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Observational Study
. 2025 Feb;18(2):e017380.
doi: 10.1161/CIRCIMAGING.124.017380. Epub 2025 Jan 13.

Abnormal Exercise Electrocardiography With Normal Stress Echocardiography Is Associated With Subclinical Coronary Atherosclerosis

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Free article
Observational Study

Abnormal Exercise Electrocardiography With Normal Stress Echocardiography Is Associated With Subclinical Coronary Atherosclerosis

Jessica M Duran et al. Circ Cardiovasc Imaging. 2025 Feb.
Free article

Abstract

Background: Patients with abnormal (positive) exercise electrocardiography, but normal stress echocardiography (+ECG/-Echo), have an increased risk of adverse cardiovascular events compared with patients with a normal (negative) ECG and a normal stress Echo (-ECG/-Echo). However, it is unclear if +ECG/-Echo discordance is associated with a greater burden of subclinical coronary atherosclerosis.

Methods: Project Baseline Health Study participants who underwent a stress Echo and coronary artery calcium (CAC) scan were stratified by stress Echo result: -ECG/-Echo or +ECG/-Echo. Multivariable regression investigated the association between stress Echo results and CAC burden. Event-free survival from a composite of adverse cardiovascular events was compared between groups.

Results: Among 1630 asymptomatic participants in this observational cohort study, 1503 (92.2%) had a -ECG/-Echo, 105 (6.4%) had a +ECG/-Echo, and 22 (1.3%) had a +Echo. The +ECG/-Echo group had a significantly greater burden of coronary atherosclerosis than the -ECG/-Echo group (mean CAC score, 198±470 versus 53±186; P<0.001; CAClog, 2.2±2.7 versus 1.2±2.0; P<0.001). The -ECG/-Echo group was more likely to have CAC=0 compared with the +ECG/-Echo group (65.9% versus 53.3%; P=0.01), whereas the +ECG/-Echo group more commonly had CAC ≥100 (28.6% versus 11.4%; P<0.001). After adjustment, CAClog scores were 52% higher in the +ECG/-Echo group than in the -ECG/-Echo group (P=0.002). Compared with the -ECG/-Echo group, the +ECG/-Echo group was 4.5× more likely to have a CAC score ≥400 (adjusted odds ratio, 4.54 [95% CI, 1.95-10.05]; P<0.001). After a median follow-up of 4.3 years, a trend toward increased adverse cardiovascular events was observed among participants with +ECG/-Echo.

Conclusions: Individuals with a +ECG/-Echo have a higher burden of subclinical coronary atherosclerosis than those with a -ECG/-Echo, which may explain, at least in part, the increased risk for adverse cardiac events in this population. Further study is needed to determine the optimal strategy for mitigating cardiovascular risk in these patients.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03154346.

Keywords: cohort studies; coronary artery disease; echocardiography, stress; electrocardiography; follow-up studies.

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Conflict of interest statement

All authors acknowledge institutional research grants from Verily Life Sciences. Dr Haddad received an institutional research grant from Actelion Ltd within the last 2 years and an institutional research grant from Precordior Ltd. Dr Mahaffey reports grants from Verily, Afferent, the American Heart Association, Cardiva Medical Inc, Gilead, Luitpold, Medtronic, Merck, Eidos, Ferring, Apple Inc, Sanifit, and St. Jude; grants and personal fees from Amgen, AstraZeneca, Bayer, CSL Behring, Johnson & Johnson, Novartis, and Sanofi; and personal fees from Anthos, Applied Therapeutics, Elsevier, Inova, Intermountain Health, Medscape, Mount Sinai, Mundi Pharma, Myokardia, Novo Nordisk, Otsuka, Portola, SmartMedics, and Theravance outside the submitted study. Dr Hernandez reports grants from Verily; grants and personal fees from AstraZeneca, Amgen, Bayer, Merck, and Novartis; and personal fees from Boston Scientific outside the submitted work. Dr Cauwenberghs reports grants from the Research Foundation Flanders. Dr Bloomfield reports grants from the NIH (U01-HL146382-03, Rx01-MD013493-03, D43TW009337, U01-HL123336-06, U01-HL142099-03, and D43 TW011625-01) and royalties or licensing fees from UpToDate. The other authors report no conflicts.

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