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Enhanced status of inflammation and endothelial activation in subjects with familial hypercholesterolaemia and their related unaffected family members: a case control study

BACKGROUND: Familial hypercholesterolaemia (FH) leads to premature coronary artery diseases (CAD) which pathophysiologically can be measured by inflammation, endothelial activation and oxidative stress status. However, the status of these biomarkers among related unaffected relatives of FH cases and...

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Autores principales: Rahman, Thuhairah, Hamzan, Nur Suhana, Mokhsin, Atiqah, Rahmat, Radzi, Ibrahim, Zubin Othman, Razali, Rafezah, Thevarajah, Malathi, Nawawi, Hapizah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404314/
https://www.ncbi.nlm.nih.gov/pubmed/28438163
http://dx.doi.org/10.1186/s12944-017-0470-1
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author Rahman, Thuhairah
Hamzan, Nur Suhana
Mokhsin, Atiqah
Rahmat, Radzi
Ibrahim, Zubin Othman
Razali, Rafezah
Thevarajah, Malathi
Nawawi, Hapizah
author_facet Rahman, Thuhairah
Hamzan, Nur Suhana
Mokhsin, Atiqah
Rahmat, Radzi
Ibrahim, Zubin Othman
Razali, Rafezah
Thevarajah, Malathi
Nawawi, Hapizah
author_sort Rahman, Thuhairah
collection PubMed
description BACKGROUND: Familial hypercholesterolaemia (FH) leads to premature coronary artery diseases (CAD) which pathophysiologically can be measured by inflammation, endothelial activation and oxidative stress status. However, the status of these biomarkers among related unaffected relatives of FH cases and whether FH is an independent predictor of these biomarkers have not been well established. Thus, this study aims to (1) compare the biomarkers of inflammation, endothelial activation and oxidative stress between patients with FH, their related unaffected relatives (RUC) and normolipaemic subjects (NC) (2)determine whether FH is an independent predictor of these biomarkers. METHODS: One hundred thirty-one FH patients, 68 RUC and 214 matched NC were recruited. Fasting lipid profile, biomarkers of inflammation (hsCRP), endothelial activation (sICAM-1 and E-selectin) and oxidative stress [oxidized LDL (oxLDL), malondialdehyde (MDA) and F2-isoprostanes (ISP)] were analyzed and independent predictor was determined using binary logistic regression analysis. RESULTS: hsCRP was higher in FH and RUC compared to NC (mean ± SD = 1.53 ± 1.24 mg/L and mean ± SD = 2.54 ± 2.30 vs 1.10 ± 0.89 mg/L, p < 0.05). sICAM-1 and E-selectin were higher in FH compared to NC (mean ± SD = 947 ± 742 vs 655 ± 191 ng/mL, p < 0.001 and 175 ± 131 vs 21.6 ± 10.7 ng/mL, p < 0.001 respectively) while sICAM-1 concentration was higher in RUC compared to NC (mean ± SD = 945 ± 379 vs 655 ± 191 ng/mL, p < 0.01). Biomarkers of oxidation (ox-LDL, MDA and ISP) were elevated in FH compared to NC [mean ± SD = (48.2 ± 26.8 vs 27.3 ± 13.2 mU/L, p < 0.001), (2.57 ± 1.3 vs 1.20 ± 0.30 nmol/mL, p < 0.001) and (645 ± 396 vs 398 ± 20.5 pg/L, p < 0.001) respectively], but no significant differences were observed between RUC and NC (p > 0.05). FH was an independent predictor for sICAM-1 (p = 0.007), ox-LDL (p < 0.001) and MDA (p < 0.001) while RUC independently predicted for sICAM-1 (p < 0.001). CONCLUSION: The screening for FH is vital as all biomarkers associated with atherogenesis are higher in these subjects and FH also independently predict biomarkers of endothelial activation and oxidative stress. Furthermore, despite not fulfilling the diagnostic criteria for FH, related unaffected family members that may not phenotypically express the mutation may still be at risk of developing CAD as reflected from the enhanced inflammatory and endothelial activation status observed in this group. This highlights the need to not only conduct family tracing in indexed FH cases, but also assess the coronary risk among family members that do not fulfil the FH diagnostic criteria.
