High serum alkaline phosphatase in relation to cerebral small vessel disease


      • Higher alkaline phosphatase (ALP) is associated with cerebral white matter lesions.
      • Higher serum levels of alkaline phosphatase are associated with cerebral infarct.
      • C-reactive protein and ALP are independently associated with brain lesion.
      • Conjoint effect of C-reactive protein and ALP on cerebral small vessel disease.



      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.


      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.


      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.


      We found that higher serum levels of ALP are independently associated with WMH and cerebral infarct, but not with cerebral microbleeds.


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