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Current Proteomics

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ISSN (Print): 1570-1646
ISSN (Online): 1875-6247

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Research Article

High-Sensitivity C-Reactive Protein and Lipoprotein-Associated Phospholipase A2 in Predicting Recurrence and Severity of Stenosis in Symptomatic Intracranial Atherosclerotic Disease

Author(s): Soumya Krishnamoorthy , Deepa Damayanthi, Srinivas Gopala, Rejith Paul and P.N. Sylaja*

Volume 18, Issue 2, 2021

Published on: 14 April, 2020

Page: [231 - 236] Pages: 6

DOI: 10.2174/1570164617666200414123848

Price: $65

Abstract

Background: Symptomatic intracranial atherosclerotic Disease (sICAD) is associated with the risk of recurrence of cerebral ischemic events in 4-19% of stroke patients annually. Previous studies indicate elevated high-sensitivity C-Reactive Protein (hs-CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) to be associated with risk of recurrence.

Objective: This prospective, observational study investigated serum levels of hs-CRP and the activity of Lp-PLA2 in patients with sICAD in predicting the risk of long-term stroke recurrence.

Methods: We enrolled 48 patients with sICAD at 3 months from onset. The demographics, clinical, and imaging characteristics were recorded. Serum hs-CRP and Lp-PLA2 activity were assessed using automated high-sensitivity C-reactive protein assay and photometric technique, respectively. Patients were followed up at 6 months and 1 year and the presence of new vascular events was recorded.

Results: The mean age of our study population was 59.5 ± 10.3 years and 91.7% were men. Four patients developed recurrent strokes during follow-up. The mean Hs-CRP was elevated in patients with events than in patients without events (5.9 ± 10.4 mg/L vs. 1.7 ± 2.4 mg/L, P=0.03). However, there was no significant association of mean Lp-PLA2 activity (118.3±42.9 nmol/min/ml vs. 111.9 ± 34.2 nmol/min/ml, P=0.73) with recurrence. Elevation of hs-CRP (3.02 ± 4.8 mg/L vs. 0.95 ± 0.57mg/L, P=0.02) and Lp-PLA2 activity (120.1±40.3 nmol/min/ml vs. 103.3 ± 23.9 nmol/min/ml, P=0.04) was correlated with high-grade stenosis in these patients.

Conclusion: Our study suggests serum levels of hs-CRP may serve as a predictor of long-term stroke recurrence risk in sICAD and elevation of hs-CRP and Lp-PLA2 correlated with the severity of stenosis in symptomatic intracranial atherosclerotic disease.

Keywords: Biomarker, intracranial atherosclerosis, high sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, stroke recurrence, plaque.

