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Management of Dyslipidaemias: Enhancing Lipid Modification to Reduce Cardiovascular Risk
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Management of Dyslipidaemias: Enhancing Lipid Modification to Reduce Cardiovascular Risk

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

Deadline for manuscript submissions: 20 June 2025 | Viewed by 16214

Special Issue Editors

Dr. Daniel Gaudet

E-Mail Website
Guest Editor
Clinical Lipidology and Rare Lipid Disorders Unit, Department of Medicine, Université de Montréal Community Gene Medicine Center, Lipid Clinic Chicoutimi Hospital and ECOGENE-21 Clinical and Translational Research Center, Chicoutimi, QC G7H 7K9, Canada
Interests: management of dyslipidemia and associated risks
Dr. Etienne Khoury

E-Mail Website
Guest Editor
Community Gene Medicine Center, Department of Medicine, Université de Montréal, Chicoutimi, QC G7H 7K9, Canada
Interests: management of dyslipidemia and associated risks

Special Issue Information

Dear Colleagues,

Cardiovascular disease (CVD) is a leading cause of death in several developed countries, with low-density lipoproteins (LDL), among other atherogenic lipoproteins such as lipoprotein remnants (e.g., very low-density lipoproteins (VLDL) and chylomicron remnants), being considered as the key causal factors or contributors to the development of atherosclerosis. 

Continued research and new observational studies as well as interventional trials have revealed that beyond LDL-Cholesterol (LDL-C) levels, the identification of markers (biological, environmental, and genetic) associated with remnant metabolism could enhance CV risk prediction and optimize treatment strategies. However, many conditions of rare and severe causes of atherogenic lipid disorders, such as homozygous familial hypercholesterolemia (HoFH), refractory hypercholesterolemia and severe hypertriglyceridemia, pose significant challenges for lipid management. Patients with these conditions cannot attain the desired thresholds of lipid parameters and continue to experience CV events, despite being treated with maximally tolerated lipid-lowering therapies (LLT). 

LLTs are evolving rapidly, and several agents have now included new inhibitors such as PCSK9, ANGPLT3 and APOC3 as targets. Future directions might also involve additional therapies derived from new mechanisms of action or signaling pathways that will potentially allow for the development of new classes of drugs targeting lipoprotein metabolism for CVD prevention. The impact of other fat-related disorders, such as non-alcoholic steatohepatitis (NASH), which is shown to be associated with increased risk of CV events, is also worth mentioning; however, the underlying mechanisms between NASH and CVD in respect to their targeted interventions still remain unknown.

We take this opportunity to extend an invitation to researchers and clinical practitioners to contribute to a Special Issue of the Journal of Clinical Medicine titled, ‘Management of Dyslipidemia: Enhancing Lipid Modification to Reduce Cardiovascular Risk.’ We will accept submissions of original research, comprehensive review articles, and innovative protocols that highlight the recent research progress, including, but not limited to, novel mechanistic pathways and/or the identification of emerging avenues for therapies aimed at refining CV risk management.

Dr. Daniel Gaudet
Dr. Etienne Khoury
Guest Editors

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Keywords

  • cardiovascular disease
  • dyslipidemia
  • lipoprotein remnant
  • emerging lipid-lowering therapies
  • rare and severe causes of atherogenic lipid disorders
  • cardiovascular risk-related biomarkers
  • drug safety and efficacy

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Published Papers (9 papers)

