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Showing papers in "Current Atherosclerosis Reports in 2016"


Journal ArticleDOI
TL;DR: The complex relationship between obesity and cardiovascular disorders, in particular coronary atherosclerosis, heart failure, and atrial fibrillation is summarized.
Abstract: In the USA, 69 % of adults are either overweight or obese and 35 % are obese. Obesity is associated with an increased incidence of various cardiovascular disorders. Obesity is a risk marker for cardiovascular disease, in that it is associated with a much higher prevalence of comorbidities such as diabetes, hypertension, and metabolic syndrome, which then increase the risk for cardiovascular disease. However, in addition, obesity may also be an independent risk factor for the development of cardiovascular disease. Furthermore, although obesity has been shown to be an independent risk factor for several cardiovascular diseases, it is often associated with improved survival once the diagnosis of the cardiovascular disease has been made, leading to the term “obesity paradox.” Several pathways linking obesity and cardiovascular disease have been described. In this review, we attempt to summarize the complex relationship between obesity and cardiovascular disorders, in particular coronary atherosclerosis, heart failure, and atrial fibrillation.

206 citations


Journal ArticleDOI
TL;DR: This review offers an in-depth analysis of atherosclerosis and the related interplay between dyslipidemia/hypertension and critically appraises the current diagnosis, etiology, and therapeutic options.
Abstract: Atherosclerosis is the narrowing of arteries due to the accumulation of macrophages overloaded with lipids resulting in foam cell formation, and these events occur preferentially at the branching points of arteries which are particularly susceptible to hyperlipidemic stress-induced inflammation and oxidative stress. The different stages of atherogenesis rely on oxidative stress, endothelial dysfunction, and inflammation, and hypertension or dyslipidemia can independently trigger these stages. Dyslipidemia and hypertension are pathological conditions that damage the endothelium, triggering cell proliferation, vascular remodeling, apoptosis, and increased cellular permeability with increased adhesion molecules that bind monocytes and T lymphocytes to create a vicious cocktail of pathophysiological factors. Correspondingly, the factors are redirected by chemo-attractants and pro-inflammatory cytokines into the intima of the vasculature, where monocytes differentiate into macrophages taking up oxidized LDL uncontrollably to form foam cells and atherosclerotic lesions. Moreover, endothelial damage also causes loss of vasomotor activity, disproportionate vascular contractility, and elevation of blood pressure in dyslipidemic patients, while in hypertensive patients, further elevation of blood pressure occurs, creating a self-perpetuating vicious cycle that aggravates the development and progression of atherosclerotic lesions. This review offers an in-depth analysis of atherosclerosis and the related interplay between dyslipidemia/hypertension and critically appraises the current diagnosis, etiology, and therapeutic options.

142 citations


Journal ArticleDOI
TL;DR: The importance of addressing obesity in patients with OSA, as a strategy to reduce the burden of cardiovascular risk factors in this population, is discussed.
Abstract: Obstructive sleep apnea (OSA) is common in the general population and highly prevalent in patients with cardiovascular disease. In this paper, we review (1) the pathophysiological mechanisms of OSA that may causally contribute to cardiovascular disease; (2) current evidence regarding the association between OSA and hypertension, stroke, ischemic heart disease, heart failure, atrial fibrillation, and cardiovascular mortality; and (3) the impact of continuous positive airway pressure (CPAP) treatment on cardiovascular risk factors and outcomes. We emphasize the importance of obesity as a comorbidity of OSA and a confounder in the association between OSA and cardiovascular disease. We also discuss the importance of addressing obesity in patients with OSA, as a strategy to reduce the burden of cardiovascular risk factors in this population. Implications for the approach of patients' OSA in clinical practice and future research directions are discussed.

