PMID- 34185068
OWN - NLM
STAT- MEDLINE
DCOM- 20220105
LR  - 20221110
IS  - 2574-3805 (Electronic)
IS  - 2574-3805 (Linking)
VI  - 4
IP  - 6
DP  - 2021 Jun 1
TI  - Assessment of Coronary Artery Disease With Computed Tomography Angiography and 
      Inflammatory and Immune Activation Biomarkers Among Adults With HIV Eligible for 
      Primary Cardiovascular Prevention.
PG  - e2114923
LID - 10.1001/jamanetworkopen.2021.14923 [doi]
LID - e2114923
AB  - IMPORTANCE: Cardiovascular disease (CVD) is increased among people with HIV 
      (PWH), but little is known regarding the prevalence and extent of coronary artery 
      disease (CAD) and associated biological factors in PWH with low to moderate 
      traditional CVD risk. OBJECTIVES: To determine unique factors associated with CVD 
      in PWH and to assess CAD by coronary computed tomography angiography (CTA) and 
      critical pathways of arterial inflammation and immune activation. DESIGN, 
      SETTING, AND PARTICIPANTS: This cohort study among male and female PWH, aged 40 
      to 75 years, without known CVD, receiving stable antiretroviral therapy, and with 
      low to moderate atherosclerotic cardiovascular disease (ASCVD) risk according to 
      the 2013 American College of Cardiology/American Heart Association pooled cohort 
      equation, was part of the Randomized Trial to Prevent Vascular Events in HIV 
      (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among PWH 
      conducted at 31 US sites. Participants were enrolled from May 2015 to February 
      2018. Data analysis was conducted from May to December 2020. EXPOSURE: HIV 
      disease. MAIN OUTCOMES AND MEASURES: The primary outcome was the prevalence and 
      composition of CAD assessed by coronary CTA and, secondarily, the association of 
      CAD with traditional risk indices and circulating biomarkers, including insulin, 
      monocyte chemoattractant protein 1 (MCP-1), interleukin (IL) 6, soluble CD14 
      (sCD14), sCD163, lipoprotein-associated phospholipase A2 (LpPLA2), oxidized 
      low-density lipoprotein (oxLDL), and high-sensitivity C-reactive protein (hsCRP). 
      RESULTS: The sample included 755 participants, with a mean (SD) age of 51 (6) 
      years, 124 (16%) female participants, 267 (35%) Black or African American 
      participants, 182 (24%) Latinx participants, a low median (interquartile range) 
      ASCVD risk (4.5% [2.6%-6.8%]), and well-controlled viremia. Overall, plaque was 
      seen in 368 participants (49%), including among 52 of 175 participants (30%) with 
      atherosclerotic CVD (ASCVD) risk of less than 2.5%. Luminal obstruction of at 
      least 50% was rare (25 [3%]), but vulnerable plaque and high Leaman score (ie, 
      >5) were more frequently observed (172 of 755 [23%] and 118 of 743 [16%], 
      respectively). Overall, 251 of 718 participants (35%) demonstrated coronary 
      artery calcium score scores greater than 0. IL-6, LpPLA2, oxLDL, and MCP-1 levels 
      were higher in those with plaque compared with those without (eg, median [IQR] 
      IL-6 level, 1.71 [1.05-3.04] pg/mL vs 1.45 [0.96-2.60] pg/mL; P = .008). LpPLA2 
      and IL-6 levels were associated with plaque in adjusted modeling, independent of 
      traditional risk indices and HIV parameters (eg, IL-6: adjusted odds ratio, 1.07; 
      95% CI, 1.02-1.12; P = .01). CONCLUSIONS AND RELEVANCE: In this study of a large 
      primary prevention cohort of individuals with well-controlled HIV and low to 
      moderate ASCVD risk, CAD, including noncalcified, nonobstructive, and vulnerable 
      plaque, was highly prevalent. Participants with plaque demonstrated higher levels 
      of immune activation and arterial inflammation, independent of traditional ASCVD 
      risk and HIV parameters.
FAU - Hoffmann, Udo
AU  - Hoffmann U
AD  - Massachusetts General Hospital, Boston.
FAU - Lu, Michael T
AU  - Lu MT
AD  - Massachusetts General Hospital, Boston.
FAU - Foldyna, Borek
AU  - Foldyna B
AD  - Massachusetts General Hospital, Boston.
FAU - Zanni, Markella V
AU  - Zanni MV
AD  - Massachusetts General Hospital, Boston.
FAU - Karady, Julia
AU  - Karady J
AD  - Massachusetts General Hospital, Boston.
