"Targeting Residual Cardiovascular Risk": The Road towards Precision Medicine Strategies

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

Deadline for manuscript submissions: closed (21 June 2023) | Viewed by 13931

Special Issue Editor


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Guest Editor
Department of Cardiology, Parma University Hospital, Parma, Italy
Interests: traditional and non-traditional cardiovascular risk factors; antithrombotic therapy; lipid lowering therapy; inflammation; diabetes; cardiovascular risk stratification; precision medicine

Special Issue Information

Dear Colleagues,

Coronary artery disease (CAD) remains one of the most common causes of mortality and morbidity worldwide, despite significant progresses in this field. Indeed, patients with established CAD are at high risk for recurrent major cardiovascular and cerebral events (MACCE), and even with evidence-based secondary preventive strategies, a consistent residual risk persists.

In recent years, new approaches targeting residual risk pathways have been developed, including nonstatin-lipid lowering therapy, antithrombotic drugs, anti-inflammatory therapies and drugs affecting the cardiometabolic pathway, such as sodium-glucose cotransporter-2 inhibitors. Furthermore, there is increasing evidence concerning the role of non-traditional cardiovascular risk factors, such as acute and chronic exposure to environmental stressors (e.g., air pollution), sleep deprivation, and psychosocial stress, in the modulation of pathways involved in residual CV risk.

Thus, now more than ever, there is a need for a personalized approach to target the right pathway or multiple pathways that may be differently involved from one patient to another, providing a tailored treatment, the cornerstone of precision medicine.

The goal of this Special Issue is therefore to update clinicians on the current strategies and most recent advances in risk stratification, diagnosis, and therapies in patients with established CAD.

Dr. Giulia Magnani
Guest Editor

Manuscript Submission Information

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Keywords

  •  Coronary artery disease
  •  Residual cardiovascular risk
  •  Traditional and non-traditional cardiovascular risk factors
  •  Risk stratification
  •  Lipid-lowering therapy
  •  Antithrombotic therapy
  •  Anti-inflammatory therapy
  •  Cardiometabolic pathway
  •  Sodium-glucose cotransporter-2 inhibitors

Published Papers (6 papers)

