Editorial

Open AccessEditorial

Dyslipidemia and Cardiovascular Disease: Current Knowledge, Existing Challenges, and New Opportunities for Management Strategies

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Zhiyong Du

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Yanwen Qin

J. Clin. Med. 2023, 12(1), 363; https://doi.org/10.3390/jcm12010363 - 03 Jan 2023

Cited by 1 | Viewed by 2398

Abstract

Cardiovascular disease is the leading cause of morbidity and mortality worldwide, and dyslipidemia is one of the major risk factors [...] Full article

(This article belongs to the Special Issue Dyslipidemia and Cardiovascular Disease)

Research

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Open AccessArticle

Uncovering Predictors of Lipid Goal Attainment in Type 2 Diabetes Outpatients Using Logic Learning Machine: Insights from the AMD Annals and AMD Artificial Intelligence Study Group

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Davide Masi

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Rita Zilich

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Riccardo Candido

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Annalisa Giancaterini

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J. Clin. Med. 2023, 12(12), 4095; https://doi.org/10.3390/jcm12124095 - 16 Jun 2023

Viewed by 600

Abstract

Identifying and treating lipid abnormalities is crucial for preventing cardiovascular disease in diabetic patients, yet only two-thirds of patients reach recommended cholesterol levels. Elucidating the factors associated with lipid goal attainment represents an unmet clinical need. To address this knowledge gap, we conducted [...] Read more.

Identifying and treating lipid abnormalities is crucial for preventing cardiovascular disease in diabetic patients, yet only two-thirds of patients reach recommended cholesterol levels. Elucidating the factors associated with lipid goal attainment represents an unmet clinical need. To address this knowledge gap, we conducted a real-world analysis of the lipid profiles of 11.252 patients from the Annals of the Italian Association of Medical Diabetologists (AMD) database from 2005 to 2019. We used a Logic Learning Machine (LLM) to extract and classify the most relevant variables predicting the achievement of a low-density lipoprotein cholesterol (LDL-C) value lower than 100 mg/dL (2.60 mmol/L) within two years of the start of lipid-lowering therapy. Our analysis showed that 61.4% of the patients achieved the treatment goal. The LLM model demonstrated good predictive performance, with a precision of 0.78, accuracy of 0.69, recall of 0.70, F1 Score of 0.74, and ROC-AUC of 0.79. The most significant predictors of achieving the treatment goal were LDL-C values at the start of lipid-lowering therapy and their reduction after six months. Other predictors of a greater likelihood of reaching the target included high-density lipoprotein cholesterol, albuminuria, and body mass index at baseline, as well as younger age, male sex, more follow-up visits, no therapy discontinuation, higher Q-score, lower blood glucose and HbA1c levels, and the use of anti-hypertensive medication. At baseline, for each LDL-C range analysed, the LLM model also provided the minimum reduction that needs to be achieved by the next six-month visit to increase the likelihood of reaching the therapeutic goal within two years. These findings could serve as a useful tool to inform therapeutic decisions and to encourage further in-depth analysis and testing. Full article

(This article belongs to the Special Issue Dyslipidemia and Cardiovascular Disease)

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Open AccessArticle

Mitochondrial Heteroplasmy as a Marker for Premature Coronary Artery Disease: Analysis of the Poly-C Tract of the Control Region Sequence

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Francisco González-Urbistondo

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Alberto Alen

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Daniel Vázquez-Coto

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Mar González-Fernández

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J. Clin. Med. 2023, 12(6), 2133; https://doi.org/10.3390/jcm12062133 - 08 Mar 2023

Cited by 1 | Viewed by 854

Abstract

Mitochondrial DNA (mtDNA) differs from the nuclear genome in many aspects: a maternal inheritance pattern; being more prone to acquire somatic de novo mutations, accumulative with age; and the possible coexistence of different mtDNA alleles (heteroplasmy). Mitochondria are key cellular organelles responsible for [...] Read more.

