Novel Size-Based High-Density Lipoprotein Subspecies and Incident Vascular Events

Austin Deets; Parag H. Joshi; Alvin Chandra; Kavisha Singh; Amit Khera; Salim S. Virani; Christie M. Ballantyne; James D. Otvos; Robin P.F. Dullaart; Eke G. Gruppen; Margery A. Connelly; Colby Ayers; Ann Marie Navar; Ambarish Pandey; John T. Wilkins; Anand Rohatgi

doi:10.1161/JAHA.123.031160

Novel Size-Based High-Density Lipoprotein Subspecies and Incident Vascular Events

Austin Deets, Parag H. Joshi, Alvin Chandra, Kavisha Singh, Amit Khera, Salim S. Virani, Christie M. Ballantyne, James D. Otvos, Robin P.F. Dullaart, Eke G. Gruppen, Margery A. Connelly, Colby Ayers, Ann Marie Navar, Ambarish Pandey, John T. Wilkins, Anand Rohatgi^*

^*Corresponding author for this work

Medicine, Cardiology Division

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

4 Scopus citations

Abstract

BACKGROUND: High-density lipoprotein (HDL) particle concentration likely outperforms HDL cholesterol in predicting atherosclerotic cardiovascular events. Whether size-based HDL subspecies explain the atheroprotective associations of HDL particle concentration remains unknown. Our objective was to assess whether levels of specific size-based HDL subspecies associate with atherosclerotic cardiovascular disease in a multiethnic pooled cohort and improve risk prediction beyond traditional atherosclerotic cardiovascular disease risk factors. METHODS AND RESULTS: Seven HDL size-based subspecies were quantified by nuclear magnetic resonance (LP4 algorithm; H1=smallest; H7=largest) among participants without prior atherosclerotic cardiovascular disease in ARIC (Atherosclerosis Risk in Communities), MESA (Multi-Ethnic Study of Atherosclerosis), PREVEND (Prevention of Renal and Vascular Endstage Disease), and DHS (Dallas Heart Study) cohorts (n=15 371 people). Multivariable Cox proportional hazards models were used to evaluate the association between HDL subspecies and incident myocardial infarction (MI) or ischemic stroke at follow-up (average 8–10 years) adjusting for HDL cholesterol and risk factors. Improvement in risk prediction was assessed via discrimination and reclassification analysis. Within the pooled cohort (median age 57 years; female 54%; Black 22%) higher H1 (small) and H4 (medium) concentrations were inversely associated with incident MI (hazard ratio [HR]/SD, H1 0.88 [95% CI, 0.81–0.94]; H4 0.89 [95% CI, 0.82–0.97]). H4 but not H1 improved risk prediction indices for incident MI. Increasing H2 and H4 were inversely associated with improved risk prediction indices for composite end point of stroke, MI, and cardiovascular death (HR/SD, H2 0.94 [95% CI, 0.88–0.99]; H4 0.91 [95% CI, 0.85–0.98]). Levels of the large subspecies (H6 and H7) were not associated with any vascular end point. CONCLUSIONS: Two of 7 HDL size-based subspecies modestly improved risk prediction for MI and composite vascular end points in a large multiethnic pooled cohort. These findings support assessment of precise HDL subspecies for future studies regarding clinical utility.

Original language	English (US)
Article number	e031160
Journal	Journal of the American Heart Association
Volume	12
Issue number	21
DOIs	https://doi.org/10.1161/JAHA.123.031160
State	Published - Nov 7 2023

Funding

M. A. Connelly is employed by Labcorp and is a stock shareholder of LabCorp. C. Ayers has funding from the National Institutes of Health. A. Rohatgi has disclosures for CSL Limited, Raydel, and HDL Diagnostics as a consultant and for CSL and Quest for research grants. Dr Joshi has disclosures related to Honoraria for Regeneron and Bayer, as well as Research Grants for American Heart Association, Novo Nordisk, GlaxoSmithKline, Sanofi/Regeneron, AstraZeneca, and NASA and is a stock shareholder for G3 Therapeutics. Dr Virani has disclosures related to honoraria for American College of Cardiology (associate editor for Innovations, ACC.org). Dr Ballantyne has disclosures related to Abbott Diagnostics, Genentech, Amgen, Arrowhead, Astra Zeneca, Esperion, Gilead, Matinas BioPharma Inc, Novartis, Novo Nordisk, Regeneron, Sanofi-Synthelabo, Illumina, Pfizer, Merck, Althera, Roche Diagnostic, Amarin, Denka Seiken, and New Amsterdam, as well as research grants with Abbott Diagnostic, Akcea, Amgen, Esperion, Novartis, Regeneron, Roche Diagnostic, Ionis, and Arrowhead. J. D. Otvos is employed by Labcorp. Dr Wilkins has disclosures related to 3M and National Heart, Lung, and Blood Institute grant support, as well as disclosures related to research support from the National Institute on Aging GEMSSTAR Grant (1R03AG067960–01), and the National Institute on Minority Health and Disparities (R01MD017529), Applied Therapeutics This work was supported by National Heart, Lung, and Blood Institute and National Institutes of Health; K24HL146838 and R01HL136724.

