Publications by authors named "Ignatios Ikonomidis"

222 Publications

Association of COVID-19 with impaired endothelial glycocalyx, vascular function and myocardial deformation 4 months after infection.

Eur J Heart Fail 2021 Aug 20. Epub 2021 Aug 20.

Laboratory of Preventive Cardiology, Second Cardiology Department, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Aims: SARS-CoV-2 infection may lead to endothelial and vascular dysfunction. We investigated alterations of arterial stiffness, endothelial coronary and myocardial function markers 4 months after COVID-19 infection.

Methods And Results: In a case-control prospective study, we included 70 patients 4 months after COVID-19 infection, 70 age- and sex-matched untreated hypertensive patients (positive control) and 70 healthy individuals. We measured (i) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV), (v) global left and right ventricular longitudinal strain (GLS), and (vi) malondialdehyde (MDA), an oxidative stress marker, thrombomodulin and von Willebrand factor as endothelial biomarkers. COVID-19 patients had similar CFR and FMD as hypertensives (2.48 ± 0.41 vs. 2.58 ± 0.88, P = 0.562, and 5.86 ± 2.82% vs. 5.80 ± 2.07%, P = 0.872, respectively) but lower values than controls (3.42 ± 0.65, P = 0.0135, and 9.06 ± 2.11%, P = 0.002, respectively). Compared to controls, both COVID-19 and hypertensives had greater PBR5-25 (2.07 ± 0.15 µm and 2.07 ± 0.26 µm, P = 0.8 vs. 1.89 ± 0.17 µm, P = 0.001), higher PWV (carotid-femoral PWV 12.09 ± 2.50 vs. 11.92 ± 2.94, P = 0.7 vs. 10.04 ± 1.80 m/s, P = 0.036) and impaired left and right ventricular GLS (-19.50 ± 2.56% vs. -19.23 ± 2.67%, P = 0.864 vs. -21.98 ± 1.51%, P = 0.020 and -16.99 ± 3.17% vs. -18.63 ± 3.20%, P = 0.002 vs. -20.51 ± 2.28%, P < 0.001). MDA and thrombomodulin were higher in COVID-19 patients than both hypertensives and controls (10.67 ± 0.32 vs 1.76 ± 0.03, P = 0.003 vs. 1.01 ± 0.05 nmol/L, P = 0.001 and 3716.63 ± 188.36 vs. 3114.46 ± 179.18 pg/mL, P = 0.017 vs. 2590.02 ± 156.51 pg/mL, P < 0.001). Residual cardiovascular symptoms at 4 months were associated with oxidative stress and endothelial dysfunction markers.

Conclusions: SARS-CoV-2 may cause endothelial and vascular dysfunction linked to impaired cardiac performance 4 months after infection.
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http://dx.doi.org/10.1002/ejhf.2326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426810PMC
August 2021

Updated knowledge and practical implementations of stress echocardiography in ischemic and non-ischemic cardiac diseases: an expert consensus of the Working Group of Echocardiography of the Hellenic Society of Cardiology.

Hellenic J Cardiol 2021 Jul 27. Epub 2021 Jul 27.

Metropolitan Hospital Center, Piraeus, Greece; Hamersmith University Hospital, London, UK.

Stress echocardiography (SE) is a well-established and valid technique, widely-used for the diagnostic evaluation of patients with ischemic and non-ischemic cardiac diseases. This statement of the Echocardiography Working Group of the Hellenic Society of Cardiology summarizes the consensus of the writing group regarding the applications of SE, based on the expertise of their members and on a critical review of current medical literature. The main objectives of the consensus document include a comprehensive review of SE methodology and training, focusing on the preparation, the protocols used and the analysis of the SE images and an updated, evidence-based knowledge about SE applications on ischemic and non-ischemic heart diseases, such as in cardiomyopathies, heart failure and valvular heart disease.
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http://dx.doi.org/10.1016/j.hjc.2021.07.006DOI Listing
July 2021

May We Use Non-Invasive Indices of Aortic Stiffness and Endothelial Glycocalyx as Biomarkers for Idiopathic Pulmonary Artery Hypertension Follow-Up?

Medicina (Kaunas) 2021 Jun 1;57(6). Epub 2021 Jun 1.

2nd Department of Critical Care, Medical School, National and Kapodistrian University of Athens, ATTIKON University Hospital, 12462 Athens, Greece.

Idiopathic pulmonary arterial hypertension (IPAH) initial evaluation and follow-up, a rare and incurable disease if left untreated, is based on a multiparametric approach (functional status of the patient, biomarkers, hemodynamic parameters and imaging evaluation of right heart impairment). Arterial stiffness (AS) and endothelial glycocalyx are indices of systemic circulation. We present the 3-years follow-up of a female IPAH patient. We propose aortic stiffness and endothelial glycocalyx indices as non-invasive markers of either improvement or deterioration of IPAH disease.
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http://dx.doi.org/10.3390/medicina57060558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230127PMC
June 2021

Effects of hormone replacement therapy on endothelial function, arterial stiffness and myocardial deformation in women with Turner syndrome.

J Hypertens 2021 Oct;39(10):2051-2057

2nd Department of Cardiology.

Objectives: Turner syndrome (TS) is associated with increased cardiovascular risk. We investigated whether hormone replacement therapy (HRT) affects endothelial function, arterial stiffness and myocardial deformation in women with TS.

