Plasma Levels of Protein Z in Ischemic Stroke: A Systematic Review and Meta-Analysis

Artur Słomka; Mariusz Kowalewski; Ewa Żekanowska; Piotr Suwalski; Roberto Lorusso; John W. Eikelboom

doi:10.1055/s-0040-1708878

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2020; 120(05): 815-822
DOI: 10.1055/s-0040-1708878

Stroke, Systemic or Venous Thromboembolism

Georg Thieme Verlag KG Stuttgart · New York

Plasma Levels of Protein Z in Ischemic Stroke: A Systematic Review and Meta-Analysis

Authors

Artur Słomka

¹Department of Pathophysiology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland
Mariusz Kowalewski

²Clinical Department of Cardiac Surgery, Central Clinical Hospital of the Ministry of Interior and Administration, Centre of Postgraduate Medical Education, Warsaw, Poland

³Department of Cardio-Thoracic Surgery, Heart and Vascular Centre, Maastricht University Medical Centre, Maastricht, The Netherlands

⁴Thoracic Research Centre, Innovative Medical Forum, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland
Ewa Żekanowska

¹Department of Pathophysiology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland
Piotr Suwalski

²Clinical Department of Cardiac Surgery, Central Clinical Hospital of the Ministry of Interior and Administration, Centre of Postgraduate Medical Education, Warsaw, Poland
Roberto Lorusso

³Department of Cardio-Thoracic Surgery, Heart and Vascular Centre, Maastricht University Medical Centre, Maastricht, The Netherlands
John W. Eikelboom

⁵Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada

Abstract

The association between blood levels of protein Z (PZ) and risk of ischemic stroke remains poorly understood. We aimed to assess this potential relationship through a meta-analysis of case–control studies. PubMed, Scopus, Web of Science Core Collection, and the Cochrane Library were searched from April 1984 to April 2019. We selected case–control studies comparing PZ levels in adult patients with ischemic stroke and controls without ischemic stroke. Six case–control studies, with a total of 1,011 ischemic stroke patients and 1,128 controls, were included. Patients in the acute phase of ischemic stroke showed significantly higher levels of PZ compared with patients in the convalescent phase (standardized mean difference [SMD]: 0.289 mg/L; 95% confidence interval [CI]: 0.010, 0.569; p = 0.043). No significant differences in PZ levels were found between patients and controls in the acute phase (SMD: −0.059 mg/L; 95% CI: −0.570, 0.452; p = 0.821) or in the convalescent phase of ischemic stroke (SMD: −0.341 mg/L; 95% CI: −0.736, 0.055; p = 0.091). Subgroup analysis indicated that older patients (≥ 50 years old) had lower PZ levels than similarly aged controls. In contrast, when the study groups came from the United States and Australia or Europe no significant differences in PZ levels existed between patients and controls. No association between PZ and ischemic stroke was identified in this meta-analysis. The acute phase of ischemic stroke was associated with higher levels of PZ.

Keywords

ischemic stroke - protein Z - systematic review - meta-analysis

Full Text

References

References
1 Benjamin EJ, Muntner P, Alonso A. , et al; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2019 Update: a report from the American Heart Association. Circulation 2019; 139 (10) e56-e528
2 Sommer CJ. Ischemic stroke: experimental models and reality. Acta Neuropathol 2017; 133 (02) 245-261
3 Lansberg MG, O'Donnell MJ, Khatri P. , et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012. ;141: 601-636
4 Huang X, Swanson R, Kroh HK, Bock PE. Protein Z-dependent protease inhibitor (ZPI) is a physiologically significant inhibitor of prothrombinase function. J Biol Chem 2019; 294 (19) 7644-7657
5 Han X, Fiehler R, Broze Jr GJ. Characterization of the protein Z-dependent protease inhibitor. Blood 2000; 96 (09) 3049-3055
6 Sofi F, Cesari F, Abbate R, Gensini GF, Broze Jr G, Fedi S. A meta-analysis of potential risks of low levels of protein Z for diseases related to vascular thrombosis. Thromb Haemost 2010; 103 (04) 749-756
7 Vasse M, Denoyelle C, Corbière C, Litzler PY, Legrand E, Vannier JP. Human endothelial cells synthesize protein Z, but not the protein Z dependent inhibitor. Thromb Haemost 2006; 95 (03) 519-523
8 Butschkau A, Wagner NM, Genz B, Vollmar B. Protein z exerts pro-angiogenic effects and upregulates CXCR4. PLoS One 2014; 9 (12) e113554
9 Vasse M, Guegan-Massardier E, Borg JY, Woimant F, Soria C. Frequency of protein Z deficiency in patients with ischaemic stroke. Lancet 2001; 357 (9260): 933-934
10 Lopaciuk S, Bykowska K, Kwiecinski H, Czlonkowska A, Kuczynska-Zardzewialy A. Protein Z in young survivors of ischemic stroke. Thromb Haemost 2002; 88 (03) 536
11 Kobelt K, Biasiutti FD, Mattle HP, Lämmle B, Wuillemin WA. Protein Z in ischaemic stroke. Br J Haematol 2001; 114 (01) 169-173
12 Heeb MJ, Paganini-Hill A, Griffin JH, Fisher M. Low protein Z levels and risk of ischemic stroke: differences by diabetic status and gender. Blood Cells Mol Dis 2002; 29 (02) 139-144
13 McQuillan AM, Eikelboom JW, Hankey GJ. , et al. Protein Z in ischemic stroke and its etiologic subtypes. Stroke 2003; 34 (10) 2415-2419
14 van Goor MP, Dippel DW, Jie KS, de Maat MP, Koudstaal PJ, Leebeek FW. Low protein Z levels but not the protein Z gene G79A polymorphism are a risk factor for ischemic stroke. Thromb Res 2008; 123 (02) 213-218
15 Zhang L, Segal AZ, Leifer D. , et al. Circulating protein Z concentration, PROZ variants, and unexplained cerebral infarction in young and middle-aged adults. Thromb Haemost 2017; 117 (01) 149-157
16 Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. PLoS Med 2009; 6: 1000097
17 Broze Jr GJ, Miletich JP. Human Protein Z. J Clin Invest 1984; 73 (04) 933-938
18 Wells GA, Shea B, O'Connell D. , et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp . Accessed May 1, 2019
19 Luo X, Ou R, Dutta R, Tian Y, Xiong H, Shang H. Association between serum vitamin D levels and Parkinson's disease: a systematic review and meta-analysis. Front Neurol 2018; 9: 909
20 Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315 (7109): 629-634
21 Kemkes-Matthes B, Matthes KJ. Protein Z, a new haemostatic factor, in liver diseases. Haemostasis 1995; 25 (06) 312-316
22 Miletich JP, Broze Jr GJ. Human plasma protein Z antigen: range in normal subjects and effect of warfarin therapy. Blood 1987; 69 (06) 1580-1586
23 Vossen CY, Hasstedt SJ, Rosendaal FR. , et al. Heritability of plasma concentrations of clotting factors and measures of a prethrombotic state in a protein C-deficient family. J Thromb Haemost 2004; 2 (02) 242-247
24 Santacroce R, Cappucci F, Di Perna P, Sessa F, Margaglione M. Protein Z gene polymorphisms are associated with protein Z plasma levels. J Thromb Haemost 2004; 2 (07) 1197-1199
25 Santacroce R, Sarno M, Cappucci F. , et al. Low protein Z levels and risk of occurrence of deep vein thrombosis. J Thromb Haemost 2006; 4 (11) 2417-2422
26 Le Cam-Duchez V, Barbay V, Bal Dit Sollier C. , et al. Haplotypic or genotypic combinations of three protein Z polymorphisms influence protein Z plasma level. Thromb Haemost 2009; 101 (01) 212-214
27 Lichy C, Kropp S, Dong-Si T. , et al. A common polymorphism of the protein Z gene is associated with protein Z plasma levels and with risk of cerebral ischemia in the young. Stroke 2004; 35 (01) 40-45
28 Staton J, Sayer M, Hankey GJ, Cole V, Thom J, Eikelboom JW. Protein Z gene polymorphisms, protein Z concentrations, and ischemic stroke. Stroke 2005; 36 (06) 1123-1127
29 Greten J, Kreis I, Liliensiek B. , et al. Localisation of protein Z in vascular lesions of patients with atherosclerosis. Vasa 1998; 27 (03) 144-148
30 Husain S, Andrews NP, Mulcahy D, Panza JA, Quyyumi AA. Aspirin improves endothelial dysfunction in atherosclerosis. Circulation 1998; 97 (08) 716-720
31 Reriani MK, Dunlay SM, Gupta B. , et al. Effects of statins on coronary and peripheral endothelial function in humans: a systematic review and meta-analysis of randomized controlled trials. Eur J Cardiovasc Prev Rehabil 2011; 18 (05) 704-716
32 Peller M, Ozierański K, Balsam P, Grabowski M, Filipiak KJ, Opolski G. Influence of beta-blockers on endothelial function: A meta-analysis of randomized controlled trials. Cardiol J 2015; 22 (06) 708-716
33 Pardos-Gea J, Ordi-Ros J, Serrano S, Balada E, Nicolau I, Vilardell M. Protein Z levels and anti-protein Z antibodies in patients with arterial and venous thrombosis. Thromb Res 2008; 121 (06) 727-734
34 Cesari F, Gori AM, Fedi S, Abbate R, Gensini GF, Sofi F. Modifications of protein Z and interleukin-6 during the acute phase of coronary artery disease. Blood Coagul Fibrinolysis 2007; 18 (01) 85-86
35 Girard TJ, Lasky NM, Tuley EA, Broze Jr GJ. Protein Z, protein Z-dependent protease inhibitor (serpinA10), and the acute-phase response. J Thromb Haemost 2013; 11 (02) 375-378

Supplementary Material

Supplementary Material (PDF)