Anti-varicella Zoster Virus IgG and hsCRP Levels Correlate with Progression of Coronary Artery Atherosclerosis
-
Hamed Fouladseresht
,
Atefe Ghamar Talepoor
,
Shirin Farjadian
,
Shahdad Khosropanah
,
Mehrnoosh Doroudchi
Abstract
The relationship between high levels of anti-Varicella Zoster Virus (VZV) IgG in cerebrospinal fluid (CSF) and cerebrovascular atherosclerosis commends a possible similar association in other vessels. We aimed to investigate the association of VZV-seropositivity with coronary artery atherosclerosis. We recruited 88 newly diagnosed patients with more than 50% stenosis in at least one of the main coronary arteries. As the control group, 99 age-matched individuals with normal/insignificant coronary artery findings were included. Clinical, paraclinical, and demographical data were gathered at the time of sampling. High‐sensitivity C‐reactive protein (hsCRP) levels were measured by nephelometry. VZV-seropositivity was determined by measuring of anti-VZV IgG level in plasma. Multivariable logistic regression was used to evaluate the correlation of data with coronary vascular atherosclerosis. The frequency of VZV-seropositivity was significantly higher in the atherosclerosis group compared to the controls (OR=1.88; 95%CI=1.03-3.44). The plasma levels of anti-VZV IgG were significantly higher in patients with atherosclerosis (Median=2.70, IQR=1.53-4.30 AU/mL) than in the controls (Median=2.10, IQR=1.70-3.10 AU/mL, p=0.034). The hsCRP levels in patients and controls were 5.19±2.00 and 1.51±1.07 mg/L, respectively. The correlation between hsCRP and anti-VZV IgG level in plasma was observed (r=0.40, p<0.001). The levels of hsCRP and anti-VZV IgG increased based on the number of diseased vessels but only the difference in hsCRP levels reached a significant level (p<0.001 and p=0.168, respectively). Our data suggest that VZV-seropositivity and hsCRP elevation jointly increase the risk of atherosclerosis. The multifactorial nature of atherosclerosis; however, leaves more options for the inflammatory milieu to be generated.
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2. Gershon AA, Breuer J, Cohen JI, Cohrs RJ, Gershon MD, Gilden D, et al. Varicella zoster virus infection. Nat Rev Dis Primers 2015; 1:15016.
3. Yawn BP, Wollan PC, Nagel MA, Gilden D, editors. Risk of stroke and myocardial infarction after herpes zoster in older adults in a US community population. Mayo Clin Proc; 2016: Elsevier.
4. Sundström K, Weibull CE, Söderberg-Löfdal K, Bergström T, Sparén P, Arnheim-Dahlström L. Incidence of herpes zoster and associated events including stroke—a population-based cohort study. BMC Infect Dis 2015; 15(1):488.
5. Breuer J, Pacou M, Gautier A, Brown MM. Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study in the UK. Neurology 2014; 83(2):e27-e33.
6. Zhu Y, Xian X, Wang Z, Bi Y, Chen Q, Han X, et al. Research Progress on the Relationship between Atherosclerosis and Inflammation. Biomolecules 2018; 8(3).
7. Shapiro MD, Fazio S. From lipids to inflammation: new approaches to reducing atherosclerotic risk. Circ Res 2016; 118(4):732-49.
8. Ridker PM. How common is residual inflammatory risk? Circ Res 2017; 120(4):617-9.
9. Minassian C, Thomas SL, Smeeth L, Douglas I, Brauer R, Langan SM. Acute cardiovascular events after herpes zoster: a self-controlled case series analysis in vaccinated and unvaccinated older residents of the United States. PLoS Med 2015; 12(12):e1001919.
10. Nagel M, Traktinskiy I, Azarkh Y, Kleinschmidt-DeMasters B, Hedley-Whyte T, Russman A, et al. Varicella zoster virus vasculopathy: analysis of virus-infected arteries. Neurology 2011; 77(4):364-70.
11. Elkind MS. The varicella zoster virus vasculopathies: Clinical, CSF, imaging, and virologic features. Neurology 2009; 72(11):1028-30.