Methods: Twenty-five women with TS were studied in the estrogen phase of the HRT and two months after discontinuation of HRT. The following measurements were made: flow-mediated dilation (FMD) of the brachial artery, pulse wave velocity (PWV-Complior) and central systolic blood pressure (cSBP), carotid intima-media thickness (cIMT), aortic (Ao) elastic indexes - namely Ao strain, distensibility, stiffness index and pressure strain modulus (Ep) - and left ventricular (LV) global longitudinal strain (GLS) using speckle-tracking echocardiography. Ten healthy female of similar age and BMI served as a control group.

Results: Compared to controls, women with TS on HRT had higher PWV (9.1 ± 2.4 vs. 7.5 ± 0.5 m/s), cSBP (130 ± 15 vs. 121 ± 6 mmHg), cIMT (0.66 ± 0.06 vs. 0.55 ± 0.05 mm), aortic stiffness index, Ep and LA strain, and lower FMD (7.2 ± 4 vs. 10.5 ± 2.3%), Ao strain, Ao distensibility and GLS (-18.8 ± 2.7 vs. -21.9 ± 1.5%) (P < 0.05 for all comparisons). Two months after discontinuation of HRT, all women increased FMD (11.7 ± 6 vs. 7.2 ± 4%) and reduced PWV (7.8 ± 1.7 vs. 9.1 ± 2.4 m/s) and cSBP (123 ± 14 vs. 130 ± 15 mmHg). There were no statistically significant changes in BMI, cIMT and GLS (P > 0.05 for all comparisons). The percentage decrease of cSBP was associated with the percentage decrease of PWV (r = 0.54) and reversely related with the percentage increase of FMD (r = -0.57; P < 0.05 for all comparisons).

Conclusions: HRT in women with TS may deteriorate endothelial function contributing to increased arterial stiffness and central arterial blood pressure.
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http://dx.doi.org/10.1097/HJH.0000000000002903DOI Listing
October 2021

Differential effects of heat-not-burn and conventional cigarettes on coronary flow, myocardial and vascular function.

Sci Rep 2021 Jun 3;11(1):11808. Epub 2021 Jun 3.

2nd Cardiology Department, Attikon Hospital, National and Kapodistrian University of Athens, Rimini 1, Haidari, 12462, Athens, Greece.

We compared the effects of Heat-not-Burn cigarette (HNBC) to those of tobacco cigarette (Tcig), on myocardial, coronary and arterial function as well as on oxidative stress and platelet activation in 75 smokers. In the acute study, 50 smokers were randomised into smoking a single Tcig or a HNBC and after 60 min were crossed-over to the alternate smoking. For chronic phase, 50 smokers were switched to HNBC and were compared with an external group of 25 Tcig smokers before and after 1 month. Exhaled carbon monoxide (CO), pulse wave velocity (PWV), malondialdehyde (MDA) and thromboxane B2 (TxB2) were assessed in the acute and chronic study. Global longitudinal strain (GLS), myocardial work index (GWI), wasted myocardial work (GWW), coronary flow reserve (CFR), total arterial compliance (TAC) and flow-mediated dilation (FMD) were assessed in the chronic study. Acute HNBC smoking caused a smaller increase of PWV than Tcig (change 1.1 vs 0.54 m/s, p < 0.05) without change in CO and biomarkers in contrast to Tcig. Compared to Tcig, switching to HNBC for 1-month improved CO, FMD, CFR, TAC, GLS, GWW, MDA, TxB2 (differences 10.42 ppm, 4.3%, 0.98, 1.8 mL/mmHg, 2.35%, 19.72 mmHg%, 0.38 nmol/L and 45 pg/mL respectively, p < 0.05). HNBCs exert a less detrimental effect on vascular and cardiac function than tobacco cigarettes.Trial registration Registered on https://clinicaltrials.gov/ (NCT03452124, 02/03/2018).
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http://dx.doi.org/10.1038/s41598-021-91245-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175445PMC
June 2021

Effects of Anti-Inflammatory Treatment and Surgical Intervention on Endothelial Glycocalyx, Peripheral and Coronary Microcirculatory Function and Myocardial Deformation in Inflammatory Bowel Disease Patients: A Two-Arms Two-Stage Clinical Trial.

Diagnostics (Basel) 2021 May 30;11(6). Epub 2021 May 30.

2nd Academic Department of Surgery, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece.

Sixty inflammatory bowel disease (IBD) patients (45 Crohn disease and 15 ulcerative colitis, 40 ± 13 years, 53% male) were examined at baseline and 4 months after intervention (surgical (35 patients) or anti-TNFa treatment (25 patients)). IBD severity, using Mayo score, Harvey-Bradshaw Index (HBI) and biomarkers, was correlated with cardiovascular markers. At baseline, the disease severity, the white blood cells (WBC) values and the reducing power (RP) were significantly correlated with the aortic pulse wave velocity (PWV) ( = 0.4, = 0.44 and = 0.48, < 0.05) and the lateral mitral E' velocity ( = 0.35, < 0.05 and = 0.3, < 0.05). Four months after intervention, there was a reduction of WBC (1962.8/mm ± 0.425/mm, < 0.001), C-reactive protein (CRP) (8.1 mg/L ± 1.7 mg/L, < 0.001), malondialdehyde (MDA) (0.81 nmol/mg ± 0.37, < 0.05) and glycocalyx perfused boundary region (PBR 5-25) (0.24 μm ± 0.05 μm, < 0.01). Moreover, the brachial flow mediated dilatation (FMD), the coronary flow reserve (CFR) and the left ventricle global longitudinal strain (LV GLS) were significantly improved for both groups (4.5% ± 0.9%, 0.55 ± 0.08, 1.4% ± 0.35%, < 0.01), while a more significant improvement of PWV/GLS was noticed in the anti-TNFa group. IBD severity is associated with vascular endothelial, cardiac diastolic, and coronary microcirculatory dysfunction. The systemic inflammatory inhibition and the local surgical intervention lead to significant improvement in endothelial function, coronary microcirculation and myocardial deformation.
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http://dx.doi.org/10.3390/diagnostics11060993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227308PMC
May 2021

Type 1 Diabetes Mellitus in the SARS-CoV-2 Pandemic: Oxidative Stress as a Major Pathophysiological Mechanism Linked to Adverse Clinical Outcomes.

Antioxidants (Basel) 2021 May 9;10(5). Epub 2021 May 9.

Second Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.

Recent reports have demonstrated the association between type 1 diabetes mellitus (T1DM) and increased morbidity and mortality rates during coronavirus disease (COVID-19) infection, setting a priority of these patients for vaccination. Impaired innate and adaptive immunity observed in T1DM seem to play a major role. Severe, life-threatening COVID-19 disease is characterized by the excessive release of pro-inflammatory cytokines, known as a "cytokine storm". Patients with T1DM present elevated levels of cytokines including interleukin-1a (IL), IL-1β, IL-2, IL-6 and tumor necrosis factor alpha (TNF-α), suggesting the pre-existence of chronic inflammation, which, in turn, has been considered the major risk factor of adverse COVID-19 outcomes in many cohorts. Even more importantly, oxidative stress is a key player in COVID-19 pathogenesis and determines disease severity. It is well-known that extreme glucose excursions, the prominent feature of T1DM, are a potent mediator of oxidative stress through several pathways including the activation of protein kinase C (PKC) and the increased production of advanced glycation end products (AGEs). Additionally, chronic endothelial dysfunction and the hypercoagulant state observed in T1DM, in combination with the direct damage of endothelial cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may result in endothelial and microcirculation impairment, which contribute to the pathogenesis of acute respiratory syndrome and multi-organ failure. The binding of SARS-CoV-2 to angiotensin converting enzyme 2 (ACE2) receptors in pancreatic b-cells permits the direct destruction of b-cells, which contributes to the development of new-onset diabetes and the induction of diabetic ketoacidosis (DKA) in patients with T1DM. Large clinical studies are required to clarify the exact pathways through which T1DM results in worse COVID-19 outcomes.
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http://dx.doi.org/10.3390/antiox10050752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151267PMC
May 2021

Association of ventricular-arterial interaction with the response to cardiac resynchronization therapy.

Eur J Heart Fail 2021 07 28;23(7):1238-1240. Epub 2021 Apr 28.

2nd Cardiology Department, Attikon Hospital, University of Athens, Athens, Greece.

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http://dx.doi.org/10.1002/ejhf.2186DOI Listing
July 2021

Myocardial Work: Methodology and Clinical Applications.

Diagnostics (Basel) 2021 Mar 22;11(3). Epub 2021 Mar 22.

Echocardiography Laboratory, 2nd Cardiology Department, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, 12462 Athens, Greece.

A precise and accurate assessment of left ventricular (LV) contractility is of utmost importance in terms of prognosis in most cardiac pathologies. Given the limitations of ejection fraction (EF) and global longitudinal strain (GLS) due to their load dependency, a novel imaging tool called myocardial work (MW) has emerged as a promising method for LV performance evaluation. MW is a novel, less load-dependent method based on computation of myocardial strain-arterial blood pressure curves. This method provides a more detailed assessment of segmental and global LV function incorporating the patient's LV pressure and is derived by brachial artery pressure utilizing an empiric reference curve adjusted to the duration of the isovolumic and ejection phases as determined by echocardiography. The clinical implications of this unique method have been expanding in the last few years, which attest to the robust additive role of MW in routine practice.
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http://dx.doi.org/10.3390/diagnostics11030573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004587PMC
March 2021

An indirect effect of covid-19 on the heart: A case report.

JRSM Cardiovasc Dis 2021 Jan-Dec;10:2048004020974238. Epub 2021 Mar 12.

Echocardiography Laboratory, 2 Cardiology Department, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece.

Covid-19 virus has been recognized to develop major cardiac complications. The indirect effect of the virus though, in terms of fear for hospital admissions, constitutes a greater threat. In this case we present a 69-year old male patient who suffered from a myocardial infarction that has not been given the proper attention due to the fear of in-hospital contact with covid patients. The result was the delayed revascularization and eventually the development of heart failure. This case presents the full range of covid-19 affection to the heart and raises the public awareness for not underestimating symptoms suggesting life-threatening conditions.
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http://dx.doi.org/10.1177/2048004020974238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968005PMC
March 2021

Is there any true distinction in extreme dipping versus nondipping or dipping phenotype regarding hypertension-mediated organ damage in newly diagnosed and never-treated hypertensive patients?

J Hum Hypertens 2021 Feb 15. Epub 2021 Feb 15.

2nd Department of Cardiology, Medical School, National and Kapodistrian University of Athens, ATTIKON Hospital, Athens, Greece.

