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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.

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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
2025-10-15 18:13:51
@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}},
}