Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease最新文献

{"title":"Predictors of Survival in Patients With Ischemic Stroke and Active Cancer: A Prospective, Multicenter, Observational Study","authors":"Y. Gon, M. Sakaguchi, H. Yamagami, Soichiro Abe, H. Hashimoto, N. Ohara, D. Takahashi, Yuko Abe, Tsutomu Takahashi, T. Kitano, Shuhei Okazaki, K. Todo, Tsutomu Sasaki, Satoshi Hattori, H. Mochizuki","doi":"10.1101/2023.05.08.23289699","DOIUrl":"https://doi.org/10.1101/2023.05.08.23289699","url":null,"abstract":"Background: Patients with ischemic stroke and active cancer have a poor prognosis; however, supporting evidence remains limited. Methods: We conducted a prospective, multicenter, observational study in Japan including patients with acute ischemic stroke and active cancer to investigate the prognostic factors. We followed up the patients for 1 year after stroke onset. The patients were divided into two groups according to cryptogenic stroke and known etiologies (small vessel occlusion, large artery atherosclerosis, cardioembolism, other determined etiology) and survival was compared. The hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were calculated using Cox regression models. Results: We identified 135 eligible patients (39% women; median age, 75 years). Of these, 51% had distant metastasis. A total of 65 (48%) and 70 (52%) patients had cryptogenic stroke and known etiologies, respectively. Patients with cryptogenic stroke had significantly shorter survival than those with known etiologies (HR [95% CI], 3.11 [1.82-5.25]). The multivariate Cox regression analysis revealed that distant metastasis, plasma D-dimer levels, deep venous thrombosis and/or pulmonary embolism complications at stroke onset were independent predictors of mortality after adjusting for potential confounders. Cryptogenic stroke was associated with prognosis in univariate analysis but not significant in multivariate analysis. The plasma D-dimer levels stratified the prognosis of patients with ischemic stroke and active cancer. Conclusions: The prognosis of patients with acute ischemic stroke and active cancer varies considerably depending on stroke mechanism, distant metastasis, and coagulation abnormalities. Coagulation abnormalities are crucial in determining the prognosis of such patients.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74120218","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":"Treatment of Slow‐Flow After Primary Percutaneous Coronary Intervention With Flow‐Mediated Hyperemia: The Randomized RAIN‐FLOW Study","authors":"J. Gómez-Lara, M. Gracida, F. Rivero, A. Gutiérrez-Barrios, Guillem Muntané-Carol, R. Romaguera, L. Fuentes, Ana Marcano, G. Roura, J. Ferreiro, L. Teruel, S. Brugaletta, F. Alfonso, J. Comín-Colet, J. Gomez-Hospital","doi":"10.1101/2023.02.21.23286266","DOIUrl":"https://doi.org/10.1101/2023.02.21.23286266","url":null,"abstract":"Background: ST-segment Elevation Myocardial Infarction (STEMI) complicated with no reflow after primary percutaneous coronary intervention is associated with adverse outcomes. Although several hyperemic drugs have shown to improve the Thrombolysis In Myocardial Infarction (TIMI) flow, optimal treatment of no reflow remains unsettled. Saline infusion at 20 ml/min via a dedicated microcatheter causes (flow-mediated) hyperemia. The objective is to compare the efficacy of pharmacologic vs. flow-mediated hyperemia in STEMI patients complicated with no reflow. Methods: STEMI patients with no reflow were randomized to receive either adenosine or nitroprusside vs. flow-mediated hyperemia. The angiographic corrected TIMI Frame Count (cTFC) and the Minimal Microcirculatory Resistance (MMR), as assessed with intracoronary pressure-thermistor wire, dedicated microcatheter and thermodilution techniques, were compared after study interventions. Results: Sixty-seven were included (30 allocated to pharmacologic and 37 to flow-mediated hyperemia). After study interventions, cTFC (40.2{+/-}23.1 vs. 39.2{+/-} 20.7; p=0.858) and MMR (753.6{+/-}661.5 vs. 993.3{+/-}740.8 Wood units; p=0.174) were similar between groups. TIMI 3 flow was observed in 26.7% vs. 27.0% (p=0.899). Flow-mediated hyperemia showed two different thermodilution patterns during saline infusion