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International Journal of Molecular... Feb 2022Atherosclerosis has been known in medicine for several centuries. As early as 1755, the Swedish anatomist Albrecht von Haller used the term "atheroma" to describe... (Review)
Review
Atherosclerosis has been known in medicine for several centuries. As early as 1755, the Swedish anatomist Albrecht von Haller used the term "atheroma" to describe vascular lesions. Atherosclerosis may originate from an unbalanced diet or bad habits, and is mainly found in developed countries. Clinical trials have been conducted to establish the causes of atherosclerosis, and also to develop treatments for this disease. However, prevention of the disease has always been better than treatment, so vaccination may be the key to saving thousands of lives. The creation of a vaccine may be directly related to the study of autoimmune processes occurring in the body, immunity. This review considers the issues related to the involvement of the immune response in the development of atherosclerotic lesions. Modern concepts of atherogenesis, immune inflammation in atherosclerosis, and potential vaccine targets are also discussed. There is a particular focus on experimental and clinical data supporting the development of immune therapies to reduce cardiovascular risk.
Topics: Adaptive Immunity; Atherosclerosis; Drug Development; Humans; Vaccination
PubMed: 35269559
DOI: 10.3390/ijms23052417 -
Nature Medicine Sep 2023Elevated triglycerides and non-high-density lipoprotein cholesterol (HDL-C) are risk factors for atherosclerotic cardiovascular disease (ASCVD). ARO-ANG3 is an RNA... (Randomized Controlled Trial)
Randomized Controlled Trial
Elevated triglycerides and non-high-density lipoprotein cholesterol (HDL-C) are risk factors for atherosclerotic cardiovascular disease (ASCVD). ARO-ANG3 is an RNA interference therapy that targets angiopoietin-like protein 3 (ANGPTL3), a regulator of lipoprotein metabolism. This first-in-human, phase 1, randomized, placebo-controlled, open-label trial investigated single and repeat ARO-ANG3 doses in four cohorts of fifty-two healthy participants and one cohort of nine participants with hepatic steatosis, part of a basket trial. Safety (primary objective) and pharmacokinetics (in healthy participants) and pharmacodynamics (secondary objectives) of ARO-ANG3 were evaluated. ARO-ANG3 was generally well tolerated, with similar frequencies of treatment-emergent adverse events in active and placebo groups. Systemic absorption of ARO-ANG3 in healthy participants was rapid and sustained, with a mean T of 6.0-10.5 h and clearance from plasma within 24-48 h after dosing with a mean t of 3.9-6.6 h. In healthy participants, ARO-ANG3 treatment reduced ANGPTL3 (mean -45% to -78%) 85 days after dose. Reductions in triglyceride (median -34% to -54%) and non-HDL-C (mean -18% to -29%) (exploratory endpoints) concentrations occurred with the three highest doses. These early-phase data support ANGPTL3 as a potential therapeutic target for ASCVD treatment. ClinicalTrials.gov identifier: NCT03747224.
