Cosimo Andrea Stamerra, Paolo Di Giosia, Paolo Giorgini, Tannaz Jamialahmadi, Amirhossein Sahebkar
{"title":"Cardiovascular Effects of Stimulators of Soluble Guanylate Cyclase Administration: A Meta-analysis of Randomized Controlled Trials.","authors":"Cosimo Andrea Stamerra, Paolo Di Giosia, Paolo Giorgini, Tannaz Jamialahmadi, Amirhossein Sahebkar","doi":"10.1007/s11883-024-01197-4","DOIUrl":"10.1007/s11883-024-01197-4","url":null,"abstract":"<p><strong>Purpose of review: </strong>Heart failure (HF) is one of the main causes of cardiovascular mortality in the western world. Despite great advances in treatment, recurrence and mortality rates remain high. Soluble guanylate cyclase is an enzyme which, by producing cGMP, is responsible for the effects of vasodilation, reduction of cardiac pre- and after-load and, therefore, the improvement of myocardial performance. Thus, a new therapeutic strategy is represented by the stimulators of soluble guanylate cyclase (sGCs). The aim of this meta-analysis was to analyze the effects deriving from the administration of sGCs, in subjects affected by HF. A systematic literature search of Medline, SCOPUS, and Google Scholar was conducted up to December 2022 to identify RCTs assessing the cardiovascular effects, as NT-pro-BNP values and ejection fraction (EF), and all-cause mortality, of the sGCs. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence interval (CI) as summary statistics.</p><p><strong>Recent findings: </strong>The results obtained documented a statistically significant improvement in NT-proBNP values (SMD: - 0.258; 95% CI: - 0.398, - 0.118; p < 0.001) and EF (WMD: 0.948; 95% CI: 0.485, 1.411; p < 0.001) in subjects treated with sGCs; however, no significant change was found in the all-cause mortality rate (RR 0.96; 95% CI 0.868 to 1.072; I2, p = 0). The sGCs represent a valid therapeutic option in subjects suffering from HF, leading to an improvement in cardiac performance.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":" ","pages":"177-187"},"PeriodicalIF":5.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angela Pirillo, Lale Tokgözoğlu, Alberico L Catapano
{"title":"European Lipid Guidelines and Cardiovascular Risk Estimation: Current Status and Future Challenges.","authors":"Angela Pirillo, Lale Tokgözoğlu, Alberico L Catapano","doi":"10.1007/s11883-024-01194-7","DOIUrl":"10.1007/s11883-024-01194-7","url":null,"abstract":"<p><strong>Purpose of review: </strong>Genetic, experimental, epidemiologic, and clinical data support the causal role of elevated levels of low-density lipoprotein cholesterol (LDL-C) in atherosclerosis and cardiovascular disease (CVD). The recommendations of the 2019 European guidelines are based on the concept of differential CV risk, which in turn defines the LDL-C goals that should be achieved.</p><p><strong>Recent findings: </strong>The 2019 ESC/EAS guidelines for dyslipidaemia use the Systematic COronary Risk Evaluation (SCORE) model to assess CV risk, which provides a 10-year risk of fatal CV event. The SCORE model has recently been updated to reflect current rates of cardiovascular disease in Europe. The new SCORE2 model provides estimates of the 10-year risk of fatal and non-fatal CVD events in people aged 40-69 years, thus improving the identification of individuals at higher risk of a CVD event. However, as in the SCORE age is the main determinant of risk, young people have a relatively low estimated 10-year risk of a CV event even with high levels of one or more causal risk factors. Individuals with familial hypercholesterolaemia, who have elevated LDL-C levels from birth and have a high risk of premature CVD, are one example. The concept of cumulative LDL exposure is thus becoming increasingly important. This is also supported by Mendelian randomisation studies showing that carrying genetic variants associated with lower LDL-C levels reduces CV risk. These observations have introduced the concept of \"cholesterol-years\", which takes into account both LDL-C levels and time of exposure. It is crucial that future European guidelines pay more attention to this point.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":" ","pages":"133-137"},"PeriodicalIF":5.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gene Editing for the Treatment of Hypercholesterolemia.","authors":"Menno Hoekstra, Miranda Van Eck","doi":"10.1007/s11883-024-01198-3","DOIUrl":"10.1007/s11883-024-01198-3","url":null,"abstract":"<p><strong>Purpose of review: </strong>Here, we summarize the key findings from preclinical studies that tested the concept that editing of hepatic genes can lower plasma low-density lipoprotein (LDL)-cholesterol levels to subsequently reduce atherosclerotic cardiovascular disease risk.