Mitochondrial DNA (mtDNA) differs from the nuclear genome in many aspects: a maternal inheritance pattern; being more prone to acquire somatic de novo mutations, accumulative with age; and the possible coexistence of different mtDNA alleles (heteroplasmy). Mitochondria are key cellular organelles responsible for energy production and involved in complex mechanisms, including atherosclerosis. In this scenario, we aimed to evaluate mtDNA variants that could be associated with premature cardiovascular disease. We evaluated 188 consecutive patients presenting with premature myocardial infarction with ST elevation (STEMI) confirmed by coronary angiogram. mtDNA polymorphisms and clinical data were evaluated and compared with 271 individuals from the same population (control group). Tobacco consumption (80.85% vs. 21.21%, p < 0.01) and dyslipidemia (38.83% vs. 28.41%, p = 0.02) were significantly more frequent among STEMI patients. Moreover, C16223T mtDNA mutation and poly-C heteroplasmy were significantly more frequent among premature STEMI male patients than in controls. The OR associated C16223T mtDNA with the increased presence of cardiovascular risk factors. Our data suggest that mtDNA 16223T and heteroplasmy may be associated with unstable premature atherosclerosis disease in men. Moreover, the presence of cardiovascular risk factors (CVRFs) was associated with C16223T mtDNA, with a cumulative effect. Protective mitochondrial pathways are potential therapeutic targets. Preventing exposure to the damaging mechanisms associated with CVRFs is of utmost importance. Full article

(This article belongs to the Special Issue Dyslipidemia and Cardiovascular Disease)

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Open AccessArticle

Genetic Association between the Levels of Plasma Lipids and the Risk of Aortic Aneurysm and Aortic Dissection: A Two-Sample Mendelian Randomization Study

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J. Clin. Med. 2023, 12(5), 1991; https://doi.org/10.3390/jcm12051991 - 02 Mar 2023

Viewed by 1349

Abstract

Although a growing number of studies have attempted to uncover the relationship between plasma lipids and the risk of aortic aneurysm (AA), it remains controversial. Meanwhile, the relationship between plasma lipids and the risk of aortic dissection (AD) has not been reported on. [...] Read more.

Although a growing number of studies have attempted to uncover the relationship between plasma lipids and the risk of aortic aneurysm (AA), it remains controversial. Meanwhile, the relationship between plasma lipids and the risk of aortic dissection (AD) has not been reported on. We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the potential relationship between genetically predicted plasma levels of lipids and the risk of AA and AD. Summary data on the relationship between genetic variants and plasma lipids were obtained from the UK Biobank and Global Lipids Genetics Consortium studies, and data on the association between genetic variants and AA or AD were taken from the FinnGen consortium study. Inverse-variance weighted (IVW) and four other MR analysis methods were used to evaluate effect estimates. Results showed that genetically predicted plasma levels of low-density lipoprotein cholesterol, total cholesterol, or triglycerides were positively correlated with the risk of AA, and plasma levels of high-density lipoprotein cholesterol were negatively correlated with the risk of AA. However, no causal relationship was found between elevated lipid levels and the risk of AD. Our study revealed a causal relationship between plasma lipids and the risk of AA, while plasma lipids had no effect on the risk of AD. Full article

(This article belongs to the Special Issue Dyslipidemia and Cardiovascular Disease)

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Open AccessArticle

Opportunistic Genetic Screening for Familial Hypercholesterolemia in Heart Transplant Patients

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J. Clin. Med. 2023, 12(3), 1233; https://doi.org/10.3390/jcm12031233 - 03 Feb 2023

Cited by 1 | Viewed by 1022

Abstract

Heart transplantation remains the gold standard for the treatment of advanced heart failure (HF). Identification of the etiology of HF is mandatory, as the specific pathology can determine subsequent treatment. Early identification of familial hypercholesterolemia (FH), the most common genetic disorder associated with [...] Read more.

Heart transplantation remains the gold standard for the treatment of advanced heart failure (HF). Identification of the etiology of HF is mandatory, as the specific pathology can determine subsequent treatment. Early identification of familial hypercholesterolemia (FH), the most common genetic disorder associated with premature cardiovascular disease, has a potential important impact on clinical management and public health. We evaluated the genetic information in the genes associated with FH in a cohort of 140 heart-transplanted patients. All patients underwent NGS genetic testing including LDLR, APOB, and PCSK9. We identified four carriers of rare pathogenic variants in LDLR and APOB. Although all four identified carriers had dyslipidemia, only the one carrying the pathogenic variant LDLR c.676T>C was transplanted due to CAD. Another patient with heart valvular disease was carrier of the controversial LDLR c.2096C>T. Two additional patients with non-ischemic dilated cardiomyopathy were carriers of variants in APOB (c.4672A>G and c.5600G>A). In our cohort, we identified the genetic cause of FH in patients that otherwise would not have been diagnosed. Opportunistic genetic testing for FH provides important information to perform personalized medicine and risk stratification not only for patients but also for relatives at concealed high cardiovascular risk. Including the LDLR gene in standard NGS cardiovascular diagnostics panels should be considered. Full article