120 citations


Journal ArticleDOI
TL;DR: This review aims to highlight the recent literature which examines CHD in ethnic minorities and future directions in research and care.
Abstract: Heart disease remains the leading cause of death in the USA. Overall, heart disease accounts for about 1 in 4 deaths with coronary heart disease (CHD) being responsible for over 370,000 deaths per year. It has frequently and repeatedly been shown that some minority groups in the USA have higher rates of traditional CHD risk factors, different rates of treatment with revascularization procedures, and excess morbidity and mortality from CHD when compared to the non-Hispanic white population. Numerous investigations have been made into the causes of these disparities. This review aims to highlight the recent literature which examines CHD in ethnic minorities and future directions in research and care.

113 citations


Journal ArticleDOI
TL;DR: Findings include that consumption of water-soluble, viscous-forming fibers can reduce total and low-density lipoprotein cholesterol levels by about 5–10 %; and medium to high molecular weight fibers are more effective in reducing lipid levels.
Abstract: Consumption of dietary soluble fibers has been associated with health benefits such as reduced lipid levels, lower blood pressure, improved blood glucose control, weight loss, improved immune function, and reduced inflammation. Many of these health benefits relate to a reduced risk of developing cardiovascular disease. In this paper, we have reviewed recent studies on the hypocholesterolemic effects of dietary soluble fibers as well as fiber-rich foods. Findings include the following: (a) consumption of water-soluble, viscous-forming fibers can reduce total and low-density lipoprotein cholesterol levels by about 5–10 %; (b) minimal changes of high-density lipoprotein cholesterol or triglyceride levels were observed; (c) cholesterol-lowering properties of soluble fibers depend on their physical and chemical properties; and (d) medium to high molecular weight fibers are more effective in reducing lipid levels. Hypocholesterolemic benefits were also observed with some fiber-rich foods, such as whole oats, whole barley, legumes, peas, beans, flax seeds, apples, and citrus foods.

97 citations


Journal ArticleDOI
TL;DR: The design of a large phase 3 program is being considered to gain more information on efficacy and safety of ETC-1002 in combination with statins and when added to ezetimibe in statin-intolerant patients.
Abstract: Bempedoic acid (ETC-1002), a novel therapeutic approach for low-density lipoprotein cholesterol (LDL-C) lowering, inhibits ATP citrate lyase (ACL), an enzyme involved in fatty acid and cholesterol synthesis. Although rodent studies suggested potential effects of ACL inhibition on both fatty acid and cholesterol synthesis, studies in humans show an effect only on cholesterol synthesis. In phase 2 studies, ETC-1002 reduced LDL-C as monotherapy, combined with ezetimibe, and added to statin therapy, with LDL-C lowering most pronounced when ETC-1002 was combined with ezetimibe in patients who cannot tolerate statins. Whether clinically relevant favorable effects on other cardiometabolic risk factors such as hyperglycemia and insulin resistance occur in humans is unknown and requires further investigation. Promising phase 2 results have led to the design of a large phase 3 program to gain more information on efficacy and safety of ETC-1002 in combination with statins and when added to ezetimibe in statin-intolerant patients.

71 citations


Journal ArticleDOI
TL;DR: Grounding in the principles of PET imaging of atherosclerosis, the radioligands in use and in development, its research and clinical applications, and future developments for the field are provided.
Abstract: Atherosclerosis is a leading cause of morbidity and mortality. It is now widely recognized that the disease is more than simply a flow-limiting process and that the atheromatous plaque represents a nidus for inflammation with a consequent risk of plaque rupture and atherothrombosis, leading to myocardial infarction or stroke. However, widely used conventional clinical imaging techniques remain anatomically focused, assessing only the degree of arterial stenosis caused by plaques. Positron emission tomography (PET) has allowed the metabolic processes within the plaque to be detected and quantified directly. The increasing armory of radiotracers has facilitated the imaging of distinct metabolic aspects of atherogenesis and plaque destabilization, including macrophage-mediated inflammatory change, hypoxia, and microcalcification. This imaging modality has not only furthered our understanding of the disease process in vivo with new insights into mechanisms but has also been utilized as a non-invasive endpoint measure in the development of novel treatments for atherosclerotic disease. This review provides grounding in the principles of PET imaging of atherosclerosis, the radioligands in use and in development, its research and clinical applications, and future developments for the field.

