Showing papers in "Current Atherosclerosis Reports in 2022"
20 citations
TL;DR: In this article , a review seeks to consolidate available data on long-term cardiovascular complications of COVID-19 infection, including myocarditis, pericarditis, acute coronary syndrome, heart failure, pulmonary hypertension, right ventricular dysfunction, myocardial fibrosis, hypertension, and diabetes mellitus.
Abstract: COVID-19 is now a global pandemic and the illness affects multiple organ systems, including the cardiovascular system. Long-term cardiovascular consequences of COVID-19 are not yet fully characterized. This review seeks to consolidate available data on long-term cardiovascular complications of COVID-19 infection. Acute cardiovascular complications of COVID-19 infection include myocarditis, pericarditis, acute coronary syndrome, heart failure, pulmonary hypertension, right ventricular dysfunction, and arrhythmia. Long-term follow-up shows increased incidence of arrhythmia, heart failure, acute coronary syndrome, right ventricular dysfunction, myocardial fibrosis, hypertension, and diabetes mellitus. There is increased mortality in COVID-19 patients after hospital discharge, and initial myocardial injury is associated with increased mortality. Emerging data demonstrates increased incidence of cardiovascular illness and structural changes in recovered COVID-19 patients. Future research will be important in understanding the clinical significance of these structural abnormalities, and to determine the effect of vaccines on preventing long-term cardiovascular complications.
20 citations
TL;DR: In this article , the authors defined the role of PCSK9 in the realm of inflammation, pathogen infections and cellular proliferation in various cancers and associated metastases, and provided links between PCSK-9 and inflammation/atherosclerosis, viral infections and cancer/metastasis.
Abstract: Since the discovery of PCSK9 in 2003, this proprotein convertase was shown to target specific receptors for degradation in endosomes/lysosomes, including LDLR and other family members and hence to enhance the levels of circulating LDL-cholesterol (LDLc). Accordingly, inhibitors of PCSK9, including monoclonal antibodies blocking its circulating activity and siRNA silencers of its hepatic expression, are now used in clinics worldwide to treat hypercholesterolemia patients effectively and safely in combination with statins and/or ezetimibe. These powerful treatments reduce the incidence of atherosclerosis by at least 20%. Since 2008, novel targets of PCSK9 began to be defined, thereby expanding its roles beyond LDLc regulation into the realm of inflammation, pathogen infections and cellular proliferation in various cancers and associated metastases. Some pathogens such as dengue virus exploit the ability of PCSK9 to target the LDLR for degradation to enhance their ability to infect cells. Aside from increasing the degradation of the LDLR and its family members VLDLR, ApoER2 and LRP1, circulating PCSK9 also reduces the levels of other receptors such as CD36 (implicated in fatty acid uptake), oxidized LDLR receptor (that clears oxidized LDLc) as well as major histocompatibility class-I (MHC-I) receptors (implicated in the immune response to antigens). Thus, these novel targets provided links between PCSK9 and inflammation/atherosclerosis, viral infections and cancer/metastasis. The functional activities of PCSK9, accelerated the development of novel therapies to inhibit PCSK9 functions, including small molecular inhibitors, long-term vaccines, and possibly CRISPR-based silencing of hepatic expression of PCSK9. The future of inhibitors/silencers of PCSK9 function or expression looks bright, as these are expected to provide a modern armamentarium to treat various pathologies beyond hypercholesterolemia and its effects on atherosclerosis.
17 citations
TL;DR: The vascular endothelium represents the first barrier that prevents the entry of lipoproteins and leukocytes into the vessel wall, thereby controlling two key events in the pathogenesis of atherosclerosis as discussed by the authors .
Abstract: In this review, we summarize current insights into the versatile roles of endothelial cells in atherogenesis.The vascular endothelium represents the first barrier that prevents the entry of lipoproteins and leukocytes into the vessel wall, thereby controlling two key events in the pathogenesis of atherosclerosis. Disturbance of endothelial homeostasis increases vascular permeability, inflammation, and cellular trans-differentiation, which not only promotes the build-up of atherosclerotic plaques but is also involved in life-threatening thromboembolic complications such as plaque rupture and erosion. In this review, we focus on recent findings on endothelial lipoprotein transport, inflammation, cellular transitions, and barrier function. By using cutting-edge technologies such as single-cell sequencing, epigenetics, and cell fate mapping, novel regulatory mechanisms and endothelial cell phenotypes have been discovered, which have not only challenged established concepts of endothelial activation, but have also led to a different view of the disease.
