medRxiv - Cardiovascular Medicine最新文献

{"title":"Comparing Three Evidence-Based Strategies to Reduce Cardiovascular Disease Burden: An Individual-Based Cardiometabolic Policy Simulation","authors":"Sylvia Lutze, Steve Bachmeier, Alison Bowman, Nicole DeCleene, Hussain Jafari, Matthew Kappel, Caroline Kinuthia, Paulina Lindstedt, Megan Lindstrom, Rajan Mudambi, Christian Razo, Kjell Swedin, Abraham Flaxman, Gregory A. Roth","doi":"10.1101/2024.08.01.24311387","DOIUrl":"https://doi.org/10.1101/2024.08.01.24311387","url":null,"abstract":"Background: Understanding the real-world impact of clinical trials is important for informing health care policy. This is particularly true when trials are designed to show changes in surrogate endpoints such as changes in risk factors rather than events or mortality. We developed an agent-based microsimulation that estimates the population-level benefits in each US state for cardiometabolic health interventions shown to improve risk factors.\u0000Methods: We designed a large-scale, location-specific agent-based simulation model with a population of 51 million in silico individuals and estimated results for the years 2023 to 2040 in 30-day steps for each of the 50 states and District of Columbia. Input data reflected current cardiometabolic health in each state and the effects of interventions and risk factors on outcomes. We constructed three health policy intervention scenarios based on successful randomized controlled trials designed to improve cardiometabolic population health: improved access to fixed-dose combination (FDC) antihypertensive medication, a pharmacist-led intervention to increase adherence to statin and antihypertensives medications at the time they are initiated (Pharmacy), and a community-based lifestyle and behavior intervention designed to prevent diabetes (Community). Outcomes included myocardial infarction, ischemic and non-ischemic heart failure, and ischemic stroke events, deaths, and disability-adjusted life years (DALYs).\u0000Results: Our simulation included a representative population of the United States, accurate at the age, sex, and state level, with individual people simulated over 17 years. By the year 2040, the FDC intervention was estimated to have prevented 776,000 (95% UI 578,000?956,000) CVD DALYs and 44,600 (95% UI 32,700?55,600) deaths annually. Reductions in ischemic heart disease deaths accounted for 76.5% of the total reductions in CVD deaths. The Pharmacist intervention prevented 170,000 (95% UI 129,000?208,000) CVD DALYs, and the Community intervention prevented 152,000 (95% UI 128,000?173,000) CVD DALYs. Conclusions: A fixed-dose combination of antihypertensives could prevent 1.2% of total CVD DALYs, with smaller benefits from adherence and lifestyle-focused programs and impact of interventions varying by state. The greatest reduction was in incident myocardial infarctions and ischemic heart disease deaths. Providing accurate population-level estimates at the state level can help local health policy decision-makers implement the most impactful interventions.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IMPACT OF THE COVID-19 PANDEMIC ON ADHERENCE TO CARDIOVASCULAR MEDICATIONS AMONG CHRONICALLY TREATED PATIENTS IN ALBERTA","authors":"Finlay A. McAlister, Anamaria Savu, Luan Manh Chu, Douglas C Dover, Padma Kaul","doi":"10.1101/2024.07.31.24311323","DOIUrl":"https://doi.org/10.1101/2024.07.31.24311323","url":null,"abstract":"Background: Some studies have suggested that the COVID-19 pandemic negatively impacted patient adherence with chronic therapies. We designed this study to explore whether cardiovascular drug adherence patterns changed in chronically treated patients during the COVID-19 pandemic. Methods: Retrospective cohort study examining drug dispensation data for all Alberta residents older than 18 years who were chronic users of at least one cardiovascular drug class, defined as receiving at least one prescription per annum for any agent in that drug class from March 15, 2017 to March 14, 2023 and 2 or more prescriptions within 365 days during either the pre-pandemic phase (March 15, 2018 to March 14, 2020) or the pandemic phase (March 15, 2020 to March 14, 2022). We calculated the proportion of days covered (PDC) for each drug class per patient and used generalized estimating equation logistic regression to estimate the effect of time period (pandemic versus pre-pandemic) on achievement of good adherence (PDC>0.8) after adjusting for age, sex, socioeconomic status, and comorbidities. Results: We evaluated 548,601 chronic users of at least one cardiovascular drug class between March 15, 2018 and March 14, 2022. The