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Keywords = Lp(a), cardiovascular risk

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22 pages, 5182 KiB  
Article
Effects of High-Phenolic Extra Virgin Olive Oil (EVOO) on the Lipid Profile of Patients with Hyperlipidemia: A Randomized Clinical Trial
by Christos Kourek, Emmanouil Makaris, Prokopios Magiatis, Virginia Zouganeli, Vassiliki Benetou, Alexandros Briasoulis, Andrew Xanthopoulos, Ioannis Paraskevaidis, Eleni Melliou, Georgios Koudounis and Philippos Orfanos
Nutrients 2025, 17(15), 2543; https://doi.org/10.3390/nu17152543 - 2 Aug 2025
Viewed by 500
Abstract
Background/Objectives: Hyperlipidemia is a major risk factor for cardiovascular disease and atherosclerosis. Polyphenols found in polyphenol-rich extra virgin olive oil (EVOO) have been shown to possess strong antioxidant, anti-inflammatory, and cardioprotective properties. The present study aimed to assess the effects of two types [...] Read more.
Background/Objectives: Hyperlipidemia is a major risk factor for cardiovascular disease and atherosclerosis. Polyphenols found in polyphenol-rich extra virgin olive oil (EVOO) have been shown to possess strong antioxidant, anti-inflammatory, and cardioprotective properties. The present study aimed to assess the effects of two types of EVOO with different polyphenol content and dosages on the lipid profile of hyperlipidemic patients. Methods: In this single-blind, randomized clinical trial, 50 hyperlipidemic patients were randomized to receive either a higher-dose, lower-phenolic EVOO (414 mg/kg phenols, 20 g/day) or a lower-dose, higher-phenolic EVOO (1021 mg/kg phenols, 8 g/day), for a period of 4 weeks. These doses were selected to ensure equivalent daily polyphenol intake in both groups (~8.3 mg of total phenols/day), based on chemical analysis performed using NMR spectroscopy. The volumes used (8–20 g/day) reflect typical daily EVOO intake and were well tolerated by participants. A group of 20 healthy individuals, separated into two groups, also received the two types of EVOO, respectively, for the same duration. Primary endpoints included blood levels of total blood cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, lipoprotein-a (Lpa), and apolipoproteins A1 and B. Measurements were performed at baseline and at the end of the 4-week intervention. Linear mixed models were performed for the data analysis. Results: The higher-phenolic, lower-dose EVOO group showed a more favorable change in total blood cholesterol (p = 0.045) compared to the lower-phenolic, higher-dose group. EVOO intake was associated with a significant increase in HDL (p < 0.001) and reduction in Lp(a) (p = 0.040) among hyperlipidemic patients in comparison to healthy individuals. Conclusions: EVOO consumption significantly improved the lipid profile of hyperlipidemic patients. Higher-phenolic EVOO at lower dosages appears to be more effective in improving the lipid profile than lower-phenolic EVOO in higher dosages. Full article
(This article belongs to the Section Clinical Nutrition)
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14 pages, 898 KiB  
Article
Cardiovascular Risk in Rheumatic Patients Treated with JAK Inhibitors: The Role of Traditional and Emerging Biomarkers in a Pilot Study
by Diana Popescu, Minerva Codruta Badescu, Elena Rezus, Daniela Maria Tanase, Anca Ouatu, Nicoleta Dima, Oana-Nicoleta Buliga-Finis, Evelina Maria Gosav, Damiana Costin and Ciprian Rezus
J. Clin. Med. 2025, 14(15), 5433; https://doi.org/10.3390/jcm14155433 - 1 Aug 2025
Viewed by 184
Abstract
Background: Despite therapeutic advances, morbidity and mortality remain high in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), primarily due to increased cardiovascular risk. Objectives: Our study aimed to evaluate the cardiovascular risk profile and biomarker dynamics in patients with RA and [...] Read more.
