High-density lipoprotein cholesterol efflux capacity is not associated with atherosclerosis and prevalence of cardiovascular outcome: The CODAM study

Tatjana Josefs; Kristiaan Wouters; Uwe J F Tietge; Wijtske Annema; Robin P F Dullaart; Tomas Vaisar; Ilja C W Arts; Carla J H van der Kallen; Coen D A Stehouwer; Casper G Schalkwijk; Ira J Goldberg; Edward A Fisher; Marleen M J van Greevenbroek

doi:10.1016/j.jacl.2019.10.012

High-density lipoprotein cholesterol efflux capacity is not associated with atherosclerosis and prevalence of cardiovascular outcome: The CODAM study

Tatjana Josefs, Kristiaan Wouters, Uwe J F Tietge, Wijtske Annema, Robin P F Dullaart, Tomas Vaisar, Ilja C W Arts, Carla J H van der Kallen, Coen D A Stehouwer, Casper G Schalkwijk, Ira J Goldberg, Edward A Fisher, Marleen M J van Greevenbroek^*

^*Corresponding author for this work

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

85 Downloads (Pure)

Abstract

BACKGROUND: Cholesterol Efflux Capacity (CEC) is considered to be a key atheroprotective property of high-density lipoproteins (HDL). However, the role of HDL-CEC in atherosclerosis and cardiovascular (CV) risk is still controversial, and data in individuals with diabetes are limited.

OBJECTIVE: In this study, we have investigated the relationship of CEC and other HDL characteristics with clinical and subclinical atherosclerosis in subjects with elevated cardiovascular diseases (CVD) risk and Type 2 Diabetes Mellitus (T2DM).

METHODS: Using multiple linear regression analyses, we determined the relationship of HDL-CEC with carotid intima-media thickness (cIMT, Z-Score), an endothelial dysfunction (EnD) Score (Z-Score), prevalent CVD (n = 150 cases) and history of CV events (CVE, n = 85 cases) in an observational cohort (CODAM, n = 574, 59.6 ± 0.3 yr, 61.3% men, 24.4% T2DM). Stratified analyses were performed to determine if the associations differed between individuals with normal glucose metabolism (NGM) and those with disturbed glucose metabolism.

RESULTS: HDL-CEC was not associated with either marker of atherosclerosis (cIMT, EnD Score) nor with CVD or CVE. In contrast, other HDL characteristics that is, HDL-Cholesterol (HDL-C, Z-Score), apolipoprotein A-I (apoA-I, Z-Score), HDL size (Z-Score) and HDL particle number (HDL-P, Z-Score) were inversely and significantly associated with the EnD Score (s -0.226 to -0.097, P < .05) and CVE (ORs 0.61 to 0.68, P < .05). In stratified analyses, HDL size and HDL-P were significantly associated with the EnD Score in individuals with NGM (Pinteraction .039 and .005, respectively), but not in those with (pre)diabetes. HDL-C and apoA-I were inversely associated with prevalent CVD in individuals with (pre)diabetes (Pinteraction = .074 and .034, respectively), but not in those with NGM.

CONCLUSION: HDL-CEC is not associated with clinical or subclinical atherosclerosis, neither in the whole population nor in individuals with (pre)diabetes, while other HDL characteristics show atheroprotective associations. The atheroprotective associations of HDL-size and HDL-P are lost in (pre)diabetes, while higher concentrations of HDL-C and apoA-I are associated with a lower prevalence of CVD in (pre)diabetes.