Topics: Humans; Triglycerides; Angiopoietin-Like Protein 3; RNA Interference; Cholesterol; Atherosclerosis
PubMed: 37626170
DOI: 10.1038/s41591-023-02494-2 -
Vascular Health and Risk Management 2023Multiple lines of evidence confirm that the cumulative burden of low-density lipoprotein cholesterol (LDL-C) is causally related to the development of atherosclerotic... (Review)
Review
Multiple lines of evidence confirm that the cumulative burden of low-density lipoprotein cholesterol (LDL-C) is causally related to the development of atherosclerotic cardiovascular disease (ASCVD). As such, lowering LDL-C is a central tenet in all ASCVD prevention guidelines, which recommend matching the intensity of LDL-C lowering with the absolute risk of the patient. Unfortunately, issues such as difficulty with long-term adherence to statin therapy and inability to achieve desired LDL-C thresholds with statins alone results in residual elevated ASCVD risk. Non-statin therapies generally provide similar risk reduction per mmol/L of LDL-C reduction and are included by major society guidelines as part of the treatment algorithm for managing LDL-C. Per the 2022 American College of Cardiology Expert Consensus Decision Pathway, patients with ASCVD are recommended to achieve both an LDL-C reduction ≥50% and an LDL-C threshold of <55 mg/dL in patients at very high-risk and <70 mg/dL in those not at very high risk. Patients with familial hypercholesterolemia (FH) but without ASCVD should lower LDL-C to <100 mg/dL. For patients who remain above LDL-C thresholds with maximally tolerated statin therapy plus lifestyle changes, non-statin therapy warrants strong consideration. While several non-statin therapies have been granted FDA approval for managing hypercholesterolemia (eg, ezetimibe, Proprotein Convertase Subtilisin/Kexin 9 [PCSK9] monoclonal antibodies, and bempedoic acid), the focus of the current review is on inclisiran, a novel small interfering RNA therapy that inhibits the production of the PCSK9 protein. Inclisiran is currently FDA approved as an adjunct to statin therapy in patients with clinical ASCVD or heterozygous FH who require additional LDL-lowering. The drug is administered by subcutaneous injection twice a year, after an initial baseline and 3 month dose. In this review, we sought to provide an overview of the use of inclisiran, review current trial data, and outline an approach to potential patient selection.
Topics: Humans; Proprotein Convertase 9; Cholesterol, LDL; Cardiovascular Diseases; RNA, Small Interfering; Atherosclerosis; Hyperlipoproteinemia Type II
PubMed: 37434791
DOI: 10.2147/VHRM.S338424 -
Journal of Atherosclerosis and... Nov 2023The study aimed to investigate low-density lipoprotein cholesterol (LDL-C) goal achievement rates in patients receiving LDL-C-lowering therapy using recent real-world...
AIMS
The study aimed to investigate low-density lipoprotein cholesterol (LDL-C) goal achievement rates in patients receiving LDL-C-lowering therapy using recent real-world data, following the 2017 revision of the Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases (JAS GL2017).
METHODS
Patients with documented LDL-C test results were extracted from the Medical Data Vision claims database between July 2018 and June 2021 and divided into three groups according to JAS GL2017: primary prevention high risk (Group I, LDL-C goal <120 mg/dL), secondary prevention (Group II, LDL-C goal <100 mg/dL), and secondary prevention high risk (Group III, LDL-C goal <70 mg/dL).
RESULTS
The mean LDL-C value was 108.7 mg/dL (n=125,235), 94.4 mg/dL (n=57,910), and 90.6 mg/dL (n=33,850) in Groups I, II, and III, respectively. Intensive statin monotherapy (pitavastatin, rosuvastatin, or atorvastatin) was the most frequently prescribed lipid-lowering treatment (21.6%, 30.8%, and 42.7% in Groups I, II, and III, respectively), followed by ezetimibe (2.5%, 7.1%, and 8.5% in Groups I, II, and III, respectively). LDL-C goals were achieved by 65.5%, 60.6%, and 25.4% of patients overall in Groups I, II, and III, respectively. Achievement rates were 83.9%, 75.3%, and 29.5% in patients prescribed intensive statin monotherapy and 82.3%, 86.4%, and 46.4% in those prescribed statin and ezetimibe combinations in Groups I, II, and III, respectively. In Group III, the proportion of patients with familial hypercholesterolemia prescribed statin and ezetimibe combinations achieving LDL-C goals was low (32.5%).
