title: Lipid profile components and subclinical cerebrovascular disease in the northern Manhattan study.
abstract: BACKGROUND
  Subclinical cerebrovascular disease has been associated with multiple adverse events related to aging, including stroke and dementia. The modifiable risk factors for subclinical cerebrovascular disease beyond hypertension have not been well characterized. Our objective was to examine the association between baseline, and changes over time, in lipid profile components and subclinical cerebrovascular disease on magnetic resonance imaging (MRI).
  
  
  METHODS
  Fasting plasma lipids were collected on participants in the Northern Manhattan Study, a prospective cohort study examining risk factors for cardiovascular disease in a multiethnic elderly urban-dwelling population. A subsample of the cohort underwent brain MRI between 2003 and 2008 (a median of 6.2 years, range = 0-14, after enrollment), when repeat fasting lipids were obtained. We used lipid profile components at the time of initial enrollment (n = 1,256 with lipids available) as categorical variables, as well as change in clinical categories over the two measures (n = 1,029). The main outcome measures were (1) total white matter hyperintensity volume (WMHV) using linear regression and (2) silent brain infarcts (SBI) using logistic regression.
  
  
  RESULTS
  None of the plasma lipid profile components at the time of enrollment were associated with WMHV. The association between baseline lipids and WMHV was, however, modified by apolipoprotein E (apoE) status (χ(2) with 2 degrees of freedom, p = 0.03), such that among apoE4 carriers those with total cholesterol (TC) ≥200 mg/dl had a trend towards smaller WMHV than those with TC <200 mg/dl (difference in log​WMHV -0.19, p = 0.07), while there was no difference among apoE3 carriers. When examining the association between WMHV and change in lipid profile components we noted an association with change in high-density lipoprotein cholesterol (HDL-C, >50 mg/dl for women, >40 mg/dl for men) and TC. A transition from low-risk HDL-C (>50 mg/dl for women, >40 mg/dl for men) at baseline to high-risk HDL-C at the time of MRI (vs. starting and remaining low risk) was associated with greater WMHV (difference in logWMHV 0.34, p value 0.03). We noted a similar association with transitioning to a TC ≥200 mg/dl at the time of MRI (difference in logWMHV 0.25, p value 0.006). There were no associations with baseline or change in lipid profile components with SBI.
  
  
  CONCLUSIONS
  The association of plasma lipid profile components with greater WMHV may depend on apoE genotype and worsening HDL and TC risk levels over time.
authors.affiliation: Department of Neurology, Columbia University, New York, N.Y., USA.
authors.forename: Joshua Z
authors.initials: JZ
authors.lastname: Willey
authors.forename: Hannah
authors.initials: H
authors.lastname: Gardener
authors.forename: Yeseon P
authors.initials: YP
authors.lastname: Moon
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshita
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.forename: Ying Kuen
authors.initials: YK
authors.lastname: Cheung
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Sacco
authors.forename: Mitchell S V
authors.initials: MS
authors.lastname: Elkind
authors.forename: Clinton B
authors.initials: CB
authors.lastname: Wright
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001057:Apolipoproteins E / Q000235:genetics; D002784:Cholesterol / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000209:etiology* / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D002784:Cholesterol