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Pharmacological Lipid Strategies for Cardiovascular Disease Prevention

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

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 36290

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Special Issue Editor

Dr. Francesca Zimetti

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Guest Editor

Department of Food and Drugs, University of Parma, Parma, Italy
Interests: high-density lipoprotein (HDL) functions; cardiovascular pharmacology; atherosclerosis; inflammation; lipid metabolism; lipids in neurodegenerative diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Although statins have led to a remarkable lowering of low-density lipoprotein (LDL) cholesterol in blood plasma and a parallel significant reduction in cardiovascular events, cardiovascular disease (CVD) remains the main cause of mortality worldwide due to the so-called “residual cardiovascular risk”. In this context, much effort is being made to identify and develop novel therapeutic approaches. The recent introduction of antibodies targeting PCSK9 has further improved cardiovascular outcomes and represents a novel alternative therapeutic strategy for many patients, including those intolerant to statins. Moreover, several other promising pharmacological strategies targeting lipid and lipoprotein metabolism are under investigation.

This Special Issue aims to provide researchers with an opportunity to publish both original research and review articles related to recent advances in the CV field, with a particular focus on the pharmacology of novel lipid- and lipoprotein-modifying strategies that have potential use in the clinic for preventing CVD in the near future.

Dr. Francesca Zimetti
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

lipids
lipoprotein
lipid metabolism
cardiovascular disease
atherosclerosis

Published Papers (13 papers)

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Research

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10 pages, 1177 KiB

Open AccessArticle

PCSK9 Levels and Metabolic Profiles in Elderly Subjects with Different Glucose Tolerance under Statin Therapy

by Kari A. Mäkelä, Jari Jokelainen, Ville Stenbäck, Juha Auvinen, Marjo-Riitta Järvelin, Mikko Tulppo, Juhani Leppäluoto, Sirkka Keinänen-Kiukaanniemi and Karl-Heinz Herzig

J. Clin. Med. 2021, 10(5), 994; https://doi.org/10.3390/jcm10050994 - 2 Mar 2021

Cited by 2 | Viewed by 2315

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades low-density lipoprotein cholesterol (LDL-C) receptors, and thus regulates the LDL-C levels in the circulation. Type 2 diabetics often have elevated LDL-C levels. However, the functions of PCSK9 in patients with alterations of glu-cose metabolism and statin therapy are still unclear. Method: we investigated a large cohort of 608 subjects, born in 1945 in Oulu, Finland (Oulu Cohort 1945). We studied the effects of PSCK9 lev-els with different glucose tolerances (normal glucose tolerance (NGT), prediabetes (PreDM) or type 2 diabetes (T2D)) with and without statin medication, and analyzed clinical data, NMR metabolomics and PCSK9 plasma levels. Results: PCSK9 plasma levels did not significantly differ between the three groups. Statin therapy significantly increased the PCSK9 levels in NGT, PreDM and T2D groups compared with subjects with no statins. In the NGT group, negative associations between PCSK9 and LDL-C, intermediate-density lipoprotein cholesterol (IDL-C), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol and LDL and IDL triglycerides were observed under statin medication. In contrast, in the PreDM and T2D groups, these associa-tions were lost. Conclusions: our data suggest that in subjects with abnormal glucose metabolism and statin therapy, the significant PCSK9-mediated effects on the lipid metabolites are lost com-pared to NGT subjects, but statins reduced the LDL-C and VLDL-C levels. Full article

(This article belongs to the Special Issue Pharmacological Lipid Strategies for Cardiovascular Disease Prevention)

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8 pages, 1102 KiB

Open AccessArticle

Evaluation of Transthoracic Echocardiography in the Assessment of Atherosclerosis of the Left Main Coronary Artery: Comparison with Optical Frequency Domain Imaging (a Pilot Study)

by Fabien Labombarda, Vincent Roule, Idir Rebouh, Massimiliano Ruscica, Gerald F. Watts and Cesare R. Sirtori