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Research

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15 pages, 249 KiB  
Article
Is Insulin Resistance an Independent Predictor of Atherosclerosis?
by Małgorzata Landowska, Bernadetta Kałuża, Cezary Watała, Emilia Babula, Aleksandra Żuk-Łapan, Kinga Woźniak, Aleksandra Kargul, Jonasz Jurek, Tomasz Korcz, Małgorzata Cicha-Brzezińska and Edward Franek
J. Clin. Med. 2025, 14(3), 969; https://doi.org/10.3390/jcm14030969 (registering DOI) - 3 Feb 2025
Abstract
Background: Insulin resistance (IR) is a condition that precedes the onset of type 2 diabetes mellitus (T2DM), which is regarded as an established risk factor for atherosclerosis (AS). Considering that the same metabolic changes as those caused by IR are evidenced to promote [...] Read more.
Background: Insulin resistance (IR) is a condition that precedes the onset of type 2 diabetes mellitus (T2DM), which is regarded as an established risk factor for atherosclerosis (AS). Considering that the same metabolic changes as those caused by IR are evidenced to promote the development of AS, we investigated whether IR estimated by the homeostasis model assessment of IR (HOMA-IR) could predict the occurrence of preclinical AS. Methods: The study participants were divided into two groups based on the presence of IR diagnosed during the baseline hospitalization and defined as a HOMA-IR value equal to or higher than 2.5. After a follow-up period of at least four years, a total of 79 (n = 79) were prospectively assessed in terms of the presence of preclinical AS, determined by either an abnormally low ankle–brachial index (ABI) (ABI < 0.9) or an increased carotid intima media thickness (CIMT) (CIMT > 1 mm). Results: Using the multivariate logistic regression analysis, it was demonstrated that the HOMA-IR was associated with an abnormally low ABI (odds ratio: 1.609, 95% confidence interval (CI): [1.041–2.487], p = 0.032). The Cox regression model revealed that the HOMA-IR was a predictor of both an abnormal ABI (hazard ratio: 1.435, CI: [1.076–1.913], p = 0.014) and increased CIMT (hazard ratio: 1.419, CI: [1.033–1.948], p = 0.031), independently of age, sex, dyslipidemia, smoking, triglycerides (TG), low-density lipoproteins (LDL), high-density lipoproteins (HDL), and total cholesterol levels. Conclusions: IR, as estimated by the HOMA-IR, may be considered as a predictor of preclinical AS, independently of cardiovascular risk factors. Full article
(This article belongs to the Special Issue Management of Dyslipidaemias: Enhancing Lipid Modification to Reduce Cardiovascular Risk)
12 pages, 228 KiB  
Article
Statin Use and Major Adverse Cardiovascular Events Among Patients with Ischemic Heart Diseases: A Multi-Center Retrospective Study
by Awatif Hafiz, Sarah Aljohani, Hussam Kutbi, Nayyara Fatani, Lama Alkhathran, Majd Alyaqub, Meshal S. Alhamed, Abdulrhaman O. Alhaqbani, Abdulrahman A. Alhadlaq, Mohammed A. Alsalman, Majed S. Al Yami and Omar A. Almohammed
J. Clin. Med. 2025, 14(3), 908; https://doi.org/10.3390/jcm14030908 - 30 Jan 2025
Viewed by 342
Abstract
Objective: The objective of this study was to evaluate the effects of adherence to the ACC/AHA 2018 dyslipidemia guidelines on patient management of lipid-lowering therapy in patients with ischemic heart diseases (IHD) and its correlation with major adverse cardiovascular events (MACEs), including [...] Read more.