</p><p><strong>Recent findings: </strong>Selective delivery of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated gene editing tools targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to hepatocytes, i.e., through encapsulation into N-acetylgalactosamine-coupled lipid nanoparticles, is able to induce a stable ~ 90% decrease in plasma PCSK9 levels and a concomitant 60% reduction in LDL-cholesterol levels in mice and non-humane primates. Studies in mice have shown that this state-of-the-art technology can be extended to include additional targets related to dyslipidemia such as angiopoietin-like 3 and several apolipoproteins. The use of gene editors holds great promise to lower plasma LDL-cholesterol levels also in the human setting. However, gene editing safety has to be guaranteed before this approach can become a clinical success.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":" ","pages":"139-146"},"PeriodicalIF":5.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anandita Agarwala, Ramsha Asim, Christie M Ballantyne
{"title":"Oral PCSK9 Inhibitors.","authors":"Anandita Agarwala, Ramsha Asim, Christie M Ballantyne","doi":"10.1007/s11883-024-01199-2","DOIUrl":"10.1007/s11883-024-01199-2","url":null,"abstract":"<p><strong>Purpose of review: </strong>In this review, we will discuss the data from early clinical studies of MK-0616 and summarize clinical trials of other oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.</p><p><strong>Recent findings: </strong>The success of PCSK9 inhibition with monoclonal antibody injections has fueled the development of additional therapies targeting PCSK9, including oral formulations, the most advanced of which is MK-0616. MK-0616 is a novel, orally administered macrocyclic peptide that binds to PCSK9 and inhibits binding of PCSK9 to the LDL receptor, thereby decreasing plasma levels of LDL-C. Clinical trial data on the safety and efficacy of MK-0616 are promising and report LDL-C-lowering efficacy comparable to that provided by injectable PCSK9 inhibitors. Ongoing and future studies of oral PCSK9 inhibitors in development will evaluate the safety, efficacy, and effectiveness of these agents and their potential role in preventing cardiovascular disease events.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":" ","pages":"147-152"},"PeriodicalIF":5.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ellen M van der Ark-Vonk, Mike V Puijk, Gerard Pasterkamp, Sander W van der Laan
{"title":"The Effects of FABP4 on Cardiovascular Disease in the Aging Population.","authors":"Ellen M van der Ark-Vonk, Mike V Puijk, Gerard Pasterkamp, Sander W van der Laan","doi":"10.1007/s11883-024-01196-5","DOIUrl":"10.1007/s11883-024-01196-5","url":null,"abstract":"<p><strong>Purpose of review: </strong>Fatty acid-binding protein 4 (FABP4) plays a role in lipid metabolism and cardiovascular health. In this paper, we cover FABP4 biology, its implications in atherosclerosis from observational studies, genetic factors affecting FABP4 serum levels, and ongoing drug development to target FABP4 and offer insights into future FABP4 research.</p><p><strong>Recent findings: </strong>FABP4 impacts cells through JAK2/STAT2 and c-kit pathways, increasing inflammatory and adhesion-related proteins. In addition, FABP4 induces angiogenesis and vascular smooth muscle cell proliferation and migration. FABP4 is established as a reliable predictive biomarker for cardiovascular disease in specific at-risk groups. Genetic studies robustly link PPARG and FABP4 variants to FABP4 serum levels. Considering the potential effects on atherosclerotic lesion development, drug discovery programs have been initiated in search for potent inhibitors of FABP4. Elevated FABP4 levels indicate an increased cardiovascular risk and is causally related to acceleration of atherosclerotic disease, However, clinical trials for FABP4 inhibition are lacking, possibly due to concerns about available compounds' side effects. Further research on FABP4 genetics and its putative causal role in cardiovascular disease is needed, particularly in aging subgroups.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":" ","pages":"163-175"},"PeriodicalIF":5.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ann Le, Helen Peng, Danielle Golinsky, Matteo Di Scipio, Ricky Lali, Guillaume Paré
