Cellular Adhesion Molecules in Young Adulthood and Cardiac Function in Later Life

Ravi B. Patel; Laura A. Colangelo; Alexander P. Reiner; Myron D. Gross; David R. Jacobs; Lenore J. Launer; Joao A.C. Lima; Donald M. Lloyd-Jones; Sanjiv J. Shah

doi:10.1016/j.jacc.2020.02.060

Cellular Adhesion Molecules in Young Adulthood and Cardiac Function in Later Life

Ravi B. Patel, Laura A. Colangelo, Alexander P. Reiner, Myron D. Gross, David R. Jacobs, Lenore J. Launer, Joao A.C. Lima, Donald M. Lloyd-Jones, Sanjiv J. Shah

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	2156-2165
Number of pages	10
Journal	Journal of the American College of Cardiology
Volume	75
Issue number	17
DOIs	https://doi.org/10.1016/j.jacc.2020.02.060
State	Published - May 5 2020

Bibliographical note

Funding Information:
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.

Funding Information:
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.

Publisher Copyright:
© 2020 American College of Cardiology Foundation

Keywords

cardiac mechanics
cellular adhesion molecules
heart failure with preserved ejection fraction
pathogenesis
subclinical
Prospective Studies
Ventricular Function, Left/physiology
Humans
Cell Adhesion Molecules/blood
European Continental Ancestry Group
Male
Stroke Volume/physiology
Intercellular Adhesion Molecule-1/blood
Cell Adhesion/physiology
Young Adult
E-Selectin/blood
Sex Factors
Adult
Biomarkers/blood
Female
African Continental Ancestry Group
Coronary Artery Disease/blood
Cohort Studies

PubMed: MeSH publication types

Multicenter Study
Journal Article
Research Support, N.I.H., Extramural

Publisher link

10.1016/j.jacc.2020.02.060

Find It

Find It at U of M Libraries

Cite this

@article{4e1749bb1f4946999311a27debf25c60,

title = "Cellular Adhesion Molecules in Young Adulthood and Cardiac Function in Later Life",

abstract = "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.",

keywords = "cardiac mechanics, cellular adhesion molecules, heart failure with preserved ejection fraction, pathogenesis, subclinical, Prospective Studies, Ventricular Function, Left/physiology, Humans, Cell Adhesion Molecules/blood, European Continental Ancestry Group, Male, Stroke Volume/physiology, Intercellular Adhesion Molecule-1/blood, Cell Adhesion/physiology, Young Adult, E-Selectin/blood, Sex Factors, Adult, Biomarkers/blood, Female, African Continental Ancestry Group, Coronary Artery Disease/blood, Cohort Studies",

author = "Patel, {Ravi B.} and Colangelo, {Laura A.} and Reiner, {Alexander P.} and Gross, {Myron D.} and Jacobs, {David R.} and Launer, {Lenore J.} and Lima, {Joao A.C.} and Lloyd-Jones, {Donald M.} and Shah, {Sanjiv J.}",

note = "Funding Information: 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. Funding Information: 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. Publisher Copyright: {\textcopyright} 2020 American College of Cardiology Foundation",

year = "2020",

month = may,

day = "5",

doi = "10.1016/j.jacc.2020.02.060",

language = "English (US)",

volume = "75",

pages = "2156--2165",

journal = "Journal of the American College of Cardiology.",

issn = "0735-1097",

publisher = "Elsevier USA",

number = "17",

}

TY - JOUR

T1 - Cellular Adhesion Molecules in Young Adulthood and Cardiac Function in Later Life

AU - Patel, Ravi B.

AU - Colangelo, Laura A.

AU - Reiner, Alexander P.

AU - Gross, Myron D.

AU - Jacobs, David R.

AU - Launer, Lenore J.

AU - Lima, Joao A.C.

AU - Lloyd-Jones, Donald M.

AU - Shah, Sanjiv J.

N1 - Funding Information: 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. Funding Information: 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. Publisher Copyright: © 2020 American College of Cardiology Foundation

PY - 2020/5/5

Y1 - 2020/5/5

N2 - 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.

AB - 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.

KW - cardiac mechanics

KW - cellular adhesion molecules

KW - heart failure with preserved ejection fraction

KW - pathogenesis

KW - subclinical

KW - Prospective Studies

KW - Ventricular Function, Left/physiology

KW - Humans

KW - Cell Adhesion Molecules/blood

KW - European Continental Ancestry Group

KW - Male

KW - Stroke Volume/physiology

KW - Intercellular Adhesion Molecule-1/blood

KW - Cell Adhesion/physiology

KW - Young Adult

KW - E-Selectin/blood

KW - Sex Factors

KW - Adult

KW - Biomarkers/blood

KW - Female

KW - African Continental Ancestry Group

KW - Coronary Artery Disease/blood

KW - Cohort Studies

UR - http://www.scopus.com/inward/record.url?scp=85083521338&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85083521338&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2020.02.060

DO - 10.1016/j.jacc.2020.02.060

M3 - Article

C2 - 32194198

AN - SCOPUS:85083521338

SN - 0735-1097

VL - 75

SP - 2156

EP - 2165

JO - Journal of the American College of Cardiology.

JF - Journal of the American College of Cardiology.

IS - 17

ER -

Cellular Adhesion Molecules in Young Adulthood and Cardiac Function in Later Life

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

Publisher link

Find It

Other files and links

Fingerprint

Cite this