Original language	English
Pages (from-to)	122-132.e4
Number of pages	15
Journal	Journal of Clinical Lipidology
Volume	14
Issue number	1
DOIs	https://doi.org/10.1016/j.jacl.2019.10.012
Publication status	Published - 2020

Keywords

ARTERY-DISEASE
Atherosclerosis
CAROTID ATHEROSCLEROSIS
CORONARY-HEART-DISEASE
Cardiovascular diseases
Cholesterol efflux capacity
DIABETES-MELLITUS
HDL CHOLESTEROL
High-density lipoprotein
INSULIN-RESISTANCE
MEDIA THICKNESS MEASUREMENTS
NUCLEAR-MAGNETIC-RESONANCE
PARTICLE-SIZE
RISK
HIGH-RISK

Access to Document

10.1016/j.jacl.2019.10.012

Full textFinal published version, 599 KBLicence: Taverne

Cite this

Josefs, T., Wouters, K., Tietge, U. J. F., Annema, W., Dullaart, R. P. F., Vaisar, T., Arts, I. C. W., van der Kallen, C. J. H., Stehouwer, C. D. A., Schalkwijk, C. G., Goldberg, I. J., Fisher, E. A., & van Greevenbroek, M. M. J. (2020). High-density lipoprotein cholesterol efflux capacity is not associated with atherosclerosis and prevalence of cardiovascular outcome: The CODAM study. Journal of Clinical Lipidology, 14(1), 122-132.e4. https://doi.org/10.1016/j.jacl.2019.10.012

@article{554bbe19cfb3432eaafd5caefb8f4ffd,

title = "High-density lipoprotein cholesterol efflux capacity is not associated with atherosclerosis and prevalence of cardiovascular outcome: The CODAM study",

abstract = "BACKGROUND: Cholesterol Efflux Capacity (CEC) is considered to be a key atheroprotective property of high-density lipoproteins (HDL). However, the role of HDL-CEC in atherosclerosis and cardiovascular (CV) risk is still controversial, and data in individuals with diabetes are limited.OBJECTIVE: In this study, we have investigated the relationship of CEC and other HDL characteristics with clinical and subclinical atherosclerosis in subjects with elevated cardiovascular diseases (CVD) risk and Type 2 Diabetes Mellitus (T2DM).METHODS: Using multiple linear regression analyses, we determined the relationship of HDL-CEC with carotid intima-media thickness (cIMT, Z-Score), an endothelial dysfunction (EnD) Score (Z-Score), prevalent CVD (n = 150 cases) and history of CV events (CVE, n = 85 cases) in an observational cohort (CODAM, n = 574, 59.6 ± 0.3 yr, 61.3% men, 24.4% T2DM). Stratified analyses were performed to determine if the associations differed between individuals with normal glucose metabolism (NGM) and those with disturbed glucose metabolism.RESULTS: HDL-CEC was not associated with either marker of atherosclerosis (cIMT, EnD Score) nor with CVD or CVE. In contrast, other HDL characteristics that is, HDL-Cholesterol (HDL-C, Z-Score), apolipoprotein A-I (apoA-I, Z-Score), HDL size (Z-Score) and HDL particle number (HDL-P, Z-Score) were inversely and significantly associated with the EnD Score (s -0.226 to -0.097, P < .05) and CVE (ORs 0.61 to 0.68, P < .05). In stratified analyses, HDL size and HDL-P were significantly associated with the EnD Score in individuals with NGM (Pinteraction .039 and .005, respectively), but not in those with (pre)diabetes. HDL-C and apoA-I were inversely associated with prevalent CVD in individuals with (pre)diabetes (Pinteraction = .074 and .034, respectively), but not in those with NGM.CONCLUSION: HDL-CEC is not associated with clinical or subclinical atherosclerosis, neither in the whole population nor in individuals with (pre)diabetes, while other HDL characteristics show atheroprotective associations. The atheroprotective associations of HDL-size and HDL-P are lost in (pre)diabetes, while higher concentrations of HDL-C and apoA-I are associated with a lower prevalence of CVD in (pre)diabetes.",

keywords = "ARTERY-DISEASE, Atherosclerosis, CAROTID ATHEROSCLEROSIS, CORONARY-HEART-DISEASE, Cardiovascular diseases, Cholesterol efflux capacity, DIABETES-MELLITUS, HDL CHOLESTEROL, High-density lipoprotein, INSULIN-RESISTANCE, MEDIA THICKNESS MEASUREMENTS, NUCLEAR-MAGNETIC-RESONANCE, PARTICLE-SIZE, RISK, HIGH-RISK",

