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Cardiovascular and Metabolic Disease: New Treatment and Future Directions—the 3rd...
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Cardiovascular and Metabolic Disease: New Treatment and Future Directions—the 3rd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 6868

Special Issue Editor

Dr. Alfredo Caturano

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Guest Editor
Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
Interests: cardiovascular pharmacology; diabetes pharmacology; brugada syndrome; NAFLD; cardiovascular risk
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. In 2019, it has been estimated that 17.9 million people died from CVDs (32% of all global deaths). Of these deaths, 85% were due to heart attack and stroke. These data are usually powered by the coexistence of metabolic diseases, in particular diabetes. In fact, about 422 million people worldwide have diabetes, the majority living in low- and middle-income countries, and 1.5 million deaths are directly attributed to diabetes each year. It is vital to detect CVDs and metabolic disease as early as possible, as most cases can be prevented by addressing behavioral risk factors such as tobacco use, unhealthy diet and obesity, physical inactivity, and harmful use of alcohol. Moreover, we are the main actors and observers of the innovations in every field of CVDs and metabolic disease treatment, from the pharmacological approach, with the advent of sodium glucose cotransporter 2 inhibitors for both heart failure and diabetes, to the improvement of new less-invasive and invasive techniques such as immediate revascularization in both heart and brain infarction and new methods of mechanical cardiac support and multiorgan transplantation for the most advanced forms of heart failure.

Given the complexity of this topic and its impact on clinical practice and public health, Biomedicines is launching a Special Issue entitled “Cardiovascular and Metabolic Disease: New Treatments and Future Directions” with the aim of gathering accurate and up-to-date scientific information on all aspects of new and upcoming treatment opportunities for CVDs and metabolic diseases. It is my privilege to invite you and your co-workers to share their experience and expertise by submitting original research articles, systematic reviews and review articles reporting new ideas and recent advances in this topic.

Dr. Alfredo Caturano
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. Biomedicines is an international peer-reviewed open access monthly 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

  • cardiovascular disease
  • metabolic disease
  • diabetes
  • therapy
  • drugs
  • implantable device
  • heart failure
  • heart transplantation
  • cardiac surgery
  • future directions

Related Special Issues

Published Papers (8 papers)

