title: Association between Serum Alkaline Phosphatase Level and Cerebral Small Vessel Disease.
abstract: BACKGROUND
  Serum alkaline phosphatase (ALP) is a marker of vascular calcification. A high serum ALP level is associated with an increase in cardiovascular events, and predicts poor functional outcome in patients with stroke. We investigated whether serum ALP was associated with cerebral small vessel disease (cSVD) and large cerebral artery stenosis (LCAS).
  
  
  METHODS
  We evaluated vascular risk factors, brain magnetic resonance images (MRIs), and MR angiograms from 1,011 neurologically healthy participants. The presence of silent lacunar infarction (SLI) and moderate-to-severe cerebral white matter hyperintensities (MS-cWMH) were evaluated as indices of cSVD on brain MRIs. Findings of extracranial arterial stenosis (ECAS) or intracranial arterial stenosis (ICAS) were considered to be indices of LCAS on MR angiograms.
  
  
  RESULTS
  Subjects with SLI (odds ratio [OR]: 2.09; 95% confidence interval [CI]: 1.27-3.42; p = 0.004) and MS-cWMH (OR: 1.48; 95% CI; 1.03-2.13, p = 0.036) were significantly more likely to have ALP levels in the third tertile (ALP ≥ 195 IU/L) than the first tertile (ALP ≤ 155 IU/L), after adjusting for cardiovascular risk factors. The mean serum ALP level was significantly higher in patients with SLI or MS-cWMH compared to patients without those findings. After adjustment for confounding factors, the multivariate model found that the statistical significance of serum ALP remained when the presence of SLI (OR: 1.05 per 10 IU/L increase in ALP; 95% CI: 1.02-1.08; p = 0.003) or MS-cWMH (OR: 1.03 per 10 IU/L increase in ALP; 95% CI: 1.00-1.06; p = 0.025) were added to the model. There were no differences in the proportions of patients with LCAS, ICAS, and ECAS across the serum ALP tertiles.
  
  
  CONCLUSIONS
  Our study of neurologically healthy participants found a positive association between serum ALP level and indicators of cSVD, but no association between serum ALP level and the indicators of LCAS.
authors.affiliation: Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Han-Bin
authors.initials: HB
authors.lastname: Lee
authors.affiliation: Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Jinkwon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Radiology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Sang-Heum
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, South Korea.|Catholic Kwandong University International St. Mary's Hospital, Incheon Metropolitan City, South Korea.
authors.forename: Soonhag
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Ok-Joon
authors.initials: OJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Seung-Hun
authors.initials: SH
authors.lastname: Oh
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology; D059345:Cerebral Small Vessel Diseases / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000453:epidemiology; D059409:Stroke, Lacunar / Q000097:blood / Q000453:epidemiology
chemical_list: D000469:Alkaline Phosphatase