66 citations


Journal ArticleDOI
TL;DR: Awareness of differences in the underlying pathophysiology of coronary disease in women compared to men may lead to improved gender-based diagnostic and treatment modalities, until more studies are performed, efforts should be directed toward improving delivery of current, gender-neutral guidelines in women.
Abstract: Purpose of Review Increased awareness of cardiovascular disease in women has prompted studies to investigate gender-related disparities in acute coronary syndromes (ACSs). In this review, we discuss findings from current literature on the clinical presentation, pathophysiology, diagnosis, and management of ACS in women as compared to men.

62 citations


Journal ArticleDOI
TL;DR: Encouraging results from clinical trials using antisense oligonucleotide, which selectively inhibits apoC-III, indicate that modulating apo C-III may be a potent therapeutic approach to managing dyslipidemia and cardiovascular disease risk.
Abstract: ApoC-III was discovered almost 50 years ago, but for many years, it did not attract much attention. However, as epidemiological and Mendelian randomization studies have associated apoC-III with low levels of triglycerides and decreased incidence of cardiovascular disease (CVD), it has emerged as a novel and potentially powerful therapeutic approach to managing dyslipidemia and CVD risk. The atherogenicity of apoC-III has been attributed to both direct lipoprotein lipase-mediated mechanisms and indirect mechanisms, such as promoting secretion of triglyceride-rich lipoproteins (TRLs), provoking proinflammatory responses in vascular cells and impairing LPL-independent hepatic clearance of TRL remnants. Encouraging results from clinical trials using antisense oligonucleotide, which selectively inhibits apoC-III, indicate that modulating apoC-III may be a potent therapeutic approach to managing dyslipidemia and cardiovascular disease risk.

60 citations


Journal ArticleDOI
TL;DR: The mechanism of cholesterol efflux and the emerging evidence on the association betweenolesterol efflux capacity and cardiovascular disease in human studies are reviewed and the completed and ongoing trials of novel therapies targeting different aspects of HDL cholesterolefflux are reviewed.
Abstract: Low high-density lipoprotein cholesterol (HDL-C) levels are associated with incident cardiovascular events; however, many therapies targeting increases in HDL-C have failed to show consistent clinical benefit. Thus, focus has recently shifted toward measuring high-density lipoprotein (HDL) function. HDL is the key mediator of reverse cholesterol transport, the process of cholesterol extraction from foam cells, and eventual excretion into the biliary system. Cholesterol efflux from peripheral macrophages to HDL particles has been associated with atherosclerosis in both animals and humans. We review the mechanism of cholesterol efflux and the emerging evidence on the association between cholesterol efflux capacity and cardiovascular disease in human studies. We also focus on the completed and ongoing trials of novel therapies targeting different aspects of HDL cholesterol efflux.

52 citations


Journal ArticleDOI
TL;DR: Based on the evidence, metformin has been shown to decrease the incidence of type 2 diabetes, and compares favorably to other weight-loss medications in terms of efficacy as well as safety, and should be considered for a treatment indication in patients with these conditions.
Abstract: Metformin is not currently used for weight loss or diabetes prevention because it lacks an FDA indication for obesity and/or pre-diabetes treatment. Based on the evidence, metformin has been shown to decrease the incidence of type 2 diabetes, and compares favorably to other weight-loss medications in terms of efficacy as well as safety. Thus, metformin should be considered for a treatment indication in patients with these conditions.

Journal ArticleDOI
TL;DR: Although well-designed randomized controlled trials with CHD events as endpoints are missing, several large prospective cohort studies have recently been published on the relationship between cis-MUFA and CHD risk.
Abstract: The effects of cis-monounsaturated fatty acids (cis-MUFAs) on the risk of coronary heart disease (CHD) and on CHD mortality are not clear. Also, dietary recommendations for cis-MUFA as derived by various organizations are not in agreement. Earlier studies have mainly focused on the effects of cis-MUFA on serum lipids and lipoproteins. More recent studies, however, have also addressed effects of cis-MUFA on other non-traditional CHD risk markers such as vascular function markers, postprandial vascular function, and energy intake and metabolism. Although well-designed randomized controlled trials with CHD events as endpoints are missing, several large prospective cohort studies have recently been published on the relationship between cis-MUFA and CHD risk. The aim of this paper is to review these new studies that have been published in the last 3 years on the effects of cis-MUFA on cardiovascular risk markers and CHD.