Background: Despite therapeutic advances, morbidity and mortality remain high in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), primarily due to increased cardiovascular risk. Objectives: Our study aimed to evaluate the cardiovascular risk profile and biomarker dynamics in patients with RA and PsA treated with Janus kinase inhibitors (JAKis). To our knowledge, this is the first study assessing Lp(a) levels in this context. Methods: This prospective, observational study assessed 48 adult patients. The follow-up period was 12 months. Traditional cardiovascular risk factors and biological markers, including lipid profile, lipoprotein(a) [Lp(a)], and uric acid (UA), were assessed at baseline and follow-up. Correlations between JAKi therapy, lipid profile changes, and cardiovascular risk factors were investigated. Cox regression analysis was used to identify predictors of non-major cardiovascular events. Results: A strong positive correlation was observed between baseline and 12-month Lp(a) levels (r = 0.926), despite minor statistical shifts. No major cardiovascular events occurred during follow-up; however, 47.9% of patients experienced non-major cardiovascular events (e.g., uncontrolled arterial hypertension, exertional angina, and new-onset arrhythmias). Active smoking [hazard ratio (HR) 9.853, p = 0.005], obesity (HR 3.7460, p = 0.050), and arterial hypertension (HR 1.219, p = 0.021) were independent predictors of these events. UA (HR 1.515, p = 0.040) and total cholesterol (TC) (HR 1.019, p = 0.034) were significant biochemical predictors as well. Elevated baseline Lp(a) combined with these factors was associated with an increased event rate, particularly after age 60. Conclusions: Traditional cardiovascular risk factors remain highly prevalent and predictive, underscoring the need for comprehensive cardiovascular risk management. Lp(a) remained stable and may serve as a complementary biomarker for risk stratification in JAKi-treated patients. Full article
(This article belongs to the Section Immunology)
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12 pages, 1408 KiB  
Article
Association of Lipoprotein A rs10455872 Polymorphism with Childhood Obesity and Obesity-Related Outcomes
by Ayşen Haksayar, Mustafa Metin Donma, Bahadır Batar, Buse Tepe, Birol Topçu and Orkide Donma
Diagnostics 2025, 15(14), 1809; https://doi.org/10.3390/diagnostics15141809 - 18 Jul 2025
Viewed by 366
Abstract
Background/Objectives: Obesity is associated with cardiovascular disease worldwide. An increased lipoprotein A (LpA) level is an independent risk factor for cardiovascular disease in children. Genetic polymorphisms of the LPA gene may play an important role in susceptibility to obesity. The aim of this [...] Read more.
Background/Objectives: Obesity is associated with cardiovascular disease worldwide. An increased lipoprotein A (LpA) level is an independent risk factor for cardiovascular disease in children. Genetic polymorphisms of the LPA gene may play an important role in susceptibility to obesity. The aim of this study was to investigate the association of LPA rs10455872 polymorphism with the risk and clinical phenotypes of childhood obesity. Methods: This study included 103 children with obesity and 77 healthy controls. Genotyping of the LPA rs10455872 polymorphism was performed using real-time PCR. Results: The genotype distributions of the LPA rs10455872 polymorphism did not differ significantly between children with obesity and healthy children (p = 0.563). A marked difference in insulin levels was observed between children with obesity carrying the AG (16.90 IU/mL) and AA (25.57 IU/mL) genotypes. A marked difference was also observed in CRP levels between children with obesity with the AG (2.31 mg/L) and AA (4.25 mg/L) genotypes. After correcting for multiple comparisons using the false discovery rate (FDR), significant differences were found between AG and AA genotypes in vitamin B12 (adjusted p = 0.024). Serum iron showed a borderline association (adjusted p = 0.072). A statistically significant correlation was found between the metabolic syndrome index and body fat ratio among children with obesity with the AA genotype (p = 0.028). Conclusions: Although limited by the small number of children with obesity with the AG genotype, some differences were noted between the AG and AA genotypes. These exploratory findings require further investigation in adequately powered studies. In children with obesity with the AA genotype, the metabolic syndrome index increases as the body fat ratio increases. Full article
(This article belongs to the Special Issue Advances in Laboratory Markers of Human Disease)
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15 pages, 740 KiB  
Article
Effects of Janus Kinase Inhibitors on Cardio-Vascular Risk in Rheumatic Diseases: A Prospective Pilot Study
by Diana Popescu, Minerva Codruta Badescu, Elena Rezus, Daniela Maria Tanase, Anca Ouatu, Nicoleta Dima, Oana-Nicoleta Buliga-Finis, Evelina Maria Gosav and Ciprian Rezus
J. Clin. Med. 2025, 14(13), 4676; https://doi.org/10.3390/jcm14134676 - 2 Jul 2025
Viewed by 436
Abstract
Background/Objectives: Patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) exhibit increased cardiovascular risk, partly attributed to persistent systemic inflammation. Janus kinase inhibitors (JAKi) effectively reduce inflammation, but their impact on cardiovascular risk remains unclear. This pilot study aimed to evaluate the effect [...] Read more.
