Sodium-glucose cotransporter 2 inhibitors attenuate vascular calcification by suppressing endoplasmic reticulum protein thioredoxin domain containing 5 dependent osteogenic reprogramming.

AIMS: Vascular calcification is strongly linked to the development of major adverse cardiovascular events, but effective treatments are lacking. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an emerging category of oral hypoglycemic drugs that have displayed marked effects on metabolic and cardiovascular diseases, including recently reported vascular medial calcification. However, the roles and underlying mechanisms of SGLT2 inhibitors in vascular calcification have not been fully elucidated. Thus, we aimed to further determine whether SGLT2 inhibitors protect against vascular calcification and to investigate the mechanisms involved. METHODS AND RESULTS: A computed tomography angiography investigation of coronary arteries from 1554 patients with type 2 diabetes revealed that SGLT2 inhibitor use was correlated with a lower Agatston calcification score. In the vitamin D3 overdose, 5/6 nephrectomy chronic kidney disease-induced medial calcification and Western diet-induced atherosclerotic intimal calcification models, dapagliflozin (DAPA) substantially alleviated vascular calcification in the aorta. Furthermore, we showed that DAPA reduced vascular calcification via Runx2-dependent osteogenic transdifferentiation in vascular smooth muscle cells (VSMCs). Transcriptome profiling revealed that thioredoxin domain containing 5 (TXNDC5) was involved in the attenuation of vascular calcification by DAPA. Rescue experiments showed that DAPA-induced TXNDC5 downregulation in VSMCs blocked the protective effect on vascular calcification. Furthermore, TXNDC5 downregulation disrupted protein folding-dependent Runx2 stability and promoted subsequent proteasomal degradation. Moreover, DAPA downregulated TXNDC5 expression via amelioration of oxidative stress and ATF6-dependent endoplasmic reticulum stress. Consistently, the class effects of SGLT2 inhibitors on vascular calcification were validated with empagliflozin in intimal and medial calcification models. CONCLUSIONS: SGLT2 inhibitors ameliorate vascular calcification through blocking endoplasmic reticulum stress-dependent TXNDC5 upregulation and promoting subsequent Runx2 proteasomal degradation, suggesting that SGLT2 inhibitors are potentially beneficial for vascular calcification treatment and prevention.

The outcome and related risk factors of unvaccinated patients with end-stage kidney disease during the Omicron pandemic: a multicentre retrospective study.

OBJECTIVES: The study aims to identify the outcome and the related factors of unvaccinated patients with end-stage kidney disease during the Omicron pandemic. DESIGN: A multicentre retrospective study of patients with end-stage kidney disease undergone maintenance haemodialysis (HD) in China. SETTING: 6 HD centres in China. PARTICIPANTS: A total of 654 HD patients who tested positive for SARS-CoV-2 were ultimately included in the study. OUTCOME MEASURES: The primary outcomes of interest were adverse outcomes, including hospitalisation due to COVID-19 and all-cause mortality. RESULTS: The average age of the patients was 57 years, with 33.6% of them being over 65 years. Among the patients, 57.5% were male. During the follow-up period, 158 patients (24.2%) experienced adverse outcomes, and 93 patients (14.2%) died. The majority of patients (88/158) developed adverse outcomes within 30 days, and most deaths (77/93) occurred within 1 month. An advanced multivariable Cox regression analysis identified that adverse outcomes were associated with various factors while all-cause mortality was related to advanced age, male gender, high levels of C reactive protein (CRP) and low levels of prealbumin. The Kaplan-Meier curves demonstrated significantly higher all-cause mortality rates in the older, male, high CRP and low prealbumin subgroups. CONCLUSIONS: Among unvaccinated HD patients with confirmed Omicron infections, various factors were found to be linked to adverse outcomes. Notably, age, sex, CRP and prealbumin had a substantial impact on the risk of all-cause mortality.

B-type natriuretic peptide levels at admission predict the prognosis of patients with infective endocarditis undergoing cardiac surgery.

Purpose: The objective of this study was to explore the relationship between elevated B-type natriuretic peptide (BNP) levels and the prognosis of patients with infective endocarditis (IE) undergoing cardiac surgery. Methods: In total, 162 IE patients with recorded BNP levels upon admission were included in the present study. The primary end point was all-cause mortality. Results: Multivariate Cox analysis revealed a significant association between log BNP and all-cause mortality. Kaplan-Meier analysis revealed a poorer prognosis for patients with BNP levels ≥ the 75th percentile. Furthermore, the linear trend test indicated a significant link between BNP quartiles and the primary end point within the models. Conclusion: Elevated BNP levels upon admission could predict all-cause mortality in IE patients undergoing cardiac surgery.

Infective endocarditis (IE) refers to an infection affecting the heart lining, heart valves or blood vessels. Despite advancements in medical and surgical interventions, the overall mortality rate remains high among IE patients after surgery. B-type natriuretic peptide (BNP) is a peptide released in response to increased stress on the ventricular and atrial walls and is commonly used as a biomarker for heart failure. This study was aimed to assess the potential of BNP in predicting all-cause mortality in IE patients. The results indicate that elevated BNP levels upon admission could predict a worse prognosis following endocarditis surgery. Additionally, elevated BNP levels upon admission were associated with an increased risk of death.