Objective: The objective of this study was to evaluate the effects of adherence to the ACC/AHA 2018 dyslipidemia guidelines on patient management of lipid-lowering therapy in patients with ischemic heart diseases (IHD) and its correlation with major adverse cardiovascular events (MACEs), including non-fatal MI, stroke, death, hospitalization for revascularization, and peripheral arterial disease. Methods: A multi-center retrospective observational study was conducted in patients with IHD between January 2019 and December 2020, who were followed for two years. The primary objective was to assess statin utilization and adherence to the 2018 ACC/AHA guidelines and the associated influence on MACE outcomes. Inferential statistical analyses, including chi-square tests and the Mann–Whitney test, were conducted to assess the associations between adherence to the guidelines, MACE rates, and LDL-C goal achievement. Results: The study included 1011 patients with ischemic heart disease (IHD), predominantly male (78.2%), with a mean age of 59 ± 10.9 years. Non-adherent patients had higher baseline LDL-C levels (3.0 ± 1.1 mmol/L vs. 2.7 ± 1.2 mmol/L; p = 0.0005), while adherent patients were more likely to be on cardiovascular medications, including statins (78.4% vs. 57.4%), aspirin (74.2% vs. 56.3%), and P2Y12 inhibitors (69.5% vs. 48.4%), compared to non-adherent patients. Adherence was associated with lower non-fatal MI rates (9.3% vs. 21.1%, p < 0.0001) and fewer revascularizations (9.3% vs. 16.8%; p = 0.0024). Additionally, 49.2% of adherent patients achieved target LDL-C goals, compared to 30.5% of the non-adherent patients (p < 0.0001). Notably, there were no significant differences in stroke, peripheral arterial disease, or mortality rates. Conclusions: The achievement of target LDL-C goals and reduced MACEs was observed with adherence to the 2018 ACC/AHA dyslipidemia guidelines. However, lipid management in IHD patients remains sub-optimal, highlighting opportunities for further enhancement. Full article
(This article belongs to the Special Issue Management of Dyslipidaemias: Enhancing Lipid Modification to Reduce Cardiovascular Risk)
13 pages, 1291 KiB  
Article
The Dynamics of Cardiovascular Risk—An Analysis of the Prospective Urban Rural Epidemiology (PURE) Poland Cohort Study
by Paweł Lubieniecki, Łukasz Lewandowski, Maria Wołyniec, Katarzyna Połtyn-Zaradna, Katarzyna Zatońska and Andrzej Szuba
J. Clin. Med. 2024, 13(13), 3728; https://doi.org/10.3390/jcm13133728 - 26 Jun 2024
Viewed by 1278
Abstract
Background: The purpose of this study was to analyze the major cardiovascular risk (CVR) factors and their trends in the study population. Methods: The results of subjects in the Polish Prospective Urban and Rural Epidemiological Study (PURE) study group were interpreted. [...] Read more.
Background: The purpose of this study was to analyze the major cardiovascular risk (CVR) factors and their trends in the study population. Methods: The results of subjects in the Polish Prospective Urban and Rural Epidemiological Study (PURE) study group were interpreted. CVR was calculated for each participant according to the Systematic Coronary Risk Evaluation (SCORE2) scale or the Systematic Coronary Risk Evaluation–Older Persons (SCORE2–OP) scale. Data from the beginning of the analysis (2013) and nine years later (2022) were included. In addition, the use of lipid–lowering therapy (LLT) and meeting the low–density lipoprotein cholesterol (LDL–c) target criterion at the beginning and end of the study were analyzed. Results: Patients in the high and very high CVR groups who had abnormal LDL–c results accounted for 64% and 91% of their group in 2013 and 70% and 92% in 2022, respectively. Conclusions: Regardless of age, patients using LLT at the start of the analysis had a greater increase in future CVR, especially if they had lipid abnormalities at the start of the study. This may be due to reverse causality and multimorbidity in these patients, highlighting the importance of appropriate treatment of lipid abnormalities. Full article
(This article belongs to the Special Issue Management of Dyslipidaemias: Enhancing Lipid Modification to Reduce Cardiovascular Risk)
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10 pages, 632 KiB  
Article
Lipid-Lowering Therapy in PURE Poland Cohort Study
by Paweł Lubieniecki, Maria Wołyniec, Katarzyna Połtyn-Zaradna, Katarzyna Zatońska and Andrzej Szuba
J. Clin. Med. 2024, 13(1), 60; https://doi.org/10.3390/jcm13010060 - 22 Dec 2023
Cited by 2 | Viewed by 1112
