title: Biomarkers of cardiovascular stress and subclinical atherosclerosis in the community.
abstract: BACKGROUND
  Biomarkers of cardiovascular stress have been associated with incident cardiovascular outcomes. Their relations with measures of subclinical atherosclerosis, as assessed by carotid intima-media thickness, have not been well described.
  
  
  METHODS
  We measured plasma growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin I (hsTnI) in 3111 Framingham Offspring participants who also underwent carotid ultrasonography during the sixth examination (1995-1998, mean age 58 years, 54% women). Carotid measurements included maximal internal carotid artery (ICA) intima-media thickness (IMT), plaque presence (defined as ICA IMT >1.5 mm), and mean common carotid artery IMT. We carried out multivariable regressions for carotid measurements vs biomarkers using linear and logistic models; P < 0.0056 was deemed statistically significant.
  
  
  RESULTS
  Maximal ICA IMT was significantly associated with plasma GDF-15 [β-estimate 0.04 per 1-U increase in log(GDF-15), SE 0.01, P < 0.0001]. Similarly, the odds of having carotid plaque increased 33% [odds ratio 1.33 per 1-U increase in log(GDF-15), 95% CI 1.20-1.48, P < 0.0001]. In contrast, there was no significant association of maximal ICA IMT or plaque presence with sST2 or hsTnI, and none of the 3 biomarkers was significantly associated with mean CCA IMT. GDF-15 was a stronger predictor of maximal ICA thickness and plaque presence compared with BNP and CRP when these conventional biomarkers were tested together.
  
  
  CONCLUSIONS
  Increased GDF-15 concentrations are associated with subclinical atherosclerosis, including maximal ICA IMT and carotid plaque presence. Future studies investigating the role of GDF-15 for screening and management of patients with subclinical atherosclerosis are warranted.
authors.affiliation: Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;
authors.forename: Deepa M
authors.initials: DM
authors.lastname: Gopal
authors.affiliation: Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA; Department of Mathematics and Statistics, Boston University, Boston, MA;
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.affiliation: Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA;
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
authors.affiliation: Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA;
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Medicine, Mount Auburn Hospital, Boston, MA;
authors.forename: Anahita
authors.initials: A
authors.lastname: Ghorbani
authors.affiliation: Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany;
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
authors.affiliation: Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany;
authors.forename: Tibor
authors.initials: T
authors.lastname: Kempf
authors.affiliation: Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA; Department of Mathematics and Statistics, Boston University, Boston, MA;
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.affiliation: Department of Radiology, Tufts Medical Center, Boston, MA;
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Polak
authors.affiliation: Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA; Cardiology and Preventive Medicine and.
authors.forename: Vasan S
authors.initials: VS
authors.lastname: Ramachandran
authors.affiliation: Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA; Division of Cardiovascular Medicine, Division of Medicine, Vanderbilt University, Nashville, TN.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.affiliation: Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA; Cardiovascular Medicine Section, Department of Medicine, Boston University School of Medicine, Boston, MA; jennifer.ho@bmc.org.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Ho
mesh_terms: D050197:Atherosclerosis / Q000097:blood* / Q000000981:diagnostic imaging; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011956:Receptors, Cell Surface / Q000097:blood; D015203:Reproducibility of Results; D019210:Troponin I / Q000097:blood
chemical_list: D015415:Biomarkers; D055436:Growth Differentiation Factor 15; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011956:Receptors, Cell Surface; D019210:Troponin I; D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein