Low-grade endotoxemia and risk of recurrent thrombosis in primary antiphospholipid syndrome. The multicenter ATHERO-APS study
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/160674 |
Resumo: | Introduction: Low-grade endotoxemia is associated with systemic inflammation, enhanced oxidative stress and cardiovascular events in different clinical settings, but its possible role as “second hit” in patients with primary antiphospholipid syndrome (PAPS) has never been investigated. Purpose: To evaluate the relationship between plasma lipopolysaccharide (LPS) levels, oxidative stress markers and risk of thrombosis in the prospective multicenter ATHERO-APS study. Methods: Baseline LPS, soluble NADPH-oxidase 2-derived peptide (sNOX-dp), H2O2 production, hydrogen peroxide breakdown activity (HBA), and nitric oxide (NO) bioavailability were compared in 97 PAPS, 16 non-thrombotic aPL carriers and 21 controls (CTRL) matched for age and sex. Correlations among laboratory variables were explored by Rho Spearman's correlation (rS). Cox-regression analysis was performed to assess the association between LPS and risk for a composite outcome of cardiovascular death, venous and arterial thromboembolism. Results: In the whole cohort (median age 51 years (IQR 43–60), 72 % female), PAPS demonstrated higher levels of LPS, sNOX-dp and H2O2 and lower levels of NO and HBA compared to non-thrombotic aPL carriers and CTRL. LPS levels were inversely correlated with HBA (rS: −0.295, p = 0.001) and NO (rS: −0.322, p < 0.001) and directly correlated with sNOX-dp (rS:0.469, p < 0.001) and H202 (rS:0.282, p < 0.001). PAPS showed higher levels of LPS, sNOX-dp and H2O2 and lower levels of NO and HBA compared to aPL carriers and CTRL. After a 4.7 years follow-up of, 11 composite outcomes were reported in PAPS (2.5 per 100 patient-years) while none was observed in aPL carriers. On Cox-regression analysis, patients with LPS above the median (>23.1 pg/ml) had a 5-fold increased risk of composite outcome compared to those with LPS below the median, after adjustment for sex, age, diabetes, and global antiphospholipid syndrome score. Conclusion: Low-grade endotoxemia is associated with an increased oxidative stress and a higher risk of thrombosis in PAPS. Its prognostic value in carriers needs to be investigated in larger cohorts. |
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Low-grade endotoxemia and risk of recurrent thrombosis in primary antiphospholipid syndrome. The multicenter ATHERO-APS studyAntiphospholipid syndromeEndotoxemiaLipopolysaccharideThromboembolismHematologySDG 3 - Good Health and Well-beingIntroduction: Low-grade endotoxemia is associated with systemic inflammation, enhanced oxidative stress and cardiovascular events in different clinical settings, but its possible role as “second hit” in patients with primary antiphospholipid syndrome (PAPS) has never been investigated. Purpose: To evaluate the relationship between plasma lipopolysaccharide (LPS) levels, oxidative stress markers and risk of thrombosis in the prospective multicenter ATHERO-APS study. Methods: Baseline LPS, soluble NADPH-oxidase 2-derived peptide (sNOX-dp), H2O2 production, hydrogen peroxide breakdown activity (HBA), and nitric oxide (NO) bioavailability were compared in 97 PAPS, 16 non-thrombotic aPL carriers and 21 controls (CTRL) matched for age and sex. Correlations among laboratory variables were explored by Rho Spearman's correlation (rS). Cox-regression analysis was performed to assess the association between LPS and risk for a composite outcome of cardiovascular death, venous and arterial thromboembolism. Results: In the whole cohort (median age 51 years (IQR 43–60), 72 % female), PAPS demonstrated higher levels of LPS, sNOX-dp and H2O2 and lower levels of NO and HBA compared to non-thrombotic aPL carriers and CTRL. LPS levels were inversely correlated with HBA (rS: −0.295, p = 0.001) and NO (rS: −0.322, p < 0.001) and directly correlated with sNOX-dp (rS:0.469, p < 0.001) and H202 (rS:0.282, p < 0.001). PAPS showed higher levels of LPS, sNOX-dp and H2O2 and lower levels of NO and HBA compared to aPL carriers and CTRL. After a 4.7 years follow-up of, 11 composite outcomes were reported in PAPS (2.5 per 100 patient-years) while none was observed in aPL carriers. On Cox-regression analysis, patients with LPS above the median (>23.1 pg/ml) had a 5-fold increased risk of composite outcome compared to those with LPS below the median, after adjustment for sex, age, diabetes, and global antiphospholipid syndrome score. Conclusion: Low-grade endotoxemia is associated with an increased oxidative stress and a higher risk of thrombosis in PAPS. Its prognostic value in carriers needs to be investigated in larger cohorts.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNBucci, TommasoAmes, Paul R.J.Cammisotto, VittoriaCardamone, ChiaraCiampa, AntonioMangoni, BiancaTriggiani, MassimoCarnevale, RobertoLip, Gregory Y.H.Pastori, DanielePignatelli, Pasquale2023-11-28T22:37:49Z2023-112023-11-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article8application/pdfhttp://hdl.handle.net/10362/160674eng0049-3848PURE: 76751704https://doi.org/10.1016/j.thromres.2023.10.006info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:43:25Zoai:run.unl.pt:10362/160674Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:58:10.181181Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Low-grade endotoxemia and risk of recurrent thrombosis in primary antiphospholipid syndrome. The multicenter ATHERO-APS study |
