High serum alkaline phosphatase in relation to cerebral small vessel disease.
OBJECTIVE
Vascular calcification is related with cerebral small vessel disease. We investigated whether alkaline phosphatase (ALP), a marker of vascular calcificiation, is related to cerebral small vessel disease.


METHODS
We included 1082 neurologically healthy subjects who underwent brain magnetic resonance image for a routine health checkup. ALP levels were divided into quartiles. We used quantile regression and logistic regression to evaluate the associations of ALP with white matter hyperintensities (WMH), cerebral infarct and cerebral microbleeds.


RESULTS
Subjects with higher ALP were more likely to have a large WMH volume. The adjusted difference of WMH volume between the highest and the lowest quartiles was 0.27 mL (95% confidence interval [CI]; 0.22-0.31 mL). In addition, cerebral infarct was more prevalent in subjects with higher ALP. Compared to the lowest quartile, adjusted odds ratios of having cerebral infarct for the highest quartile was 2.60 (95% CI, 1.10-6.10). No association was found between ALP and cerebral microbleeds. In addition, we found a conjoint effect of ALP and C-reactive protein(CRP) on cerebral small vessel disease. Compared with subjects with low ALP (≤63 IU/L) and low CRP (≤0.5 mg/dl), those with high ALP (>63 IU/L) and high CRP (>0.5 mg/dl) had larger WMH volume (adjusted difference 0.39 mL; 95% CI 0.37-0.42 mL) and a 3-fold (adjusted OR. 3.37; 95% CI, 1.61-7.03) risk of cerebral infarct.


CONCLUSIONS
We found that higher serum levels of ALP are independently associated with WMH and cerebral infarct, but not with cerebral microbleeds.
Department of Neurology, Dongguk University Ilsan Hospital, Goyang, Republic of Korea.
Wi-Sun
WS
Ryu
Department of Neurology, Seoul National University Hospital, 28 Yongon-dong, Jongno-gu, Seoul 110-744, Republic of Korea. Electronic address: sb0516@snu.ac.kr.
Seung-Hoon
SH
Lee
Department of Neurology, Seoul National University Hospital, 28 Yongon-dong, Jongno-gu, Seoul 110-744, Republic of Korea.
Chi Kyung
CK
Kim
Department of Neurology, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.
Beom Joon
BJ
Kim
Department of Neurology, Seoul National University Boramae Hospital, Seoul, Republic of Korea.
Hyung-Min
HM
Kwon
Department of Neurology, Seoul National University Hospital, 28 Yongon-dong, Jongno-gu, Seoul 110-744, Republic of Korea. Electronic address: bwyoon@snu.ac.kr.
Byung-Woo
BW
Yoon
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood*; D001921:Brain / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D002114:Calcinosis / Q000473:pathology; D002544:Cerebral Infarction / Q000097:blood / Q000175:diagnosis; D059345:Cerebral Small Vessel Diseases / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D012044:Regression Analysis; D012307:Risk Factors
D002097:C-Reactive Protein; D000469:Alkaline Phosphatase
All cerebrovascular disease/stroke; Cohort studies; Infarction; MRI; Volumetric MRI