indicative of the severity of the no reflow phenomenon. In-hospital death and non-fatal heart failure were observed in 10.4% and 26.9%, respectively. Conclusions: Both treatments showed similar (and limited) efficacy restoring coronary flow. Flow-mediated hyperemia with thermodilution pattern assessment allowed the simultaneous characterization of the no reflow degree and response to hyperemia. No reflow was associated with a high rate of adverse outcomes. Further research is warranted to prevent and to treat no reflow in STEMI patients (NCT04685941).","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88007298","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":"Predicting Arterial Thrombotic Events Following Peripheral Revascularization Using Objective Viscoelastic Data","authors":"M. Majumdar, Ryan P. Hall, Zach M. Feldman, Guillaume Goudot, Natalie Sumetsky, Samuel Jessula, Amanda Kirshkaln, Tiffany R. Bellomo, D. Chang, J. Cardenas, R. Patell, M. Eagleton, A. Dua","doi":"10.1182/blood-2022-164832","DOIUrl":"https://doi.org/10.1182/blood-2022-164832","url":null,"abstract":"Background Peripheral artery disease is endemic in our globally aging population, with >200 million affected worldwide. Graft/stent thrombosis after revascularization is common and frequently results in amputation, major adverse cardiovascular events, and cardiovascular mortality. Optimizing medications to decrease thrombosis is of paramount importance; however, limited guidance exists on how to use and monitor antithrombotic therapy in this heterogeneous population. Thromboelastography with platelet mapping (TEG‐PM) provides comprehensive coagulation metrics and may be integral to the next stage of patient‐centered thrombophrophylaxis. This prospective study aimed to determine if TEG‐PM could predict subacute graft/stent thrombosis following lower extremity revascularization, and if objective cut point values could be established to identify those high‐risk patients. Methods and Results We conducted a single‐center prospective observational study of patients undergoing lower extremity revascularization. Patients were followed up for the composite end point postoperative graft/stent thrombosis at 1 year. TEG‐PM analysis of the time point before thrombosis in the event group was compared with the last postoperative visit in the nonevent group. Cox proportional hazards analysis examined the association of TEG‐PM metrics to thrombosis. Cut point analysis explored the predictive capacity of TEG‐PM metrics for those at high risk. A total of 162 patients were analyzed, of whom 30 (18.5%) experienced graft/stent thrombosis. Patients with thrombosis had significantly greater platelet aggregation (79.7±15.7 versus 58.5±26.4) and lower platelet inhibition (20.7±15.6% versus 41.1±26.6%) (all P<0.01). Cox proportional hazards analysis revealed that for every 1% increase in platelet aggregation, the hazard of experiencing an event during the study period increased by 5% (hazard ratio, 1.05 [95% CI, 1.02–1.07]; P<0.01). An optimal cut point of >70.8% platelet aggregation and/or <29.2% platelet inhibition identifies those at high risk of thrombosis with 87% sensitivity and 70% to 71% specificity. Conclusions Among patients undergoing lower extremity revascularization, increased platelet reactivity was predictive of subacute postoperative graft/stent thrombosis. On the basis of the cut points of >70.8% platelet aggregation and <29.2% platelet inhibition, consideration of an alternative or augmented antithrombotic regimen for high‐risk patients may decrease the risk of postoperative thrombotic events.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73804187","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":"Safety of Catheter Ablation Therapy for Atrial Fibrillation in Cardiac Amyloidosis","authors":"H. Alhassan, A. Kainat, J. Donohue, S. Baumgartner, Harriet S. Akunor, S. Saba, Sandeep K Jain, P. Soman","doi":"10.1161/circ.146.suppl_1.10321","DOIUrl":"https://doi.org/10.1161/circ.146.suppl_1.10321","url":null,"abstract":"Background Despite the high burden of atrial fibrillation in cardiac amyloidosis (CA), the safety of catheter ablation therapy in CA is not well established. We sought to examine short‐term safety outcomes following atrial fibrillation ablation in patients with CA compared with matched patients with dilated cardiomyopathy (DCM). Methods and Results Using data from the National Inpatient Sample, we identified all hospitalizations for atrial fibrillation ablation from the fourth quarter of 2015 through 2019. Admissions for CA and DCM were matched in a 1:5 ratio using propensity scores based on the following sociodemographics: age, sex, race or ethnicity, payor, median income, comorbidities, and hospital characteristics. We compared in‐hospital outcomes between both cardiomyopathies. We identified 1395 unweighted hospitalizations (representing 6750 national hospitalizations) for atrial fibrillation ablation, out of which 45 (3.2%) were admissions for CA. Compared with DCM, patients with CA were older (72.9 versus 65.1 years), had a higher burden of prior stroke (20.0% versus 8.6%) and chronic kidney disease (53.3% versus 33.6%), and were less likely to have a prior implantable cardioverter‐defibrillator (4.4% versus 23.0%). We successfully matched 42 CAs to 210 DCM hospitalizations. After matching, there was no difference in total complications (14.3% versus 10.5%, P=0.60), length‐of‐stay (3.1 versus 2.1 days, P=0.23), home disposition (97.6% versus 96.2%, P=0.65), and total charges ($137 250 versus $133 910, P=0.24). Conclusions In this nationally representative study of atrial fibrillation catheter ablation in CA, short‐term safety outcomes and complication rates were similar to a propensity score‐matched cohort of DCM. Further studies exploring long‐term safety outcomes are needed.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78051877","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":"Corin Missense Variants, Blood Pressure, and Hypertension in 11 322 Black Individuals: Insights From REGARDS and the Jackson Heart Study.","authors":"Vibhu Parcha, Marguerite R Irvin, Leslie A Lange, Nicole D Armstrong, Akhil Pampana, Mariah Meyer, Suzanne E Judd, Garima Arora, Pankaj Arora","doi":"10.1161/JAHA.121.025582","DOIUrl":"10.1161/JAHA.121.025582","url":null,"abstract":"<p><p>Background Corin enzyme contributes to the processing of inactive natriuretic peptides to bioactive hormones. In Black individuals, Corin gene variants (rs111253292 [Q568P] and rs75770792 [T555I]) have been previously reported to have a modest association with blood pressure (BP) and hypertension. Methods and Results We evaluated the association of Corin genotype with BP traits, prevalent hypertension, and incident hypertension among self-identified 11 322 Black Americans in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study and the JHS (Jackson Heart Study) using multivariable-adjusted regression modeling. Multivariable-adjusted genotype-stratified differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide) and BNP (B-type natriuretic peptide) levels were assessed. Genotype-stratified <i>NPPA</i> and <i>NPPB</i> expression differences in healthy organ donor left atrial and left ventricular heart tissue (N=15) were also examined. The rs111253292 genotype was not associated with systolic BP (β±SE, 0.42±0.58; -1.24±0.82), diastolic BP (0.51±0.33; -0.41±0.46), mean arterial pressure (0.48±0.38; -0.68±0.51), and prevalent hypertension (odds ratio [OR], 0.93 [95% CI, 0.80-1.09]; OR, 0.79 [95% CI, 0.61-1.01]) in both REGARDS and JHS, respectively. The rs75770792 genotype was not associated with systolic BP (0.48±0.58; -1.26±0.81), diastolic BP (0.52±0.33; -0.33±0.45), mean arterial pressure (0.50±0.38; -0.63±0.50), and prevalent hypertension (OR, 1.02 [95% CI, 0.84-1.23]; OR, 0.87 [95% CI, 0.67-1.13]) in both cohorts, respectively. The Corin genotype was also not associated with incident hypertension (OR, 1.35 [95% CI, 0.94-1.93]; OR, 0.95 [95% CI, 0.64-1.39]) in the study cohorts. The NT-proBNP levels in REGARDS and BNP levels in JHS were similar between the Corin genotype groups. In heart tissue, the <i>NPPA</i> and <i>NPPB</i> expression was similar between the genotype groups. Conclusions <i>Corin</i> gene variants observed more commonly in Black individuals are not associated with differences in NP expression, circulating NP levels, and BP or hypertension as previously reported in candidate gene studies. Understanding the genetic determinants of complex cardiovascular traits in underrepresented populations requires further evaluation.</p>","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76336205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Common and Rare Genetic Variation in the 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Gene and Cataract Risk.","authors":"Jonas Ghouse, Gustav Ahlberg, Anne Guldhammer Skov, Henning Bundgaard, Morten S Olesen","doi":"10.1161/JAHA.122.025361","DOIUrl":"10.1161/JAHA.122.025361","url":null,"abstract":"<p><p>Background Results from animal models and observational studies have raised concerns regarding the potential cataractogenic effects of statin treatment. We investigated whether common and rare genetic variants in <i>HMGCR</i> are associated with cataract risk, to gauge the likely long-term effects of statin treatment on lenticular opacities. Methods and Results We used genotyping data and exome sequencing data of unrelated European individuals in the UK Biobank to test the association between genetically proxied inhibition of <i>HMGCR</i> and cataract risk. First, we constructed an <i>HMGCR</i> genetic score consisting of 5 common variants weighted by their association with low-density lipoprotein cholesterol. Second, we analyzed exome sequencing data to identify carriers of predicted loss-of-function mutations in <i>HMGCR</i>. Common and rare variants in aggregate were then tested for association with cataract and cataract surgery. In an analysis of >402 000 individuals, a 38.7 mg/dL (1 mmol/L) reduction in low-density lipoprotein C by the <i>HMGCR</i> genetic score was associated with higher risk for cataract (odds ratio, 1.14 [95% CI, 1.00-1.39], <i>P</i>=0.045) and cataract surgery (odds ratio, 1.25 [95% CI, 1.06-1.48], <i>P</i>=0.009). Among 169 172 individuals with <i>HMGCR</i> sequencing data, we identified 32 participants (0.02%), who carried a rare <i>HMGCR</i> predicted loss-of-function variant. Compared with noncarriers, heterozygous carriers of <i>HMGCR</i> predicted loss-of-function had a higher risk of developing cataract (odds ratio, 4.54 [95% CI, 1.96-10.53], <i>P</i>=0.001) and cataract surgery (odds ratio, 5.27 [95% CI, 2.27-12.25]<i>, P</i>=5.37×10^-4). In exploratory analyses, we found no significant association between genetically proxied inhibition of <i>PCSK9, NPC1L1</i>, or circulating low-density lipoprotein cholesterol levels (<i>P</i>>0.05 for all) and cataract risk. Conclusions We found that genetically proxied inhibition of the <i>HMGCR</i> gene mimicking long-term statin treatment associated with higher risk of cataract. Clinical trials with longer follow-up are needed to confirm these findings.</p>","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82447364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation Between Cardiac Images, Biomarkers, and Amyloid Load in Wild-Type Transthyretin Amyloid Cardiomyopathy.","authors":"Mami Morioka, Seiji Takashio, Naoya Nakashima, Masato Nishi, Akira Fujiyama, Kyoko Hirakawa, Shinsuke Hanatani, Hiroki Usuku, Eiichiro Yamamoto, Masafumi Kidoh, Seitaro Oda, Kenichi Matsushita, Mitsuharu Ueda, Kenichi Tsujita","doi":"10.1161/JAHA.121.024717","DOIUrl":"10.1161/JAHA.121.024717","url":null,"abstract":"<p><p>Background Several imaging parameters and biomarkers provide diagnostic and prognostic information for wild-type transthyretin amyloid cardiomyopathy. However, the relevance of these parameters and their association with cardiac amyloid load requires further substantiation. We aimed to elucidate the association of imaging parameters obtained using ^99mTc-labeled pyrophosphate scintigraphy, cardiovascular magnetic resonance imaging, global longitudinal strain (GLS), and cardiac biomarkers with cardiac amyloid load in patients with wild-type transthyretin amyloid cardiomyopathy. Methods and Results Eighty-eight patients with wild-type transthyretin amyloid cardiomyopathy who underwent ^99mTc-labeled pyrophosphate scintigraphy and cardiovascular magnetic resonance were retrospectively evaluated. Quantitative cardiac amyloid load was obtained from 61 patients after myocardial biopsy. Correlations were assessed using Pearson's correlation coefficient applied to medical record data. The mean heart to contralateral