Dipping phenomena is defined as nocturnal BP fall >10% during 24-h ambulatory blood pressure (BP) monitoring (ABPM) which carries a favorable cardiovascular risk (CVR) prognosis due to reduced 24-h hypertension burden. To date, extreme dipping phenotype (defined as BP decrease ≥20%) has led to controversial prognostic results regarding CVR. We aimed to explore hypertension-mediated organ damage (HMOD) in extreme dippers compared to the other dipping phenotypes (nondipping, dipping). From 490 consecutive patients with newly diagnosed never-treated arterial hypertension (mean age 51 ± 11 years, 294 males) subjected to 24-h ABPM, we studied 52 extreme dippers, 52 age- and gender-matched nondippers, and 52 age- and gender-matched dippers. All patients were subjected to arterial stiffness (PWV), 24-h microalbumin levels, carotid intima-media thickness (cIMT), diastolic dysfunction (E/Ea), and left ventricular mass index (LVMI) evaluation. ANOVA analysis found no differences regarding HMOD between groups. Multiple regression analysis revealed the following independent direct relationships between: (i) office SBP and PWV in nondippers (β = 0.35, p = 0.01) and extreme dippers (β = 0.49, p < 0.001), (ii) office SBP and E/Ea in extreme dippers (β = 0.39, p = 0.007), (iii) 24-h diurnal and nocturnal SBP and E/Ea in dippers (β = 0.40, p = 0.004, β = 0.39, p = 0.005, and β = 0.40, p = 0.004, respectively), and (iv) 24-h and nocturnal SBP and LVMI in nondippers (β = 0.29, p = 0.04 and β = 0.36, p = 0.009, respectively). In the early phases of untreated-arterial hypertension disease, extreme dipping phenotype in middle-aged hypertensives does not imply an adverse or favorable prognosis regarding the incidence of HMOD either as continuous variables or as abnormal HMOD compared to other dipping phenotypes.
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http://dx.doi.org/10.1038/s41371-021-00491-xDOI Listing
February 2021

The association of bullous pemphigoid with dipeptidyl-peptidase 4 inhibitors: a ten-year prospective observational study.

BMC Endocr Disord 2021 Feb 11;21(1):23. Epub 2021 Feb 11.

Second Department of Dermatology and Venereology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Background: Bullous pemphigoid is the most common bullous chronic autoimmune skin disease. Recent studies have suggested dipeptidyl-peptidase 4 inhibitors as possible predisposing agents of bullous pemphigoid. The objective of our study was to prospectively estimate the association between gliptins and the development of bullous pemphigoid.

Methods: We conducted a prospective study which included all patients diagnosed with biopsy-proven bullous pemphigoid in the Dermatology Department of our hospital between April 1, 2009 and December 31,2019. The diagnosis of bullous pemphigoid was based on specific clinical, histological and immunological features.

Results: Overall 113 consecutive patients (age 75 ± 13 years, 62 females) with the diagnosis of bullous pemphigoid were enrolled. Seventy-six patients (67.3%) suffered from type 2 Diabetes and 52 (46%) were treated with dipeptidyl-peptidase 4 inhibitors. The most frequent prescribed gliptin was vildagliptin, being administered to 45 cases (39.8% of total patients enrolled, 86.5% of the patients treated with gliptins). Gliptins were withdrawn immediately after the diagnosis of bullous pemphigoid, which together with steroid administration led to remission of the rash.

Conclusions: This study revealed that treatment with dipeptidyl-peptidase 4 inhibitors, especially vildagliptin, is significantly associated with an increased risk of bullous pemphigoid development.
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http://dx.doi.org/10.1186/s12902-021-00689-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879621PMC
February 2021

Hypertension-mediated organ damage regression associates with blood pressure variability improvement three years after successful treatment initiation in essential hypertension.

J Clin Hypertens (Greenwich) 2021 06 7;23(6):1150-1158. Epub 2021 Feb 7.

2nd Department of Cardiology Medical School, University of Athens, ATTIKON Hospital, Athens, Greece.

Blood pressure variability (BPV) has been associated with the development, progression, and severity of cardiovascular (CV) organ damage and an increased risk of CV morbidity and mortality. We aimed to explore any association between short-term BPV reduction and hypertension-mediated organ damage (HMOD) regression in hypertensive patients 3-year post-treatment initiation regarding BP control. 24-h ambulatory blood pressure monitoring (24 h ABPM) was performed at baseline in 180 newly diagnosed and never-treated hypertensive patients. We measured 24 h average systolic (24 h SBP) and diastolic BP (24 h DBP) as well as 24 h systolic (sBPV) and diastolic BPV (dBPV). Patients were initially evaluated and 3 years later regarding arterial stiffness (PWV), left ventricular hypertrophy (LVMI), carotid intima-media thickness (cIMT), 24 h microalbumin levels (MAU), and coronary flow reserve (CFR). Successful BP treatment was defined as 24 h SBP/DBP < 130/80 mm Hg based on 2nd ABPM and subsequently, patients were characterized as controlled (n = 119, age = 53 ± 11 years) or non-controlled (n = 61, age = 47 ± 11 years) regarding their BP levels. In the whole population and the controlled group, 24 h SBP/DBP, sBPV/dBPV, LVMI, and IMT were decreased. Additionally, LVMI improvement was related with both sBPV (p < .001) and dBPV reduction (r = .18, p = .02 and r = .20, p = .03, respectively). In non-controlled hypertensives, PWV was increased. In multiple linear regression analysis, sBPV and dBPV reduction predicted LVMI improvement in total population and controlled group independently of initial office SBP, mean BP, and 24 h-SBP levels. In middle-aged hypertensive patients, a 3-year antihypertensive treatment within normal BP limits, confirmed by 24-h ABPM, leads to CV risk reduction associated with sBPV and dBPV improvement.
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http://dx.doi.org/10.1111/jch.14209DOI Listing
June 2021

Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study.

Basic Res Cardiol 2021 02 6;116(1). Epub 2021 Feb 6.

2nd Department of Cardiology, Medical School, Attikon Hospital, National and Kapodistrian University of Athens, Rimini 1, Haidari, 12462, Athens, Greece.

Aims: Remote ischemic conditioning (RIC) alleviates ischemia-reperfusion injury via several pathways, including micro-RNAs (miRs) expression and oxidative stress modulation. We investigated the effects of RIC on endothelial glycocalyx, arterial stiffness, LV remodelling, and the underlying mediators within the vasculature as a target for protection.

Methods And Results: We block-randomised 270 patients within 48 h of STEMI post-PCI to either one or two cycles of bilateral brachial cuff inflation, and a control group without RIC. We measured: (a) the perfusion boundary region (PBR) of the sublingual arterial microvessels to assess glycocalyx integrity; (b) the carotid-femoral pulse wave velocity (PWV); (c) miR-144,-150,-21,-208, nitrate-nitrite (NOx) and malondialdehyde (MDA) plasma levels at baseline (T0) and 40 min after RIC onset (T3); and (d) LV volumes at baseline and after one year. Compared to baseline, there was a greater PBR and PWV decrease, miR-144 and NOx levels increase (p < 0.05) at T3 following single- than double-cycle inflation (PBR:ΔT0-T3 = 0.249 ± 0.033 vs 0.126 ± 0.034 μm, p = 0.03 and PWV:0.4 ± 0.21 vs -1.02 ± 0.24 m/s, p = 0.03). Increased miR-150,-21,-208 (p < 0.05) and reduced MDA was observed after both protocols. Increased miR-144 was related to PWV reduction (r = 0.763, p < 0.001) after the first-cycle inflation in both protocols. After one year, single-cycle RIC was associated with LV end-systolic volume reduction (LVESV) > 15% (odds-ratio of 3.75, p = 0.029). MiR-144 and PWV changes post-RIC were interrelated and associated with LVESV reduction at follow-up (r = 0.40 and 0.37, p < 0.05), in the single-cycle RIC.

Conclusion: RIC evokes "vascular conditioning" likely by upregulation of cardio-protective microRNAs, NOx production, and oxidative stress reduction, facilitating reverse LV remodelling.

Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT03984123.
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http://dx.doi.org/10.1007/s00395-021-00851-1DOI Listing
February 2021

The Effect of Antioxidant and Anti-Inflammatory Capacity of Diet on Psoriasis and Psoriatic Arthritis Phenotype: Nutrition as Therapeutic Tool?

Antioxidants (Basel) 2021 Jan 22;10(2). Epub 2021 Jan 22.

Second Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.

Chronic inflammation and increased oxidative stress are contributing factors to many non-communicable diseases. A growing body of evidence indicates that dietary nutrients can activate the immune system and may lead to the overproduction of pro-inflammatory cytokines. Fatty acids as macronutrients are key players for immunomodulation, with n-3 polyunsaturated fatty acids having the most beneficial effect, while polyphenols and carotenoids seem to be the most promising antioxidants. Psoriasis is a chronic, immune-mediated inflammatory disease with multifactorial etiology. Obesity is a major risk factor for psoriasis, which leads to worse clinical outcomes. Weight loss interventions and, generally, dietary regimens such as gluten-free and Mediterranean diet or supplement use may potentially improve psoriasis' natural course and response to therapy. However, data about more sophisticated nutritional patterns, such as ketogenic, very low-carb or specific macro- and micro-nutrient substitution, are scarce. This review aims to present the effect of strictly structured dietary nutrients, that are known to affect glucose/lipid metabolism and insulin responses, on chronic inflammation and immunity, and to discuss the utility of nutritional regimens as possible therapeutic tools for psoriasis and psoriatic arthritis.
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http://dx.doi.org/10.3390/antiox10020157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912156PMC
January 2021

It's Not All about Echocardiography. Open the Lung Window for the Cardiac Emergencies.

Medicina (Kaunas) 2021 Jan 14;57(1). Epub 2021 Jan 14.

Emergency Medicine Clinic, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece.

In the acute cardiac care setting, undifferentiated clinical presentations such as dyspnea, chest pain, shock, and cardiac arrest are common diagnostic challenges for the clinician. Lung ultrasonography is a well-established diagnostic tool which can be integrated in simplified decision making algorithms during the initial approach of the patient, in order to differentiate accurately cardiac from non-cardiac causes and improve the management of time-sensitive cardiovascular emergencies.
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http://dx.doi.org/10.3390/medicina57010069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828810PMC
January 2021

Prevalence of patent foramen ovale in the Greek population is high and impacts on the interpretation of the risk of paradoxical embolism (RoPE) score.

Ther Adv Neurol Disord 2020 10;13:1756286420964673. Epub 2020 Oct 10.

2nd Department of Neurology, Aristotle University of Thessaloniki, AHEPA University Hospital, S.Kyriakidi 1, Thessaloniki, 54636, Greece.

Background: The risk of paradoxical embolism (RoPE) score calculates the probability that patent foramen ovale (PFO) is causally related to stroke (PFO attributable fraction, PFOAF), based on PFO prevalence in patients with cryptogenic stroke (CS) compared with that in the general population. The latter has been estimated at 25%; however, PFO prevalence in nonselected populations varies widely.