Background/Objectives: Patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) exhibit increased cardiovascular risk, partly attributed to persistent systemic inflammation. Janus kinase inhibitors (JAKi) effectively reduce inflammation, but their impact on cardiovascular risk remains unclear. This pilot study aimed to evaluate the effect of JAKi therapy on systemic inflammation and lipid markers, correlate traditional cardiovascular risk factors with biological parameters, and quantify subclinical atherosclerosis progression. Methods: We conducted a prospective, single-center study including 48 patients receiving JAKi. Clinical, inflammatory, lipid, and vascular parameters were assessed at baseline (T0) and after 12 months (T1). Primary endpoints included changes in carotid intima-media thickness (cIMT), ankle-brachial index (ABI), and carotid plaque presence. Results: Mean cIMT significantly decreased from 0.29 mm to 0.125 mm (p = 0.019), while ABI improved modestly, but not significantly (0.125 to 0.04, p = 0.103). Carotid plaque prevalence increased slightly from 39.6% to 47.9%, p = 0.159. C-reactive protein (CRP) levels declined significantly, while interleukin (IL)-1β levels increased. Lipoprotein(a) [Lp(a)] levels decreased significantly (mean reduction −7.96 mmol/L, p = 0.001). Multivariate regression identified Lp(a) as an independent predictor of carotid plaque at both T0 (p = 0.011) and T1 (p = 0.005). Baseline ABI was a significant predictor of acute cardiovascular events [hazard ratio (HR): 4.614, 95% CI: 1.034–20.596, p = 0.045]. Conclusions: JAKi therapy significantly reduced systemic inflammation and cIMT in patients with autoimmune rheumatic diseases, suggesting a potential benefit in attenuating early vascular changes. However, residual cardiovascular risk remains in patients with low ABI and elevated Lp(a), warranting close monitoring. Full article
(This article belongs to the Special Issue Cardiovascular Risks in Autoimmune and Inflammatory Diseases)
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23 pages, 858 KiB  
Article
An Adapted Cardioprotective Diet with or Without Phytosterol and/or Krill Oil Supplementation in Familial Hypercholesterolemia: Results of a Pilot Randomized Clinical Trial
by Erlon Oliveira de Abreu-Silva, Rachel Helena Vieira Machado, Bianca Rodrigues dos Santos, Flávia Cristina Soares Kojima, Renato Hideo Nakagawa Santos, Karina do Lago Negrelli, Letícia Barbante Rodrigues, Pedro Gabriel Melo de Barros e Silva, Andressa Gusmão de Lima, João Gabriel Sanchez, Fernanda Jafet El Khouri, Ângela Cristine Bersch-Ferreira, Adriana Bastos Carvalho, Thaís Martins de Oliveira, Maria Cristina Izar, Geni Rodrigues Sampaio, Nágila Raquel Teixeira Damasceno, Marcelo Macedo Rogero, Elizabeth Aparecida Ferraz da Silva Torres, Flávia De Conti Cartolano, Julia Pinheiro Krey, Patrícia Vieira de Luca, Cristiane Kovacs Amaral, Elisa Maia dos Santos, Rodrigo Morel Vieira de Melo, Eduardo Gomes Lima, André de Luca dos Santos, Thiago Gomes Heck, Ana Paula Perillo Ferreira Carvalho, Silvia Bueno Garofallo, Alexandre Biasi Cavalcanti and Aline Marcadentiadd Show full author list remove Hide full author list
Nutrients 2025, 17(12), 2008; https://doi.org/10.3390/nu17122008 - 15 Jun 2025
Viewed by 1188
Abstract
Background/Objectives: Familial hypercholesterolemia (FH) is an increasingly common inherited disorder that increases cardiovascular risk. Despite the importance of lifestyle interventions, adherence to a healthy diet among individuals with FH remains suboptimal. This pilot, multicenter, double-blind, placebo-controlled randomized trial aimed to evaluate the feasibility [...] Read more.
Background/Objectives: Familial hypercholesterolemia (FH) is an increasingly common inherited disorder that increases cardiovascular risk. Despite the importance of lifestyle interventions, adherence to a healthy diet among individuals with FH remains suboptimal. This pilot, multicenter, double-blind, placebo-controlled randomized trial aimed to evaluate the feasibility and preliminary effects of a culturally adapted cardioprotective diet (DICA-FH), alone or in combination with phytosterol and/or krill oil supplementation, on lipid parameters in Brazilian adults with probable or definitive FH. Methods: Between May and August 2023, 58 participants were enrolled across nine Brazilian centers and randomized (1:1:1:1) into four groups: DICA-FH + phytosterol placebo + krill oil placebo; DICA-FH + phytosterol 2 g/day + krill oil placebo; DICA-FH + phytosterol placebo + krill oil 2 g/day; and DICA-FH + phytosterol 2 g/day + krill oil 2 g/day. Interventions lasted 120 days. The primary outcomes were mean low-density lipoprotein cholesterol (LDL-c) and lipoprotein(a) (Lp[a]) levels, as well as adherence to treatment at follow-up. Secondary outcomes included mean levels of other lipids, frequency of adverse events, and assessment of protocol implementation components. All data were presented separately for the allocation groups: phytosterol vs. placebo and krill oil vs. placebo. Results: Mean age was 54.5 ± 13.7 years, and 58.6% were women. Both adherence to protocol (91.8% attendance; 79.1% investigational product intake) and retention (86.2%) were high. No significant differences between groups were found for LDL-c or Lp(a). However, regardless of allocation to active supplementation or placebo, a significant reduction in Lp(a) concentrations was observed following the DICA-FH intervention (median difference: −3.8 mg/dL [interquartile range: −7.5 to −1.2]; p < 0.01). Significant reductions in oxidized LDL (LDL-ox) and LDL-ox/LDL-c ratio were also observed in the overall sample (p < 0.01). Although not statistically significant, all groups showed improvements in diet quality after 120 days. No serious adverse events related to the interventions were reported. Additionally, most protocol implementation components were successfully achieved. Conclusions: The DICA-FH strategy, with or without supplementation, was safe and well-tolerated. Although not powered to detect clinical efficacy (which is acceptable in exploratory pilot trials), the study supports the feasibility of a larger trial and highlights the potential of dietary interventions in the management of HF. Full article
(This article belongs to the Special Issue Lipids and Lipoproteins in Cardiovascular Diseases)
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40 pages, 2483 KiB  
Review
Biological and Biosimilar Medicines in Contemporary Pharmacotherapy for Metabolic Syndrome
by Wiktoria Górecka, Daria Berezovska, Monika Mrozińska, Grażyna Nowicka and Monika E. Czerwińska
Pharmaceutics 2025, 17(6), 768; https://doi.org/10.3390/pharmaceutics17060768 - 11 Jun 2025
Viewed by 1349
Abstract
The discovery of new drugs offers valuable alternatives, particularly for treating diseases that are resistant to existing therapies or involving complex, multi-organ conditions such as metabolic syndrome. Although treatment algorithms are generally well established and primarily based on synthetic pharmaceuticals, they are increasingly [...] Read more.