AD  - MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, 
      Semmelweis University, Budapest, Hungary.
FAU - Taron, Jana
AU  - Taron J
AD  - Massachusetts General Hospital, Boston.
AD  - University Hospital Freiburg, Freiburg, Germany.
FAU - Zhai, Bingxue K
AU  - Zhai BK
AD  - Massachusetts General Hospital, Boston.
AD  - Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Burdo, Tricia
AU  - Burdo T
AD  - Temple University, Philadelphia, Pennsylvania.
FAU - Fitch, Kathleen V
AU  - Fitch KV
AD  - Massachusetts General Hospital, Boston.
FAU - Kileel, Emma M
AU  - Kileel EM
AD  - Massachusetts General Hospital, Boston.
FAU - Williams, Kenneth
AU  - Williams K
AD  - Boston College, Boston, Massachusetts.
FAU - Fichtenbaum, Carl J
AU  - Fichtenbaum CJ
AD  - University of Cincinnati, Cincinnati, Ohio.
FAU - Overton, Edgar T
AU  - Overton ET
AD  - University of Alabama, Birmingham.
FAU - Malvestutto, Carlos
AU  - Malvestutto C
AD  - Ohio State University, Columbus.
FAU - Aberg, Judith
AU  - Aberg J
AD  - Icahn School of Medicine at Mount Sinai, New York, New York.
FAU - Currier, Judith
AU  - Currier J
AD  - University of California at Los Angeles.
FAU - Sponseller, Craig A
AU  - Sponseller CA
AD  - Kowa Pharmaceuticals America, Montgomery, Alabama.
FAU - Melbourne, Kathleen
AU  - Melbourne K
AD  - Gilead Sciences, Foster City, California.
FAU - Floris-Moore, Michelle
AU  - Floris-Moore M
AD  - University of North Carolina, Chapel Hill.
FAU - Van Dam, Cornelius
AU  - Van Dam C
AD  - Greensboro Clinical Research Site, Cone Health, Greensboro, North Carolina.
FAU - Keefer, Michael C
AU  - Keefer MC
AD  - University of Rochester Adult HIV Therapeutic Strategies Network Clinical 
      Research Site, Rochester, New York.
FAU - Koletar, Susan L
AU  - Koletar SL
AD  - Ohio State University, Columbus.
FAU - Douglas, Pamela S
AU  - Douglas PS
AD  - Duke Clinical Research Institute, Duke University School of Medicine, Durham, 
      North Carolina.
FAU - Ribaudo, Heather
AU  - Ribaudo H
AD  - Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public 
      Health, Boston, Massachusetts.
FAU - Mayrhofer, Thomas
AU  - Mayrhofer T
AD  - Massachusetts General Hospital, Boston.
AD  - School of Business Studies, Stralsund University of Applied Sciences, Stralsund, 
      Germany.
FAU - Grinspoon, Steven K
AU  - Grinspoon SK
AD  - Massachusetts General Hospital, Boston.
CN  - REPRIEVE trial
LA  - eng
GR  - P30 DK040561/DK/NIDDK NIH HHS/United States
GR  - UM1 AI069470/AI/NIAID NIH HHS/United States
GR  - U01 HL123339/HL/NHLBI NIH HHS/United States
GR  - UM1 AI069463/AI/NIAID NIH HHS/United States
GR  - U01 HL123336/HL/NHLBI NIH HHS/United States
GR  - UM1 AI069511/AI/NIAID NIH HHS/United States
GR  - UM1 AI068636/AI/NIAID NIH HHS/United States
GR  - UM1 AI069494/AI/NIAID NIH HHS/United States
GR  - UM1 AI069423/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210601
PL  - United States
TA  - JAMA Netw Open
JT  - JAMA network open
JID - 101729235
RN  - 0 (Biomarkers)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers/*analysis/blood
MH  - Cohort Studies
MH  - Computed Tomography Angiography/methods/*statistics & numerical data
MH  - Coronary Artery Disease/*blood/epidemiology
MH  - Female
MH  - HIV Infections/*blood/epidemiology
MH  - Humans
MH  - Male
MH  - Middle Aged
PMC - PMC8243232
COIS- Conflict of Interest Disclosures: Dr Hoffmann reported receiving personal fees 
      from Duke University, consulting fees from Recor Medical, and grants from Kowa, 
      AstraZeneca, Medimmune, and HeartFlow on behalf of Massachusetts General Hospital 
      (MGH) outside the submitted work. Dr Lu reported using the AstraZeneca computed 