Methods: Since PFO prevalence in Greece remains unknown, we evaluated it and we calculated PFOAF stratified by RoPE score in a cohort of patients with CS ⩽55 years old. PFO was detected according to the international consensus transcranial Doppler (TCD) criteria in 124 healthy subjects (H), in 102 patients with CS, and in 56 patients with stroke of known cause (nonCS). Each subject underwent unilateral middle cerebral artery recording after infusion of agitated saline, at rest, and after a controlled Valsalva maneuver. We characterized PFO as large (>20 microbubbles or curtain), moderate (11-20), and small (⩽10).

Results: PFO was detected in 42.7% of H, 49% of CS, and 25% of nonCS ( = 0.013). Large PFOs were numerically higher in CS [28.4% (29/102)] compared with H [19.3% (24/124);  = 0.1] and to nonCS [7.1% (4/56),  = 0.04]. The median RoPE score in patients with CS and PFO was seven. Even patients with very high RoPE score (9-10) had moderate PFOAF (57%). For any individual stratum up to RopE score 8, PFOAF was <33%.

Conclusions: PFO prevalence in the Greek population is much higher than the widely accepted 25%. PFO may be the cause of stroke in one out of nine Greek patients with CS. Among Greek CS patients who harbor a PFO, the latter is causal in one out of five. The established RoPE score cutoff of ⩾7 for having a probable PFO-associated stroke may overestimate the probability in patients deriving from populations with high PFO prevalence.
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http://dx.doi.org/10.1177/1756286420964673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758802PMC
October 2020

Echocardiography, an Indispensable Tool for the Management of Diabetics, with or without Coronary Artery Disease, in Clinical Practice.

Medicina (Kaunas) 2020 Dec 18;56(12). Epub 2020 Dec 18.

Second Department of Internal Medicine, 'Attikon University Hospital', Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.

Diabetes mellitus is a major factor contributing to the development of cardiovascular disease. As morbidity and mortality rates rise dramatically, when target organ damage develops pre-symptomatic assessment is critical for the management of diabetic patients. Echocardiography is a noninvasive and reproducible method that may aid in risk stratification and in evaluation of treatment effects. The aim of this review is to analyze the echocardiographic techniques which can detect early alteration in cardiac function in patients with diabetes.
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http://dx.doi.org/10.3390/medicina56120709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767240PMC
December 2020

PCSK9 in Myocardial Infarction and Cardioprotection: Importance of Lipid Metabolism and Inflammation.

Front Physiol 2020 12;11:602497. Epub 2020 Nov 12.

Institute for Physiology, Justus-Liebig University Giessen, Giessen, Germany.

Extensive evidence from epidemiologic, genetic, and clinical intervention studies has indisputably shown that elevated low-density lipoprotein cholesterol (LDL-C) concentrations play a central role in the pathophysiology of atherosclerotic cardiovascular disease. Apart from LDL-C, also triglycerides independently modulate cardiovascular risk. Reduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for reducing plasma LDL-C, but it is also associated with a reduction in triglyceride levels potentially through modulation of the expression of free fatty acid transporters. Preclinical data indicate that PCSK9 is up-regulated in the ischaemic heart and decreasing PCSK9 expression impacts on infarct size, post infarct inflammation and remodeling as well as cardiac dysfunction following ischaemia/reperfusion. Clinical data support that notion in that PCSK9 inhibition is associated with reductions in the incidence of myocardial infarction, stroke, and coronary revascularization and an improvement of endothelial function in subjects with increased cardiovascular risk. The aim of the current review is to summarize the current knowledge on the importance of free fatty acid metabolism on myocardial ischaemia/reperfusion injury and to provide an update on recent evidence on the role of hyperlipidemia and PCSK9 in myocardial infarction and cardioprotection.
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http://dx.doi.org/10.3389/fphys.2020.602497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688516PMC
November 2020

The Dual Role of Echocardiography in the Diagnosis of Acute Cardiac Complications and Treatment Monitoring for Coronavirus Disease 2019 (COVID-19).

Front Cardiovasc Med 2020 2;7:129. Epub 2020 Sep 2.

2nd Department of Cardiology, COVID-19 Infection Reference Center, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.

The Coronavirus Disease 2019 (COVID-19) pandemic, being caused by an easily and rapidly spreading novel betacoronavirus, has created a state of emergency for people, the scientific community, healthcare systems and states, while the global financial consequences are still unfolding. Cardiovascular complications have been reported for COVID-19-infected patients and are associated with a worse prognosis. ECG and biomarkers may raise suspicion of cardiac involvement. However, transthoracic echocardiography is a fast and reliable bedside method to establish the diagnosis of cardiac complications, including acute coronary syndromes, pericarditis, myocarditis, and pulmonary embolism. Early detection of cardiac dysfunction by speckle tracking echocardiography during off-line analysis may be used to identify a high-risk population for development of heart failure in the acute setting. Precautionary measures are mandatory for operators and equipment to avoid viral dispersion. No specific treatment is yet available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2), and a variety of antiviral, immune-modifying, and antioxidant agents are therefore under intense investigation. Echocardiography, including assessment of myocardial deformation, may provide a useful tool to monitor the effects of the various treatment regimens on cardiac function both acutely and in the midterm.
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http://dx.doi.org/10.3389/fcvm.2020.00129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492803PMC
September 2020

Echocardiography in Autoimmune Rheumatic Diseases for Diagnosis and Prognosis of Cardiovascular Complications.

Medicina (Kaunas) 2020 Sep 1;56(9). Epub 2020 Sep 1.

Second Department of Dermatology and Venereology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.