The discovery of new drugs offers valuable alternatives, particularly for treating diseases that are resistant to existing therapies or involving complex, multi-organ conditions such as metabolic syndrome. Although treatment algorithms are generally well established and primarily based on synthetic pharmaceuticals, they are increasingly being supplemented by biological and biosimilar agents. This trend is particularly evident in the development and advancement of anti-diabetic and hypolipemic therapies. This review explores advances in the treatment of hypercholesterolemia and hypertriglyceridemia, elevated lipoprotein(a) [Lp(a)], diabetes, and obesity associated with metabolic syndrome. It focuses mainly on biopharmaceuticals such as proteins and nucleotide-based drugs (antisense oligonucleotides, small interfering RNA), but also on dipeptidyl peptidase-4 (DPP-4) inhibitors classified as incretin drugs along with glucagon-like peptide-1 (GLP-1) analogues. Due to the substantial role of SGLT-2 (sodium/glucose cotransporter 2) inhibitors in novel diabetes therapies, especially for managing cardiovascular risk, this group of compounds was also included in this review. Many clinical data in the field of effectiveness of biopharmaceuticals in metabolic disorders are provided. Therefore, in this review, we mainly include a brief history of drug development and approval, first synthesis and structure modifications, which relevantly influence pharmacokinetics, and safety. We provide only brief comparison of biological drugs with metformin and sulphonylureas derivatives. Databases such as PubMed, Scopus, and Google Scholar are searched for the period between 2000 and 2024. Full article
(This article belongs to the Section Biologics and Biosimilars)
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22 pages, 292 KiB  
Review
Lp(a)-Lowering Agents in Development: A New Era in Tackling the Burden of Cardiovascular Risk?
by Niki Katsiki, Michal Vrablik, Maciej Banach and Ioanna Gouni-Berthold
Pharmaceuticals 2025, 18(5), 753; https://doi.org/10.3390/ph18050753 - 19 May 2025
Viewed by 2714
Abstract
Lipoprotein (a) [Lp(a)] has been recognized as an independent, inherited, causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, thus representing a major target of residual CV risk. Currently, no drug has been officially approved for lowering Lp(a) levels, and [...] Read more.
Lipoprotein (a) [Lp(a)] has been recognized as an independent, inherited, causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, thus representing a major target of residual CV risk. Currently, no drug has been officially approved for lowering Lp(a) levels, and in clinical practice, Lp(a) is mainly used to (re)define CV risk, particularly in individuals at borderline CV risk and people with a family history of premature coronary heart disease, according to various guidelines. Specific Lp(a)-targeted antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) agents have been developed to produce substantial Lp(a) reductions via the inhibition of apo(a) synthesis in the liver. These drugs are conjugated to N-acetylgalactosamine (GalNAc) to ensure their binding to asialoglycoproteins, which are specifically expressed on the surface of the hepatocytes. Such drugs include pelacarsen (an injectable ASO) and olpasiran, zerlasiran, and lepodisiran (injectable siRNA agents). Muvalaplin represents another therapeutic option to lower Lp(a) levels, since it is an oral selective small molecule inhibitor of Lp(a) formation, thus potentially exerting certain advantages in terms of its clinical use. The present narrative review summarizes the available clinical data on the efficacy and safety of these investigational Lp(a)-lowering therapies, as reported in phase 1 and 2 trials. The effects of these drugs on other [aside from Lp(a)] lipid parameters are also discussed. The phase 3 CV trial outcomes are ongoing for some of these agents (i.e., pelacarsen, olpasiran, and lepodisiran) and are briefly mentioned. Overall, there is an urgent need for evidence-based guidelines on Lp(a) reduction in daily clinical practice, following the results of the phase 3 CV trials, as well as for establishing the ideal Lp(a) quantification method (i.e., using an apo(a) isoform-independent assay with appropriate calibrators, reporting the Lp(a) level in molar units). Full article
(This article belongs to the Section Pharmacology)
13 pages, 1042 KiB  
Review
Lipoprotein(a) and Effects of Diet: Time for Reassessment
by Byambaa Enkhmaa and Lars Berglund
Nutrients 2025, 17(10), 1714; https://doi.org/10.3390/nu17101714 - 19 May 2025
Viewed by 2150
Abstract
Dietary modification is a critical tool in the prevention of cardiovascular disease (CVD). While the role of saturated fat (SFA) intake is well established in affecting LDL cholesterol concentrations, diet impacts on lipoprotein(a) (Lp(a)) have been less studied. Lp(a) is a prevalent, strong, [...] Read more.