most frequently dispensed cardiovascular drug classes were ACEi/ARB (67.6%), statins (53.8%), beta-blockers (21.0%), and calcium channel blockers (20.7%); the most frequent diagnoses were hypertension (77.2%), diabetes mellitus (30.6%), and ischemic heart disease (19.6%), although 55.4% of the patients had Charlson Comorbidity Index scores of 0. The mean PDC for cardiovascular drug use in our cohort was 85.7% (median 93%) pre-pandemic and 87.0% (median 94%) during the pandemic. The proportion exhibiting good adherence (PDC>0.8) increased from 72.8% pre-pandemic to 75.4% during the pandemic (p<0.001). During the pandemic, users of cardiovascular drugs were more likely to exhibit good adherence (PDC>0.8) than they were in the pre-pandemic period: aOR ranged from 1.05 (95%CI 1.00-1.11) for mineralocorticoid receptor antagonists to 1.16 (1.15-1.17) for statins. Conclusion: Chronic users of cardiovascular drugs exhibited higher adherence measures during the COVID-19 pandemic than prior to the pandemic.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141886795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLC25A26-mediated SAM compartmentalization coordinates translation and bioenergetics during cardiac hypertrophy","authors":"Ningning Guo, Jian Lv, Yu Fang, Qiuxiao Guo, Jiajie Li, Junmei Wang, Xiao Ma, Qingqing Yan, Fuqing Jiang, Shuiyun Wang, Li Wang, Zhihua Wang","doi":"10.1101/2024.07.30.24311193","DOIUrl":"https://doi.org/10.1101/2024.07.30.24311193","url":null,"abstract":"BACKGROUND: The heart undergoes hypertrophy as a compensatory mechanism to cope with increased hemodynamic stress, and it can transition into a primary driver of heart failure. Pathological cardiac hypertrophy is characterized by excess protein synthesis. Protein translation is an energy-intensive process that necessitates an inherent mechanism to flexibly fine-tune intracellular bioenergetics according to the translation status; however, such a molecular link remains lacking.\u0000METHODS: Slc25a26 knockout and cardiac-specific conditional knockout mouse models were generated to explore its function in vivo. Reconstructed adeno-associated virus was used to overexpress Slc25a26 in vivo. Cardiac hypertrophy was established by transaortic constriction (TAC) surgery. Neonatal rat ventricular myocytes were isolated and cultured to evaluate the role of SLC25A26 in cardiomyocyte growth and mitochondrial biology in vitro. RNA sequencing was conducted to explore the regulatory mechanism by SLC25A26. m1A-modified tRNAs were profiled by RNA immuno-precipitation sequencing. Label-free proteomics was performed to profile the nascent peptides affected by S-adenosylmethionine (SAM).\u0000RESULTS: We show that cardiomyocytes are among the top cell types expressing the SAM transporter SLC25A26, which maintains low-level cytoplasmic SAM in the heart. SAM biosynthesis is activated during cardiac hypertrophy, and feedforwardly mobilizes the mitochondrial translocation of SLC25A26 to shuttle excessive SAM into mitochondria. Systemic deletion of Slc25a26 causes embryonic lethality. Cardiac-specific deletion of Slc25a26 causes spontaneous heart failure and exacerbates cardiac hypertrophy induced by transaortic constriction. SLC25A26 overexpression, both before or after TAC surgery, rescues the hypertrophic pathologies and protects from heart failure. Mechanistically, SLC25A26 maintains low-level cytoplasmic SAM to restrict tRNA m1A modifications, particularly at A58 and A75, therefore decelerating translation initiation and modulating tRNA usage. Simultaneously, SLC25A26-mediated SAM accumulation in mitochondria maintains mitochondrial fitness for optimal energy production.\u0000CONCLUSIONS: These findings reveal a previously unrecognized role of SLC25A26-mediated SAM compartmentalization in synchronizing translation and bioenergetics. Targeting intracellular SAM distribution would be a promising therapeutic strategy to treat cardiac hypertrophy and heart failure.