16 citations
TL;DR: In this paper , a clear link between excessive alcohol consumption and cardiovascular disease (CVD) has been established, but no consensus exists on the effects of moderate alcohol consumption on CVD.
Abstract: A clear link between excessive alcohol consumption and cardiovascular disease (CVD) has been established, but no consensus exists on the effects of moderate alcohol consumption on CVD.A lower risk of coronary heart disease and myocardial infarction among moderate drinkers compared to abstainers has been consistently observed in epidemiological studies and meta-analyses of these studies. However, ambiguity remains on the effect of alcohol on other CVDs and all-cause mortality. Short-term randomized controlled trials (RCT) have identified potentially beneficial effects of alcohol consumption on cardiovascular risk factors, but studies investigating genetic polymorphisms that influence alcohol consumption (i.e., Mendelian randomization) have yielded inconclusive results. To date, a long-term RCT providing causal evidence is lacking but urgently needed. Triangulation of evidence from different study designs, including long-term RCTs, pragmatic trials and the evaluation of policy measures, combined will lead to the best available evidence.
15 citations
TL;DR: A recent review as mentioned in this paper summarizes the mechanistic evidence for differences among omega-3 fatty acids (n3-FAs) on the development and manifestations of atherothrombotic disease.
Abstract: Abstract Purpose of Review The omega-3 fatty acids (n3-FAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have recently undergone testing for their ability to reduce residual cardiovascular (CV) risk among statin-treated subjects. The outcome trials have yielded highly inconsistent results, perhaps attributable to variations in dosage, formulation, and composition. In particular, CV trials using icosapent ethyl (IPE), a highly purified ethyl ester of EPA, reproducibly reduced CV events and progression of atherosclerosis compared with mixed EPA/DHA treatments. This review summarizes the mechanistic evidence for differences among n3-FAs on the development and manifestations of atherothrombotic disease. Recent Findings Large randomized clinical trials with n3-FAs have produced discordant outcomes despite similar patient profiles, doses, and triglyceride (TG)-lowering effects. A large, randomized trial with IPE, a prescription EPA only formulation, showed robust reduction in CV events in statin treated patients in a manner proportional to achieved blood EPA concentrations. Multiple trials using mixed EPA/DHA formulations have not shown such benefits, despite similar TG lowering. These inconsistencies have inspired investigations into mechanistic differences among n3-FAs, as EPA and DHA have distinct membrane interactions, metabolic products, effects on cholesterol efflux, antioxidant properties, and tissue distribution. EPA maintains normal membrane cholesterol distribution, enhances endothelial function, and in combination with statins improves features implicated in plaque stability and reduces lipid content of plaques. Summary Insights into reductions in residual CV risk have emerged from clinical trials using different formulations of n3-FAs. Among high-risk patients on contemporary care, mixed n3-FA formulations showed no reduction in CV events. The distinct benefits of IPE in multiple trials may arise from pleiotropic actions that correlate with on-treatment EPA levels beyond TG-lowering. These effects include altered platelet function, inflammation, cholesterol distribution, and endothelial dysfunction. Elucidating such mechanisms of vascular protection for EPA may lead to new interventions for atherosclerosis, a disease that continues to expand worldwide.
15 citations
TL;DR: Results from imaging studies are highlighted that have not only documented the remarkable heterogeneity of body fat topography but also the importance of visceral adiposity as a key body fat depot associated with cardiovascular disease risk and type 2 diabetes.
13 citations
TL;DR: The role of the wall shear stress in the development of atherosclerosis and its complications is discussed and areas with chronically low, oscillating wallShear stress are most prone to plaque development and include outer bifurcation walls and inner walls of arches.
11 citations
TL;DR: Clinical studies highlight that GLP-1RA to treat obesity, alongside their concomitant cardioprotective effects, have become a hallmark in clinical science.