Dietary modification is a critical tool in the prevention of cardiovascular disease (CVD). While the role of saturated fat (SFA) intake is well established in affecting LDL cholesterol concentrations, diet impacts on lipoprotein(a) (Lp(a)) have been less studied. Lp(a) is a prevalent, strong, and highly heritable risk factor for CVD and a therapeutic target for CVD risk management. While significant insights have been made into the genetic regulation of Lp(a), our understanding of any metabolic impact on Lp(a) by other factors, including diets, is limited. For many years, Lp(a) was not considered to be subject to dietary regulation, but there is now clear evidence of a dietary impact, in particular variability in SFA intake, on Lp(a) concentrations. The present narrative review aims to provide an updated view on dietary regulation of Lp(a), moving beyond studies testing the effect of reducing SFA intake, to include new evidence from clinical trials on the impact of an increased sugar intake and ketogenic diets. In addition to describing an opposite effect of SFA on Lp(a) and LDL cholesterol concentrations, with a rise in Lp(a) during a reduced SFA intake, this review also provides new data on the role of apolipoprotein(a) size polymorphism, a major genetic regulator of Lp(a) concentrations. Beyond an impact on Lp(a) concentrations, the extent to which diet might impact Lp(a)’s molecular and metabolic properties including its lipidomic composition remains unknown. Taken together, evidence shows the presence of a dietary modulation of Lp(a) beyond its genetic control and points to the need to better understand Lp(a)’s cardiovascular risk factor properties, including metabolomics/lipidomics characteristics. This also raises the issue whether diet should be a component of elevated Lp(a) management, and this needs to be addressed in future studies. Full article
(This article belongs to the Special Issue Nutrients: 15th Anniversary)
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13 pages, 1096 KiB  
Article
The Influence of Genotype on the Cardiopulmonary Test Response in Patients Affected by Hypertrophic Cardiomyopathy
by Maria Felicia Gagliardi, Gabriella Malfatto, Claudia Baratto, Alessia Giglio, Valeria Rella, Paolo Cerea, Davide Mariani, Sabrina Salerno, Silvia Ravaro, Silvia Castelletti, Gerardina Fratianni, Chiara Alberio, Matteo Pedrazzini, Mariam Khujadze, Luigi P. Badano, Denisa Muraru, Gianfranco Parati, Franco Cecchi, Sergio Caravita and Lia Crotti
Cardiogenetics 2025, 15(2), 12; https://doi.org/10.3390/cardiogenetics15020012 - 29 Apr 2025
Viewed by 1054
Abstract
In hypertrophic cardiomyopathy (HCM), the presence of pathogenic/likely pathogenic (P/LP) disease-causing genetic variants may indicate a worse prognosis. Few data exist on the effects of these genetic variants on cardiopulmonary exercise test (CPET) performance in HCM patients. We analysed asymptomatic and slightly symptomatic [...] Read more.
In hypertrophic cardiomyopathy (HCM), the presence of pathogenic/likely pathogenic (P/LP) disease-causing genetic variants may indicate a worse prognosis. Few data exist on the effects of these genetic variants on cardiopulmonary exercise test (CPET) performance in HCM patients. We analysed asymptomatic and slightly symptomatic HCM patients (NYHA I-II) whose genetic analysis and CPET were available; at baseline, left ventricular function was normal and severe left ventricular outflow trait obstruction was excluded. Out of 120 HCM patients, we excluded 13 carrying variants of uncertain significance; of the remaining 107 patients, 54 were genotype negative [gene (−)], and 53 had a P/LP variant in sarcomeric genes [gene (+)]. Patients in the two groups had similar NYHA class, cardiovascular risk factors and echocardiographic characteristics. Gene (+) patients showed a lower peak VO2% and O2 pulse % (p < 0.05). Moreover, among gene (+), patients with P/LP variants in the so called “thin-filament” genes (TNNT2, TPM1 and MYL3) had the poorest CPET results. In asymptomatic or slightly symptomatic HCM patients with similar echocardiographic characteristics, exercise tolerance is affected by the genetic background. Indeed, exercise capacity is poorer in gene (+) compared to gene (−) patients and those carrying P/LP variants in “thin-filament” genes show the worst performance. Full article
(This article belongs to the Section Cardiovascular Genetics in Clinical Practice)
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15 pages, 1754 KiB  
Article
Maternal Nutritional Programming: Sex-Specific Cardiovascular and Immune Outcomes Following Perinatal High-Fat Diet Exposure
by Yasir Alsiraj, Hong Huang, Robin Shoemaker, Brandon Schanbacher, Margaret Murphy, Peter Giannone and John A. Bauer
Nutrients 2025, 17(9), 1464; https://doi.org/10.3390/nu17091464 - 26 Apr 2025
Viewed by 517
Abstract
Background: The long-term effects of a perinatal high-fat diet on the cardiovascular function of offspring are not well elucidated. We hypothesize that perinatal exposure to a high-fat diet alters adult cardiovascular and immune responses in a sex-specific manner. Methods: Male and female offspring [...] Read more.
