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

Vats, Sakshi; Sundquist, Kristina; Grundberg, Anton; Sundquist, Jan; Wang, Xiao; Zarrouk, Moncef; Gottsäter, Anders; Memon, Ashfaque A

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

Mark

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

(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: https://lup.lub.lu.se/record/fca19bc6-3eaa-4b85-92a9-0f6accd2b804

author

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

organization

publishing date

2024-08-27

type

Contribution to journal

publication status

published

subject

Cardiac and Cardiovascular Systems

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

scopus:85202468151
pmid:39192217

ISSN

1471-2261

DOI

10.1186/s12872-024-04131-3

language

English

LU publication?

yes

additional info

id

fca19bc6-3eaa-4b85-92a9-0f6accd2b804

date added to LUP

2024-09-02 13:22:16

date last changed

2024-09-03 04:00:43

@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}},
}

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