      tomography core laboratory for clinical trials outside the submitted work. Dr 
      Taron reported receiving grants from Deutsche Forschungsgesellschaft during the 
      conduct of the study and personal fees from Siemens Healthcare outside the 
      submitted work. Dr Burdo reported holding equity in and serving as a member of 
      the scientific advisory board of Excision BioTherapuetics outside the submitted 
      work. Ms Fitch reported receiving travel support from the American College of 
      Cardiology and the Infectious Disease Society of America and personal fees from 
      Gilead Sciences outside the submitted work. Dr Fichtenbaum reported receiving 
      grants from ViiV Healthcare, Janssen Pharmaceuticals, Merck, CytoDyn, Amgen, and 
      Abbvie outside the submitted work. Dr Overton reported receiving personal fees 
      from Merck, ViiV Healthcare, and Theratechnologies outside the submitted work. Dr 
      Malvestutto reported participating in advisory board meetings for ViiV Healthcare 
      outside the submitted work. Dr Aberg reported receiving grants from Atea, ViiV 
      Healthcare, and Frontier Technology, institutional support for multicenter trials 
      from Gilead Sciences, Janssen Pharmaceuticals, Merck, and ViiV Healthcare, 
      serving on the scientific advisory boards of Gilead Sciences, Janssen 
      Pharmaceuticals, Merck, and ViiV Healthcare, personal fees from 
      Theratechnologies, and grants from Pfizer and Regeneron outside the submitted 
      work. Dr Currier reported serving as a scientific advisor for Merck outside the 
      submitted work. Dr Sponseller reported being employed by Kowa. Dr Melbourne 
      reported being employed by Gilead Sciences. Dr Ribaudo reported receiving grants 
      from the National Institutes of Health (NIH)/National Institute of Allergy and 
      Infectious Diseases (NIAID) and from the NIH/National Heart, Lung, and Blood 
      Institute (NHLBI) outside the submitted work. Dr Grinspoon reported receiving 
      personal and consulting fees from Theratechnologies and ViiV Healthcare outside 
      the submitted work. No other disclosures were reported.
FIR - Khodabakhshian, Aleen
IR  - Khodabakhshian A
FIR - Sbrolla, Amy
IR  - Sbrolla A
FIR - Sha, Beverly E
IR  - Sha BE
FIR - Costanza, Christie Lyn
IR  - Costanza CL
FIR - Hawkins, Claudia A
IR  - Hawkins CA
FIR - Reynolds, Connor
IR  - Reynolds C
FIR - Van Dam, Cornelius N
IR  - Van Dam CN
FIR - Berrner, Dan
IR  - Berrner D
FIR - Choi, David
IR  - Choi D
FIR - Nemeth, Jamie L
IR  - Nemeth JL
FIR - Jacobson, Jeffrey M
IR  - Jacobson JM
FIR - Gottesman, Joan
IR  - Gottesman J
FIR - Dwyer, John
IR  - Dwyer J
FIR - Koethe, John R
IR  - Koethe JR
FIR - Santana, Jorge L
IR  - Santana JL
FIR - Pasternak, Julie
IR  - Pasternak J
FIR - Ho, Ken S
IR  - Ho KS
FIR - Sobieszczyk, Magdalena E
IR  - Sobieszczyk ME
FIR - Mall, Mark
IR  - Mall M
FIR - Huaman, Moises S
IR  - Huaman MS
FIR - Truong, Quynh
IR  - Truong Q
FIR - Fry, Rebecca
IR  - Fry R
FIR - O'Donnell, Robert T
IR  - O'Donnell RT
FIR - Arduino, Roberto C
IR  - Arduino RC
FIR - Chinchay Collahua, Romina
IR  - Chinchay Collahua R
FIR - Barcavage, Shaun
IR  - Barcavage S
FIR - Swaminathan, Shobha
IR  - Swaminathan S
FIR - Perez-Frontera, Sigrid
IR  - Perez-Frontera S
FIR - Stroberg, Todd
IR  - Stroberg T
EDAT- 2021/06/30 06:00
MHDA- 2022/01/06 06:00
PMCR- 2021/06/29
CRDT- 2021/06/29 12:17
PHST- 2021/06/29 12:17 [entrez]
PHST- 2021/06/30 06:00 [pubmed]
PHST- 2022/01/06 06:00 [medline]
PHST- 2021/06/29 00:00 [pmc-release]
AID - 2781497 [pii]
AID - zoi210454 [pii]
AID - 10.1001/jamanetworkopen.2021.14923 [doi]
PST - epublish
SO  - JAMA Netw Open. 2021 Jun 1;4(6):e2114923. doi: 
      10.1001/jamanetworkopen.2021.14923.