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The relationship between soluble CD40 ligand level and atherosclerosis in white-coat hypertension

Journal of Human Hypertension volume 32, pages 40–45 (2018)Cite this article

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Abstract

This study was designed to examine the distribution of plasma soluble CD40 ligand (sCD40L), and its relationship with carotid intima-media thickness (CIMT) in healthy controls and subjects with white-coat hypertension (WCH) or hypertension (HT). Thirty-five patients with HT, 35 patients with WCH, and 35 healthy controls were enrolled. The normal group (CIMT < 0.9 mm), subclinical atherosclerosis group (0.9 mm ≤ CIMT < 1.2 mm) and atherosclerosis group (CIMT ≥ 1.2 mm) were grouped based on the value of CIMT. The highest level of sCD40L was observed in HT group, followed by WCH group and healthy controls. The level of sCD40L was significantly increased in atherosclerosis group compared with subclinical atherosclerosis group and healthy controls. In the WCH group, sCD40L level was significantly and positively correlated with CIMT and systolic blood pressure. Multiple logistic regression indicated that sCD40L was a risk factor for increased CIMT (odds ratio, 1.504; 95% confidence interval, 1.054–1.956, P < 0.001). The data provided evidence that sCD40L levels in subjects with WCH and HT were significantly and consistently higher than those in healthy controls. SCD40L may represent a potential non-invasive atherosclerosis marker in WCH patients.

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References

  1. Leung AA, Nerenberg K, Daskalopoulou SS, McBrien K, Zarnke KB, Dasgupta K, et al. Hypertension Canada’s 2016 Canadian hypertension education program guidelines for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol. 2016;32:569–88.

    Article  Google Scholar 

  2. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2224–60.

    Article  Google Scholar 

  3. Taylor J. 2013 ESH/ESC guidelines for the management of arterial hypertension. Eur Heart J. 2013;34:2108–9.

    Article  Google Scholar 

  4. Richardson ME. An evidence-based practice case study: white coat hypertension. Plast Surg Nurs. 2015;35:11–12.

    Article  Google Scholar 

  5. Mancia G, Bombelli M, Facchetti R, Madotto F, Quarti-Trevano F, Grassi G, et al. Increased long-term risk of new-onset diabetes mellitus in white-coat and masked hypertension. J Hypertens. 2009;27:1672–8.

    Article  CAS  Google Scholar 

  6. Fagard RH, Cornelissen VA. Incidence of cardiovascular events in white-coat, masked and sustained hypertension versus true normotension: a meta-analysis. J Hypertens. 2007;25:2193–8.

    Article  CAS  Google Scholar 

  7. Verdecchia P, Reboldi GP, Angeli F, Schillaci G, Schwartz JE, Pickering TG, et al. Short- and long-term incidence of stroke in white-coat hypertension. Hypertension. 2005;45:203–8.

    Article  CAS  Google Scholar 

  8. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34:2159–219.

    Article  Google Scholar 

  9. McEvoy JW, Nasir K, DeFilippis AP, Lima JA, Bluemke DA, Hundley WG, et al. Relationship of cigarette smoking with inflammation and subclinical vascular disease: the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2015;35:1002–10.

    Article  CAS  Google Scholar 

  10. Schonbeck U, Libby P. CD40 signaling and plaque instability. Circ Res. 2001;89:1092–103.

    Article  CAS  Google Scholar 

  11. Schonbeck U, Varo N, Libby P, Buring J, Ridker PM. Soluble CD40L and cardiovascular risk in women. Circulation. 2001;104:2266–8.

    Article  CAS  Google Scholar 

  12. Desideri G, Panichi V, Paoletti S, Grassi D, Bigazzi R, Beati S, et al. Soluble CD40 ligand is predictive of combined cardiovascular morbidity and mortality in patients on haemodialysis at a relatively short-term follow-up. Nephrol Dial Transplant. 2011;26:2983–8.

    Article  CAS  Google Scholar 

  13. Yuan M, Fu H, Ren L, Wang H, Guo W. Soluble CD40 ligand promotes macrophage foam cell formation in the etiology of atherosclerosis. Cardiology. 2015;131:1–12.

    Article  CAS  Google Scholar 

  14. Zhang B, Wu T, Chen M, Zhou Y, Yi D, Guo R. The CD40/CD40L system: a new therapeutic target for disease. Immunol Lett. 2013;153:58–61.

    Article  CAS  Google Scholar 

  15. Hassan GS, Merhi Y, Mourad W. CD40 ligand: a neo-inflammatory molecule in vascular diseases. Immunobiology. 2012;217:521–32.

    Article  CAS  Google Scholar 

  16. Chakrabarti S, Rizvi M, Pathak D, Kirber MT, Freedman JE. Hypoxia influences CD40-CD40L mediated inflammation in endothelial and monocytic cells. Immunol Lett. 2009;122:170–84.

