Gretell Henriquez-Santos, Ji-Eun Kim, Sant J Kumar, Alicia A Livinski, Jacqueline B Vo, Fang Zhu, Jungnam Joo, Joseph J Shearer, Maryam Hashemian, Véronique L Roger
{"title":"Cardiovascular Risk, Health Metrics, and Cancer Prediction: A Scoping Review.","authors":"Gretell Henriquez-Santos, Ji-Eun Kim, Sant J Kumar, Alicia A Livinski, Jacqueline B Vo, Fang Zhu, Jungnam Joo, Joseph J Shearer, Maryam Hashemian, Véronique L Roger","doi":"10.1016/j.jaccao.2025.05.011","DOIUrl":"https://doi.org/10.1016/j.jaccao.2025.05.011","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease (CVD) and cancer are leading global causes of morbidity and mortality. Given the shared risk factors, it is plausible that CVD risk scores and cardiovascular health (CVH) metrics could predict cancer risk.</p><p><strong>Objectives: </strong>The authors sought to identify and summarize studies examining the association between CVD risk scores, CVH metrics, and incident cancer.</p><p><strong>Methods: </strong>A systematic search of 4 databases (Embase, PubMed, Scopus, Web of Science: Core) was conducted in April 2024 without language or date restrictions. Five reviewers (G.H., J.K., S.J.K., M.H., V.L.R.) independently screened records using Covidence software and extracted data from eligible prospective studies (adults aged ≥18 years; cancer incidence as outcome; CVD risk scores or CVH metrics as exposure).</p><p><strong>Results: </strong>Of 4,165 records screened, 13 studies (14 CVD or CVH metrics) were included. Heterogeneity between scales precluded a meta-analysis. Four studies evaluated CVD risk scores (eg, atherosclerotic CVD) and 10 reported CVH metrics (eg, the American Heart Association's Life's Simple 7). Sample sizes ranged from 1,880 to 342,226, with median follow-up from 8.1 to 29.6 years. The majority included all types of cancer (71.4%), including breast, lung, colorectal, and prostate cancer types, with cancer events ranging from 387 to 11,643. Higher CVD risk scores were consistently associated with increased cancer risk incidence (HRs: 1.16-3.71). Ideal CVH metrics were associated with reduced risk (HRs: 0.49-0.95).</p><p><strong>Conclusions: </strong>Despite heterogeneity in CVD risk metrics and cancer types, most studies suggested that worse CVD risk scores or CVH metrics predict greater cancer risk. Future studies should focus on specific CVD risk metrics and cancer types to produce evidence suitable for a meta-analysis.</p>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":" ","pages":""},"PeriodicalIF":12.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Orly Leiva, Olivia Liu, Anthony Kanelidis, Stanley Swat, Leo Gozdecki, Mark Belkin, Jonathan Grinstein, Sara Kalantari, Gene Kim, Jeanne DeCara, Ben Chung, Anand Patel, Olatoyosi Odenike, Eric H Yang, Michelle Bloom, Jose Alvarez-Cardona, Joan How, Gabriela Hobbs
{"title":"Beyond Thrombosis: Pulmonary Hypertension and Heart Failure in Patients With Myeloproliferative Neoplasms: JACC: CardioOncology State-of-the-Art Review.","authors":"Orly Leiva, Olivia Liu, Anthony Kanelidis, Stanley Swat, Leo Gozdecki, Mark Belkin, Jonathan Grinstein, Sara Kalantari, Gene Kim, Jeanne DeCara, Ben Chung, Anand Patel, Olatoyosi Odenike, Eric H Yang, Michelle Bloom, Jose Alvarez-Cardona, Joan How, Gabriela Hobbs","doi":"10.1016/j.jaccao.2025.05.010","DOIUrl":"https://doi.org/10.1016/j.jaccao.2025.05.010","url":null,"abstract":"<p><p>Patients with myeloproliferative neoplasms (MPNs) are at increased risk for cardiovascular disease. Although thrombosis is a well-recognized complication, emerging evidence indicates that nonthrombotic conditions, including heart failure (HF) and pulmonary hypertension (PH), are also prevalent and associated with adverse cardiovascular and hematologic outcomes. Clinical and preclinical data suggest a shared pathophysiology linking MPNs to the development and progression of cardiomyopathy, HF, and both precapillary and postcapillary PH. Recent studies further support a bidirectional relationship, in which HF and PH are associated with hematologic progression and vice versa. Elucidating the mechanisms underlying these interactions may uncover novel therapeutic targets and inform clinical management. Here, the authors review the pathophysiology and impact of HF and PH in patients with MPNs.</p>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":" ","pages":""},"PeriodicalIF":12.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoxi Meng, Tiffany Eulalio, Yoonji Kim, John Easton, Heather L Mulder, Emily Walker, Geoffrey Neale, Nan Song, Kyla Shelton, Rebecca M Howell, Mengqi Xing, Sedigheh Mirzaei, Deo Kumar Srivastava, Bonnie Ky, Stephanie B Dixon, Melissa M Hudson, Kirsten K Ness, Gregory T Armstrong, Zhaoming Wang