(This article belongs to the Special Issue Dyslipidemia and Cardiovascular Disease)

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Open AccessCommunication

Metabolomic Approach to Screening Homozygotes in Chinese Patients with Severe Familial Hypercholesterolemia

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J. Clin. Med. 2023, 12(2), 483; https://doi.org/10.3390/jcm12020483 - 06 Jan 2023

Cited by 2 | Viewed by 980

Abstract

Homozygous familial hypercholesterolemia (HoFH) is a rare inborn-errors-of-metabolism disorder characterized by devastatingly elevated low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease. The gold standard for screening and diagnosing HoFH is genetic testing. In China, it is expensive and is always recommended for the [...] Read more.

Homozygous familial hypercholesterolemia (HoFH) is a rare inborn-errors-of-metabolism disorder characterized by devastatingly elevated low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease. The gold standard for screening and diagnosing HoFH is genetic testing. In China, it is expensive and is always recommended for the most likely HoFH subjects with aggressive LDL-C phenotype. However, the LDL-C levels of HoFH patients and a substantial proportion of heterozygous FH (HeFH) patients overlapped considerably. Here, we performed a cost-effective metabolomic profiling on genetically diagnosed HoFH (n = 69) and HeFH patients (n = 101) with overlapping LDL-C levels, aiming to discovery a unique metabolic pattern for screening homozygotes in patients with severe FH. We demonstrated a differential serum metabolome profile in HoFH patients compared to HeFH patients. Twenty-one metabolomic alterations showed independent capability in differentiating HoFH from severe HeFH. The combined model based on seven identified metabolites yielded a corrected diagnosis in 91.3% of HoFH cases with an area under the curve value of 0.939. Collectively, this study demonstrated that metabolomic profiling serves as a useful and economical approach to preselecting homozygotes in FH patients with severe hypercholesterolemia and may help clinicians to conduct selective genetic confirmation testing and familial cascade screening. Full article

(This article belongs to the Special Issue Dyslipidemia and Cardiovascular Disease)

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Open AccessArticle

Myeloperoxidase Levels in Pericardial Fluid Is Independently Associated with Postoperative Atrial Fibrillation after Isolated Coronary Artery Bypass Surgery

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J. Clin. Med. 2022, 11(23), 7018; https://doi.org/10.3390/jcm11237018 - 28 Nov 2022

Cited by 1 | Viewed by 801

Abstract

Background: Postoperative atrial fibrillation (POAF) is the most common complication after surgery for atherosclerotic cardiovascular disease (ASCVD) and leads to extended hospital stays and increased mortality. Myeloperoxidase (MPO) in postoperative pericardial drainage fluid is associated with an increased risk of POAF; however, the [...] Read more.

Background: Postoperative atrial fibrillation (POAF) is the most common complication after surgery for atherosclerotic cardiovascular disease (ASCVD) and leads to extended hospital stays and increased mortality. Myeloperoxidase (MPO) in postoperative pericardial drainage fluid is associated with an increased risk of POAF; however, the correlations between MPO in intraoperative pericardial fluid and POAF remain largely unknown. The aim of the study was to evaluate whether MPO is associated with POAF. Methods: A total of 97 patients with no history of atrial arrhythmia who had undergone coronary artery bypass surgery (CABG) were identified. We prospectively measured the levels of MPO in intraoperative pericardial fluid and blood using the human magnetic Luminex assay. Then, the occurrence of atrial fibrillation was continuously observed by postoperative ECG and telemetry strips until discharge. Results: Our data showed that POAF occurred in 24 of 97 patients (24.74%). MPO levels in blood were higher in the POAF group than the SR group (p = 0.064). Patients with POAF had significantly higher intraoperative pericardial fluid MPO levels than patients who remained in SR (p = 0.021). There was no significant correlation between pericardial fluid MPO levels and blood MPO levels (r = −0.47, p = 0.770). In a multivariable logistic regression model, pericardial fluid MPO levels were significantly associated with a higher risk of POAF (odds ratio = 1.016, 95% confidence interval, 1.001–1.031; p = 0.031). Conclusions: Higher intraoperative pericardial fluid MPO levels are linked with POAF in patients undergoing CABG. This finding provides insight into a possible mechanism of MPO in pericardial fluid increase susceptibility to developing POAF in patients undergoing CABG. Full article

