Author + information
- Received February 25, 2020
- Accepted February 28, 2020
- Published online April 27, 2020.
- Ravi B. Patel, MDa,b,∗ (, )@RBPatelMD,
- Laura A. Colangelo, MSb,
- Alexander P. Reiner, MD, MScc,
- Myron D. Gross, PhDd,
- David R. Jacobs Jr., PhDe,
- Lenore J. Launer, PhDf,
- Joao A.C. Lima, MDg,
- Donald M. Lloyd-Jones, MD, ScMa,b and
- Sanjiv J. Shah, MDa
- aDivision of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- bDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- cDepartment of Epidemiology, University of Washington, Seattle, Washington
- dDepartment of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, Minnesota
- eDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota
- fLaboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, Maryland
- gDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland
- ↵∗Address for correspondence:
Dr. Ravi B. Patel, Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, 676 N. St. Clair Street, Suite 600, Chicago, Illinois 60611.
Background E-selectin and intercellular adhesion molecule (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 This study sought 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 (Y) 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 body mass index. 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 body mass index and black race with worse GLS. Neither E-selectin nor ICAM-1 was 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 HF with preserved ejection fraction.
- cardiac mechanics
- cellular adhesion molecules
- heart failure with preserved ejection fraction
Dr. 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 in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I). This manuscript has been reviewed by CARDIA for scientific content. Dr. Shah has received research grants from Actelion, AstraZeneca, Corvia, and Novartis; and has received consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiora, Eisai, Ironwood, Merck, MyoKardia, Novartis, Sanofi, and United Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 25, 2020.
- Accepted February 28, 2020.
- 2020 American College of Cardiology Foundation
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