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Association between blood pressure traits, hypertension, antihypertensive drugs and calcific aortic valve stenosis: a mendelian randomization study

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Journal of Geriatric Cardiology 2025年第03期 351-360页

作者： Wen-Hua LEI Jia-Liang ZHANG Yan-Biao LIAO Yan WANG Fei XU YaoYu ZHANG Yanjiani XU Jing ZHOU Fang-Yang HUANG Mao CHEN Department of Cardiology West China HospitalSichuan University Laboratory of Cardiac Structure and Function Institute of Cardiovascular DiseasesWest China HospitalSichuan University

Background Hypertension is associated with an increased risk of calcific aortic valve stenosis(CAVS). However, the directionality of causation between blood pressure traits and aortic stenosis is unclear, as is the benefit of antihypertensive drugs for *** Using genome-wide association studies(GWAS) summary statistics, we performed bidirectional two-sample univariable mendelian randomization(UVMR) to assess the causal associations of systolic blood pressure(SBP), diastolic blood pressure(DBP), and pulse pressure(PP) with CAVS. Multivariable mendelian randomization(MVMR) was conducted to evaluate the direct effect of hypertension on CAVS, adjusting for confounders. Drug target mendelian randomization(MR) and summary-level MR(SMR) were used to estimate the effects of 12 classes of antihypertensive drugs and their target genes on CAVS risk. Inverse variance weighting was the primary MR method, with sensitivity analyses to validate *** UVMR showed SBP, DBP, and PP have causal effects on CAVS, with no significant reverse causality. MVMR confirmed the causality between hypertension and CAVS after adjusting for confounders. Drug-target MR analyses indicated that calcium channel blockers(CCBs), loop diuretics, and thiazide diuretics via SBP lowering exerted protective effects on CAVS *** analysis showed that the CCBs target gene CACNA2D2 and ARBs target gene AGTR1 were positively associated with CAVS risk, while diuretics target genes SLC12A5 and SLC12A1 were negatively associated with aortic stenosis *** Hypertension has a causal relationship with CAVS. Managing SBP in hypertensive patients with CCBs may prevent CAVS. ARBs might exert protective effects on CAVS independent of blood pressure reduction. The relationship between diuretics and CAVS is complex, with opposite effects through different mechanisms.

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Association between blood pressure traits, hypertension, antihypertensive drugs and calcific aortic valve stenosis: a mendelian randomization study

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Journal of Geriatric Cardiology 2025年第3期22卷 351-360页

作者： Lei, Wen-Hua Zhang, Jia-Liang Liao, Yan-Biao Wang, Yan Xu, Fei Zhang, Yao-Yu Xu, Yanjiani Zhou, Jing Huang, Fang-Yang Chen, Mao Department of Cardiology West China Hospital Sichuan University No.37 Guoxue Street Chengdu 610041 China Laboratory of Cardiac Structure and Function Institute of Cardiovascular Diseases West China Hospital Sichuan University Chengdu China

Background Hypertension is associated with an increased risk of calcific aortic valve stenosis (CAVS). However, the directionality of causation between blood pressure traits and aortic stenosis is unclear, as is the benefit of antihypertensive drugs for CAVS. Methods Using genome-wide association studies (GWAS) summary statistics, we performed bidirectional two-sample univariable mendelian randomization (UVMR) to assess the causal associations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) with CAVS. Multivariable mendelian randomization (MVMR) was conducted to evaluate the direct effect of hypertension on CAVS, adjusting for confounders. Drug target mendelian randomization (MR) and summary-level MR (SMR) were used to estimate the effects of 12 classes of antihypertensive drugs and their target genes on CAVS risk. Inverse variance weighting was the primary MR method, with sensitivity analyses to validate results. Results UVMR showed SBP, DBP, and PP have causal effects on CAVS, with no significant reverse causality. MVMR confirmed the causality between hypertension and CAVS after adjusting for confounders. Drug-target MR analyses indicated that calcium channel blockers (CCBs), loop diuretics, and thiazide diuretics via SBP lowering exerted protective effects on CAVS risk. SMR analysis showed that the CCBs target gene CACNA2D2 and ARBs target gene AGTR1 were positively associated with CAVS risk, while diuretics target genes SLC12A5 and SLC12A1 were negatively associated with aortic stenosis risk. Conclusions Hypertension has a causal relationship with CAVS. Managing SBP in hypertensive patients with CCBs may prevent CAVS. ARBs might exert protective effects on CAVS independent of blood pressure reduction. The relationship between diuretics and CAVS is complex, with opposite effects through different mechanisms. © 2025 JGC All rights reserved.

