Hemoglobin homeostasis in abdominal aortic aneurysm : diagnostic and prognostic potential of hemoglobin/heme and scavenger molecules
(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)
- 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
- 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
- © 2024. The Author(s).
- 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 < 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}}, }