12. Nagel M, Forghani B, Mahalingam R, Wellish M, Cohrs R, Russman A, et al. The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy. Neurology 2007; 68(13):1069-73.
13. Wang CC, Lin CL, Chang YJ, Wang GJ, Sung FC, Kao CH. Herpes zoster infection associated with acute coronary syndrome: a population‐based retrospective cohort study. Br J Dermatol 2014; 170(5):1122-9.
14. Pesonen E, Andsberg E, Öhlin H, Puolakkainen M, Rautelin H, Sarna S, et al. Dual role of infections as risk factors for coronary heart disease. Atherosclerosis 2007; 192(2):370-5.
15. Erskine N, Tran H, Levin L, Ulbricht C, Fingeroth J, Kiefe C, et al. A systematic review and meta-analysis on herpes zoster and the risk of cardiac and cerebrovascular events. PLoS One 2017; 12(7):e0181565.
16. Sproston NR, Ashworth JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol 2018; 9:754.
17. Hage FG, Szalai AJ. C-reactive protein gene polymorphisms, C-reactive protein blood levels, and cardiovascular disease risk. J Am Coll Cardiol 2007; 50(12):1115-22.
18. Ramamoorthy RD, Nallasamy V, Raghavendra Reddy NE, Maruthappan Y. A review of C-reactive protein: A diagnostic indicator in periodontal medicine. J Pharm Bioallied Sci 2012; 4(Suppl 2):S422.
19. Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein (a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA 2001; 285(19):2481-5.
20. Lowe GD, Yarnell JW, Rumley A, Bainton D, Sweetnam PM. C-reactive protein, fibrin D-dimer, and incident ischemic heart disease in the Speedwell study: are inflammation and fibrin turnover linked in pathogenesis? Arterioscler Thromb Vasc Biol 2001; 21(4):603-10.
21. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002; 347(20):1557-65.
22. Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, et al. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 2000; 321(7255):199-204.
23. Roivainen M, Viik-Kajander M, Palosuo T, Toivanen P, Leinonen M, Saikku P, et al. Infections, inflammation, and the risk of coronary heart disease. Circulation 2000; 101(3):252-7.
24. Kim JY, Park G-H, Kim MJ, Sim HB, Lee WJ, Lee S-J, et al. Usefulness of Inflammatory Markers for the Prediction of Postherpetic Neuralgia in Patients with Acute Herpes Zoster. Ann Dermatol 2018; 30(2):158-63.
25. Skripuletz T, Pars K, Schulte A, Schwenkenbecher P, Yildiz Ö, Ganzenmueller T, et al. Varicella zoster virus infections in neurological patients: a clinical study. BMC Infect Dis 2018; 18(1):238.
26. Maleki A, Ghanavati R, Montazeri M, Forughi S, Nabatchi B. Prevalence of Coronary Artery Disease and the Associated Risk Factors in the Adult Population of Borujerd City, Iran. J Tehran Heart Cent 2019; 14(1):1.
27. Esteban-Hernandez J, San JRM, Gil R, Anegón M, Gil A. Association between herpetic burden and chronic ischemic heart disease: matched case-control study. Med Clin (Barc) 2011; 137(4):157-60.
28. Tezcan ME, Teksut TK, Oenal AB, Oeztuerk MA. Reactivated varicella zoster virus may cause peripheral arterial thrombosis. J Rheumatol 2010; 37(8):1785-6.
29. Nagel MA, Gilden D. Developments in varicella zoster virus vasculopathy. Curr Neurol Neurosci Rep 2016; 16(2):12.
30. Blumenthal D, Shacham-Shmueli E, Bokstein F, Schmid D, Cohrs R, Nagel M, et al. Zoster sine herpete: virologic verification by detection of anti-VZV IgG antibody in CSF. Neurology 2011; 76(5):484-5.
31. Smith-Norowitz TA, Saadia TA, Norowitz KB, Joks R, Durkin HG, Kohlhoff S. Negative IgG varicella zoster virus antibody status: immune responses pre and post re-immunization. Infect Dis Ther 2018; 7(1):175-81.