title |
Low-grade endotoxemia and risk of recurrent thrombosis in primary antiphospholipid syndrome. The multicenter ATHERO-APS study |
spellingShingle |
Low-grade endotoxemia and risk of recurrent thrombosis in primary antiphospholipid syndrome. The multicenter ATHERO-APS study Bucci, Tommaso Antiphospholipid syndrome Endotoxemia Lipopolysaccharide Thromboembolism Hematology SDG 3 - Good Health and Well-being |
title_short |
Low-grade endotoxemia and risk of recurrent thrombosis in primary antiphospholipid syndrome. The multicenter ATHERO-APS study |
title_full |
Low-grade endotoxemia and risk of recurrent thrombosis in primary antiphospholipid syndrome. The multicenter ATHERO-APS study |
title_fullStr |
Low-grade endotoxemia and risk of recurrent thrombosis in primary antiphospholipid syndrome. The multicenter ATHERO-APS study |
title_full_unstemmed |
Low-grade endotoxemia and risk of recurrent thrombosis in primary antiphospholipid syndrome. The multicenter ATHERO-APS study |
title_sort |
Low-grade endotoxemia and risk of recurrent thrombosis in primary antiphospholipid syndrome. The multicenter ATHERO-APS study |
author |
Bucci, Tommaso |
author_facet |
Bucci, Tommaso Ames, Paul R.J. Cammisotto, Vittoria Cardamone, Chiara Ciampa, Antonio Mangoni, Bianca Triggiani, Massimo Carnevale, Roberto Lip, Gregory Y.H. Pastori, Daniele Pignatelli, Pasquale |
author_role |
author |
author2 |
Ames, Paul R.J. Cammisotto, Vittoria Cardamone, Chiara Ciampa, Antonio Mangoni, Bianca Triggiani, Massimo Carnevale, Roberto Lip, Gregory Y.H. Pastori, Daniele Pignatelli, Pasquale |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) RUN |
dc.contributor.author.fl_str_mv |
Bucci, Tommaso Ames, Paul R.J. Cammisotto, Vittoria Cardamone, Chiara Ciampa, Antonio Mangoni, Bianca Triggiani, Massimo Carnevale, Roberto Lip, Gregory Y.H. Pastori, Daniele Pignatelli, Pasquale |
dc.subject.por.fl_str_mv |
Antiphospholipid syndrome Endotoxemia Lipopolysaccharide Thromboembolism Hematology SDG 3 - Good Health and Well-being |
topic |
Antiphospholipid syndrome Endotoxemia Lipopolysaccharide Thromboembolism Hematology SDG 3 - Good Health and Well-being |
description |
Introduction: Low-grade endotoxemia is associated with systemic inflammation, enhanced oxidative stress and cardiovascular events in different clinical settings, but its possible role as “second hit” in patients with primary antiphospholipid syndrome (PAPS) has never been investigated. Purpose: To evaluate the relationship between plasma lipopolysaccharide (LPS) levels, oxidative stress markers and risk of thrombosis in the prospective multicenter ATHERO-APS study. Methods: Baseline LPS, soluble NADPH-oxidase 2-derived peptide (sNOX-dp), H2O2 production, hydrogen peroxide breakdown activity (HBA), and nitric oxide (NO) bioavailability were compared in 97 PAPS, 16 non-thrombotic aPL carriers and 21 controls (CTRL) matched for age and sex. Correlations among laboratory variables were explored by Rho Spearman's correlation (rS). Cox-regression analysis was performed to assess the association between LPS and risk for a composite outcome of cardiovascular death, venous and arterial thromboembolism. Results: In the whole cohort (median age 51 years (IQR 43–60), 72 % female), PAPS demonstrated higher levels of LPS, sNOX-dp and H2O2 and lower levels of NO and HBA compared to non-thrombotic aPL carriers and CTRL. LPS levels were inversely correlated with HBA (rS: −0.295, p = 0.001) and NO (rS: −0.322, p < 0.001) and directly correlated with sNOX-dp (rS:0.469, p < 0.001) and H202 (rS:0.282, p < 0.001). PAPS showed higher levels of LPS, sNOX-dp and H2O2 and lower levels of NO and HBA compared to aPL carriers and CTRL. After a 4.7 years follow-up of, 11 composite outcomes were reported in PAPS (2.5 per 100 patient-years) while none was observed in aPL carriers. On Cox-regression analysis, patients with LPS above the median (>23.1 pg/ml) had a 5-fold increased risk of composite outcome compared to those with LPS below the median, after adjustment for sex, age, diabetes, and global antiphospholipid syndrome score. Conclusion: Low-grade endotoxemia is associated with an increased oxidative stress and a higher risk of thrombosis in PAPS. Its prognostic value in carriers needs to be investigated in larger cohorts. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-11-28T22:37:49Z 2023-11 2023-11-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/160674 |
url |
http://hdl.handle.net/10362/160674 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0049-3848 PURE: 76751704 https://doi.org/10.1016/j.thromres.2023.10.006 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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8 application/pdf |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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