Article
Cardiac & Cardiovascular Systems
Qin Wang, Clare Oliver-Williams, Olli T. Raitakari, Jorma Viikari, Terho Lehtimaki, Mika Kahonen, Marjo-Riitta Jarvelin, Veikko Salomaa, Markus Perola, John Danesh, Johannes Kettunen, Adam S. Butterworth, Michael Holmes, Mika Ala-Korpela
Summary: The study found that genetic mimicry of ANGPTL4 inhibition and LPL enhancement have similar metabolic effects, while genetic mimicry of ANGPTL3 inhibition showed differing metabolic effects, suggesting potential involvement of pathways independent of LPL. Inhibition of ANGPTL4 and enhancement of LPL through genetic mimicry were associated with a lower risk of coronary heart disease and type 2 diabetes.
EUROPEAN HEART JOURNAL
(2021)
Article
Endocrinology & Metabolism
Yunpeng Guan, Xiaoyu Hou, Peipei Tian, Luping Ren, Yong Tang, An Song, Jiajun Zhao, Ling Gao, Guangyao Song
Summary: The study investigated mechanisms of postprandial hypertriglyceridemia (PPT) through analyzing serum lipid and apolipoprotein levels before and after a high-fat meal. Results showed significantly higher levels of various parameters in the PPT group, indicating that elevated ApoCIII levels may be a risk factor for PPT.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Patricia Recio-Lopez, Ismael Valladolid-Acebes, Philipp Hadwiger, Markus Hossbach, Monika Krampert, Carla Prata, Per-Olof Berggren, Lisa Juntti-Berggren
Summary: In this study, siRNAs were developed to silence apoCIII in vivo and it was found that this approach can result in metabolic improvements. Reduction of apoCIII expression led to increased LPL activity, lower triglyceride levels, reduced liver fat, ceased weight gain, enhanced insulin sensitivity, and improved glucose homeostasis.
Article
Cardiac & Cardiovascular Systems
Aliza Hussain, Caroline Sun, Elizabeth Selvin, Vijay Nambi, Josef Coresh, Xiaoming Jia, Christie M. Ballantyne, Ron C. Hoogeveen
Summary: Despite statin and antihypertensive therapies, older Americans continue to have high ASCVD risk. Novel measures of triglyceride-rich lipoproteins are associated with ASCVD, and genetic polymorphisms related to triglyceride catabolism are potential therapeutic targets. In older adults, LDL-TG and ANGPTL3 are independent predictors of ASCVD events after adjustment for traditional risk factors.
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2022)
Article
Endocrinology & Metabolism
Marissa Lightbourne, Anna Wolska, Brent S. Abel, Kristina Rother, Mary Walter, Yevgeniya Kushchayeva, Sungyoung Auh, Robert D. Shamburek, Alan T. Remaley, Ranganath Muniyappa, Rebecca J. Brown
Summary: Patients with lipodystrophy exhibit hypertriglyceridemia and elevated levels of LPL modulators, which can be reduced after metreleptin treatment. Elevations in LPL inhibitors such as apoC-III and ANGPTL8 may contribute to hypertriglyceridemia in lipodystrophy, and reductions in these factors may mediate improvements in triglyceride levels with metreleptin therapy.
JOURNAL OF THE ENDOCRINE SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Kelli L. Sylvers-Davie, Ashley Segura-Roman, Alicia M. Salvi, Kylie J. Schache, Brandon S. J. Davies
Summary: High plasma TG and low HDL-C levels are risk factors for atherosclerosis and cardiovascular disease, regulated in part by ANGPTL3. This study found that ANGPTL8 is not necessary for EL inhibition, indicating that targeting ANGPTL8 for hypertriglyceridemia or cardiovascular disease may have different outcomes than targeting ANGPTL3.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Najia Jin, William F. Matter, Laura F. Michael, Yuewei Qian, Tarun Gheyi, Leticia Cano, Carlos Perez, Celia Lafuente, Howard B. Broughton, Alfonso Espada
Summary: The study shows that angiopoietin-like proteins 3 and 8 (ANGPTL3/8) can inhibit the enzymatic activities of lipoprotein lipase (LPL) by promoting furin-mediated cleavage of LPL. This effect is stronger than using ANGPTL3 or ANGPTL8 alone.
