Statin use and risk of tuberculosis: a systemic review of observational studies

Abstract

Statin intake may be linked with a lower risk of several infectious diseases, including tuberculosis, which is an important cause of mortality worldwide. The aim of this study was to investigate the definite impacts of statins on the risk of tuberculosis (TB) in diabetic patients and in the general population. Methods: Four databases were thoroughly searched from inception up to July 2019. Articles in any language were included if they assessed and clarified statin intake, presented the risk of TB in diabetes mellitus (DM) patients or the general population, and reported odds ratios (ORs), relative risks (RRs), or hazard ratios (HRs) or contained data for relevant calculation. RRs with 95% confidence intervals (CIs) were pooled using random-effects models regardless of heterogeneity quantified by Cochran's Q and I 2 statistics. Results: Six articles reporting observational studies involving 2 073 968 patients were included. Four reported cohort studies, one a nested case-control study, and one was an abstract. Statin use significantly reduced the risk of TB in DM patients by 22% (pooled RR 0.78, 95% CI 0.63-0.95), with severe heterogeneity (I 2 = 76.1%). Statin intake also significantly decreased the risk of TB in the general population by 40% (pooled RR 0.60, 95% CI 0.50-0.71), with severe heterogeneity (I 2 = 57.7%). Conclusions: Statin use is related to a considerably lower risk of TB in both DM patients and the general population. However, these conclusions should be interpreted with caution given the possible remaining confounding, and call for large-size and multicenter randomized controlled studies in the future.

The association of atherosclerotic cardiovascular disease and statin use with inflammation and treatment outcomes in tuberculosis

“…Statins are commonly used agents used to reduce serum lipids and systemic inflammation to improve outcomes in patients with a history of or at risk for ASCVD. Prior systematic reviews have shown that statin use reduces TB incidence, both in patients with DM and in the general population 28 , 29 . Preclinical studies in macrophage and mouse models have demonstrated that statins enhance autophagy and phagosome maturation 24 , increase the proportion of NK cells, and increase secretion of the pro-inflammatory cytokines IL-1β and IL-12p70, thereby reducing the lung bacillary burden in M. tuberculosis -infected mice 24 , 49 .…”

“…As adjunctive therapy, statins improve sterilizing activities of the first-line anti-tubercular regimen in murine models 24 – 27 . Though systematic reviews have shown that statin use reduces the incidence of active TB 28 , 29 , there is no clinical evidence on whether statins have salutary effects in TB patients after adjusting for confounding factors 30 .…”

The Association of Atherosclerotic Cardiovascular Disease and Statin Use With Inflammation and Treatment Outcomes in Tuberculosis

“…Statins are commonly used agents used to reduce serum lipids and systemic in ammation in patients with a history of or at risk for ASCVD. Prior systematic reviews have shown that statin use reduces TB incidence both in patients with DM and in the general population 23,24 . Preclinical studies in macrophage and mouse models have demonstrated that statins enhance autophagy and phagosome maturation 19 , increase the proportion of NK cells, and increase secretion of the pro-in ammatory cytokines IL-1β and IL-12p70, thereby reducing the lung bacillary burden in M. tuberculosis-infected mice 19,42 .…”

“…As adjunctive therapy, statins improve sterilizing activities of the rst-line anti-tubercular regimen in murine models [19][20][21][22] . Though systematic reviews have shown that statin use reduces the incidence of active TB 23,24 , there is no clinical evidence on whether statins have salutary effects in TB patients after adjusting for confounding factors 25 .…”

Are There Sex-Specific Differences in Response to Adjunctive Host-Directed Therapies for Tuberculosis?

“…In addition to their cholesterol-lowering properties, β-Hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have been shown to have broad anti-inflammatory and immunomodulatory properties (22,23), and their use has been associated with significantly decreased risk of TB (24). Statins have been shown to have antimicrobial and immunomodulatory activity in mouse models of infection against intracellular pathogens, including Salmonella enterica and Chlamydia pneumoniae.…”