Author + information
- Received February 25, 2020
- Accepted February 28, 2020
- Published online March 16, 2020.
- Ravi B. Patel, MD1,2,∗ (, )
- Laura A. Colangelo, MS2,
- Alexander P. Reiner, MD MSc3,
- Myron D. Gross, PhD4,
- David R. Jacobs Jr., PhD5,
- Lenore J. Launer, PhD6,
- Joao A.C. Lima, MD7,
- Donald M. Lloyd-Jones, MD ScM1,2 and
- Sanjiv J. Shah, MD1
- 1Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
- 2Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
- 3Department of Epidemiology, University of Washington, Seattle, WA
- 4Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN
- 5Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN
- 6Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, MD
- 7Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD
- ↵∗Address for Correspondence: Ravi B. Patel, MD Division of Cardiology, Department of Medicine Northwestern University Feinberg School of Medicine 676 N. St Clair St, Suite 600 Chicago, Illinois 60611 Telephone: (312) 503-5779 Fax: (312) 695-0063 Twitter: @RBPatelMD
Background E-selectin and intercellular adhesion molecule-1 (ICAM-1) are biomarkers of endothelial activation, which has been implicated in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFpEF). However, the temporal associations between E-selectin and ICAM-1 with subclinical cardiac dysfunction are unclear.
Objectives To assess the longitudinal associations of E-selectin and ICAM-1 with subclinical alterations in cardiac function.
Methods In the Coronary Artery Disease Risk Development in Young Adults study, a cohort of black and white young adults, we evaluated the associations of E-selectin and ICAM-1, obtained at year 7 (Y7) and Y15 examinations, with cardiac function assessed at Y30 after adjustment for key covariates.
Results Higher E-selectin (n=1,810) and ICAM-1 (n=1,548) at Y7 were associated with black race, smoking, hypertension, and higher BMI. After multivariable adjustment, higher E-selectin at Y7 (β-coefficient per 1-SD higher: 0.22, SE: 0.06, P<0.001) and Y15 (β-coefficient per 1-SD higher: 0.19, SE: 0.06, P=0.002) was associated with worse left ventricular (LV) global longitudinal strain (GLS). Additionally, higher Y15 ICAM-1 (β-coefficient per 1-SD higher: 0.18, SE: 0.06, P=0.004) and its increase from Y7 to Y15 (β-coefficient per 1-SD higher: 0.16, SE: 0.07, P=0.03) were also independently associated with worse LV GLS. E-selectin and ICAM-1 partially mediated the associations between higher BMI and black race with worse GLS. Neither E-selectin nor ICAM-1 were associated with measures of LV diastolic function after multivariable adjustment.
Conclusion Circulating levels of E-selectin and ICAM-1 and increases in ICAM-1 over the course of young adulthood are associated with worse indices of LV systolic function in midlife. These findings suggest associations of endothelial activation with subclinical HFpEF.
- cellular adhesion molecules
- heart failure with preserved ejection fraction
- cardiac mechanics
Disclosures: Dr. Shah has received research grants from Actelion, AstraZeneca, Corvia, and Novartis, and consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Cardiora, Eisai, Ironwood, Merck, MyoKardia, Novartis, Sanofi, and United Therapeutics. The remaining authors have nothing to disclose.
Funding: Dr. Ravi Patel is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number T32HL069771. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I & HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I). This manuscript has been reviewed by CARDIA for scientific content.
- Received February 25, 2020.
- Accepted February 28, 2020.
- 2020 American College of Cardiology Foundation
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