11 citations
TL;DR: This article reviews recent progress regarding the role of CR in CVD prevention via reduction of cardiometabolic risk factors and promoting atherosclerotic stability and concludes that calorie restriction may be an approach to reduce the development of atherosclerosis.
9 citations
TL;DR: It is shown that inclisiran provides robust and durable reductions of PCSK9 and LDL-C levels, with a dosing schedule of once every 6 months after the initial and 3-month doses, and the administration schedule may improve patients’ compliance given the favourable safety profile of the drug.
TL;DR: GLP-1RAs have robust weight loss benefits and are expected to have a critical role in the management of obesity in the coming years and upcoming studies will evaluate the durability of weight loss achieved with GLP- 1RAs and the impact on cardiovascular outcomes.
TL;DR: In this paper , the potential mechanism connecting hypertriglyceridemia (HTG) and ASCVD risk and the potential efficacy of HTG-targeting therapies in ASCVD prevention were discussed.
Abstract: Recent studies indicate an association between hypertriglyceridemia (HTG) and atherosclerotic cardiovascular disease (ASCVD). The purpose of this review is to discuss the potential mechanism connecting HTG and ASCVD risk and the potential efficacy of HTG-targeting therapies in ASCVD prevention.HTG, with elevations in triglyceride-rich lipoproteins (TGRL) and their remnants, are causal ASCVD risk factors. The mechanisms whereby HTG increases ASCVD risk are not well understood but may include multiple factors. Inflammation plays a crucial role in atherosclerosis. TGRL compared to low-density lipoproteins (LDL) correlate better with inflammation. TGRL remnants can penetrate endothelium and interact with macrophages leading to foam cell formation and inflammation in arterial walls, thereby contributing to atherogenesis. In addition, circulating monocytes can take up TGRL and become lipid-laden foamy monocytes, which infiltrate the arterial wall and may also contribute to atherogenesis. Novel therapies targeting HTG or inflammation are in development and have potential of reducing residual ASCVD risk associated with HTG. Clinical and preclinical studies show a causal role of HTG in promoting ASCVD, in which inflammation plays a vital role. Novel therapies targeting HTG or inflammation have potential of reducing residual ASCVD risk.
TL;DR: The background for familial hypercholesterolemia and elevated lipoprotein(a) as risk factors for cardiovascular disease and the consequences of the fact that LDL cholesterol measurements/calculations include the cholesterol present in lipop protein(a).
TL;DR: The majority of international guidelines for cardiovascular disease (CVD) prevention recommend moderate intake of low fat or fat-free products, and limiting full fat dairy food because of its high saturated fatty acid content as discussed by the authors .
Abstract: The majority of international guidelines for cardiovascular disease (CVD) prevention recommend moderate intake of low fat or fat-free products, and limiting full fat dairy food because of its high saturated fatty acid content. Recent equivocal observational studies and greater understanding of the complex nature of dairy foods has led to reappraisal for some types of dairy foods.Current guidelines from major cardiovascular societies have differed; interpretation of major observational studies has been inconsistent. Apart from the adverse effect of butter, consumption of more complex dairy products notably fermented varieties, yogurt in particular, appears to be inversely associated with outcomes of CVD and type 2 diabetes (T2D). Reduced fat in dairy food appears advantageous but is no longer a unanimous view although is preferred for people at increased CVD risk and dyslipidemia. Changed evidence has led to new advice regarding consumption of some dairy foods. The apparent beneficial effects of cheese, fermented milk, and yogurt allow for increased consumption of nutritious staple foods. Reduced fat yogurt may be desirable as part of diets for individuals with CVD or T2D.
TL;DR: RNA therapeutics are a new and rapidly expanding class of drugs to prevent or treat a wide spectrum of diseases as discussed by the authors , which are designed to regulate gene expression in a transient manner and offer the versatility to replace, supplement, correct, suppress, or eliminate the expression of a targeted gene.