J. Clin. Med. 2021, 10(2), 256; https://doi.org/10.3390/jcm10020256 - 12 Jan 2021

Cited by 1 | Viewed by 1628

Abstract

Background: Risk stratification using non-invasive imaging of the coronary vessels is emerging as an optimal standard of care for patients with dyslipidemias. Of particular interest is the evaluation of the left main coronary artery (LMCA), where calcium deposition appears to be a predictor of cardiovascular events. Methods: In coronary patients, we evaluated wall thickness and internal diameter of the LMCA examined by transthoracic echocardiography (TTE) and compared these with findings obtained by optical frequency domain imaging (OFDI), this latter also used to evaluate calcium deposition. Results: A significant positive correlation between TTE and OFDI for the anterior wall thickness (r = 0.41, p = 0.043) and internal diameter (r = 0.36, p = 0.048) of the LMCA was detected. Echocardiographic wall measurements were higher in patients with fibro-calcific plaques. The receiver operating characteristic (ROC) curve showed that an anterior wall thickness of LMCA ≥ 1.4 mm was predictive of fibro-calcific plaque (area under the curve = 0.815 and p = 0.006), sensitivity and specificity being 76.9% and 80%, respectively (Youden’s Index = 0.56). Conclusions: Measurement of anterior wall thickness of the LMCA by TTE and OFDI appears to be closely correlated and may predict the presence of coronary calcification. Full article

(This article belongs to the Special Issue Pharmacological Lipid Strategies for Cardiovascular Disease Prevention)

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13 pages, 4445 KiB

Open AccessArticle

Identifying Markers of Cardiovascular Event-Free Survival in Familial Hypercholesterolemia

by Etienne Khoury, Diane Brisson, Nathalie Roy, Gérald Tremblay and Daniel Gaudet

J. Clin. Med. 2021, 10(1), 64; https://doi.org/10.3390/jcm10010064 - 27 Dec 2020

Cited by 9 | Viewed by 1995

Abstract

Familial hypercholesterolemia (FH) is an autosomal dominant trait characterized by elevated low-density lipoprotein-cholesterol (LDL-C) concentrations appearing at birth and is associated with increased risk of premature atherosclerotic cardiovascular disease (CVD). However, in some cases, FH subjects over 70 years of age have surprisingly never experienced any CVD symptoms throughout their entire lives. The objective of this study consists of identifying biological and environmental markers acting as cardioprotective factors and associated with unexpected survival in FH. Upon age and reported cardiovascular events (CVE) stratification, we identified a total of 458 French–Canadian FH subjects with premature reported CVE, and 1297 young adults as well as 24 elderly subjects (≥70 years) who have never reported CVE requiring hospitalization. Logistic regression models were used to depict cardioprotective markers among FH survivors (≥70 years). Regression analyses of the FH cohort showed that female sex (odds ratio (OR) = 12.92 (4.23–39.46); p < 0.0001), high levels of high-density lipoprotein (HDL)-C (OR = 6.76 (2.43–18.79); p = 0.0002) and elevated concentrations of adiponectin (OR = 71.40 (5.20–980.47); p = 0.001) were significant contributory factors in reducing FH-related CVD risk. Notably, female (OR = 11.45 (1.25–105.98); p = 0.031) and high HDL-C (OR = 9.78 (1.75–54.67); p = 0.009) were shown to be significant covariates associated with survival in FH. Non-smoking (OR = 11.73 (4.36–31.56); p < 0.0001) was also identified as an environmental factor associated with CVE-free survival. Based on this configured model of premature CVE occurrence, these results demonstrated that, beyond LDL-C levels, female sex, high HDL-C, elevated adiponectin and non-smoking are important markers that contribute to a reduced risk of CVD and CVE-free survival in FH. Full article

(This article belongs to the Special Issue Pharmacological Lipid Strategies for Cardiovascular Disease Prevention)

