TY - JOUR
T1 - Circulating biomarker correlates of left atrial size and myocardial extracellular volume fraction among persons living with and without HIV
AU - Peterson, Tess E.
AU - Landon, Christian
AU - Haberlen, Sabina A.
AU - Bhondoekhan, Fiona
AU - Plankey, Michael W.
AU - Palella, Frank J.
AU - Piggott, Damani A.
AU - Margolick, Joseph B.
AU - Brown, Todd T.
AU - Post, Wendy S.
AU - Wu, Katherine C.
N1 - Funding Information:
This study was funded by the United States National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI): R01 HL126552 (KCW and WSP) and U01-DA036297 (ALIVE data collection). Data in this manuscript collected by MACS and WIHS, now the MACS/WIHS Combined Cohort Study (MWCCS), was supported by the NIH: U01-HL146201, U01-HL146193, U01-HL146240, and U01-HL146205 (MACS, WIHS data collection). Full MWCCS acknowledgement may be found at https://statepi.jhsph.edu/mwccs/acknowledgements/ . TEP is supported by NIH/NHLBI Award Number T32 HL007227. TTB is supported in part by K24 AI120834. Architect i2000sR assays for galectin-3, high sensitivity troponin I, and N-terminal prohormone of brain natriuretic peptide were provided by Abbott under a research agreement. This work was also supported in part by a generous grant from Dr. Nancy Grasmick.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - Extracellular volume fraction
KW - Fibrosis
KW - Human immunodeficiency virus
KW - Inflammation
KW - Left atrial volume
KW - Myocardial disease
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U2 - 10.1186/s12872-022-02835-y
DO - 10.1186/s12872-022-02835-y
M3 - Article
C2 - 36057773
AN - SCOPUS:85137159797
SN - 1471-2261
VL - 22
JO - BMC Cardiovascular Disorders
JF - BMC Cardiovascular Disorders
IS - 1
M1 - 393
ER -