Journal ArticleDOI
TL;DR: The current knowledge of the role of S1P and its receptors in endothelial function in health and disease is reviewed, and the therapeutic potential of targeting S1PR not only for disorders of the arterial endothelium but also the microvasculature is discussed.
Abstract: Numerous preclinical studies indicate that sustained endothelial activation significantly contributes to tissue edema, perpetuates the inflammatory response, and exacerbates tissue injury ultimately resulting in organ failure. However, no specific therapies aimed at restoring endothelial function are available as yet. Sphingosine-1-phosphate (S1P) is emerging as a potent modulator of endothelial function and endothelial responses to injury. Recent studies indicate that S1PR are attractive targets to treat not only disorders of the arterial endothelium but also microvascular dysfunction caused by ischemic or inflammatory injury. In this article, we will review the current knowledge of the role of S1P and its receptors in endothelial function in health and disease, and we will discuss the therapeutic potential of targeting S1PR not only for disorders of the arterial endothelium but also the microvasculature. The therapeutic targeting of S1PR in the endothelium could help to bridge the gap between biomedical research in vascular biology and clinical practice.

Journal ArticleDOI
TL;DR: This review provides updates in gender disparities in the management of risk factors, treatments, and outcomes of coronary heart disease.
Abstract: Coronary heart disease (CHD), traditionally considered a male disease, causes far more deaths in women than cancer. The prevalence of CHD is lower in women at any age, but with advancing age, this differential decreases. The clinical outcomes including myocardial infarction mortality, all-cause mortality, and reinfarction rates are also worse in women with cardiovascular diseases (CVD) than in men. Yet, women appear to be underdiagnosed and undertreated for coronary heart disease. There is still a gap in the knowledge, understanding, and general awareness of CHD in women. This review provides updates in gender disparities in the management of risk factors, treatments, and outcomes of coronary heart disease.

Journal ArticleDOI
TL;DR: The paper presents evolution of plaque with a focus on the pathophysiologic cascade leading to arterial hardening and the factors which influence the understanding of atherosclerotic disease formation and cardiovascular risk including arterial stiffness, tissue morphological characteristics, and image-based elasticity measurement.
Abstract: Functional and structural changes in the common carotid artery are biomarkers for cardiovascular risk. Current methods for measuring functional changes include pulse wave velocity, compliance, distensibility, strain, stress, stiffness, and elasticity derived from arterial waveforms. The review is focused on the ultrasound-based carotid artery elasticity and stiffness measurements covering the physics of elasticity and linking it to biological evolution of arterial stiffness. The paper also presents evolution of plaque with a focus on the pathophysiologic cascade leading to arterial hardening. Using the concept of strain, and image-based elasticity, the paper then reviews the lumen diameter and carotid intima-media thickness measurements in combined temporal and spatial domains. Finally, the review presents the factors which influence the understanding of atherosclerotic disease formation and cardiovascular risk including arterial stiffness, tissue morphological characteristics, and image-based elasticity measurement.

