Relationship of fibroblast growth factor 21 with subclinical atherosclerosis and cardiovascular events: Multi-Ethnic Study of Atherosclerosis

Kwok Leung Ong, Steven Campbell, Ben J. Wu, Robyn L. McClelland, John Kokkinos, Moyses Szklo, Joseph F. Polak, Matthew A. Allison, Kerry Anne Rye

Research output: Contribution to journalArticle

Abstract

Background and aims: Fibroblast growth factor 21 (FGF21) has been suggested as a novel biomarker for cardiovascular disease (CVD), especially in people with high CVD risk. However, it is not known whether FGF21 is a CVD biomarker in an initially healthy cohort. We therefore investigated the relationship of plasma FGF21 levels with measures of subclinical atherosclerosis and cardiovascular events in Multi-Ethnic Study of Atherosclerosis participants without known CVD at baseline. Methods: A total of 5788 participants had plasma FGF21 levels measured at the baseline exam (2000–2002). Carotid intima-media thickness (IMT), ankle-brachial index (ABI) and coronary artery calcification (CAC) were measured at baseline. Participants were followed up for incident CVD events over a median period of 14 years. Results: In cross-sectional analyses adjusting for socio-demographic variables, participants with higher FGF21 levels had higher carotid IMT, lower ABI, and higher prevalence of CAC (p < 0.001). However, these associations were not significant after simultaneously adjusting for demographic, socioeconomic and lifestyle factors, traditional CVD risk factors, and biomarkers of inflammation and hemostasis. Among 5768 patients with follow-up data, 820 developed incident CVD endpoints. Higher baseline FGF21 levels were not associated with the risk for incident CVD endpoints after adjusting for multiple confounding factors (odds ratio 1.03; 95% confidence interval, 0.94–1.12, per SD increase in ln-transformed FGF21 levels). Conclusions: Although FGF21 has been suggested as a CVD biomarker for people with high CVD risk, our findings do not support a role of FGF21 as a CVD biomarker in those without a history of CVD.

Original languageEnglish (US)
Pages (from-to)46-53
Number of pages8
JournalAtherosclerosis
Volume287
DOIs
StatePublished - Aug 1 2019

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Atherosclerosis
Cardiovascular Diseases
Biomarkers
Ankle Brachial Index
Carotid Intima-Media Thickness
fibroblast growth factor 21
Coronary Vessels
Demography
Brachial Artery
Hemostasis
Life Style
Cross-Sectional Studies
Odds Ratio
Confidence Intervals
Inflammation

Keywords

  • Ankle-brachial index
  • Cardiovascular disease
  • Carotid intima-media thickness
  • Coronary artery calcification
  • Fibroblast growth factor 21

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Relationship of fibroblast growth factor 21 with subclinical atherosclerosis and cardiovascular events : Multi-Ethnic Study of Atherosclerosis. / Ong, Kwok Leung; Campbell, Steven; Wu, Ben J.; McClelland, Robyn L.; Kokkinos, John; Szklo, Moyses; Polak, Joseph F.; Allison, Matthew A.; Rye, Kerry Anne.

In: Atherosclerosis, Vol. 287, 01.08.2019, p. 46-53.

Research output: Contribution to journalArticle

Ong, Kwok Leung ; Campbell, Steven ; Wu, Ben J. ; McClelland, Robyn L. ; Kokkinos, John ; Szklo, Moyses ; Polak, Joseph F. ; Allison, Matthew A. ; Rye, Kerry Anne. / Relationship of fibroblast growth factor 21 with subclinical atherosclerosis and cardiovascular events : Multi-Ethnic Study of Atherosclerosis. In: Atherosclerosis. 2019 ; Vol. 287. pp. 46-53.
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abstract = "Background and aims: Fibroblast growth factor 21 (FGF21) has been suggested as a novel biomarker for cardiovascular disease (CVD), especially in people with high CVD risk. However, it is not known whether FGF21 is a CVD biomarker in an initially healthy cohort. We therefore investigated the relationship of plasma FGF21 levels with measures of subclinical atherosclerosis and cardiovascular events in Multi-Ethnic Study of Atherosclerosis participants without known CVD at baseline. Methods: A total of 5788 participants had plasma FGF21 levels measured at the baseline exam (2000–2002). Carotid intima-media thickness (IMT), ankle-brachial index (ABI) and coronary artery calcification (CAC) were measured at baseline. Participants were followed up for incident CVD events over a median period of 14 years. Results: In cross-sectional analyses adjusting for socio-demographic variables, participants with higher FGF21 levels had higher carotid IMT, lower ABI, and higher prevalence of CAC (p < 0.001). However, these associations were not significant after simultaneously adjusting for demographic, socioeconomic and lifestyle factors, traditional CVD risk factors, and biomarkers of inflammation and hemostasis. Among 5768 patients with follow-up data, 820 developed incident CVD endpoints. Higher baseline FGF21 levels were not associated with the risk for incident CVD endpoints after adjusting for multiple confounding factors (odds ratio 1.03; 95{\%} confidence interval, 0.94–1.12, per SD increase in ln-transformed FGF21 levels). Conclusions: Although FGF21 has been suggested as a CVD biomarker for people with high CVD risk, our findings do not support a role of FGF21 as a CVD biomarker in those without a history of CVD.",
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T1 - Relationship of fibroblast growth factor 21 with subclinical atherosclerosis and cardiovascular events

