New Advances in Dyslipidemia

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiovascular Medicine".

Deadline for manuscript submissions: closed (20 August 2023) | Viewed by 58370

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Special Issue Editor


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Guest Editor
Division of Cardiology, University of California, Irvine, CA 92697, USA
Interests: preventive cardiology; cardiovascular epidemiology; dyslipidemia; diabetes; subclinical atherosclerosis

Special Issue Information

Dear Colleagues,

More than 50 years ago, the Framingham Heart Study and other major epidemiologic studies identified total cholesterol, and later low-density lipoprotein-cholesterol (and inversely, high-density lipoprotein-cholesterol) as important risk factors for ASCVD. More recently, lipoprotein(a) has been confirmed as a genetic risk factor for ASCVD. While statin therapies have become the standard of care in the past quarter century, the advent of newer non-statin therapies offers a significant opportunity to address residual ASCVD risk beyond statin therapy.  

Dyslipidemia is an important risk factor for atherosclerotic cardiovascular disease (ASCVD).  However, despite current traditional therapies (e.g., statins), significant residual risk for ASCVD risk remains, warranting the need to better understand newer therapeutic options for reducing such risk.  This Special Issue will address newer concepts in the evaluation and management of dyslipidemia, including the rationale for newer goals in lipid treatment given recent international guidelines, global trends in the epidemiology of dyslipidemia, newer concepts and therapies in the evaluation and management of familial hypercholesterolemia, newer therapies for LDL-C lowering beyond statin therapy, the status of lipoprotein(a) as a causal risk factor and newer therapeutic approaches to address it, the evaluation and management of dyslipidemia in children, newer and emerging therapies for hypertriglyceridemia, and nutraceuticals to address dyslipidemia in COVID-19 patients.

This Special Issue will discuss the latest clinical trials and other research developments regarding newer and emerging therapies for the management of dyslipidemia to reduce ASCVD residual risk. The hope is to provide clinicians with the latest information on key aspects of the evaluation and treatment of dyslipidemia, including newer non-statin approaches for reducing ASCVD residual risk, such as settings of elevated LDL-C, lipoprotein(a), and familial hypercholesterolemia.

We are seeking papers on novel topics that help advance the evaluation and management of different aspects of dyslipidemia.

Prof. Dr. Nathan D. Wong
Guest Editor

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Keywords

  • dyslipidemia
  • cardiovascular disease
  • prevention
  • treatment
  • risk factors

Published Papers (13 papers)

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Editorial

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3 pages, 185 KiB  
Editorial
Is Lipoprotein(a) the Most Important Predictor of Residual Atherosclerotic Cardiovascular Disease Risk?
by Nathan D. Wong
J. Clin. Med. 2022, 11(15), 4380; https://doi.org/10.3390/jcm11154380 - 28 Jul 2022
Viewed by 1480
Abstract
Lipoprotein(a) is an underrecognized, but significant genetic risk factor for atherosclerotic cardiovascular disease (ASCVD), shown to be causal from data from prospective epidemiologic studies, Mendelian randomization, and genome wide association studies [...] Full article
(This article belongs to the Special Issue New Advances in Dyslipidemia)

Research

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0 pages, 586 KiB  
Article
Dyslipidemia Treatment and Lipid Control in US Adults with Diabetes by Sociodemographic and Cardiovascular Risk Groups in the NIH Precision Medicine Initiative All of Us Research Program
by Meleeka Akbarpour, Divya Devineni, Yufan Gong and Nathan D. Wong
J. Clin. Med. 2023, 12(4), 1668; https://doi.org/10.3390/jcm12041668 - 20 Feb 2023
Cited by 3 | Viewed by 2819 | Correction
Abstract
Real-world data on lipid levels and treatment among adults with diabetes mellitus (DM) are relatively limited. We studied lipid levels and treatment status in patients with DM across cardiovascular disease (CVD) risk groups and sociodemographic factors. In the All of Us Research Program, [...] Read more.
Real-world data on lipid levels and treatment among adults with diabetes mellitus (DM) are relatively limited. We studied lipid levels and treatment status in patients with DM across cardiovascular disease (CVD) risk groups and sociodemographic factors. In the All of Us Research Program, we categorized DM as (1) moderate risk (≤1 CVD risk factor), (2) high risk (≥2 CVD risk factors), and (3) DM with atherosclerotic CVD (ASCVD). We examined the use of statin and non-statin therapy as well as LDL-C and triglyceride levels. We studied 81,332 participants with DM, which included 22.3% non-Hispanic Black and 17.2% Hispanic. A total of 31.1% had ≤1 DM risk factor, 30.3% had ≥2 DM risk factors, and 38.6% of participants had DM with ASCVD. Only 18.2% of those with DM and ASCVD were on high-intensity statins. Overall, 5.1% were using ezetimibe and 0.6% PCSK9 inhibitors. Among those with DM and ASCVD, only 21.1% had LDL-C < 70 mg/dL. Overall, 1.9% of participants with triglycerides ≥ 150 mg/dL were on icosapent ethyl. Those with DM and ASCVD were more likely to be on high-intensity statins, ezetimibe, and icosapent ethyl. Guideline-recommended use of high-intensity statins and non-statin therapy among our higher risk DM patients is lacking, with LDL-C inadequately controlled. Full article
(This article belongs to the Special Issue New Advances in Dyslipidemia)
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Review