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12 pages, 716 KiB

Open AccessArticle

Factors Associated with the Prescribing of High-Intensity Statins

by Armando Chaure-Pardos, Sara Malo, María José Rabanaque, Federico Arribas, Belén Moreno-Franco and Isabel Aguilar-Palacio

J. Clin. Med. 2020, 9(12), 3850; https://doi.org/10.3390/jcm9123850 - 27 Nov 2020

Cited by 3 | Viewed by 1979

Abstract

In this study, we investigated the relationship between sociodemographic, clinical, anthropometric, and lifestyle characteristics and the type of statin prescribed for primary prevention of cardiovascular disease (CVD). We conducted an observational study in workers who began statin treatment. Statin therapy was categorized as “high-intensity” or “low–moderate-intensity”. Workers were classified according to the alignment of their statin therapy with the recommended management practices. Logistic regression models were used to evaluate the association between the different variables studied and the probability of being prescribed high-intensity statins. The only variables associated with a higher probability of being treated with high-intensity statins were increased physical activity (>40 versus <20 METs (metabolic equivalent of task) h/wk; odds ratio (OR), 1.65; 95%CI, 1.08–2.50) and, in diabetics, higher low-density lipoprotein cholesterol (LDL-C) levels (≥155 mg/dL versus <155 mg/dL; OR, 4.96; 95%CI, 1.29–19.10). The model that best predicted treatment intensity included LDL-C, diabetes, hypertension, smoking, and age (area under the Receiver Operating Characteristic curve (AUC), 0.620; 95%CI, 0.574–0.666). The prescribing and type of statin used in primary CVD prevention did not correspond with the indications in current guidelines. The probability of receiving high-intensity statins was higher in diabetics with high LDL-C levels and in more physically active individuals. These findings underscore the great variability and uncertainty in the prescribing of statins. Full article

(This article belongs to the Special Issue Pharmacological Lipid Strategies for Cardiovascular Disease Prevention)

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11 pages, 594 KiB

Open AccessArticle

Analysis of Arterial Stiffness and Sexual Function after Adding on PCSK9 Inhibitor Treatment in Male Patients with Familial Hypercholesterolemia: A Single Lipid Center Real-World Experience

by Roberto Scicali, Giorgio Ivan Russo, Marina Di Mauro, Flavia Manuele, Grazia Di Marco, Antonino Di Pino, Viviana Ferrara, Agata Maria Rabuazzo, Salvatore Piro, Giuseppe Morgia and Francesco Purrello

J. Clin. Med. 2020, 9(11), 3597; https://doi.org/10.3390/jcm9113597 - 8 Nov 2020

Cited by 11 | Viewed by 2254

Abstract

Familial hypercholesterolemia (FH) subjects have high low-density lipoprotein cholesterol (LDL-C) and may be at high risk of erectile dysfunction and atherosclerotic cardiovascular diseases. We evaluated the effect of PCSK9-i on sexual function evaluated by the Male Sexual Health Questionnaire (MSHQ) and the International Index of Erectile Function (IIEF-5) questionnaire and on pulse wave velocity (PWV) in FH male subjects. In this prospective observational study, we evaluated 30 FH male patients on high-intensity statins plus ezetimibe and with an LDL-C off-target. All patients added PCSK9-i treatment and obtained clinical assessment at baseline and after six months of PCSK9-i. As expected, LDL-C significantly decreased after adding-on PCSK9-i (−48.73%, p < 0.001). MSHQ and PWV significantly improved after adding-on PCSK9-i (for MSHQ 93.63 ± 6.28 vs. 105.41 ± 5.86, p < 0.05; for PWV 9.86 ± 1.51 vs. 7.7 ± 1.42, p < 0.05); no significant change of IIEF-5 was found. Finally, a simple regression showed that ∆ MSHQ was significantly associated with ∆ LDL-C and ∆ PWV (p value for both <0.05). In conclusion, PCSK9-i therapy significantly improves lipid profile, PWV, and sexual function in FH male patients; our results support the favorable function of PCSK9-i on these parameters. Full article