    Article  CAS  Google Scholar 

  17. Rizvi M, Pathak D, Freedman JE, Chakrabarti S. CD40-CD40 ligand interactions in oxidative stress, inflammation and vascular disease. Trends Mol Med. 2008;14:530–8.

    Article  CAS  Google Scholar 

  18. O’Brien E, Waeber B, Parati G, Staessen J, Myers MG. Blood pressure measuring devices: recommendations of the European Society of Hypertension. BMJ. 2001;322:531–6.

    Article  Google Scholar 

  19. Cardellini M, Marini MA, Frontoni S, Hribal ML, Andreozzi F, Perticone F, et al. Carotid artery intima-media thickness is associated with insulin-mediated glucose disposal in nondiabetic normotensive offspring of type 2 diabetic patients. Am J Physiol Endocrinol Metab. 2007;292:E347–52.

    Article  CAS  Google Scholar 

  20. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007;28:1462–536.

    PubMed  Google Scholar 

  21. Zhao P, Fang WJ, Chai L, Ruan J, Zheng Y, Jiang WQ, et al. The prognostic value of plasma soluble CD40 ligand levels in patients with nasopharyngeal carcinoma. Clin Chim Acta. 2015;447:66–70.

    Article  CAS  Google Scholar 

  22. Surgit O, Erturk M, Akgul O, Pusuroglu H, Korkmaz AF, Isiksacan N, et al. Assessment of mean platelet volume and soluble CD40 ligand levels in patients with non-dipper hypertension, dippers and normotensives. Clin Exp Hypertens. 2015;37:70–4.

    Article  CAS  Google Scholar 

  23. Fleg JL, Forman DE, Berra K, Bittner V, Blumenthal JA, Chen MA, et al. Secondary prevention of atherosclerotic cardiovascular disease in older adults: a scientific statement from the American Heart Association. Circulation. 2013;128:2422–46

    Article  Google Scholar 

  24. Lobbes MB, Lutgens E, Heeneman S, Cleutjens KB, Kooi ME, van Engelshoven JM, et al. Is there more than C-reactive protein and fibrinogen? The prognostic value of soluble CD40 ligand, interleukin-6 and oxidized low-density lipoprotein with respect to coronary and cerebral vascular disease. Atherosclerosis. 2006;187:18–25.

    Article  CAS  Google Scholar 

  25. Bisoendial RJ, Boekholdt SM, Vergeer M, Stroes ES, Kastelein JJ. C-reactive protein is a mediator of cardiovascular disease. Eur Heart J. 2010;31:2087–91.

    Article  CAS  Google Scholar 

  26. Schulz S, Ludike H, Lierath M, Schlitt A, Werdan K, Hofmann B, et al. C-reactive protein levels and genetic variants of CRP as prognostic markers for combined cardiovascular endpoint (cardiovascular death, death from stroke, myocardial infarction, and stroke/TIA). Cytokine. 2016;88:71–76.

    Article  CAS  Google Scholar 

  27. Ferreira V, van Dijk KW, Groen AK, Vos RM, van der Kaa J, Gijbels MJ, et al. Macrophage-specific inhibition of NF-kappaB activation reduces foam-cell formation. Atherosclerosis. 2007;192:283–90.

    Article  CAS  Google Scholar 

  28. Chen TH, Shih CY, Hsu WL, Chou TC. Mechanisms of Nifedipine-downregulated CD40L/sCD40L signaling in collagen stimulated human platelets. PLoS ONE. 2015;10:e127054.

    Google Scholar 

  29. Kunjathoor VV, Febbraio M, Podrez EA, Moore KJ, Andersson L, Koehn S, et al. Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J Biol Chem. 2002;277:49982–8.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank all the participating volunteers for their efforts and contributions. This work was supported by grants from the Guangdong Natural Science Foundation (No. 2015A030313660), the Technology Project Foundation of Guangzhou (No. 2014y2-00140, No. 1563000381, No. 201604020018, No. 201604020186) and the Technology Project Foundation of Guangdong Province (No. 2014B020212008).

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  1. Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Disease, Guangdong General Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, 510080, China

    Yu-qing Huang, LI Jie, Ji-yan Chen, Cheng Huang & Ying-qing Feng

  2. Department of General Practice, Community Health Center of Liaobu County, Dongguan, Guangdong, 523400, China

    Song-tao Tang

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  1. Yu-qing Huang
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Correspondence to Ying-qing Feng.

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Huang, Yq., Jie, L., Chen, Jy. et al. The relationship between soluble CD40 ligand level and atherosclerosis in white-coat hypertension. J Hum Hypertens 32, 40–45 (2018). https://doi.org/10.1038/s41371-017-0016-z

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