Abstract: RNA therapeutics are a new and rapidly expanding class of drugs to prevent or treat a wide spectrum of diseases. We discuss the defining characteristics of the diverse family of molecules under the RNA therapeutics umbrella.RNA therapeutics are designed to regulate gene expression in a transient manner. For example, depending upon the strategy employed, RNA therapies offer the versatility to replace, supplement, correct, suppress, or eliminate the expression of a targeted gene. RNA therapies include antisense nucleotides, microRNAs and small interfering RNAs, RNA aptamers, and messenger RNAs. Further, we discuss the mechanism(s) by which different RNA therapies either reduce or increase the expression of their targets. We review the RNA therapeutics approved (and those in trials) to treat cardiovascular indications. RNA-based therapeutics are a new, rapidly growing class of drugs that will offer new alternatives for an increasing array of cardiovascular conditions.
TL;DR: In this article , the authors reviewed the pathogenic interrelationship between NAFLD and dyslipidemia, elucidates underlying pathophysiological mechanisms and focuses on management approaches for patients with NAFLDM.
Abstract: Abstract Purpose of Review Patients with non-alcoholic fatty liver disease (NAFLD), often considered as the hepatic manifestation of the metabolic syndrome, represent a population at high cardiovascular risk and frequently suffer from atherogenic dyslipidemia. This article reviews the pathogenic interrelationship between NAFLD and dyslipidemia, elucidates underlying pathophysiological mechanisms and focuses on management approaches for dyslipidemic patients with NAFLD. Recent Findings Atherogenic dyslipidemia in patients with NAFLD results from hepatic and peripheral insulin resistance along with associated alterations of hepatic glucose and lipoprotein metabolism, gut dysbiosis, and genetic factors. Summary Since atherogenic dyslipidemia and NAFLD share a bi-directional relationship and are both major driving forces of atherosclerotic cardiovascular disease (ASCVD) development, early detection and adequate treatment are warranted. Thus, integrative screening and management programs are urgently needed. A stepwise approach for dyslipidemic patients with NAFLD includes (i) characterization of dyslipidemia phenotype, (ii) individual risk stratification, (iii) definition of treatment targets, (iv) lifestyle modification, and (v) pharmacotherapy if indicated.
TL;DR: A deeper understanding of the sex differences in the risk factors and plaque morphology of coronary atherosclerosis may lead to improved outcomes of CVD in women.
TL;DR: The role of lipoprotein(a) in cardiovascular risk and in aortic valve stenosis in familial hypercholesterolemia, as well as its association with their phenotype, and strategies to identify this high-risk population are reviewed.
TL;DR: In this article , the authors identified and discussed nutrigenetic studies assessing the interactions between cholesteryl ester transfer protein (CETP) SNPs and dietary factors on blood lipids.
Abstract: An abnormal lipid profile is considered a main risk factor for cardiovascular diseases and evidence suggests that single nucleotide polymorphisms (SNPs) in the cholesteryl ester transfer protein (CETP) gene contribute to variations in lipid levels in response to dietary intake. The objective of this review was to identify and discuss nutrigenetic studies assessing the interactions between CETP SNPs and dietary factors on blood lipids.Relevant articles were obtained through a literature search of PubMed and Google Scholar through to July 2021. An article was included if it examined an interaction between CETP SNPs and dietary factors on blood lipids. From 49 eligible nutrigenetic studies, 27 studies reported significant interactions between 8 CETP SNPs and 17 dietary factors on blood lipids in 18 ethnicities. The discrepancies in the study findings could be attributed to genetic heterogeneity, and differences in sample size, study design, lifestyle and measurement of dietary intake. The most extensively studied ethnicities were those of Caucasian populations and majority of the studies reported an interaction with dietary fat intake. The rs708272 (TaqIB) was the most widely studied CETP SNP, where 'B1' allele was associated with higher CETP activity, resulting in lower high-density lipoprotein cholesterol and higher serum triglycerides under the influence of high dietary fat intake. Overall, the findings suggest that CETP SNPs might alter blood lipid profiles by modifying responses to diet, but further large studies in multiple ethnic groups are warranted to identify individuals at risk of adverse lipid response to diet.
TL;DR: The recommendation to consume a plant-based diet to reduce cardiovascular risk remains an evidence-based strategy based on observational studies, although heterogeneity exists, and small mortality risks from some animal proteins, notably processed meats.