Autoimmune rheumatic diseases are systemic diseases frequently affecting the heart and vessels. The main cardiovascular complications are pericarditis, myocarditis, valvular disease, obstructive coronary artery disease and coronary microcirculatory dysfunction, cardiac failure and pulmonary hypertension. Echocardiography, including transthoracic two and three-dimensional echocardiography, Doppler imaging, myocardial deformation and transesophageal echo, is an established and widely available imaging technique for the identification of cardiovascular manifestations that are crucial for prognosis in rheumatic diseases. Echocardiography is also important for monitoring the impact of drug treatment on cardiac function, coronary microcirculatory function, valvular function and pulmonary artery pressures. In this article we summarize established and evolving knowledge on the role of echocardiography for diagnosis and prognosis of cardiovascular abnormalities in rheumatic diseases.
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http://dx.doi.org/10.3390/medicina56090445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558642PMC
September 2020

Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19.

Food Chem Toxicol 2020 Nov 18;145:111694. Epub 2020 Aug 18.

2nd Department of Cardiology, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, 12462, Athens, Greece.

We investigated the effects of tocilizumab on endothelial glycocalyx, a determinant of vascular permeability, and myocardial function in rheumatoid arthritis (RA). Eighty RA patients were randomized to tocilizumab (n = 40) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and glucocorticoids (GC) (n = 40) for 3 months. Forty healthy subjects with similar age and sex served as controls. We measured: (a)perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), (b)pulse wave velocity (PWV), (c)global LV longitudinal strain (GLS), (d)global work index (GWI) using speckle tracking echocardiography and e)C-reactive protein (CRP), malondialdehyde (MDA) and protein carbonyls (PCs) as oxidative stress markers at baseline and post-treatment. Compared to controls, RA patients had impaired glycocalyx and myocardial deformation markers (P < 0.05). Compared with baseline, tocilizumab reduced PBR(2.14 ± 0.2 versus 1.97 ± 0.2 μm; P < 0.05) while no significant differences were observed post-csDMARDs + GC(P > 0.05). Compared with csDMARDs + GC, tocilizumab achieved a greater increase of GLS, GWI and reduction of MDA, PCs and CRP(P < 0.05). The percent improvement of glycocalyx thickness (PBR) was associated with the percent decrease of PWV, MDA, PCs and the percent improvement of GLS and GWI(P < 0.05). Tocilizumab improves endothelial function leading to a greater increase of effective myocardial work than csDMARDs + GC through a profound reduction of inflammatory burden and oxidative stress. This mechanism may explain the effects of tocilizumab on COVID-19. CLINICAL TRIAL REGISTRATION: url: https://www.clinicaltrials.gov. Unique identifier: NCT03288584.
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http://dx.doi.org/10.1016/j.fct.2020.111694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434461PMC
November 2020

Sex-related associations of high-density lipoprotein cholesterol with aortic stiffness and endothelial glycocalyx integrity in treated hypertensive patients.

J Clin Hypertens (Greenwich) 2020 10 13;22(10):1827-1834. Epub 2020 Aug 13.

2nd Department of Cardiology, Medical School, ATTIKON Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Smoking, a well-recognized major cardiovascular (CV) risk factor, impairs endothelial function and increases aortic stiffness which indicates subclinical organ damage in hypertensive patients. Loss of endothelial glycocalyx (EG) integrity, as part of the endothelium, represents endothelial dysfunction. The authors aimed to investigate the role of increased HDL cholesterol levels (HDL-C), which usually are considered protective against CV disease, in aortic stiffness and endothelial integrity in middle-aged treated hypertensive patients regarding smoking habit. The authors studied 193 treated hypertensive patients ≥40 years (mean age = 61±11 years, 58% females), divided in four groups regarding sex and smoking. Increased perfusion boundary region of the 5-9 μm diameter sublingual arterial microvessels (PBR ) was measured as a noninvasive accurate index of reduced EG thickness. Aortic stiffness was estimated by carotid-femoral pulse wave velocity (PWV). In the whole population, an inverse weak relationship was found between HDL-C and PWV (r = -.15, P = .03) and PBR (ρ = -.15, P = .03). Moreover, HDL-C was negatively related to PBR in males (r = -.29, P = .008) either smokers (r = -.35, P < .05) or non-smokers (r = -.27, P < .05) and PWV in female non-smokers (r = -.28, P = .009). In a multiple linear regression analysis, using age, weight, smoking, HDL-C, and LDL-C as independent variables, we found that HDL-C independently predicts PWV in the whole population (β = -.14, P = .02) and PBR in male hypertensive patients (β = -.28, P = .01). Higher HDL-C levels are associated with reduced aortic stiffness in hypertensive patients, while they protect EG and subsequently endothelial function in middle-aged, treated hypertensive male patients (either smokers or not).
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http://dx.doi.org/10.1111/jch.14002DOI Listing
October 2020

Are Unattended Blood Pressure Measurements Necessary in All Patients Visiting an Outpatient Cardiology Clinic?

High Blood Press Cardiovasc Prev 2020 Oct 27;27(5):389-397. Epub 2020 Jul 27.

2nd Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Attikon Hospital, 83, Agiou Ioannou Theologou, Holargos, 155 61, Athens, Greece.

Introduction: Unattended automatic office blood pressure (BP) measurement has given new evidence regarding treatment goals.

Aim: We aimed to explore any differences between unattended and conventional office BP measurements in different groups of patients visiting a European Society of Hypertension (ESH)  Excellence Centre.