author = "Tatjana Josefs and Kristiaan Wouters and Tietge, {Uwe J F} and Wijtske Annema and Dullaart, {Robin P F} and Tomas Vaisar and Arts, {Ilja C W} and {van der Kallen}, {Carla J H} and Stehouwer, {Coen D A} and Schalkwijk, {Casper G} and Goldberg, {Ira J} and Fisher, {Edward A} and {van Greevenbroek}, {Marleen M J}",

year = "2020",

doi = "10.1016/j.jacl.2019.10.012",

language = "English",

volume = "14",

pages = "122--132.e4",

journal = "Journal of Clinical Lipidology",

issn = "1933-2874",

publisher = "Elsevier BV",

number = "1",

}

Josefs, T, Wouters, K, Tietge, UJF, Annema, W, Dullaart, RPF, Vaisar, T, Arts, ICW , van der Kallen, CJH, Stehouwer, CDA, Schalkwijk, CG, Goldberg, IJ, Fisher, EA & van Greevenbroek, MMJ 2020, 'High-density lipoprotein cholesterol efflux capacity is not associated with atherosclerosis and prevalence of cardiovascular outcome: The CODAM study', Journal of Clinical Lipidology, vol. 14, no. 1, pp. 122-132.e4. https://doi.org/10.1016/j.jacl.2019.10.012

TY - JOUR

T1 - High-density lipoprotein cholesterol efflux capacity is not associated with atherosclerosis and prevalence of cardiovascular outcome

T2 - The CODAM study

AU - Josefs, Tatjana

AU - Wouters, Kristiaan

AU - Tietge, Uwe J F

AU - Annema, Wijtske

AU - Dullaart, Robin P F

AU - Vaisar, Tomas

AU - Arts, Ilja C W

AU - van der Kallen, Carla J H

AU - Stehouwer, Coen D A

AU - Schalkwijk, Casper G

AU - Goldberg, Ira J

AU - Fisher, Edward A

AU - van Greevenbroek, Marleen M J

PY - 2020

Y1 - 2020

N2 - BACKGROUND: Cholesterol Efflux Capacity (CEC) is considered to be a key atheroprotective property of high-density lipoproteins (HDL). However, the role of HDL-CEC in atherosclerosis and cardiovascular (CV) risk is still controversial, and data in individuals with diabetes are limited.OBJECTIVE: In this study, we have investigated the relationship of CEC and other HDL characteristics with clinical and subclinical atherosclerosis in subjects with elevated cardiovascular diseases (CVD) risk and Type 2 Diabetes Mellitus (T2DM).METHODS: Using multiple linear regression analyses, we determined the relationship of HDL-CEC with carotid intima-media thickness (cIMT, Z-Score), an endothelial dysfunction (EnD) Score (Z-Score), prevalent CVD (n = 150 cases) and history of CV events (CVE, n = 85 cases) in an observational cohort (CODAM, n = 574, 59.6 ± 0.3 yr, 61.3% men, 24.4% T2DM). Stratified analyses were performed to determine if the associations differed between individuals with normal glucose metabolism (NGM) and those with disturbed glucose metabolism.RESULTS: HDL-CEC was not associated with either marker of atherosclerosis (cIMT, EnD Score) nor with CVD or CVE. In contrast, other HDL characteristics that is, HDL-Cholesterol (HDL-C, Z-Score), apolipoprotein A-I (apoA-I, Z-Score), HDL size (Z-Score) and HDL particle number (HDL-P, Z-Score) were inversely and significantly associated with the EnD Score (s -0.226 to -0.097, P < .05) and CVE (ORs 0.61 to 0.68, P < .05). In stratified analyses, HDL size and HDL-P were significantly associated with the EnD Score in individuals with NGM (Pinteraction .039 and .005, respectively), but not in those with (pre)diabetes. HDL-C and apoA-I were inversely associated with prevalent CVD in individuals with (pre)diabetes (Pinteraction = .074 and .034, respectively), but not in those with NGM.CONCLUSION: HDL-CEC is not associated with clinical or subclinical atherosclerosis, neither in the whole population nor in individuals with (pre)diabetes, while other HDL characteristics show atheroprotective associations. The atheroprotective associations of HDL-size and HDL-P are lost in (pre)diabetes, while higher concentrations of HDL-C and apoA-I are associated with a lower prevalence of CVD in (pre)diabetes.

