Lipids and atherosclerosis in COVID era

Since the emergence of the pandemic due to COVID-19, we have come to learn that it is not a simple viral pneumonia. The virus also binds to endothelial cells, myocardial cells, renal tubular cells among others and triggers a multisystem inflammation, cytokine storm and thromboembolism. This can lead to cardiovascular complications such as acute coronary syndromes, myocarditis and arrythmia and multiorgan failure. The medications we use to treat the disease have drug interactions and cardiovascular consequences. With increased risk of inflammation and thrombosis, patients with atherosclerotic vascular disease and hyperlipidemia are a vulnerable group requiring frequent and continued medical attention. The COVID-19 pandemic has significantly affected the heart healthy lifestyle and access to healthcare of our patients.

In this webinar, we will discuss the consequences of COVID-19 infection for atherosclerotic vascular disease, lipids and lipid lowering medications.
  • Endothelium and inflammation – interplay with COVID - Prof. Caligiuri
  • What we learned from previous ARDSs and how should we approach lipid lowering therapy in the COVID19 era? - Prof. Soran
  • Drug-drug interactions for lipid-lowering therapy - Prof. Corsini
  • Live Q&A
  • Chair: Prof. Tokgözoğlu
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    Giuseppina Caligiuri
    MD, PhD, Research Director, Inserm, Paris, France
    Dr Giuseppina Caligiuri is an expert in molecular mechanisms underlying the interplay between inflammation and vascular biology. She has been particularly focused on the regulatory functions of CD31, the most abundant endothelial surface glycoprotein endowed with critical co-signaling properties in cardiovascular physiology and pathology.[1,2]

    Regulation of endothelial function face to a systemic inflammatory process is crucial for the clinical outcome of pulmonary and systemic circulation. In the case of sepsis, the eradication of the pathogen may be useless because the uncontrolled release of vasoactive mediators acting on the hemodynamics (vasoplegia, peripheral hypoperfusion) as well as of factors affecting the endothelial barrier and anti-coagulant functions of organ microvessels in response to pathogens (oedema and disseminated intravascular coagulation) eventually lead leading to multi-organ failure and fatal outcome.

    Intriguingly, the loss of CD31 favours the occurrence of oedema and disseminated intravascular coagulation and aggravates the outcome of septic choc, in mice,[3] suggesting that the massive cytokine release and inappropriate intravascular activation of homeostasis observed in patients affected by the most severe forms of COVID-19 may in part be due to a defective control of immune effectors within the circulation.

    While waiting for an effective vaccine, multiple endothelial/inflammatory mechanisms and potential therapeutic solutions, including the use of anti-cytokine biologicals,[4] can be envisaged to prevent cardiovascular fatal complications in patients with Covid-19.

    1. Caligiuri G.Mechanotransduction, immunoregulation, and metabolic functions of CD31 in cardiovascular pathophysiology. Cardiovasc Res. 2019 Jul 1;115(9):1425-1434.
    2. Caligiuri G. CD31 as a Therapeutic Target in Atherosclerosis. Circ Res. 2020 Apr 24;126(9):1178-1189).
    3. Luo L et al. PECAM-1 protects against DIC by dampening inflammatory responses via inhibiting macrophage pyroptosis and restoring vascular barrier integrity. Transl Res. 2020;222:1-16
    4. Xu X et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020;117:10970-10975
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    Alberto Corsini
    PharmD, PhD, Professor of Pharmacology, University of Milan, Italy
    Since 1999, I was interested in the problem of drug-drug interaction (DDI) as related to lipid lowering therapy. In particular, as a pharmacologist, I was focused in understanding the different spectrum of drug interactions, which are important determinants of safety in patients with hypercholesterolemia. Although statin treatment is generally well-tolerated, the most common adverse effect is myopathy. The rate of myopathy with statin monotherapy is low, but factors that raise the circulating concentrations of statins, such as DDIs, can increase the risk of these adverse event. This is particular relevant especially in those requiring long-term therapy with drugs that are well-known CYP3A substrates and/or inhibitors. The issue of DDI has to be addressed in patients at high cardiovascular risk that usually received multiple medications necessary to provide optimal care, ‘polytherapy’ increases the risk of DDIs and consequent adverse drug reactions.

