title: Adiposity has no direct effect on carotid intima-media thickness in adolescents and young adults: Use of structural equation modeling to elucidate indirect & direct pathways.
abstract: BACKGROUND
  Carotid intima-media thickness (cIMT) is associated with CV events in adults. Thicker cIMT is found in youth with CV risk factors including obesity. Which risk factors have the most effect upon cIMT in youth and whether obesity has direct or indirect effects is not known. We used structural equation modeling to elucidate direct and indirect pathways through which obesity and other risk factors were associated with cIMT.
  
  
  METHODS
  We collected demographics, anthropometrics and laboratory data on 784 subjects age 10-24 years (mean 18.0 ± 3.3 years). Common, bulb and internal carotid cIMT were measured by ultrasound. Multivariable regression analysis was performed to assess independent determinants of cIMT. Analyses were repeated with structural equation modeling to determine direct and indirect effects.
  
  
  RESULTS
  Multivariable regression models explained 11%-22% of variation of cIMT. Age, sex and systolic blood pressure (BP) z-score were significant determinants of all cIMT segments. Body mass index (BMI) z-score, race, presence of type 2 diabetes mellitus (T2DM), hemoglobin A1c (HbA1c) and non-HDL were significant for some segments (all p = 0.05). The largest direct effect on cIMT was age (0.312) followed by BP (0.228), Blood glucose control (0.108) and non-HDL (0.134). BMI only had a significant indirect effect through blood glucose control, BP & non-HDL. High sensitivity C-reactive protein (CRP) had a small indirect effect through blood glucose control (all p = 0.05).
  
  
  CONCLUSIONS
  Age and BP are the major factors with direct effect on cIMT. Glucose and non-HDL were also important in this cohort with a high prevalence of T2DM. BMI only has indirect effects, through other risk factors. Traditional CV risk factors have important direct effects on cIMT in the young, but adiposity exerts its influence only through other CV risk factors.
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati, USA.
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Khoury
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati, USA.
authors.forename: Connie E
authors.initials: CE
authors.lastname: McCoy
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Shah
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kimball
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati, USA.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Dolan
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati, USA. Electronic address: Elaine.urbina@cchmc.org.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Urbina
mesh_terms: D050154:Adiposity; D000293:Adolescent; D000367:Age Factors; D001794:Blood Pressure; D015992:Body Mass Index; D002339:Carotid Arteries / Q000000981:diagnostic imaging* / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D016009:Chi-Square Distribution; D002648:Child; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D009765:Obesity / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology*; D009820:Ohio / Q000453:epidemiology; D011237:Predictive Value of Tests; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors; D066253:Vascular Remodeling; D055815:Young Adult
keywords: Carotid arteries; Obesity; Pediatrics; Risk factors; Statistics