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16 pages, 3125 KiB  
Review
Evolution of More Aggressive LDL-Cholesterol Targets and Therapies for Cardiovascular Disease Prevention
by Jeffrey E. Jones, Kevin S. Tang, Ailin Barseghian and Nathan D. Wong
J. Clin. Med. 2023, 12(23), 7432; https://doi.org/10.3390/jcm12237432 - 30 Nov 2023
Cited by 2 | Viewed by 3796
Abstract
Over the last half-century, discussions on the exact targets for low-density lipoprotein cholesterol (LDL-C) reduction have evolved towards a more aggressive approach with lower LDL-C targets, particularly for high-risk patients with pre-existing atherosclerotic cardiovascular disease (ASCVD). A wealth of cardiovascular outcome trials have [...] Read more.
Over the last half-century, discussions on the exact targets for low-density lipoprotein cholesterol (LDL-C) reduction have evolved towards a more aggressive approach with lower LDL-C targets, particularly for high-risk patients with pre-existing atherosclerotic cardiovascular disease (ASCVD). A wealth of cardiovascular outcome trials have shown the efficacy of statin therapy in general, as well as the incremental impact of high-intensity statin therapy in particular. More recent trials have further demonstrated the impact of non-statin therapies, including ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, and, most recently, bempedoic acid, on reducing ASCVD outcomes. The availability of these and other newer therapies has prompted clinicians to strive for lower LDL-C targets to address residual ASCVD risk after statin therapy. This paper will provide an overview of the historical trends in lipid management and therapeutics and review the current state of evidence for lower LDL-C targets in clinical guidelines and recommendations. Full article
(This article belongs to the Special Issue New Advances in Dyslipidemia)
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39 pages, 598 KiB  
Review
Lipid-Lowering Nutraceuticals for an Integrative Approach to Dyslipidemia
by Brian Cheung, Geeta Sikand, Elizabeth H. Dineen, Shaista Malik and Ailin Barseghian El-Farra
J. Clin. Med. 2023, 12(10), 3414; https://doi.org/10.3390/jcm12103414 - 11 May 2023
Cited by 4 | Viewed by 3539
Abstract
Dyslipidemia is a treatable risk factor for atherosclerotic cardiovascular disease that can be addressed through lifestyle changes and/or lipid-lowering therapies. Adherence to statins can be a clinical challenge in some patients due to statin-associated muscle symptoms and other side effects. There is a [...] Read more.
Dyslipidemia is a treatable risk factor for atherosclerotic cardiovascular disease that can be addressed through lifestyle changes and/or lipid-lowering therapies. Adherence to statins can be a clinical challenge in some patients due to statin-associated muscle symptoms and other side effects. There is a growing interest in integrative cardiology and nutraceuticals in the management of dyslipidemia, as some patients desire or are actively seeking a more natural approach. These agents have been used in patients with and without established atherosclerotic cardiovascular disease. We provide an updated review of the evidence on many new and emerging nutraceuticals. We describe the mechanism of action, lipid-lowering effects, and side effects of many nutraceuticals, including red yeast rice, bergamot and others. Full article
(This article belongs to the Special Issue New Advances in Dyslipidemia)
16 pages, 1745 KiB  
Review
Current and Emerging Therapies for Atherosclerotic Cardiovascular Disease Risk Reduction in Hypertriglyceridemia
by Reed Mszar, Sarah Bart, Alexander Sakers, Daniel Soffer and Dean G. Karalis
J. Clin. Med. 2023, 12(4), 1382; https://doi.org/10.3390/jcm12041382 - 9 Feb 2023
Cited by 4 | Viewed by 3846
Abstract
Hypertriglyceridemia (HTG) is a prevalent medical condition in patients with cardiometabolic risk factors and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), if left undiagnosed and undertreated. Current guidelines identify HTG as a risk-enhancing factor and, as a result, recommend [...] Read more.
Hypertriglyceridemia (HTG) is a prevalent medical condition in patients with cardiometabolic risk factors and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), if left undiagnosed and undertreated. Current guidelines identify HTG as a risk-enhancing factor and, as a result, recommend clinical evaluation and lifestyle-based interventions to address potential secondary causes of elevated triglyceride (TG) levels. For individuals with mild to moderate HTG at risk of ASCVD, statin therapy alone or in combination with other lipid-lowering medications known to decrease ASCVD risk are guideline-endorsed. In addition to lifestyle modifications, patients with severe HTG at risk of acute pancreatitis may benefit from fibrates, mixed formulation omega-3 fatty acids, and niacin; however, evidence does not support their use for ASCVD risk reduction in the contemporary statin era. Novel therapeutics including those that target apoC-III and ANGPTL3 have shown to be safe, well-tolerated, and effective for lowering TG levels. Given the growing burden of cardiometabolic disease and risk factors, public health and health policy strategies are urgently needed to enhance access to effective pharmacotherapies, affordable and nutritious food options, and timely health care services. Full article