Journal ArticleDOI
TL;DR: A recombinant adeno-associated virus vector carrying a low-density lipoprotein receptor (LDLR) transgene which has recently entered phase 1/2a testing is discussed and a summary of key gene therapy approaches for HoFH in pre-clinical development is included, including RNA silencing of HMG-CoA reductase and induced pluripotent stem cell transplant therapy.
Abstract: Homozygous familial hypercholesterolemia (HoFH) is a life-threatening Mendelian disorder with a mean life expectancy of 33 years despite maximally tolerated standard lipid-lowering therapies. This disease is an ideal candidate for gene therapy, and in the last few years, a number of exciting developments have brought this approach closer to the clinic than ever before. In this review, we discuss in detail the most advanced of these developments, a recombinant adeno-associated virus (AAV) vector carrying a low-density lipoprotein receptor (LDLR) transgene which has recently entered phase 1/2a testing. We also review ongoing development of approaches to enhance transgene expression, improve the efficiency of hepatocyte transduction, and minimize the AAV capsid-specific adaptive immune response. We include a summary of key gene therapy approaches for HoFH in pre-clinical development, including RNA silencing of t he gene encoding HMG-CoA reductase (HMGCR) and induced pluripotent stem cell transplant therapy.

Journal ArticleDOI
TL;DR: Interventions designed to improve statin adherence should take gender-specific challenges into consideration such as women being older at the time of increased CVD risk, higher rates of statin intolerance, and potentially greater caregiving responsibilities.
Abstract: Cardiovascular disease (CVD) continues to be the leading cause of death for men and women in the USA. Statins have contributed significantly to noted declines in cardiovascular-related mortality in the last decade; however, the benefit of statins is inequitable across genders. Women continue to be less likely to take statins and to meet target LDL goals than men. As a possible contributing factor to this disparity, we explore the evidence for gender-based differences in provision of, and adherence to statins. Compared with men, women are less likely to adhere to statins. Potential reasons for this gender difference in use of statins can be observed across all phases of adherence including both intentional and unintentional non-adherence. Notable gender-specific contributing factors for statin non-adherence include decreased provider and patient awareness of CVD risk among women, higher risk of statin intolerance among women, and competing demands associated with family caregiving responsibilities. Similar to limitations in the broader CVD literature, there is inadequate inclusion of gender-specific analyses in statin-related trials. Gender-based disparities in statin adherence can be linked to both provider level, psychosocial, and medication intolerance factors. Interventions designed to improve statin adherence should take gender-specific challenges into consideration such as women being older at the time of increased CVD risk, higher rates of statin intolerance, and potentially greater caregiving responsibilities.

Journal ArticleDOI
TL;DR: By combining dietary cholesterol reduction with other cholesterol-lowering modalities, it should be possible to substantially reduce atherosclerosis throughout life short of using cholesterol- Lowering drugs that act systemically.
Abstract: An ongoing dispute in the nutrition field is whether dietary cholesterol contributes significantly to elevated serum cholesterol and to atherosclerotic disease. Carefully controlled metabolic studies have shown that high-cholesterol intakes cause moderate increases in serum cholesterol levels. It is been difficult to verify this in population studies because of confounding factors. Nonetheless, meta-analysis of controlled studies documents a cholesterol-raising action of dietary cholesterol. Most of this effect occurs in low-density lipoproteins (LDLs), but the cholesterol content of other lipoproteins can be increased as well. Moreover, population studies strongly suggest that dietary cholesterol is atherogenic beyond any rise in LDL concentrations. It must be emphasized that dietary cholesterol is only one of several dietary factors influencing serum cholesterol levels. Others include saturated fatty acids, trans fatty acids, soluble fiber, and total caloric intake. To achieve substantial serum cholesterol lowering, favorable changes in all of these factors must be combined. To maximize cardiovascular risk reduction, a lifetime of a healthy diet is needed. Reduced cholesterol intake is only one of several factors required to achieve such a diet. In addition, reduction of cholesterol absorption can enhance serum cholesterol lowering. This can be attained by the addition of plant sterols or plant stanols to the diet or by use of ezetimibe, a cholesterol absorption blocker. By combining dietary cholesterol reduction with other cholesterol-lowering modalities, it should be possible to substantially reduce atherosclerosis throughout life short of using cholesterol-lowering drugs that act systemically.