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Research

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18 pages, 907 KiB  
Article
Does Metabolic Syndrome and Its Components Have Prognostic Significance for Renal and Cardiovascular Outcomes in IgA Nephropathy?
by Balázs Sági, Tibor Vas, Botond Csiky, Judit Nagy and Tibor József Kovács
Biomedicines 2024, 12(6), 1250; https://doi.org/10.3390/biomedicines12061250 - 4 Jun 2024
Viewed by 180
Abstract
Background: Patients with IgA nephropathy (IgAN), a chronic kidney disease (CKD), are significantly more likely to have cardiovascular (CV) mortality and morbidity than the general population. The occurrence of metabolic syndrome (MetS) and metabolic risk factors are independent risk factors for CV disease [...] Read more.
Background: Patients with IgA nephropathy (IgAN), a chronic kidney disease (CKD), are significantly more likely to have cardiovascular (CV) mortality and morbidity than the general population. The occurrence of metabolic syndrome (MetS) and metabolic risk factors are independent risk factors for CV disease and renal progression. The purpose of this study was to determine how metabolic characteristics in a homogeneous population of CKD patients relate to prognosis. Methods: A total of 145 patients with CKD stages 1–4 diagnosed with IgA nephropathy (92 men and 53 women, aged 54.7 ± 13 years) were examined and monitored for a median of 190 months. All-cause mortality and any CV event, such as stroke, myocardial infarction, revascularization (CV), end-stage renal disease, and renal replacement therapy (renal), have been included in the composite endpoints (CV and renal). Results: Patients with MetS had significantly more primary endpoint events (23/65 patients vs. 15/60 patients, p < 0.001) compared to the non-MetS group. The MetS group had a statistically significant increase in both primary renal and CV endpoints (18/65 vs. 10/60, p = 0.001), and in CV endpoint events (7/65 vs. 6/60, p = 0.029) among the secondary endpoints (CV and renal separately). Based on Cox regression analysis, the main endpoint independent predictors of survival were dyslipidemia, eGFR, hemoglobin, urine albuminuria, and diabetes mellitus. Independent predictors of secondary renal endpoints were dyslipidemia, hemoglobin, urine albumin, and eGFR. Predictors of secondary cardiovascular endpoints were gender, BMI, and diabetes. When Kaplan–Meier curves were analyzed at the combined endpoints (CV and renal) or each endpoint independently, significant differences were seen between MetS and non-MetS. With more MetS components, the primary endpoint rate increased significantly (MetS comp. 0 vs. MetS comp. 2+, primary endpoints, p = 0.012). Conclusions: Our results show that the metabolic profile has a prognostic role not only for renal endpoints but also for CV endpoints in IgAN. BMI, hyperuricemia, hypertension, and diabetes have a predictive value for the prognosis of IgA nephropathy. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions—the 3rd Edition)
11 pages, 4641 KiB  
Article
Continuous Monitoring of Advanced Hemodynamic Parameters during Hemodialysis Demonstrated Early Variations in Patients Experiencing Intradialytic Hypotension
by Yotam Kolben, Ittamar Gork, David Peled, Shani Amitay, Peleg Moshel, Nir Goldstein, Arik Ben Ishay, Meir Fons, Michael Tabi, Arik Eisenkraft, Yftach Gepner and Dean Nachman
Biomedicines 2024, 12(6), 1177; https://doi.org/10.3390/biomedicines12061177 - 25 May 2024
Viewed by 372
Abstract
Intradialytic hypotension (IDH) is a severe complication of hemodialysis (HD) with a significant impact on morbidity and mortality. In this study, we used a wearable device for the continuous monitoring of hemodynamic vitals to detect hemodynamic changes during HD and attempted to identify [...] Read more.