ratio, native T1, extracellular volume, and GLS were 1.91±0.36, 1419.4±56.4 ms, 56.5±13.6%, and -9.4±2.5%, respectively. Median high-sensitivity cardiac troponin T (hs-cTnT) and BNP (B-type natriuretic peptide) levels were 0.0478 (0.0334-0.0691) ng/mL and 213.8 (125.8-392.7) pg/mL, respectively. The mean cardiac amyloid load was 22.9±15.0%. The heart to contralateral ratio correlated significantly with native T1 (<i>r</i>=0.397), extracellular volume (<i>r</i>=0.477), GLS (<i>r</i>=0.363), cardiac amyloid load (<i>r</i>=0.379), and Ln (hs-cTnT) (<i>r</i>=0.247). Further, cardiac amyloid load correlated significantly with native T1 (<i>r</i>=0.509), extracellular volume (<i>r</i>=0.310), GLS (<i>r</i>=0.446), and Ln (hs-cTnT) (<i>r</i>=0.354). Compared with BNP, hs-cTnT levels better correlated with several imaging parameters and cardiac amyloid load. Conclusions Increased cardiac amyloid load correlated with increased ^99mTc-labeled pyrophosphate positivity, native T1, extracellular volume, and hs-cTnT levels, and an impaired GLS, suggesting that imaging parameters and cardiac biomarkers may reflect histological and functional changes attributable to amyloid deposition in the myocardium.</p>","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85257516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone Deacetylase 6 Inhibitor JS28 Prevents Pathological Gene Expression in Cardiac Myocytes.","authors":"Vivien Ngo, Bernd K Fleischmann, Manfred Jung, Lutz Hein, Achim Lother","doi":"10.1161/JAHA.122.025857","DOIUrl":"10.1161/JAHA.122.025857","url":null,"abstract":"<p><p>Background Epigenetic modulators have been proposed as promising new drug targets to treat adverse remodeling in heart failure. Here, we evaluated the potential of 4 epigenetic drugs, including the recently developed histone deacetylase 6 (HDAC6) inhibitor JS28, to prevent endothelin-1 induced pathological gene expression in cardiac myocytes and analyzed the chromatin binding profile of the respective inhibitor targets. Methods and Results Cardiac myocytes were differentiated and puromycin-selected from mouse embryonic stem cells and treated with endothelin-1 to induce pathological gene expression (938 differentially expressed genes, q<0.05). Dysregulation of gene expression was at least in part prevented by epigenetic inhibitors, including the pan-BRD (bromodomain-containing protein) inhibitor bromosporine (290/938 genes), the BET (bromodomain and extraterminal) inhibitor JQ1 (288/938), the broad-spectrum HDAC inhibitor suberoylanilide hydroxamic acid (227/938), and the HDAC6 inhibitor JS28 (210/938). Although the 4 compounds were similarly effective toward pathological gene expression, JS28 demonstrated the least adverse effects on physiological gene expression. Genome-wide chromatin binding profiles revealed that HDAC6 binding sites were preferentially associated with promoters of genes involved in RNA processing. In contrast, BRD4 binding was associated with genes involved in core cardiac myocyte functions, for example, myocyte contractility, and showed enrichment at enhancers and intronic regions. These distinct chromatin binding profiles of HDAC6 and BRD4 might explain the different effects of their inhibitors on pathological versus physiological gene expression. Conclusions In summary, we demonstrated, that the HDAC6 inhibitor JS28 effectively prevented the adverse effects of endothelin-1 on gene expression with minor impact on physiological gene expression in cardiac myocytes. Selective HDAC6 inhibition by JS28 appears to be a promising strategy for future evaluation in vivo and potential translation into clinical application.