Background: Primary aldosteronism (PA) is a common cause of secondary hypertension and confers a higher risk of stroke. The treatment strategies of PA mainly include medical and adrenalectomy treatment, while there is still no solid conclusion on how these two different treatment strategies mitigate the detrimental effect of PA on stroke. Methods: PubMed, Embase, and Cochrane Library were searched for studies comparing stroke events in patients with PA receiving medical treatment versus adrenalectomy treatment published up to 19 March 2022, including patients with essential hypertension as a control group. We used either fixed or random effect models according to the heterogeneities. Sensitivity analysis was conducted by deleting each study one at a time. Results: We reviewed 201 articles, and three studies met the final criteria, including 3244 PA patients with medical treatment, 1611 PA patients with adrenalectomy treatment, and 20,568 EH patients. Patients with PA post adrenalectomy were observed with a significantly decreased risk of stroke compared to patients receiving medical treatment (OR: 0.57, 95% CI: 0.35–0.93, p = 0.03), and with no difference when compared to patients with essential hypertension. Patients with PA receiving medical treatment were still observed with higher stroke risks (OR: 1.88, 95% CI: 1.68–2.11, p < 0.00001) than patients with essential hypertension. Conclusion: PA is a critical modifiable risk factor for stroke. Adrenalectomy has a superior performance in the mitigation of stroke risks among patients with PA.
19 February 2024 in Animal Models and Experimental Medicine
Background: Calcific aortic valve stenosis (CAVS) is one of the most challenging heart diseases in clinical with rapidly increasing prevalence. However, study of the mechanism and treatment of CAVS is hampered by the lack of suitable, robust and efficient models that develop hemodynamically significant stenosis and typical calcium deposition. Here, we aim to establish a mouse model to mimic the development and features of CAVS.Methods: The model was established via aortic valve wire injury (AVWI) combined with vitamin D subcutaneous injected in wild type C57/BL6 mice. Serial transthoracic echocardiography was applied to evaluate aortic jet peak velocity and mean gradient. Histopathological specimens were collected and examined in respect of valve thickening, calcium deposition, collagen accumulation, osteogenic differentiation and inflammation.Results: Serial transthoracic echocardiography revealed that aortic jet peak velocity and mean gradient increased from 7 days post model establishment in a time dependent manner and tended to be stable at 28 days. Compared with the sham group, simple AVWI or the vitamin D group, the hybrid model group showed typical pathological features of CAVS, including hemodynamic alterations, increased aortic valve thickening, calcium deposition, collagen accumulation at 28 days. In addition, osteogenic differentiation, fibrosis and inflammation, which play critical roles in the development of CAVS, were observed in the hybrid model.Conclusions: We established a novel mouse model of CAVS that could be induced efficiently, robustly and economically, and without genetic intervention. It provides a fast track to explore the underlying mechanisms of CAVS and to identify more effective pharmacological targets.
Background: Significant sex differences exist in atrial fibrillation (AF). Better understanding of its underlying mechanism would help AF management. This study aimed to investigate the contribution of circulating metabolites to sex differences in AF and the association between them. Methods: A total of 108 patients with AF were enrolled. Untargeted metabolomics were performed in plasma samples of male and female patients. Correlation analysis with clinical characteristics and Mendelian randomization were used to identify sex-specific metabolites associated with AF, which was further validated in additional patients. Transcriptomics data of the left atrium were used to investigate the molecular alteration of the left atrium responding to identified sex-specific circulating metabolites. The effect of selected sex-specific metabolites on cardiomyocytes was further investigated. Results: A total of 60 annotated metabolites were found with different levels between male and female patients. Among these sex-specific metabolites, three metabolites, 7-Methylguanosine, succinic acid, and N-Undecylbenzenesulfonic acid, were positively related to the left atrial remodeling. Additionally, succinic acid was significantly associated with increased risk of AF (OR = 1.26; 95% CI: 1.13 to 1.40; p < 0.001). And, SUCLA2, the gene of succinic acid metabolism, was significantly increased in the left atrium of male patients (fold change = 1.53; p = 0.008). Treatment with succinic acid led to cardiomyocyte hypertrophy and mitochondrial dysfunction. Conclusions: This study highlights sex differences in circulating metabolites in patients with AF and identifies the associations between sex-specific metabolites and AF. succinic acid, which is much higher in male patients, contributes to the process of AF.
30 November 2021 in International Journal of Hypertension
Few studies have considered psychosocial characteristics when investigating the associations between sleep duration and blood pressure (BP). In this study, we took propensity score matching (PSM) to adjust for psychosocial characteristics when comparing BP between individuals with short sleep duration and those with normal sleep duration. A total of 429 participants were included. 72 participants with sleep duration ≤6 h and 65 participants with sleep duration >6 h were matched after PSM. We compared office BP, 24-hour BP, and prevalence of hypertension in the populations before and after PSM, respectively. In the unmatched population, participants with sleep duration ≤6 h were observed with higher office diastolic BP (DBP) and 24-h systolic BP (SBP)/DBP (all ). In the matched populations, the differences between the two groups (sleep duration ≤6 h vs. sleep duration >6 h) in office DBP (88.4 ± 10.9 vs. 82.5 ± 11.1 mm Hg; ), 24-h SBP (134.7 ± 12.0 vs. 129.3 ± 11.6 mm Hg; ), and 24-h DBP (83.4 ± 9.9 vs. 78.1 ± 10.1 mm Hg; ) become more significant. Participants with sleep duration ≤6 h only show higher prevalence of hypertension based on 24-h BP data, while analysis after PSM further revealed that these with sleep duration ≤6 h presented about 20% higher prevalence of elevated BP up to office diagnosed hypertension threshold. Therefore, psychosocial characteristics accompanied with short sleep duration should be fully valued in individuals at risks for elevated BP. This trial is registered with NCT03866226.
Background and objective: Evidence of percutaneous left atrial appendage closure (LAAC) and oral anticoagulants (OACs) in non-valvular atrial fibrillation (NVAF) patients with intermediate-to-borderline high stroke risk is scarce. We aimed to compare the efficacy and safety of these treatments in the latter clinical population. Methods: This retrospective cohort study included NVAF patients with CHA2DS2-VA scores of 1–2 and used 1:1 propensity score matching (184 patients per group) to compare efficacy and safety outcomes. The primary efficacy outcome was a composite of stroke, transient ischemic attacks, systemic embolism, and cardiovascular death during follow-up. Adverse safety events were categorized into peri-procedure (LAAC group) and non-procedural (both groups) events. Results: Over a mean follow-up of 48.93 ± 28.50 months, a total of 26 patients (7.07%) reached the primary composite efficacy endpoint. The LAAC group showed a significantly higher incidence of the efficacy endpoint compared to the OAC group (HR = 3.09; 95% CI 1.22–7.85; log-rank p = 0.01). Procedure-related events occurred in five LAAC patients (one contributing to primary endpoint), while non-procedural bleeding rates were similar (0.54% vs. 1.09%; p = 0.56). Subgroup analyses suggested concomitant ablation of NVAF in LAAC group did not significantly improve efficacy composite endpoints (HR = 0.47). Conclusions: In NVAF patients with intermediate-to-high stroke risk, OACs were more effective than LAAC in preventing thromboembolic events, with comparable rates of clinically relevant bleeding.