ACS CHEMICAL BIOLOGY
(2021)
Review
Hematology
Henry N. Ginsberg, Ira J. Goldberg
Summary: The positive relationship between increased levels of circulating triglycerides and cardiovascular events has been observed for decades. Inhibitors of APOC3 and ANGPTL3 that reduce circulating triglycerides are poised to enter clinical practice, driven by genetic cohort studies. This review discusses the biology of how these inhibitors affect circulating lipoproteins and the current state of clinical development using monoclonal antibodies, antisense oligonucleotides, and silencing RNAs targeting APOC3 and ANGPTL3.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ching-Yen Lin, Pei-Yi Chen, Hao-Jen Hsu, Wan-Yun Gao, Ming-Jiuan Wu, Jui-Hung Yen
Summary: This study investigated the lipid-lowering effects of nobiletin and its underlying molecular mechanisms. The results showed that nobiletin can regulate lipid metabolism by targeting the LXR alpha-ANGPTL3-LPL axis. Animal studies also showed that nobiletin can reduce plasma triglycerides and cholesterol levels. These findings suggest that nobiletin may be a potential inhibitor for dyslipidemia and atherosclerotic cardiovascular diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Kendall H. Burks, Debapriya Basu, Ira J. Goldberg, Nathan O. Stitziel
Summary: ANGPTL3 has been identified as a therapeutic target for reducing plasma lipids, including atherogenic lipoproteins and LDL cholesterol. Therapeutic agents such as evinacumab (a monoclonal antibody), vupanorsen (an antisense oligonucleotide), and others have been developed to inhibit ANGPTL3. Vaccination and gene editing strategies for ANGPTL3 are also being explored. The success of ANGPTL3 inhibition therapies underscores its importance in treating refractory hypertriglyceridemia and hypercholesterolemia.
BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Medicine, General & Internal
Qidi Ying, Dick C. Chan, Jing Pang, Santica M. Marcovina, Peter Hugh R. Barrett, Gerald F. Watts
Summary: Alirocumab lowers plasma Lp(a) concentration in patients by a dual mode of action, increasing the clearance and decreasing the production of Lp(a) particles. In patients with high apo(a) concentrations, alirocumab primarily reduces apo(a) pool size by increasing the fractional catabolic rate (FCR) of apo(a). By contrast, in patients with very high apo(a) concentrations, alirocumab significantly lowers apo(a) pool size through both increased apo(a) FCR and decreased production rate.
JOURNAL OF INTERNAL MEDICINE
(2022)
Review
Cardiac & Cardiovascular Systems
Late Tokgozoglu, Peter Libby
Summary: Lipid risk factors for cardiovascular disease depend on both lifestyle and additional measures for optimum control. Recent genetic findings have identified novel targets for lipid-lowering therapy, providing new avenues for management. New treatments targeting triglyceride-rich lipoproteins and lipoprotein(a) have emerged and shown improved efficacy and tolerability. Gene-editing approaches are also being explored in lipid management.
EUROPEAN HEART JOURNAL
(2022)
Article
Cardiac & Cardiovascular Systems
Tahir Mahmood, Jessica Minnier, Matthew K. Ito, Qian H. Li, Andrew Koren, Ivy W. Kam, Sergio Fazio, Michael D. Shapiro
Summary: This study aimed to investigate the prevalence of discordant plasma LDL-C/Lp(a) response to the PCSK9 inhibitor alirocumab, and a high prevalence of discordant response was observed, suggesting that alirocumab may reduce Lp(a) through alternative pathways.
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yan Q. Chen, Eugene Y. Zhen, Anna M. Russell, Mariam Ehsani, Robert W. Siegel, Yuewei Qian, Robert J. Konrad
Summary: After feeding, the activity of lipid-metabolizing enzyme lipoprotein lipase (LPL) in adipose tissue needs to be maximized, which is inhibited by angiopoietin-like protein 4 (ANGPTL4). However, this inhibition is blocked by ANGPTL8 through the formation of ANGPTL4/8 complexes. Recent research has shown that ANGPTL4/8 not only protects LPL but also interacts with tissue plasminogen activator (tPA) and plasminogen to generate plasmin, which cleaves ANGPTL4/8 and restores LPL activity. These findings shed light on the intricate regulation of LPL activity in response to feeding.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Jordan M. Kraaijenhof, Tycho R. Tromp, Nick S. Nurmohamed, Laurens F. Reeskamp, Marije Langenkamp, Johannes H. M. Levels, S. Matthijs Boekholdt, Nicholas J. Wareham, Menno Hoekstra, Erik S. G. Stroes, G. Kees Hovingh, Aldo Grefhorst
Summary: The study found that while ANGPTL3 predominantly resides on HDL, its activity is highest when bound to LDL particles.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Pharmacology & Pharmacy
Ulrich Laufs, Alberico Luigi Catapano, Raffaele De Caterina, Francois Schiele, Alessandro Sionis, Azfar Zaman, J. Wouter Jukema
Summary: This study evaluated the impact of the ESC/EAS 2019 dyslipidaemia guidelines on lipid-lowering therapy in ACS patients. Results showed that lipid testing was performed earlier in 2022 compared to 2018, and there was an increase in testing for non-HDL-C, lipoprotein(a), and ApoB. Majority of patients were receiving lipid-lowering therapy at discharge and there was a higher proportion of patients receiving statin plus ezetimibe combination therapy in 2022. LDL-C levels were lower in 2022 and more patients achieved LDL-C goals.
