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Advances in Cardiovascular Pharmacology: The Era of Targeted Therapies in Cardiology 2.0

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A special issue of Biomedicines (ISSN 2227-9059).

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 25836

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Dr. Francesco Massari

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Guest Editor

Cardiology Department, Perinei Hospital, Bari, Italy
Interests: heart failure; cardiomyopathies; cardiac physiology; cardiorenal syndrome; cardiovascular pharmacology
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Pietro Scicchitano

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Guest Editor

Cardiology Department, Perinei Hospital, Bari, Italy
Interests: noninvasive assessment; heart failure; arrhythmias; preventive cardiology; cardiovascular pharmacology; cardio-oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Despite primary and secondary prevention protocols, the mortality and morbidity rates still remain higher (about 4–17%).

Recently, pharmacological industries have introduced new drugs that are proven to dramatically impact residual atherothrombotic risk and positively influence the outcome of invalidating pathologies, such as heart failure.

Specifically, cardiovascular pharmacology is now experiencing a new approach to cardiac diseases—the molecular “influence” of gene transcription and transduction in order to target the inner mechanism, which could be responsible for the onset and progression of CVDs.

Recent innovations in the field of non-invasive treatment of CVDs are focusing on three main issues: 1. specifically identifying and treating the core cause of the illness; 2. avoiding adverse events related to pharmacological treatments; 3. improving the adherence to and persistence of therapies.

The aim of this Special Issue is to provide a detailed overview of new pharmacological approaches to CVDs.

Authors are invited to contribute original basic research, prospective studies, and systematic reviews in the field of pharmacological approaches to cardiac and vascular diseases by outlining the most recent advances in therapies and treatments.

Dr. Francesco Massari
Dr. Pietro Scicchitano
Guest Editors

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Keywords

cardiovascular pharmacology
target therapy
siRNA
lipid management
heart failure
prognosis

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Published Papers (9 papers)

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Research

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23 pages, 2853 KiB

Open AccessArticle

Moderate-Intensity Exercise Improves Mesenteric Arterial Function in Male UC Davis Type-2 Diabetes Mellitus (UCD-T2DM) Rats: A Shift in the Relative Importance of Endothelium-Derived Relaxing Factors (EDRF)

by Md Rahatullah Razan, Said Amissi, Rifat Ara Islam, James L. Graham, Kimber L. Stanhope, Peter J. Havel and Roshanak Rahimian

Biomedicines 2023, 11(4), 1129; https://doi.org/10.3390/biomedicines11041129 - 8 Apr 2023

Cited by 3 | Viewed by 2071

Abstract

The beneficial cardiovascular effects of exercise are well documented, however the mechanisms by which exercise improves vascular function in diabetes are not fully understood. This study investigates whether there are (1) improvements in blood pressure and endothelium-dependent vasorelaxation (EDV) and (2) alterations in the relative contribution of endothelium-derived relaxing factors (EDRF) in modulating mesenteric arterial reactivity in male UC Davis type-2 diabetes mellitus (UCD-T2DM) rats, following an 8-week moderate-intensity exercise (MIE) intervention. EDV to acetylcholine (ACh) was measured before and after exposure to pharmacological inhibitors. Contractile responses to phenylephrine and myogenic tone were determined. The arterial expressions of endothelial nitric oxide (NO) synthase (eNOS), cyclooxygenase (COX), and calcium-activated potassium channel (K_Ca) channels were also measured. T2DM significantly impaired EDV, increased contractile responses and myogenic tone. The impairment of EDV was accompanied by elevated NO and COX importance, whereas the contribution of prostanoid- and NO-independent (endothelium-derived hyperpolarization, EDH) relaxation was not apparent compared to controls. MIE 1) enhanced EDV, while it reduced contractile responses, myogenic tone and systolic blood pressure (SBP), and 2) caused a shift away from a reliance on COX toward a greater reliance on EDH in diabetic arteries. We provide the first evidence of the beneficial effects of MIE via the altered importance of EDRF in mesenteric arterial relaxation in male UCD-T2DM rats. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Pharmacology: The Era of Targeted Therapies in Cardiology 2.0)