AB - BACKGROUND: Cholesterol Efflux Capacity (CEC) is considered to be a key atheroprotective property of high-density lipoproteins (HDL). However, the role of HDL-CEC in atherosclerosis and cardiovascular (CV) risk is still controversial, and data in individuals with diabetes are limited.OBJECTIVE: In this study, we have investigated the relationship of CEC and other HDL characteristics with clinical and subclinical atherosclerosis in subjects with elevated cardiovascular diseases (CVD) risk and Type 2 Diabetes Mellitus (T2DM).METHODS: Using multiple linear regression analyses, we determined the relationship of HDL-CEC with carotid intima-media thickness (cIMT, Z-Score), an endothelial dysfunction (EnD) Score (Z-Score), prevalent CVD (n = 150 cases) and history of CV events (CVE, n = 85 cases) in an observational cohort (CODAM, n = 574, 59.6 ± 0.3 yr, 61.3% men, 24.4% T2DM). Stratified analyses were performed to determine if the associations differed between individuals with normal glucose metabolism (NGM) and those with disturbed glucose metabolism.RESULTS: HDL-CEC was not associated with either marker of atherosclerosis (cIMT, EnD Score) nor with CVD or CVE. In contrast, other HDL characteristics that is, HDL-Cholesterol (HDL-C, Z-Score), apolipoprotein A-I (apoA-I, Z-Score), HDL size (Z-Score) and HDL particle number (HDL-P, Z-Score) were inversely and significantly associated with the EnD Score (s -0.226 to -0.097, P < .05) and CVE (ORs 0.61 to 0.68, P < .05). In stratified analyses, HDL size and HDL-P were significantly associated with the EnD Score in individuals with NGM (Pinteraction .039 and .005, respectively), but not in those with (pre)diabetes. HDL-C and apoA-I were inversely associated with prevalent CVD in individuals with (pre)diabetes (Pinteraction = .074 and .034, respectively), but not in those with NGM.CONCLUSION: HDL-CEC is not associated with clinical or subclinical atherosclerosis, neither in the whole population nor in individuals with (pre)diabetes, while other HDL characteristics show atheroprotective associations. The atheroprotective associations of HDL-size and HDL-P are lost in (pre)diabetes, while higher concentrations of HDL-C and apoA-I are associated with a lower prevalence of CVD in (pre)diabetes.

KW - ARTERY-DISEASE

KW - Atherosclerosis

KW - CAROTID ATHEROSCLEROSIS

KW - CORONARY-HEART-DISEASE

KW - Cardiovascular diseases

KW - Cholesterol efflux capacity

KW - DIABETES-MELLITUS

KW - HDL CHOLESTEROL

KW - High-density lipoprotein

KW - INSULIN-RESISTANCE

KW - MEDIA THICKNESS MEASUREMENTS

KW - NUCLEAR-MAGNETIC-RESONANCE

KW - PARTICLE-SIZE

KW - RISK

KW - HIGH-RISK

U2 - 10.1016/j.jacl.2019.10.012

DO - 10.1016/j.jacl.2019.10.012

M3 - Article

C2 - 31791716

SN - 1933-2874

VL - 14

SP - 122-132.e4

JO - Journal of Clinical Lipidology

JF - Journal of Clinical Lipidology

IS - 1

ER -

High-density lipoprotein cholesterol efflux capacity is not associated with atherosclerosis and prevalence of cardiovascular outcome: The CODAM study

Abstract

Keywords

Access to Document

Fingerprint

Cite this