Circulating biomarker correlates of left atrial size and myocardial extracellular volume fraction among persons living with and without HIV.


Journal

BMC cardiovascular disorders
ISSN: 1471-2261
Titre abrégé: BMC Cardiovasc Disord
Pays: England
ID NLM: 100968539

Informations de publication

Date de publication:
03 09 2022
Historique:
received: 05 07 2022
accepted: 26 08 2022
entrez: 3 9 2022
pubmed: 4 9 2022
medline: 9 9 2022
Statut: epublish

Résumé

Infection with human immunodeficiency virus (HIV) is associated with higher risk for myocardial disease despite modern combination antiretroviral therapy (cART). Factors contributing to this excess risk, however, remain poorly characterized. We aimed to assess cross-sectional relationships between elevations of left atrial volume index (LAVI) and myocardial extracellular volume (ECV) fraction that have been reported in persons living with HIV and levels of circulating biomarkers of inflammation, fibrosis, and myocyte stretch among persons living with and without HIV (PLWH, PLWOH). Participants from three cohorts of PLWH and PLWOH underwent cardiovascular magnetic resonance imaging for measurement of LAVI and ECV. Levels of circulating proteins (IL-6, sCD14, galectin-3, NT-proBNP, GDF-15, TIMP-2, MMP-2, and hsTnI) were measured using immunoassays. Associations were assessed using logistic and linear regression, adjusting for demographics, substance use, and clinical characteristics. Among 381 participants with and without HIV, median age (IQR) was 55.1 (51.2, 58.4) years, 28% were female, 69% were Black, and 46% were current smokers. Sixty-two percent were PLWH (n = 235), of whom 88% were receiving cART and 72% were virally suppressed. PLWH had higher levels of sCD14 (p = < 0.001), GDF-15 (p = < 0.001), and NT-proBNP (p = 0.03) compared to PLWOH, while levels of other biomarkers did not differ by HIV serostatus, including IL-6 (p = 0.84). Among PLWH, higher sCD14, GDF-15, and NT-proBNP were also associated with lower CD4 + cell count, and higher NT-proBNP was associated with detectable HIV viral load. NT-proBNP was associated with elevated LAVI (OR: 1.79 [95% CI: 1.31, 2.44]; p < 0.001) with no evidence of effect measure modification by HIV serostatus. Other associations between HIV-associated biomarkers and LAVI or ECV were small or imprecise. Our findings suggest that elevated levels of sCD14, GDF-15, and NT-proBNP among PLWH compared to PLWOH observed in the current cART era may only minimally reflect HIV-associated elevations in LAVI and ECV. Future studies of excess risk of myocardial disease among contemporary cohorts of PLWH should investigate mechanisms other than those connoted by the studied biomarkers.

Sections du résumé

BACKGROUND
Infection with human immunodeficiency virus (HIV) is associated with higher risk for myocardial disease despite modern combination antiretroviral therapy (cART). Factors contributing to this excess risk, however, remain poorly characterized. We aimed to assess cross-sectional relationships between elevations of left atrial volume index (LAVI) and myocardial extracellular volume (ECV) fraction that have been reported in persons living with HIV and levels of circulating biomarkers of inflammation, fibrosis, and myocyte stretch among persons living with and without HIV (PLWH, PLWOH).
METHODS
Participants from three cohorts of PLWH and PLWOH underwent cardiovascular magnetic resonance imaging for measurement of LAVI and ECV. Levels of circulating proteins (IL-6, sCD14, galectin-3, NT-proBNP, GDF-15, TIMP-2, MMP-2, and hsTnI) were measured using immunoassays. Associations were assessed using logistic and linear regression, adjusting for demographics, substance use, and clinical characteristics.
RESULTS
Among 381 participants with and without HIV, median age (IQR) was 55.1 (51.2, 58.4) years, 28% were female, 69% were Black, and 46% were current smokers. Sixty-two percent were PLWH (n = 235), of whom 88% were receiving cART and 72% were virally suppressed. PLWH had higher levels of sCD14 (p = < 0.001), GDF-15 (p = < 0.001), and NT-proBNP (p = 0.03) compared to PLWOH, while levels of other biomarkers did not differ by HIV serostatus, including IL-6 (p = 0.84). Among PLWH, higher sCD14, GDF-15, and NT-proBNP were also associated with lower CD4 + cell count, and higher NT-proBNP was associated with detectable HIV viral load. NT-proBNP was associated with elevated LAVI (OR: 1.79 [95% CI: 1.31, 2.44]; p < 0.001) with no evidence of effect measure modification by HIV serostatus. Other associations between HIV-associated biomarkers and LAVI or ECV were small or imprecise.
CONCLUSIONS
Our findings suggest that elevated levels of sCD14, GDF-15, and NT-proBNP among PLWH compared to PLWOH observed in the current cART era may only minimally reflect HIV-associated elevations in LAVI and ECV. Future studies of excess risk of myocardial disease among contemporary cohorts of PLWH should investigate mechanisms other than those connoted by the studied biomarkers.

Identifiants

pubmed: 36057773
doi: 10.1186/s12872-022-02835-y
pii: 10.1186/s12872-022-02835-y
pmc: PMC9441072
doi:

Substances chimiques

Biomarkers 0
Growth Differentiation Factor 15 0
Interleukin-6 0
Lipopolysaccharide Receptors 0
Peptide Fragments 0
Natriuretic Peptide, Brain 114471-18-0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

393

Subventions

Organisme : NHLBI NIH HHS
ID : U01 HL146205
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL126552
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007227
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA036297
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146201
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146193
Pays : United States
Organisme : NIAID NIH HHS
ID : K24 AI120834
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146240
Pays : United States

Informations de copyright

© 2022. The Author(s).

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Auteurs

Tess E Peterson (TE)

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. tpeter34@jhmi.edu.

Christian Landon (C)

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Sabina A Haberlen (SA)

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Fiona Bhondoekhan (F)

Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA.

Michael W Plankey (MW)

Department of Medicine, Georgetown University Medical Center, Washington, DC, USA.

Frank J Palella (FJ)

Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Damani A Piggott (DA)

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Joseph B Margolick (JB)

Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Todd T Brown (TT)

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Wendy S Post (WS)

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Katherine C Wu (KC)

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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Classifications MeSH