Statins can increase the risk of herpes zoster infection in Asia

  • H.-H. Chen
  • C.-L. Lin
  • C.-J. Yeh
  • S.-Y. Yeh
  • C.-H. KaoEmail author


This study evaluated whether statin therapy increases the risk of herpes zoster (HZ) infection in Asia. This retrospective cohort study used the Longitudinal Health Insurance Database (LHID2000). From the LHID2000, patients aged 20 years were divided into two cohorts according to their statin use and were matched at a 1:1 ratio according to propensity scores, which were calculated using a logistic regression for estimating the probability of treatment assignment. The primary outcome was HZ infection. All patients were followed from the index date until the date of HZ infection, withdrawal from the insurance system, or the end of 2011. The study included 53,069 patients receiving statin therapy as a statin cohort and 53,069 patients without statin therapy as a nonstatin cohort. The mean follow-up durations for the statin cohort and nonstatin cohort were 4.89 [standard deviation (SD) = 2.86] years and 4.75 (SD = 2.90) years, respectively. The patients in the statin cohort had a 21 % higher risk of contracting HZ infection than the patients in the nonstatin cohort [95 % confidence interval (CI) = 1.13–1.29]. The incidence of HZ infection increased with the Charlson comorbidity index (CCI) score in both cohorts. A high mean defined daily dose of the six types of statins considered in this study was associated with a significantly increased risk of HZ infection. Statin therapy can increase HZ infection in Asia. More benefit–risk evaluations for statin use are necessary in Asia.


Statin Propensity Score Statin Therapy Herpes Zoster Charlson Comorbidity Index 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Ethics statement

The National Health Insurance Research Database (NHIRD) encrypts patient personal information to protect privacy and provides researchers with anonymous identification numbers associated with relevant claims information, including sex, date of birth, medical services received, and prescriptions. Patient consent is not required to access the NHIRD. This study was approved by the Institutional Review Board (IRB) of China Medical University (CMU-REC-101-012). The IRB specifically waived the consent requirement.


Conception/design: Hsin-Hung Chen, Chia-Hung Kao.

Provision of study material or patients: Hsin-Hung Chen, Chia-Hung Kao.

Collection and/or assembly of data: Hsin-Hung Chen, Cheng-Li Lin, Chia-Hung Kao.

Data analysis and interpretation: Hsin-Hung Chen, Cheng-Li Lin, Chia-Hung Kao.

Manuscript writing: all authors.

Final approval of manuscript: all authors.


This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW104-TDU-B-212-113002); China Medical University Hospital, Academia Sinica Taiwan Biobank, Stroke Biosignature Project (BM104010092); NRPB Stroke Clinical Trial Consortium (MOST 103-2325-B-039 -006); Tseng-Lien Lin Foundation, Taichung, Taiwan; Taiwan Brain Disease Foundation, Taipei, Taiwan; Katsuzo and Kiyo Aoshima Memorial Funds, Japan; and Health and Welfare Surcharge of Tobacco Products, China Medical University Hospital Cancer Research Center of Excellence (MOHW104-TDU-B-212-124-002, Taiwan). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.

Conflict of interest

All authors declare that they have no conflict of interest.