CONCLUSIONS
The proportion of patients achieving LDL-C goals for secondary prevention in the high-risk group remains low even with statin and ezetimibe combination therapy.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Goals; Cardiovascular Diseases; Japan; Treatment Outcome; Ezetimibe; Atherosclerosis; Anticholesteremic Agents
PubMed: 36928267
DOI: 10.5551/jat.63940 -
Advanced Science (Weinheim,... Dec 2023With the changing disease spectrum, atherosclerosis has become increasingly prevalent worldwide and the associated diseases have emerged as the leading cause of death.... (Review)
Review
With the changing disease spectrum, atherosclerosis has become increasingly prevalent worldwide and the associated diseases have emerged as the leading cause of death. Due to their fascinating physical, chemical, and biological characteristics, nanomaterials are regarded as a promising tool to tackle enormous challenges in medicine. The emerging discipline of nanomedicine has filled a huge application gap in the atherosclerotic field, ushering a new generation of diagnosis and treatment strategies. Herein, based on the essential pathogenic contributors of atherogenesis, as well as the distinct composition/structural characteristics, synthesis strategies, and surface design of nanoplatforms, the three major application branches (nanodiagnosis, nanotherapy, and nanotheranostic) of nanomedicine in atherosclerosis are elaborated. Then, state-of-art studies containing a sequence of representative and significant achievements are summarized in detail with an emphasis on the intrinsic interaction/relationship between nanomedicines and atherosclerosis. Particularly, attention is paid to the biosafety of nanomedicines, which aims to pave the way for future clinical translation of this burgeoning field. Finally, this comprehensive review is concluded by proposing unresolved key scientific issues and sharing the vision and expectation for the future, fully elucidating the closed loop from atherogenesis to the application paradigm of nanomedicines for advancing the early achievement of clinical applications.
Topics: Humans; Nanomedicine; Atherosclerosis; Nanostructures
PubMed: 37897322
DOI: 10.1002/advs.202304294 -
Endocrinology and Metabolism Clinics of... Sep 2022Based on decades of both basic science and epidemiologic research, there is overwhelming evidence for the causal relationship between high levels of cholesterol,... (Review)
Review
Based on decades of both basic science and epidemiologic research, there is overwhelming evidence for the causal relationship between high levels of cholesterol, especially low-density lipoprotein cholesterol and cardiovascular disease. Risk evaluation and monitoring the response to lipid-lowering therapies are heavily dependent on the accurate assessment of plasma lipoproteins in the clinical laboratory. This article provides an update of lipoprotein metabolism as it relates to atherosclerosis and how diagnostic measures of lipids and lipoproteins can serve as markers of cardiovascular risk, with a focus on recent advances in cardiovascular risk marker testing.
Topics: Atherosclerosis; Biomarkers; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Humans; Lipoproteins
PubMed: 35963624
DOI: 10.1016/j.ecl.2022.02.009 -
Arteriosclerosis, Thrombosis, and... Apr 2020The immune system's role in atherosclerosis has long been an important research topic and is increasingly investigated for therapeutic and diagnostic purposes.... (Review)
Review
The immune system's role in atherosclerosis has long been an important research topic and is increasingly investigated for therapeutic and diagnostic purposes. Therefore, noninvasive imaging of hematopoietic organs and immune cells will undoubtedly improve atherosclerosis phenotyping and serve as a monitoring method for immunotherapeutic treatments. Among the available imaging techniques, positron emission tomography's unique features make it an ideal tool to quantitatively image the immune response in the context of atherosclerosis and afford reliable readouts to guide medical interventions in cardiovascular disease. Here, we summarize the state of the art in the field of atherosclerosis positron emission tomography immunoimaging and provide an outlook on current and future applications.
Topics: Atherosclerosis; Hematopoietic System; Humans; Nanoparticles; Phagocytes; Plaque, Atherosclerotic; Positron-Emission Tomography; Radioimmunodetection; Radiopharmaceuticals
PubMed: 32078338
DOI: 10.1161/ATVBAHA.119.313455 -
The Medical Clinics of North America Sep 2023Atherosclerotic disease, including stroke and myocardial infarction, is the leading cause of morbidity and mortality worldwide. Atherosclerotic plaque formation occurs... (Review)
Review
Atherosclerotic disease, including stroke and myocardial infarction, is the leading cause of morbidity and mortality worldwide. Atherosclerotic plaque formation occurs in the setting of excess oxidative and hemodynamic stress and is perpetuated by smoking, poor diet, dyslipidemia, hypertension, and diabetes. Plaque may rupture, resulting in acute thrombotic events. Smoking cessation, lifestyle modification, risk factor optimization, and antithrombotic therapies are the mainstays of atherosclerotic disease management and are the cornerstones to reduce morbidity and mortality in this high-risk patient population. Novel therapeutics are in development and will add to the growing armamentarium available to physicians who manage atherosclerotic disease.