{"title":"Epigenetic Age Acceleration Mediates Treatment Effects on Cardiometabolic and Cardiovascular Risk in Childhood Cancer Survivors.","authors":"Xiaoxi Meng, Tiffany Eulalio, Yoonji Kim, John Easton, Heather L Mulder, Emily Walker, Geoffrey Neale, Nan Song, Kyla Shelton, Rebecca M Howell, Mengqi Xing, Sedigheh Mirzaei, Deo Kumar Srivastava, Bonnie Ky, Stephanie B Dixon, Melissa M Hudson, Kirsten K Ness, Gregory T Armstrong, Zhaoming Wang","doi":"10.1016/j.jaccao.2025.06.001","DOIUrl":"10.1016/j.jaccao.2025.06.001","url":null,"abstract":"<p><strong>Background: </strong>Childhood cancer survivors are at increased risk for epigenetic age acceleration (EAA) and subsequent morbidities, including cardiometabolic risk factors (CMRFs) and cardiovascular diseases, because of prior genotoxic treatments.</p><p><strong>Objectives: </strong>The aim of this study was to evaluate the mediating role of EAA in the relationship between cancer treatment exposures and risk for CMRFs and cardiovascular diseases.</p><p><strong>Methods: </strong>This study included 2,939 5-year survivors from SJLIFE (St. Jude Lifetime Cohort) who underwent DNA methylation profiling using peripheral blood mononuclear cells. EAA was calculated using 3 established epigenetic clocks: DunedinPACE, PCPhenoAge, and GrimAge2. Treatment data, including body region-specific radiotherapy (RT) and chemotherapeutic agents such as anthracyclines and corticosteroids, were abstracted from medical records. Outcomes included 3 CMRFs (abnormal glucose metabolism, hypertension, and obesity) and 2 cardiovascular diseases (cardiomyopathy and myocardial infarction). Mediation analysis was conducted to quantify the extent to which EAA mediated the association between each treatment exposure and each clinical outcome.</p><p><strong>Results: </strong>EAA partially mediated the associations between abdominal RT and abnormal glucose metabolism (DunedinPACE 35.4%, GrimAge2 16.2%), between abdominal RT (DunedinPACE 25.9%) or anthracyclines (DunedinPACE 12.5%) and hypertension, and between corticosteroids and obesity (DunedinPACE 8.6%). EAA also mediated the associations between heart RT and cardiomyopathy (PCPhenoAge 30.3%, DunedinPACE 19.9%, GrimAge2 14.4%) and myocardial infarction (PCPhenoAge 24.1%, DunedinPACE 15.5%, GrimAge2 13.2%), and anthracyclines and cardiomyopathy (GrimAge2 6.0%, PCPhenoAge 5.2%, DunedinPACE 3.9%).</p><p><strong>Conclusions: </strong>EAA accounted for a substantial proportion of the association between cancer treatment exposures and risk for CMRFs and cardiovascular diseases. These findings provide insight into biological aging as a potential mechanistic pathway and support the development of interventions targeting accelerated aging to mitigate long-term treatment-related toxicities and reduce premature mortality in this high-risk population.</p>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":" ","pages":""},"PeriodicalIF":12.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Theodorus W Kouwenberg, Elvira C van Dalen, Renée L Mulder, Saro Armenian, Elizabeth A M Feijen, Eric J Chow, Helen Kosmidis, Britta J Vormoor-Bürger, Chikako Kiyotani, Paul C Nathan, Livia Kapusta, Heynric B Grotenhuis, Frederike K Engels, Arco J Teske, Athanasios Tragiannidis, Martijn G Slieker, Shuichi Ozono, Anju Nohria, Tomáš Sláma, Roderick Skinner, Melissa M Hudson, Leontien C M Kremer, Matthew J Ehrhardt, Annelies M C Mavinkurve-Groothuis
{"title":"IGHG Recommendations for Anthracycline and Anthraquinone Cardiac Dysfunction Equivalence Ratios After Childhood Cancer: JACC: CardioOncology Expert Panel.","authors":"Theodorus W Kouwenberg, Elvira C van Dalen, Renée L Mulder, Saro Armenian, Elizabeth A M Feijen, Eric J Chow, Helen Kosmidis, Britta J Vormoor-Bürger, Chikako Kiyotani, Paul C Nathan, Livia Kapusta, Heynric B Grotenhuis, Frederike K Engels, Arco J Teske, Athanasios Tragiannidis, Martijn G Slieker, Shuichi Ozono, Anju Nohria, Tomáš Sláma, Roderick Skinner, Melissa M Hudson, Leontien C M Kremer, Matthew J Ehrhardt, Annelies M C Mavinkurve-Groothuis","doi":"10.1016/j.jaccao.2025.05.009","DOIUrl":"10.1016/j.jaccao.2025.05.009","url":null,"abstract":"<p><p>Anthracycline and anthraquinone agents are major contributors to cancer therapy-related cardiac dysfunction in childhood cancer. However, evidence-based equivalence ratios for estimating individual risk have not been incorporated into international surveillance guidelines. The