Alkaline phosphatase and cardiovascular disease

Gjin Ndrepepa


Alkaline phosphatase (AP) is a plasma membrane-anchored enzyme that is widely distributed in nature from bacteria to humans. AP has a broad specificity and catalyzes the hydrolysis of phosphate monoesters from a wide range of substrates. The best known physiological function of AP is participation in the bone mineralization by increasing the availability of phosphate that is used for hydroxyapatite synthesis. Measurement of AP activity in plasma is widely used for the diagnosis of bone and liver diseases. Population-based longitudinal studies strongly suggest an association between elevated AP and increased risk of incident cardiovascular disease (CVD) or all-cause mortality. Elevated AP in subjects with pre-existing coronary heart disease (CHD) is associated with the increased risk of mortality with no evidence for a stronger association between AP and mortality in these subjects compared to subjects free of CHD. AP is associated with cardiometabolic risk factors including conventional CVD risk factors, metabolic syndrome, systemic inflammation, vitamin D deficiency and various morbid conditions that may signify a poor CVD risk profile or impact unfavorably on prognosis. Experimental studies strongly suggest an involvement of AP in the vascular calcification and, through this mechanism, a direct role of the enzyme in the pathophysiology of CVD. However, criteria for a causal relationship between AP and CVD or mortality remain unfulfilled. Further explorations of the molecular mechanisms of the involvement of AP in the pathophysiology of CVD and the use of the enzyme as a therapeutic target to reduce CVD risk remain to be elucidated in future studies.