T2 - Multi-Ethnic Study of Atherosclerosis

AU - Ong, Kwok Leung

AU - Campbell, Steven

AU - Wu, Ben J.

AU - McClelland, Robyn L.

AU - Kokkinos, John

AU - Szklo, Moyses

AU - Polak, Joseph F.

AU - Allison, Matthew A.

AU - Rye, Kerry Anne

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Background and aims: Fibroblast growth factor 21 (FGF21) has been suggested as a novel biomarker for cardiovascular disease (CVD), especially in people with high CVD risk. However, it is not known whether FGF21 is a CVD biomarker in an initially healthy cohort. We therefore investigated the relationship of plasma FGF21 levels with measures of subclinical atherosclerosis and cardiovascular events in Multi-Ethnic Study of Atherosclerosis participants without known CVD at baseline. Methods: A total of 5788 participants had plasma FGF21 levels measured at the baseline exam (2000–2002). Carotid intima-media thickness (IMT), ankle-brachial index (ABI) and coronary artery calcification (CAC) were measured at baseline. Participants were followed up for incident CVD events over a median period of 14 years. Results: In cross-sectional analyses adjusting for socio-demographic variables, participants with higher FGF21 levels had higher carotid IMT, lower ABI, and higher prevalence of CAC (p < 0.001). However, these associations were not significant after simultaneously adjusting for demographic, socioeconomic and lifestyle factors, traditional CVD risk factors, and biomarkers of inflammation and hemostasis. Among 5768 patients with follow-up data, 820 developed incident CVD endpoints. Higher baseline FGF21 levels were not associated with the risk for incident CVD endpoints after adjusting for multiple confounding factors (odds ratio 1.03; 95% confidence interval, 0.94–1.12, per SD increase in ln-transformed FGF21 levels). Conclusions: Although FGF21 has been suggested as a CVD biomarker for people with high CVD risk, our findings do not support a role of FGF21 as a CVD biomarker in those without a history of CVD.

AB - Background and aims: Fibroblast growth factor 21 (FGF21) has been suggested as a novel biomarker for cardiovascular disease (CVD), especially in people with high CVD risk. However, it is not known whether FGF21 is a CVD biomarker in an initially healthy cohort. We therefore investigated the relationship of plasma FGF21 levels with measures of subclinical atherosclerosis and cardiovascular events in Multi-Ethnic Study of Atherosclerosis participants without known CVD at baseline. Methods: A total of 5788 participants had plasma FGF21 levels measured at the baseline exam (2000–2002). Carotid intima-media thickness (IMT), ankle-brachial index (ABI) and coronary artery calcification (CAC) were measured at baseline. Participants were followed up for incident CVD events over a median period of 14 years. Results: In cross-sectional analyses adjusting for socio-demographic variables, participants with higher FGF21 levels had higher carotid IMT, lower ABI, and higher prevalence of CAC (p < 0.001). However, these associations were not significant after simultaneously adjusting for demographic, socioeconomic and lifestyle factors, traditional CVD risk factors, and biomarkers of inflammation and hemostasis. Among 5768 patients with follow-up data, 820 developed incident CVD endpoints. Higher baseline FGF21 levels were not associated with the risk for incident CVD endpoints after adjusting for multiple confounding factors (odds ratio 1.03; 95% confidence interval, 0.94–1.12, per SD increase in ln-transformed FGF21 levels). Conclusions: Although FGF21 has been suggested as a CVD biomarker for people with high CVD risk, our findings do not support a role of FGF21 as a CVD biomarker in those without a history of CVD.

KW - Ankle-brachial index

KW - Cardiovascular disease

KW - Carotid intima-media thickness

KW - Coronary artery calcification

KW - Fibroblast growth factor 21

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