Plasma acylcarnitines and progression of carotid artery atherosclerosis in HIV infection

Simin Hua; Justin M. Scott; David B. Hanna; Sabina A. Haberlen; Sanjiv J. Shah; Howard N. Hodis; Alan L. Landay; Jason M. Lazar; Jorge R. Kizer; Bing Yu; Wendy S. Post; Kathryn Anastos; Robert C. Kaplan; Clary B. Clish; Qibin Qi

doi:10.1097/QAD.0000000000002142

Plasma acylcarnitines and progression of carotid artery atherosclerosis in HIV infection

Simin Hua, Justin M. Scott, David B. Hanna, Sabina A. Haberlen, Sanjiv J. Shah, Howard N. Hodis, Alan L. Landay, Jason M. Lazar, Jorge R. Kizer, Bing Yu, Wendy S. Post, Kathryn Anastos, Robert C. Kaplan, Clary B. Clish, Qibin Qi

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

3 Scopus citations

Abstract

To evaluate plasma acylcarnitine profiles and their relationships with progression of carotid artery atherosclerosis among individuals with and without HIV infection.Design:Prospective cohort studies of 499 HIV-positive and 206 HIV-negative individuals from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study.Methods:Twenty-four acylcarnitine species were measured in plasma samples of participants at baseline. Carotid artery plaque was assessed using repeated B-mode carotid artery ultrasound imaging in 2004-2013. We examined the associations of individual and aggregate short-chain (C2-C7), medium-chain (C8-C14) and long-chain acylcarnitines (C16-C26) with incident carotid artery plaque over 7 years.Results:Among 24 acylcarnitine species, C8-carnitines and C20:4-carnitines showed significantly lower levels comparing HIV-positive to HIV-negative individuals (false discovery rate adjusted P<0.05); and C20-carnitines and C26-carnitines showed significantly higher levels in HIV positive using antiretroviral therapy than those without antiretroviral therapy (false discovery rate adjusted P<0.05). In the univariate analyses, higher aggregated short-chain and long-chain acylcarnitine scores were associated with increased risk of carotid artery plaque [risk ratios (RRs)=1.22 (95% confidence interval 1.02-1.45) and 1.20 (1.02-1.41) per SD increment, respectively]. The association for the short-chain acylcarnitine score remained significant [RR=1.23 (1.05-1.44)] after multivariate adjustment (including traditional cardiovascular disease risk factors). This association was more evident in HIV-positive individuals without persistent viral suppression [RR=1.37 (1.11-1.69)] compared with those with persistent viral suppression during follow-up [RR=1.03 (0.76-1.40)] or HIV-negative individuals [RR=1.02 (0.69-1.52)].Conclusion:In two HIV cohorts, plasma levels of most acylcarnitines were not significantly different between HIV-positive and HIV-negative individuals. However, higher levels of aggregated short-chain acylcarnitines were associated with progression of carotid artery atherosclerosis.

Original language	English (US)
Pages (from-to)	1043-1052
Number of pages	10
Journal	AIDS
Volume	33
Issue number	6
DOIs	https://doi.org/10.1097/QAD.0000000000002142
State	Published - May 1 2019

Keywords

HIV infection
acylcarnitines
atherosclerosis
cardiovascular disease
carotid artery
metabolomics

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

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

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10.1097/QAD.0000000000002142

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@article{a2508fccd9a944f3929982006093b85b,

title = "Plasma acylcarnitines and progression of carotid artery atherosclerosis in HIV infection",

abstract = "To evaluate plasma acylcarnitine profiles and their relationships with progression of carotid artery atherosclerosis among individuals with and without HIV infection.Design:Prospective cohort studies of 499 HIV-positive and 206 HIV-negative individuals from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study.Methods:Twenty-four acylcarnitine species were measured in plasma samples of participants at baseline. Carotid artery plaque was assessed using repeated B-mode carotid artery ultrasound imaging in 2004-2013. We examined the associations of individual and aggregate short-chain (C2-C7), medium-chain (C8-C14) and long-chain acylcarnitines (C16-C26) with incident carotid artery plaque over 7 years.Results:Among 24 acylcarnitine species, C8-carnitines and C20:4-carnitines showed significantly lower levels comparing HIV-positive to HIV-negative individuals (false discovery rate adjusted P<0.05); and C20-carnitines and C26-carnitines showed significantly higher levels in HIV positive using antiretroviral therapy than those without antiretroviral therapy (false discovery rate adjusted P<0.05). In the univariate analyses, higher aggregated short-chain and long-chain acylcarnitine scores were associated with increased risk of carotid artery plaque [risk ratios (RRs)=1.22 (95% confidence interval 1.02-1.45) and 1.20 (1.02-1.41) per SD increment, respectively]. The association for the short-chain acylcarnitine score remained significant [RR=1.23 (1.05-1.44)] after multivariate adjustment (including traditional cardiovascular disease risk factors). This association was more evident in HIV-positive individuals without persistent viral suppression [RR=1.37 (1.11-1.69)] compared with those with persistent viral suppression during follow-up [RR=1.03 (0.76-1.40)] or HIV-negative individuals [RR=1.02 (0.69-1.52)].Conclusion:In two HIV cohorts, plasma levels of most acylcarnitines were not significantly different between HIV-positive and HIV-negative individuals. However, higher levels of aggregated short-chain acylcarnitines were associated with progression of carotid artery atherosclerosis.",