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141886794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in bioprosthetic valve failure after aortic valve replacement in patients with immune mediated inflammatory diseases","authors":"Christopher Sefton, Davis Leaphart, Benjamin Klein, Garrett Santini, Aditi Patel, M. Elaine Husni, Patrick Vargo, Eric E. Roselli, Lars Svensson, Amar Krishnaswamy, Samir R. Kapadia, Venu Menon, Umesh N. Khot, Heba Wassif","doi":"10.1101/2024.07.31.24311322","DOIUrl":"https://doi.org/10.1101/2024.07.31.24311322","url":null,"abstract":"Introduction:\u0000Immune-mediated inflammatory disease (IMID) is a subset of autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and psoriasis that is emerging as a risk factor for many cardiovascular diseases including valvular disease. Objectives:\u0000To determine whether IMID is associated with frequent and early development of bioprosthetic valve failure (BVF) after surgical aortic valve replacement (SAVR) and transcatheter valve replacement (TAVR). Methods:\u0000Serial echocardiograms for patients who underwent SAVR and TAVR at Cleveland Clinic between 2000 and 2022 were assessed for time to development of BVF after procedure. ICD10 codes were used to stratify to those with and without IMID. Kaplan-Meier curve and cox proportional hazard regression analysis were used to assess for differences in development of BVF after TAVR and SAVR. Results:\u0000351 TAVR patients (52 IMID and 299 controls) and 1961 SAVR patients (300 IMID and 1661 controls) were included. BVF after TAVR occurred in 12 (23.1%) IMID and 21 (7.0%) control patients, respectively, yielding an adjusted hazard ratio of 4.02 (1.81 - 8.92). Time to 50% of patients developing BVF was earlier among IMID, occurring at 6.6 years IMID and not reached in controls (p < 0.001). There were no significant differences in prevalence and time to development of BVF in IMID vs controls after SAVR. Conclusion:\u0000After TAVR, BVF occurred earlier and more frequently in patients with IMID than controls. This risk should be included during shared decision making among IMID patients considered for TAVR, and may warrant more frequent monitoring post procedure. These differences in BVF were not seen after SAVR.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ClinGen Hereditary Cardiovascular Disease Gene Curation Expert Panel: Reappraisal of Genes associated with Hypertrophic Cardiomyopathy","authors":"Sophie Hespe, Amber Waddell, Babken Asatryan, Emma Owens, Courtney Thaxton, Mhy-lanie Adduru, Kailyn Anderson, Emily Brown, Lily Hoffman-Andrews, Elizabeth Jordan, Katherine Josephs, Megan Mayers, Stacey Peters, Fergus Stafford, Richard Douglas Bagnall, Lucas Bronicki, Bert Callewaert, C. Anwar Chahal, Cynthia A. James, Olga Jarinova, Andrew P Landstrom, Elizabeth M. McNally, Brittney Murray, Laura Muiño-Mosquera, Victoria N. Parikh, Chloe Reuter, Roddy Walsh, Bess Wayburn, James Ware, Jodie Ingles","doi":"10.1101/2024.07.29.24311195","DOIUrl":"https://doi.org/10.1101/2024.07.29.24311195","url":null,"abstract":"Background: Hypertrophic cardiomyopathy (HCM) is an inherited cardiac condition affecting ~1 in 500 and exhibits marked genetic heterogeneity. Previously published in 2019, 57 HCM-associated genes were curated providing the first systematic evaluation of gene-disease validity. Here we report work by the ClinGen Hereditary Cardiovascular Disorders Gene Curation Expert Panel (HCVD-GCEP) to reappraise the clinical validity of previously curated and new putative HCM genes. Methods: The ClinGen systematic gene curation framework was used to re-classify the gene-disease relationships for HCM and related syndromic entities involving left ventricular hypertrophy. Genes previously curated were included if their classification was not definitive, and if the time since curation was >2-3 years. New genes with literature assertions for HCM were included for initial evaluation. Existing genes were curated for new inheritance patterns where evidence existed. Curations were presented on twice monthly calls, with the HCVD-GCEP composed of 29 individuals from 21 institutions across 6 countries.\u0000Results: Thirty-one genes were re-curated and an additional 5 new potential HCM-associated genes were curated. Among the re-curated genes, 17 (55%) genes changed classification: 1 limited and 4 disputed (from no known disease relationship), 9 disputed (from limited), and 3 definitive (from moderate). Among these, 3 (10%) genes had a clinically relevant upgrade, including TNNC1, a 9th sarcomere gene with definitive HCM association. With new evidence, two genes were curated for multiple inheritance patterns (TRIM63, disputed for autosomal dominant but moderate for autosomal recessive; ALPK3, strong for autosomal dominant and definitive for recessive). CSRP3 was curated for a semi-dominant mode of inheritance (definitive). Nine (29%) genes were downgraded to disputed, further discouraging clinical reporting of variants in these genes. Five genes recently reported to cause HCM were curated: RPS6KB1 and RBM20 (limited), KLHL24 and MT-TI (moderate), and FHOD3 (definitive).\u0000Conclusions: We report 29 genes with definitive, strong or moderate evidence of causation for HCM or isolated LVH, including sarcomere, sarcomere-associated and syndromic conditions.