TL;DR: In this article , a review summarizes recent literature on diet and food insecurity in SGM adults and their contribution to cardiovascular disease (CVD) risk in this population, and concludes that there is no evidence on the relationship between food insecurity and CVD risk.
Abstract: Sexual and gender minority (SGM) adults experience significant cardiovascular health disparities, yet little is known about diet and food insecurity in this population. This review summarizes recent literature on diet and food insecurity in SGM adults and their contribution to cardiovascular disease (CVD) risk in this population. Existing evidence on diet and food insecurity disparities among SGM adults is inconclusive and research examining their link with CVD risk in SGM adults is limited. The majority of existing studies lack standardized and validated assessments of diet and food insecurity. Correlates of unhealthy diet and food insecurity among SGM adults are poorly understood. Research examining the associations between diet and food insecurity with CVD risk in SGM adults is limited. Longitudinal studies are needed to investigate whether diet and food insecurity contribute to the cardiovascular health disparities observed in SGM adults.
TL;DR: There are multiple LPA-directed therapies in clinical development targeting LPA mRNA that have shown to lower Lp(a) plasma levels for up to 90% as mentioned in this paper , however, lifestyle interventions have no effect on LDL-C-mediated ASCVD risk.
Abstract: Over the past decades, genetic and observational evidence has positioned lipoprotein(a) as novel important and independent risk factor for cardiovascular disease (ASCVD) and aortic valve stenosis.As Lp(a) levels are determined genetically, lifestyle interventions have no effect on Lp(a)-mediated ASCVD risk. While traditional low-density lipoprotein cholesterol (LDL-C) can now be effectively lowered in the vast majority of patients, current lipid lowering therapies have no clinically relevant Lp(a) lowering effect. There are multiple Lp(a)-directed therapies in clinical development targeting LPA mRNA that have shown to lower Lp(a) plasma levels for up to 90%: pelacarsen, olpasiran, and SLN360. Pelacarsen is currently investigated in a phase 3 cardiovascular outcome trial expected to finish in 2024, while olpasiran is about to proceed to phase 3 and SLN360's phase 1 outcomes were recently published. If proven efficacious, Lp(a) will soon become the next pathway to target in ASCVD risk management.
TL;DR: In this article , the role of excess free cholesterol (FC) bioavailability in atherosclerosis vs. atheroprotection was highlighted and the potential mechanisms contributing to this paradox were summarized.
Abstract: As both a cholesterol acceptor and carrier in the reverse cholesterol transport (RCT) pathway, high-density lipoprotein (HDL) is putatively atheroprotective. However, current pharmacological therapies to increase plasma HDL cholesterol (HDL-c) concentration have paradoxically failed to prevent or reduce atherosclerosis and cardiovascular disease (CVD). Given that free cholesterol (FC) transfer between surfaces of lipoproteins and cells is reversible, excess plasma FC can be transferred to the cells of peripheral tissue sites resulting in atherosclerosis. Here, we summarize potential mechanisms contributing to this paradox and highlight the role of excess free cholesterol (FC) bioavailability in atherosclerosis vs. atheroprotection.Recent findings have established a complex relationship between HDL-c concentration and atherosclerosis. Systemic scavenger receptor class B type 1 (SR-B1) knock out (KO) mice exhibit with increased diet-induced atherosclerosis despite having an elevated plasma HDL-c concentration compared to wild type (WT) mice. The greater bioavailability of HDL-FC in SR-B1 vs. WT mice is associated with a higher FC content in multiple cell types and tissue sites. These results suggest that dysfunctional HDL with high FC bioavailability is atheroprone despite high HDL-c concentration. Past oversimplification of HDL-c involvement in cholesterol transport has led to the failures in HDL targeted therapy. Evidence suggests that FC-mediated functionality of HDL is of higher importance than its quantity; as a result, deciphering the regulatory mechanisms by which HDL-FC bioavailability can induce atherosclerosis can have far-reaching clinical implications.
TL;DR: The characteristics of lipid disorders and the possible management with dyslipidemia in pregnant women and the decisions on lipid-lowering therapy in pregnant patients should be individualized are reviewed.
TL;DR: There is a need to adopt updated methods for determining LDL-C and to develop better biomarkers that more accurately reflect the abundance of TRL remnant particles.