{"title":"What Causes Premature Coronary Artery Disease?","authors":"Ann Le, Helen Peng, Danielle Golinsky, Matteo Di Scipio, Ricky Lali, Guillaume Paré","doi":"10.1007/s11883-024-01200-y","DOIUrl":"https://doi.org/10.1007/s11883-024-01200-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose of Review</h3><p>This review provides an overview of genetic and non-genetic causes of premature coronary artery disease (pCAD).</p><h3 data-test=\"abstract-sub-heading\">Recent Findings</h3><p>pCAD refers to coronary artery disease (CAD) occurring before the age of 65 years in women and 55 years in men. Both genetic and non-genetic risk factors may contribute to the onset of pCAD. Recent advances in the genetic epidemiology of pCAD have revealed the importance of both monogenic and polygenic contributions to pCAD. Familial hypercholesterolemia (FH) is the most common monogenic disorder associated with atherosclerotic pCAD. However, clinical overreliance on monogenic genes can result in overlooked genetic causes of pCAD, especially polygenic contributions. Non-genetic factors, notably smoking and drug use, are also important contributors to pCAD. Cigarette smoking has been observed in 25.5% of pCAD patients relative to 12.2% of non-pCAD patients. Finally, myocardial infarction (MI) associated with spontaneous coronary artery dissection (SCAD) may result in similar clinical presentations as atherosclerotic pCAD.</p><h3 data-test=\"abstract-sub-heading\">Summary</h3><p>Recognizing the genetic and non-genetic causes underlying pCAD is important for appropriate prevention and treatment. Despite recent progress, pCAD remains incompletely understood, highlighting the need for both awareness and research.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":"117 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140583094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anders Berg Wulff, Børge G Nordestgaard, Anne Langsted
{"title":"Novel Therapies for Lipoprotein(a): Update in Cardiovascular Risk Estimation and Treatment.","authors":"Anders Berg Wulff, Børge G Nordestgaard, Anne Langsted","doi":"10.1007/s11883-024-01192-9","DOIUrl":"10.1007/s11883-024-01192-9","url":null,"abstract":"<p><strong>Purpose of review: </strong>Lipoprotein(a) is an important causal risk factor for cardiovascular disease but currently no available medication effectively reduces lipoprotein(a). This review discusses recent findings regarding lipoprotein(a) as a causal risk factor and therapeutic target in cardiovascular disease, it reviews current clinical recommendations, and summarizes new lipoprotein(a) lowering drugs.</p><p><strong>Recent findings: </strong>Epidemiological and genetic studies have established lipoprotein(a) as a causal risk factor for cardiovascular disease and mortality. Guidelines worldwide now recommend lipoprotein(a) to be measured once in a lifetime, to offer patients with high lipoprotein(a) lifestyle advise and initiate other cardiovascular medications. Clinical trials including antisense oligonucleotides, small interfering RNAs, and an oral lipoprotein(a) inhibitor have shown great effect on lowering lipoprotein(a) with reductions up to 106%, without any major adverse effects. Recent clinical phase 1 and 2 trials show encouraging results and ongoing phase 3 trials will hopefully result in the introduction of specific lipoprotein(a) lowering drugs to lower the risk of cardiovascular disease.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":" ","pages":"111-118"},"PeriodicalIF":5.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melody Hermel, Andrew Chiou, Abdul Mannan Khan Minhas, Maha Inam, Carly E Waldman, Eventine Youngblood, Sandeep Mehta, Leandro Slipczuk, Sana Sheikh, Chelsea Meloche, Adeel Khoja, Salim S Virani
{"title":"Highlights of Cardiovascular Disease Prevention Studies Presented at the 2023 American Heart Association Scientific Sessions.","authors":"Melody Hermel, Andrew Chiou, Abdul Mannan Khan Minhas, Maha Inam, Carly E Waldman, Eventine Youngblood, Sandeep Mehta, Leandro Slipczuk, Sana Sheikh, Chelsea Meloche, Adeel Khoja, Salim S Virani","doi":"10.1007/s11883-024-01193-8","DOIUrl":"10.1007/s11883-024-01193-8","url":null,"abstract":"<p><strong>Purpose of review: </strong>Focused review highlighting ten select studies presented at the 2023 American Heart Association (AHA) Scientific Sessions.</p><p><strong>Recent findings: </strong>Included studies assessed semaglutide and cardiovascular outcomes in overweight or obese patients without diabetes (SELECT); dapagliflozin in patients with acute myocardial infarction without diabetes (DAPA-MI); effects of dietary sodium on systolic blood pressure in middle-aged individuals (CARDIA-SSBP); long-term blood pressure control after hypertensive pregnancy with physician guided self-management (POP-HT); effect and safety of zilebesiran, an RNA interference therapy, for sustained blood pressure reduction (KARDIA-1); recaticimab add-on therapy in patients with non-familial hypercholesterolemia and mixed hyperlipidemia (REMAIN-2); efficacy and safety of lepodisiran an extended duration short-interfering RNA targeting lipoprotein(a); safety and pharmacodynamic effects of an investigational DNA base editing medicine that inactivates the PCSK9 gene and lowers LDL cholesterol (VERVE-101); automated referral to centralized pharmacy services for evidence-based statin initiation in high-risk patients; and effects of intensive blood pressure lowering in reducing risk of cardiovascular events (ESPRIT). Research presented at the 2023 AHA Scientific Sessions emphasized innovative strategies in cardiovascular disease prevention and management.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":" ","pages":"119-131"},"PeriodicalIF":5.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marly van Assen, Ashley Beecy, Gabrielle Gershon, Janice Newsome, Hari Trivedi, Judy Gichoya