VASCULAR PHARMACOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Manuel C. Olma, Serdar Tutuncu, Cornelia Fiessler, Claudia Kunze, Michael Kraemer, Lena Steindorf-Sabath, Muhammad Jawad-Ul-Qamar, Paulus Kirchhof, Ulrich Laufs, Johannes Schurig, Peter Kraft, Joachim Roether, Albrecht Guenther, Goetz Thomalla, Boris Dimitrijeski, Darius G. Nabavi, Roland Veltkamp, Peter U. Heuschmann, Karl Georg Haeusler, Matthias Endres
Summary: This study aims to analyze the frequency and type of abnormal ECG findings, subsequent changes in medical treatment, and their association with cardiovascular outcomes in patients with acute ischemic stroke. The results show that systematic in-hospital Holter ECG reveals abnormal findings in 1 of 5 patients with acute stroke, and mortality was lower at 24 months in patients with systematic ECG recording in the hospital.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Cardiac & Cardiovascular Systems
Stephan Stoebe, Joscha Kandels, Michael Metze, Bhupendar Tayal, Ulrich Laufs, Andreas Hagendorff
Summary: This study evaluated the prognostic value of left ventricular hypertrophy (LVH), diastolic dysfunction, and right ventricular (RV) load in patients with moderate aortic valve stenosis (AS). The presence of 2 or more pathophysiological changes was found to be a strong predictor of worse outcomes in terms of aortic valve area, pressure gradient, longitudinal strain, and survival without aortic valve replacement.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Erik S. G. Stroes, Harold E. Bays, Maciej Banach, Alberico L. Catapano, P. Barton Duell, Ulrich Laufs, G. B. John Mancini, Kausik K. Ray, William J. Sasiela, Yang Zhang, Antonio M. Gotto
Summary: This study demonstrates that bempedoic acid can reduce hsCRP levels in patients at risk of atherosclerotic cardiovascular disease. The changes in hsCRP and LDL-C are related, but the effect of bempedoic acid on hsCRP is independent of LDL-C lowering.
Article
Cardiac & Cardiovascular Systems
Jannis Stader, Marios Antoniadis, Matti Ussat, Rolf Wachter, Daniel Lavall, Michael Metze, Martin Neef, Christian Spies, Ulrich Laufs, Karsten Lenk
Summary: This study compared the novel method of Quantitative Flow Ratio (QFR) with the established invasive measurements of coronary blood flow using Instantaneous Wave-free Ratio (iFR) or Resting Full-cycle Ratio (RFR) in daily cathlab routine. The results showed a significant correlation between QFR and iFR or RFR, with QFR measurement requiring less time and lower radiation dose.
CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
(2023)
Article
Medical Laboratory Technology
Romy Gessner, Christiane Gaertner, Maria Schmidt, Felix Eckelt, Kerstin Wirkner, Markus Loeffler, Tobias Uhe, Berend Isermann, Ulrich Laufs, Thorsten Kaiser, Rolf Wachter
Summary: This study aims to systematically examine the differences between in-hospital patients with no diagnosed cardiac diseases and a population-based cohort. Retrospective analyses were performed in two independent cohorts, revealing that male sex and older age were associated with higher serum concentrations of hs-cTnT in hospitalized patients compared to the population-based cohort. These findings suggest that age, sex, and hospitalization itself are correlated with elevated hs-cTnT concentrations.
