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Open Access 01-12-2022 | Stroke | Research

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

Authors: Zhongzhong Liu, Xuemei Lin, Lingxia Zeng, Qingli Lu, Pei Liu, Jing Wang, Yan Liu, Qiaoqiao Chang, Yan Wang, Chensheng Song, Fang Wang, Yaling Shi, Guozheng Liu, Qing Wang, Songdi Wu

Published in: BMC Neurology | Issue 1/2022

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.

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Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2019;394(10204):1145–58. https://doi.org/10.1016/S0140-6736(19)30427-1.CrossRefPubMedPubMedCentral

Mendelson SJ, Prabhakaran S. Diagnosis and management of transient ischemic attack and acute ischemic stroke: a review. JAMA. 2021;325(11):1088–98. https://doi.org/10.1001/jama.2020.26867.CrossRefPubMed

Brichacek AL, Brown CM. Alkaline phosphatase: a potential biomarker for stroke and implications for treatment. Metab Brain Dis. 2019;34(1):3–19. https://doi.org/10.1007/s11011-018-0322-3.CrossRefPubMed

Kim J, Song TJ, Song D, Lee HS, Nam CM, Nam HS, et al. Serum alkaline phosphatase and phosphate in cerebral atherosclerosis and functional outcomes after cerebral infarction. Stroke. 2013;44(12):3547–9. https://doi.org/10.1161/STROKEAHA.113.002959.CrossRefPubMed

Matsushita K, Coresh J, Sang Y, Chalmers J, Fox C, Guallar E, et al. Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol. 2015;3(7):514–25. https://doi.org/10.1016/S2213-8587(15)00040-6.CrossRefPubMedPubMedCentral

El Husseini N, Kaskar O, Goldstein LB. Chronic kidney disease and stroke. Adv Chronic Kidney Dis. 2014;21(6):500–8. https://doi.org/10.1053/j.ackd.2014.09.001.CrossRefPubMed

Regidor DL, Kovesdy CP, Mehrotra R, Rambod M, Jing J, McAllister CJ, et al. Serum alkaline phosphatase predicts mortality among maintenance hemodialysis patients. J Am Soc Nephrol. 2008;19(11):2193–203. https://doi.org/10.1681/ASN.2008010014.CrossRefPubMedPubMedCentral

Kovesdy CP, Ureche V, Lu JL, Kalantar-Zadeh K. Outcome predictability of serum alkaline phosphatase in men with pre-dialysis CKD. Nephrol Dial Transplant. 2010;25(9):3003–11. https://doi.org/10.1093/ndt/gfq144.CrossRefPubMedPubMedCentral

Zou FTYWW. Design and implementation of management system for stroke data mining based on non-structured electronic medical record. China Digital Medicine. 2015;10(2):41–4. https://doi.org/10.3969/j.issn.1673-7571.2015.3.014.CrossRef

10.

Wang Y, Zhao X, Liu L, Soo YO, Pu Y, Pan Y, et al. Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: the Chinese Intracranial Atherosclerosis (CICAS) Study. Stroke. 2014;45(3):663–9. https://doi.org/10.1161/STROKEAHA.113.003508.CrossRefPubMed

11.

Teo BW, Xu H, Wang D, Li J, Sinha AK, Shuter B, et al. GFR estimating equations in a multiethnic Asian population. Am J Kidney Dis. 2011;58(1):56–63. https://doi.org/10.1053/j.ajkd.2011.02.393.CrossRefPubMed

12.

Wang X, Luo Y, Wang Y, Wang C, Zhao X, Wang D, et al. Comparison of associations of outcomes after stroke with estimated GFR using Chinese modifications of the MDRD study and CKD-EPI creatinine equations: results from the China National Stroke Registry. Am J Kidney Dis. 2014;63(1):59–67. https://doi.org/10.1053/j.ajkd.2013.08.008.CrossRefPubMed

13.

