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Observational Study
. 2025 Dec 2;24(1):453.
doi: 10.1186/s12933-025-03006-x.

Prognostic implications of quantified coronary atherosclerosis and myocardial perfusion in diabetes

Matias Mäenpää  1 , Ruurt A Jukema  2 , Pepijn van Diemen  2 , Sarah Bär  3   4 , Pieter G Raijmakers  2 , Ralf Sprengers  2 , Roel S Driessen  2 , Jeroen J Bax  5 , Paul Knaapen  2 , Juhani Knuuti  3   6 , Ibrahim Danad  7 , Antti Saraste  3   8 , Teemu Maaniitty  3   6
Affiliations
Observational Study

Prognostic implications of quantified coronary atherosclerosis and myocardial perfusion in diabetes

Matias Mäenpää et al. Cardiovasc Diabetol. .

Abstract

Background: Coronary artery disease (CAD) is a major contributor to cardiovascular events in individuals with diabetes. Quantification of coronary atherosclerotic burden is now feasible from coronary computed tomography angiography (CTA) whereas positron emission tomography (PET) enables quantitative assessment of myocardial perfusion. We studied the prognostic implications of quantitatively measured coronary plaque burden and myocardial perfusion in diabetic vs. non-diabetic patients with suspected CAD.

Methods: In this observational cohort study, 1311 symptomatic patients with suspected CAD underwent coronary CTA and [15O]H2O PET perfusion imaging. Coronary plaque burden was quantified using artificial intelligence-based analysis and reported as percent atheroma volume (PAV). Myocardial perfusion was assessed as regional stress myocardial blood flow (sMBF), with abnormal perfusion defined as ≥ 2 adjacent segments with sMBF < 2.3 ml/g/min. The composite endpoint was all-cause death, myocardial infarction (MI), or unstable angina pectoris (UAP) over 7 years.

Results: Among the 1311 patients, 251 (19%) had diabetes and 134 (10%) experienced an adverse event during follow-up. The annual event rate was low (0.8% [95% CI 0.6-1.1%]) in non-diabetic patients with normal myocardial perfusion and increased significantly with the presence of either diabetes (2.3% [95% CI 1.4-3.8%]), abnormal perfusion (2.6% [95% CI 2.1-3.3%]), or both (3.2% [95% CI 2.1-4.8%]) (p < 0.001). Among patients with normal myocardial perfusion, those with diabetes had two-fold PAV as compared with non-diabetic individuals (median 8.2% vs. 4.1%, p < 0.001). In multivariable Cox regression models, both PAV (HR 1.03 [95% CI 1.01-1.05] per 1% increase, p < 0.001) and regional sMBF (HR 1.04 [95% CI 1.01-1.07] per 0.1 ml/g/min decrease, p = 0.016) were independent predictors of adverse outcome in non-diabetic patients. In diabetic patients, only PAV (HR 1.04 [95% CI 1.01-1.07], p = 0.014) was predictive, whereas sMBF was not.

Conclusions: Coronary atherosclerotic plaque burden appears as an important predictor of long-term cardiovascular outcomes both in diabetic and non-diabetic patients. In patients with diabetes, normal myocardial perfusion does not necessarily imply low event risk, partly attributable to higher coronary plaque burden. Quantitative imaging methods for detailed CAD phenotyping shed light on the complex relationship between diabetes and clinical outcomes.

Keywords: Cardiac complications; Coronary artery disease; Coronary computed tomography angiography; Diabetes; Positron emission tomography; Prognosis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was investigator-initiated and complies with the Declaration of Helsinki. The ethics committees of the Hospital District of Southwest Finland and Amsterdam University Medical Center approved the study protocol and waived the need for informed consent due to the retrospective nature and observational study design. Consent for publication: Not applicable. Competing interests: Dr. Bär received research grants to the institution from Medis Medical Imaging Systems, Bangerter-Rhyner Stiftung (Basel, Switzerland) and Abbott, outside the submitted work, speaker fees from Cleerly inc. and travel fees from Sanofi. Dr. Knuuti received consultancy fees from GE Healthcare and Synektik and speaker fees from Siemens, outside of the submitted work. Dr. Saraste received consultancy fees from Astra Zeneca and Pfizer, and speaker fees from Abbott, Astra Zeneca, Janssen, Novartis and Pfizer. Dr. Bax received speaker fees from Abbott. Dr. Danad is a member of Cleerly Scientific Advisory Board. Dr. Knaapen has received research grants from Cleerly, Inc. and HeartFlow. Dr. Sprengers receive speaker fees from Boehringer-Ingelheim, Ferrer, MSD and Siemens, outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

Fig. 1
Fig. 1
Patient inclusion/exclusion criteria. CTA computed tomography angiography, PET positron emission tomography, CAD coronary artery disease, PCI percutaneous coronary intervention, CABG coronary artery bypass graft, MI myocardial infarction
Fig. 2
Fig. 2
Bar chart (left) showing annual composite adverse event % rates (with 95% CI) stratified by myocardial perfusion and diabetes. Box plots (right) showing quantitative percent atheroma volume (PAV) and coronary diameter stenosis degree (median, 25-75th percentiles, and outliers similarly stratified by myocardial perfusion and diabetes. Comprehensive statistics are provided in Table 1. *Indicates statistical significance p < 0.05
Fig. 3
Fig. 3
Kaplan–Meier survival curves for non-diabetic and diabetic patients stratified by binary PET perfusion finding
See this image and copyright information in PMC

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