(This article belongs to the Special Issue Pharmacological Lipid Strategies for Cardiovascular Disease Prevention)

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13 pages, 950 KiB

Open AccessArticle

Low Plasma Lecithin: Cholesterol Acyltransferase (LCAT) Concentration Predicts Chronic Kidney Disease

by Andrea Baragetti, Alice Ossoli, Arianna Strazzella, Sara Simonelli, Ivano Baragetti, Liliana Grigore, Fabio Pellegatta, Alberico L. Catapano, Giuseppe Danilo Norata and Laura Calabresi

J. Clin. Med. 2020, 9(7), 2289; https://doi.org/10.3390/jcm9072289 - 18 Jul 2020

Cited by 20 | Viewed by 2414

Abstract

Low high-density lipoprotein-cholesterol (HDL-c) is the most remarkable lipid trait both in mild-to-moderate chronic kidney disease (CKD) patients as well as in advanced renal disease stages, and we have previously shown that reduced lecithin:cholesterol acyltransferase (LCAT) concentration is a major determinant of the low HDL phenotype. In the present study, we test the hypothesis that reduced LCAT concentration in CKD contributes to the progression of renal damage. The study includes two cohorts of subjects selected from the PLIC study: a cohort of 164 patients with CKD (NefroPLIC cohort) and a cohort of 164 subjects selected from the PLIC participants with a basal estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m² (PLIC cohort). When the NefroPLIC patients were categorized according to the LCAT concentration, patients in the 1st tertile showed the highest event rate at follow-up with an event hazard ratio significantly higher compared to the 3rd LCAT tertile. Moreover, in the PLIC cohort, subjects in the 1st LCAT tertile showed a significantly faster impairment of kidney function compared to subjects in the 3rd LCAT tertile. Serum from subjects in the 1st LCAT tertile promoted a higher reactive oxygen species (ROS) production in renal cells compared to serum from subjects in the third LCAT tertile, and this effect was contrasted by pre-incubation with recombinant human LCAT (rhLCAT). The present study shows that reduced plasma LCAT concentration predicts CKD progression over time in patients with renal dysfunction, and, even more striking, it predicts the impairment of kidney function in the general population. Full article

(This article belongs to the Special Issue Pharmacological Lipid Strategies for Cardiovascular Disease Prevention)

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9 pages, 989 KiB

Open AccessArticle

Anti-atherogenic Modification of Serum Lipoprotein Function in Patients with Rheumatoid Arthritis after Tocilizumab Treatment, a Pilot Study

by Daniela Greco, Roberta Gualtierotti, Pasquale Agosti, Maria Pia Adorni, Francesca Ingegnoli, Matteo Rota, Franco Bernini, Pier Luigi Meroni and Nicoletta Ronda

J. Clin. Med. 2020, 9(7), 2157; https://doi.org/10.3390/jcm9072157 - 8 Jul 2020

Cited by 20 | Viewed by 2115

Abstract

Lipid metabolism derangement contributes to increased cardiovascular risk in Rheumatoid Arthritis (RA). It is still debated whether and how tocilizumab, an interleukin-6 receptor inhibitor used in active RA, impacts cardiovascular risk. We studied the effect of tocilizumab on the regulation of macrophage cholesterol homeostasis, measuring patient serum ability to respectively load (cholesterol loading capacity, CLC) and discharge (cholesterol efflux capacity, CEC) cells with cholesterol. Patients with RA (n = 8) were studied before and after 4 and 12 weeks of tocilizumab treatment. CLC was measured by a fluorimetric assay of intracellular cholesterol content in human macrophages and CEC was measured for the three main pathways, mediated by the transporters Scavenger Receptor class B-type I (SR-BI), ATP binding cassette-G1 (ABCG1) and -A1 (ABCA1) in specific cell models. After 12 weeks of tocilizumab treatment, serum LDL cholesterol levels were increased, while CLC was reduced. HDL cholesterol levels were unchanged, but CEC was significantly ameliorated for the SR-BI and ABCG1 pathways with respect to baseline. Tocilizumab reduces LDL pro-atherogenic potential despite increasing their serum levels and increases HDL protective activity in RA. The data of our pilot study suggest that tocilizumab regulates lipoprotein function in selected patient populations and lay the groundwork for future larger studies. Full article