Quinn TJ, Dawson J, Walters MR, Lees KR. Functional outcome measures in contemporary stroke trials. Int J Stroke. 2009;4(3):200–5. https://doi.org/10.1111/j.1747-4949.2009.00271.x.CrossRefPubMed

14.

Schumann G, Klauke R, Canalias F, Bossert-Reuther S, Franck PF, Gella FJ, et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. Part 9: reference procedure for the measurement of catalytic concentration of alkaline phosphatase International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Scientific Division, Committee on Reference Systems of Enzymes (C-RSE) (1)). Clin Chem Lab Med. 2011;49(9):1439–46. https://doi.org/10.1515/CCLM.2011.621.CrossRefPubMed

15.

Pratibha S, Praveen-Kumar S, Agadi JB. Increased serum alkaline phosphatase and serum phosphate as predictors of mortality after stroke. J Clin Diagn Res. 2014;8(8):CC01-3. https://doi.org/10.7860/JCDR/2014/8350.4649.CrossRef

16.

Tan LM, Wang L, Chen JJ, Li H, Luo WB. Diagnostic performance of bone metabolic indexes for the detection of stroke. Saudi Med J. 2017;38(1):30–5. https://doi.org/10.15537/smj.2017.1.15813.CrossRefPubMedPubMedCentral

17.

Zhong C, You S, Chen J, Zhai G, Du H, Luo Y, et al. Serum alkaline phosphatase, phosphate, and in-hospital mortality in acute ischemic stroke patients. J Stroke Cerebrovasc Dis. 2018;27(1):257–66. https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.08.041.CrossRefPubMed

18.

Lomashvili KA, Garg P, Narisawa S, Millan JL, O’Neill WC. Upregulation of alkaline phosphatase and pyrophosphate hydrolysis: potential mechanism for uremic vascular calcification. Kidney Int. 2008;73(9):1024–30. https://doi.org/10.1038/ki.2008.26.CrossRefPubMedPubMedCentral

19.

Haarhaus M, Brandenburg V, Kalantar-Zadeh K, Stenvinkel P, Magnusson P. Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD. Nat Rev Nephrol. 2017;13(7):429–42. https://doi.org/10.1038/nrneph.2017.60.CrossRefPubMed

20.

Waziri B, Duarte R, Naicker S. High serum alkaline phosphatase, hypercalcaemia, race, and mortality in South African maintenance haemodialysis patients. Int J Nephrol. 2017;2017:2795432. https://doi.org/10.1155/2017/2795432.CrossRefPubMedPubMedCentral

21.

Ryu WS, Lee SH, Kim CK, Kim BJ, Yoon BW. Increased serum alkaline phosphatase as a predictor of long-term mortality after stroke. Neurology. 2010;75(22):1995–2002. https://doi.org/10.1212/WNL.0b013e3181ff966a.CrossRefPubMed

22.

Zong L, Wang X, Li Z, Zhao X, Liu L, Li H, et al. Alkaline phosphatase and outcomes in patients with preserved renal function: results from China National Stroke Registry. Stroke. 2018;49(5):1176–82. https://doi.org/10.1161/strokeaha.118.020237.CrossRefPubMed

23.

Rader BA. Alkaline phosphatase, an unconventional immune protein. Front Immunol. 2017;8:897. https://doi.org/10.3389/fimmu.2017.00897.CrossRefPubMedPubMedCentral

24.

Nwafor DC, Brichacek AL, Ali A, Brown CM. Tissue-nonspecific alkaline phosphatase in central nervous system health and disease: a focus on brain microvascular endothelial cells. Int J Mol Sci. 2021;22(10):5257. https://doi.org/10.3390/ijms22105257.CrossRefPubMedPubMedCentral

25.

Shimizu Y, Imano H, Ohira T, Kitamura A, Kiyama M, Okada T, et al. Alkaline phosphatase and risk of stroke among Japanese: the Circulatory Risk in Communities Study (CIRCS). J Stroke Cerebrovasc Dis. 2013;22(7):1046–55. https://doi.org/10.1016/j.jstrokecerebrovasdis.2012.06.009.CrossRefPubMed

26.

