Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Hemoglobin homeostasis in abdominal aortic aneurysm : diagnostic and prognostic potential of hemoglobin/heme and scavenger molecules

Vats, Sakshi LU ; Sundquist, Kristina LU ; Grundberg, Anton LU ; Sundquist, Jan LU ; Wang, Xiao LU ; Zarrouk, Moncef LU ; Gottsäter, Anders LU and Memon, Ashfaque A LU orcid (2024) In BMC Cardiovascular Disorders 24(1).
Abstract

BACKGROUND: There is increasing evidence implicating hemoglobin/heme and their scavengers in oxidative stress-mediated pathologies, but information is limited in abdominal aortic aneurysm (AAA).

METHODS AND RESULTS: In this case-control study, we assessed heme/heme-related markers in 142 men with AAA and 279 men with a normal aortic diameter consecutively recruited from an ultrasound screening program in Sweden. Enzyme-linked immunosorbent assays (ELISAs) were used to measure heme oxygenase-1 (HO-1) and hemopexin (Hpx) plasma levels, colorimetric assays for cell-free heme and whole blood hemoglobin (Hb) levels, and droplet digital PCR (ddPCR) and real-time PCR to determine haptoglobin (Hp) (pheno)type and genotype, respectively.... (More)

BACKGROUND: There is increasing evidence implicating hemoglobin/heme and their scavengers in oxidative stress-mediated pathologies, but information is limited in abdominal aortic aneurysm (AAA).

METHODS AND RESULTS: In this case-control study, we assessed heme/heme-related markers in 142 men with AAA and 279 men with a normal aortic diameter consecutively recruited from an ultrasound screening program in Sweden. Enzyme-linked immunosorbent assays (ELISAs) were used to measure heme oxygenase-1 (HO-1) and hemopexin (Hpx) plasma levels, colorimetric assays for cell-free heme and whole blood hemoglobin (Hb) levels, and droplet digital PCR (ddPCR) and real-time PCR to determine haptoglobin (Hp) (pheno)type and genotype, respectively. Hpx and heme plasma levels at baseline were elevated, while HO-1 levels were lower in men with AAA (p < 0.001) and were significantly associated with AAA prevalence independently of potential confounders. A combination of heme and HO-1 showed the best diagnostic potential based on the area under the curve (AUC): 0.76, sensitivity: 80%, specificity: 48%. Additionally, when previously described inflammatory biomarker interleukin-6 (IL-6), was added to our model it significantly improved the diagnostic value (AUC: 0.87, sensitivity: 80%, specificity: 79%) compared to IL-6 alone (AUC: 0.73, sensitivity: 80%, specificity: 49%). Finally, Hb (positively) and Hpx (negatively) levels at baseline were associated with AAA growth rate (mm/year), and their combination showed the best prognostic value for discriminating fast and slow-growing AAA (AUC: 0.76, sensitivity: 80%, specificity: 62%).

CONCLUSIONS: This study reports the distinct disruption of heme and related markers in both the development and progression of AAA, underscoring their potential in aiding risk stratification and therapeutic strategies.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Aortic Aneurysm, Abdominal/blood, Male, Biomarkers/blood, Heme Oxygenase-1/blood, Aged, Case-Control Studies, Hemopexin, Heme, Haptoglobins/analysis, Middle Aged, Sweden/epidemiology, Hemoglobins/metabolism, Prognosis, Predictive Value of Tests, Homeostasis, Interleukin-6/blood, Enzyme-Linked Immunosorbent Assay
in
BMC Cardiovascular Disorders
volume
24
issue
1
article number
452
publisher
BioMed Central (BMC)
external identifiers
  • pmid:39192217
  • scopus:85202468151
ISSN
1471-2261
DOI
10.1186/s12872-024-04131-3
language
English
LU publication?
yes
additional info
© 2024. The Author(s).
id
fca19bc6-3eaa-4b85-92a9-0f6accd2b804
date added to LUP
2024-09-02 13:22:16
date last changed
2025-05-14 02:52:57
@article{fca19bc6-3eaa-4b85-92a9-0f6accd2b804,
  abstract     = {{<p>BACKGROUND: There is increasing evidence implicating hemoglobin/heme and their scavengers in oxidative stress-mediated pathologies, but information is limited in abdominal aortic aneurysm (AAA).</p><p>METHODS AND RESULTS: In this case-control study, we assessed heme/heme-related markers in 142 men with AAA and 279 men with a normal aortic diameter consecutively recruited from an ultrasound screening program in Sweden. Enzyme-linked immunosorbent assays (ELISAs) were used to measure heme oxygenase-1 (HO-1) and hemopexin (Hpx) plasma levels, colorimetric assays for cell-free heme and whole blood hemoglobin (Hb) levels, and droplet digital PCR (ddPCR) and real-time PCR to determine haptoglobin (Hp) (pheno)type and genotype, respectively. Hpx and heme plasma levels at baseline were elevated, while HO-1 levels were lower in men with AAA (p &lt; 0.001) and were significantly associated with AAA prevalence independently of potential confounders. A combination of heme and HO-1 showed the best diagnostic potential based on the area under the curve (AUC): 0.76, sensitivity: 80%, specificity: 48%. Additionally, when previously described inflammatory biomarker interleukin-6 (IL-6), was added to our model it significantly improved the diagnostic value (AUC: 0.87, sensitivity: 80%, specificity: 79%) compared to IL-6 alone (AUC: 0.73, sensitivity: 80%, specificity: 49%). Finally, Hb (positively) and Hpx (negatively) levels at baseline were associated with AAA growth rate (mm/year), and their combination showed the best prognostic value for discriminating fast and slow-growing AAA (AUC: 0.76, sensitivity: 80%, specificity: 62%).</p><p>CONCLUSIONS: This study reports the distinct disruption of heme and related markers in both the development and progression of AAA, underscoring their potential in aiding risk stratification and therapeutic strategies.</p>}},
  author       = {{Vats, Sakshi and Sundquist, Kristina and Grundberg, Anton and Sundquist, Jan and Wang, Xiao and Zarrouk, Moncef and Gottsäter, Anders and Memon, Ashfaque A}},
  issn         = {{1471-2261}},
  keywords     = {{Humans; Aortic Aneurysm, Abdominal/blood; Male; Biomarkers/blood; Heme Oxygenase-1/blood; Aged; Case-Control Studies; Hemopexin; Heme; Haptoglobins/analysis; Middle Aged; Sweden/epidemiology; Hemoglobins/metabolism; Prognosis; Predictive Value of Tests; Homeostasis; Interleukin-6/blood; Enzyme-Linked Immunosorbent Assay}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Cardiovascular Disorders}},
  title        = {{Hemoglobin homeostasis in abdominal aortic aneurysm : diagnostic and prognostic potential of hemoglobin/heme and scavenger molecules}},
  url          = {{http://dx.doi.org/10.1186/s12872-024-04131-3}},
  doi          = {{10.1186/s12872-024-04131-3}},
  volume       = {{24}},
  year         = {{2024}},
}