(This article belongs to the Special Issue Pharmacological Lipid Strategies for Cardiovascular Disease Prevention)

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12 pages, 1037 KiB

Open AccessArticle

The Impact of the 2019 European Guideline for Cardiovascular Risk Management: A Cross-Sectional Study in General Practice

by Rahel Meier, Yael Rachamin, Thomas Rosemann and Stefan Markun

J. Clin. Med. 2020, 9(7), 2140; https://doi.org/10.3390/jcm9072140 - 7 Jul 2020

Cited by 11 | Viewed by 2913

Abstract

The aim of this study was to assess the impact of the 2019 published European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline on cardiovascular (CV) risk management compared with its predecessor from 2016 in a cohort in general practice. We performed a cross-sectional retrospective study with data from electronic medical records. The study cohort included 103,351 patients with known CV risk. We assessed changes in CV risk classification and low-density lipoprotein cholesterol (LDL-C) target values, the impact on LDL-C achievement rates, and the current lipid-lowering treatments. Under the 2019 ESC guideline, CV risk categories changed in 27.5% of patients, LDL-C target levels decreased in 71.4% of patients, and LDL-C target achievement rate dropped from 31.1% to 16.5%. Among non-achievers according to the 2019 guideline, 52.2% lacked lipid-lowering drugs entirely, and 41.5% had conventional drugs at a submaximal intensity. Of patients in the high-risk and very high-risk categories, at least 5% failed to achieve the LDL-C target level despite treatment at maximal intensity with conventional lipid-lowering drugs, making them eligible for PCSK-9 inhibitors. In conclusion, the 2019 ESC/EAS guideline lowered LDL-C target values for the majority of patients in general practice and halved LDL-C target achievement rates. There is still a large undeveloped potential to lower CV risk by introducing conventional lipid-lowering drugs, particularly in patients at high or very high CV risk. A substantial proportion of the patients can only achieve their LDL-C targets using PCSK-9 inhibitors, which would currently require an at least 10-fold increase in prescribing of these drugs. Full article

(This article belongs to the Special Issue Pharmacological Lipid Strategies for Cardiovascular Disease Prevention)

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8 pages, 1292 KiB

Open AccessArticle

Age-Dependent Efficacy of Ezetimibe for Low-Density Lipoprotein Cholesterol Reduction in Japanese Patients with or without Type 2 Diabetes Mellitus

by Satoshi Yamaguchi, Kageyuki Oba, Moritake Higa, Osamu Arasaki and Michio Shimabukuro

J. Clin. Med. 2020, 9(6), 1675; https://doi.org/10.3390/jcm9061675 - 1 Jun 2020

Viewed by 2224

Abstract

Ezetimibe reduces cardiovascular risk by lowering the levels of low-density lipoprotein cholesterol (LDL-C). However, there is limited information regarding the factors associated with ezetimibe-mediated LDL-C reduction. We investigated the factors associated with LDL-C reduction after ezetimibe administration in Japanese patients with or without type 2 diabetes mellitus (T2DM). This single-center retrospective observational study enrolled a total of 266 consecutive ezetimibe-naïve patients, of which 154 were excluded because of either switching from statin or fenofibrate to ezetimibe (n = 52) or ezetimibe discontinuation (n = 102). Finally, 112 patients were eligible for analysis. To identify the factors influencing LDL-C levels, univariate and multivariate linear regression analyses were performed after 52 weeks of ezetimibe treatment. Overall, advanced age, T2DM, and high baseline LDL-C were significantly associated with a greater decrease in LDL-C levels. In the non-T2DM group, advanced age and high baseline LDL-C were associated with greater decrease in LDL-C levels. In the T2DM group, baseline LDL-C was the only factor that influenced the change in LDL-C levels. Advanced age was significantly associated with higher LDL-C reduction in non-T2DM patients, but not in T2DM patients. Ezetimibe use might be beneficial in older patients without T2DM. The lack of association between age and the LDL-C lowering effect by ezetimibe in patients with T2DM may be due to yet unknown mechanism except low statistical power. Full article