关键词： antihypertensive drugs blood pressure blood pressure traits aortic stenosis calcific aortic valve stenosis calcific aortic valve stenosis cavs Mendelian randomization hypertension

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Age-associated methionine sulfoxide reductase A protects against valvular interstitial cell senescence and valvular calcification

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GeroScience 2025年 1-21页

作者： Li, Qing Song, Chengxiang Wei, Zisong Zhou, Hao Wang, Shuoding Li, Hongde Yang, Haoran Luo, Qiang Li, Junli Chen, Mao Laboratory of Cardiac Structure and Function Institute of Cardiovascular Diseases West China Hospital Sichuan University Chengdu 610041 China Cardiac Structure and Function Research Key Laboratory of Sichuan Province West China Hospital Sichuan University Chengdu 610041 China National Clinical Research Center for Geriatrics The Center of Gerontology and Geriatrics West China Hospital Sichuan University Chengdu 610041 China Department of Cardiology West China Hospital Sichuan University Chengdu 610041 China Department of Clinical Research Management West China Hospital Sichuan University Chengdu 610041 China

Calcific aortic valve disease (CAVD) is a cardiovascular disease prevalent in the aging population, resulting in high morbidity and mortality rates. However, the molecular mechanisms underlying CAVD remain unclear. We initially conducted an RNA sequencing analysis of aortic valve leaflets from rats of different ages to identify key genes involved in valvular aging and calcification. Bioinformatics analysis demonstrated that methionine sulfoxide reductase A (MSRA) was crucial to valvular calcification and senescence. To further investigate whether and how MSRA influences CAVD pathogenesis, we utilized two in vitro models: a human valvular interstitial cell (VIC) calcification model induced by osteogenic medium, and a VIC senescence model induced by hydrogen peroxide. Western blotting, immunofluorescence, flow cytometry, and alkaline phosphatase staining were conducted to evaluate the changes in calcific nodule formation and senescent markers. In vivo, ApoE−/− mice were treated either a normal chow or a high-cholesterol chow to determine the effects of MSRA overexpression on aortic valve calcification and senescence. MSRA silencing increased the osteogenic differentiation and senescence of VIC, whereas its overexpression produced the opposite effects. Similarly, we found that MSRA overexpression reduced calcium deposition and decreased the levels of senescent markers in ApoE−/− mice. Further mechanism experiments showed that MSRA suppressed osteoblastic differentiation via inhibiting the toll-like receptor (TLR2)/nuclear factor-κB (NF-κB) pathway. Our findings demonstrate that MSRA ameliorates valvular calcification and senescence by inhibiting TLR2/NF-κB pathway, highlighting MSRA as a promising target for treating age-associated CAVD. © The Author(s) 2025.

关键词： Calcific aortic valve disease Methionine sulfoxide reductase A Nuclear factor-κB Senescence Toll-like receptor 2

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M2 macrophage-derived exosome-modified bioprosthetic heart valves with enhanced anti-inflammatory, anticoagulant and anticalcification properties

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Materials and Design 2025年 254卷

作者： Chen, Jingruo Li, Shufen Chen, Xiaoting Qu, Tianyi Chen, Ming Chai, Zheng Zhuang, Weihua Hu, Wenchuang [Walter] Chen, Mao Laboratory of Cardiac Structure and Function Institute of Cardiovascular Diseases West China Hospital Sichuan University Chengdu610041 China Cardiac Structure and Function Research Key Laboratory of Sichuan Province West China Hospital Sichuan University Chengdu610041 China Animal Experimental Center West China Hospital Sichuan University Chengdu610041 China Precision Medicine Translational Research Center West China Hospital Sichuan University Chengdu610213 China Department of Cardiology West China Hospital Sichuan University No.37 Guoxue Alley Chengdu610041 China

