Author + information
- Received May 25, 2016
- Revision received January 15, 2017
- Accepted January 17, 2017
- Published online March 5, 2018.
- Peter H. Stone, MDa,∗ (, )
- Akiko Maehara, MDb,
- Ahmet Umit Coskun, PhDa,
- Charles C. Maynard, PhDc,
- Marina Zaromytidou, MD, PhDa,
- Gerasimos Siasos, MD, PhDa,
- Ioannis Andreou, MD, PhDa,
- Dimitris Fotiadis, PhDd,
- Kostas Stefanou, PhDd,
- Michail Papafaklis, MD, PhDd,
- Lampros Michalis, MD, PhDd,
- Alexandra J. Lansky, MDe,
- Gary S. Mintz, MDb,
- Patrick W. Serruys, MD, PhDf,
- Charles L. Feldman, ScDa and
- Gregg W. Stone, MDb
- aCardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School Boston, Massachusetts
- bDivision of Cardiology, New York Presbyterian Hospital, Columbia University Medical Center, and the Cardiovascular Research Foundation, New York, New York
- cDepartment of Health Services, University of Washington, Seattle, Washington
- dDepartment of Materials Science and Engineering, University of Ioannina, Ioannina, Greece
- eSection of Cardiology, Yale University School of Medicine, New Haven, Connecticut
- fInternational Centre for Cardiovascular Health, Imperial College, London, United Kingdom
- ↵∗Address for correspondence:
Dr. Peter H. Stone, Cardiovascular Division, Brigham & Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
Objectives This study sought to determine whether low endothelial shear stress (ESS) adds independent prognostication for future major adverse cardiac events (MACE) in coronary lesions in patients with high-risk acute coronary syndrome (ACS) from the United States and Europe.
Background Low ESS is a proinflammatory, proatherogenic stimulus associated with coronary plaque development, progression, and destabilization in human-like animal models and in humans. Previous natural history studies including baseline ESS characterization investigated low-risk patients.
Methods In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, 697 patients with ACS underwent 3-vessel intracoronary imaging. Independent predictors of MACE attributable to untreated nonculprit (nc) coronary lesions during 3.4-year follow-up were large plaque burden (PB), small minimum lumen area (MLA), and thin-cap fibroatheroma (TCFA) morphology. In this analysis, baseline ESS of nc lesions leading to new MACE (nc-MACE lesions) and randomly selected control nc lesions without MACE (nc-non-MACE lesions) were calculated. A propensity score for ESS was constructed for each lesion, and the relationship between ESS and subsequent nc-MACE was examined.
Results A total of 145 lesions were analyzed in 97 patients: 23 nc-MACE lesions (13 TCFAs, 10 thick-cap fibroatheromas [ThCFAs]), and 122 nc-non-MACE lesions (63 TCFAs, 59 ThCFAs). Low local ESS (<1.3 Pa) was strongly associated with subsequent nc-MACE compared with physiological/high ESS (≥1.3 Pa) (23 of 101 [22.8%]) versus (0 of 44 [0%]). In propensity-adjusted Cox regression, low ESS was strongly associated with MACE (hazard ratio: 4.34; 95% confidence interval: 1.89 to 10.00; p < 0.001). Categorizing plaques by anatomic risk (high risk: ≥2 high-risk characteristics PB ≥70%, MLA ≤4 mm2, or TCFA), high anatomic risk, and low ESS were prognostically synergistic: 3-year nc-MACE rates were 52.1% versus 14.4% versus 0.0% in high-anatomic risk/low-ESS, low-anatomic risk/low-ESS, and physiological/high-ESS lesions, respectively (p < 0.0001). No lesion without low ESS led to nc-MACE during follow-up, regardless of PB, MLA, or lesion phenotype at baseline.
Conclusions Local low ESS provides incremental risk stratification of untreated coronary lesions in high-risk patients, beyond measures of PB, MLA, and morphology.
The authors acknowledge with grateful appreciation the support from the Schaubert Family, as well as support from the George D. Behrakis Cardiovascular Research Fellowship Program. Dr. Maehara has received research grants from Boston Scientific and St. Jude Medical; and is a consultant for OCT Medical Imaging. Dr. Mintz has received grant support from Volcano and Boston Scientific; and honoraria from Volcano and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Renu Virmani, MD, served as the Guest Editor for this paper.
- Received May 25, 2016.
- Revision received January 15, 2017.
- Accepted January 17, 2017.
- 2018 American College of Cardiology Foundation
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