Background: The long-term effects of a perinatal high-fat diet on the cardiovascular function of offspring are not well elucidated. We hypothesize that perinatal exposure to a high-fat diet alters adult cardiovascular and immune responses in a sex-specific manner. Methods: Male and female offspring were born to perinatal high-fat (pHFD) or control diet (pCD)-fed C57BL/6 mothers and weaned to a control diet. Cardiovascular function (baseline and response to an acute isoproterenol stress test) was quantified at 8 weeks of age, and acute blood inflammatory response to a single low dose of lipopolysaccharide at 9 weeks of age. Results: Male pHFD offspring had identical baseline cardiovascular function compared to pCD mice but a blunted response to isoproterenol (20–45% reductions in cardiac output, stroke volume, and left ventricular fractional shortening). In contrast, baseline cardiovascular parameters were reduced in female pHFD compared to pCD offspring, but there was no effect of perinatal diet on response to isoproterenol. Concentrations of TNF-α and IL-6 in plasma two hours after a low-dose LPS administration were highest in female pCD mice. Conclusions: Perinatal high-fat diet exposure resulted in sex-specific adaptations in cardiovascular function and immune response. Female offspring displayed baseline impairments, whereas male offspring showed latent vulnerability under stress. These differences may reflect underlying hormonal or epigenetic mechanisms that diverge by sex. Future studies should examine the roles of sex hormones and gene regulation pathways to better understand these dimorphic outcomes. These findings emphasize the importance of maternal diet in shaping offspring cardiometabolic risks and highlight potential avenues for nutritional interventions during pregnancy. Full article
(This article belongs to the Special Issue Dietary Components, Oxidative Stress and Metabolic Diseases)
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15 pages, 1654 KiB  
Review
Lipoprotein(a): Assessing the Current Knowledge and Gaps in Screening and Treatment—A Narrative Review
by Octavian Amaritei, Oana Laura Mierlan, Cristian Gutu and Gabriela Gurau
J. Cardiovasc. Dev. Dis. 2025, 12(5), 169; https://doi.org/10.3390/jcdd12050169 - 26 Apr 2025
Viewed by 1505
Abstract
Atherosclerotic cardiovascular disease (ASCVD) has long been screened using the traditional lipid profile, mainly focusing on LDL cholesterol. However, despite growing evidence supporting lipoprotein(a) [Lp(a)] as an independent risk factor involved in atherosclerosis, its clinical use remains limited. This review examines the reasons [...] Read more.
Atherosclerotic cardiovascular disease (ASCVD) has long been screened using the traditional lipid profile, mainly focusing on LDL cholesterol. However, despite growing evidence supporting lipoprotein(a) [Lp(a)] as an independent risk factor involved in atherosclerosis, its clinical use remains limited. This review examines the reasons behind the limited use of Lp(a) screening in clinical practice, assessing its role in cardiovascular risk, comparing it to traditional lipid markers and evaluating current assessment methods. It also explores existing and emerging treatments, including gene-silencing therapies, for managing elevated Lp(a) levels. One in four clinicians does not routinely check Lp(a) levels, which proves a lack of awareness amongst them. The reasons for that are implied to be that the cost is too high and that available treatments are scarce. The traditional lipid profile, including LDL, high-density lipoprotein (HDL) and triglycerides, continues to be the gold standard for CV risk assessment. One limitation of using Lp(a) in clinical practice is the significant variability in apo(a) sizes, which results from the presence of multiple isoforms determined by the number of kringle domains. This structural diversity poses challenges in standardizing measurement methods, affecting the accuracy and comparability of results. While statins have a minimal impact on Lp(a), PCSK9-i lowers its levels by 20–25%, although this class is not prescribed primarily for this reason. Lastly, gene-silencing therapies, which achieve the greatest reduction in Lp(a) levels, are still in phase III trials, and there is still a need to examine whether this reduction translates into CV benefits. These limitations should not discourage further research, because ASCVD’s complexity requires a more tailored approach. Current lipid-lowering therapy still fails in a minority of cases, as evidenced by new-onset cardiovascular events in patients with well-controlled LDL levels. There is a need for future interventional studies to assess whether a reduction in Lp(a) by PCSK9-i really translates into CV benefits, independent of LDL. Full article
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13 pages, 721 KiB  
Article
Lifestyle Modification in Prediabetes and Diabetes: A Large Population Analysis
by Michael L. Dansinger, Joi A. Gleason, Julia Maddalena, Bela F. Asztalos and Margaret R. Diffenderfer
Nutrients 2025, 17(8), 1333; https://doi.org/10.3390/nu17081333 - 11 Apr 2025
Viewed by 2219
Abstract
Background/Aims: Diabetes mellitus is a major cause of atherosclerotic cardiovascular disease (ASCVD). We examined a large population and tested the efficacy of a voluntary lifestyle program in prediabetic and diabetic subjects. Methods: Of 133,764 subjects, 56.3% were healthy, 36.2% were prediabetic, [...] Read more.