(This article belongs to the Special Issue New Advances in Dyslipidemia)
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13 pages, 1271 KiB  
Review
Evinacumab, an ANGPTL3 Inhibitor, in the Treatment of Dyslipidemia
by Bożena Sosnowska, Weronika Adach, Stanisław Surma, Robert S. Rosenson and Maciej Banach
J. Clin. Med. 2023, 12(1), 168; https://doi.org/10.3390/jcm12010168 - 25 Dec 2022
Cited by 18 | Viewed by 4442
Abstract
Familial hypercholesterolemia (FH) is an inherited disorder. The level of low-density lipoprotein cholesterol (LDL-C) in patients with homozygous FH can be twice as high as that in patients with heterozygous FH. The inhibition of ANGPTL3 shows an important therapeutic approach in reducing LDL-C [...] Read more.
Familial hypercholesterolemia (FH) is an inherited disorder. The level of low-density lipoprotein cholesterol (LDL-C) in patients with homozygous FH can be twice as high as that in patients with heterozygous FH. The inhibition of ANGPTL3 shows an important therapeutic approach in reducing LDL-C and triglycerides (TG) levels and, thus, is a potentially effective strategy in the treatment of FH. Evinacumab is a monoclonal antibody inhibiting circulating ANGPTL3, available under the trade name Evkeeza® for the treatment of homozygous FH. It was reported that evinacumab is effective and safe in patients with homozygous and heterozygous FH, as well as resistant hypercholesterolemia and hypertriglyceridemia. This paper summarizes existing knowledge on the role of ANGPTL3, 4, and 8 proteins in lipoprotein metabolism, the findings from clinical trials with evinacumab, a fully human ANGPTL3 mAb, and the place for this new agent in lipid-lowering therapy. Full article
(This article belongs to the Special Issue New Advances in Dyslipidemia)
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12 pages, 244 KiB  
Review
Comparison of Current International Guidelines for the Management of Dyslipidemia
by Sevda Aygun and Lale Tokgozoglu
J. Clin. Med. 2022, 11(23), 7249; https://doi.org/10.3390/jcm11237249 - 6 Dec 2022
Cited by 19 | Viewed by 6915
Abstract
The dyslipidemia guidelines of the three major societies have been revised recently in light of new evidence. LDL-C is the primary target in the ESC, AHA/ACC/Multisociety and Canadian Cardiovascular Society (CCS) guidelines. These guidelines uniformly recommend intensifying lipid-lowering treatment with increased risk; however, [...] Read more.
The dyslipidemia guidelines of the three major societies have been revised recently in light of new evidence. LDL-C is the primary target in the ESC, AHA/ACC/Multisociety and Canadian Cardiovascular Society (CCS) guidelines. These guidelines uniformly recommend intensifying lipid-lowering treatment with increased risk; however, the risk estimation systems are different across the guidelines. The ESC guidelines have LDL-C goals which have become more stringent over the years and advocate the use of statin and, if necessary, non-statin therapies to obtain these goals. AHA/ACC/Multisociety guidelines have LDL-C thresholds and advocate combination therapy less liberally and for selected patients. All three guidelines acknowledge the importance of shared decision making. Despite some divergent approaches and recommendations, the main principles and messages are the same across the guidelines. To combat the epidemic of cardiovascular disease, our focus should be not on the differences but on implementing the guidelines in our region. Full article
(This article belongs to the Special Issue New Advances in Dyslipidemia)
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15 pages, 555 KiB  
Review
New Trends and Therapies for Familial Hypercholesterolemia
by Fahad Alnouri and Raul D. Santos
J. Clin. Med. 2022, 11(22), 6638; https://doi.org/10.3390/jcm11226638 - 9 Nov 2022
Cited by 4 | Viewed by 6584
Abstract
Familial hypercholesterolemia (FH) is associated with an elevated risk of atherosclerosis. The finding of monogenic defects indicates higher atherosclerotic risk in comparison with hypercholesterolemia of other etiologies. However, in heterozygous FH, cardiovascular risk is heterogeneous and depends not only on high cholesterol levels [...] Read more.