Topics: Humans; Atherosclerosis; Myocardial Infarction; Risk Factors; Smoking; Diabetes Mellitus
PubMed: 37541708
DOI: 10.1016/j.mcna.2023.04.004 -
International Journal of Molecular... Apr 2023Polyphenols have attracted tremendous attention due to their pro-health properties, including their antioxidant, anti-inflammatory, antibacterial and neuroprotective... (Review)
Review
Polyphenols have attracted tremendous attention due to their pro-health properties, including their antioxidant, anti-inflammatory, antibacterial and neuroprotective activities. Atherosclerosis is a vascular disorder underlying several CVDs. One of the main risk factors causing atherosclerosis is the type and quality of food consumed. Therefore, polyphenols represent promising agents in the prevention and treatment of atherosclerosis, as demonstrated by in vitro, animal, preclinical and clinical studies. However, most polyphenols cannot be absorbed directly by the small intestine. Gut microbiota play a crucial role in converting dietary polyphenols into absorbable bioactive substances. An increasing understanding of the field has confirmed that specific GM taxa strains mediate the gut microbiota-atherosclerosis axis. The present study explores the anti-atherosclerotic properties and associated underlying mechanisms of polyphenols. Moreover, it provides a basis for better understanding the relationship between dietary polyphenols, gut microbiota, and cardiovascular benefits.
Topics: Animals; Polyphenols; Gastrointestinal Microbiome; Risk Factors; Anti-Inflammatory Agents; Atherosclerosis
PubMed: 37108307
DOI: 10.3390/ijms24087146 -
Indian Heart Journal Mar 2024Lp(a) is a genetically determined, heritable, independent and causal risk factor for ASCVD. About 1 in 5 people worldwide have elevated Lp(a) (>50 mg/dL or... (Review)
Review
Lp(a) is a genetically determined, heritable, independent and causal risk factor for ASCVD. About 1 in 5 people worldwide have elevated Lp(a) (>50 mg/dL or >125 nmol/L) whereas in Indians it is 25 %. Epidemiological, genome-wide association and mendelian randomization studies have demonstrated an association between elevated Lp(a) levels and increased incidence of myocardial infarction, aortic valve stenosis, ischemic stroke, heart failure, CV and all-cause mortality. The increased Lp(a)-mediated CV risk is mediated by pro-inflammatory, pro-thrombotic and pro-atherogenic processes, leading to progression of atherosclerosis and increased risk of thrombosis. Lp(a) level reaches peak by 5 years of age and remains stable over time. Levels are not much influenced by dietary and environmental factors but it can vary in certain clinical situations like thyroid diseases, chronic kidney disease, inflammation and sepsis. It should be measured at least once in life time. Cascade testing for high Lp(a) is recommended in the settings of FH, family history of (very) high Lp(a), and personal or family history of ASCVD. In the absence of specific Lp(a)-lowering therapies, comprehensive risk factor management is recommended as per guidelines for individuals with elevated Lp(a). PCSK9 inhibitors and Inclisiran reduce Lp(a) by 25%. Pelacarsen is an antisense oligonucleotide and is found to reduce Lp(a) by 80%. In a recent Indian study of 1,021 CAD patients, presence of elevated Lp(a) (>50 mg/dL) correlated with severe angiographic disease. 37% of ACS patients exhibited elevated Lp(a) and it was higher in young CAD patients with FH (43%).
Topics: Humans; Proprotein Convertase 9; Lipoprotein(a); Genome-Wide Association Study; Risk Factors; Atherosclerosis; Hyperlipidemias
PubMed: 38160790
DOI: 10.1016/j.ihj.2023.12.010