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipoprotein retention and inflammation due to regurgitant blood flow as part of the natural history of degenerative ascending aortic aneurysms","authors":"David Freiholtz, Karin Lång, Otto Bergman, Christian Olsson, Malin Granbom Koski, Michael Dismorr, Cecilia Österholm, Kenneth Caidahl, Anders Franco-Cereceda, Per Eriksson, Anton Gisterå, Hanna M. Björck","doi":"10.1101/2024.07.29.24311194","DOIUrl":"https://doi.org/10.1101/2024.07.29.24311194","url":null,"abstract":"BACKGROUND: An abnormal accumulation of immune cells and a disrupted lipoprotein metabolism has previously been described as part of the pathogenesis of ascending aortic aneurysm in patients with tricuspid aortic valves. The factor driving the accumulation of immune cells remains unclear; however, it may be considered in light of the observation that proximal aortic dilatation often occurs alongside aortic regurgitation but rarely with aortic stenosis. In the present study we aim to investigate the natural history of ascending aortic aneurysm in patients with tricuspid aortic valves by assessing the association between aortic regurgitation and vascular deterioration.\u0000MATERIAL AND METHODS: Patients tricuspid aortic valves undergoing elective open-heart surgery for ascending aortic- and/or aortic valve replacement were included. Aortic specimens from organ donors were obtained through the University of Miami Tissue Bank, USA. Protein expression/localization and differences in aortic intima-media gene expression were assessed using immunohistochemistry and transcriptomics, respectively. Ten-year aortic growth was measured using echocardiography. In total 142 patients were included across experiments (mRNA expression n=44, immunohistochemistry n=49, 10-year follow-up n=49).\u0000RESULTS: Aortic regurgitation was associated with the presence of oxidized apolipoprotein B-containing lipoproteins and infiltrating CD68+ cells in the non-dilated ascending aortic media, which was not observed in aortas of patients with aortic stenosis. Assessing factors influencing lipoprotein retention showed increased levels of genes encoding core proteins of proteoglycans (HSPG2, CSPG4, ACAN, and BGN) in patients with regurgitant valves, compared with aortas from patients with stenotic valves. Moreover, dilated aortas of patients with aortic regurgitation exhibited higher levels of the receptor for oxidized low-density lipoprotein, OLR1, which correlated positively with inflammatory markers in both dilated and non-dilated aortas. Surgical replacement of regurgitant aortic valves mitigated long-term aortic growth, in contrast to replacement of stenotic valves, which was associated with continuous aortic dilation.\u0000CONCLUSIONS: The natural history of ascending aortic aneurysm in patients with tricuspid aortic valves involves medial lipoprotein retention and oxidation with subsequent OLR1-driven pathological inflammation, and can be mitigated by replacement of the regurgitant aortic valve.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation and reproducibility of mapping positron emission tomography uptake in the aortic wall and thrombus","authors":"Mireia Bragulat-Arevalo, Marta Ferrer-Cornet, Lydia Dux-Santoy, Ruper Olivero-Soldevilla, Marvin Garcia-Reyes, Gisela Teixido-Tura, Juan Garrido-Oliver, Laura Galian-Gay, Pere Lopez-Gutierrez, Alberto Morales-Galan, Alba Catala-Santarrufina, Jose Ramon Garcia-Garzon, Noemi Martinez-Esquerda, Javier Solsona, Ignacio Ferreira-Gonzalez, Sergi Bellmunt-Montoya, Jose Rodriguez-Palomares, Andrea Guala","doi":"10.1101/2024.07.30.24311215","DOIUrl":"https://doi.org/10.1101/2024.07.30.24311215","url":null,"abstract":"INTRODUCTION: Aortic aneurysms are prevalent diseases of the aorta, with limited knowledge about their aetiology, progression, and risk, and no effective pharmacological treatment. 18F-fluorodesoxyglucose Positron Emission Tomography (18F-FDG PET) provides molecular level information of glucose activity, serving as potential analogue of vascular inflammation, which may be relevant to improve knowledge and clinical management of aortic aneurysms. Nonetheless, current clinical assessment of 18F-FDG uptake presents several limitations.\u0000PURPOSE: The aim of this study was to develop, test and validate an innovative aortic wall uptake mapping.