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Background: Although a range of renin-angiotensin-aldosterone system (RAAS) modulators are available for blood pressure lowering, the optimal choice within this class remains unclear. We aimed to compare the efficacy and safety of RAAS modulators in the adult hypertensive population. Methods: A systematic literature search was performed in PubMed, CENTRAL, and Embase. The primary efficacy outcome was all-cause mortality and the secondary efficacy outcome was cardiovascular mortality. Tolerability outcome was discontinuation due to adverse events. Safety outcomes included the occurrence of cough, dizziness, edema, hyperkalemia, and hypotension. Network meta-analyses were performed utilizing a random-effects model within a frequentist framework. Results: We finally identified 51 articles from 49 randomized controlled trials. When compared to placebo, mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of all-cause mortality (odds ratio (OR) 0.83; 95% confidence interval (CI) 0.74–0.92) and cardiovascular mortality (OR 0.79; 95% CI 0.68–0.93), while none of other RAAS modulators significantly lowered the risk of all-cause or cardiovascular mortality. Individual comparisons indicated that MRAs were associated with a significantly lower risk of all-cause mortality than the other RAAS modulators (reduction: 16% compared with angiotensin-converting enzyme inhibitors (ACEIs), 14% compared with angiotensin receptor blockers (ARBs), and 22% compared with direct renin inhibitors (DRIs)). No difference in discontinuation due to adverse events was found in a comparison of RAAS modulators with placebo. With regard to safety outcomes, ACEIs have a higher risk of cough (OR 4.68; 95% CI 1.61–13.60), ARBs have a higher risk of dizziness (OR 1.42; 95% CI 1.06–1.91), hypotension (OR 2.10; 95% CI 1.02–4.34), and hyperkalemia (OR 1.99; 95% CI 1.17–3.41), and MRAs had a higher risk of hyperkalemia (OR 2.68; 95% CI 1.99–3.62) when compared to placebo. Conclusions: MRAs were the only RAAS modulators with a survival benefit in adults with hypertension, although they carried a higher risk of hyperkalemia. Our data challenge current hypertension guidelines which recommend MRAs as fourth-line therapy, and suggest that MRAs should be prescribed earlier and more widely. Registration: PROSPERO identifier number CRD42023405714. [ABSTRACT FROM AUTHOR]

Background: Individuals in the workplace are exposed to various environments, tasks, and schedules. Previous studies have indicated a link between occupational exposures and an increased risk of chronic kidney disease (CKD). However, the social conditions of the work environment may also be a crucial contributing factor to CKD. Furthermore, individuals may encounter multiple occupational-related risk factors simultaneously, underscoring the importance of investigating the joint risk of different working conditions on CKD. Methods: A prospective analysis of 65,069 UK Biobank participants aged 40 to 69 years without CKD at baseline (2006–2010) was performed. A self-administered questionnaire assessed working conditions and a working conditions risk score were developed. Participants who answered "sometimes" or "often" exposure to occupational heat or occupational secondhand cigarette smoke; involved in shift work or heavy workloads ("usually" or "always"), were grouped as high-risk working conditions. Each working condition was scored as 1 if grouped as high-risk, and 0 if not. The working conditions risk score was equal to the sum of these four working conditions. Cox proportional hazard regression models were used to estimate the associations between working conditions and CKD incidence. Results: The mean follow-up time was 6.7 years. After adjusting for demographic, lifestyle, and working time factors, the hazard ratios for the development of CKD for heavy workloads, shift work, occupational secondhand cigarette smoke exposure, and occupational heat exposure were 1.24 (95%CI = 1.03, 1.51), 1.33 (95%CI = 1.10, 1.62), 1.13 (95%CI = 1.01, 1.26), 1.11 (95%CI = 0.99, 1.24), respectively. The risk of CKD was found to be significantly associated with an increasing working conditions risk score. Individuals with a working conditions risk score of 4 had an 88.0% (95% CI = 1.05, 3.35) higher risk of developing CKD when compared to those with a working conditions risk score of 0. Conclusions: Adverse working conditions, particularly when considered in combination, can significantly elevate the risk of chronic kidney disease (CKD). These results provide a reference for implementing measures to prevent CKD. [ABSTRACT FROM AUTHOR]