

References

  1. 1.Pugliesi, G. M., Onyeji, P., Verolino, G., MomplaisirOnyeji, S., Fazzini, L., Łajczak, P., Toukam, M. S. M., Sala, D., Quartieri, E. A., Lenzi, M. C., Perego, G. B., & Calderone, D. (2026). Sex differences among young patients with ST-segment-elevation myocardial infarction: A systematic review and meta-analysis. Journal of the American Heart Association, 15(10), e046648. https://doi.org/10.1161/JAHA.125.046648
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