(This article belongs to the Special Issue Pharmacological Lipid Strategies for Cardiovascular Disease Prevention)

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Review

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25 pages, 17975 KiB

Open AccessReview

Modulation of Bile Acid Metabolism to Improve Plasma Lipid and Lipoprotein Profiles

by Boyan Zhang, Folkert Kuipers, Jan Freark de Boer and Jan Albert Kuivenhoven

J. Clin. Med. 2022, 11(1), 4; https://doi.org/10.3390/jcm11010004 - 21 Dec 2021

Cited by 18 | Viewed by 6770

Abstract

New drugs targeting bile acid metabolism are currently being evaluated in clinical studies for their potential to treat cholestatic liver diseases, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Changes in bile acid metabolism, however, translate into an alteration of plasma cholesterol and triglyceride concentrations, which may also affect cardiovascular outcomes in such patients. This review attempts to gain insight into this matter and improve our understanding of the interactions between bile acid and lipid metabolism. Bile acid sequestrants (BAS), which bind bile acids in the intestine and promote their faecal excretion, have long been used in the clinic to reduce LDL cholesterol and, thereby, atherosclerotic cardiovascular disease (ASCVD) risk. However, BAS modestly but consistently increase plasma triglycerides, which is considered a causal risk factor for ASCVD. Like BAS, inhibitors of the apical sodium-dependent bile acid transporter (ASBTi’s) reduce intestinal bile acid absorption. ASBTi’s show effects that are quite similar to those obtained with BAS, which is anticipated when considering that accelerated faecal loss of bile acids is compensated by an increased hepatic synthesis of bile acids from cholesterol. Oppositely, treatment with farnesoid X receptor agonists, resulting in inhibition of bile acid synthesis, appears to be associated with increased LDL cholesterol. In conclusion, the increasing efforts to employ drugs that intervene in bile acid metabolism and signalling pathways for the treatment of metabolic diseases such as NAFLD warrants reinforcing interactions between the bile acid and lipid and lipoprotein research fields. This review may be considered as the first step in this process. Full article

(This article belongs to the Special Issue Pharmacological Lipid Strategies for Cardiovascular Disease Prevention)

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24 pages, 954 KiB

Open AccessReview

Dysfunctional High-Density Lipoproteins in Type 2 Diabetes Mellitus: Molecular Mechanisms and Therapeutic Implications

by Isabella Bonilha, Francesca Zimetti, Ilaria Zanotti, Bianca Papotti and Andrei C. Sposito

J. Clin. Med. 2021, 10(11), 2233; https://doi.org/10.3390/jcm10112233 - 21 May 2021

Cited by 16 | Viewed by 2668

Abstract

High density lipoproteins (HDLs) are commonly known for their anti-atherogenic properties that include functions such as the promotion of cholesterol efflux and reverse cholesterol transport, as well as antioxidant and anti-inflammatory activities. However, because of some chronic inflammatory diseases, such as type 2 diabetes mellitus (T2DM), significant changes occur in HDLs in terms of both structure and composition. These alterations lead to the loss of HDLs’ physiological functions, to transformation into dysfunctional lipoproteins, and to increased risk of cardiovascular disease (CVD). In this review, we describe the main HDL structural/functional alterations observed in T2DM and the molecular mechanisms involved in these T2DM-derived modifications. Finally, the main available therapeutic interventions targeting HDL in diabetes are discussed. Full article

