• 1.

    WHO, 2018. WHO Fact Sheets, Global Tuberculosis Report 2017. Available at: http://www.who.int/tb/publications/factsheet_global.pdf?ua=1. Accessed June 6, 2018.

    • Search Google Scholar
    • Export Citation
  • 2.

    Schlossberg D, 2017. Tuberculosis and Nontuberculous Mycobacterial Infections. Washington, DC: ASM press.

  • 3.

    Ferebee SH, 1970. Controlled chemoprophylaxis trials in tuberculosis. a general review. Bibl Tuberc 26: 28106.

  • 4.

    Dheda K, Barry CE 3rd, Maartens G, 2016. Tuberculosis. Lancet 387: 12111226.

  • 5.

    Istvan ES, Deisenhofer J, 2001. Structural mechanism for statin inhibition of HMG-CoA reductase. Science 292: 11601164.

  • 6.

    Collins R et al. 2016. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet 388: 25322561.

  • 7.

    Lai CC, Lee MT, Lee SH, Hsu WT, Chang SS, Chen SC, Lee CC, 2016. Statin treatment is associated with a decreased risk of active tuberculosis: an analysis of a nationally representative cohort. Thorax 71: 646651.

    • Search Google Scholar
    • Export Citation
  • 8.

    Su VY, Su WJ, Yen YF, Pan SW, Chuang PH, Feng JY, Chou KT, Yang KY, Lee YC, Chen TJ, 2017. Statin use is associated with a lower risk of TB. Chest 152: 598606.

  • 9.

    Kang YA, Choi NK, Seong JM, Heo EY, Koo BK, Hwang SS, Park BJ, Yim JJ, Lee CH, 2014. The effects of statin use on the development of tuberculosis among patients with diabetes mellitus. Int J Tuberc Lung Dis 18: 717724.

    • Search Google Scholar
    • Export Citation
  • 10.

    Kwon SU, Yun SC, Kim MC, Kim BJ, Lee SH, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH, 2016. Risk of stroke and transient ischaemic attack after herpes zoster. Clin Microbiol Infect 22: 542548.

    • Search Google Scholar
    • Export Citation
  • 11.

    Kim MC, Yun SC, Lee HB, Lee PH, Lee SW, Choi SH, Kim YS, Woo JH, Kim SH, Kwon SU, 2017. Herpes zoster increases the risk of stroke and myocardial infarction. J Am Coll Cardiol 70: 295296.

    • Search Google Scholar
    • Export Citation
  • 12.

    Kim MC, Yun SC, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH, 2018. Statins increase the risk of herpes zoster: a propensity score-matched analysis. PLoS One 13: e0198263.

    • Search Google Scholar
    • Export Citation
  • 13.

    Lee J, Lee JS, Park SH, Shin SA, Kim K, 2017. Cohort profile: the national health insurance service-national sample cohort (NHIS-NSC), South Korea. Int J Epidemiol 46: e15.

    • Search Google Scholar
    • Export Citation
  • 14.

    Wang R, Lagakos SW, Ware JH, Hunter DJ, Drazen JM, 2007. Statistics in medicine–reporting of subgroup analyses in clinical trials. N Engl J Med 357: 21892194.

    • Search Google Scholar
    • Export Citation
  • 15.

    Gatfield J, Pieters J, 2000. Essential role for cholesterol in entry of mycobacteria into macrophages. Science 288: 16471650.

  • 16.

    Pandey AK, Sassetti CM, 2008. Mycobacterial persistence requires the utilization of host cholesterol. Proc Natl Acad Sci USA 105: 43764380.

    • Search Google Scholar
    • Export Citation
  • 17.

    Parihar SP, Guler R, Khutlang R, Lang DM, Hurdayal R, Mhlanga MM, Suzuki H, Marais AD, Brombacher F, 2014. Statin therapy reduces the mycobacterium tuberculosis burden in human macrophages and in mice by enhancing autophagy and phagosome maturation. J Infect Dis 209: 754763.

    • Search Google Scholar
    • Export Citation
  • 18.

    Skerry C, Pinn ML, Bruiners N, Pine R, Gennaro ML, Karakousis PC, 2014. Simvastatin increases the in vivo activity of the first-line tuberculosis regimen. J Antimicrob Chemother 69: 24532457.

    • Search Google Scholar
    • Export Citation
  • 19.

    Dutta NK, Bruiners N, Pinn ML, Zimmerman MD, Prideaux B, Dartois V, Gennaro ML, Karakousis PC, 2016. Statin adjunctive therapy shortens the duration of TB treatment in mice. J Antimicrob Chemother 71: 15701577.

    • Search Google Scholar
    • Export Citation
  • 20.

    Thomsen RW, Riis A, Kornum JB, Christensen S, Johnsen SP, Sorensen HT, 2008. Preadmission use of statins and outcomes after hospitalization with pneumonia: population-based cohort study of 29,900 patients. Arch Intern Med 168: 20812087.

    • Search Google Scholar
    • Export Citation
  • 21.

    Douglas I, Evans S, Smeeth L, 2011. Effect of statin treatment on short term mortality after pneumonia episode: cohort study. BMJ 342: d1642.

  • 22.

    Makris D, Manoulakas E, Komnos A, Papakrivou E, Tzovaras N, Hovas A, Zintzaras E, Zakynthinos E, 2011. Effect of pravastatin on the frequency of ventilator-associated pneumonia and on intensive care unit mortality: open-label, randomized study. Crit Care Med 39: 24402446.