Abstract
The aim of this study is to present data on the use of lipid-lowering therapy (LLT) in relation to calculated cardiovascular risk (CVR) and an additionally defined target LDL-C concentration. The cohort consisted of 1287 participants in the Polish edition of the Prospective [...] Read more.
The aim of this study is to present data on the use of lipid-lowering therapy (LLT) in relation to calculated cardiovascular risk (CVR) and an additionally defined target LDL-C concentration. The cohort consisted of 1287 participants in the Polish edition of the Prospective Urban and Rural Epidemiological Study (PURE). CVR was calculated for each participant using the SCORE2 or SCORE2-OP scale, and for patients with diabetes mellitus (DM), chronic kidney disease (CKD) or atherosclerotic cardiovascular disease (ASCVD) according to the respective criteria. In the cohort analysed, 107 of 212 people (50.5%) in the low cardiovascular risk (CVR) group, 284 of 414 people (68.6%) in the moderate CVR group, 562 of 612 people (91.8%) in the high CVR group and 48 of 49 people (98%) in the very high CVR group did not meet the target LDL-c criterion. Of those in the low CVR group, 86% of participants were not receiving lipid-lowering therapy (LLT); in the moderate CVR group, the proportion was 77.8%; in the high CVR group, 68.1% and in the very high CVR group, 75%. In each cardiovascular risk group, participants who did not meet the target LDL-c concentration criterion and did not take LLT made up the larger group. Full article
(This article belongs to the Special Issue Management of Dyslipidaemias: Enhancing Lipid Modification to Reduce Cardiovascular Risk)
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14 pages, 1256 KiB  
Article
Efficacy and Safety of Statin Treatment in Children with Familial Hypercholesterolemia: Outcomes of 20 Years of Experience
by Radosław Motkowski, Paweł Abramowicz, Jolanta Kubalska, Bożena Mikołuć and Jerzy Konstantynowicz
J. Clin. Med. 2023, 12(23), 7197; https://doi.org/10.3390/jcm12237197 - 21 Nov 2023
Cited by 1 | Viewed by 1982
Abstract
Background: The objective of this retrospective cohort study was to present the experience of 20-year-long comprehensive care of pediatric patients with familial hypercholesterolemia (FH) in a single academic center. Methods and Results: The study included 84 children aged 1–18 years with FH. For [...] Read more.
Background: The objective of this retrospective cohort study was to present the experience of 20-year-long comprehensive care of pediatric patients with familial hypercholesterolemia (FH) in a single academic center. Methods and Results: The study included 84 children aged 1–18 years with FH. For the whole study group, 535 medical visits were recorded. The mean follow-up period was 33.6 months. Molecular testing performed in 55 children (65%) provided genetic confirmation of the diagnosis in 36 children (43%). Twenty-seven children (32%) were treated pharmacologically with statins. Follow-up during the treatment averaged 29 months. Treatment with statins was associated with a mean reduction in total cholesterol and LDL-cholesterol levels of 24 and 33% from the baseline. Symptoms of statin intolerance occurred incidentally and did not require amendment in the treatment protocol. Significantly higher values of body weight, height, and BMI were found only among girls older than 10 years who were treated with statins. Conclusions: These data confirm a high efficacy and a good safety profile of statin treatment in children with FH, demonstrating no harm to physical development. However, there is a need for further cause-and-effect research regarding associations between long-term treatment with low-cholesterol, low-fat diets, statin therapy, and excessive weight gain. Full article
(This article belongs to the Special Issue Management of Dyslipidaemias: Enhancing Lipid Modification to Reduce Cardiovascular Risk)
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Review