Glutaraldehyde (Glut) cross-linked bioprosthetic heart valves (BHVs) have shown great performance in the replacement treatment of severe valvular heart diseases in recent years due to the rapid development of transcatheter aortic valve replacement (TAVR) and the aging population. However, the durability of BHVs suffers from inflammation, limited endothelialization, thrombus formation and calcification during clinical application, which makes it urgently to prolong the service life of BHVs. To this end, we introduced exosomes derived from M2 macrophages to the surface of Glut cross-linked bovine pericardium (Glut-BP) to develop a novel kind of BHVs, namely M2-EXO-BP, to improve the durability of Glut-BP. Compared with Glut-BP, M2-EXO-BP presented significantly improved biocompatibility and endothelialization. Moreover, M2-EXO-BP also reduced the adhesion of platelets and the formation of thrombi during the ex-vivo arterial-venous blood circulation experiment. In addition, calcification of M2-EXO-BP after 60 days of subcutaneous implantation in SD rats was obvious reduced compared with Glut-BP. Importantly, in vitro and in vivo studies confirmed that M2-EXO-BP could efficiently reduce inflammation levels compared with Glut-BP. In summary, these results suggest that BHVs modified with exosomes from M2 macrophages might be an interesting strategy to improve the durability of BHVs. © 2025 The Authors

关键词： Heart valve prostheses

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Disease trajectories and medical expenditures of older adults with disabilities: insights from China’s long-term care insurance program

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BMC Geriatrics 2025年第1期25卷 1-10页

作者： Zeng, Lijun Tan, Huaicheng Yang, Shujuan Hou, Lisha Wu, Jinhui Dong, Birong Gordon, Adam Dou, Qingyu Laboratory of Cardiac Structure and Function Institute of Cardiovascular Diseases West China Hospital Sichuan University Chengdu China Department of Biotherapy Cancer Center West China Hospital Sichuan University Chengdu China West China School of Public Health and West China Fourth Hospital Sichuan University Chengdu China International Institute of Spatial Lifecourse Health (ISLE) Wuhan University Wuhan China National Clinical Research Center for Geriatrics Center of Gerontology and Geriatrics West China Hospital Sichuan University No. 37 Guoxue Alley Wuhou District Chengdu 610041 China Academic Centre for Healthy Ageing Barts Health NHS Trust Queen Mary University of London London United Kingdom

Background: In China, long-term care (LTC) system has been implemented in recent years to improve the quality of care for older adults. To address healthcare needs of older adults with disabilities, this study investigated the disease trajectory and medical expenditures. Methods: This study included older adults aged 65 and above with disabilities, using data from China’s Long-Term Care Insurance (LTCI) program since July 2017. The participants were followed until June 2021. Diagnoses and hospitalization costs were extracted from electronic medical records and the medical insurance system. Disease trajectory networks were constructed by identifying and linking disease pairs with overlapping conditions. Medical expenditures associated with specific diseases were then calculated. Results: The study included 30,003 participants with a mean age of 79.6 ± 11.1 years, 57.0% of whom were female. After a mean follow-up of 21 ± 16 months, 17,428 (58.1%) deaths occurred. The diseases with the highest hazard ratios (HRs) included septic shock (HR 3.59, 95% CI, 3.36–3.84), respiratory failure (HR 3.19, 95% CI, 3.05–3.34), sepsis (HR 2.98, 95% CI, 2.80–3.18), malnutrition (HR 2.38, 95% CI, 2.27–2.48), and decubitus ulcer (HR 2.27, 95% CI, 2.14–2.41). Disease trajectories indicated that mortality was closely associated with malnutrition related diseases (anemia, hypoproteinemia, and malnutrition), pneumonia, and organ failure (respiratory failure and heart failure). Among the top 30 diseases leading to frequent hospitalization, intracerebral hemorrhage (47,882.4 CNY), sepsis (37,978.2 CNY), and respiratory failure (25,921.1 CNY) accounted for the highest total medical costs. Conclusions: The study revealed that malnutrition and infection-related diseases contributed significantly to mortality among older adults with disabilities, with the latter also driving higher medical costs. These findings could inform updates to LTCI policies by emphasizing adequate nutritional support and

关键词： Disability Disease trajectory Long-term care Medical expenditures Nutrition

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Radiomics of baseline epicardial adipose tissue predicts left ventricular mass regression after transcatheter aortic valve replacement

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Journal of Geriatric Cardiology 2024年第12期21卷 1109-1118页

作者： Yi ZHANG Hao-Ran YANG Xing-Yu JI Tian-Yuan XIONG Mao CHEN Department of Cardiology West China HospitalSichuan UniversityChengduChina Cardiac Structure and Function Research Key Laboratory of Sichuan Province West China HospitalSichuan UniversityChengduChina