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Research

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14 pages, 1226 KiB  
Article
Lipoprotein (a), Inflammation, and Atherosclerosis
by Stefania Angela Di Fusco, Aldo Pietro Maggioni, Pietro Scicchitano, Marco Zuin, Emilia D’Elia and Furio Colivicchi
J. Clin. Med. 2023, 12(7), 2529; https://doi.org/10.3390/jcm12072529 - 27 Mar 2023
Cited by 12 | Viewed by 2527
Abstract
Growing evidence has shown that high levels of lipoprotein (a) (Lp(a)) and chronic inflammation may be responsible for the residual risk of cardiovascular events in patients managed with an optimal evidence-based approach. Clinical studies have demonstrated a correlation between higher Lp(a) levels and [...] Read more.
Growing evidence has shown that high levels of lipoprotein (a) (Lp(a)) and chronic inflammation may be responsible for the residual risk of cardiovascular events in patients managed with an optimal evidence-based approach. Clinical studies have demonstrated a correlation between higher Lp(a) levels and several atherosclerotic diseases including ischemic heart disease, stroke, and degenerative calcific aortic stenosis. The threshold value of Lp(a) serum concentrations associated with a significantly increased cardiovascular risk is >125 nmol/L (50 mg/dL). Current available lipid-lowering drugs have modest-to-no impact on Lp(a) levels. Chronic inflammation is a further condition potentially implicated in residual cardiovascular risk. Consistent evidence has shown an increased risk of cardiovascular events in patients with high sensitivity C reactive protein (>2 mg/dL), an inflammation biomarker. A number of anti-inflammatory drugs have been investigated in patients with or at risk of cardiovascular disease. Of these, canakinumab and colchicine have been found to be associated with cardiovascular risk reduction. Ongoing research aimed at improving risk stratification on the basis of Lp(a) and vessel inflammation assessment may help refine patient management. Furthermore, the identification of these conditions as cardiovascular risk factors has led to increased investigation into diagnostic and therapeutic strategies targeting them in order to reduce atherosclerotic cardiovascular disease burden. Full article
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22 pages, 2270 KiB  
Article
The Oscillometric Pulse Wave Analysis Is Useful in Evaluating the Arterial Stiffness of Obese Children with Relevant Cardiometabolic Risks
by Monica Simina Mihuta, Corina Paul, Andreea Borlea, Cristina Mihaela Cepeha, Iulian Puiu Velea, Ioana Mozos and Dana Stoian
J. Clin. Med. 2022, 11(17), 5078; https://doi.org/10.3390/jcm11175078 - 29 Aug 2022
Cited by 8 | Viewed by 1821
Abstract
Early detection of all complications of childhood obesity is imperative in order to minimize effects. Obesity causes vascular disruptions, including early increased arterial stiffness and high blood pressure. This study’s aim is to assess the reliability of pulse wave analysis (PWA) in obese [...] Read more.
Early detection of all complications of childhood obesity is imperative in order to minimize effects. Obesity causes vascular disruptions, including early increased arterial stiffness and high blood pressure. This study’s aim is to assess the reliability of pulse wave analysis (PWA) in obese children and how additional risk factors influence the evaluated parameters. We analyzed 55 children aged 6–18 years old by measuring their pulse wave velocity (PWV), augmentation index (AIx), peripheral blood pressure (SBP, DBP), heart rate, central blood pressure (cSBP, cDBP) and central pulse pressure (cPP). We used the oscillometric IEM Mobil-O-Graph and performed a single-point brachial measurement. The subjects were divided into two groups: obese (n = 30) and normal-weight (n = 25) and were clinically and anamnestically assessed. BMI and waist circumference are significantly correlated to higher values for PWV, SBP, DBP, cSBP, and cDBP. Weight significantly predicts PWV, SBP, DBP and cPP. The risk factors that significantly influence the PWA and BP values are: a cardiometabolically risky pregnancy (higher PWV, AIx, SBP), active and passive smoking (higher PWV, SBP, cSBP, cDBP), sleep deprivation (higher PWV, SBP, cSBP) and sedentariness (higher PWV, AIx, peripheral and central BP). We conclude that obese children with specific additional cardiometabolic risk factors present increased arterial stiffness and higher blood pressure values. Full article
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11 pages, 464 KiB  
Article
Management of High-Risk Hypercholesterolemic Patients and PCSK9 Inhibitors Reimbursement Policies: Data from a Cohort of Italian Hypercholesterolemic Outpatients
by Federica Fogacci, Marina Giovannini, Elisa Grandi, Egidio Imbalzano, Daniela Degli Esposti, Claudio Borghi and Arrigo F. G. Cicero
J. Clin. Med. 2022, 11(16), 4701; https://doi.org/10.3390/jcm11164701 - 11 Aug 2022
Cited by 8 | Viewed by 1930
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are effective and safe lipid-lowering treatments (LLT). The primary endpoint of the study was to assess the prevalence of patients eligible for treatment with PCSK9 inhibitors in a real-life clinical setting in Italy before and after [...] Read more.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are effective and safe lipid-lowering treatments (LLT). The primary endpoint of the study was to assess the prevalence of patients eligible for treatment with PCSK9 inhibitors in a real-life clinical setting in Italy before and after the recent enlargement of reimbursement criteria. For this study, we consecutively considered the clinical record forms of 6231 outpatients consecutively admitted at the Lipid Clinic of the University Hospital of Bologna (Italy). Patients were stratified according to whether they were allowed or not allowed to access to treatment with PCSK9 inhibitors based on national prescription criteria and reimbursement rules issued by the Italian Medicines Agency (AIFA). According to the indications of the European Medicines Agency (EMA), 986 patients were candidates to treatment with PCSK9 inhibitors. However, following the prescription criteria issued by AIFA, only 180 patients were allowed to access to PCSK9 inhibitors before reimbursement criteria enlargement while 322 (+14.4%) with the current ones. Based on our observations, low-cost tailored therapeutic interventions for individual patients can significantly reduce the number of patients potentially needing treatment with PCSK9 inhibitors among those who are not allowed to access to the treatment. The application of enlarged reimbursement criteria for PCSK9 inhibitors could mildly improve possibility to adequately manage high-risk hypercholesterolemic subjects in the setting of an outpatient lipid clinic. Full article
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Review

