title: Clinical correlates of change in inflammatory biomarkers: The Framingham Heart Study.
abstract: OBJECTIVE
  Traditional clinical risk factors are associated with inflammation cross-sectionally, but associations of longitudinal variation in inflammatory biomarkers with corresponding changes in clinical risk factors are incompletely described. We sought to analyze clinical factors associated with change in inflammation in the community.
  
  
  METHODS
  We studied 3013 Framingham Offspring (n = 2735) and Omni Cohort (n = 278) participants (mean age 59 years, 55% women, 9% ethnic/racial minority) who attended two consecutive examination cycles (mean 6.7 years apart). We selected ten inflammatory biomarkers representing distinctive biological functions: C-reactive protein (CRP), intercellular adhesion molecule-1, interleukin-6, isoprostanes, lipoprotein-associated phospholipase-2 (Lp-PLA2) activity, Lp-PLA2-mass, monocyte chemoattractant protein-1, osteoprotegerin, P-selectin, and tumor necrosis factor receptor II (TNFRII). We constructed multivariable-adjusted regression models to assess the relations of baseline, follow-up and change in clinical risk factors with change in biomarker concentrations over time.
  
  
  RESULTS
  Baseline, follow-up and change in clinical risk factors explain a moderate amount of the variation in biomarker concentrations across 2 consecutive examinations (ranging from r(2) = 0.28 [TNFRII] up to 0.52 [Lp-PLA2-mass]). In multivariable models, increasing body-mass index, smoking initiation, worsening lipid profile, and increasing waist size were associated with increasing concentrations of several biomarkers. Conversely, hypercholesterolemia therapy and hormone replacement cessation were associated with decreasing concentrations of biomarkers such as CRP, Lp-PLA2-mass and activity.
  
  
  CONCLUSIONS
  Cardiovascular risk factors have different patterns of association with longitudinal change in inflammatory biomarkers and explain modest amounts of variability in biomarker concentrations. Nevertheless, a substantial proportion of longitudinal change in inflammatory markers is not explained by traditional risk factors.
authors.affiliation: Framingham Heart Study, Framingham, MA 01702-5827, USA.
authors.forename: Joao D
authors.initials: JD
authors.lastname: Fontes
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Yamamoto
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Dhayana
authors.initials: D
authors.lastname: Dallmeier
authors.forename: Michiel
authors.initials: M
authors.lastname: Rienstra
authors.forename: Renate B
authors.initials: RB
authors.lastname: Schnabel
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: John F
authors.initials: JF
authors.lastname: Keaney
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000276:immunology / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D028421:Isoprostanes / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood; D019007:P-Selectin / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012307:Risk Factors; D014657:Vasculitis / Q000453:epidemiology* / Q000276:immunology / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C508600:IL6 protein, human; D015850:Interleukin-6; D028421:Isoprostanes; D053244:Osteoprotegerin; D019007:P-Selectin; D047889:Receptors, Tumor Necrosis Factor, Type II; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase