Pub Date : 2024-09-13DOI: 10.1101/2024.09.12.24313331
LAWRENCE N. SCOTTEN, Dylan Goode, Rolland Siegel, David J. Blundon, James W. Dutton, Hadi Mohammadi
Objective: -In vitro evaluation of several prototype mechanical valves compared to present-day SAVR prosthetic valves. Method: -simulated normal cardiac pressures and flows -gravity pressure head column tester flows -recorded valve hydrodynamics and kinematics Results: -valves superior in performance to clinical controls Conclusions: -Prototype MHV candidates outperform the closing performance of present-day SAVR prosthetic valves, including bioprosthetic control.
{"title":"Challenging the Chronic Perverse Bias in Prosthetic Valve Design: A Pathway Opens for Advanced Mechanical Valves.","authors":"LAWRENCE N. SCOTTEN, Dylan Goode, Rolland Siegel, David J. Blundon, James W. Dutton, Hadi Mohammadi","doi":"10.1101/2024.09.12.24313331","DOIUrl":"https://doi.org/10.1101/2024.09.12.24313331","url":null,"abstract":"Objective:\u0000-In vitro evaluation of several prototype mechanical valves compared to present-day SAVR prosthetic valves.\u0000Method:\u0000-simulated normal cardiac pressures and flows\u0000-gravity pressure head column tester flows\u0000-recorded valve hydrodynamics and kinematics\u0000Results:\u0000-valves superior in performance to clinical controls\u0000Conclusions:\u0000-Prototype MHV candidates outperform the closing performance of present-day SAVR prosthetic valves, including bioprosthetic control.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258373","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}
Background: There is a significant lack of effective pharmaceutical interventions for treating coronary artery calcification (CAC). Severe CAC (sCAC) poses a formidable challenge to interventional surgery and exhibits robust associations with adverse cardiovascular outcomes. Therefore, it is imperative to develop tools capable of early-stage detection and risk assessment for both CAC and sCAC. This study aims to develop and validate nomograms for the accurate prediction of CAC and sCAC. Methods: This retrospective cross-sectional study was conducted in Taizhou, Jiangsu Province, China. CAC assessment was performed using non-gated thoracic CT scans. Demographic data and clinical information were collected from patients who were then randomly divided into a training set (70%) or a validation set (30%). Least absolute shrinkage and selection operator (LASSO) regression as well as multiple logistic regression analyses were utilized to identify predictive factors for both CAC and sCAC development. Nomograms were developed to predict the occurrence of CAC or sCAC events. The models' performance was evaluated through discrimination analysis, calibration analysis, as well as assessment of their clinical utility. Results: This study included 666 patients with an average age of 75 years, of whom 56% were male. 391 patients had CAC, with sCAC in 134 cases. Through LASSO and multiple logistic regression analysis, age increase, hypertension, carotid artery calcification, CHD, and CHADS2 score were identified for the CAC risk predictive nomogram with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.845(95%CI 0.809-0.881) in the training set and 0.810(95%CI 0.751-0.870) in the validation set. Serum calcium level, carotid artery calcification, and CHD were identified for the sCAC risk predictive nomogram with an AUC of 0.863(95%CI 0.825-0.901) in the training set and 0.817(95%CI 0.744-0.890) in the validation set. Calibration plots indicated that two models exhibited good calibration ability. According to the decision curve analysis (DCA) results, both models have demonstrated a positive net benefit within a wide range of risks. Conclusions: The present study has successfully developed and validated two nomograms to accurately predict CAC and sCAC, both of which have demonstrated robust predictive capabilities.
{"title":"Development and Validation of Nomograms for predicting Coronary Artery Calcification and Severe Coronary Artery Calcification: a retrospective cross-sectional study","authors":"Peng Xue, Ling Lin, Peishan Li, Zhengting Deng, Xiaohu Chen, Yanshuang Zhuang","doi":"10.1101/2024.09.12.24313598","DOIUrl":"https://doi.org/10.1101/2024.09.12.24313598","url":null,"abstract":"Background: There is a significant lack of effective pharmaceutical interventions for treating coronary artery calcification (CAC). Severe CAC (sCAC) poses a formidable challenge to interventional surgery and exhibits robust associations with adverse cardiovascular outcomes. Therefore, it is imperative to develop tools capable of early-stage detection and risk assessment for both CAC and sCAC. This study aims to develop and validate nomograms for the accurate prediction of CAC and sCAC. Methods: This retrospective cross-sectional study was conducted in Taizhou, Jiangsu Province, China. CAC assessment was performed using non-gated thoracic CT scans. Demographic data and clinical information were collected from patients who were then randomly divided into a training set (70%) or a validation set (30%). Least absolute shrinkage and selection operator (LASSO) regression as well as multiple logistic regression analyses were utilized to identify predictive factors for both CAC and sCAC development. Nomograms were developed to predict the occurrence of CAC or sCAC events. The models' performance was evaluated through discrimination analysis, calibration analysis, as well as assessment of their clinical utility. Results: This study included 666 patients with an average age of 75 years, of whom 56% were male. 391 patients had CAC, with sCAC in 134 cases. Through LASSO and multiple logistic regression analysis, age increase, hypertension, carotid artery calcification, CHD, and CHADS2 score were identified for the CAC risk predictive nomogram with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.845(95%CI 0.809-0.881) in the training set and 0.810(95%CI 0.751-0.870) in the validation set. Serum calcium level, carotid artery calcification, and CHD were identified for the sCAC risk predictive nomogram with an AUC of 0.863(95%CI 0.825-0.901) in the training set and 0.817(95%CI 0.744-0.890) in the validation set. Calibration plots indicated that two models exhibited good calibration ability. According to the decision curve analysis (DCA) results, both models have demonstrated a positive net benefit within a wide range of risks. Conclusions: The present study has successfully developed and validated two nomograms to accurately predict CAC and sCAC, both of which have demonstrated robust predictive capabilities.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258374","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}
Pub Date : 2024-09-12DOI: 10.1101/2024.09.10.24313445
Steven J Cassady, Post-Deployment Cardiopulmonary Evaluation Network, Thomas J Abitante, Gregory Pappas, Thomas Alexander, Michael Falvo
Background: Environmental factors, such as exposure to airborne hazards, contribute to cardiac remodeling through a variety of mechanisms including direct cardiotoxicity. Left ventricular concentric remodeling (LVCR) is a pathological process of adaptive myocardial change that may represent a precursor state for systolic and diastolic dysfunction and left ventricular hypertrophy. Given that potentially cardiotoxic airborne hazards, such as those produced by open burn pits, have been found to occur in excess in active military combat zones, deployed veterans may be at increased risk for adverse cardiac remodeling, but this has not been thoroughly investigated. Methods: 139 veterans of Southwest Asia Theater of Military Operations underwent transthoracic echocardiography, cardiopulmonary exercise testing (CPET), and health questionnaires. Two-dimensional echocardiography was used to quantify relative wall thickness (RWT) to classify left ventricular (LV) geometry as normal, concentric/eccentric hypertrophy, or LVCR. Observed rates of LVCR were compared to those reported in the Framingham Heart Study, and CPET results were compared between those with and without LVCR. We examined the association between RWT and select CPET outcomes via an adjusted multivariate regression model. Results: The prevalence of LVCR in the veteran sample (30.2%) was elevated compared to the Framingham Heart Study cohort (6-16%). Demographics and risk factors were similar between veterans with LVCR and normal geometry; however, veterans with LVCR had reduced exercise capacity (VO2, 23.7 vs 26.2 ml/kg/min, p<0.05), more inefficient exercise ventilation (VE/V?CO2 nadir: 26.8 vs 25.2, p<0.05), and increased heart rate (HR) reserve (24.7 vs 17.4, p<0.05). RWT was independently associated only with peak HR attained and HR reserve. Conclusions: In our sample of deployed veterans without significant risk factors, the observed rates of LVCR are 2- to 5-fold greater than those reported in a historical civilian cohort. Further, veterans with LVCR also had impaired exercise performance relative to those with normal LV geometry despite otherwise appearing similar. These findings underscore the importance of cardiovascular assessments as part of a dyspnea evaluation for deployed veterans with airborne hazards exposure and raise concerns about their long-term cardiovascular health.
{"title":"Left ventricular concentric remodeling is highly common among veterans previously deployed to Southwest Asia Theater of Military Operations and associated with impaired exercise performance.","authors":"Steven J Cassady, Post-Deployment Cardiopulmonary Evaluation Network, Thomas J Abitante, Gregory Pappas, Thomas Alexander, Michael Falvo","doi":"10.1101/2024.09.10.24313445","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313445","url":null,"abstract":"Background:\u0000Environmental factors, such as exposure to airborne hazards, contribute to cardiac remodeling through a variety of mechanisms including direct cardiotoxicity. Left ventricular concentric remodeling (LVCR) is a pathological process of adaptive myocardial change that may represent a precursor state for systolic and diastolic dysfunction and left ventricular hypertrophy. Given that potentially cardiotoxic airborne hazards, such as those produced by open burn pits, have been found to occur in excess in active military combat zones, deployed veterans may be at increased risk for adverse cardiac remodeling, but this has not been thoroughly investigated.\u0000Methods:\u0000139 veterans of Southwest Asia Theater of Military Operations underwent transthoracic echocardiography, cardiopulmonary exercise testing (CPET), and health questionnaires. Two-dimensional echocardiography was used to quantify relative wall thickness (RWT) to classify left ventricular (LV) geometry as normal, concentric/eccentric hypertrophy, or LVCR. Observed rates of LVCR were compared to those reported in the Framingham Heart Study, and CPET results were compared between those with and without LVCR. We examined the association between RWT and select CPET outcomes via an adjusted multivariate regression model.\u0000Results:\u0000The prevalence of LVCR in the veteran sample (30.2%) was elevated compared to the Framingham Heart Study cohort (6-16%). Demographics and risk factors were similar between veterans with LVCR and normal geometry; however, veterans with LVCR had reduced exercise capacity (VO2, 23.7 vs 26.2 ml/kg/min, p<0.05), more inefficient exercise ventilation (VE/V?CO2 nadir: 26.8 vs 25.2, p<0.05), and increased heart rate (HR) reserve (24.7 vs 17.4, p<0.05). RWT was independently associated only with peak HR attained and HR reserve. Conclusions:\u0000In our sample of deployed veterans without significant risk factors, the observed rates of LVCR are 2- to 5-fold greater than those reported in a historical civilian cohort. Further, veterans with LVCR also had impaired exercise performance relative to those with normal LV geometry despite otherwise appearing similar. These findings underscore the importance of cardiovascular assessments as part of a dyspnea evaluation for deployed veterans with airborne hazards exposure and raise concerns about their long-term cardiovascular health.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218923","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}
Pub Date : 2024-09-11DOI: 10.1101/2024.09.10.24313412
Lucas Kleebank Fernandes, Gisele Brasil Nobre Chaves Rangel, Renan Luis Martins, Danilo Fernando Martin, Moacir Fernandes de Godoy
Objective: To identify the prevalence of modifiable and non-modifiable risk factors related to cardiovascular diseases [CVDs] in the nursing team of a tertiary hospital in the interior of the state of Sao Paulo and suggest preventive practices. Methods: This is a prospective-analytical epidemiological study, of a quantitative nature, carried out on 226 employees, in two stages: collection of self-declared data and measurement of anthropometric data. Results: Risk factors such as family history of CVD (82.7%), alcoholism (57.1%), sedentary lifestyle (49.1%), insufficient sleep time (27.9%), high consumption of processed meals (98.2%) and sugary beverages (81.7%) were observed, among others. From anthropometric data, it was identified that 69.4% of participants are overweight (38.7%) or obese (30.6%) - evidenced by high waist circumference (48.6%) and a high waist-to-hip ratio (64.0%) - in addition to 17.1% who had blood pressure levels indicative of arterial hypertension. The majority reported not having a diagnosis of CVDs (76.1%), however, among those who do, more than half (53.7%) do not treat them properly. Conclusion: It is observed that the prevalence of CVDs is not irrelevant in the group evaluated and that there is the presence of risk factors indicating a tendency for participants to develop new CVDs or worsen existing ones, due to the presence of harmful habits associated with an unhealthy lifestyle and lack of adherence to treatments. This study suggests the implementation of multidisciplinary action programs with employees, so that the main areas identified as deficient are addressed.
{"title":"Cardiovascular Risk Factors in Nurses at a Teaching Hospital","authors":"Lucas Kleebank Fernandes, Gisele Brasil Nobre Chaves Rangel, Renan Luis Martins, Danilo Fernando Martin, Moacir Fernandes de Godoy","doi":"10.1101/2024.09.10.24313412","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313412","url":null,"abstract":"Objective: To identify the prevalence of modifiable and non-modifiable risk factors related to cardiovascular diseases [CVDs] in the nursing team of a tertiary hospital in the interior of the state of Sao Paulo and suggest preventive practices. Methods: This is a prospective-analytical epidemiological study, of a quantitative nature, carried out on 226 employees, in two stages: collection of self-declared data and measurement of anthropometric data. Results: Risk factors such as family history of CVD (82.7%), alcoholism (57.1%), sedentary lifestyle (49.1%), insufficient sleep time (27.9%), high consumption of processed meals (98.2%) and sugary beverages (81.7%) were observed, among others. From anthropometric data, it was identified that 69.4% of participants are overweight (38.7%) or obese (30.6%) - evidenced by high waist circumference (48.6%) and a high waist-to-hip ratio (64.0%) - in addition to 17.1% who had blood pressure levels indicative of arterial hypertension. The majority reported not having a diagnosis of CVDs (76.1%), however, among those who do, more than half (53.7%) do not treat them properly. Conclusion: It is observed that the prevalence of CVDs is not irrelevant in the group evaluated and that there is the presence of risk factors indicating a tendency for participants to develop new CVDs or worsen existing ones, due to the presence of harmful habits associated with an unhealthy lifestyle and lack of adherence to treatments. This study suggests the implementation of multidisciplinary action programs with employees, so that the main areas identified as deficient are addressed.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218966","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}
Pub Date : 2024-09-10DOI: 10.1101/2024.09.09.24313318
Huiqi Qu, JuFang Wang, Alexandre Rosa Campos, Hakon Hakonarson, Arthur Feldman
Background: Bcl-2-associated athanogene 3 (BAG3) plays an important function in cellular protein quality control (PQC) maintaining proteome stability. Mutations in the BAG3 gene result in cardiomyopathies. Due to its roles in cardiomyopathies and the complexity of BAG3-protein interactions, it is important to understand these protein interactions given the importance of the multifunctional cochaperone BAG3 in cardiomyocytes, using an in vitro cardiomyocyte model. Methods: The experimental assay was done using high pressure liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in the human AC16 cardiomyocyte cell line with the BioID technology. Results: Proteins with BAG3-interaction were identified in all the 28 hallmark gene sets enriched in idiopathic cardiomyopathies and/or ischemic disease. Among the 24 hallmark gene sets enriched in both idiopathic cardiomyopathies and ischemic disease, 15 gene sets had at least 3 proteins with BAG3-interaction. Conclusions: This study highlights BAG3 protein interactions, unveiling the key gene sets affected in cardiomyopathies, which help to explain the molecular mechanisms of the cardioprotective effects of BAG3. In addition, this study also highlighted the complexity of proteins with BAG3 interactions, implying unwanted effects of BAG3.
{"title":"Role of BAG3 protein interactions in cardiomyopathies","authors":"Huiqi Qu, JuFang Wang, Alexandre Rosa Campos, Hakon Hakonarson, Arthur Feldman","doi":"10.1101/2024.09.09.24313318","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313318","url":null,"abstract":"Background: Bcl-2-associated athanogene 3 (BAG3) plays an important function in cellular protein quality control (PQC) maintaining proteome stability. Mutations in the BAG3 gene result in cardiomyopathies. Due to its roles in cardiomyopathies and the complexity of BAG3-protein interactions, it is important to understand these protein interactions given the importance of the multifunctional cochaperone BAG3 in cardiomyocytes, using an in vitro cardiomyocyte model.\u0000Methods: The experimental assay was done using high pressure liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in the human AC16 cardiomyocyte cell line with the BioID technology.\u0000Results: Proteins with BAG3-interaction were identified in all the 28 hallmark gene sets enriched in idiopathic cardiomyopathies and/or ischemic disease. Among the 24 hallmark gene sets enriched in both idiopathic cardiomyopathies and ischemic disease, 15 gene sets had at least 3 proteins with BAG3-interaction.\u0000Conclusions: This study highlights BAG3 protein interactions, unveiling the key gene sets affected in cardiomyopathies, which help to explain the molecular mechanisms of the cardioprotective effects of BAG3. In addition, this study also highlighted the complexity of proteins with BAG3 interactions, implying unwanted effects of BAG3.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227466","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}
Pub Date : 2024-09-10DOI: 10.1101/2024.09.08.24313086
Timothy C Shuey, Stephen Voyce, Laney K. Jones, Alicia Johns, Caroline F. deRichemond, Scott A. LeMaire, Braxton Lagerman, Shikhar Agarwal
Background: A comprehensive real-world analysis of residual risk factors for recurrent major adverse cardiovascular events (MACE) following hospital admission for acute coronary syndrome (ACS) is lacking. The objectives of this study were: 1) to describe population trends for outcomes, risk factors, and medication prescribing patterns post-ACS and 2) to identify factors associated with recurrent MACE. Methods: A retrospective cohort study of 4,884 post-ACS patients admitted at a large integrated healthcare system between 2015-2021 was performed to investigate the relationship between recurrent MACE (ACS, cerebrovascular events, all-cause mortality, and unplanned revascularization), modifiable risk factor trends, and medical therapy prescribing patterns. Patients were separated into 2 cohorts based upon whether they experienced recurrent MACE following the initial hospitalization. Data were obtained via programmatic extraction from the electronic health record. Descriptive statistics were performed. Generalized linear models were used to assess risk factor trends and pairwise comparisons were performed between time points. Results: Median length of follow-up after ACS was 31.2 months. Recurrent MACE occurred in 28% of patients. Despite 95.9% of all patients receiving prescriptions for high-intensity statins, >40% did not achieve LDL-C goal of <70 mg/dL, and only 11.6% and 2.6% of all patients were prescribed ezetimibe or proprotein convertase subtilisin kexin type 9 inhibiting monoclonal antibodies, respectively. Although >30.0% of patients had triglycerides ≥150 mg/dL at all time points, ≤6% were prescribed any non-statin triglyceride lowering therapy and 0.6% were prescribed icosapent ethyl. Persistent hypertriglyceridemia (≥150 mg/dL) was associated with recurrent MACE at 6-, 12-, and 24-months post-ACS (p<0.05), and the relative risk ranged between 1.20-1.35 at those timepoints. Conclusions: This study demonstrates the need for more comprehensive post-ACS care to address residual cardiometabolic risk factors and suboptimal prescribing patterns for indicated therapies. Targeted strategies are needed to address hypertriglyceridemia for cardiovascular risk reduction.
{"title":"Analysis of Residual Risk and Recurrent Event Trends Following Acute Coronary Syndrome: A Cohort Study","authors":"Timothy C Shuey, Stephen Voyce, Laney K. Jones, Alicia Johns, Caroline F. deRichemond, Scott A. LeMaire, Braxton Lagerman, Shikhar Agarwal","doi":"10.1101/2024.09.08.24313086","DOIUrl":"https://doi.org/10.1101/2024.09.08.24313086","url":null,"abstract":"Background: A comprehensive real-world analysis of residual risk factors for recurrent major adverse cardiovascular events (MACE) following hospital admission for acute coronary syndrome (ACS) is lacking. The objectives of this study were: 1) to describe population trends for outcomes, risk factors, and medication prescribing patterns post-ACS and 2) to identify factors associated with recurrent MACE.\u0000Methods: A retrospective cohort study of 4,884 post-ACS patients admitted at a large integrated healthcare system between 2015-2021 was performed to investigate the relationship between recurrent MACE (ACS, cerebrovascular events, all-cause mortality, and unplanned revascularization), modifiable risk factor trends, and medical therapy prescribing patterns. Patients were separated into 2 cohorts based upon whether they experienced recurrent MACE following the initial hospitalization. Data were obtained via programmatic extraction from the electronic health record. Descriptive statistics were performed. Generalized linear models were used to assess risk factor trends and pairwise comparisons were performed between time points. Results: Median length of follow-up after ACS was 31.2 months. Recurrent MACE occurred in 28% of patients. Despite 95.9% of all patients receiving prescriptions for high-intensity statins, >40% did not achieve LDL-C goal of <70 mg/dL, and only 11.6% and 2.6% of all patients were prescribed ezetimibe or proprotein convertase subtilisin kexin type 9 inhibiting monoclonal antibodies, respectively. Although >30.0% of patients had triglycerides ≥150 mg/dL at all time points, ≤6% were prescribed any non-statin triglyceride lowering therapy and 0.6% were prescribed icosapent ethyl. Persistent hypertriglyceridemia (≥150 mg/dL) was associated with recurrent MACE at 6-, 12-, and 24-months post-ACS (p<0.05), and the relative risk ranged between 1.20-1.35 at those timepoints. Conclusions: This study demonstrates the need for more comprehensive post-ACS care to address residual cardiometabolic risk factors and suboptimal prescribing patterns for indicated therapies. Targeted strategies are needed to address hypertriglyceridemia for cardiovascular risk reduction.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218924","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}
Pub Date : 2024-09-10DOI: 10.1101/2024.09.09.24313367
Zhongheng Li, Maimaitiyasen Duolikun, Hangyu Chen, Lei Zhang, Yishuo Liu, Ruining Li, Dan Li, Long Chen, lijie sun
Background: Studies have reported that 5hmC features in cell-free DNA (cfDNA) could serve as early warning biomarkers for the occurrence and progression of COVID-19, as well as myocardial injury. However, its roles in the occurrence and progression of acute coronary syndrome (ACS) following COVID-19 infection has not been fully studied. Methods: Firstly, we used the 5hmC-Seal technique to obtain genome-wide 5hmC profiles from plasma cfDNA of 24 ACS2N patients (individuals experiencing ACS onset within 2 months after COVID-19 infection), 28 ACS2W patients (individuals experiencing ACS onset beyond 2 months after COVID-19 infection), and 16 ACS patients (patients with ACS without COVID-19 infection). Secondly, we performed GO, KEGG analysis on the differentially expressed genes and identified a series of immune and inflammation related genes. Thirdly, the distribution of immune cells in different groups of patients was studied by immune infiltration analysis. Finally, we performed PPI network analysis on these genes to identify potential key target genes. Results: In this study, we firstly found that there was a significant difference in 5hmC levels between ACS2N patients and ACS patients, while the difference between ACS2W and ACS was not significant. Secondly, it was found that neutrophils were abnormally activated in the ACS2N group. Finally, a target gene phosphodiesterase 4D (PDE4D) was found to be highly expressed in the ACS2N group by PPI network analysis of the differential genes and validated with external datasets. Conclusions: Our study suggested that 5hmC markers extracted from plasma cfDNA could differentiate between ACS2N and ACS patients. In addition, we observed that neutrophils exhibited abnormal activation in ACS2N patients. Further analysis showed that COVID-19 infection may affect the occurrence and development of ACS by abnormally up-regulating PDE4D gene expression.
{"title":"5-hydroxymethylcytosine Epigenetic Markers in COVID-19-Associated Acute Coronary Syndrome: Insights into Neutrophil Activation and PDE4D Upregulation","authors":"Zhongheng Li, Maimaitiyasen Duolikun, Hangyu Chen, Lei Zhang, Yishuo Liu, Ruining Li, Dan Li, Long Chen, lijie sun","doi":"10.1101/2024.09.09.24313367","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313367","url":null,"abstract":"Background: Studies have reported that 5hmC features in cell-free DNA (cfDNA) could serve as early warning biomarkers for the occurrence and progression of COVID-19, as well as myocardial injury. However, its roles in the occurrence and progression of acute coronary syndrome (ACS) following COVID-19 infection has not been fully studied.\u0000Methods: Firstly, we used the 5hmC-Seal technique to obtain genome-wide 5hmC profiles from plasma cfDNA of 24 ACS2N patients (individuals experiencing ACS onset within 2 months after COVID-19 infection), 28 ACS2W patients (individuals experiencing ACS onset beyond 2 months after COVID-19 infection), and 16 ACS patients (patients with ACS without COVID-19 infection). Secondly, we performed GO, KEGG analysis on the differentially expressed genes and identified a series of immune and inflammation related genes. Thirdly, the distribution of immune cells in different groups of patients was studied by immune infiltration analysis. Finally, we performed PPI network analysis on these genes to identify potential key target genes.\u0000Results: In this study, we firstly found that there was a significant difference in 5hmC levels between ACS2N patients and ACS patients, while the difference between ACS2W and ACS was not significant. Secondly, it was found that neutrophils were abnormally activated in the ACS2N group. Finally, a target gene phosphodiesterase 4D (PDE4D) was found to be highly expressed in the ACS2N group by PPI network analysis of the differential genes and validated with external datasets.\u0000Conclusions: Our study suggested that 5hmC markers extracted from plasma cfDNA could differentiate between ACS2N and ACS patients. In addition, we observed that neutrophils exhibited abnormal activation in ACS2N patients. Further analysis showed that COVID-19 infection may affect the occurrence and development of ACS by abnormally up-regulating PDE4D gene expression.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218925","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}
Pub Date : 2024-09-09DOI: 10.1101/2024.09.05.24313129
Hannah Foote, Audrey Bowen, Sarah Cotterill, Emma Patchwood
Mental health difficulties are common post stroke and developing support for psychological adjustment is a research priority. Wellbeing After Stroke (WAterS) is a nine week, online, group based Acceptance and Commitment Therapy (ACT) informed intervention, delivered by trained third sector practitioners, supervised by a clinical neuropsychologist. This study aimed to explore the acceptability of WAterS from the stroke survivors perspective. Semi structured interviews were conducted with twelve stroke survivors who received WAterS. The interview schedule was informed by theorised components of acceptability, including understanding, burden and perception of effectiveness. The data were analysed inductively and deductively using Template Analysis. Six qualitative themes were generated. Results indicate the intervention was mostly understandable and participants were able to engage with ACT and apply it to life. Online delivery reduced burden in accessing the intervention, and was acceptable when supported by live facilitation and a physical handbook. Group cohesion and understanding was facilitated by practitioners. The social aspect of the group was beneficial. Attending WAterS supported some participants to seek further support; others were left feeling unsupported when the intervention ended. To conclude: Stroke survivors valued attending an online, group ACT informed intervention, delivered by practitioners. This is a promising avenue in increasing the reach of interventions to support wellbeing.
{"title":"An online, group Acceptance and Commitment Therapy is acceptable to stroke survivors: A qualitative interview study","authors":"Hannah Foote, Audrey Bowen, Sarah Cotterill, Emma Patchwood","doi":"10.1101/2024.09.05.24313129","DOIUrl":"https://doi.org/10.1101/2024.09.05.24313129","url":null,"abstract":"Mental health difficulties are common post stroke and developing support for psychological adjustment is a research priority. Wellbeing After Stroke (WAterS) is a nine week, online, group based Acceptance and Commitment Therapy (ACT) informed intervention, delivered by trained third sector practitioners, supervised by a clinical neuropsychologist. This study aimed to explore the acceptability of WAterS from the stroke survivors perspective. Semi structured interviews were conducted with twelve stroke survivors who received WAterS. The interview schedule was informed by theorised components of acceptability, including understanding, burden and perception of effectiveness. The data were analysed inductively and deductively using Template Analysis. Six qualitative themes were generated. Results indicate the intervention was mostly understandable and participants were able to engage with ACT and apply it to life. Online delivery reduced burden in accessing the intervention, and was acceptable when supported by live facilitation and a physical handbook. Group cohesion and understanding was facilitated by practitioners. The social aspect of the group was beneficial. Attending WAterS supported some participants to seek further support; others were left feeling unsupported when the intervention ended. To conclude: Stroke survivors valued attending an online, group ACT informed intervention, delivered by practitioners. This is a promising avenue in increasing the reach of interventions to support wellbeing.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218927","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}
Pub Date : 2024-09-07DOI: 10.1101/2024.09.06.24313220
Michal Ambroziak, Jakub Franke, Anna Wojcicka, Monika Kolanowska, Andrzej Budaj
Aim. The aim of the study was to investigate the role of genetic variants in young patients (aged <50 years) with myocardial infarction (MI) and a family history of premature atherosclerosis. Methods and Results. The studied group consisted of 70 patients aged 26-49 (mean 43.1, SD ±4.3), 17 women and 53 men, with MI and with a family history of premature atherosclerosis, defined as MI or ischaemic stroke in first-degree relatives at age <65 years in women or <55 years in men. The total DNA was extracted from the peripheral blood samples. The targeted enrichment library was prepared and analyzed using the Next-Generation Sequencing method. Statistical analyses were performed using the R software package (http://www.r-project.org/). The results of sequencing were compared to data from the reference control population consisting of 597 people with no history of MI (418 women, 179 men) aged 18-83 (mean 40.5, SD ± 12.4) as a whole and after matching with a studied group by age and gender in a proportion 1:3 (210 people, 51 women, 159 men, aged 18-77, mean 42.1, SD ±10.6) using Propensity Score Matching. Risks associated with detected variants were evaluated using Fisher?s exact test based on the allelic frequencies of variants in both groups. SYNE1 gene variant rs36215567 (NM_182961.4: c.20396+22A>G) occurs with a significantly higher incidence in the studied group when compared to the control population with OR 4.80 95%CI 1.43-14.45 (p=0.005) as well as when compared to the control population matched by age and gender OR 9.31 95%CI 1.64-95.41 (p=0.004). There were no statistically significant differences in the incidence of variants related to familial hypercholesterolemia such as LDLR c.667G>A, PCSK9 c.658-36G>A, and APOB c.12382G>A between both cohorts. Conclusion. A novel variant of the SYNE1 gene is associated with myocardial infarction in young patients with a family history of premature atherosclerosis.
{"title":"SYNE1 gene novel variant is associated with myocardial infarction in young people with a family history of premature atherosclerosis.","authors":"Michal Ambroziak, Jakub Franke, Anna Wojcicka, Monika Kolanowska, Andrzej Budaj","doi":"10.1101/2024.09.06.24313220","DOIUrl":"https://doi.org/10.1101/2024.09.06.24313220","url":null,"abstract":"Aim. The aim of the study was to investigate the role of genetic variants in young patients (aged <50 years) with myocardial infarction (MI) and a family history of premature atherosclerosis.\u0000Methods and Results. The studied group consisted of 70 patients aged 26-49 (mean 43.1, SD ±4.3), 17 women and 53 men, with MI and with a family history of premature atherosclerosis, defined as MI or ischaemic stroke in first-degree relatives at age <65 years in women or <55 years in men. The total DNA was extracted from the peripheral blood samples. The targeted enrichment library was prepared and analyzed using the Next-Generation Sequencing method. Statistical analyses were performed using the R software package (http://www.r-project.org/). The results of sequencing were compared to data from the reference control population consisting of 597 people with no history of MI (418 women, 179 men) aged 18-83 (mean 40.5, SD ± 12.4) as a whole and after matching with a studied group by age and gender in a proportion 1:3 (210 people, 51 women, 159 men, aged 18-77, mean 42.1, SD ±10.6) using Propensity Score Matching. Risks associated with detected variants were evaluated using Fisher?s exact test based on the allelic frequencies of variants in both groups.\u0000SYNE1 gene variant rs36215567 (NM_182961.4: c.20396+22A>G) occurs with a significantly higher incidence in the studied group when compared to the control population with OR 4.80 95%CI 1.43-14.45 (p=0.005) as well as when compared to the control population matched by age and gender OR 9.31 95%CI 1.64-95.41 (p=0.004). There were no statistically significant differences in the incidence of variants related to familial hypercholesterolemia such as LDLR c.667G>A, PCSK9 c.658-36G>A, and APOB c.12382G>A between both cohorts.\u0000Conclusion. A novel variant of the SYNE1 gene is associated with myocardial infarction in young patients with a family history of premature atherosclerosis.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218926","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}
Background The effects of statins on drug-eluting stents (DESs) and drug-coated stents (DCSs) for femoropopliteal (FP) lesions are not well known. Therefore, this multicenter retrospective evaluated the impact of statins on DES and DCS patency. Methods Between January 2018 and December 2021, 449 patients were treated with DES and DCS at eight cardiovascular centers in Japan (LEADers FP registry). These lesions were divided into statin-treated and non-statin-treated arms. After propensity score matching, the effects of statins on DES and DCS were evaluated. The 2-year primary outcome measure was stent patency. The secondary outcomes included secondary patency, clinically driven target lesion revascularization (CD-TLR), limb salvage, major adverse limb events (MALE, CD-TLR+ major amputation), and a composite of overall survival and MALE or all-cause death at 2 years. Results After propensity score matching, the baseline and procedural characteristics did not differ significantly between the 135 patient pairs in the statin and non-statin groups. The primary patency at two years was significantly better in the statin group than in the non-statin group (86.9% vs. 75.1%, p=0.041). Regarding the secondary endpoints, the statin group demonstrated significantly superior secondary patency and freedom from MALE or all-cause mortality (95.5% vs. 87.0%, p=0.023 and 73.7% vs. 60.0%, p=0.012, respectively). Conclusions The results of this retrospective multicenter study demonstrated the superior primary patency in the statin group compared with the non-statin group at two years. These findings suggest that statins improve patency in patients undergoing DES and DCS.
背景他汀类药物对股骨头（FP）病变的药物洗脱支架（DES）和药物涂层支架（DCS）的影响尚不十分清楚。因此，这项多中心回顾性研究评估了他汀类药物对DES和DCS通畅性的影响。方法在2018年1月至2021年12月期间，日本8个心血管中心（LEADers FP登记处）对449名患者进行了DES和DCS治疗。这些病变被分为他汀治疗组和非他汀治疗组。经过倾向评分匹配后，评估了他汀类药物对 DES 和 DCS 的影响。2年的主要结果是支架通畅率。次要结局包括次要通畅率、临床驱动的靶病变血运重建（CD-TLR）、肢体挽救、主要肢体不良事件（MALE、CD-TLR+ 主要截肢），以及2年总生存率和MALE或全因死亡的复合结果。他汀类药物组两年后的主要通畅率明显优于非他汀类药物组（86.9% 对 75.1%，P=0.041）。在次要终点方面，他汀类药物组的次要通畅率和无MALE或全因死亡率明显优于非他汀类药物组（分别为95.5% vs. 87.0%，p=0.023和73.7% vs. 60.0%，p=0.012）。这些研究结果表明，他汀类药物可改善接受 DES 和 DCS 患者的通畅率。
{"title":"Effects of Statin Therapy in Patients Treated with Drug-Eluting and Drug-Coated Stents for Femoropopliteal Lesions: STAR-FP Study Outcomes","authors":"Tatsuro Takei, Takahiro Tokuda, Naoki Yoshioka, Kenji Ogata, Akiko Tanaka, Shunsuke Kojima, Kohei Yamaguchi, Takashi Yanagiuchi, Tatsuya Nakama","doi":"10.1101/2024.09.06.24313216","DOIUrl":"https://doi.org/10.1101/2024.09.06.24313216","url":null,"abstract":"Background\u0000The effects of statins on drug-eluting stents (DESs) and drug-coated stents (DCSs) for femoropopliteal (FP) lesions are not well known. Therefore, this multicenter retrospective evaluated the impact of statins on DES and DCS patency.\u0000Methods\u0000Between January 2018 and December 2021, 449 patients were treated with DES and DCS at eight cardiovascular centers in Japan (LEADers FP registry). These lesions were divided into statin-treated and non-statin-treated arms. After propensity score matching, the effects of statins on DES and DCS were evaluated. The 2-year primary outcome measure was stent patency. The secondary outcomes included secondary patency, clinically driven target lesion revascularization (CD-TLR), limb salvage, major adverse limb events (MALE, CD-TLR+ major amputation), and a composite of overall survival and MALE or all-cause death at 2 years.\u0000Results\u0000After propensity score matching, the baseline and procedural characteristics did not differ significantly between the 135 patient pairs in the statin and non-statin groups. The primary patency at two years was significantly better in the statin group than in the non-statin group (86.9% vs. 75.1%, p=0.041). Regarding the secondary endpoints, the statin group demonstrated significantly superior secondary patency and freedom from MALE or all-cause mortality (95.5% vs. 87.0%, p=0.023 and 73.7% vs. 60.0%, p=0.012, respectively).\u0000Conclusions\u0000The results of this retrospective multicenter study demonstrated the superior primary patency in the statin group compared with the non-statin group at two years. These findings suggest that statins improve patency in patients undergoing DES and DCS.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218928","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}
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