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spelling pubmed-54043142017-04-27 Enhanced status of inflammation and endothelial activation in subjects with familial hypercholesterolaemia and their related unaffected family members: a case control study Rahman, Thuhairah Hamzan, Nur Suhana Mokhsin, Atiqah Rahmat, Radzi Ibrahim, Zubin Othman Razali, Rafezah Thevarajah, Malathi Nawawi, Hapizah Lipids Health Dis Research BACKGROUND: Familial hypercholesterolaemia (FH) leads to premature coronary artery diseases (CAD) which pathophysiologically can be measured by inflammation, endothelial activation and oxidative stress status. However, the status of these biomarkers among related unaffected relatives of FH cases and whether FH is an independent predictor of these biomarkers have not been well established. Thus, this study aims to (1) compare the biomarkers of inflammation, endothelial activation and oxidative stress between patients with FH, their related unaffected relatives (RUC) and normolipaemic subjects (NC) (2)determine whether FH is an independent predictor of these biomarkers. METHODS: One hundred thirty-one FH patients, 68 RUC and 214 matched NC were recruited. Fasting lipid profile, biomarkers of inflammation (hsCRP), endothelial activation (sICAM-1 and E-selectin) and oxidative stress [oxidized LDL (oxLDL), malondialdehyde (MDA) and F2-isoprostanes (ISP)] were analyzed and independent predictor was determined using binary logistic regression analysis. RESULTS: hsCRP was higher in FH and RUC compared to NC (mean ± SD = 1.53 ± 1.24 mg/L and mean ± SD = 2.54 ± 2.30 vs 1.10 ± 0.89 mg/L, p < 0.05). sICAM-1 and E-selectin were higher in FH compared to NC (mean ± SD = 947 ± 742 vs 655 ± 191 ng/mL, p < 0.001 and 175 ± 131 vs 21.6 ± 10.7 ng/mL, p < 0.001 respectively) while sICAM-1 concentration was higher in RUC compared to NC (mean ± SD = 945 ± 379 vs 655 ± 191 ng/mL, p < 0.01). Biomarkers of oxidation (ox-LDL, MDA and ISP) were elevated in FH compared to NC [mean ± SD = (48.2 ± 26.8 vs 27.3 ± 13.2 mU/L, p < 0.001), (2.57 ± 1.3 vs 1.20 ± 0.30 nmol/mL, p < 0.001) and (645 ± 396 vs 398 ± 20.5 pg/L, p < 0.001) respectively], but no significant differences were observed between RUC and NC (p > 0.05). FH was an independent predictor for sICAM-1 (p = 0.007), ox-LDL (p < 0.001) and MDA (p < 0.001) while RUC independently predicted for sICAM-1 (p < 0.001). CONCLUSION: The screening for FH is vital as all biomarkers associated with atherogenesis are higher in these subjects and FH also independently predict biomarkers of endothelial activation and oxidative stress. Furthermore, despite not fulfilling the diagnostic criteria for FH, related unaffected family members that may not phenotypically express the mutation may still be at risk of developing CAD as reflected from the enhanced inflammatory and endothelial activation status observed in this group. This highlights the need to not only conduct family tracing in indexed FH cases, but also assess the coronary risk among family members that do not fulfil the FH diagnostic criteria. BioMed Central 2017-04-24 /pmc/articles/PMC5404314/ /pubmed/28438163 http://dx.doi.org/10.1186/s12944-017-0470-1 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Rahman, Thuhairah
Hamzan, Nur Suhana
Mokhsin, Atiqah
Rahmat, Radzi
Ibrahim, Zubin Othman
Razali, Rafezah
Thevarajah, Malathi
Nawawi, Hapizah
Enhanced status of inflammation and endothelial activation in subjects with familial hypercholesterolaemia and their related unaffected family members: a case control study
title Enhanced status of inflammation and endothelial activation in subjects with familial hypercholesterolaemia and their related unaffected family members: a case control study
title_full Enhanced status of inflammation and endothelial activation in subjects with familial hypercholesterolaemia and their related unaffected family members: a case control study
title_fullStr Enhanced status of inflammation and endothelial activation in subjects with familial hypercholesterolaemia and their related unaffected family members: a case control study
title_full_unstemmed Enhanced status of inflammation and endothelial activation in subjects with familial hypercholesterolaemia and their related unaffected family members: a case control study
title_short Enhanced status of inflammation and endothelial activation in subjects with familial hypercholesterolaemia and their related unaffected family members: a case control study
title_sort enhanced status of inflammation and endothelial activation in subjects with familial hypercholesterolaemia and their related unaffected family members: a case control study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404314/
https://www.ncbi.nlm.nih.gov/pubmed/28438163
http://dx.doi.org/10.1186/s12944-017-0470-1
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