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33 pages, 679 KiB  
Review
Nanotechnology and Artificial Intelligence in Dyslipidemia Management—Cardiovascular Disease: Advances, Challenges, and Future Perspectives
by Ewelina Młynarska, Kinga Bojdo, Hanna Frankenstein, Natalia Kustosik, Weronika Mstowska, Aleksandra Przybylak, Jacek Rysz and Beata Franczyk
J. Clin. Med. 2025, 14(3), 887; https://doi.org/10.3390/jcm14030887 - 29 Jan 2025
Viewed by 323
Abstract
This narrative review explores emerging technologies in dyslipidemia management, focusing on nanotechnology and artificial intelligence (AI). It examines the current treatment recommendations and contrasts them with the future prospects enabled by these innovations. Nanotechnology shows significant potential in enhancing drug delivery systems, enabling [...] Read more.
This narrative review explores emerging technologies in dyslipidemia management, focusing on nanotechnology and artificial intelligence (AI). It examines the current treatment recommendations and contrasts them with the future prospects enabled by these innovations. Nanotechnology shows significant potential in enhancing drug delivery systems, enabling more targeted and efficient lipid-lowering therapies. In parallel, AI offers advancements in diagnostics, cardiovascular risk prediction, and personalized treatment strategies. AI-based decision support systems and machine learning algorithms are particularly promising for analyzing large datasets and delivering evidence-based recommendations. Together, these technologies hold the potential to revolutionize dyslipidemia management, improving outcomes and optimizing patient care. In addition, this review covers key topics such as cardiovascular disease biomarkers and risk factors, providing insights into the current methods for assessing cardiovascular risk. It also discusses the current understanding of dyslipidemia, including pathophysiology and clinical management. Together, these insights and technologies hold the potential to revolutionize dyslipidemia management, improving outcomes and optimizing patient care. Full article
(This article belongs to the Special Issue Management of Dyslipidaemias: Enhancing Lipid Modification to Reduce Cardiovascular Risk)
21 pages, 359 KiB  
Review
The Hurdle of Access to Emerging Therapies and Potential Solutions in the Management of Dyslipidemias
by Brett S. Mansfield, Farzahna Mohamed, Miriam Larouche and Frederick J. Raal
J. Clin. Med. 2024, 13(14), 4160; https://doi.org/10.3390/jcm13144160 - 16 Jul 2024
Cited by 1 | Viewed by 1190
Abstract
This review explores the many barriers to accessing lipid-lowering therapies (LLTs) for the prevention and management of atherosclerotic cardiovascular disease (ASCVD). Geographical, knowledge, and regulatory barriers significantly impede access to LLTs, exacerbating disparities in healthcare infrastructure and affordability. We highlight the importance of [...] Read more.
This review explores the many barriers to accessing lipid-lowering therapies (LLTs) for the prevention and management of atherosclerotic cardiovascular disease (ASCVD). Geographical, knowledge, and regulatory barriers significantly impede access to LLTs, exacerbating disparities in healthcare infrastructure and affordability. We highlight the importance of policy reforms, including pricing regulations and reimbursement policies, for enhancing affordability and streamlining regulatory processes. Innovative funding models, such as value-based pricing and outcome-based payment arrangements, have been recommended to make novel LLTs more accessible. Public health interventions, including community-based programs and telemedicine, can be utilized to reach underserved populations and improve medication adherence. Education and advocacy initiatives led by patient advocacy groups and healthcare providers play a crucial role in raising awareness and empowering patients. Despite the barriers to access, novel LLTs present a big opportunity to reduce the burden of ASCVD, emphasizing the need for collaborative efforts among policymakers, healthcare providers, industry stakeholders, and patient advocacy groups to address these barriers to improve access to LLTs globally. Full article
(This article belongs to the Special Issue Management of Dyslipidaemias: Enhancing Lipid Modification to Reduce Cardiovascular Risk)
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18 pages, 319 KiB  
Review
Lifestyle and Lipoprotein(a) Levels: Does a Specific Counseling Make Sense?
by Federica Fogacci, Valentina Di Micoli, Pierre Sabouret, Marina Giovannini and Arrigo F. G. Cicero
J. Clin. Med. 2024, 13(3), 751; https://doi.org/10.3390/jcm13030751 - 28 Jan 2024
Cited by 4 | Viewed by 8369
Abstract
Lipoprotein(Lp)(a) is a variant of low-density lipoprotein (LDL), bound to apolipoprotein B100, whose levels are associated with a significant increase in the risk of atherosclerosis-related cardiovascular events, but also to aortic stenosis and atrial fibrillation. Since plasma levels of Lp(a) are commonly considered [...] Read more.
Lipoprotein(Lp)(a) is a variant of low-density lipoprotein (LDL), bound to apolipoprotein B100, whose levels are associated with a significant increase in the risk of atherosclerosis-related cardiovascular events, but also to aortic stenosis and atrial fibrillation. Since plasma levels of Lp(a) are commonly considered resistant to lifestyle changes, we critically reviewed the available evidence on the effect of weight loss, dietary supplements, and physical activity on this risk factor. In our review, we observed that relevant body weight loss, a relatively high intake of saturated fatty acids, the consumption of red wine, and intense physical exercise seems to be associated with significantly lower plasma Lp(a) levels. On the contrary, foods rich in trans-unsaturated fatty acids are associated with increased Lp(a) levels. With regard to dietary supplements, coenzyme Q10, L-Carnitine, and flaxseed exert a mild but significant lowering effect on plasma Lp(a). Full article
(This article belongs to the Special Issue Management of Dyslipidaemias: Enhancing Lipid Modification to Reduce Cardiovascular Risk)