\u0000METHODS: PET/magnetic resonance (MR) data from 72 patients were acquired. The aortic lumen was segmented, and 9 anatomical landmarks were identified to create a standardised aortic lumen discretization including up to 80 patches. Black-blood MR images were used to guide thrombus segmentation if present, which was merged with lumen segmentation to generate a thoraco-abdominal aortic wall mask. This mask was then expanded by 1 to 5 mm in the inward and outward directions, resulting in an aortic wall volume of interest. Median and percentile 95th standard uptake value (SUV) was calculated on each aortic patch. A second observer performed the same analysis on 23 randomly selected patients for inter-observer reproducibility assessment. Validation was performed by comparisons with regional SUV measured by a nuclear medicine expert.\u0000RESULTS: The technique was highly feasible, permitting the analysis of all 72 patients and in the 99.6% of aortic wall patches. The image analysis workflow was highly reproducible, resulting in Dice scores of 0.90 [0.57, 0.91] and 0.85 [0.78, 0.88] for aortic and thrombus segmentations, respectively, and in excellent co-localization for anatomical references (5.74 [3.62, 8.73] mm). The inter-observer reproducibility of aortic wall SUV mapping was excellent (ICC between 0.924 and 0.945), with limited differences with respect to aortic wall thickness and similar performances for SUV quantification in the thrombus. The validation of regional SUV values showed good agreement, with limited impact of aortic wall thickness values. A balance between reproducibility and accuracy was obtained with a volume of interest of 6 mm thickness. CONCLUSIONS: An image analysis implementation based on multi-modality PET/MR data provides reproducible and accurate quantitative aortic wall 18F-FDG uptake maps. This approach may enable exploring local factors related to an inflammatory vascular state, with possible repercussions in clinical practice.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141865976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of circulating T-cell subsets in carotid artery stiffness: the Multi-Ethnic Study of Atherosclerosis.","authors":"Theodore M DeConne, Petra Buzkova, Ryan Pewowaruk, Joseph AC Delaney, Bruce M. Psaty, Russell P. Tracy, Margaret F. Doyle, Colleen M Sitlani, Alan L. Landay, Sally Huber, Timothy M. Hughes, Alain G Bertoni, Adam D. Gepner, Nels C. Olson, Jingzhong Ding","doi":"10.1101/2024.07.29.24311196","DOIUrl":"https://doi.org/10.1101/2024.07.29.24311196","url":null,"abstract":"Background: Arterial stiffness measured by total pulse wave velocity (T-PWV) is associated with increased risk of multiple age-related diseases. T-PWV can be described by structural (S-PWV) and load-dependent (LD-PWV) arterial stiffening. T-cells have been associated with arterial remodeling, blood pressure, and arterial stiffness in humans and animals; however, it is unknown whether T-cells are related to S-PWV or LD-PWV. Therefore, we evaluated the cross-sectional associations of peripheral T-cell subpopulations with T-PWV, S-PWV, and LD-PWV stiffness. Methods: Peripheral blood T-cells were characterized using flow cytometry and the carotid artery was measured using B-mode ultrasound to calculate T-PWV at the baseline examination in a subset of the Multi-Ethnic Study of Atherosclerosis (MESA, n=1,984). A participant-specific exponential model was used to calculate S-PWV and LD-PWV based on elastic modulus and blood pressure gradients. The associations between five primary (p-significance<0.01) and twenty-five exploratory (p-significance<0.05) immune cell subpopulations, per 1-SD increment, and arterial stiffness measures were assessed using adjusted, linear regressions. Results: For the primary analysis, higher CD4+CD28-CD57+ T-cells were associated with higher LD-PWV (?=0.04 m/s, p<0.01) after adjusting for co-variates. For the exploratory analysis, T-cell subpopulations that commonly shift with aging towards memory and differentiated/immunosenescent phenotypes were associated with greater T-PWV, S-PWV, and LD-PWV after adjusting for co-variates. Conclusions: In this cross-sectional study, several T-cell subpopulations commonly associated with aging were related with measures of arterial stiffness. Longitudinal studies that examine changes in T-cell subpopulations and measures of arterial stiffness are warranted.