Background Epicardial adipose tissue(EAT)radiomics derived from cardiac computed tomography(CT)images may pr-ovide insights into EAT characteristics,which can further predict regression of left ventricular mass index(LVMI)after transcath-eter aortic valve replacement(TAVR).This study aimed to develop and validate a radiomics nomogram based on pre-procedural EAT CT to predict inadequate LVMI regression following *** Inadequate LVMI regression was defined asΔLVMI%<15%at one-year post *** features from pre-procedural CT images were selected mainly by least absolute shrinkage and selection operator *** patients were ran-domly divided into the training and validation cohorts to establish and evaluate three feature classifier models based on the selec-ted features,using which the Radiomics scores(Radscores)were then calculated.A radiomics nomogram was constructed using independent risk factors and further assessed using area under the curve,calibration curve,and decision curve *** A total of 144 consecutive TAVR patients(42 patients with inadequate and 102 patients with adequate LVMI regres-sion)were randomly assigned to the training and validation cohorts(116 patients and 28 patients,respectively).A total of 1130 radiomics features from each patient yielded 6 features for the Radscore construction after selection,with logistic regression and support vector machine models ***,a nomogram based solely on the Radscore was constructed,with an area under the curve of 0.743 in the validation cohort,along with favorable decision curve analysis and calibration *** The developed radiomics nomogram,serving as a non-invasive tool,achieved satisfactory preoperative predic-tion of inadequate LVMI regression in TAVR patients,thereby facilitating clinical management.

关键词： thereby valve replacement

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Causal effect of psoriasis on aortic valve stenosis:a two-sample Mendelian randomization study

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Journal of Geriatric Cardiology 2024年第9期21卷 865-873页

作者： Ke-Xin JIANG Yan WANG Yu-Tong LIU Yanjiani XU Fang-Yang HUANG Mao CHEN Department of Cardiology West China HospitalSichuan UniversityChengduChina Laboratory of Cardiac Structure and Function Institute of Cardiovascular DiseasesWest China HospitalSichuan UniversityChengduChina West China School of Medicine Sichuan UniversityChengduSichuanChina

Background Epidemiological studies have suggested a potential connection between psoriasis and an increased risk of aortic valve stenosis(AS),though the impact of psoriasis on AS progression remains *** study aims to investigate the causal relationship between psoriasis and AS using Mendelian randomization(MR)analysis,as well as to uncover potential mechanisms underlying this *** A two-sample MR analysis was conducted using publicly available summary statistics from genome-wide association studies(GWAS)of psoriasis and ***-eQTL and significant genes were identified for each causal single-nucleotide polymorphisms(SNPs),followed by pathway enrichment and protein-protein interaction(PPI)analysis for functional *** genes were pinpointed by *** transcriptional profile of AS population was acquired,and interconnected genes networks were clustered using Molecular Complex Detection(MCODE).Results Our results demonstrate a significant causal relationship between psoriasis and AS,with a genetic predisposition to psoriasis associated with a higher AS risk(odds ratio:1.46).Pathway and PPI analyses unveiled 15 hub genes,including HLA-C,HLA-B,ISG15,IFIT3,and MX2,along with immune-related pathways linking psoriasis and ***,the transcriptional profiling of the AS database highlighted the significant involvement of adaptive immune cells in AS ***,among the 15 hub genes,ISG15,MX2,OAS3,OASL,IFI6,and EPSTI1 exhibited higher expression in the AS *** Our study provides compelling evidence supporting a causal relationship between psoriasis and ***,the identified hub genes and immune-related pathways may play an important role in the development of both diseases.

关键词： psoriasis stenosis involvement

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Author Correction: PDCD6 regulates lactate metabolism to modulate LC3-associated phagocytosis and antibacterial defense

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Nature communications 2025年第1期16卷 1541页

