Association of apolipoproteins C-I and C-II truncations with coronary heart disease and progression of coronary artery calcium: Multi-Ethnic Study of Atherosclerosis.


Journal

Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543

Informations de publication

Date de publication:
09 2023
Historique:
received: 28 03 2023
revised: 18 07 2023
accepted: 02 08 2023
medline: 4 9 2023
pubmed: 14 8 2023
entrez: 13 8 2023
Statut: ppublish

Résumé

Higher truncated-to-native proteoform ratios of apolipoproteins (apo) C-I (C-I'/C-I) and C-II (C-II'/C-II) are associated with less atherogenic lipid profiles. We examined prospective relationships of C-I'/C-II and C-II'/C-II with coronary heart disease (CHD) and coronary artery calcium (CAC). ApoC-I and apoC-II proteoforms were measured by mass spectrometry immunoassay in 5790 MESA baseline plasma samples. CHD events (myocardial infarction, resuscitated cardiac arrest, fatal CHD, n = 434) were evaluated for up to 17 years. CAC was measured 1-4 times over 10 years for incident CAC (if baseline CAC = 0), and changes (follow-up adjusted for baseline) in CAC score and density (if baseline CAC>0). C-II'/C-II was inversely associated with CHD (n = 434 events) after adjusting for non-lipid cardiovascular risk factors (Hazard ratio: 0.89 [95% CI: 0.81-0.98] per SD), however, the association was attenuated after further adjustment for HDL levels (0.93 [0.83-1.03]). There was no association between C-I'/C-I and CHD (0.98 [0.88-1.08]). C-II'/C-II was positively associated with changes in CAC score (3.4% [95%CI: 0.6, 6.3]) and density (6.3% [0.3, 4.2]), while C-I'/C-I was inversely associated with incident CAC (Risk ratio: 0.89 [95% CI: 0.81, 0.98]) in fully adjusted models that included plasma lipids. Total apoC-I and apoC-II concentrations were not associated with CHD, incident CAC or change in CAC score. Increased apoC-II truncation was associated with reduced CHD, possibly explained by differences in lipid metabolism. Increased apoC-I and apoC-II truncations were also associated with less CAC progression and/or development of denser coronary plaques.

Sections du résumé

BACKGROUND AND AIMS
Higher truncated-to-native proteoform ratios of apolipoproteins (apo) C-I (C-I'/C-I) and C-II (C-II'/C-II) are associated with less atherogenic lipid profiles. We examined prospective relationships of C-I'/C-II and C-II'/C-II with coronary heart disease (CHD) and coronary artery calcium (CAC).
METHODS
ApoC-I and apoC-II proteoforms were measured by mass spectrometry immunoassay in 5790 MESA baseline plasma samples. CHD events (myocardial infarction, resuscitated cardiac arrest, fatal CHD, n = 434) were evaluated for up to 17 years. CAC was measured 1-4 times over 10 years for incident CAC (if baseline CAC = 0), and changes (follow-up adjusted for baseline) in CAC score and density (if baseline CAC>0).
RESULTS
C-II'/C-II was inversely associated with CHD (n = 434 events) after adjusting for non-lipid cardiovascular risk factors (Hazard ratio: 0.89 [95% CI: 0.81-0.98] per SD), however, the association was attenuated after further adjustment for HDL levels (0.93 [0.83-1.03]). There was no association between C-I'/C-I and CHD (0.98 [0.88-1.08]). C-II'/C-II was positively associated with changes in CAC score (3.4% [95%CI: 0.6, 6.3]) and density (6.3% [0.3, 4.2]), while C-I'/C-I was inversely associated with incident CAC (Risk ratio: 0.89 [95% CI: 0.81, 0.98]) in fully adjusted models that included plasma lipids. Total apoC-I and apoC-II concentrations were not associated with CHD, incident CAC or change in CAC score.
CONCLUSIONS
Increased apoC-II truncation was associated with reduced CHD, possibly explained by differences in lipid metabolism. Increased apoC-I and apoC-II truncations were also associated with less CAC progression and/or development of denser coronary plaques.

Identifiants

pubmed: 37573768
pii: S0021-9150(23)05128-6
doi: 10.1016/j.atherosclerosis.2023.117214
pii:
doi:

Substances chimiques

Calcium SY7Q814VUP
Calcium, Dietary 0
Apolipoproteins C 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

117214

Subventions

Organisme : NCATS NIH HHS
ID : UL1 TR001420
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001079
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000040
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95169
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95168
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95167
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95166
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95165
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92020D00007
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95164
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92020D00004
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95163
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92020D00006
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95162
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92020D00003
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95161
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92020D00002
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95160
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92020D00005
Pays : United States
Organisme : NHLBI NIH HHS
ID : N01HC95159
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201500003I
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92020D00001
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL138969
Pays : United States

Informations de copyright

Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of competing interest Jeremy Furtado is currently an employee of Biogen. The other authors have nothing to disclose.

Auteurs

Juraj Koska (J)

Phoenix VA Health Care System, 650 E Indian School Rd CS111E, Phoenix, AZ, 85012, USA. Electronic address: juraj.koska@va.gov.

Yueming Hu (Y)

Isoformix Inc., 9830 S. 51st Suite B-113, Phoenix, AZ, 85044, USA.

Jeremy Furtado (J)

Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA.

Dean Billheimer (D)

Mel and Enid Zuckerman College of Public Health, University of Arizona, 1295 N Martin Ave, Tucson, AZ, 85724, USA.

Dobrin Nedelkov (D)

Isoformix Inc., 9830 S. 51st Suite B-113, Phoenix, AZ, 85044, USA.

Matthew Allison (M)

Department of Family Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.

Matthew J Budoff (MJ)

Lundquist Institute at Harbor-University of California, Los Angeles (UCLA), 1124 W Carson St., Torrance, CA, 90502, USA.

Robyn L McClelland (RL)

Department of Biostatistics, University of Washington, 6200 NE 74th St. Bldg. 29 Suite 210, Seattle, WA, 98115, USA.

Peter Reaven (P)

College of Health Solutions, Arizona State University, 550 N 3rd St, Phoenix, AZ, 85004, USA.

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Classifications MeSH