Other

Jump to: Research, Review

7 pages, 654 KiB  
Brief Report
Clinical Expression of Familial Hypercholesterolemia in Patients from France and French Canada Carrying Identical-by-Descent Pathogenic LDLR Gene Variants: A Proof-of-Concept Study
by Miriam Larouche, Olivier Bluteau, Alain Carrié, Alex Lauzière, Etienne Khoury, Diane Brisson, Daniel Gaudet and Antonio Gallo
J. Clin. Med. 2024, 13(19), 5725; https://doi.org/10.3390/jcm13195725 - 26 Sep 2024
Viewed by 895
Abstract
Background: Studying patients carrying identical-by-descent (IBD) pathogenic gene variants allows us to control for the disease-causing genetic background and to more accurately document the impact of modifiers. Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-c) levels and premature atherosclerosis and [...] Read more.
Background: Studying patients carrying identical-by-descent (IBD) pathogenic gene variants allows us to control for the disease-causing genetic background and to more accurately document the impact of modifiers. Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-c) levels and premature atherosclerosis and is often caused by defects in the LDLR gene. There is a high prevalence of FH in French Canada as a result of a founder effect from France in the 17th century. Several FH patients currently living in French Canada (founder population) and in France (colonizing population) carry IBD FH-causing variants. The expression of FH is affected by environmental and genetic modifiers, and patients with IBD variants may present different characteristics. Methods: In this study, we compared FH clinical expression patients carrying IBD LDLR pathogenic variants living in France or Canada. Four IBD variants, namely c.259T>G p.(Trp87Gly), c.2000G>A p.(Cys667Tyr), c.682G>A p.(Glu228Lys), and c.1048C>T p.(Arg350*), were selected. Untreated plasma lipid profiles, the apolipoprotein E (APOE) genotype, cardiovascular risk factors, and the occurrence of symptomatic ASCVD were compared in 105 adult carriers (30 from France and 75 from French Canada). Results: All parameters were similar between the two populations, except for untreated total cholesterol (10.14 ± 1.89 mmol/L vs. 8.65 ± 1.84 mmol/L, p = 0.0006) and LDL-c concentrations (7.94 ± 1.86 mmol/L vs. 6.93 ± 1.78 mmol/L, p = 0.016), which were significantly higher in FH patients living in France, an observation that was revealed across all studied LDLR variants. Conclusions: This study illustrates that FH patients sharing IBD pathogenic LDLR variants that have evolved in different geographic, cultural, and socio-economic environments for hundreds of years differ in terms of cholesterol levels, highlighting the importance of better understanding the interplay between genetic and environmental modulators of FH expression. Full article
(This article belongs to the Special Issue Management of Dyslipidaemias: Enhancing Lipid Modification to Reduce Cardiovascular Risk)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Review on gene-based emerging therapies for lipid disorders

Title: LCAT Deficiency

 
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