Shimizu Y, Nakazato M, Sekita T, Kadota K, Yamasaki H, Takamura N, et al. Association between alkaline phosphatase and hypertension in a rural Japanese population: the Nagasaki Islands study. J Physiol Anthropol. 2013;32(1):10. https://doi.org/10.1186/1880-6805-32-10.CrossRefPubMedPubMedCentral

27.

el Hafny B, Bourre JM, Roux F. Synergistic stimulation of gamma-glutamyl transpeptidase and alkaline phosphatase activities by retinoic acid and astroglial factors in immortalized rat brain microvessel endothelial cells. J Cell Physiol. 1996;167(3):451–60. https://doi.org/10.1002/(SICI)1097-4652(199606)167:3%3c451::AID-JCP9%3e3.0.CO;2-O.CrossRefPubMed

28.

Deracinois B, Duban-Deweer S, Pottiez G, Cecchelli R, Karamanos Y, Flahaut C. TNAP and EHD1 are over-expressed in bovine brain capillary endothelial cells after the re-induction of blood-brain barrier properties. PLoS One. 2012;7(10):e48428. https://doi.org/10.1371/journal.pone.0048428.CrossRefPubMedPubMedCentral

29.

Calhau C, Martel F, Pinheiro-Silva S, Pinheiro H, Soares-da-Silva P, Hipolito-Reis C, et al. Modulation of insulin transport in rat brain microvessel endothelial cells by an ecto-phosphatase activity. J Cell Biochem. 2002;84(2):389–400. https://doi.org/10.1002/jcb.10027.CrossRefPubMed

30.

Huizinga R, Kreft KL, Onderwater S, Boonstra JG, Brands R, Hintzen RQ, et al. Endotoxin- and ATP-neutralizing activity of alkaline phosphatase as a strategy to limit neuroinflammation. J Neuroinflammation. 2012;9:266. https://doi.org/10.1186/1742-2094-9-266.CrossRefPubMedPubMedCentral

31.

Langhorne P, Stott DJ, Robertson L, MacDonald J, Jones L, McAlpine C, et al. Medical complications after stroke: a multicenter study. Stroke. 2000;31(6):1223–9. https://doi.org/10.1161/01.str.31.6.1223.CrossRefPubMed

32.

Vernino S, Brown RD Jr, Sejvar JJ, Sicks JD, Petty GW, O’Fallon WM. Cause-specific mortality after first cerebral infarction: a population-based study. Stroke. 2003;34(8):1828–32. https://doi.org/10.1161/01.STR.0000080534.98416.A0.CrossRefPubMed

33.

Lee HB, Kim J, Kim SH, Kim S, Kim OJ, Oh SH. Association between serum alkaline phosphatase level and cerebral small vessel disease. PLoS One. 2015;10(11):e0143355. https://doi.org/10.1371/journal.pone.0143355.CrossRefPubMedPubMedCentral

34.

Sigrist MK, McIntyre CW. Vascular calcification is associated with impaired microcirculatory function in chronic haemodialysis patients. Nephron Clin Pract. 2008;108(2):c121–6. https://doi.org/10.1159/000114202.CrossRefPubMed

Title: 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
Authors: Zhongzhong Liu
Xuemei Lin
Lingxia Zeng
Qingli Lu
Pei Liu
Jing Wang
Yan Liu
Qiaoqiao Chang
Yan Wang
Chensheng Song
Fang Wang
Yaling Shi
Guozheng Liu
Qing Wang
Songdi Wu
Publication date: 01-12-2022
Publisher: BioMed Central
Keyword: Stroke
Published in: BMC Neurology / Issue 1/2022
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-022-02779-y

Keynote webinar | Spotlight on medication adherence

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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

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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