Background/Aims: Diabetes mellitus is a major cause of atherosclerotic cardiovascular disease (ASCVD). We examined a large population and tested the efficacy of a voluntary lifestyle program in prediabetic and diabetic subjects. Methods: Of 133,764 subjects, 56.3% were healthy, 36.2% were prediabetic, and 7.5% were diabetic. Fasting serum measurements of glucose, insulin, adiponectin, glycosylated hemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), glycated serum protein (GSP), fibrinogen, myeloperoxidase (MPO), lipoprotein-associated phospholipase A2 (LpPLA2), as well as standard lipids, direct low-density lipoprotein cholesterol (LDL-C), and small dense LDL-C (sdLDL-C) were performed using standard automated assays. Follow-up sampling at 6–12 months occurred in 20.1% of the prediabetic and 22.2% of the diabetic subjects; of these, 12.2% of the prediabetic and 9.7% of the diabetic subjects participated in a voluntary, real-world, digital dietitian-directed lifestyle-modification program with a 10-year diabetes risk being calculated using a biochemical model (Framingham). Results: Prediabetic and diabetic subjects had significantly elevated triglycerides, sdLDL-C, and hs-CRP and decreased HDL-C. They were insulin resistant as compared to healthy subjects, but only diabetics had significant reductions in insulin production. Lifestyle modification significantly reduced diabetes risk by 45.6% in prediabetics and significantly increased (2.4-fold) the percentage of diabetics that were in remission at follow-up (8.2% versus 3.4%) with increased weight loss (6.5 versus 2.0 pounds). Lifestyle intervention resulted in significant favorable effects on many metabolic markers. Conclusions: The measurement of fasting glucose and insulin is essential for the detection of decreased insulin production in diabetics. A digital lifestyle program can have favorable effects on ASCVD risk factors and diabetic status. Full article
(This article belongs to the Special Issue Impact of Lipids on Cardiovascular Health)
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19 pages, 11461 KiB  
Article
Lipoprotein(a) and Risk of Incident Atherosclerotic Cardiovascular Disease: Impact of High-Sensitivity C-Reactive Protein and Risk Variability Among Human Clinical Subgroups
by Ron C. Hoogeveen, Margaret R. Diffenderfer, Elise Lim, Ching-Ti Liu, Hiroaki Ikezaki, Weihua Guan, Michael Y. Tsai and Christie M. Ballantyne
Nutrients 2025, 17(8), 1324; https://doi.org/10.3390/nu17081324 - 11 Apr 2025
Cited by 1 | Viewed by 1666
Abstract
Background/Objectives: Elevated lipoprotein(a) [Lp(a)] is associated with increased incidence of atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the utility of Lp(a) as an ASCVD risk-enhancing factor, as recommended by the 2019 ACC/AHA guidelines on ASCVD primary prevention, and to determine whether C-reactive [...] Read more.
Background/Objectives: Elevated lipoprotein(a) [Lp(a)] is associated with increased incidence of atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the utility of Lp(a) as an ASCVD risk-enhancing factor, as recommended by the 2019 ACC/AHA guidelines on ASCVD primary prevention, and to determine whether C-reactive protein (CRP) modifies the association of elevated Lp(a) with ASCVD risk. Methods: Lp(a), high sensitivity CRP (hs-CRP), and other ASCVD risk factors, including blood lipids, blood pressure, diabetes status, body weight and height, and smoking, were measured in 15,933 participants (median age 61.7 years with 25th–75th percentiles 57–68 years, 56.7% female, 19.7% Black, free of ASCVD at baseline) in the Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and Multi-Ethnic Study of Atherosclerosis. Participants were followed for 10 years for incident ASCVD (coronary heart disease (CHD) or stroke) and CHD (including angioplasty and/or coronary artery bypass but minus stroke). These endpoints occurred in 9.7% and 7.4% of subjects, respectively. Results: Compared with the lowest Lp(a) category (<10 mg/dL), the highest Lp(a) category (≥50 mg/dL) carried a significantly increased incidence of ASCVD (hazard ratio [HR] = 1.31; 95% confidence interval [CI] 1.15–1.50; p < 0.001) and CHD (HR = 1.49; 95%CI 1.27–1.75; p < 0.001). The association of elevated Lp(a) with incident ASCVD was stronger in males and non-Black individuals and was independent of diabetes status. Lp(a) levels ≥ 50 mg/dL predicted the 10-year ASCVD risk for those at intermediate risk (≥7.5%, HR = 1.32; 95%CI 1.15–1.52; p < 0.001). There was a significant interaction between Lp(a) and hs-CRP; individuals with concomitant elevated levels of Lp(a) and hs-CRP had the highest ASCVD risk. Conclusions: Elevated Lp(a) levels were associated with increased ASCVD risk, particularly in individuals with concomitantly elevated hs-CRP levels and those at intermediate 10-year ASCVD risk. Full article
(This article belongs to the Special Issue Impact of Lipids on Cardiovascular Health)
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27 pages, 6854 KiB  
Article
Development of Rapidly Dissolving Microneedles Integrated with Valsartan-Loaded Nanoliposomes for Transdermal Drug Delivery: In Vitro and Ex Vivo Evaluation
by Ramsha Khalid, Syed Mahmood, Zarif Mohamed Sofian, Zamri Chik and Yi Ge
Pharmaceutics 2025, 17(4), 483; https://doi.org/10.3390/pharmaceutics17040483 - 7 Apr 2025
Cited by 1 | Viewed by 1285 | Correction
Abstract
Background: Hypertension (HTN) is recognized as a major risk factor for cardiovascular disease, chronic kidney disease, and peripheral artery disease. Valsartan (VAL), an angiotensin receptor blocker drug for hypertension, has been limited due to its poor solubility and poor absorption from the GIT, [...] Read more.