32. Ihara H, Miyachi M, Imafuku S. Relationship between serum anti‐varicella zoster virus antibody titer and time from onset of herpes zoster. J Dermatol 2018; 45(2):189-93.
33. Uthman I, Taher A, Khalil I. Hughes syndrome associated with varicella infection. Rheumatol Int 2001; 20(4):167-8.
34. Massano J, Ferreira D, Toledo T, Mansilha A, Azevedo E, Carvalho M. Stroke and multiple peripheral thrombotic events in an adult with varicella. Eur J Neurol 2008; 15(10):e90-e1.
35. Blum A, Peleg A, Weinberg M. Anti-cytomegalovirus (CMV) IgG antibody titer in patients with risk factors to atherosclerosis. Clin Exp Med 2003; 3(3):157-60.
36. Nagel MA, Traktinskiy I, Stenmark KR, Frid MG, Choe A, Gilden D. Varicella-zoster virus vasculopathy: immune characteristics of virus-infected arteries. Neurology 2013; 80(1):62-8.
37. Rosenfeld ME, Campbell LA. Pathogens and atherosclerosis: update on the potential contribution of multiple infectious organisms to the pathogenesis of atherosclerosis. Thromb Haemost 2011; 106(11):858-67.
38. Auer J, Berent R, Lassnig E, Eber B. C-reactive protein and coronary artery disease. Jpn Heart J 2002; 43(6):607-19.
39. Guilford T, Morris D, Gray D, Venketaraman V. Atherosclerosis: pathogenesis and increased occurrence in individuals with HIV and Mycobacterium tuberculosis infection. HIV AIDS (Auckl) 2010; 2:211.
40. Okamoto S, Hata A, Sadaoka K, Yamanishi K, Mori Y. Comparison of varicella-zoster virus-specific immunity of patients with diabetes mellitus and healthy individuals. J Infect Dis 2009; 200(10):1606-10.
41. Brisson M, Edmunds W, Law B, Gay N, Walld R, Brownell M, et al. Epidemiology of varicella zoster virus infection in Canada and the United Kingdom–corrigendum. Epidemiol Infect 2015; 143(6):1332-.
42. Spence JD, Pilote L. Importance of sex and gender in atherosclerosis and cardiovascular disease. atherosclerosis 2015; 241(1):208-10.
43. Thomas SL, Hall AJ. What does epidemiology tell us about risk factors for herpes zoster? Lancet Infect Dis 2004; 4(1):26-33.
44. Gialloreti LE, Merito M, Pezzotti P, Naldi L, Gatti A, Beillat M, et al. Epidemiology and economic burden of herpes zoster and post-herpetic neuralgia in Italy: a retrospective, population-based study. BMC Infect Dis 2010; 10(1):230.
2. Gershon AA, Breuer J, Cohen JI, Cohrs RJ, Gershon MD, Gilden D, et al. Varicella zoster virus infection. Nat Rev Dis Primers 2015; 1:15016.
3. Yawn BP, Wollan PC, Nagel MA, Gilden D, editors. Risk of stroke and myocardial infarction after herpes zoster in older adults in a US community population. Mayo Clin Proc; 2016: Elsevier.
4. Sundström K, Weibull CE, Söderberg-Löfdal K, Bergström T, Sparén P, Arnheim-Dahlström L. Incidence of herpes zoster and associated events including stroke—a population-based cohort study. BMC Infect Dis 2015; 15(1):488.
5. Breuer J, Pacou M, Gautier A, Brown MM. Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study in the UK. Neurology 2014; 83(2):e27-e33.
6. Zhu Y, Xian X, Wang Z, Bi Y, Chen Q, Han X, et al. Research Progress on the Relationship between Atherosclerosis and Inflammation. Biomolecules 2018; 8(3).
7. Shapiro MD, Fazio S. From lipids to inflammation: new approaches to reducing atherosclerotic risk. Circ Res 2016; 118(4):732-49.