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Graphical Abstract

[1]
Chimowitz, M.I.; Lynn, M.J.; Derdeyn, C.P.; Turan, T.N.; Fiorella, D.; Lane, B.F.; Janis, L.S.; Lutsep, H.L.; Barnwell, S.L.; Waters, M.F.; Hoh, B.L.; Hourihane, J.M.; Levy, E.I.; Alexandrov, A.V.; Harrigan, M.R.; Chiu, D.; Klucznik, R.P.; Clark, J.M.; McDougall, C.G.; Johnson, M.D.; Pride, G.L., Jr; Torbey, M.T.; Zaidat, O.O.; Rumboldt, Z.; Cloft, H.J. SAMMPRIS trial investigators. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N. Engl. J. Med., 2011, 365(11), 993-1003.
[http://dx.doi.org/10.1056/NEJMoa1105335] [PMID: 21899409]
[2]
Kate, M.; Sylaja, P.N.; Kesavadas, C.; Thomas, B. Imaging and clinical predictors of unfavorable outcome in medically treated symptomatic intracranial atherosclerotic disease. J. Stroke Cerebrovasc. Dis., 2014, 23(5), 973-978.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.08.002] [PMID: 24119624]
[3]
Mazighi, M.; Tanasescu, R.; Ducrocq, X.; Vicaut, E.; Bracard, S.; Houdart, E.; Woimant, F. Prospective study of symptomatic atherothrombotic intracranial stenoses: The GESICA study. Neurology, 2006, 66(8), 1187-1191.
[http://dx.doi.org/10.1212/01.wnl.0000208404.94585.b2] [PMID: 16636236]
[4]
Skarpathiotakis, M.; Mandell, D.M.; Swartz, R.H.; Tomlinson, G.; Mikulis, D.J. Intracranial atherosclerotic plaque enhancement in patients with ischemic stroke. AJNR Am. J. Neuroradiol., 2013, 34(2), 299-304.
[http://dx.doi.org/10.3174/ajnr.A3209] [PMID: 22859280]
[5]
Jeon, S.B.; Chun, S.; Choi-Kwon, S.; Chi, H.S.; Nah, H.W.; Kwon, S.U.; Kim, W.K.; Kim, J.S. Biomarkers and location of atherosclerosis: matrix metalloproteinase-2 may be related to intracranial atherosclerosis. Atherosclerosis, 2012, 223(2), 442-447.
[http://dx.doi.org/10.1016/j.atherosclerosis.2012.04.013] [PMID: 22727191]
[6]
López-Cancio, E.; Galán, A.; Dorado, L.; Jiménez, M.; Hernández, M.; Millán, M.; Reverté, S.; Suñol, A.; Barallat, J.; Massuet, A.; Alzamora, M.T.; Dávalos, A.; Arenillas, J.F. Biological signatures of asymptomatic extra- and intracranial atherosclerosis: the Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) study. Stroke, 2012, 43(10), 2712-2719.
[http://dx.doi.org/10.1161/STROKEAHA.112.661702] [PMID: 22798326]
[7]
Arenillas, J.F.; Molina, C.A.; Chacón, P.; Rovira, A.; Montaner, J.; Coscojuela, P.; Sánchez, E.; Quintana, M.; Alvarez-Sabín, J. High lipoprotein (a), diabetes, and the extent of symptomatic intracranial atherosclerosis. Neurology, 2004, 63(1), 27-32.
[http://dx.doi.org/10.1212/01.WNL.0000132637.30287.B4] [PMID: 15249606]
[8]
Kim, B.S.; Jung, H.S.; Bang, O.Y.; Chung, C.S.; Lee, K.H.; Kim, G.M. Elevated serum lipoprotein(a) as a potential predictor for combined intracranial and extracranial artery stenosis in patients with ischemic stroke. Atherosclerosis, 2010, 212(2), 682-688.
[http://dx.doi.org/10.1016/j.atherosclerosis.2010.07.007] [PMID: 20691971]
[9]
Bang, O.Y.; Saver, J.L.; Ovbiagele, B.; Choi, Y.J.; Yoon, S.R.; Lee, K.H. Adiponectin levels in patients with intracranial atherosclerosis. Neurology, 2007, 68(22), 1931-1937.
[http://dx.doi.org/10.1212/01.wnl.0000263186.20988.9f] [PMID: 17536050]
[10]
Hoshi, T.; Kitagawa, K.; Yamagami, H.; Furukado, S.; Hougaku, H.; Hori, M. Relation between interleukin-6 level and subclinical intracranial large-artery atherosclerosis. Atherosclerosis, 2008, 197(1), 326-332.
[http://dx.doi.org/10.1016/j.atherosclerosis.2007.05.013] [PMID: 17604035]
[11]
Purroy, F.; Montaner, J.; Molina, C.A.; Delgado, P.; Arenillas, J.F.; Chacon, P.; Quintana, M.; Alvarez-Sabin, J. C-reactive protein predicts further ischemic events in transient ischemic attack patients. Acta Neurol. Scand., 2007, 115(1), 60-66.
[http://dx.doi.org/10.1111/j.1600-0404.2006.00715.x] [PMID: 17156267]
[12]
Massot, A.; Pelegri, D.; Penalba, A.; Arenillas, J.; Boada, C.; Giralt, D.; Ribó, M.; Molina, C.A.; Rosell, A.; Alvarez-Sabín, J.; Chacón, P.; Rovira, A.; Delgado, P.; Montaner, J. Lipoprotein-associated phospholipase A2 testing usefulness among patients with symptomatic intracranial atherosclerotic disease. Atherosclerosis, 2011, 218(1), 181-187.
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.04.031] [PMID: 21620406]
[13]
Arenillas, J.F.; Alvarez-Sabín, J.; Molina, C.A.; Chacón, P.; Montaner, J.; Rovira, A.; Ibarra, B.; Quintana, M. C-reactive protein predicts further ischemic events in first-ever transient ischemic attack or stroke patients with intracranial large-artery occlusive disease. Stroke, 2003, 34(10), 2463-2468.
