Statins may help reduce tuberculosis risk
Statins appear to have a dose-dependent association with the risk of tuberculosis (TB), with a nationwide population-based study showing that statin users have 47 percent lower incidence of TB compared with nonusers.
“To our knowledge, this is the largest cohort study of TB risk among statin users to date … [and the] results support the hypothesis that statins may decrease the risk of TB disease,” the authors said.
The study used data from the Taiwan National Health Insurance Research Database, including 102,424 statin users and 202,718 age-, sex- and enrolment date-matched nonusers. The mean age of the two cohorts was 58.02 years. All individuals were followed up for incident TB disease—the primary outcome of interest—until the completion of the study. None had a prior diagnosis of the infectious disease.
Overall, 1,264 individuals (0.41 percent) developed subsequent TB disease. Using the claims database of Taipei Veterans 49 General Hospital, the identification of those with TB was validated and confirmed to be accurate, with a sensitivity of 96.3 percent and excellent interobserver agreement (κ=1.00). [Chest 2017;doi:10.1016/j.chest.2017.04.170]
Multivariate analysis found a protective association between statin and the risk of TB (hazard ratio [HR] 0.53; 95 percent CI, 0.47 to 0.61; p<0.001), with a dose-response effect. Among statin users, incident TB disease risk was lowest among those who took >365 cumulative defined daily doses (cDDDs; HR, 0.27; 0.22 to 0.33; p<0.001), followed by those with 180 to 365 cDDDs (HR, 0.57; 0.45 to 0.72; p<0.001). Those with <180 cDDDs had an HR of 1.06 (0.91 to 1.24; p=0.477). DDDs of statins were standardized by using the ATC-DDD scheme of the World Health Organization.
Independent risk factors for new TB disease included age ≥65 years (HR, 1.60; p<0.001), male sex (HR, 3.68; p<0.001), diabetes mellitus (HR, 1.22; p=0.006), heart failure (HR, 1.51; p=0.015), chronic obstructive pulmonary disease (HR, 1.72; p<0.001), asthma (HR, 1.51; p=0.002) and systemic glucocorticoid use (HR, 1.47; p<0.001).
“The possible mechanism for the observed association between statin use and TB risk is that statin prevents infection in patients exposed to Mycobacterium tuberculosis and reduces TB reactivation,” the authors noted.
“Cholesterol plays an important role in the pathophysiology of TB infections, affecting the phagocytosis of M. tuberculosis into host macrophages, phagosome formation and maturation, and the energy generation of intracellular M. tuberculosis,” they continued. [Int J Tuberc Lung Dis 2014;18:717–24; Mol Cell Biochem 2004;258:219–22; Proc Natl Acad Sci USA 2005;102:4033–8; J Biol Chem 2008;283:35745–55; J Bacteriol 2009;191:6584–91]
The authors pointed out that statins have been shown to reduce the cholesterol levels in phagosomes in human macrophages and in experimental mouse models, as well as counteract the M. tuberculosis-induced inhibition of phagosomal maturation.
“Furthermore, statins have anti-inflammatory and immunomodulatory properties, thereby potentially resulting in reduced reactivation of latent TB, and the use of statins has been found to modulate the levels of T cells and cytokines during sepsis infection,” they said. [Front Microbiol 2011;2:2]
The study might be limited by the lack of data on some potential risk factors (eg, obesity, smoking, alcohol use, malnutrition), as well as by the reliance on administrative claims data recorded by physicians or hospitals with respect to statin prescriptions and TB diagnoses.
Despite the said limitations, the present data provide evidence of a dose-dependent benefit of statins on TB risk. Further well-designed studies are needed to distinguish the effects of different statins on the infectious disease, the authors said.