8. Ridker PM. How common is residual inflammatory risk? Circ Res 2017; 120(4):617-9.
9. Minassian C, Thomas SL, Smeeth L, Douglas I, Brauer R, Langan SM. Acute cardiovascular events after herpes zoster: a self-controlled case series analysis in vaccinated and unvaccinated older residents of the United States. PLoS Med 2015; 12(12):e1001919.
10. Nagel M, Traktinskiy I, Azarkh Y, Kleinschmidt-DeMasters B, Hedley-Whyte T, Russman A, et al. Varicella zoster virus vasculopathy: analysis of virus-infected arteries. Neurology 2011; 77(4):364-70.
11. Elkind MS. The varicella zoster virus vasculopathies: Clinical, CSF, imaging, and virologic features. Neurology 2009; 72(11):1028-30.
12. Nagel M, Forghani B, Mahalingam R, Wellish M, Cohrs R, Russman A, et al. The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy. Neurology 2007; 68(13):1069-73.
13. Wang CC, Lin CL, Chang YJ, Wang GJ, Sung FC, Kao CH. Herpes zoster infection associated with acute coronary syndrome: a population‐based retrospective cohort study. Br J Dermatol 2014; 170(5):1122-9.
14. Pesonen E, Andsberg E, Öhlin H, Puolakkainen M, Rautelin H, Sarna S, et al. Dual role of infections as risk factors for coronary heart disease. Atherosclerosis 2007; 192(2):370-5.
15. Erskine N, Tran H, Levin L, Ulbricht C, Fingeroth J, Kiefe C, et al. A systematic review and meta-analysis on herpes zoster and the risk of cardiac and cerebrovascular events. PLoS One 2017; 12(7):e0181565.
16. Sproston NR, Ashworth JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol 2018; 9:754.
17. Hage FG, Szalai AJ. C-reactive protein gene polymorphisms, C-reactive protein blood levels, and cardiovascular disease risk. J Am Coll Cardiol 2007; 50(12):1115-22.
18. Ramamoorthy RD, Nallasamy V, Raghavendra Reddy NE, Maruthappan Y. A review of C-reactive protein: A diagnostic indicator in periodontal medicine. J Pharm Bioallied Sci 2012; 4(Suppl 2):S422.
19. Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein (a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA 2001; 285(19):2481-5.
20. Lowe GD, Yarnell JW, Rumley A, Bainton D, Sweetnam PM. C-reactive protein, fibrin D-dimer, and incident ischemic heart disease in the Speedwell study: are inflammation and fibrin turnover linked in pathogenesis? Arterioscler Thromb Vasc Biol 2001; 21(4):603-10.
21. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002; 347(20):1557-65.
22. Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, et al. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 2000; 321(7255):199-204.
23. Roivainen M, Viik-Kajander M, Palosuo T, Toivanen P, Leinonen M, Saikku P, et al. Infections, inflammation, and the risk of coronary heart disease. Circulation 2000; 101(3):252-7.
24. Kim JY, Park G-H, Kim MJ, Sim HB, Lee WJ, Lee S-J, et al. Usefulness of Inflammatory Markers for the Prediction of Postherpetic Neuralgia in Patients with Acute Herpes Zoster. Ann Dermatol 2018; 30(2):158-63.
25. Skripuletz T, Pars K, Schulte A, Schwenkenbecher P, Yildiz Ö, Ganzenmueller T, et al. Varicella zoster virus infections in neurological patients: a clinical study. BMC Infect Dis 2018; 18(1):238.
26. Maleki A, Ghanavati R, Montazeri M, Forughi S, Nabatchi B. Prevalence of Coronary Artery Disease and the Associated Risk Factors in the Adult Population of Borujerd City, Iran. J Tehran Heart Cent 2019; 14(1):1.
27. Esteban-Hernandez J, San JRM, Gil R, Anegón M, Gil A. Association between herpetic burden and chronic ischemic heart disease: matched case-control study. Med Clin (Barc) 2011; 137(4):157-60.
28. Tezcan ME, Teksut TK, Oenal AB, Oeztuerk MA. Reactivated varicella zoster virus may cause peripheral arterial thrombosis. J Rheumatol 2010; 37(8):1785-6.
