RESUMEN
Objectives: Tuberculosis is a major cause of global morbidity and mortality. Statins could be associated with a lower risk of some infectious diseases, including tuberculosis. Statins could reduce the risk of latent tuberculosis infection and active tuberculosis, acting as an adjuvant in treating tuberculosis. This study aimed to determine if statins reduce the risk of active tuberculosis. Methods: We systematically analyzed 8 databases from inception to December 2021. We included articles without language restriction if they met our inclusion and exclusion criteria and the PECO strategy (Population: adults without active pulmonary tuberculosis; Exposure: treatment with any statin; Comparator: no use of statins; Outcome: active tuberculosis). Odds Ratios (ORs) with 95% confidence intervals (CIs) were pooled using random- effects models regardless of heterogeneity quantified by Cochran's Q and I2 statistics. We performed subgroup analyses according to the participants' diabetic status and follow-up length (≤10 years or >10 years). Results: Twelve articles reporting observational studies involving 3.038.043 participants, including at least 32.668 cases of active tuberculosis. Eight reported retrospective cohort studies, three nested case-control study, and one was a case control study.According to our meta-analysis, statins may reduce the risk of active tuberculosis, in the general population (OR 0.66; 95% CI, 0.54-0.81), in non-diabetic (OR 0.66; 95% CI, 0.54-0.80) and in diabetic patients (OR 0.65; 95% CI, 0.49-0.87). This protective effect did not differ according to the participants' diabetic status nor follow-up length (test for subgroup differences I2=0). We found significant clinical and methodological heterogeneity. Similarly, the forest plot, and the I2 and Chi2 statistics suggested considerable statistical heterogeneity (I2=95%, p<0.05, respectively). Of the 12 included studies, 9 were at low risk of bias and 3 were at high risk of bias. Similarly, according to the funnel plot, it is very likely that there are important publication biases. Conclusion: Statin use may significantly reduce the risk of tuberculosis in the general population, diabetic and non-diabetic patients. Nevertheless, caution should be exercised when interpreting these conclusions, due to the quality of the evidence, the heterogeneity of the studies, the presence of bias, and the difficulty in extrapolating these results to populations of other races and ethnicities.
RESUMEN
Objectives: Previous observational studies have suggested an association between periodontal disease (PD) and cardiovascular and cerebrovascular diseases. Nonetheless, evidence linking PD with coronary heart disease (CHD) and acute coronary syndrome (ACS) is still contradictory. We aim to systematically review the role of PD as a risk factor for ACS (myocardial infarction and unstable angina). Methods: The protocol was registered in PROSPERO (CRD42021286278) and we followed the recommendations of the PRISMA and AMSTAR 2 guidelines. We systematically searched for 7 databases and electronic thesis repositories from inception to February 2022. We included articles without language restriction following the PECO strategy (population: "adult participants"; exposure: "periodontal disease"; comparator: "no periodontal disease"; outcome: "acute coronary syndrome" OR "acute myocardial infarction" OR "unstable angina"). Odds ratios (OR) with 95% confidence intervals (95% CI) were pooled using random effects and heterogeneity was quantified by Cochran's Q and Higgins' I2 statistics. Subgroup analyses were carried out according to the participants' sex, type of diagnosis of PD, type of study, and continent of origin of studies. Results: We included 46 papers (17 cohort, 25 case-control, and 4 cross-sectional studies) that met the inclusion criteria. This meta-analysis includes a total of 6,806,286 participants and at least 68,932 ACS events, mainly myocardial infarction (MI). In accordance with our results, PD is associated with a higher risk of ACS (OR 1.35; 95% CI 1.25-1.45). However, clinical and methodological heterogeneity was significant (I2=86%, p<0.05). In the sensitivity analysis, the exclusion of some studies with "extreme" results (outliers) did not significantly affect the overall estimate or heterogeneity. In subgroup analysis, we found no statistically significant differences between men and women according to subgroup difference tests (I2=0%, p=0.67). Conversely, there were differences according to the type of diagnosis of PD (clinical or self-reported diagnosis), type of study (cohort, case-control, or cross-sectional study), and the continent of origin (North America, South America, Asia, or Europe) of the studies (I2=79%-96%, p<0.10). Of the 46 studies, only 4 had a high risk of bias. Additionally, the funnel plot suggested publication bias. Conclusion: PD may be an important non-traditional risk factor for ACS. Although, this meta-analysis brings together more studies, and therefore more evidence, than any other previous similar study, its results should be interpreted with caution due to the great heterogeneity and the potential presence of bias.