Journal ArticleDOI
TL;DR: This review briefly summarizes inflammation as a risk factor in atherosclerosis, human disease states associated with accelerated atherosclerotic disease, and current treatment strategies for CHD targeting the inflammatory cascade.
Abstract: Inflammation is a critical component in the development of coronary heart disease (CHD), specifically in the process of atherogenesis. Human translational and preclinical studies have demonstrated that inflammation contributes to the development, sustainment, and progression of atherosclerosis, and epidemiological studies demonstrate that human diseases associated with increased systemic inflammation increase the risk of CHD-related events. Therefore, over the last decade, multiple clinical studies were designed to target the inflammatory cascade in order to reduce the risk of CHD and to identify which populations may benefit from these preventative treatment strategies. This review briefly summarizes inflammation as a risk factor in atherosclerosis, human disease states associated with accelerated atherosclerosis, and current treatment strategies for CHD targeting the inflammatory cascade.

Journal ArticleDOI
TL;DR: Evidence continues to show that high-sensitivity troponin is emerging as one of the most powerful prognostic biomarkers for the assessment of cardiovascular risk in the general population.
Abstract: Cardiac troponin has been well described as the preferred biomarker for diagnosis of myocardial infarction due to the high sensitivity and specificity for myocardial injury. Numerous other conditions apart from acute coronary syndrome can also lead to small elevations in troponin levels. However, the use of cTn as prognostic biomarker for the primary assessment of cardiovascular risk in asymptomatic patient has only recently been described. And with the development of newer generations of high-sensitivity cardiac troponin assays that can detect 10-fold lower concentrations of troponin, the potential value cTn in the prevention and management of asymptomatic cardiovascular disease has come to the fore. This review provides an overview of the transition of cardiac troponin as a marker of acute myocardial injury to one that detects sub-clinical injury. Evidence continues to show that high-sensitivity troponin is emerging as one of the most powerful prognostic biomarkers for the assessment of cardiovascular risk in the general population.

Journal ArticleDOI
TL;DR: The interactions between statins, PCSK9, LDL-C, and cardiovascular risk are multifaceted and are influenced by genetic, lifestyle, and environmental factors as well as lipid-lowering therapies.
Abstract: Purpose of Review To review the interactions between statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition.

Journal ArticleDOI
TL;DR: The current data emphasizes the need to individualize DAPT duration at the patient level to balance the clinical benefits of a reduced risk of cardiovascular ischemic events with the greater risk of clinically significant bleeding.
Abstract: Dual antiplatelet therapy (DAPT) following an acute coronary syndrome or after placement of a coronary artery stent is superior to aspirin alone for prevention of atherothrombotic events but carries an increased bleeding risk. DAPT should be continued for at least 12 months based on current guidelines. Recent randomized trials demonstrate reduced ischemic events including myocardial infarction (MI), stroke, and death with continued DAPT for up to 30 months or longer, particularly in the post-MI population. However, this clinical benefit is accompanied by an increased risk of bleeding. Additional trials show mixed safety and efficacy with duration of DAPT of less than 12 months. The current data emphasizes the need to individualize DAPT duration at the patient level to balance the clinical benefits of a reduced risk of cardiovascular ischemic events with the greater risk of clinically significant bleeding. Patients at an increased risk of ischemic events and a lower risk of bleeding should be strongly considered for prolonged DAPT beyond the 1 year currently recommended in the practice guidelines.

Journal ArticleDOI
TL;DR: This work has endeavored to provide indications for revisions after bariatric surgery and shows that prospective randomized controlled studies and long-term longitudinal population-based comparative studies greatly favor surgical intervention as opposed to traditional lifestyle, diet, and exercise programs.
Abstract: Bariatric/metabolic surgery is currently the only effective long-term treatment for morbid obesity- and obesity-related diseases such as diabetes, heart disease, hypertension, obstructive sleep apnea, and dyslipidemia. In addition, bariatric/metabolic surgery has been shown to significantly reduce the incidence of diabetes and cancer and prolong life when compared to non-surgical therapies. However, as obesity is a chronic disease, recidivism of weight and comorbid conditions can occur. In addition, the surgical construct can lead to long-term consequences such as marginal ulceration, bowel obstruction, reflux, and nutritional deficiencies. Despite these drawbacks, prospective randomized controlled studies and long-term longitudinal population-based comparative studies greatly favor surgical intervention as opposed to traditional lifestyle, diet, and exercise programs. Revisional surgery can be quite complex and technically challenging and may offer the patient a wide variety of solutions for treatment of weight recidivism and complications after primary operations. Given the paucity of high quality published data, we have endeavored to provide indications for revisions after bariatric surgery.