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13 pages, 1347 KiB

Open AccessArticle

Anaemia and Congestion in Heart Failure: Correlations and Prognostic Role

by Pietro Scicchitano, Massimo Iacoviello, Antonio Massari, Micaela De Palo, Angela Potenza, Raffaella Landriscina, Silvia Abruzzese, Maria Tangorra, Piero Guida, Marco Matteo Ciccone, Pasquale Caldarola and Francesco Massari

Biomedicines 2023, 11(3), 972; https://doi.org/10.3390/biomedicines11030972 - 21 Mar 2023

Cited by 8 | Viewed by 1808

Abstract

The aim of this study was to evaluate the relationship between anaemia and biomarkers of central/peripheral congestion in heart failure (HF) and the impact on mortality. We retrospectively evaluated 434 acute/chronic HF (AHF/CHF) patients. Anaemia was defined as haemoglobin levels <12 g/dL (women) or <13 g/dL (men). The brain natriuretic peptide (BNP) and hydration index (HI) were measured. The endpoint of the study was all-cause mortality. Anaemia occurred in 59% of patients with AHF and in 35% with CHF (p < 0.001) and showed a significant correlation with the NYHA functional class and renal function. BNP and HI were significantly higher in patients with anaemia than in those without anaemia. Independent predictors of anaemia included BNP, estimated creatinine clearance (eCrCL), and HI. The all-cause mortality rate was 21%, which was significantly higher in patients with anaemia than in those without anaemia (30% vs. 14%, p < 0.001; hazard ratio: 2.6). At multivariate Cox regression analysis, BNP, eCrCL, and HI were independent predictors for mortality (Hazard ratios: 1.0002, 0.97, and 1.05, respectively), while anaemia was not. Anaemia correlates with HF status, functional class, renal function, BNP, and HI. Anaemia was not an independent predictor for mortality, acting as a disease severity marker in congestive patients rather than as a predictor of death. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Pharmacology: The Era of Targeted Therapies in Cardiology 2.0)

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11 pages, 428 KiB

Open AccessArticle

Reinitiation and Subsequent Discontinuation of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers among New and Prevalent Users Aged 65 Years or More with Peripheral Arterial Disease

by Martin Wawruch, Jan Murin, Tomas Tesar, Miriam Petrova, Martina Paduchova, Denisa Celovska, Beata Havelkova, Michal Trnka, Lucia Masarykova, Sofa D. Alfian and Emma Aarnio

Biomedicines 2023, 11(2), 368; https://doi.org/10.3390/biomedicines11020368 - 26 Jan 2023

Cited by 1 | Viewed by 1556

Abstract

Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) are recommended in the treatment of arterial hypertension in patients with peripheral arterial disease (PAD). The aims of our study were: (a) to analyse the extent of reinitiation and subsequent discontinuation in older hypertensive PAD patients non-persistent with ACEIs/ARBs; (b) to determine patient and medication factors associated with reinitiation and subsequent discontinuation; and (c) to compare these factors between prevalent and new users. The analysis of reinitiation was performed on a sample of 1642 non-persistent patients aged ≥65 years with PAD newly diagnosed in 2012. Patients reinitiating ACEIs/ARBs were used for the analysis of subsequent discontinuation identified according to the treatment gap period of at least 6 months without any prescription of ACEI/ARB. In the group of non-persistent patients, 875 (53.3%) patients reinitiated ACEIs/ARBs during a follow-up (24.8 months on average). Within this group, subsequent discontinuation was identified in 414 (47.3%) patients. Being a new user was associated with subsequent discontinuation, but not with reinitiation. Myocardial infarction during non-persistence and after reinitiation was associated with reinitiation and lower likelihood of subsequent discontinuation, respectively. Being a prevalent or a new user is associated with the use of medication also after initial discontinuation. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Pharmacology: The Era of Targeted Therapies in Cardiology 2.0)

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19 pages, 2509 KiB

Open AccessReview

The Representation of Females in Studies on Antihypertensive Medication over the Years: A Scoping Review

by Zenab Mohseni-Alsalhi, Maud A. M. Vesseur, Nick Wilmes, Sophie A. J. S. Laven, Daniek A. M. Meijs, Eveline M. van Luik, Esmée W. P. Vaes, Cédric J. R. Dikovec, Jan Wiesenberg, Mohamad F. Almutairi, Emma B. N. J. Janssen, Sander de Haas, Marc E. A. Spaanderman and Chahinda Ghossein-Doha

Biomedicines 2023, 11(5), 1435; https://doi.org/10.3390/biomedicines11051435 - 12 May 2023

Cited by 3 | Viewed by 2320

Abstract

Background: The leading global risk factor for cardiovascular-disease-related morbidity and mortality is hypertension. In the past decade, attention has been paid to increase females’ representation. The aim of this study is to investigate whether the representation of females and presentation of sex-stratified data in studies investigating the effect of antihypertensive drugs has increased over the past decades. Methods: After systematically searching PubMed and Embase for studies evaluating the effect of the five major antihypertensive medication groups until May 2020, a scoping review was performed. The primary outcome was the proportion of included females. The secondary outcome was whether sex stratification was performed. Results: The search resulted in 73,867 articles. After the selection progress, 2046 studies were included for further analysis. These studies included 1,348,172 adults with a mean percentage of females participating of 38.1%. Female participation in antihypertensive studies showed an increase each year by 0.2% (95% CI 0.36–0.52), p < 0.01). Only 75 (3.7%) studies performed sex stratification, and this was the highest between 2011 and 2020 (7.2%). Conclusion: Female participation showed a slight increase in the past decade but is still underrepresented compared to males. As data are infrequently sex-stratified, more attention is needed to possible sex-related differences in treatment effects to different antihypertensive compounds. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Pharmacology: The Era of Targeted Therapies in Cardiology 2.0)

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16 pages, 498 KiB

Open AccessReview

HDL-Based Therapy: Vascular Protection at All Stages

by Anastasia V. Poznyak, Vasily N. Sukhorukov, Ilya I. Eremin, Irina I. Nadelyaeva, Nikita A. Gutyrchik and Alexander N. Orekhov

Biomedicines 2023, 11(3), 711; https://doi.org/10.3390/biomedicines11030711 - 27 Feb 2023

Cited by 2 | Viewed by 2344

Abstract

It is known that lipid metabolism disorders are involved in a wide range of pathologies. These pathologies include cardiovascular, metabolic, neurodegenerative diseases, and even cancer. All these diseases lead to serious health consequences, which makes it impossible to ignore them. Unfortunately, these diseases most often have a complex pathogenesis, which makes it difficult to study them and, in particular, diagnose and treat them. HDL is an important part of lipid metabolism, performing many functions under normal conditions. One of such functions is the maintaining of the reverse cholesterol transport. These functions are also implicated in pathology development. Thus, HDL contributes to vascular protection, which has been demonstrated in various conditions: Alzheimer’s disease, atherosclerosis, etc. Many studies have shown that serum levels of HDL cholesterol correlate negatively with CV risk. With these data, HDL-C is a promising therapeutic target. In this manuscript, we reviewed HDL-based therapeutic strategies that are currently being used or may be developed soon. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Pharmacology: The Era of Targeted Therapies in Cardiology 2.0)

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25 pages, 731 KiB

Open AccessReview

Hypertrophic, Dilated, and Arrhythmogenic Cardiomyopathy: Where Are We?

by Hamza El Hadi, Anne Freund, Steffen Desch, Holger Thiele and Nicolas Majunke

Biomedicines 2023, 11(2), 524; https://doi.org/10.3390/biomedicines11020524 - 11 Feb 2023

