Review ArticleAlkaline Phosphatase and Risk of Stroke Among Japanese: The Circulatory Risk in Communities Study (CIRCS)

Although serum alkaline phosphatase (ALP) levels have been associated with mortality from all-cause and from either ischemic or hemorrhagic stroke, no study has been published of the associations between ALP and the incidence of stroke. We therefore examined the associations of ALP with risk of stroke among Japanese, stratified by drinking status because ALP is known as an enzyme affected by alcohol consumption. We conducted a prospective cohort study of 10,754 Japanese subjects (4098 men and 6656 women) aged 40-69 years and living in 4 communities under systematic surveillance for stroke incidence. During the 16-year follow-up, we documented 264 strokes (164 ischemic strokes and 69 hemorrhagic strokes) for men and 225 strokes (118 ischemic strokes and 89 hemorrhagic strokes) for women. There was a U-shaped association between ALP level and stroke incidence in both men and women, which was confined primarily to nondrinkers. For nondrinkers, higher ALP levels were associated with an elevated risk of ischemic stroke for men and of hemorrhagic stroke for women, whereas lower ALP levels were associated with elevated risks of ischemic and hemorrhagic strokes in both men and women. Our data indicate that not only higher, but also lower, serum ALP level may be a predictor for the risk of stroke in nondrinking men and women.