Journal ArticleDOI
TL;DR: The potential success of cytokine-targeted therapy will be solid proof of the inflammatory hypothesis of atherothrombosis and push back early detection and monitoring to provide a greater window for disease modification.
Abstract: Macrophages influence various processes of cardiovascular inflammation. Whether they are of embryonic or post-natal hematopoietic origin, their balance in differential activation may direct the course of inflammation. Accelerated macrophage activation and accumulation through a pro-inflammatory signaling pathway may result in extensive tissue damage, adverse repair, and worsened clinical outcomes. Attenuation of such a mechanism and/or promotion of the anti-inflammatory macrophage activation may lead to early resolution of inflammation. Elucidating multiple novel mechanisms of monocyte and macrophage activation leads to a better understanding of their roles in vascular inflammation. In turn, this begets better therapeutic target identification and biomarker discovery. Combined with increasingly sensitive and specific imaging techniques, we continue to push back early detection and monitoring to provide us with a greater window for disease modification. The potential success of cytokine-targeted therapy will be solid proof of the inflammatory hypothesis of atherothrombosis.

Journal ArticleDOI
TL;DR: Current and developing therapies for reducing apoC-III levels and function to lower TGs and cardiovascular risk include existing options including statins, fibrates, thiazolidinediones, omega-3-fatty acids, and niacin, as well as an antisense oligonucleotide targeting APOC3 currently in clinical development.
Abstract: Triglyceride-rich lipoproteins (TRLs) are causal contributors to the risk of developing coronary artery disease (CAD). Apolipoprotein C-III (apoC-III) is a component of TRLs that elevates plasma triglycerides (TGs) through delaying the lipolysis of TGs and the catabolism of TRL remnants. Recent human genetics approaches have shown that heterozygous loss-of-function mutations in APOC3, the gene encoding apoC-III, lower plasma TGs and protect from CAD. This observation has spawned new interest in therapeutic efforts to target apoC-III. Here, we briefly review both currently available as well as developing therapies for reducing apoC-III levels and function to lower TGs and cardiovascular risk. These therapies include existing options including statins, fibrates, thiazolidinediones, omega-3-fatty acids, and niacin, as well as an antisense oligonucleotide targeting APOC3 currently in clinical development. We review the mechanisms of action by which these drugs reduce apoC-III and the current understanding of how reduction in apoC-III may impact CAD risk.

Journal ArticleDOI
TL;DR: Recent advances in the understanding of the biologic process of atherosclerotic calcification as well as some of the molecular imaging tools used to assess it are summarized.
Abstract: Calcification of atherosclerotic lesions was long thought to be an age - related, passive process, but increasingly data has revealed that atherosclerotic calcification is a more active process, involving complex signaling pathways and bone-like genetic programs. Initially, imaging of atherosclerotic calcification was limited to gross assessment of calcium burden, which is associated with total atherosclerotic burden and risk of cardiovascular mortality and of all cause mortality. More recently, sophisticated molecular imaging studies of the various processes involved in calcification have begun to elucidate information about plaque calcium composition and consequent vulnerability to rupture, leading to hard cardiovascular events like myocardial infarction. As such, there has been renewed interest in imaging calcification to advance risk assessment accuracy in an evolving era of precision medicine. Here we summarize recent advances in our understanding of the biologic process of atherosclerotic calcification as well as some of the molecular imaging tools used to assess it.

