A1 Refereed original research article in a scientific journal
Sex differences in plaque burden and outcomes in symptomatic patients with suspected coronary artery disease
Authors: Molnar, David; Knuuti, Juhani; Bax, Jeroen J.; Saraste, Antti; Maaniitty, Teemu
Publisher: Elsevier BV
Publication year: 2026
Journal: International Journal of Cardiology
Article number: 134023
Volume: 444
ISSN: 0167-5273
eISSN: 1874-1754
DOI: https://doi.org/10.1016/j.ijcard.2025.134023
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Partially Open Access publication channel
Web address : https://doi.org/10.1016/j.ijcard.2025.134023
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/505853536
Self-archived copy's licence: CC BY
Self-archived copy's version: Publisher`s PDF
BackgroundSex-related differences in coronary artery disease (CAD) burden and outcomes are increasingly recognized but not fully understood, particularly when assessed using advanced imaging techniques.ObjectivesTo investigate sex differences in coronary plaque characteristics and their association with long-term cardiovascular outcomes in symptomatic patients undergoing coronary computed tomography angiography (CTA).MethodsA total of 2271 symptomatic patients without prior obstructive CAD underwent CTA, followed by artificial intelligence-based quantitative plaque analysis (AI-QCT) extracting plaque features including total plaque volume (TPV), non-calcified plaque (NCP), low-density plaque (LDP), and calcified plaque (CP). CAD severity was classified in accordance with CAD-RADS. Long-term outcomes, including myocardial infarction (MI), acute coronary syndrome (ACS) and death, were tracked over a median follow-up of 7.3 years. Analyses were stratified by sex and CAD-RADS category.ResultsWomen (n = 1316) were older but had significantly lower plaque burden across all CAD-RADS categories compared to men (n = 955). Despite this, women had non-negligible number of MI (n = 31) and ACS (n = 46), with the highest rate in CAD-RADS 3 (1.1 % MI and 1.6 % ACS), whereas in men (totally 37 MI, 54 ACS), event rates were highest in CAD-RADS 4 (1.9 % MI and 2.5 % ACS). No cardiovascular events were recorded in CAD-RADS 0 for either sex. In multivariable Cox regression, stenosis severity was the strongest predictor of events in men, while TPV was more predictive in women. In gradient boosting machine (GBM) analysis, TPV and stenosis severity had the highest overall relative importance in explaining events.ConclusionsThis study demonstrates important sex-based differences in CAD phenotype and prognosis. Women had lower plaque burden, yet experienced adverse events with lower CAD-RADS, suggesting that current risk stratification may underestimate their risk. AI-QCT provides enhanced plaque characterization, which may in the future improve individualized assessment, especially in women.
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Funding information in the publication:
The study was funded by the Finnish Foundation for Cardiovascular Research, Finnish State Research Funding, and the Research Council of Finland. Cleerly, Inc. performed the image analysis without costs and provided an unrestricted research grant for the University of Turku. Dr. Molnar's work has been co-funded by the European Union's Horizon Europe Framework program for research and innovation 2021–2027 under the Marie Sklodowska-Curie grant agreement No. 101126611, the Swedish Medical Society, the Swedish Heart-Lung Foundation, the Swedish Heart Union and the Gothenburg Medical Society. Dr. Knuuti received consultancy fees from GE Healthcare and Synektik and speaker fees from Bayer, Lundbeck, Boehringer-Ingelheim, Pfizer and Siemens, outside of the submitted work. Dr. Bax received speaker fees from Abbott, outside of the submitted work. Dr. Saraste received consultancy fees from Astra Zeneca, Novo Nordisk and Pfizer, and speaker fees from Abbott, Astra Zeneca, BMS, Janssen and Pfizer outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