    Hypercholesterolemia has been reported to be one of the most common comorbidities in patients with COVID-19 and, recently, an observational study demonstrated that in-hospital use of statins was associated with substantial improvement in survival among patients hospitalized with COVID-19.

    The COVID-19 pandemic has driven unprecedented efforts to identify possible therapeutic strategies for the treatment of COVID patients. Over 100 different off-label and experimental drugs are under investigations from antiviral agents (e.g. lopinavir/ritonavir, darunavir/ritonavir, atazanavir, remdesivir) to hydroxychloroquine and to biotechnological drugs such as tocilizumab. Many of the tested drugs including cytokine modulators are inducer or inhibitor of several cytochromes involved in drug metabolism as well as of drug transporters such as P-gp. For example, tocilizumab (anti-IL-6 receptor antibody) may reverse the “inhibitory” effect of IL-6 on CYP substrates, resulting in a “normalization” of CYP activities and increased clearance of atorvastatin and simvastatin.

    The potential DDI occurring between statins, other lipid lowering agents and drugs actually under investigation in COVID patients is the one of the topics discussed in the present EAS webinar
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    Handrean Soran
    MBChB, MSc, MD, FRCP, CCST in Endocrinology and Diabetes, University of Manchester, UK
    Dr Handrean Soran is Consultant Physician and Endocrinologist & Honorary Senior Lecturer at Manchester University Trust. He has a specialist interest in lipidology, atherosclerosis, cardiovascular risk, parathyroid, calcium and bone metabolism. He provides a tertiary centre service for lipoprotein disorders, as well as calcium and metabolic bone diseases. His research work is mainly focused on cardiovascular risk, low-density lipoprotein (LDL) quality, high-density lipoprotein (HDL) functionality, micro- and macro-vascular complications of diabetes & obesity and the effect of metabolic surgery induced weight loss as well as pharmacological agents on these complications. Dr Soran is on the editorial board of Atherosclerosis Journal. Dr Soran authored more than 145 peer reviewed publications and a number of book chapters.
    Dr Soran leads cardiovascular and trials team and Lipid Research group at Manchester University NHS Trust and Lipoprotein Research Group at University of Manchester. He acted as the UK chief investigator for more than 15 multicentre clinical trials and principal investigator for more than 25 multicentre clinical trials and studies. He also acted as a member of the steering committee of many large multinational randomised control trials.
    He successfully supervised many MD and PhD students and currently has one MD and four PhD students. Dr Soran Leads Manchester Endocrinology and Diabetes Specialty Certificate Examination (SCE) course which attracts many national and international delegates. He also organises annual UK Lipid Forum and North West Endocrinology and Atherosclerosis update symposiums. Each of these annual symposiums attracts 120-150 delegates across United Kingdom.
    Dr Soran is the Chair of HEART UK’s medical, scientific and research committee, co-chair of the National Familial Hypercholesterolemia task force in UK, a member of UK lipoprotein apheresis committee and European Atherosclerosis Society’s Familial Hypercholestrolaemia Collaborative Study (FHSC) executive committee. He also served as the President of the Lipid, Metabolism and Vascular Section of the Royal Society of Medicine and remains a member of the section’s council.
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    Lale Tokgözoğlu
    Professor of Cardiology, Hacettepe University, Ankara, Turkey
    S. Lale Tokgözoğlu, M.D., F.A.C.C., F.E.S.C. was born in 1959 in Ankara, Turkey. She graduated from the Hacettepe University Faculty of Medicine in 1982 on the honor roll. After finishing the Internal Medicine Residency program in the Hacettepe University Faculty of Medicine Department of Internal Medicine on 1988, she completed a fellowship program on Cardiology and Atherosclerosis at the Baylor College of Medicine in Houston, Texas. Dr. Tokgözoğlu returned to the Hacettepe University in 1991 to become Associate Professor of Cardiology, and later Professor of Cardiology in 1998.