keywords = "HIV infection, acylcarnitines, atherosclerosis, cardiovascular disease, carotid artery, metabolomics",

author = "Simin Hua and Scott, {Justin M.} and Hanna, {David B.} and Haberlen, {Sabina A.} and Shah, {Sanjiv J.} and Hodis, {Howard N.} and Landay, {Alan L.} and Lazar, {Jason M.} and Kizer, {Jorge R.} and Bing Yu and Post, {Wendy S.} and Kathryn Anastos and Kaplan, {Robert C.} and Clish, {Clary B.} and Qibin Qi",

note = "Funding Information: and Anjali Sharma), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen and Audrey French), U01-AI-034993; Metropolitan Washington WIHS (Seble Kassaye), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (Adaora Adimora), U01-AI-103390; Connie Wofsy Women{\textquoteright}s HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Joel Milam), U01-HD-032632 (WIHS I–WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA) and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD) and the NIH Office of Research on Women{\textquoteright}s Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA), UL1-TR000454 (Atlanta CTSA) and P30-AI-050410 (UNC CFAR). Funding Information: MACS (Principal Investigators): Johns Hopkins University Bloomberg School of Public Health (Joseph Margolick, Todd Brown), U01-AI35042; Northwestern University (Steven Wolinsky), U01-AI35039; University of California, Los Angeles (Roger Detels, Otoniel Martinez-Maza, Otto Yang), U01-AI35040; University of Pittsburgh (Charles Rinaldo, Lawrence Kingsley, Jeremy Martinson), U01-AI35041; the Center for Analysis and Management of MACS, Johns Hopkins University Bloomberg School of Public Health (Lisa Jacobson, Gypsyamber D{\textquoteright}Souza), UM1-AI35043. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional cofunding from the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA) and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR001079 (JHU ICTR) from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH), Johns Hopkins ICTR or NCATS. The MACS website is located at http:// aidscohortstudy.org/. Funding Information: The study was supported by the National Heart, Lung, and Blood Institute (NHLBI) K01HL129892 to Q.Q., and other funding sources for this study include R01HL140976 to Q.Q., R01HL126543, R01HL132794, R01HL083760 and R01HL095140 to R.C.K., R01HL095129 to W.S.P., K01HL137557 to D.B.H. and Feldstein Medical Foundation Research Grant to Q.Q. Publisher Copyright: {\textcopyright} 2019 Wolters Kluwer Health, Inc. All rights reserved.",

year = "2019",

month = may,

day = "1",

doi = "10.1097/QAD.0000000000002142",

language = "English (US)",

volume = "33",

pages = "1043--1052",

journal = "AIDS",

issn = "0269-9370",

publisher = "Lippincott Williams and Wilkins",

number = "6",

}

TY - JOUR

T1 - Plasma acylcarnitines and progression of carotid artery atherosclerosis in HIV infection

AU - Hua, Simin

AU - Scott, Justin M.

AU - Hanna, David B.

AU - Haberlen, Sabina A.

AU - Shah, Sanjiv J.

AU - Hodis, Howard N.

AU - Landay, Alan L.

AU - Lazar, Jason M.

AU - Kizer, Jorge R.

AU - Yu, Bing

AU - Post, Wendy S.

AU - Anastos, Kathryn

AU - Kaplan, Robert C.

AU - Clish, Clary B.