{"title":"Implications of Bias in Artificial Intelligence: Considerations for Cardiovascular Imaging.","authors":"Marly van Assen, Ashley Beecy, Gabrielle Gershon, Janice Newsome, Hari Trivedi, Judy Gichoya","doi":"10.1007/s11883-024-01190-x","DOIUrl":"10.1007/s11883-024-01190-x","url":null,"abstract":"<p><strong>Purpose of review: </strong>Bias in artificial intelligence (AI) models can result in unintended consequences. In cardiovascular imaging, biased AI models used in clinical practice can negatively affect patient outcomes. Biased AI models result from decisions made when training and evaluating a model. This paper is a comprehensive guide for AI development teams to understand assumptions in datasets and chosen metrics for outcome/ground truth, and how this translates to real-world performance for cardiovascular disease (CVD).</p><p><strong>Recent findings: </strong>CVDs are the number one cause of mortality worldwide; however, the prevalence, burden, and outcomes of CVD vary across gender and race. Several biomarkers are also shown to vary among different populations and ethnic/racial groups. Inequalities in clinical trial inclusion, clinical presentation, diagnosis, and treatment are preserved in health data that is ultimately used to train AI algorithms, leading to potential biases in model performance. Despite the notion that AI models themselves are biased, AI can also help to mitigate bias (e.g., bias auditing tools). In this review paper, we describe in detail implicit and explicit biases in the care of cardiovascular disease that may be present in existing datasets but are not obvious to model developers. We review disparities in CVD outcomes across different genders and race groups, differences in treatment of historically marginalized groups, and disparities in clinical trials for various cardiovascular diseases and outcomes. Thereafter, we summarize some CVD AI literature that shows bias in CVD AI as well as approaches that AI is being used to mitigate CVD bias.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":" ","pages":"91-102"},"PeriodicalIF":5.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vojtech Kratky, Anna Valerianova, Zdenka Hruskova, Vladimir Tesar, Jan Malik
{"title":"Increased Cardiovascular Risk in Young Patients with CKD and the Role of Lipid-Lowering Therapy.","authors":"Vojtech Kratky, Anna Valerianova, Zdenka Hruskova, Vladimir Tesar, Jan Malik","doi":"10.1007/s11883-024-01191-w","DOIUrl":"10.1007/s11883-024-01191-w","url":null,"abstract":"<p><strong>Purpose of review: </strong>Chronic kidney disease (CKD) is associated with a significantly increased risk of cardiovascular disease (CVD). This review summarizes known risk factors, pathophysiological mechanisms, and current therapeutic possibilities, focusing on lipid-lowering therapy in CKD.</p><p><strong>Recent findings: </strong>Novel data on lipid-lowering therapy in CKD mainly stem from clinical trials and clinical studies. In addition to traditional CVD risk factors, patients with CKD often present with non-traditional risk factors that include, e.g., anemia, proteinuria, or calcium-phosphate imbalance. Dyslipidemia remains an important contributing CVD risk factor in CKD, although the mechanisms involved differ from the general population. While statins are the most commonly used lipid-lowering therapy in CKD patients, some statins may require dose reduction. Importantly, statins showed diminished beneficial effect on cardiovascular events in patients with severe CKD and hypercholesterolemia despite high CVD risk and effective reduction of LDL cholesterol. Ezetimibe enables the reduction of the dose of statins and their putative toxicity and, in combination with statins, reduces CVD endpoints in CKD patients. The use of novel drugs such as PCSK9 inhibitors is safe in CKD, but their potential to reduce cardiovascular events in CKD needs to be elucidated in future studies.</p>","PeriodicalId":10875,"journal":{"name":"Current Atherosclerosis Reports","volume":" ","pages":"103-109"},"PeriodicalIF":5.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}