29. Nagel MA, Gilden D. Developments in varicella zoster virus vasculopathy. Curr Neurol Neurosci Rep 2016; 16(2):12.
30. Blumenthal D, Shacham-Shmueli E, Bokstein F, Schmid D, Cohrs R, Nagel M, et al. Zoster sine herpete: virologic verification by detection of anti-VZV IgG antibody in CSF. Neurology 2011; 76(5):484-5.
31. Smith-Norowitz TA, Saadia TA, Norowitz KB, Joks R, Durkin HG, Kohlhoff S. Negative IgG varicella zoster virus antibody status: immune responses pre and post re-immunization. Infect Dis Ther 2018; 7(1):175-81.
32. Ihara H, Miyachi M, Imafuku S. Relationship between serum anti‐varicella zoster virus antibody titer and time from onset of herpes zoster. J Dermatol 2018; 45(2):189-93.
33. Uthman I, Taher A, Khalil I. Hughes syndrome associated with varicella infection. Rheumatol Int 2001; 20(4):167-8.
34. Massano J, Ferreira D, Toledo T, Mansilha A, Azevedo E, Carvalho M. Stroke and multiple peripheral thrombotic events in an adult with varicella. Eur J Neurol 2008; 15(10):e90-e1.
35. Blum A, Peleg A, Weinberg M. Anti-cytomegalovirus (CMV) IgG antibody titer in patients with risk factors to atherosclerosis. Clin Exp Med 2003; 3(3):157-60.
36. Nagel MA, Traktinskiy I, Stenmark KR, Frid MG, Choe A, Gilden D. Varicella-zoster virus vasculopathy: immune characteristics of virus-infected arteries. Neurology 2013; 80(1):62-8.
37. Rosenfeld ME, Campbell LA. Pathogens and atherosclerosis: update on the potential contribution of multiple infectious organisms to the pathogenesis of atherosclerosis. Thromb Haemost 2011; 106(11):858-67.
38. Auer J, Berent R, Lassnig E, Eber B. C-reactive protein and coronary artery disease. Jpn Heart J 2002; 43(6):607-19.
39. Guilford T, Morris D, Gray D, Venketaraman V. Atherosclerosis: pathogenesis and increased occurrence in individuals with HIV and Mycobacterium tuberculosis infection. HIV AIDS (Auckl) 2010; 2:211.
40. Okamoto S, Hata A, Sadaoka K, Yamanishi K, Mori Y. Comparison of varicella-zoster virus-specific immunity of patients with diabetes mellitus and healthy individuals. J Infect Dis 2009; 200(10):1606-10.
41. Brisson M, Edmunds W, Law B, Gay N, Walld R, Brownell M, et al. Epidemiology of varicella zoster virus infection in Canada and the United Kingdom–corrigendum. Epidemiol Infect 2015; 143(6):1332-.
42. Spence JD, Pilote L. Importance of sex and gender in atherosclerosis and cardiovascular disease. atherosclerosis 2015; 241(1):208-10.
43. Thomas SL, Hall AJ. What does epidemiology tell us about risk factors for herpes zoster? Lancet Infect Dis 2004; 4(1):26-33.
44. Gialloreti LE, Merito M, Pezzotti P, Naldi L, Gatti A, Beillat M, et al. Epidemiology and economic burden of herpes zoster and post-herpetic neuralgia in Italy: a retrospective, population-based study. BMC Infect Dis 2010; 10(1):230.
| Files | ||
| Issue | Vol 18, No 5 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v18i5.1924 | |
| PMID | 32245298 | |
| Keywords | ||
| Atherosclerosis C-reactive protein Immunoglobulin G Varicella-zoster virus | ||
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How to Cite
1.
Fouladseresht H, Ghamar Talepoor A, Farjadian S, Khosropanah S, Doroudchi M. Anti-varicella Zoster Virus IgG and hsCRP Levels Correlate with Progression of Coronary Artery Atherosclerosis. Iran J Allergy Asthma Immunol. 2019;18(5):543-553.