(This article belongs to the Special Issue Pharmacological Lipid Strategies for Cardiovascular Disease Prevention)

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13 pages, 2127 KiB

Open AccessReview

The Investigative Role of Statins in Ameliorating Lower Urinary Tract Symptoms (LUTS): A Systematic Review

by Giorgio Ivan Russo, Gaetano Larganà, Arcangelo Sebastianelli, Andrea Cocci, Marina Di Mauro, Ilenia Rapallo, Giuseppe Morgia, Matteo Mario Morgia, Sandro La Vignera, Rosita Condorelli, Aldo E. Calogero, Iacopo Olivotto, Simone Morselli, Sergio Serni and Mauro Gacci

J. Clin. Med. 2021, 10(3), 416; https://doi.org/10.3390/jcm10030416 - 22 Jan 2021

Cited by 3 | Viewed by 2789

Abstract

Previous data have shown that patients with metabolic syndrome (MetS) and lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement (BPE) could be refractory to the medical treatment. In this context, the evidence suggests a role for statin use in LUTS/BPE patients. The present systematic review aimed to evaluate the impact of statins on the treatment of men with LUTS/BPE. This review has been registered on PROSPERO (CRD42019120729). A systematic review of English-language literature was performed up to January 2020 in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA statement) criteria. Retrieved studies had to include adults with LUTS connected to BPE treated with statins drugs for metabolic syndrome. After removing duplicates, a total of 381 studies were identified by the literature search and independently screened. Of these articles, 10 fit the inclusion criteria and were further assessed for eligibility. Data from our systematic review suggest that a long-term therapy with statins, at least 6 months, is required to achieve significant impacts on prostate tissue and LUTS. Moreover, besides statins’ direct activity, the risk reduction of LUTS might be connected to the improvement of hypercholesterolemia and MetS. The role of statins for the treatment of LUTS/BPE may be beneficial; however, evidence from robust studies is not enough, and more clinical trial are required. Full article

(This article belongs to the Special Issue Pharmacological Lipid Strategies for Cardiovascular Disease Prevention)

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23 pages, 381 KiB

Open AccessReview

Lipoprotein(a) Lowering—From Lipoprotein Apheresis to Antisense Oligonucleotide Approach

by Maria Francesca Greco, Cesare R. Sirtori, Alberto Corsini, Marat Ezhov, Tiziana Sampietro and Massimiliano Ruscica

J. Clin. Med. 2020, 9(7), 2103; https://doi.org/10.3390/jcm9072103 - 3 Jul 2020

Cited by 20 | Viewed by 3422

Abstract

It is well-known that elevated lipoprotein(a)—Lp(a)—levels are associated with a higher risk of cardiovascular (CV) mortality and all-cause mortality, although a standard pharmacotherapeutic approach is still undefined for patients with high CV risk dependent on hyperlipoproteinemia(a). Combined with high Lp(a) levels, familial hypercholesterolemia (FH) leads to a greater CVD risk. In suspected FH patients, the proportion of cases explained by a rise of Lp(a) levels ranges between 5% and 20%. In the absence of a specific pharmacological approach able to lower Lp(a) to the extent required to achieve CV benefits, the most effective strategy today is lipoprotein apheresis (LA). Although limited, a clear effect on Lp(a) is exerted by PCSK9 antagonists, with apparently different mechanisms when given with statins (raised catabolism) or as monotherapy (reduced production). In the era of RNA-based therapies, a new dawn is represented by the use of antisense oligonucleotides APO(a)L_rx, able to reduce Lp(a) from 35% to over 80%, with generally modest injection site reactions. The improved knowledge of Lp(a) atherogenicity and possible prevention will be of benefit for patients with residual CV risk remaining after the most effective available lipid-lowering agents. Full article

(This article belongs to the Special Issue Pharmacological Lipid Strategies for Cardiovascular Disease Prevention)

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