TL;DR: Bempedoic acid is a prodrug converted to its active metabolite by very-long-chain acyl-CoA synthetase 1 which is present mostly in the liver and absent in skeletal muscles as discussed by the authors .
Abstract: The aim of creating an orally active non-statin cholesterol-lowering drug was achieved with bempedoic acid, a small linear molecule providing both a significant low-density lipoprotein cholesterol (LDL-C) reduction and an anti-inflammatory effect by decreasing high-sensitivity C-reactive protein. Bempedoic acid antagonizes ATP citrate-lyase, a cytosolic enzyme upstream of HMGCoA reductase which is the rate-limiting step of cholesterol biosynthesis. Bempedoic acid is a pro-drug converted to its active metabolite by very-long-chain acyl-CoA synthetase 1 which is present mostly in the liver and absent in skeletal muscles. This limits the risk of myalgia and myopathy. The remit of this review is to give clinical insights on the safety and efficacy of bempedoic acid and to understand for whom it should be prescribed.Bempedoic acid with a single daily dose (180 mg) reduces LDL-C by a mean 24.5% when given alone, by 18% when given on top of a major statin and by 38-40% when given in a fixed-dose combination with ezetimibe. Bempedoic acid does not lead to the risk of new-onset diabetes, and moderately improves the glycaemic profile. The extensive knowledge on bempedoic acid mechanism, metabolism and side effects has led to an improved understanding of the potential benefits of this agent and offers a possible alternative to cardiologists and clinical practitioners somewhat worn out today by the occurrence of the muscular side effects of statins.
TL;DR: In this paper , the authors investigated the role and mechanism of HDL in cardiovascular risk determination and found that HDL-C reduction is related to a raised coronary risk, while HDL-c elevations may be linked to non-vascular diseases, such as age-related macular disease.
Abstract: High-density lipoproteins (HDL) are responsible for the transport in plasma of a large fraction of circulating lipids, in part from tissue mobilization. The evaluation of HDL-associated cholesterol (HDL-C) has provided a standard method for assessing cardiovascular (CV) risk, as supported by many contributions on the mechanism of this arterial benefit. The present review article will attempt to investigate novel findings on the role and mechanism of HDL in CV risk determination.The most recent research has been aimed to the understanding of how a raised functional capacity of HDL, rather than elevated levels per se, may be responsible for the postulated CV protection. Markedly elevated HDL-C levels appear instead to be associated to a raised coronary risk, indicative of a U-shaped relationship. While HDL-C reduction is definitely related to a raised CV risk, HDL-C elevations may be linked to non-vascular diseases, such as age-related macular disease. The description of anti-inflammatory, anti-oxidative and anti-infectious properties has indicated potential newer areas for diagnostic and therapeutic approaches. In the last two decades inconclusive data have arisen from clinical trials attempting to increase HDL-C pharmacologically or by way of recombinant protein infusions (most frequently with the mutant A-I Milano); prevention of stent occlusion or heart failure treatment have shown instead significant promise. Targeted clinical studies are still ongoing.
TL;DR: In this article , a review highlights major studies across a broad array of topics presented at the virtual 2021 American Heart Association (AHA) Scientific Session highlighted the importance of interventions for cardiovascular disease prevention.
Abstract: This review highlights major studies across a broad array of topics presented at the virtual 2021 American Heart Association (AHA) Scientific Sessions.Assessed studies examine a remotely delivered hypertension and lipid program in 10,000 patients across a diverse healthcare network; a cluster-randomized trial of a village doctor-led intervention for hypertension control; empagliflozin in heart failure with preserved ejection fraction (EMPEROR-Preserved); efficacy and safety of empagliflozin in hospitalized heart failure patients (EMPULSE); icosapent ethyl versus placebo in outpatients with coronavirus disease 2019 (PREPARE-IT 2); clinical safety, pharmacokinetics, and low-density lipoprotein cholesterol-lowering efficacy of MK-0161, an oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor; and effects of aspirin on dementia and cognitive impairment in the ASCEND trial. Research presented at the 2021 AHA Scientific Sessions emphasized the importance of interventions for cardiovascular disease prevention.