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141865974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of somatic mutations in myeloid cells of men with chronic heart failure - interaction between loss of Y chromosome and clonal hematopoiesis","authors":"Sebastian Cremer, Moritz von Scheidt, Klara Kirschbaum, Lukas Tombor, Silvia Mas-Peiro, Tina Rasper, Wesley Abplanalp, Johannes Krefting, David Leistner, Thimoteus Speer, Heribert Schunkert, Stefanie Dimmeler, Andreas M. Zeiher","doi":"10.1101/2024.07.30.24310319","DOIUrl":"https://doi.org/10.1101/2024.07.30.24310319","url":null,"abstract":"Age-associated clonal hematopoiesis of indeterminate potential (CHIP) has been associated with increased incidence and worse prognosis of chronic heart failure. CHIP is driven by somatic mutations in hematopoietic stem and progenitor cells (HSPC). Mosaic loss of the Y chromosome (LOY), the most common somatic mutation in blood cells of men, also correlates with clonal expansion of myeloid cells, increases with age and was experimentally shown to lead to diffuse cardiac fibrosis and subsequent heart failure in mice. However, the prognostic significance of LOY as well as its potential interaction with CHIP in patients with chronic heart failure is unknown. We investigated the prevalence and prognostic significance of the extent of LOY and the two most common CHIP-driver mutations DNMT3A and TET2 in 705 male patients with established chronic heart failure across the entire spectrum of left ventricular ejection fraction. Both, LOY and DNMT3A/TET2 mutations, increased with age, and LOY co-occurred with DNMT3A/TET2 mutations in 27.1% of men at age > 70 years. LOY was an independent predictor of death during 3-years of follow-up across the entire spectrum of left ventricular ejection fraction. The co-occurrence of harboring LOY and DNMT3A/TET2 mutations significantly contributed to the observed increased mortality observed in carriers of DNMT3A/TET2 mutations. The detrimental effect of LOY on prognosis was confirmed in a validation cohort of patients with ischemic heart disease. scRNA sequencing of peripheral blood cells in patients with chronic ischemic heart failure showed increased profibrotic signaling in LOY monocytes with elevated markers of monocyte mediated inflammation and profibrotic cardiac remodeling (S100A8, TLR2, CLEC4D) and reduced expression of TGF-beta inhibiting genes (SMAD7, TGIF2). The proinflammatory phenotype of LOY monocytes was further amplified in LOY monocytes of patients simultaneously harboring DNMT3A mutations, who displayed heightened expression of alarmins (S100A8, HMGB2) and interferon signaling related genes (IFNGR1, TRIM56, CD84) compared to patients without CHIP mutations. Thus, the age-associated acquisition of somatic mutations in blood cells of men with chronic heart failure is associated with increased mortality, with loss of Y chromosome emerging as an independent predictor of all-cause death across the entire spectrum of left ventricular function.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141865973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Singing on Vascular Health in Older Adults with Coronary Artery Disease: A Randomized Trial","authors":"Mehri BagheriMohamadiPour, Muhammad Hammad, Alexis Visotcky, Rodney Sparapani, Jacquelyn Kulinski","doi":"10.1101/2024.07.25.24311033","DOIUrl":"https://doi.org/10.1101/2024.07.25.24311033","url":null,"abstract":"Background: The impact of singing on cardiovascular health has not been extensively studied. The aim of this study is to investigate the effect of singing on cardiovascular biomarkers in an aging population with coronary artery disease. Methods: Participants had three study visits separated by 2-7 days, according to a randomized, single-blind, cross-over, controlled design: (1) a 30-minute period of coached singing from an in-person music therapist, (2) a 30-minute period of singing along to an instructional video and (3) a 30-minute rest (control). Primary outcomes included macrovascular endothelial function assessed by brachial artery flow-mediated dilation and microvascular function assessed by peripheral arterial tonometry (Framingham reactive hyperemia index; fRHI). Heart rate variability was a secondary outcome.\u0000Results: Sixty-five subjects (mean age 67.7± 0.8, 40% women) completed the study. Compared to control, there was an increase in fRHI for the singing video intervention (estimate 0.54, SE 0.25, p=0.005) but not for the coaching intervention (estimate 0.11, SE 0.18, p=0.570). There was no change in macrovascular function with either intervention. The low frequency/high frequency (LF/HF) ratio increased by 2.80 (SE 1.03, p=0.008), and the LnHF power decreased by -0.90 ms2 (SE 0.29, p=0.003) with the video (during to pre-change). When assessing post- to pre- change, the coaching intervention showed a significant change of -0.62 ms2 (SE 0.29, p=0.036) in LnHF power. Conclusions: Singing along to an instructional video for 30 minutes improved microvascular, but not macrovascular, endothelial function, in older patients with CAD. HRV changes with singing are similar to that of exercise.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141771902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}