AU - Qi, Qibin

N1 - Funding Information: and Anjali Sharma), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen and Audrey French), U01-AI-034993; Metropolitan Washington WIHS (Seble Kassaye), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (Adaora Adimora), U01-AI-103390; Connie Wofsy Women’s HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Joel Milam), U01-HD-032632 (WIHS I–WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA) and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD) and the NIH Office of Research on Women’s Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA), UL1-TR000454 (Atlanta CTSA) and P30-AI-050410 (UNC CFAR). Funding Information: MACS (Principal Investigators): Johns Hopkins University Bloomberg School of Public Health (Joseph Margolick, Todd Brown), U01-AI35042; Northwestern University (Steven Wolinsky), U01-AI35039; University of California, Los Angeles (Roger Detels, Otoniel Martinez-Maza, Otto Yang), U01-AI35040; University of Pittsburgh (Charles Rinaldo, Lawrence Kingsley, Jeremy Martinson), U01-AI35041; the Center for Analysis and Management of MACS, Johns Hopkins University Bloomberg School of Public Health (Lisa Jacobson, Gypsyamber D’Souza), UM1-AI35043. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional cofunding from the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA) and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR001079 (JHU ICTR) from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH), Johns Hopkins ICTR or NCATS. The MACS website is located at http:// aidscohortstudy.org/. Funding Information: The study was supported by the National Heart, Lung, and Blood Institute (NHLBI) K01HL129892 to Q.Q., and other funding sources for this study include R01HL140976 to Q.Q., R01HL126543, R01HL132794, R01HL083760 and R01HL095140 to R.C.K., R01HL095129 to W.S.P., K01HL137557 to D.B.H. and Feldstein Medical Foundation Research Grant to Q.Q. Publisher Copyright: © 2019 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - To evaluate plasma acylcarnitine profiles and their relationships with progression of carotid artery atherosclerosis among individuals with and without HIV infection.Design:Prospective cohort studies of 499 HIV-positive and 206 HIV-negative individuals from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study.Methods:Twenty-four acylcarnitine species were measured in plasma samples of participants at baseline. Carotid artery plaque was assessed using repeated B-mode carotid artery ultrasound imaging in 2004-2013. We examined the associations of individual and aggregate short-chain (C2-C7), medium-chain (C8-C14) and long-chain acylcarnitines (C16-C26) with incident carotid artery plaque over 7 years.Results:Among 24 acylcarnitine species, C8-carnitines and C20:4-carnitines showed significantly lower levels comparing HIV-positive to HIV-negative individuals (false discovery rate adjusted P<0.05); and C20-carnitines and C26-carnitines showed significantly higher levels in HIV positive using antiretroviral therapy than those without antiretroviral therapy (false discovery rate adjusted P<0.05). In the univariate analyses, higher aggregated short-chain and long-chain acylcarnitine scores were associated with increased risk of carotid artery plaque [risk ratios (RRs)=1.22 (95% confidence interval 1.02-1.45) and 1.20 (1.02-1.41) per SD increment, respectively]. The association for the short-chain acylcarnitine score remained significant [RR=1.23 (1.05-1.44)] after multivariate adjustment (including traditional cardiovascular disease risk factors). This association was more evident in HIV-positive individuals without persistent viral suppression [RR=1.37 (1.11-1.69)] compared with those with persistent viral suppression during follow-up [RR=1.03 (0.76-1.40)] or HIV-negative individuals [RR=1.02 (0.69-1.52)].Conclusion:In two HIV cohorts, plasma levels of most acylcarnitines were not significantly different between HIV-positive and HIV-negative individuals. However, higher levels of aggregated short-chain acylcarnitines were associated with progression of carotid artery atherosclerosis.

AB - To evaluate plasma acylcarnitine profiles and their relationships with progression of carotid artery atherosclerosis among individuals with and without HIV infection.Design:Prospective cohort studies of 499 HIV-positive and 206 HIV-negative individuals from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study.Methods:Twenty-four acylcarnitine species were measured in plasma samples of participants at baseline. Carotid artery plaque was assessed using repeated B-mode carotid artery ultrasound imaging in 2004-2013. We examined the associations of individual and aggregate short-chain (C2-C7), medium-chain (C8-C14) and long-chain acylcarnitines (C16-C26) with incident carotid artery plaque over 7 years.Results:Among 24 acylcarnitine species, C8-carnitines and C20:4-carnitines showed significantly lower levels comparing HIV-positive to HIV-negative individuals (false discovery rate adjusted P<0.05); and C20-carnitines and C26-carnitines showed significantly higher levels in HIV positive using antiretroviral therapy than those without antiretroviral therapy (false discovery rate adjusted P<0.05). In the univariate analyses, higher aggregated short-chain and long-chain acylcarnitine scores were associated with increased risk of carotid artery plaque [risk ratios (RRs)=1.22 (95% confidence interval 1.02-1.45) and 1.20 (1.02-1.41) per SD increment, respectively]. The association for the short-chain acylcarnitine score remained significant [RR=1.23 (1.05-1.44)] after multivariate adjustment (including traditional cardiovascular disease risk factors). This association was more evident in HIV-positive individuals without persistent viral suppression [RR=1.37 (1.11-1.69)] compared with those with persistent viral suppression during follow-up [RR=1.03 (0.76-1.40)] or HIV-negative individuals [RR=1.02 (0.69-1.52)].Conclusion:In two HIV cohorts, plasma levels of most acylcarnitines were not significantly different between HIV-positive and HIV-negative individuals. However, higher levels of aggregated short-chain acylcarnitines were associated with progression of carotid artery atherosclerosis.

KW - HIV infection

KW - acylcarnitines

KW - atherosclerosis

KW - cardiovascular disease

KW - carotid artery

KW - metabolomics

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DO - 10.1097/QAD.0000000000002142

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C2 - 30946158

AN - SCOPUS:85064239091

SN - 0269-9370

VL - 33

SP - 1043

EP - 1052

JO - AIDS

JF - AIDS

IS - 6

ER -

Plasma acylcarnitines and progression of carotid artery atherosclerosis in HIV infection

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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