Intradialytic hypotension (IDH) is a severe complication of hemodialysis (HD) with a significant impact on morbidity and mortality. In this study, we used a wearable device for the continuous monitoring of hemodynamic vitals to detect hemodynamic changes during HD and attempted to identify IDH. End-stage kidney disease patients were continuously monitored 15 min before starting the session and until 15 min after completion of the session, measuring heart rate (HR), noninvasive cuffless systolic and diastolic blood pressure (SBP and DBP), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR). Data were analyzed retrospectively and included comparing BP measured by the wearable devices (recorded continuously every 5 s) and the cuff-based devices. A total of 98 dialysis sessions were included in the final analysis, and IDH was identified in 22 sessions (22.5%). Both SBP and DBP were highly correlated (r > 0.62, p < 0.001 for all) between the wearable device and the cuff-based measurements. Based on the continuous monitoring, patients with IDH had earlier and more profound reductions in SBP and DBP during the HD treatment. In addition, nearly all of the advanced vitals differed between groups. Further studies should be conducted in order to fully understand the potential of noninvasive advanced continuous monitoring in the prediction and prevention of IDH events. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions—the 3rd Edition)
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14 pages, 849 KiB  
Article
The Randomized, Multicenter, Open-Label, Controlled POLBOS 3 Trial Comparing Regular Drug-Eluting Stents and the Sirolimus-Eluting BiOSS LIM C Dedicated Coronary Bifurcation Stent: Four-Year Results
by Robert J. Gil, Adam Kern, Krystian Bojko, Aneta Gziut-Rudkowska, Dobrin Vassilev and Jacek Bil
Biomedicines 2024, 12(5), 938; https://doi.org/10.3390/biomedicines12050938 - 23 Apr 2024
Viewed by 545
Abstract
This multicenter, randomized study aimed to compare the sirolimus-eluting BiOSS LIM C dedicated coronary bifurcation stent with second-generation -limus drug-eluting stents (rDESs) in the treatment of non-left main (non-LM) coronary bifurcation. The deployment of a single stent in the main vessel–main branch across [...] Read more.
This multicenter, randomized study aimed to compare the sirolimus-eluting BiOSS LIM C dedicated coronary bifurcation stent with second-generation -limus drug-eluting stents (rDESs) in the treatment of non-left main (non-LM) coronary bifurcation. The deployment of a single stent in the main vessel–main branch across a side branch was the default strategy in all patients. The primary endpoint was the rate of major cardiovascular events (cardiac death, myocardial infarction, and target lesion revascularization) at 48 months. We enrolled 230 patients, allocating 116 patients to the BiOSS LIM C group and 114 patients to the rDES group. Most procedures were elective (BiOSS vs. rDES: 48.3% vs. 59.6%, p = 0.09) and performed in bifurcations within the left anterior descending/diagonal branch (BiOSS vs. rDES: 51.7% vs. 61.4%, p = 0.15). At 48 months, there were no statistically significant differences between the BiOSS and rDES groups in terms of major adverse cardiovascular events (MACE), cardiac death, myocardial infarction (MI), or target lesion revascularization (TLR) as follows: MACEs—18.1% vs. 14.9%, HR 1.36, 95% CI 0.62–2.22, and p = 0.33; cardiac death—4.3% vs. 3.5%, HR 1.23, 95% CI 0.33–4.56, and p = 0.75; MI—2.6% vs. 3.5%, HR 0.73, 95% CI 0.17–3.23, and p = 0.68; and TLR—11.2% vs. 7.9%, HR 1.66, 95% CI 0.75–3.71, and p = 0.21. The implantation success rate of the BiOSS LIM C stent was very high, and the cumulative MACE rates were promising. The POLBOS 3 trial sets an important benchmark for treating non-LM coronary bifurcations (ClinicalTrials.gov NCT03548272). Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions—the 3rd Edition)
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12 pages, 1023 KiB  
Article
Electrical Activity Changes and Neurovascular Unit Markers in the Brains of Patients after Cardiac Surgery: Effects of Multi-Task Cognitive Training
by Irina Tarasova, Irina Kukhareva, Darya Kupriyanova, Tatjana Temnikova, Evgenia Gorbatovskaya and Olga Trubnikova
Biomedicines 2024, 12(4), 756; https://doi.org/10.3390/biomedicines12040756 - 28 Mar 2024
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Abstract
Background: There is growing interest in finding methods to enhance cognitive function and comprehend the neurophysiological mechanisms that underlie these improvements. It is assumed that non-pharmacological interventions have better results in cognitive recovery. The aim of this study was to assess the effect [...] Read more.