Keywords

HDL
HDL size
HDL-C
MI
multiethnic
stroke

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1161/JAHA.123.031160

Cite this

Deets, A., Joshi, P. H., Chandra, A., Singh, K., Khera, A., Virani, S. S., Ballantyne, C. M., Otvos, J. D., Dullaart, R. P. F., Gruppen, E. G., Connelly, M. A., Ayers, C., Navar, A. M., Pandey, A., Wilkins, J. T., & Rohatgi, A. (2023). Novel Size-Based High-Density Lipoprotein Subspecies and Incident Vascular Events. Journal of the American Heart Association, 12(21), Article e031160. https://doi.org/10.1161/JAHA.123.031160

@article{91fef182b68145688a7b5d3548aa9944,

title = "Novel Size-Based High-Density Lipoprotein Subspecies and Incident Vascular Events",

abstract = "BACKGROUND: High-density lipoprotein (HDL) particle concentration likely outperforms HDL cholesterol in predicting atherosclerotic cardiovascular events. Whether size-based HDL subspecies explain the atheroprotective associations of HDL particle concentration remains unknown. Our objective was to assess whether levels of specific size-based HDL subspecies associate with atherosclerotic cardiovascular disease in a multiethnic pooled cohort and improve risk prediction beyond traditional atherosclerotic cardiovascular disease risk factors. METHODS AND RESULTS: Seven HDL size-based subspecies were quantified by nuclear magnetic resonance (LP4 algorithm; H1=smallest; H7=largest) among participants without prior atherosclerotic cardiovascular disease in ARIC (Atherosclerosis Risk in Communities), MESA (Multi-Ethnic Study of Atherosclerosis), PREVEND (Prevention of Renal and Vascular Endstage Disease), and DHS (Dallas Heart Study) cohorts (n=15 371 people). Multivariable Cox proportional hazards models were used to evaluate the association between HDL subspecies and incident myocardial infarction (MI) or ischemic stroke at follow-up (average 8–10 years) adjusting for HDL cholesterol and risk factors. Improvement in risk prediction was assessed via discrimination and reclassification analysis. Within the pooled cohort (median age 57 years; female 54%; Black 22%) higher H1 (small) and H4 (medium) concentrations were inversely associated with incident MI (hazard ratio [HR]/SD, H1 0.88 [95% CI, 0.81–0.94]; H4 0.89 [95% CI, 0.82–0.97]). H4 but not H1 improved risk prediction indices for incident MI. Increasing H2 and H4 were inversely associated with improved risk prediction indices for composite end point of stroke, MI, and cardiovascular death (HR/SD, H2 0.94 [95% CI, 0.88–0.99]; H4 0.91 [95% CI, 0.85–0.98]). Levels of the large subspecies (H6 and H7) were not associated with any vascular end point. CONCLUSIONS: Two of 7 HDL size-based subspecies modestly improved risk prediction for MI and composite vascular end points in a large multiethnic pooled cohort. These findings support assessment of precise HDL subspecies for future studies regarding clinical utility.",

keywords = "HDL, HDL size, HDL-C, MI, multiethnic, stroke",

author = "Austin Deets and Joshi, {Parag H.} and Alvin Chandra and Kavisha Singh and Amit Khera and Virani, {Salim S.} and Ballantyne, {Christie M.} and Otvos, {James D.} and Dullaart, {Robin P.F.} and Gruppen, {Eke G.} and Connelly, {Margery A.} and Colby Ayers and Navar, {Ann Marie} and Ambarish Pandey and Wilkins, {John T.} and Anand Rohatgi",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. T.",

year = "2023",

month = nov,

day = "7",

doi = "10.1161/JAHA.123.031160",

language = "English (US)",

volume = "12",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "Wiley-Blackwell",

number = "21",

}

Deets, A, Joshi, PH, Chandra, A, Singh, K, Khera, A, Virani, SS, Ballantyne, CM, Otvos, JD, Dullaart, RPF, Gruppen, EG, Connelly, MA, Ayers, C, Navar, AM, Pandey, A, Wilkins, JT & Rohatgi, A 2023, 'Novel Size-Based High-Density Lipoprotein Subspecies and Incident Vascular Events', Journal of the American Heart Association, vol. 12, no. 21, e031160. https://doi.org/10.1161/JAHA.123.031160

TY - JOUR

T1 - Novel Size-Based High-Density Lipoprotein Subspecies and Incident Vascular Events

AU - Deets, Austin

AU - Joshi, Parag H.

AU - Chandra, Alvin

AU - Singh, Kavisha

AU - Khera, Amit

AU - Virani, Salim S.

AU - Ballantyne, Christie M.

AU - Otvos, James D.

AU - Dullaart, Robin P.F.

AU - Gruppen, Eke G.

AU - Connelly, Margery A.

AU - Ayers, Colby

AU - Navar, Ann Marie

AU - Pandey, Ambarish

AU - Wilkins, John T.