Familial hypercholesterolemia (FH) is associated with an elevated risk of atherosclerosis. The finding of monogenic defects indicates higher atherosclerotic risk in comparison with hypercholesterolemia of other etiologies. However, in heterozygous FH, cardiovascular risk is heterogeneous and depends not only on high cholesterol levels but also on the presence of other biomarkers and genes. The development of atherosclerosis risk scores specific for heterozygous FH and the use of subclinical coronary atherosclerosis imaging help with identifying higher-risk individuals who may benefit from further cholesterol lowering with PCSK9 inhibitors. There is no question about the extreme high risk in homozygous FH, and intensive LDL-cholesterol-lowering therapy must be started as soon as possible. These patients have gained life free of events in comparison with the past, but a high atherosclerosis residual risk persists. Furthermore, there is also the issue of aortic and supra-aortic valve disease development. Newer therapies such as inhibitors of microsomal transfer protein and angiopoietin-like protein 3 have opened the possibility of LDL-cholesterol normalization in homozygous FH and may provide an alternative to lipoprotein apheresis for these patients. Gene-based therapies may provide more definite solutions for lowering high LDL cholesterol and consequent atherosclerosis risk for people with FH. Full article
(This article belongs to the Special Issue New Advances in Dyslipidemia)
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12 pages, 268 KiB  
Review
Screening and Management of Dyslipidemia in Children and Adolescents
by Juliette M. Schefelker and Amy L. Peterson
J. Clin. Med. 2022, 11(21), 6479; https://doi.org/10.3390/jcm11216479 - 31 Oct 2022
Cited by 8 | Viewed by 3764
Abstract
This review provides an overview of pediatric dyslipidemia emphasizing screening and treatment recommendations. The presence of risk factors for cardiovascular disease in childhood poses significant risk for the development of atherosclerotic cardiovascular disease and cardiovascular events in adulthood. While atherogenic dyslipidemia is the [...] Read more.
This review provides an overview of pediatric dyslipidemia emphasizing screening and treatment recommendations. The presence of risk factors for cardiovascular disease in childhood poses significant risk for the development of atherosclerotic cardiovascular disease and cardiovascular events in adulthood. While atherogenic dyslipidemia is the most common dyslipidemia seen in children and can be suspected based on the presence of risk factors (such as obesity), familial hypercholesterolemia can be found in children with no risk factors. As such, universal cholesterol screening is recommended to identify children with these disorders in order to initiate treatment and reduce the risk of future cardiovascular disease. Treatment of pediatric dyslipidemia begins with lifestyle modifications, but primary genetic dyslipidemias may require medications such as statins. As pediatric lipid disorders often have genetic or familial components, it is important that all physicians are aware that cardiovascular risk begins in childhood, and can both identify these disorders in pediatric patients and counsel their adult patients with dyslipidemia to have their children screened. Full article
(This article belongs to the Special Issue New Advances in Dyslipidemia)
13 pages, 2095 KiB  
Review
Global Trends in the Epidemiology and Management of Dyslipidemia
by Tianxiao Liu, Dong Zhao and Yue Qi
J. Clin. Med. 2022, 11(21), 6377; https://doi.org/10.3390/jcm11216377 - 28 Oct 2022
Cited by 14 | Viewed by 6645
Abstract
Dyslipidemia, especially a circulating non-optimal level of cholesterol, is one of the most important risk factors for atherosclerotic cardiovascular disease (ASCVD), which accounts for the most deaths worldwide. Maintaining a healthy level of blood cholesterol is an important prevention strategy for ASCVD, through [...] Read more.
Dyslipidemia, especially a circulating non-optimal level of cholesterol, is one of the most important risk factors for atherosclerotic cardiovascular disease (ASCVD), which accounts for the most deaths worldwide. Maintaining a healthy level of blood cholesterol is an important prevention strategy for ASCVD, through lifestyle intervention or cholesterol-lowering therapy. Over the past three decades, the epidemiology and management of dyslipidemia has changed greatly in many countries. Therefore, it is necessary to understand the current epidemiologic features of dyslipidemia and challenges from a global perspective. Full article
(This article belongs to the Special Issue New Advances in Dyslipidemia)
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19 pages, 2351 KiB  
Review