    • Search Google Scholar
    • Export Citation
  • 23.

    Novack V, MacFadyen J, Malhotra A, Almog Y, Glynn RJ, Ridker PM, 2012. The effect of rosuvastatin on incident pneumonia: results from the JUPITER trial. CMAJ 184: E367E372.

    • Search Google Scholar
    • Export Citation
  • 24.

    Papazian L et al. 2013. Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial. JAMA 310: 16921700.

    • Search Google Scholar
    • Export Citation
  • 25.

    Alffenaar JC, Akkerman OW, van Hest R, 2016. Statin adjunctive therapy for tuberculosis treatment. Antimicrob Agents Chemother 60: 7004.

  • 26.

    Restrepo BI, 2007. Convergence of the tuberculosis and diabetes epidemics: renewal of old acquaintances. Clin Infect Dis 45: 436438.

  • 27.

    Jeon CY, Murray MB, 2008. Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies. PLoS Med 5: e152.

    • Search Google Scholar
    • Export Citation
  • 28.

    Baker MA, Lin HH, Chang HY, Murray MB, 2012. The risk of tuberculosis disease among persons with diabetes mellitus: a prospective cohort study. Clin Infect Dis 54: 818825.

    • Search Google Scholar
    • Export Citation
  • 29.

    Baker MA, Harries AD, Jeon CY, Hart JE, Kapur A, Lonnroth K, Ottmani SE, Goonesekera SD, Murray MB, 2011. The impact of diabetes on tuberculosis treatment outcomes: a systematic review. BMC Med 9: 81.

    • Search Google Scholar
    • Export Citation
  • 30.

    Jimenez-Corona ME et al. 2013. Association of diabetes and tuberculosis: impact on treatment and post-treatment outcomes. Thorax 68: 214220.

  • 31.

    Lin HH, Wu CY, Wang CH, Fu H, Lonnroth K, Chang YC, Huang YT, 2018. Association of obesity, diabetes, and risk of tuberculosis: two population-based cohorts. Clin Infect Dis 66: 699705.

    • Search Google Scholar
    • Export Citation
  • 32.

    Kim JH, Yim JJ, 2015. Achievements in and challenges of tuberculosis control in South Korea. Emerg Infect Dis 21: 19131920.

  • 33.

    Kim SH, Hong SB, Yun SC, Choi WI, Ahn JJ, Lee YJ, Lee HB, Lim CM, Koh Y; Korean Society of Critical Care Medicine HNC, 2011. Corticosteroid treatment in critically ill patients with pandemic influenza A/H1N1 2009 infection: analytic strategy using propensity scores. Am J Respir Crit Care Med 183: 12071214.

    • Search Google Scholar
    • Export Citation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 

 

Association between Tuberculosis, Statin Use, and Diabetes: A Propensity Score–Matched Analysis

View More View Less
  • 1 Division of Infectious Diseases, Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea;
  • | 2 Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;
  • | 3 Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Restricted access

Statins have anti-inflammatory and immunomodulatory properties that may affect the development of tuberculosis (TB). We assessed the association between use of statins and the risk of active TB by propensity score matching. Furthermore, we analyzed the impact of statins on TB in patients according to the presence or absence of diabetes. The study was based on the National Health Insurance database and its subset database of the “medical checkup” population of South Korea. We identified 123,468 statin users and 439,546 non–statin users. After propensity score matching, 28,018 statin users and the same number of non–statin users were finally analyzed. The development of active TB was monitored in these matched pairs over 11 years. In the propensity score–matching analysis, the number of active TB cases was 30 in 30,303 person-years (0.99 per 1,000 person-years; 95% CI, 0.64–1.35) in the statin users and 235 in 167,857 person-years (1.40 per 1,000 person-years; 95% CI, 1.22–1.58) in the non–statin users. Statin users had a significantly lower risk of TB than non–statin users: hazard ratio (HR) 0.67 (95% CI, 0.46–0.98) (P = 0.04). A subgroup analysis showed that statin use reduced the risk of TB in subjects without diabetes, but not in patients with diabetes: HRs were, respectively, 0.28 (95% CI, 0.13–0.60) (P = 0.001) and 1.05 (95% CI, 0.66–1.67) (P = 0.84). There is epidemiologic evidence that statin decreases the risk of active TB. However, the protective effect of statins against TB is attenuated by diabetes.

Author Notes

Address correspondence to Sung-Han Kim, Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88 Asanbyeongwon-Gil, Songpa-Gu, Seoul 05505, Republic of Korea. E-mail: kimsunghanmd@hotmail.com

Financial support: This study was supported by a grant from the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (grant NRF-2018R1D1A1A09082099), and the Asan Institute for Life Sciences (2018-7040).

Authors’ addresses: Min Chul Kim, Division of Infectious Diseases, Department of Internal Medicine, Chung Ang University Hospital, Seoul, Republic of Korea, E-mail: pour-soi@hanmail.net. Sung-Cheol Yun, Asan Medical Center, Department of Clinical Epidemiology and Biostatistics, Seoul, Republic of Korea, E-mail: ysch97@amc.seoul.kr. Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, and Sung-Han Kim, Department of infectious Diseases, Asan Medical Center, Seoul, Republic of Korea, E-mails: soleemd@amc.seoul.kr, sangho@amc.seoul.kr, yskim@amc.seoul.kr, junheewoo@amc.seoul.kr, and kimsunghanmd@hotmail.com.

These authors contributed equally to this work.

Save