AU - Rohatgi, Anand

PY - 2023/11/7

Y1 - 2023/11/7

N2 - BACKGROUND: High-density lipoprotein (HDL) particle concentration likely outperforms HDL cholesterol in predicting atherosclerotic cardiovascular events. Whether size-based HDL subspecies explain the atheroprotective associations of HDL particle concentration remains unknown. Our objective was to assess whether levels of specific size-based HDL subspecies associate with atherosclerotic cardiovascular disease in a multiethnic pooled cohort and improve risk prediction beyond traditional atherosclerotic cardiovascular disease risk factors. METHODS AND RESULTS: Seven HDL size-based subspecies were quantified by nuclear magnetic resonance (LP4 algorithm; H1=smallest; H7=largest) among participants without prior atherosclerotic cardiovascular disease in ARIC (Atherosclerosis Risk in Communities), MESA (Multi-Ethnic Study of Atherosclerosis), PREVEND (Prevention of Renal and Vascular Endstage Disease), and DHS (Dallas Heart Study) cohorts (n=15 371 people). Multivariable Cox proportional hazards models were used to evaluate the association between HDL subspecies and incident myocardial infarction (MI) or ischemic stroke at follow-up (average 8–10 years) adjusting for HDL cholesterol and risk factors. Improvement in risk prediction was assessed via discrimination and reclassification analysis. Within the pooled cohort (median age 57 years; female 54%; Black 22%) higher H1 (small) and H4 (medium) concentrations were inversely associated with incident MI (hazard ratio [HR]/SD, H1 0.88 [95% CI, 0.81–0.94]; H4 0.89 [95% CI, 0.82–0.97]). H4 but not H1 improved risk prediction indices for incident MI. Increasing H2 and H4 were inversely associated with improved risk prediction indices for composite end point of stroke, MI, and cardiovascular death (HR/SD, H2 0.94 [95% CI, 0.88–0.99]; H4 0.91 [95% CI, 0.85–0.98]). Levels of the large subspecies (H6 and H7) were not associated with any vascular end point. CONCLUSIONS: Two of 7 HDL size-based subspecies modestly improved risk prediction for MI and composite vascular end points in a large multiethnic pooled cohort. These findings support assessment of precise HDL subspecies for future studies regarding clinical utility.

AB - BACKGROUND: High-density lipoprotein (HDL) particle concentration likely outperforms HDL cholesterol in predicting atherosclerotic cardiovascular events. Whether size-based HDL subspecies explain the atheroprotective associations of HDL particle concentration remains unknown. Our objective was to assess whether levels of specific size-based HDL subspecies associate with atherosclerotic cardiovascular disease in a multiethnic pooled cohort and improve risk prediction beyond traditional atherosclerotic cardiovascular disease risk factors. METHODS AND RESULTS: Seven HDL size-based subspecies were quantified by nuclear magnetic resonance (LP4 algorithm; H1=smallest; H7=largest) among participants without prior atherosclerotic cardiovascular disease in ARIC (Atherosclerosis Risk in Communities), MESA (Multi-Ethnic Study of Atherosclerosis), PREVEND (Prevention of Renal and Vascular Endstage Disease), and DHS (Dallas Heart Study) cohorts (n=15 371 people). Multivariable Cox proportional hazards models were used to evaluate the association between HDL subspecies and incident myocardial infarction (MI) or ischemic stroke at follow-up (average 8–10 years) adjusting for HDL cholesterol and risk factors. Improvement in risk prediction was assessed via discrimination and reclassification analysis. Within the pooled cohort (median age 57 years; female 54%; Black 22%) higher H1 (small) and H4 (medium) concentrations were inversely associated with incident MI (hazard ratio [HR]/SD, H1 0.88 [95% CI, 0.81–0.94]; H4 0.89 [95% CI, 0.82–0.97]). H4 but not H1 improved risk prediction indices for incident MI. Increasing H2 and H4 were inversely associated with improved risk prediction indices for composite end point of stroke, MI, and cardiovascular death (HR/SD, H2 0.94 [95% CI, 0.88–0.99]; H4 0.91 [95% CI, 0.85–0.98]). Levels of the large subspecies (H6 and H7) were not associated with any vascular end point. CONCLUSIONS: Two of 7 HDL size-based subspecies modestly improved risk prediction for MI and composite vascular end points in a large multiethnic pooled cohort. These findings support assessment of precise HDL subspecies for future studies regarding clinical utility.

KW - HDL

KW - HDL size

KW - HDL-C

KW - MI

KW - multiethnic

KW - stroke

UR - http://www.scopus.com/inward/record.url?scp=85176295073&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85176295073&partnerID=8YFLogxK

U2 - 10.1161/JAHA.123.031160

DO - 10.1161/JAHA.123.031160

M3 - Article

C2 - 37929707

AN - SCOPUS:85176295073

SN - 2047-9980

VL - 12

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 21

M1 - e031160

ER -

Novel Size-Based High-Density Lipoprotein Subspecies and Incident Vascular Events

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this