作者： Lulu Sun Sijin Wu Hui Wang Tianyu Zhang Mengyu Zhang Xuepeng Bai Xiumei Zhang Bingqing Li Cai Zhang Yan Li Jun Zhou Tianliang Li Center for Cell Structure and Function Shandong Provincial Key Laboratory of Animal Resistance Biology Collaborative Innovation Center of Cell Biology in Universities of Shandong College of Life Sciences Shandong Normal University Jinan 250358 China. Academy of Pharmacy Xi'an Jiaotong-Liverpool University Suzhou 215123 China. Department of Cardiac Surgery Public Health Clinical Center Affiliated to Shandong University Jinan 250013 China. School of Health Care Security Shandong First Medical University & Shandong Academy of Medical Sciences Jinan 250117 China. Department of Pathogen Biology School of Clinical and Basic Medical Sciences Shandong First Medical University & Shandong Academy of Medical Sciences Jinan 250117 China. Institute of Immunopharmacology and Immunotherapy School of Pharmaceutical Sciences Shandong University Jinan 250012 China. Center for Cell Structure and Function Shandong Provincial Key Laboratory of Animal Resistance Biology Collaborative Innovation Center of Cell Biology in Universities of Shandong College of Life Sciences Shandong Normal University Jinan 250358 China. junzhou@***. State Key Laboratory of Medicinal Chemical Biology Haihe Laboratory of Cell Ecosystem College of Life Sciences Nankai University Tianjin 300071 China. junzhou@***. Center for Cell Structure and Function Shandong Provincial Key Laboratory of Animal Resistance Biology Collaborative Innovation Center of Cell Biology in Universities of Shandong College of Life Sciences Shandong Normal University Jinan 250358 China. li.tianliang@***.

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Transcatheter aortic valve replacement:A journey of two decades and beyond

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Chinese Medical Journal 2024年第9期137卷 1012-1015页

作者： Tianyuan Xiong Mao Chen Department of Cardiology West China HospitalSichuan UniversityChengduSichuan 610041China Laboratory of Cardiac Structure and Function Institute of Cardiovascular DiseasesWest China HospitalSichuan UniversityChengduSichuan 610041China

The number of patients with calcic aortic stenosis(AS)is 9.4 million according to 2019 Global Disease Burden estimates,which will continue to increase as the population ages.[1]For the treatment of symptomatic severe AS,transcatheter aortic valve replacement(TAVR)has evolved to be a well-established option across all risk spectra,with a rapid growth of procedures *** rise of TAVR initiates the revolution of the management of valvular heart diseases,from patient surveillance,the staging of disease,the use of multimodality imaging,the concept of the Heart Team,new designs and iterations of devices to technical innovations and the discovery of unmet clinical *** a consequence of the global adoption of TAVR,geographical differences in the epidemiology of AS and patient characteristics have also been further identi*** examination of the changing patient population,current applications and breakthroughs,and remaining challenges are crucial for the future of this ***,we discuss the temporal utilization of TAVR,the accumulation of evidence and progress of devices,the selection of patients,and some ongoing topics concerning the improvement of TAVR.

关键词： epidemiology breakthrough beyond

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Association of handgrip strength with aortic stenosis among adults aged 60 years and older:evidence from the 157097 UK Biobank participants

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Journal of Geriatric Cardiology 2024年第11期21卷 1026-1033页

作者： Cheng-Xiang SONG Qing LI Cong-Ying XIA Lu LONG Xiao-Xi ZENG Jun-Li LI Mao CHEN Laboratory of Cardiac Structure and Function Institute of Cardiovascular DiseasesWest China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Cardiology West China HospitalSichuan UniversityChengduSichuan ProvinceChina National Clinical Research Center for Geriatrics the Center of Gerontology and GeriatricsWest China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Epidemiology and Health Statistics West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduSichuan ProvinceChina West China Biomedical Big Data Center West China HospitalSichuan UniversityChengduSichuan ProvinceChina Division of Nephrology Kidney Research InstituteWest China hospitalSichuan UniversityChengduSichuan ProvinceChina

Objective To examine the association of handgrip strength with aortic stenosis incidence among adults aged 60 years and *** We conducted a cohort study using the UK Biobank data to assess the relationship between handgrip strength and incident aortic stenosis in individuals aged 60 years and *** strength was measured using a Jamar J00105 hydraulic hand *** Cox proportional hazards regression models were conducted to assess the association between handgrip strength and incident aortic *** We included 157,097 UK Biobank participants(78,151 women and 78,946 men)in our study,with mean age of 64±2.9 *** a median follow-up of 8.1(7.4–8.8)years,1543(1.0%)participants developed incident aortic *** with those with the lowest handgrip strength(tertile 1),the adjusted hazard ratios(95%confidence interval)of incident aortic stenosis in the middle(tertile 2)and the highest(tertile 3)were 0.86(0.77–0.97)and 0.76(0.67–0.87),*** Higher handgrip strength was associated with lower risk of developing aortic stenosis in older *** studies warrant preventive strategies for older adults with lower handgrip strength.

关键词： stenosis aortic strength

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