International Late Effects of Childhood Cancer Guideline Harmonization Group systematically reviewed the literature on equivalence ratios for doxorubicin, daunorubicin, epirubicin, idarubicin, and mitoxantrone. Based on available evidence, benefit-harm considerations, and expert consensus, the panel concluded that the risk of cardiac dysfunction is lower with daunorubicin and higher with mitoxantrone compared with doxorubicin (moderate-quality evidence; strong recommendation). The panel recommends using an approximate ratio of 0.6 to convert daunorubicin to a doxorubicin-equivalent dose and a ratio of 10.5 for mitoxantrone (low-quality evidence; moderate recommendation). No recommendation was made for epirubicin or idarubicin due to inconclusive evidence.</p>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":" ","pages":""},"PeriodicalIF":12.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rachele Cagnazzo, Mario Stabile, Gabriele Zoppoli, Rudolf A De Boer, Wouter C Meijers, Peter van Der Meer, Pietro Ameri
{"title":"Mismatch Between Preclinical Cardio-Oncology and Clinical Oncology Research.","authors":"Rachele Cagnazzo, Mario Stabile, Gabriele Zoppoli, Rudolf A De Boer, Wouter C Meijers, Peter van Der Meer, Pietro Ameri","doi":"10.1016/j.jaccao.2025.05.012","DOIUrl":"10.1016/j.jaccao.2025.05.012","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":" ","pages":""},"PeriodicalIF":12.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yasutomi Higashikuni MD, PhD , Colin Platt PhD , Margaret H. Hastings PhD , William C.W. Chen MD, PhD , Justin R.B. Guerra BS , Takeshi Tokuyama PhD , Fuad Gandhi Torizal DDS, PhD , Wenhao Liu MD , Takumi Obana , Abraham L. Bayer BS , Hannah Whipple BS , Alexandra Kuznetsov BA , Ashish Yeri PhD , Cole Turissini BS , Robert R. Kitchen PhD , Kota Shibayama , Takayoshi Matsumura MD, PhD , Norihiko Takeda MD, PhD , Hideki Uosaki MD, PhD , Aarti H. Asnani MD , Anthony Rosenzweig MD
{"title":"Mitigation of Doxorubicin Cardiotoxicity With Synergistic miRNA Combinations Identified Using Combinatorial Genetics en masse (CombiGEM)","authors":"Yasutomi Higashikuni MD, PhD , Colin Platt PhD , Margaret H. Hastings PhD , William C.W. Chen MD, PhD , Justin R.B. Guerra BS , Takeshi Tokuyama PhD , Fuad Gandhi Torizal DDS, PhD , Wenhao Liu MD , Takumi Obana , Abraham L. Bayer BS , Hannah Whipple BS , Alexandra Kuznetsov BA , Ashish Yeri PhD , Cole Turissini BS , Robert R. Kitchen PhD , Kota Shibayama , Takayoshi Matsumura MD, PhD , Norihiko Takeda MD, PhD , Hideki Uosaki MD, PhD , Aarti H. Asnani MD , Anthony Rosenzweig MD","doi":"10.1016/j.jaccao.2025.03.007","DOIUrl":"10.1016/j.jaccao.2025.03.007","url":null,"abstract":"<div><h3>Background</h3><div>Cardiomyocyte loss occurs in acute and chronic cardiac injury, including cardiotoxicity due to chemotherapeutics like doxorubicin, and contributes to heart failure development. There is a pressing need for cardiac-specific therapeutics that target cardiomyocyte loss, preventing chemotherapy complications without compromising chemotherapeutic efficacy.</div></div><div><h3>Objectives</h3><div>The authors employed massively parallel combinatorial genetic screening to find microRNA (miRNA) combinations that promote cardiomyocyte survival.</div></div><div><h3>Methods</h3><div>CombiGEM (combinatorial genetics en masse) screening in a cardiomyocyte cell line was followed by validation in the original cell type and screening in primary cardiomyocytes. The top combination was tested in mouse and developing zebrafish models of doxorubicin cardiotoxicity. RNA sequencing provided insight into possible mechanisms.</div></div><div><h3>Results</h3><div>Multiple miRNA combinations protected cardiomyocytes from doxorubicin in vitro. The most effective (miR-222+miR-455) appeared to act synergistically, and mitigated doxorubicin cardiotoxicity phenotypes in murine and zebrafish in vivo models. RNA sequencing revealed overlapping and synergistic regulation of relevant genes and biological processes in cardiomyocytes, including mitochondrial homeostasis, oxidative stress, muscle contraction, and others.</div></div><div><h3>Conclusions</h3><div>We identified miR-222 and miR-455 as a combination with potential therapeutic applications for cardioprotection. This study furthers our knowledge of the cardiac effects of miRNAs and their combinations and demonstrates the potential of CombiGEM for cardioprotective combinatorial therapeutic discovery.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 4","pages":"Pages 396-410"},"PeriodicalIF":12.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}