Background: There is growing interest in finding methods to enhance cognitive function and comprehend the neurophysiological mechanisms that underlie these improvements. It is assumed that non-pharmacological interventions have better results in cognitive recovery. The aim of this study was to assess the effect of multi-task cognitive training (MTT) on electroencephalographic (EEG) changes and markers of the neurovascular unit in patients undergoing coronary artery bypass grafting (CABG). Methods: This prospective cohort study involved 62 CABG patients aged 45–75 years, 30 of whom underwent a 5–7-day MTT course. The groups of patients were comparable with respect to baseline clinical and anamnestic characteristics. An EEG study was performed before surgery and 11–12 days after CABG. Markers of the neurovascular unit (S100β, NSE, and BDNF) were examined at three time points: before surgery, within the first 24 h after surgery, and 11–12 days after CABG. Results: Patients without training demonstrated higher relative theta power changes compared to the MTT patients. The course of MTT was associated with low plasma S100β concentration but high BDNF levels at the end of the training course. Conclusions: The theta activity changes and the markers of the neurovascular unit (S100β, BDNF) indicated that the severity of brain damage in cardiac surgery patients after a short course of MTT was slightly reduced. Electrical brain activity indicators and vascular markers can be informative for monitoring the process of cognitive rehabilitation in cardiac surgery patients. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions—the 3rd Edition)
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14 pages, 986 KiB  
Article
Artificial Intelligence Applied to Electrical and Non-Invasive Hemodynamic Markers in Elderly Decompensated Chronic Heart Failure Patients
by Gianfranco Piccirillo, Federica Moscucci, Martina Mezzadri, Cristina Caltabiano, Giovanni Cisaria, Guendalina Vizza, Valerio De Santis, Marco Giuffrè, Sara Stefano, Claudia Scinicariello, Myriam Carnovale, Andrea Corrao, Ilaria Lospinuso, Susanna Sciomer and Pietro Rossi
Biomedicines 2024, 12(4), 716; https://doi.org/10.3390/biomedicines12040716 - 22 Mar 2024
Viewed by 1051
Abstract
Objectives: The first aim of this study was to assess the predictive power of Tend interval (Te) and non-invasive hemodynamic markers, based on bioimpedance in decompensated chronic heart failure (CHF). The second one was to verify the possible differences in repolarization and hemodynamic [...] Read more.
Objectives: The first aim of this study was to assess the predictive power of Tend interval (Te) and non-invasive hemodynamic markers, based on bioimpedance in decompensated chronic heart failure (CHF). The second one was to verify the possible differences in repolarization and hemodynamic data between CHF patients grouped by level of left ventricular ejection fraction (LVEF). Finally, we wanted to check if repolarization and hemodynamic data changed with clinical improvement or worsening in CHF patients. Methods: Two hundred and forty-three decompensated CHF patients were studied by 5 min ECG recordings to determine the mean and standard deviation (TeSD) of Te (first study). In a subgroup of 129 patients (second study), non-invasive hemodynamic and repolarization data were recorded for further evaluation. Results: Total in-hospital and cardiovascular mortality rates were respectively 19 and 9%. Te was higher in the deceased than in surviving subjects (Te: 120 ± 28 vs. 100 ± 25 ms) and multivariable logistic regression analysis reported that Te was related to an increase of total (χ2: 35.45, odds ratio: 1.03, 95% confidence limit: 1.02–1.05, p < 0.001) and cardiovascular mortality (χ2: 32.58, odds ratio: 1.04, 95% confidence limit: 1.02–1.06, p < 0.001). Subjects with heart failure with reduced ejection fraction (HFrEF) reported higher levels of repolarization and lower non-invasive systolic hemodynamic data in comparison to those with preserved ejection fraction (HFpEF). In the subgroup, patients with the NT-proBNP reduction after therapy showed a lower rate of Te, heart rate, blood pressures, contractility index, and left ventricular ejection time in comparison with the patients without NT-proBNP reduction. Conclusion: Electrical signals from ECG and bioimpedance were capable of monitoring the patients with advanced decompensated CHF. These simple, inexpensive, non-invasive, easily repeatable, and transmissible markers could represent a tool to remotely monitor and to intercept the possible worsening of these patients early by machine learning and artificial intelligence tools. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions—the 3rd Edition)
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Review