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
(2023)
Review
Cardiac & Cardiovascular Systems
Martin Schulz, Ulrich Laufs
Summary: Primary medication non-adherence refers to the failure to fill a first prescription for a new medication. This aspect of reduced effectiveness of pharmacotherapy is often overlooked but significant. This review investigates the prevalence, impact, reasons, predictors, and interventions related to primary non-adherence to cardiovascular/cardiometabolic drugs. Current literature shows a high prevalence of primary non-adherence, with the overall rate exceeding 10%. Understanding the reasons behind patients' reluctance to follow evidence-based pharmacotherapy and implementing targeted interventions could lead to a reduction in cardiovascular diseases.
CLINICAL RESEARCH IN CARDIOLOGY
(2023)
Article
Medicine, General & Internal
Arnold von Eckardstein, Winfried Maerz, Ulrich Laufs
Summary: Many studies have found that low levels of HDL-C are associated with an increased risk of ASCVD, but clinical trials have not shown any benefit in preventing ASCVD events by drugs that increase HDL-C levels. Genetic studies also do not support a causal role for HDL-C in cardiovascular risk. The interpretation of previous data has important limitations, and further research is needed to fully understand the relationship between HDL and ASCVD.
DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT
(2023)
Article
Medicine, General & Internal
Paulina Elena Stuerzebecher, Adrienn Tuennemann-Tarr, Katja Tuppatsch, Ulrich Laufs
Summary: This study assessed the lipid management in high and very high cardiovascular risk patients and found that only a minority of patients adhere to the LDL-C goals as recommended by the 2019 ESC/EAS guidelines. This indicates opportunities for improvement in cardiovascular disease prevention in Germany.
DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT
(2023)
Article
Cardiac & Cardiovascular Systems
Michael Metze, Stephan Stoebe, Dietrich Pfeiffer, Andreas Hagendorff, Ulrich Laufs, Karsten Lenk
Summary: This case describes a 71-year-old male patient with end stage heart failure and severe mitral regurgitation who underwent percutaneous indirect mitral annuloplasty. During the procedure, the circumflex artery was compromised at two anatomic locations, but the mitral regurgitation was effectively reduced. A stent implantation was chosen as a bailout strategy to prevent artery damage and maintain the reduction in mitral regurgitation. While stent implantation in this setting is off label use and requires critical evaluation, it has been successful in similar clinical cases.
Article
Multidisciplinary Sciences
Vivien Henschke, Konstanze Hild, Erik Schilling, Jan Haas, Vanina Filipova, Stephan Erbe, Roman Konig, Judith M. Hubschen, Ulrich Laufs, Claudia Claus, Jes-Niels Boeckel
Summary: Rubella virus (RuV) infection during pregnancy can cause abortion, stillbirth, and embryonic defects, leading to congenital rubella syndrome (CRS). The molecular mechanisms of RuV-induced damage to placental endothelial cells (EC) and its control on EC function were investigated. The study found that RuV can infect EC, inducing the production of antiviral interferons and CXCL10, which inhibit angiogenesis and migration of EC.
Review
Medicine, General & Internal
Klaus G. Parhofer, Ulrich Laufs
Summary: The treatment of dyslipidemias is crucial for the prevention of cardiovascular disease. Evaluation of lipid status and monitoring of treatment effects can guide therapy. The main goal is to lower LDL-cholesterol through lifestyle changes and medication.
DEUTSCHES ARZTEBLATT INTERNATIONAL
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Ulrich Laufs, Matthias Blueher, Berend Isermann
EUROPEAN HEART JOURNAL
(2023)
Article
Cardiac & Cardiovascular Systems
Francois Schiele, Alberico L. Catapano, Raffaele De Caterina, Ulrich Laufs, J. Wouter Jukema, Azfar Zaman, Alessandro Sionis
Summary: We conducted quality control of lipid-lowering therapy in patients with acute coronary syndrome in order to propose corrective actions. Using data from the ACS EuroPath IV survey, we measured the attainment of two quality indicators related to the treatment, and proposed corrective measures to increase the attainment rate.
EUROPEAN HEART JOURNAL-ACUTE CARDIOVASCULAR CARE
(2023)
Article
Multidisciplinary Sciences
Lea Schwarzkopf, Petra Buettner, Karl Scholtyssek, Thomas Schroeter, Ruth Hiller, Gerhard Hindricks, Andreas Bollmann, Ulrich Laufs, Laura Ueberham
Summary: This study found that c-kitpos cells are common in the left atrial appendage (LAA) of cardiovascular patients, with a relatively homogenous distribution throughout the LAA. The LAA could be considered a suitable source for extracting autologous cardiac progenitor cells in living human patients.