Effect of the Renin-Angiotensin System Inhibitors on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). METHODS: PubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI. RESULTS: Thirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, -0.54 [95% CI, -0.88 to -0.21]; P=.002; I2=96%), IL-6 (WMD, -0.84 [95% CI, -1.03 to -0.64]; P<.001; I2=0%), and TNF-α (WMD, -12.75 [95% CI, -17.20 to -8.29]; P<.001; I2=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, -1.34 [95% CI, -2.65 to -0.04]; P=.04; I2=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, -1.07 to -0.27]; P=.001; I2=94%) and in patients with coronary artery disease (WMD, -0.75 [95% CI, -1.17 to -0.33]; P<.001; I2=96%). CONCLUSION: Based on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.

Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies.

BACKGROUND: Current evidence from randomized controlled trials on statins for primary prevention of cardiovascular disease (CVD) in older people, especially those aged > 75 years, is still lacking. We conducted a systematic review and meta-analysis of observational studies to extend the current evidence about the association of statin use in older people primary prevention group with risk of CVD and mortality. METHODS: PubMed, Scopus, and Embase were searched from inception until March 18, 2021. We included observational studies (cohort or nested case-control) that compared statin use vs non-use for primary prevention of CVD in older people aged ≥ 65 years; provided that each of them reported the risk estimate on at least one of the following primary outcomes: all cause-mortality, CVD death, myocardial infarction (MI), and stroke. Risk estimates of each relevant outcome were pooled as a hazard ratio (HR) with a 95% confidence interval (CI) using the random-effects meta-analysis model. The quality of the evidence was rated using the GRADE approach. RESULTS: Ten observational studies (9 cohorts and one case-control study; n = 815,667) fulfilled our criteria. The overall combined estimate suggested that statin therapy was associated with a significantly lower risk of all-cause mortality (HR: 0.86 [95% CI 0.79 to 0.93]), CVD death (HR: 0.80 [95% CI 0.78 to 0.81]), and stroke (HR: 0.85 [95% CI 0.76 to 0.94]) and a non-significant association with risk of MI (HR 0.74 [95% CI 0.53 to 1.02]). The beneficial association of statins with the risk of all-cause mortality remained significant even at higher ages (> 75 years old; HR 0.88 [95% CI 0.81 to 0.96]) and in both men (HR: 0.75 [95% CI: 0.74 to 0.76]) and women (HR 0.85 [95% CI 0.72 to 0.99]). However, this association with the risk of all-cause mortality remained significant only in those with diabetes mellitus (DM) (HR 0.82 [95% CI 0.68 to 0.98]) but not in those without DM. The level of evidence of all the primary outcomes was rated as "very low." CONCLUSIONS: Statin therapy in older people (aged ≥ 65 years) without CVD was associated with a 14%, 20%, and 15% lower risk of all-cause mortality, CVD death, and stroke, respectively. The beneficial association with the risk of all-cause mortality remained significant even at higher ages (> 75 years old), in both men and women, and in individuals with DM, but not in those without DM. These observational findings support the need for trials to test the benefits of statins in those above 75 years of age.

Association between sarcoidosis and diabetes mellitus: a systematic review and meta-analysis.

Background: Sarcoidosis is multisystem inflammatory granulomatosis that can potentially affect any organ of the human body. We aimed to estimate the prevalence of diabetes mellitus (DM) in sarcoidosis patients and determine the association between sarcoidosis and DM.Method: All relevant articles reporting the prevalence of DM in sarcoidosis published until September 19th, 2020, were retrieved from ten electronic databases. We used the random effect model to perform the meta-analysis.Results: After screening 2,122 records, we included 19 studies (n = 18,686,162). The prevalence of DM in sarcoidosis patients was 12.7% (95% CI 10-16.1). The prevalence was highest in North America with 21.3% (13.5-31.8), followed by Europe 10.4 (7.9-13.7) and Asia 10% (1.8-39.7). Sarcoidosis patients had higher rates of DM compared to controls (OR 1.75; 95% CI 1.49-2.05). Sensitivity analysis, after removing the largest weighted study, did not reveal any effect on the significance of the results (OR 1.73; 95% CI 1.33-2.25).Conclusion: The prevalence of DM in sarcoidosis is considerably high, with increased odds of DM in sarcoidosis compared to healthy controls. Further research with a wide range of confounders is required to confirm the association of sarcoidosis with DM.