Relationship between serum alkaline phosphatase and poor 3-month prognosis in acute ischemic stroke patients with preserved renal function: results from Xi’an Stroke Registry Study of China

Abstract

Background In recent years, alkaline phosphatase (ALP) has been considered as one of the independent risk factors of acute ischemic stroke (AIS) and leads to worse clinical outcomes in patients with renal failure. In this study, we aim to investigate whether serum ALP level is associated with poor early-term prognosis in relationship of AIS patients with preserved renal function. Methods A prospectively collected database of AIS patients hospitalized in the Xi’an district of China from January to December, 2015 was analyzed. The demographics, serum ALP levels and stroke outcomes of all patients at 3 months were reviewed. Patients were routinely followed-up for 3 months. Serum ALP level was analyzed as a continuous variable and quintiles (Q1-Q5). Multivariate logistic regression model and a two-piecewise linear regression model were used to investigate the relationship and to determine the threshold effect regarding serum ALP levels and poor 3-month prognosis of AIS patients with preserved renal function. Results Overall, 1922 AIS patients were enrolled with 62.3% of them being men. The risk of having a poor 3-month prognosis was significantly increased in Q1, Q2, Q3 and Q5, when compared to that in Q4 being as the reference. The highest risk was noted in Q5 (odds ratio 2.21, 95% confidence interval: 1.32–3.73, P = 0.003) after being adjusted for confounders. Further analysis revealed a J-shaped curvilinear relationship between ALP levels and a poor 3-month prognosis of strokes (optimal threshold ALP level = 90 U/L). The relationship between both parameters was not significantly affected by age, sex, drinking, hypertension and leukocyte count (stratified by 10 × 109/L) (P for interaction > 0.05). Conclusions Serum ALP was noted as an independent risk factor for a poor 3-month prognosis of AIS patients with preserved renal function. ALP levels higher than 90 U/L could cause an increased risk of a poor 3-month prognosis.

Evaluation of De Ritis (AST/ALT), ALP/ALT, and AST/ALP ratios as prognostic factors in patients with acute ischemic stroke

“…Although the exact mechanisms of higher serum ALP levels in a poor 3-month prognosis (higher mRS or mortality) are not fully understood, based on previous studies, ALP may play an important role in the permeability, maintenance, and integrity of the blood-brain barrier (BBB) and also in the transport of proteins across the barrier. Therefore, the high ALP levels may disrupt the transport of these proteins, leading to the breakdown of the BBB and neuronal death [ 24 ]. Besides, the potential association of higher levels of ALP with neuroinflammation and enhancement of vascular calcification by inactivating organic pyrophosphate, an important vascular calcification inhibitor, may be other reasons for higher ALP levels in patients with a poor prognosis [ 24 , 25 ].…”

“…Therefore, the high ALP levels may disrupt the transport of these proteins, leading to the breakdown of the BBB and neuronal death [ 24 ]. Besides, the potential association of higher levels of ALP with neuroinflammation and enhancement of vascular calcification by inactivating organic pyrophosphate, an important vascular calcification inhibitor, may be other reasons for higher ALP levels in patients with a poor prognosis [ 24 , 25 ]. However, apart from higher ALP levels in AIS patients with poor outcomes, researchers have suggested a contradictory role for AST and ALT in these patients.…”