[http://dx.doi.org/10.1161/01.STR.0000089920.93927.A7] [PMID: 14500938]
[14]
Gong, X.; Zou, X.; Liu, L.; Pu, Y.; Wang, Y.; Pan, Y.; Soo, Y.O.; Leung, T.W.; Zhao, X.; Wang, Y.; Wong, K.S. Prognostic value of inflammatory mediators in 1-year outcome of acute ischemic stroke with middle cerebral artery stenosis. Mediators Inflamm., 2013, 2013, 850714.
[http://dx.doi.org/10.1155/2013/850714] [PMID: 24023414]
[15]
Di Napoli, M.; Papa, F.; Bocola, V. C-reactive protein in ischemic stroke: an independent prognostic factor. Stroke, 2001, 32(4), 917-924.
[http://dx.doi.org/10.1161/01.STR.32.4.917] [PMID: 11283392]
[16]
Zalewski, A.; Nelson, J.J.; Hegg, L.; Macphee, C. Lp-PLA2: A new kid on the block. Clin. Chem., 2006, 52(9), 1645-1650.
[http://dx.doi.org/10.1373/clinchem.2006.070672] [PMID: 16873290]
[17]
Ballantyne, C.M.; Hoogeveen, R.C.; Bang, H.; Coresh, J.; Folsom, A.R.; Heiss, G.; Sharrett, A.R. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Circulation, 2004, 109(7), 837-842.
[http://dx.doi.org/10.1161/01.CIR.0000116763.91992.F1] [PMID: 14757686]
[18]
Elkind, M.S.V.; Tai, W.; Coates, K.; Paik, M.C.; Sacco, R.L. Lipoprotein-associated phospholipase A2 activity and risk of recurrent stroke. Cerebrovasc. Dis., 2009, 27(1), 42-50.
[http://dx.doi.org/10.1159/000172633] [PMID: 19018137]
[19]
Anderson, J.L. Lipoprotein-associated phospholipase A2: an independent predictor of coronary artery disease events in primary and secondary prevention. Am. J. Cardiol., 2008, 101(12A), 23F-33F.
[http://dx.doi.org/10.1016/j.amjcard.2008.04.015] [PMID: 18549868]
[20]
Wang, Y.; Zhang, J.; Qian, Y.; Tang, X.; Ling, H.; Chen, K.; Gao, P.; Zhu, D. Association of Lp-PLA2 Mass and aysmptomatic intracranial and extracranial arterial stenosis in hypertension patients. PLoS One, 2015, 10(6), e0130473.
[http://dx.doi.org/10.1371/journal.pone.0130473] [PMID: 26098634]
[21]
Liu, H.; Yao, Y.; Wang, Y.; Ji, L.; Zhu, K.; Hu, H.; Chen, J.; Yang, J.; Cui, Q.; Geng, B.; Liu, Q.; Li, D.; Zhou, Y. Association between high-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2 and carotid atherosclerosis: A cross-sectional study. J. Cell. Mol. Med., 2018, 22(10), 5145-5150.
[http://dx.doi.org/10.1111/jcmm.13803] [PMID: 30094934]
[22]
Zhuo, S.; Wolfert, R.L.; Yuan, C. Biochemical differences in the mass and activity tests of lipoprotein-associated phospholipase A2 explain the discordance in results between the two assay methods. Clin. Biochem., 2017, 50(18), 1209-1215.
[http://dx.doi.org/10.1016/j.clinbiochem.2017.08.019] [PMID: 28899631]
[23]
Wei, L.; Ke, Z.; Zhao, Y.; Cai, Z. The elevated lipoprotein-associated phospholipase A2 activity is associated with the occurrence and recurrence of acute cerebral infarction. Neuroreport, 2017, 28(6), 325-330.
[http://dx.doi.org/10.1097/WNR.0000000000000765] [PMID: 28272264]
[24]
Blake, G.J.; Dada, N.; Fox, J.C.; Manson, J.E.; Ridker, P.M. A prospective evaluation of lipoprotein-associated phospholipase A(2) levels and the risk of future cardiovascular events in women. J. Am. Coll. Cardiol., 2001, 38(5), 1302-1306.
[http://dx.doi.org/10.1016/S0735-1097(01)01554-6] [PMID: 11691499]
[25]
Albert, M.A.; Glynn, R.J.; Wolfert, R.L.; Ridker, P.M. The effect of statin therapy on lipoprotein associated phospholipase A2 levels. Atherosclerosis, 2005, 182(1), 193-198.
[http://dx.doi.org/10.1016/j.atherosclerosis.2005.05.006] [PMID: 15982658]
[26]
Lin, J.; Zheng, H.; Cucchiara, B.L.; Li, J.; Zhao, X.; Liang, X.; Wang, C.; Li, H.; Mullen, M.T.; Johnston, S.C.; Wang, Y.; Wang, Y. CHANCE investigators. Association of Lp-PLA2-A and early recurrence of vascular events after TIA and minor stroke. Neurology, 2015, 85(18), 1585-1591.
[http://dx.doi.org/10.1212/WNL.0000000000001938] [PMID: 26311748]
[27]
Sylaja, P.N.; Pandian, J.D.; Kaul, S.; Srivastava, M.V.P.; Khurana, D.; Schwamm, L.H.; Kesav, P.; Arora, D.; Pannu, A.; Thankachan, T.K.; Singhal, A.B. Ischemic stroke profile, risk factors, and outcomes in India: the Indo-US collaborative stroke project. Stroke, 2018, 49(1), 219-222.
[http://dx.doi.org/10.1161/STROKEAHA.117.018700] [PMID: 29167386]
[28]
Kaul, S.; Alladi, S.; Jabeen, S.A.; Bandaru, V.C.S.S.R.; Ankem, U.; Mekala, S.; Naik, G.S. Intracranial atherosclerosis is the most common stroke subtype: Ten-year data from Hyderabad stroke registry (India). Ann. Indian Acad. Neurol., 2018, 21(3), 209-213.
[http://dx.doi.org/10.4103/aian.AIAN_86_18] [PMID: 30258264]

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