</p>","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87521326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Statins for Primary Prevention of Cardiovascular Diseases With Hospitalization for COVID-19: A Nationwide Matched Population-Based Cohort Study.","authors":"Kim Bouillon, Bérangère Baricault, Laura Semenzato, Jérémie Botton, Marion Bertrand, Jérôme Drouin, Rosemary Dray-Spira, Alain Weill, Mahmoud Zureik","doi":"10.1161/JAHA.121.023357","DOIUrl":"10.1161/JAHA.121.023357","url":null,"abstract":"<p><p>Background There is little evidence on the relationship between statin use and the risk of hospitalization attributable to COVID-19. Methods and Results The French National Healthcare Data System database was used to conduct a matched-cohort study. For each adult aged ≥40 years receiving statins for the primary prevention of cardiovascular diseases, one nonuser was randomly selected and matched for year of birth, sex, residence area, and comorbidities. The association between statin use and hospitalization for COVID-19 was examined using conditional Cox proportional hazards models, adjusted for baseline characteristics, comorbidities, and long-term medications. Its association with in-hospital death from COVID-19 was also explored. All participants were followed up from February 15, 2020, to June 15, 2020. The matching procedure generated 2 058 249 adults in the statin group and 2 058 249 in the control group, composed of 46.6% of men with a mean age of 68.7 years. Statin users had a 16% lower risk of hospitalization for COVID-19 than nonusers (adjusted hazard ratio [HR], 0.84; 95% CI, 0.81-0.88). All types of statins were significantly associated with a lower risk of hospitalization, with the adjusted HR ranging from 0.75 for fluvastatin to 0.89 for atorvastatin. Low- and moderate-intensity statins also showed a lower risk compared with nonusers (HR, 0.78 [95% CI, 0.71-0.86] and HR, 0.84 [95% CI, 0.80-0.89], respectively), whereas high-intensity statins did not (HR, 1.01; 95% CI, 0.86-1.18). We found similar results with in-hospital death from COVID-19. Conclusions Our findings support that the use of statins for primary prevention is associated with lower risks of hospitalization for COVID-19 and of in-hospital death from COVID-19.</p>","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80509618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relative Contribution of Blood Pressure in Childhood, Young- and Mid-Adulthood to Large Artery Stiffness in Mid-Adulthood.","authors":"Yaxing Meng, Marie-Jeanne Buscot, Markus Juonala, Feitong Wu, Matthew K Armstrong, Brooklyn J Fraser, Katja Pahkala, Nina Hutri-Kähönen, Mika Kähönen, Tomi Laitinen, Jorma S A Viikari, Olli T Raitakari, Costan G Magnussen, James E Sharman","doi":"10.1161/JAHA.121.024394","DOIUrl":"10.1161/JAHA.121.024394","url":null,"abstract":"<p><p>Background Blood pressure associates with arterial stiffness, but the contribution of blood pressure at different life stages is unclear. We examined the relative contribution of childhood, young- and mid-adulthood blood pressure to mid-adulthood large artery stiffness. Methods and Results The sample comprised 1869 participants from the Cardiovascular Risk in Young Finns Study who had blood pressure measured in childhood (6-18 years), young-adulthood (21-30 years), and mid-adulthood (33-45 years). Markers of large artery stiffness were pulse wave velocity and carotid distensibility recorded in mid-adulthood. Bayesian relevant life course exposure models were used. For each 10-mm Hg higher cumulative systolic blood pressure across the life stages, pulse wave velocity was 0.56 m/s higher (95% credible interval: 0.49 to 0.63) and carotid distensibility was 0.13%/10 mm Hg lower (95% credible interval: -0.16 to -0.10). Of these total contributions, the highest contribution was attributed to mid-adulthood systolic blood pressure (relative weights: pulse wave velocity, childhood: 2.6%, young-adulthood: 5.4%, mid-adulthood: 92.0%; carotid distensibility, childhood: 5.6%; young-adulthood: 10.1%; mid-adulthood: 84.3%), with the greatest individual contribution coming from systolic blood pressure at the time point when pulse wave velocity and carotid distensibility were measured. The results were consistent for diastolic blood pressure, mean arterial pressure, and pulse pressure. Conclusions Although mid-adulthood blood pressure contributed most to mid-adulthood large artery stiffness, we observed small contributions from childhood and young-adulthood blood pressure. These findings suggest that the burden posed by arterial stiffness might be reduced by maintaining normal blood pressure levels at each life stage, with mid-adulthood a critical period for controlling blood pressure.</p>","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77836895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}