title: Traditional risk factors are not major contributors to the variance in carotid intima-media thickness.
abstract: OBJECTIVE
  Carotid intima-media thickness (cIMT) was a widely accepted ultrasound marker of subclinical atherosclerosis in the past. Although traditional risk factors may explain ≈50% of the variance in plaque burden, they may not explain such a high proportion of the variance in IMT, especially when measured in plaque-freel ocations. We aimed this study to identify individuals with cIMT unexplained by traditional risk factors for future environmental and genetic research.
  
  
  METHODS
  As part of the Northern Manhattan Study, 1790 stroke-free individuals (mean age, 69±9 years; 60% women; 61% Hispanic; 19% black; 18% white) were assessed for cIMT using B-mode carotid ultrasound. Multiple linear regression models were evaluated: (1) incorporating prespecified traditional risk factors; and (2) including less traditional factors, such as inflammation biomarkers, adiponectin, homocysteine, and kidney function. Standardized cIMT residual scores were constructed to select individuals with unexplained cIMT.
  
  
  RESULTS
  Mean total cIMT was 0.92±0.09 mm. The traditional model explained 11% of the variance in cIMT. Age (7%), male sex (3%), glucose (<1%), pack-years of smoking (<1%), and low-density lipoprotein cholesterol (<1%) were significant contributing factors. The model, including inflammatory biomarkers, explained 16% of the variance in cIMT. Adiponectin was the only additional significant contributor to the variance in cIMT. We identified 358 individuals (20%) with cIMT unexplained by the investigated risk factors.
  
  
  CONCLUSIONS
  Vascular risk factors explain only a small proportion of variance in cIMT. Identification of novel genetic and environmental factors underlying unexplained subclinical atherosclerosis is of utmost importance for future effective prevention of vascular disease.
authors.affiliation: Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA. trundek@med.miami.edu
authors.forename: Tatjana
authors.initials: T
authors.lastname: Rundek
authors.forename: Susan H
authors.initials: SH
authors.lastname: Blanton
authors.forename: Susanne
authors.initials: S
authors.lastname: Bartels
authors.forename: Chuanhui
authors.initials: C
authors.lastname: Dong
authors.forename: Ami
authors.initials: A
authors.lastname: Raval
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Demmer
authors.forename: Digna
authors.initials: D
authors.lastname: Cabral
authors.forename: Mitchell S V
authors.initials: MS
authors.lastname: Elkind
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Sacco
authors.forename: Moise
authors.initials: M
authors.lastname: Desvarieux
mesh_terms: D000367:Age Factors; D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000652:urine; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D059168:Carotid Intima-Media Thickness / Q000295:instrumentation; D008078:Cholesterol, LDL / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D016014:Linear Models; D008297:Male; D015233:Models, Statistical; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects / Q000097:blood / Q000473:pathology
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008078:Cholesterol, LDL
keywords: carotid intima-media thickness; carotid ultrasound; risk factors