  1. 1.
    Rabar S, Harker M, O’Flynn N, Wierzbicki AS; Guideline Development Group (2014) Lipid modification and cardiovascular risk assessment for the primary and secondary prevention of cardiovascular disease: summary of updated NICE guidance. BMJ 349:g4356PubMedCrossRefGoogle Scholar
  2. 2.
    Stone NJ, Robinson JG, Lichtenstein AH et al (2014) 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 129:S1–S45PubMedCrossRefGoogle Scholar
  3. 3.
    McFarlane SI, Muniyappa R, Francisco R, Sowers JR (2002) Clinical review 145: Pleiotropic effects of statins: lipid reduction and beyond. J Clin Endocrinol Metab 87:1451–1458PubMedCrossRefGoogle Scholar
  4. 4.
    Mihos CG, Salas MJ, Santana O (2010) The pleiotropic effects of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in cardiovascular disease: a comprehensive review. Cardiol Rev 18:298–304PubMedCrossRefGoogle Scholar
  5. 5.
    Jih JS, Chen YJ, Lin MW et al (2009) Epidemiological features and costs of herpes zoster in Taiwan: a national study 2000 to 2006. Acta Derm Venereol 89:612–616PubMedCrossRefGoogle Scholar
  6. 6.
    Heymann AD, Chodick G, Karpati T et al (2008) Diabetes as a risk factor for herpes zoster infection: results of a population-based study in Israel. Infection 36:226–230PubMedCrossRefGoogle Scholar
  7. 7.
    Terao M, Yamamoto T, Umeda J, Shirabe H (2005) Drug induced herpes zoster (Do statin induce herpes zoster?). Skin Res 4:335–338Google Scholar
  8. 8.
    Antoniou T, Zheng H, Singh S et al (2014) Statins and the risk of herpes zoster: a population-based cohort study. Clin Infect Dis 58:350–356PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Sever PS, Chang CL, Gupta AK, Whitehouse A, Poulter NR; ASCOT Investigators (2011) The Anglo-Scandinavian Cardiac Outcomes Trial: 11-year mortality follow-up of the lipid-lowering arm in the U.K. Eur Heart J 32:2525–2532PubMedCrossRefGoogle Scholar
  10. 10.
    Tleyjeh IM, Kashour T, Hakim FA et al (2009) Statins for the prevention and treatment of infections: a systematic review and meta-analysis. Arch Intern Med 169:1658–1667PubMedCrossRefGoogle Scholar
  11. 11.
    Chalmers JD, Short PM, Mandal P, Akram AR, Hill AT (2010) Statins in community acquired pneumonia: Evidence from experimental and clinical studies. Respir Med 104:1081–1091PubMedCrossRefGoogle Scholar
  12. 12.
    Istvan ES, Deisenhofer J (2001) Structural mechanism for statin inhibition of HMG-CoA reductase. Science 292:1160–1164PubMedCrossRefGoogle Scholar
  13. 13.
    Kwak B, Mulhaupt F, Myit S, Mach F (2000) Statins as a newly recognized type of immunomodulator. Nat Med 6:1399–1402PubMedCrossRefGoogle Scholar
  14. 14.
    Jain MK, Ridker PM (2005) Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov 4:977–987PubMedCrossRefGoogle Scholar
  15. 15.
    Pruefer D, Makowski J, Schnell M et al (2002) Simvastatin inhibits inflammatory properties of staphylococcus aureus alpha-toxin. Circulation 106:2104–2110PubMedCrossRefGoogle Scholar
  16. 16.
    Catron DM, Lange Y, Borensztajn J, Sylvester MD, Jones BD, Haldar K (2004) Salmonella enterica serovar Typhimurium requires nonsterol precursors of the cholesterol biosynthetic pathway for intracellular proliferation. Infect Immun 72:1036–1042PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Potena L, Frascaroli G, Grigioni F et al (2004) Hydroxymethyl-glutaryl coenzyme A reductase inhibition limits cytomegalovirus infection in human endothelial cells. Circulation 109:532–536PubMedCrossRefGoogle Scholar
  18. 18.
    Hill JM, Steiner I, Matthews KE, Trahan SG, Foster TP, Ball MJ (2005) Statins lower the risk of developing Alzheimer’s disease by limiting lipid raft endocytosis and decreasing the neuronal spread of Herpes simplex virus type 1. Med Hypotheses 64:53–58PubMedCrossRefGoogle Scholar
  19. 19.
    Hsu HY, Nicholson AC, Pomerantz KB, Kaner RJ, Hajjar DP (1995) Altered cholesterol trafficking in herpesvirus-infected arterial cells. Evidence for viral protein kinase-mediated cholesterol accumulation. J Biol Chem 270:19630–19637PubMedCrossRefGoogle Scholar
  20. 20.
    Del Pozo JL, van de Beek D, Mandrekar JN et al (2010) High serum cholesterol levels are associated with herpes zoster infection after heart transplantation. Clin Infect Dis 50:121–122PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • H.-H. Chen
    • 1
    • 2
    • 3
  • C.-L. Lin
    • 4
    • 5
  • C.-J. Yeh
    • 1
  • S.-Y. Yeh
    • 3
    • 6
  • C.-H. Kao
    • 7
    • 8
    Email author
  1. 1.Institute of Medicine and Public HealthChung Shan Medical UniversityTaichungTaiwan
  2. 2.Division of Metabolism and EndocrinologyChanghua Christian HospitalChanghuaTaiwan
  3. 3.Nantou Christian HospitalNantouTaiwan
  4. 4.Management Office for Health DataChina Medical University HospitalTaichungTaiwan
  5. 5.College of MedicineChina Medical UniversityTaichungTaiwan
  6. 6.Asia UniversityTaichungTaiwan
  7. 7.Department of Nuclear Medicine and PET CenterChina Medical University HospitalTaichungTaiwan
  8. 8.Graduate Institute of Clinical Medical Science and School of Medicine, College of MedicineChina Medical UniversityTaichungTaiwan

Personalised recommendations