title: Low serum high density lipoprotein cholesterol concentration is an independent predictor for enhanced inflammation and endothelial activation.
abstract: BACKGROUND
  Inflammation, endothelial activation and oxidative stress have been established as key events in the initiation and progression of atherosclerosis. High-density lipoprotein cholesterol (HDL-c) is protective against atherosclerosis and coronary heart disease, but its association with inflammation, endothelial activation and oxidative stress is not well established.
  
  
  OBJECTIVE
  (1) To compare the concentrations of biomarkers of inflammation, endothelial activation and oxidative stress in subjects with low HDL-c compared to normal HDL-c; (2) To examine the association and correlation between HDL-c and these biomarkers and (3) To determine whether HDL-c is an independent predictor of these biomarkers.
  
  
  METHODS
  422 subjects (mean age±SD = 43.2±11.9 years) of whom 207 had low HDL-c concentrations (HDL-c <1.0 mmol/L and <1.3 mmol/L for males and females respectively) and 215 normal controls (HDL-c ≥1.0 and ≥1.3 mmol/L for males and females respectively) were recruited in this study. The groups were matched for age, gender, ethnicity, smoking status, diabetes mellitus and hypertension. Fasting blood samples were collected for analysis of biomarkers of inflammation [high-sensitivity C-reactive protein (hsCRP) and Interleukin-6 (IL-6)], endothelial activation [soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), soluble Intercellular Adhesion Molecule-1 (sICAM-1) and E-selectin)] and oxidative stress [F2-Isoprostanes, oxidized Low Density Lipoprotein (ox-LDL) and Malondialdehyde (MDA)].
  
  
  RESULTS
  Subjects with low HDL-c had greater concentrations of inflammation, endothelial activation and oxidative stress biomarkers compared to controls. There were negative correlations between HDL-c concentration and biomarkers of inflammation (IL-6, p = 0.02), endothelial activation (sVCAM-1 and E-selectin, p = 0.029 and 0.002, respectively), and oxidative stress (MDA and F2-isoprostane, p = 0.036 and <0.0001, respectively). Multiple linear regression analysis showed HDL-c as an independent predictor of IL-6 (p = 0.02) and sVCAM-1 (p<0.03) after correcting for various confounding factors.
  
  
  CONCLUSIONS
  Low serum HDL-c concentration is strongly correlated with enhanced status of inflammation, endothelial activation and oxidative stress. It is also an independent predictor for enhanced inflammation and endothelial activation, which are pivotal in the pathogenesis of atherosclerosis and atherosclerosis-related complications.
authors.affiliation: Centre for Pathology Diagnostic and Research Laboratories (CPDRL), UniversitiTeknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia.
authors.forename: Wan Nor Hanis
authors.initials: WN
authors.lastname: Wan Ahmad
authors.affiliation: Centre for Pathology Diagnostic and Research Laboratories (CPDRL), UniversitiTeknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia.
authors.forename: Farah
authors.initials: F
authors.lastname: Sakri
authors.affiliation: Centre for Pathology Diagnostic and Research Laboratories (CPDRL), UniversitiTeknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia.
authors.forename: Atiqah
authors.initials: A
authors.lastname: Mokhsin
authors.affiliation: Centre for Pathology Diagnostic and Research Laboratories (CPDRL), UniversitiTeknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia; Cluster for Pathology and Laboratory Medicine, UniversitiTeknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia.
authors.forename: Thuhairah
authors.initials: T
authors.lastname: Rahman
authors.affiliation: Centre for Pathology Diagnostic and Research Laboratories (CPDRL), UniversitiTeknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia; Cluster for Pathology and Laboratory Medicine, UniversitiTeknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia.
authors.forename: Nadzimah
authors.initials: N
authors.lastname: Mohd Nasir
authors.affiliation: Primary Care Medicine Discipline, UniversitiTeknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia.
authors.forename: Suraya
authors.initials: S
authors.lastname: Abdul-Razak
authors.affiliation: Primary Care Medicine Discipline, UniversitiTeknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia.
authors.forename: Mazapuspavina
authors.initials: M
authors.lastname: Md Yasin
authors.affiliation: Centre for Pathology Diagnostic and Research Laboratories (CPDRL), UniversitiTeknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia; Cluster for Pathology and Laboratory Medicine, UniversitiTeknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia.
authors.forename: Aletza
authors.initials: A
authors.lastname: Mohd Ismail
authors.affiliation: Discipline of Population Health and Preventive Medicine, Faculty of Medicine, UniversitiTeknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia.
authors.forename: Zaliha
authors.initials: Z
authors.lastname: Ismail
authors.affiliation: Centre for Pathology Diagnostic and Research Laboratories (CPDRL), UniversitiTeknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia; Cluster for Pathology and Laboratory Medicine, UniversitiTeknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia.
authors.forename: Hapizah
authors.initials: H
authors.lastname: Nawawi
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; C508600:IL6 protein, human; D015850:Interleukin-6; D019010:Vascular Cell Adhesion Molecule-1; D002097:C-Reactive Protein