title: The cross-sectional association between uric acid and atherosclerosis and the role of low-grade inflammation: the CODAM study.
abstract: OBJECTIVE
  The aims of this study were to investigate (i) associations between uric acid and prevalent cardiovascular disease (CVD), ankle-arm blood pressure index (AAIx) and carotid intima-media thickness (CIMT) in the total population and in predefined subgroups according to glucose metabolism status and (ii) the extent to which these associations are explained by low-grade inflammation.
  
  
  METHODS
  Cross-sectional analyses were conducted among 530 individuals [60.6% men, mean age 58.9 years (s.d. 6.9), 52.6% normal glucose metabolism (NGM)] at increased risk of CVD from the Cohort of Diabetes and Atherosclerosis Maastricht study. A low-grade inflammation score was computed by averaging the z-scores of eight inflammation markers [CRP, TNF-α, IL-6, IL-8, serum amyloid A, intercellular adhesion molecule 1 (ICAM-1), ceruloplasmin and haptoglobin].
  
  
  RESULTS
  After adjustment for traditional CVD risk factors, plasma uric acid (per s.d. of 81 μmol/l) was associated with CVD in individuals with NGM [odds ratio (OR) = 1.66, 95% CI 1.06, 2.58] but not with disturbed glucose metabolism (DGM) (OR = 0.81, 95% CI 0.55, 1.19, P interaction = 0.165). Uric acid was associated with CIMT in the total population (β = 0.024, 95% CI 0.007, 0.042) and slightly more strongly in individuals with NGM (β = 0.030, 95% CI 0.006, 0.054) than DGM (β = 0.018, 95% CI -0.009, 0.044, P interaction = 0.443). There was no association between uric acid and AAIx in any group (P interaction = 0.058). Uric acid was associated with low-grade inflammation in the total population (β = 0.074, 95% CI 0.013, 0.134, P interaction = 0.737). Adding low-grade inflammation to the models did not attenuate any of the associations.
  
  
  CONCLUSIONS
  The associations for uric acid with CIMT, and with CVD in NGM only, were not explained by low-grade inflammation. A difference in the strength of the associations between individuals with NGM and DGM was suggested.
authors.affiliation: Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands. j.wijnands@maastrichtuniversity.nl.
authors.forename: José M A
authors.initials: JM
authors.lastname: Wijnands
authors.affiliation: Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Annelies
authors.initials: A
authors.lastname: Boonen
authors.affiliation: Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dagnelie
authors.affiliation: Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Marleen M J
authors.initials: MM
authors.lastname: van Greevenbroek
authors.affiliation: Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Carla J H
authors.initials: CJ
authors.lastname: van der Kallen
authors.affiliation: Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Isabel
authors.initials: I
authors.lastname: Ferreira
authors.affiliation: Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.affiliation: Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Edith J M
authors.initials: EJ
authors.lastname: Feskens
authors.affiliation: Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.affiliation: Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Sjef
authors.initials: S
authors.lastname: van der Linden
authors.affiliation: Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Division of Rheumatology, Department of Medicine, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), Maastricht University, CARIM School for Cardiovascular Diseases, Maastricht University, Department of Epidemiology, Maastricht University, Department of Internal Medicine, Maastricht University Medical Centre, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht and Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Ilja C W
authors.initials: IC
authors.lastname: Arts
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D059168:Carotid Intima-Media Thickness; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*
chemical_list: D015415:Biomarkers; D014527:Uric Acid
keywords: ankle–arm blood pressure index; atherosclerosis; carotid intima-media thickness; glucose metabolism; inflammation; uric acid