Frontiers in Immunology (Feb 2023)

Aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with HIV

  • Sylvester Klöcker Grønbæk,
  • Julie Høgh,
  • Andreas Dehlbæk Knudsen,
  • Michael Huy Cuong Pham,
  • Per Ejlstrup Sigvardsen,
  • Andreas Fuchs,
  • Jørgen Tobias Kühl,
  • Lars Køber,
  • Lars Køber,
  • Jan Gerstoft,
  • Jan Gerstoft,
  • Thomas Benfield,
  • Sisse Rye Ostrowski,
  • Sisse Rye Ostrowski,
  • Klaus Fuglsang Kofoed,
  • Klaus Fuglsang Kofoed,
  • Klaus Fuglsang Kofoed,
  • Susanne Dam Nielsen,
  • Susanne Dam Nielsen

DOI
https://doi.org/10.3389/fimmu.2023.1115894
Journal volume & issue
Vol. 14

Abstract

Read online

IntroductionPeople living with HIV (PLWH) are at twice the risk of developing cardiovascular diseases and have more than four times higher odds of aortic aneurysm (AA) than the uninfected population. However, biomarkers of AA in PLWH are yet to be discovered. We aimed to investigate whether circulating biomarkers reflecting platelet activation, hemostasis and endothelial disruption, i.e. sCD40L, D-dimer, syndecan-1, and thrombomodulin, were associated with AA in PLWH.MethodsFive hundred seventy one PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study ≥40 years of age with an available contrast-enhanced CT scan as well as available biomarker analyses were included. The biomarkers were analyzed on thawed plasma. For each biomarker, we defined high level as a concentration in the upper quartile and low level as a concentration below the upper quartile. For D-dimer, the cut-off was defined as the lower limit of detection. Using unadjusted and adjusted logistic and linear regression models, we analyzed associations between AA and sCD40L, D-dimer, syndecan-1, and thrombomodulin, respectively in PLWH.ResultsPLWH had median (IQR) age 52 years (47-60), 88% were male, median (IQR) time since HIV diagnosis was 15 years (8-23), and 565 (99%) were currently on antiretroviral treatment. High level of sCD40L was associated with lower odds of AA in both unadjusted (odds ratio, OR, 0.23 (95% CI 0.07-0.77; P=0.017)) and adjusted models (adjusted OR, aOR, 0.23 (95% CI 0.07-0.78; P=0.019)). Detectable level of D-dimer was associated with higher odds of AA in both unadjusted (OR 2.76 (95% CI 1.34-5.67; P=0.006)) and adjusted models (aOR 2.22 (95% CI 1.02-4.85; P=0.045)).ConclusionsSCD40L was associated with lower odds of AA whereas D-dimer was independently associated with higher odds of AA in PLWH. This calls for further investigations into specific biomarkers to aid early diagnosis of AA in PLWH.

Keywords