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16 pages, 1240 KiB  
Review
The Role of Lipoprotein(a) in Peripheral Artery Disease
by Nicholas Pavlatos and Dinesh K. Kalra
Biomedicines 2024, 12(6), 1229; https://doi.org/10.3390/biomedicines12061229 - 1 Jun 2024
Viewed by 45
Abstract
Lipoprotein(a) is a low-density-lipoprotein-like particle that consists of apolipoprotein(a) bound to apolipoprotein(b). It has emerged as an established causal risk factor for atherosclerotic cardiovascular disease, stroke, and aortic valve stenosis through multifactorial pathogenic mechanisms that include inflammation, atherogenesis, and thrombosis. Despite an estimated [...] Read more.
Lipoprotein(a) is a low-density-lipoprotein-like particle that consists of apolipoprotein(a) bound to apolipoprotein(b). It has emerged as an established causal risk factor for atherosclerotic cardiovascular disease, stroke, and aortic valve stenosis through multifactorial pathogenic mechanisms that include inflammation, atherogenesis, and thrombosis. Despite an estimated 20% of the global population having elevated lipoprotein(a) levels, testing remains underutilized due to poor awareness and a historical lack of effective and safe therapies. Although lipoprotein(a) has a strong association with coronary artery disease and cerebrovascular disease, its relationship with peripheral artery disease is less well established. In this article, we review the epidemiology, biology, and pathogenesis of lipoprotein(a) as it relates to peripheral artery disease. We also discuss emerging treatment options to help mitigate major adverse cardiac and limb events in this population. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions—the 3rd Edition)
27 pages, 1257 KiB  
Review
Zebrafish as a Model for Cardiovascular and Metabolic Disease: The Future of Precision Medicine
by Ramcharan Singh Angom and Naga Malleswara Rao Nakka
Biomedicines 2024, 12(3), 693; https://doi.org/10.3390/biomedicines12030693 - 20 Mar 2024
Viewed by 1597
Abstract
The zebrafish (Danio rerio) has emerged as an appreciated and versatile model organism for studying cardiovascular and metabolic diseases, offering unique advantages for both basic research and drug discovery. The genetic conservation between zebrafish and humans and their high fecundity and [...] Read more.
The zebrafish (Danio rerio) has emerged as an appreciated and versatile model organism for studying cardiovascular and metabolic diseases, offering unique advantages for both basic research and drug discovery. The genetic conservation between zebrafish and humans and their high fecundity and transparent embryos allow for efficient large-scale genetic and drug-oriented screening studies. Zebrafish possess a simplified cardiovascular system that shares similarities with mammals, making them particularly suitable for modeling various aspects of heart development, function, and disease. The transparency of zebrafish embryos enables the real-time visualization of cardiovascular dynamics, offering insights into early embryonic events and facilitating the study of heart-related anomalies. In metabolic research, zebrafish provide a cost-effective platform for modeling obesity, type 2 diabetes, hyperlipidemia, and other metabolic disorders. Their high reproductive rate allows for the generation of large cohorts for robust statistical analyses, while advanced genetic tools, such as CRISPR/Cas9, enable precise gene editing with which to model specific genetic mutations associated with human diseases. Zebrafish metabolic models have been instrumental in elucidating the molecular mechanisms underlying metabolic diseases, studying the effects of environmental factors, and identifying potential therapeutic targets. Additionally, the permeability of zebrafish embryos to small molecules facilitates drug discovery and screening, offering a rapid and economical approach to identifying compounds with therapeutic potential. In conclusion, zebrafish cardiovascular and metabolic disease models continue to contribute significantly to our perception of disease pathogenesis, providing a platform for translational research and developing novel therapeutic interventions. The versatility, scalability, and genetic manipulability of zebrafish position them as an invaluable asset in unraveling the complexities of cardiovascular and metabolic diseases. This review presents an overview of the zebrafish model’s key features and contributions to investigating cardiovascular and metabolic disorders. We discuss the benefits and drawbacks of using zebrafish models to study human disease and the critical findings revealed by the progress in this endeavor to date. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions—the 3rd Edition)
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8 pages, 230 KiB  
Brief Report
Effect of Hypoglycemia and Rebound Hyperglycemia on Proteomic Cardiovascular Risk Biomarkers
by Manjula Nandakumar, Thozhukat Sathyapalan, Stephen L. Atkin and Alexandra E. Butler
Biomedicines 2024, 12(6), 1137; https://doi.org/10.3390/biomedicines12061137 - 21 May 2024
Viewed by 285
Abstract
Introduction: Hypoglycemia has been associated with cardiovascular events, and glucose variability has been suggested to be associated with increased cardiovascular risk. Therefore, in this study, we examined the effect on proteomic cardiovascular risk protein markers of (i) mild iatrogenic hypoglycemia and (ii) [...] Read more.
Introduction: Hypoglycemia has been associated with cardiovascular events, and glucose variability has been suggested to be associated with increased cardiovascular risk. Therefore, in this study, we examined the effect on proteomic cardiovascular risk protein markers of (i) mild iatrogenic hypoglycemia and (ii) severe iatrogenic hypoglycemia followed by rebound hyperglycemia. Methods: Two iatrogenic hypoglycemia studies were compared; firstly, mild hypoglycemia in 18 subjects (10 type 2 diabetes (T2D), 8 controls; blood glucose to 2.8 mmoL/L (50 mg/dL) for 1 h), and secondly, severe hypoglycemia in 46 subjects (23 T2D, 23 controls; blood glucose to <2.2 mmoL/L (<40 mg/dL) transiently followed by intravenous glucose reversal giving rebound hyperglycemia). A SOMAscan assay was used to measure 54 of the 92 cardiovascular protein biomarkers that reflect biomarkers involved in inflammation, cellular metabolic processes, cell adhesion, and immune response and complement activation. Results: Baseline to euglycemia showed no change in any of the proteins measured in the T2D cohort. With severe hypoglycemia, the study controls showed an increase in Angiopoietin 1 (ANGPT1) (p < 0.01) and Dickkopf-1 (DKK1) (p < 0.01), but no changes were seen with mild hypoglycemia. In both the mild and severe hypoglycemia studies, at the point of hypoglycemia, T2D subjects showed suppression of Brother of CDO (BOC) (p < 0.01). At 1 h post-hypoglycemia, the changes in ANGPT1, DKK1, and BOC had resolved, with no additional protein biomarker changes despite rebound hyperglycemia from 1.8 ± 0.1 to 12.2 ± 2.0 mmol/L. Conclusions: Proteomic biomarkers of cardiovascular disease showed changes at hypoglycemia that resolved within 1 h following the hypoglycemic event and with no changes following hyperglycemia rebound, suggesting that any cardiovascular risk increase is due to the hypoglycemia and not due to glucose fluctuation per se. Full article
(This article belongs to the Special Issue Cardiovascular and Metabolic Disease: New Treatment and Future Directions—the 3rd Edition)
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