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15 pages, 925 KiB  
Review
Dual Antiplatelet Therapy or Antiplatelet Plus Anticoagulant Therapy in Patients with Peripheral and Chronic Coronary Artery Disease: An Updated Review
by Giulia Magnani, Andrea Denegri, Filippo Luca Gurgoglione, Federico Barocelli, Elia Indrigo, Davide Catellani, Gianluca Signoretta, Alberto Bettella, Domenico Tuttolomondo, Emilia Solinas, Francesco Nicolini, Giampaolo Niccoli and Diego Ardissino
J. Clin. Med. 2023, 12(16), 5284; https://doi.org/10.3390/jcm12165284 - 14 Aug 2023
Viewed by 1391
Abstract
Despite evidence-based therapies, patients presenting with atherosclerosis involving more than one vascular bed, such as those with peripheral artery disease (PAD) and concomitant coronary artery disease (CAD), constitute a particularly vulnerable group characterized by enhanced residual long-term risk for major adverse cardiac events [...] Read more.
Despite evidence-based therapies, patients presenting with atherosclerosis involving more than one vascular bed, such as those with peripheral artery disease (PAD) and concomitant coronary artery disease (CAD), constitute a particularly vulnerable group characterized by enhanced residual long-term risk for major adverse cardiac events (MACE), as well as major adverse limb events (MALE). The latter are progressively emerging as a difficult outcome to target, being correlated with increased mortality. Antithrombotic therapy is the mainstay of secondary prevention in both patients with PAD or CAD; however, the optimal intensity of such therapy is still a topic of debate, particularly in the post-acute and long-term setting. Recent well-powered randomized clinical trials (RCTs) have provided data in favor of a more intense antithrombotic therapy, such as prolonged dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor or a therapy with aspirin combined with an anticoagulant drug. Both approaches increase bleeding and selection of patients is a key issue. The aim of this review is, therefore, to discuss and summarize the most up-to-date available evidence for different strategies of anti-thrombotic therapies in patients with chronic PAD and CAD, particularly focusing on studies enrolling patients with both types of atherosclerotic disease and comparing a higher- versus a lower-intensity antithrombotic strategy. The final objective is to identify the optimal tailored approach in this setting, to achieve the greatest cardiovascular benefit and improve precision medicine. Full article
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13 pages, 724 KiB  
Review
Management of Non-Culprit Lesions in STEMI Patients with Multivessel Disease
by Raffaele Piccolo, Lina Manzi, Fiorenzo Simonetti, Attilio Leone, Domenico Angellotti, Maddalena Immobile Molaro, Nicola Verde, Plinio Cirillo, Luigi Di Serafino, Anna Franzone, Carmen Anna Maria Spaccarotella and Giovanni Esposito
J. Clin. Med. 2023, 12(7), 2572; https://doi.org/10.3390/jcm12072572 - 29 Mar 2023
Viewed by 3709
Abstract
Multivessel disease is observed in approximately 50% of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Data from randomized clinical trials has shown that complete revascularization in the STEMI setting improves clinical outcomes by reducing the risk of [...] Read more.
Multivessel disease is observed in approximately 50% of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Data from randomized clinical trials has shown that complete revascularization in the STEMI setting improves clinical outcomes by reducing the risk of reinfarction and urgent revascularization. However, the timing and modality of revascularization of non-culprit lesions are still debated. PCI of non-culprit lesions can be performed during the index primary PCI or as a staged procedure and can be guided by angiography, functional assessment, or intracoronary imaging. In this review, we summarize the available evidence about the management of non-culprit lesions in STEMI patients with or without cardiogenic shock. Full article
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15 pages, 5375 KiB  
Review
Endothelial Dysfunction and Arterial Stiffness in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis
by Hao Wu, Meihua Xu, Hong Hao, Michael A. Hill, Canxia Xu and Zhenguo Liu
J. Clin. Med. 2022, 11(11), 3179; https://doi.org/10.3390/jcm11113179 - 02 Jun 2022
Cited by 6 | Viewed by 1971
Abstract
Population-based studies have suggested that patients with inflammatory bowel disease (IBD) might be at an increased risk for cardiovascular diseases. A meta-analysis was performed on clinical studies to evaluate endothelial function, arterial stiffness, and carotid intima-media thickness (cIMT) in patients with IBD, after [...] Read more.
Population-based studies have suggested that patients with inflammatory bowel disease (IBD) might be at an increased risk for cardiovascular diseases. A meta-analysis was performed on clinical studies to evaluate endothelial function, arterial stiffness, and carotid intima-media thickness (cIMT) in patients with IBD, after searching PubMed, Embase, Cochrane library, and Web of Science databases. A random-effects model was used to allow for the pooling of studies and for determination of the overall effect. After exclusion, a total of 41 eligible studies with 2330 patients with IBD and 2032 matched controls were identified and included for the analysis. It was found that cIMT was significantly increased in patients with IBD as compared with that in matched controls (Cohen’s d: 0.63; 95% CI: 0.34, 0.93; I2 = 91.84%). The carotid–femoral pulse wave velocity was significantly higher in patients with IBD compared to that in matched controls (Cohen’s d: 0.76; 95% CI: 0.54, 0.98; I2 = 70.03%). The augmentation index was also significantly increased in patients with IBD compared to matched control subjects (Cohen’s d: 0.35; 95% CI: 0.08, 0.63; I2 = 61.37%). Brachial artery flow-mediated dilatation was significantly decreased in patients with IBD than that in matched controls (Cohen’s d: −0.73; 95% CI: −1.10, −0.36; I2 = 81.02%). Based on the meta-analysis, it was found that patients with IBD exhibit significant endothelial dysfunction, increased arterial stiffness, and cIMT. Thus, patients with IBD may benefit from aggressive risk stratification for cardiovascular diseases. Full article
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