Journal ArticleDOI
TL;DR: The currently available literature on thyromimetics investigated for the treatment of dyslipidemia, their rise, their downfall and the challenges for the development of novel agents are reviewed.
Abstract: The association between thyroid hormone status and plasma levels of low-density lipoprotein cholesterol has raised the awareness for the development of thyroid hormone mimetics as lipid-lowering agents. The discovery of the two main types of thyroid hormone receptors (α and β) as well as the development of novel combinatorial chemistry providing organ specificity has drastically improved the selectivity of these compounds. In the past decades, several thyroid hormone mimetics have been investigated with the purpose of lowering low-density lipoprotein cholesterol levels. However, until now, none of the thyromimetics reached the stage of completing a phase III clinical trial without deleterious side effects. Here, we review the currently available literature on thyromimetics investigated for the treatment of dyslipidemia, their rise, their downfall and the challenges for the development of novel agents.

Journal ArticleDOI
TL;DR: The updated American College of Cardiology/American Heart Association and National Lipid Association guidelines on lipid treatment are discussed, both of which endorse the importance of shared decision making and patient-centered care.
Abstract: Statin therapy is the pharmacologic foundation of cholesterol treatment and the most common class of medication prescribed in the USA. The clinical benefits of statins and their favorable side effect profile have been well established for atherosclerotic cardiovascular disease prevention. With new guidelines on the treatment of dyslipidemia being published in the last several years, a greater percentage of the population now appears eligible for statin therapy. In this review, we discuss the updated American College of Cardiology/American Heart Association and National Lipid Association guidelines on lipid treatment, both of which endorse the importance of shared decision making and patient-centered care. We discuss factors beyond traditional risk factors that may be useful in refining risk-based decision making. Furthermore, we summarize the available statins, their potential benefits and limitations, and recent evidence on safety and tolerability.

Journal ArticleDOI
TL;DR: High quality, randomized data supports the efficacy of the WATCHMAN device for stroke prevention in patients with AF andRandomized data examining surgical LAA closure and epicardial closure with the LARIAT device are lacking.
Abstract: Purpose of Review Anticoagulant therapy effectively reduces the incidence of stroke in patients with atrial fibrillation (AF) but is underutilized and frequently contraindicated. The left atrial appendage (LAA) is the primary site of thrombus formation in AF patients. Surgical and percutaneous appendage closure has been evaluated as a site-specific therapy to reduce systemic thromboembolism.

Journal ArticleDOI
TL;DR: These imaging modalities, intravascular ultrasound (IVUS), optical coherence tomography (OCT), and near-infrared spectroscopy (NIRS), have provided a method to study plaques and introduced the concept of plaque vulnerability and are being increasingly used for percutaneous coronary intervention (PCI) optimization.
Abstract: The development of multiple diagnostic intracoronary imaging modalities has increased our understanding of coronary atherosclerotic disease. These imaging modalities, intravascular ultrasound (IVUS), optical coherence tomography (OCT), and near-infrared spectroscopy (NIRS), have provided a method to study plaques and introduced the concept of plaque vulnerability. They are being increasingly used for percutaneous coronary intervention (PCI) optimization and are invaluable tools in research studying the pathophysiology of acute coronary syndrome (ACS), in-stent thrombosis and in-stent restenosis. IVUS has the ability to visualize the intracoronary lumen and the vessel wall and can be used to detect early atherosclerotic disease even in the setting of positive arterial remodeling. Studies supporting the use of IVUS to optimize stent deployment and apposition have shown a significant reduction in cardiovascular events. OCT provides even higher resolution imaging and near microscopic detail of plaques, restenoses, and thromboses; thus, it can identify the etiology of ACS. Ongoing trials are evaluating the role of OCT in PCI and using OCT to study stent endothelialization and neointimal proliferation. NIRS is a modality capable of localizing and quantifying lipid core burden. It is usually combined with IVUS and is used to characterize plaque composition. The benefits of NIRS in the setting of ACS have been limited to case reports and series. The utilization of all these intracoronary imaging modalities will continue to expand as their indications for clinical use and research grow. Studies to support their use for PCI optimization resulting in improved outcomes with potential to prevent downstream events are ongoing.