(This article belongs to the Special Issue Dyslipidemia and Cardiovascular Disease)

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Review

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Open AccessReview

Management of Statin Intolerant Patients in the Era of Novel Lipid Lowering Therapies: A Critical Approach in Clinical Practice

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Giosiana Bosco

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Francesco Di Giacomo Barbagallo

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J. Clin. Med. 2023, 12(6), 2444; https://doi.org/10.3390/jcm12062444 - 22 Mar 2023

Cited by 1 | Viewed by 1953

Abstract

Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym [...] Read more.

Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym SAMS (Statin-Associated Muscle Side Effects). These side effects are responsible for statin treatment discontinuation that results in increased cardiovascular risk. The National Lipid Association (NLA) has recently provided an updated definition of statin intolerance, and a distinction between complete and partial statin intolerance has been reported. The evaluation of symptom severity and the presence of muscle damage biomarker alterations make it essential to adopt a patient-centered approach aimed at obtaining a personalized therapeutic strategy. Firstly, it could be useful to administer a different statin, reduce the dosage or adopt an alternate dosage regimen. However, some patients are unable to tolerate any statin at every dosage, or despite taking statins at the maximum tolerated dose, they fail to achieve the recommended LDL-C target, and thus it is necessary to introduce a non-statin hypolipidemic treatment. Ezetimibe, proprotein-convertase subtilisin/kexin type 9 (PCSK9) inhibitors such as monoclonal antibodies (alirocumab and evolocumab) or RNA messenger silencing (inclisiran), bempedoic acid or nutraceuticals are non-statin lipid-lowering therapies that could be used as an alternative or in addition to statins to achieve an early and sustained LDL-C reduction in clinical practice. In this review, we evaluated SI management focusing on non-statin lipid lowering therapies and their implications in lipid lowering approaches in clinical practice. Full article

(This article belongs to the Special Issue Dyslipidemia and Cardiovascular Disease)

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Open AccessReview

Recent Advances in Gene Therapy for Familial Hypercholesterolemia: An Update Review

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J. Clin. Med. 2022, 11(22), 6773; https://doi.org/10.3390/jcm11226773 - 16 Nov 2022

Cited by 3 | Viewed by 2483

Abstract

(1) Background: Existing lipid-lowering therapies have difficulty in achieving lipid target levels in patients with familial hypercholesterolemia (FH), especially in the treatment of patients with homozygous familial hypercholesterolemia. (2) Method: All of the literature data containing “Familial hypercholesterolemia” and “Gene Therapy” in PubMed [...] Read more.

(1) Background: Existing lipid-lowering therapies have difficulty in achieving lipid target levels in patients with familial hypercholesterolemia (FH), especially in the treatment of patients with homozygous familial hypercholesterolemia. (2) Method: All of the literature data containing “Familial hypercholesterolemia” and “Gene Therapy” in PubMed and Clinical Trials from 2018 to 2022 were selected. (3) Results: The rapid development of gene therapy technology in recent years is expected to change the treatment status of FH patients. As emerging gene therapy vectors, the optimized adeno-associated viruses, exosomes, and lipid nanoparticles have demonstrated an improved safety and higher transfection efficiency. Various RNA-targeted therapies are in phase 1–3 clinical trials, such as small interfering RNA-based drugs inclisiran, ARO-ANG3, ARO-APOC3, olpasiran, SLN360, and antisense oligonucleotide-based drugs AZD8233, vupanorsen, volanesorsen, IONIS-APO(a)Rx, etc., all of which have demonstrated excellent lipid-lowering effects. With gene editing technologies, such as CRISPR-Cas 9 and meganuclease, completing animal experiments in mice or cynomolgus monkeys and demonstrating lasting lipid-lowering effects, patients with FH are expected to reach a permanent cure in the future. (4) Conclusion: Gene therapy is being widely used for the lipid-lowering treatment of FH patients and has shown excellent therapeutic promise, but the current delivery efficiency, economic burden, immunogenicity and the precision of gene therapy can be further optimized. Full article

(This article belongs to the Special Issue Dyslipidemia and Cardiovascular Disease)

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