Impact of coronary artery disease in patients with hypertrophic cardiomyopathy.

BACKGROUND: Atherosclerotic coronary artery disease (CAD) often occurs concurrently with hypertrophic cardiomyopathy (HCM). However, the influence of concomitant CAD has not been fully assessed in patients with HCM. METHODS: Invasive or computed tomography coronary angiography was performed in 461 patients with HCM at our hospital to determine the presence and severity of CAD from March 2010 to April 2022. The primary end points were all-cause, cardiovascular, and sudden cardiac deaths. The survival of HCM patients with severe CAD was compared with that of HCM patients without severe CAD. RESULTS: Of 461 patients with HCM, 235 had concomitant CAD. During the median (interquartile range) follow-up of 49 (31-80) months, 75 patients (16.3%) died. The 5-year survival estimates were 64.3%, 82.5%, and 86.0% for the severe, mild-to-moderate, and no-CAD groups, respectively (log-rank, p = 0.010). Regarding the absence of cardiovascular death, the 5-year survival estimates were 68.5% for patients with severe CAD, 86.4% for patients with mild-to-moderate CAD, and 90.2% for HCM patients with no CAD (log-rank, p = 0.001). In multivariate analyses, severe CAD was associated with all-cause and cardiovascular death after adjusting for age, left ventricular ejection fraction, hypertension, and atrial fibrillation. CONCLUSIONS: This study showed a worse prognosis among HCM patients with severe CAD than among HCM patients without severe CAD. Therefore, timely recognition of severe CAD in HCM patients and appropriate treatment are important.

Hospitalized patients with isolated distal deep vein thrombosis: anticoagulation therapy or not?

BACKGROUND: Isolated distal deep vein thrombosis (IDDVT), a disease frequently detected in hospitalized patients, can progress to proximal deep vein thrombosis (PDVT) and pulmonary embolism (PE). Here, we evaluated the effects of anticoagulation in hospitalized IDDVT patients. METHODS: We conducted a retrospective study in our hospital and enrolled hospitalized IDDVT patients diagnosed by compression ultrasonography (CUS) from January to December 2020. Participants were divided into anticoagulation (AC) and non-anticoagulation (non-AC) groups. After propensity score matching (PSM), multivariate Cox regression analyses were performed to assess whether anticoagulation was associated with PDVT/PE, and all-cause mortality. RESULTS: A total of 426 IDDVT inpatients with CUS follow-up were screened from 1502 distal DVT patients and finally enrolled. The median age was 67 years with 51.4% males and 15.5% cancer patients. The median follow-up was 11.6 months. There were 288 and 138 patients treated with or without anticoagulants, respectively. Patients in the non-AC group had less body mass index and more comorbidities. Patients in the AC group were treated with rivaroxaban or dabigatran (52.1%), low molecular weight heparin (42.7%), and warfarin (5.2%). The PSM generated 111 pairs of well-matched IDDVT patients with or without anticoagulation. The Kaplan-Meier analysis demonstrated that neither the incidence of PDVT/PE (5.4% vs. 2.7%, log-rank p = 0.313) nor all-cause mortality (27.9% vs. 18.9%, log-rank p = 0.098) was significant different between groups. Anticoagulation was not associated with PDVT/PE and all-cause mortality in the multivariable Cox regression analyses using the matched cohorts. The main risk factors for all-cause mortality were age, malignancy history, BMI, sepsis, heart failure, and white blood cell (WBC) count. CONCLUSIONS: In hospitalized IDDVT patients, the thrombosis extension rate to PDVT/PE was low. Anticoagulation did not reduce the incidence of thrombosis extension of IDDVT and was not associated with all-cause mortality.

Maintenance of recovered dilated cardiomyopathy patients with half-dose neurohumoral blockades (MED-CHARM): A protocol for an open-label, pilot, randomized trial.

Dilated cardiomyopathy (DCM) has brought great damage to the patients' health and social economy. The number of patients with recovered dilated cardiomyopathy (recDCM) has increased over the years as treatment progresses. However, there is a lack of relevant evidence to support the clinical management of patients with recDCM, thereby, the recommendations in guidelines remains sparse. Accordingly, the exploration of recDCM is important to improve patient prognosis and reduce societal burden. This is an open-label, randomized controlled, prospective study that will compare the safety and efficacy of original dose and halved dose of neurohumoral blockades for patients with recDCM. Methods: An open-label, randomized controlled, prospective study will be conducted among eligible patients with recDCM. During the pilot study phase, we will recruit 50 patients. The primary endpoint is hospitalization for heart failure or heart failure relapse within 12 months. Secondary endpoint is major adverse cardiovascular events, including cardiovascular mortality, myocardial infarction, stroke, sustained atrial tachycardia, or ventricular tachycardia. The results will be analyzed using intention-to-treatment analysis. Discussion: The study will provide important evidence of whether it is safe and effective to halve the dosage of neurohumoral blockades in recDCM patients. Trial registration number: ChiCTR2100054051 (www.chictr.org.cn).