title: Characterization of vascular disease risk in postmenopausal women and its association with cognitive performance.
abstract: OBJECTIVE
  While global measures of cardiovascular (CV) risk are used to guide prevention and treatment decisions, these estimates fail to account for the considerable interindividual variability in pre-clinical risk status. This study investigated heterogeneity in CV risk factor profiles and its association with demographic, genetic, and cognitive variables.
  
  
  METHODS
  A latent profile analysis was applied to data from 727 recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Women were cognitively healthy, within three years of their last menstrual period, and free of current or past CV disease. Education level, apolipoprotein E ε4 allele (APOE4), ethnicity, and age were modeled as predictors of latent class membership. The association between class membership, characterizing CV risk profiles, and performance on five cognitive factors was examined. A supervised random forest algorithm with a 10-fold cross-validation estimator was used to test accuracy of CV risk classification.
  
  
  RESULTS
  The best-fitting model generated two distinct phenotypic classes of CV risk 62% of women were "low-risk" and 38% "high-risk". Women classified as low-risk outperformed high-risk women on language and mental flexibility tasks (p = 0.008) and a global measure of cognition (p = 0.029). Women with a college degree or above were more likely to be in the low-risk class (OR = 1.595, p = 0.044). Older age and a Hispanic ethnicity increased the probability of being at high-risk (OR = 1.140, p = 0.002; OR = 2.622, p = 0.012; respectively). The prevalence rate of APOE-ε4 was higher in the high-risk class compared with rates in the low-risk class.
  
  
  CONCLUSIONS
  Among recently menopausal women, significant heterogeneity in CV risk is associated with education level, age, ethnicity, and genetic indicators. The model-based latent classes were also associated with cognitive function. These differences may point to phenotypes for CV disease risk. Evaluating the evolution of phenotypes could in turn clarify preclinical disease, and screening and preventive strategies. ClinicalTrials.gov NCT00154180.
authors.affiliation: Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA. nmdowlin@biostat.wisc.edu
authors.forename: N Maritza
authors.initials: NM
authors.lastname: Dowling
authors.forename: Carey E
authors.initials: CE
authors.lastname: Gleason
authors.forename: Joann E
authors.initials: JE
authors.lastname: Manson
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Miller
authors.forename: Eliot A
authors.initials: EA
authors.lastname: Brinton
authors.forename: Genevieve
authors.initials: G
authors.lastname: Neal-Perry
authors.forename: M Nanette
authors.initials: MN
authors.lastname: Santoro
authors.forename: Marcelle
authors.initials: M
authors.lastname: Cedars
authors.forename: Rogerio
authors.initials: R
authors.lastname: Lobo
authors.forename: George R
authors.initials: GR
authors.lastname: Merriam
authors.forename: Whitney
authors.initials: W
authors.lastname: Wharton
authors.forename: Frederick
authors.initials: F
authors.lastname: Naftolin
authors.forename: Hugh
authors.initials: H
authors.lastname: Taylor
authors.forename: S Mitchell
authors.initials: SM
authors.lastname: Harman
authors.forename: Sanjay
authors.initials: S
authors.lastname: Asthana
mesh_terms: D001057:Apolipoproteins E / Q000235:genetics; D001185:Artificial Intelligence; D003071:Cognition; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D014652:Vascular Diseases / Q000453:epidemiology* / Q000503:physiopathology / Q000523:psychology
chemical_list: D001057:Apolipoproteins E