Cited by 7 | Viewed by 4180

Abstract

Cardiomyopathies are a heterogeneous group of structural, mechanical, and electrical heart muscle disorders which often correlate with life-threatening arrhythmias and progressive heart failure accounting for significant cardiovascular morbidity and mortality. Currently, cardiomyopathies still represent a leading reason for heart transplantation worldwide. The last years have brought remarkable advances in the field of cardiomyopathies especially in terms of understanding the molecular basis as well as the diagnostic evaluation and management. Although most cardiomyopathy treatments had long focused on symptom management, much of the current research efforts aim to identify and act on the disease-driving mechanisms. Regarding risk assessment and primary prevention of sudden cardiac death, additional data are still pending in order to pave the way for a more refined and early patient selection for defibrillator implantation. This review summarizes the current knowledge of hypertrophic, dilated and arrhythmogenic cardiomyopathy with a particular emphasis on their pathophysiology, clinical features, and diagnostic approach. Furthermore, the relevant ongoing studies investigating novel management approaches and main gaps in knowledge are highlighted. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Pharmacology: The Era of Targeted Therapies in Cardiology 2.0)

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11 pages, 1229 KiB

Open AccessReview

Doppler Ultrasound Selection and Follow-Up of the Internal Mammary Artery as Coronary Graft

by Pietro Scicchitano, Micaela De Palo, Giuseppe Parisi, Margherita Ilaria Gioia and Marco Matteo Ciccone

Biomedicines 2023, 11(1), 66; https://doi.org/10.3390/biomedicines11010066 - 27 Dec 2022

Cited by 1 | Viewed by 5030

Abstract

The impact of coronary artery disease (CAD) on all-cause mortality and overall disabilities is well-established. Percutaneous and/or surgical coronary revascularization procedures dramatically reduced the occurrence of adverse cardiovascular events in patients suffering from atherosclerosis. Specifically, guidelines from the European Society of Cardiology on the management of myocardial revascularization promoted coronary artery by-pass graft (CABG) intervention in patients with specific alterations in the coronary tree due to the higher beneficial effects of this procedure as compared to the percutaneous one. The left internal mammary artery (LIMA) is one of the best-performing vessels in CABG procedures due to its location and its own structural characteristics. Nevertheless, the non-invasive assessment of its patency is challenging. Doppler ultrasonography (DU) might perform as a reliable technique for the non-invasive evaluation of the patency of LIMA. Data from the literature revealed that DU may detect severe (>70%) stenosis of the LIMA graft. In this case, pulsed-wave Doppler might show peak diastolic velocity/peak systolic velocity < 0.5 and diastolic fraction < 50%. A stress test might also be adopted for the evaluation of patency of LIMA through DU. The aim of this narrative review is to evaluate the impact of DU on the evaluation of the patency of LIMA graft in patients who undergo follow-up after CABG intervention. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Pharmacology: The Era of Targeted Therapies in Cardiology 2.0)

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26 pages, 4782 KiB

Open AccessSystematic Review

Sex Differences in the Anti-Hypertensive Effect of Calcium-Channel Blockers: A Systematic Review and Meta-Analysis

by Eveline M. van Luik, Esmée W. P. Vaes, Maud A. M. Vesseur, Nick Wilmes, Daniek A. M. Meijs, Sophie A. J. S. Laven, Zenab Mohseni-Alsalhi, Sander de Haas, Marc E. A. Spaanderman and Chahinda Ghossein-Doha

Biomedicines 2023, 11(6), 1622; https://doi.org/10.3390/biomedicines11061622 - 2 Jun 2023