Lipoprotein(a): Evidence for Role as a Causal Risk Factor in Cardiovascular Disease and Emerging Therapies
by Harpreet S. Bhatia and Michael J. Wilkinson
J. Clin. Med. 2022, 11(20), 6040; https://doi.org/10.3390/jcm11206040 - 13 Oct 2022
Cited by 18 | Viewed by 6062
Abstract
Lipoprotein(a) (Lp(a)) is an established risk factor for multiple cardiovascular diseases. Several lines of evidence including mechanistic, epidemiologic, and genetic studies support the role of Lp(a) as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis/calcific aortic valve disease (AS/CAVD). [...] Read more.
Lipoprotein(a) (Lp(a)) is an established risk factor for multiple cardiovascular diseases. Several lines of evidence including mechanistic, epidemiologic, and genetic studies support the role of Lp(a) as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis/calcific aortic valve disease (AS/CAVD). Limited therapies currently exist for the management of risk associated with elevated Lp(a), but several targeted therapies are currently in various stages of clinical development. In this review, we detail evidence supporting Lp(a) as a causal risk factor for ASCVD and AS/CAVD, and discuss approaches to managing Lp(a)-associated risk. Full article
(This article belongs to the Special Issue New Advances in Dyslipidemia)
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18 pages, 1740 KiB  
Review
Role of Lipid-Lowering Therapy in Peripheral Artery Disease
by Agastya D. Belur, Aangi J. Shah, Salim S. Virani, Mounica Vorla and Dinesh K. Kalra
J. Clin. Med. 2022, 11(16), 4872; https://doi.org/10.3390/jcm11164872 - 19 Aug 2022
Cited by 11 | Viewed by 2860
Abstract
Atherosclerosis is a multifactorial, lipoprotein-driven condition that leads to plaque formation within the arterial tree, leading to subsequent arterial stenosis and thrombosis that accounts for a large burden of cardiovascular morbidity and mortality globally. Atherosclerosis of the lower extremities is called peripheral artery [...] Read more.
Atherosclerosis is a multifactorial, lipoprotein-driven condition that leads to plaque formation within the arterial tree, leading to subsequent arterial stenosis and thrombosis that accounts for a large burden of cardiovascular morbidity and mortality globally. Atherosclerosis of the lower extremities is called peripheral artery disease and is a major cause of loss in mobility, amputation, and critical limb ischemia. Peripheral artery disease is a common condition with a gamut of clinical manifestations that affects an estimated 10 million people in the United States of America and 200 million people worldwide. The role of apolipoprotein B-containing lipoproteins, such as LDL and remnant lipoproteins in the development and progression of atherosclerosis, is well-established. The focus of this paper is to review existing data on lipid-lowering therapies in lower extremity atherosclerotic peripheral artery disease. Full article
(This article belongs to the Special Issue New Advances in Dyslipidemia)
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11 pages, 286 KiB  
Review
Newer and Emerging LDL-C Lowering Agents and Implications for ASCVD Residual Risk
by Rishi Rikhi and Michael D. Shapiro
J. Clin. Med. 2022, 11(15), 4611; https://doi.org/10.3390/jcm11154611 - 8 Aug 2022
Cited by 7 | Viewed by 2676
Abstract
Multiple lines of evidence demonstrate that low-density lipoprotein-cholesterol causes atherosclerotic cardiovascular disease. Thus, targeting and lowering low-density lipoprotein-cholesterol is the principal strategy to reduce cardiovascular disease risk in primary and secondary prevention. Statin therapy is the foundation of lipid-lowering treatment, but adherence rates [...] Read more.
Multiple lines of evidence demonstrate that low-density lipoprotein-cholesterol causes atherosclerotic cardiovascular disease. Thus, targeting and lowering low-density lipoprotein-cholesterol is the principal strategy to reduce cardiovascular disease risk in primary and secondary prevention. Statin therapy is the foundation of lipid-lowering treatment, but adherence rates are low, and many individuals do not attain target low-density lipoprotein-cholesterol values. Additionally, most statin-treated patients are still at considerable atherosclerotic cardiovascular disease risk, emphasizing the need for more aggressive low-density lipoprotein-cholesterol-lowering therapies. The purpose of this review is to discuss new and emerging approaches to further lower low-density lipoprotein-cholesterol, including inhibition of ATP-citrate lyase, proprotein convertase subtilisin-kexin type 9, angiopoietin-related protein 3, and cholesteryl ester transfer protein. Full article
(This article belongs to the Special Issue New Advances in Dyslipidemia)
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