Background: Hypertension (HTN) is recognized as a major risk factor for cardiovascular disease, chronic kidney disease, and peripheral artery disease. Valsartan (VAL), an angiotensin receptor blocker drug for hypertension, has been limited due to its poor solubility and poor absorption from the GIT, which leads to low oral bioavailability. Objectives/Method: In the present research, firstly, VAL-loaded nanoliposomes were formulated and optimized using the Box–Behnken design (BBD). Optimized VAL-nanoliposomes were physically characterized and their fate was examined by scanning and transmission microscopy, DSC, FTIR, XRD, and ex vivo studies using rat skin. In vitro studies using human keratinocyte (HaCaT) cells showed a decrease in cell viability as the liposome concentration increased. Secondly, the formulation of VAL-loaded nanoliposomes was integrated into dissolvable microneedles (DMNs) to deliver the VAL transdermally, crossing the skin barrier for better systemic delivery. Results: The optimized nanoliposomes showed a vesicle size of 150.23 (0.47) nm, a ZP of −23.37 (0.50) mV, and an EE% of 94.72 (0.44)%. The DMNs were fabricated using a ratio of biodegradable polymers, sodium alginate (SA), and hydroxypropyl methylcellulose (HPMC). The resulting VAL-LP-DMNs exhibited sharp pyramidal microneedles, adequate mechanical properties, effective skin insertion capability, and rapid dissolution of the microneedles in rat skin. In the ex vivo analysis, the transdermal flux of VAL was significantly (5.36 (0.39) μg/cm2/h) improved by VAL-LP-DMNs. The enhancement ratio of the VAL-LP-DMNs was 1.85. In conclusion, liposomes combined with DMNs have shown high potential and bright prospects as carriers for the transdermal delivery of VAL. Conclusions: These DMNs can be explored in studies focused on in vivo evaluations to confirm their safety, pharmacokinetics profile, and pharmacodynamic efficacy. Full article
(This article belongs to the Section Biopharmaceutics)
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14 pages, 2812 KiB  
Systematic Review
The Impact of Elevated Lipoprotein (a) Levels on Postoperative Outcomes in Carotid Endarterectomy: A Systematic Review
by João Carvalheiras Marques, Mariana Fragão Marques, Hugo Ribeiro, António Pereira Neves, Peter Zlatanovic and João Rocha Neves
J. Clin. Med. 2025, 14(7), 2253; https://doi.org/10.3390/jcm14072253 - 26 Mar 2025
Viewed by 666
Abstract
Background/Objectives: Numerous studies have highlighted lipoprotein (a) (Lp(a)) as a significant, independent risk factor for the development and progression of cardiovascular diseases, including carotid artery disease, which is strongly correlated with an elevated risk of ischemic events and stroke. This systematic review aims [...] Read more.
Background/Objectives: Numerous studies have highlighted lipoprotein (a) (Lp(a)) as a significant, independent risk factor for the development and progression of cardiovascular diseases, including carotid artery disease, which is strongly correlated with an elevated risk of ischemic events and stroke. This systematic review aims to determine the impact of elevated Lp(a) levels on the postoperative outcomes in patients undergoing carotid endarterectomy (CEA). Methods: Four electronic databases—PubMed, Scopus, Web of Science, and Cochrane Library—were employed to search for studies assessing the association between elevated Lp(a) levels and the postoperative outcomes following CEA. The effect of elevated Lp(a) levels was systematically reviewed, and the outcomes reported in each study were evaluated. The quality of the studies was evaluated using the National Heart, Lung, and Blood Institute Study Quality Assessment Tool for observational cohorts and cross-sectional studies. Results: A total of five observational studies were included, with 1450 patients. The mean age of the participants in the studies ranged from 57 to 74 years, and the percentage of males ranged from 37.22% to 68.96%. One study showed that elevated Lp(a) levels were significantly associated with major adverse cardiovascular events (MACEs) after CEA, particularly periprocedural stroke, with another manuscript suggesting a long-term predictive value for acute coronary syndromes (ACSs) within 24 months following surgery. There was no association in the included studies with carotid plaque instability, inflammation biomarkers, or restenosis. Conclusions: This systematic review suggests an association of Lp(a) levels with MACEs and ACSs after CEA although no association with restenosis and carotid plaque inflammation and/or instability. Full article
(This article belongs to the Section Vascular Medicine)
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