Cited by 2 | Viewed by 2366

Abstract

Cardiovascular disease (CVD) is the number one cause of death worldwide, with hypertension as the leading risk factor for both sexes. As sex may affect responsiveness to antihypertensive compounds, guidelines for CVD prevention might necessitate divergence between females and males. To this end, we studied the effectiveness of calcium channel blockers (CCB) on blood pressure (BP), heart rate (HR) and cardiac function between sexes. We performed a systematic review and meta-analysis on studies on CCB from inception to May 2020. Studies had to present both baseline and follow-up measurements of the outcome variables of interest and present data in a sex-stratified manner. Mean differences were calculated using a random-effects model. In total, 38 studies with 8202 participants were used for this review. In females as compared to males, systolic BP decreased by −27.6 mmHg (95%CI −36.4; −18.8) (−17.1% (95%CI −22.5;−11.6)) versus −14.4 mmHg (95%CI −19.0; −9.9) (−9.8% (95%CI −12.9;−6.7)) (between-sex difference p < 0.01), diastolic BP decreased by −14.1 (95%CI −18.8; −9.3) (−15.2%(95%CI −20.3;−10.1)) versus −10.6 mmHg (95%CI −14.0; −7.3) (−11.2% (95%CI −14.8;−7.7)) (between-sex difference p = 0.24). HR decreased by −1.8 bpm (95%CI −2.5; −1.2) (−2.5% (95%CI −3.4; −1.6)) in females compared to no change in males (0.3 bpm (95% CI −1.2; 1.8)) (between-sex difference p = 0.01). In conclusion, CCB lowers BP in both sexes, but the observed effect is larger in females as compared to males. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Pharmacology: The Era of Targeted Therapies in Cardiology 2.0)

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28 pages, 3413 KiB

Open AccessSystematic Review

Exploring Sex Differences of Beta-Blockers in the Treatment of Hypertension: A Systematic Review and Meta-Analysis

by Nick Wilmes, Eveline M. van Luik, Esmée W. P. Vaes, Maud A. M. Vesseur, Sophie A. J. S. Laven, Zenab Mohseni-Alsalhi, Daniek A. M. Meijs, Cédric J. R. Dikovec, Sander de Haas, Marc E. A. Spaanderman and Chahinda Ghossein-Doha

Biomedicines 2023, 11(5), 1494; https://doi.org/10.3390/biomedicines11051494 - 22 May 2023

Cited by 2 | Viewed by 3087

Abstract

Aims: In the prevention of cardiovascular morbidity and mortality, early recognition and adequate treatment of hypertension are of leading importance. However, the efficacy of antihypertensives may be depending on sex disparities. Our objective was to evaluate and quantify the sex-diverse effects of beta-blockers (BB) on hypertension and cardiac function. We focussed on comparing hypertensive female versus male individuals. Methods and results: A systematic search was performed for studies on BBs from inception to May 2020. A total of 66 studies were included that contained baseline and follow up measurements on blood pressure (BP), heart rate (HR), and cardiac function. Data also had to be stratified for sex. Mean differences were calculated using a random-effects model. In females as compared to males, BB treatment decreased systolic BP 11.1 mmHg (95% CI, −14.5; −7.8) vs. 11.1 mmHg (95% CI, −14.0; −8.2), diastolic BP 8.0 mmHg (95% CI, −10.6; −5.3) vs. 8.0 mmHg (95% CI, −10.1; −6.0), and HR 10.8 beats per minute (bpm) (95% CI, −17.4; −4.2) vs. 9.8 bpm (95% CI, −11.1; −8.4)), respectively, in both sexes’ absolute and relative changes comparably. Left ventricular ejection fraction increased only in males (3.7% (95% CI, 0.6; 6.9)). Changes in left ventricular mass and cardiac output (CO) were only reported in males and changed −20.6 g (95% CI, −56.3; 15.1) and −0.1 L (95% CI, −0.5; 0.2), respectively. Conclusions: BBs comparably lowered BP and HR in both sexes. The lack of change in CO in males suggests that the reduction in BP is primarily due to a decrease in vascular resistance. Furthermore, females were underrepresented compared to males. We recommend that future research should include more females and sex-stratified data when researching the treatment effects of antihypertensives. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Pharmacology: The Era of Targeted Therapies in Cardiology 2.0)

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