Methods: We performed two unattended (Microlife Watch BP Home) followed by a single attended (mercury sphygmomanometer) BP measurement in 310 patients (mean age 62 ± 15 years, 151 males, 64% hypertensives and 36% normotensive individuals) visiting our ESH Centre for a scheduled follow-up. Office BP < 140 mmHg (systolic) and < 90 mmHg (diastolic) were characterized as controlled or normal in hypertensives and normotensive individuals, respectively.

Results: Attended BP (systolic/diastolic) was higher than unattended BP in total population (p < 0.001 and p = 0.02) and hypertensives (p < 0.001). In hypertensives, attended BP was higher than unattended BP regardless of age, smoking habit, obesity or controlled BP status but it was similar to unattended in diabetic patients. In normotensive individuals, attended BP was higher than unattended BP in older (p = 0.04), non-smoker (p = 0.002) and non-diabetic (p = 0.02) subjects. Finally, unattended BP was important for treatment decisions only in a small group of non-diabetic hypertensive patients (7%) whose unattended BP was controlled while attended BP was uncontrolled.

Conclusions: Unattended BP was lower than attended BP in the majority of hypertensive patients. However, it was useful only in a small percentage of non diabetic hypertensive patients in order to take appropriate treatment plan decisions.
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http://dx.doi.org/10.1007/s40292-020-00402-0DOI Listing
October 2020

A Narrative and Critical Review of Randomized-Controlled Clinical Trials on Patent Foramen Ovale Closure for Reducing the Risk of Stroke Recurrence.

Front Neurol 2020 4;11:434. Epub 2020 Jun 4.

Second Department of Neurology, School of Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Patent foramen ovale (PFO) is a common cardiac anatomic variant that has been increasingly found in young (<60 years) cryptogenic stroke patients. Despite initial neutral randomized-controlled clinical trials (RCTs), there have been four recent RCTs providing consistent data in favor of the efficacy and safety of PFO closure compared to medical therapy for secondary stroke prevention. However, taking into consideration the high prevalence of PFO, the low risk of stroke recurrence under medical treatment and the uncommon yet severe adverse events of the intervention, patient selection is crucial for attaining meaningful clinical benefits. Thorough workup to exclude alternative causes of stroke and identification of high-risk PFOs through clinical, neuroimaging and echocardiographic criteria are essential. Cost effectiveness of the procedure cannot be proven for the time being, since there are no robust data on clinical outcome after PFO-associated stroke but only limited anecdotal data suggesting low risk for long-term disability.
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http://dx.doi.org/10.3389/fneur.2020.00434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326015PMC
June 2020

Global Longitudinal Strain of the Systemic Ventricle Is Correlated with Plasma Galectin-3 and Predicts Major Cardiovascular Events in Adult Patients with Congenital Heart Disease.

Medicina (Kaunas) 2020 Jun 22;56(6). Epub 2020 Jun 22.

Second Cardiology Department, ATTIKON University Hospital, National and Kapodistrian University of Athens, 12461 Athens, Greece.

: We sought to assess in adult congenital heart disease (ACHD) patients the prognostic value of plasma galectin-3 (Gal-3) levels and systemic ventricular global longitudinal strain (SV GLS) as well as their association with NTproBNP and arrhythmogenesis. : We studied 58 patients (26 men, mean age 37 ± 16.8 years) with various congenital heart diseases. Patients underwent echocardiogram, 24 h ambulatory ECG monitoring, while NTproBNP and Gal-3 were measured. They were followed up (median of 790.5 days -IQR 350.3 days) and major cardiovascular events (MACE) were recorded. . Mean Gal-3 levels were 17.07 ± 6.38 ng/m. Plasma Gal-3 was correlated with LogNTproBNP (r = 0.456, = 0.001).Gal-3 levels associated with supraventricular tachycardia (SVT) ( < 0.001) and ventricular tachycardia (VT) ( < 0.001), but was not associated with MACE (HR 1.018, 95% CI 0.944-1.098, = 0.641).Mean SVGLS in patients with systemic left ventricle was -15.91% ± 4.09%, which was significantly lower compared to patients with systemic right ventricle and patients with single ventricle (-11.42% ± 3.37% and -11.9% ± 5.06%, respectively, = 0.021).SV GLS correlated with plasma Gal-3 (r = 0.313, = 0.027) and logNTproBNP (r = 0.479, < 0.001). SVGLS correlated with VT arrhythmias ( = 0.004). NTproBNP predicted MACE (AUC 0.750, = 0.03). SVGLS also predicted MACE (AUC 0.745, = 0.03. In multivariate analysis, SVGLS and logNTproBNP maintained their predictive value ( = 0.004 and = 0.009, respectively) : In ACHD patients, SV GLS was found to predict MACE independently from NTproBNP and correlated with VT. Gal-3 correlated with NTproBNP and SVGLS as well as SVT and VT, but has not been shown to bear significant prognostic potential.
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http://dx.doi.org/10.3390/medicina56060305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353898PMC
June 2020

Changes in aortic stiffness and the hemodynamics following endovascular repair of the thoracic aorta of patients with blunt thoracic aortic injury.

Vasa 2020 Jun;49(4):253-255

Department of Vascular Surgery, Attikon University Hospital, Athens, National and Kapodistrian University οf Athens, Greece.

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http://dx.doi.org/10.1024/0301-1526/a000863DOI Listing
June 2020

Obesity and COVID-19: immune and metabolic derangement as a possible link to adverse clinical outcomes.

Am J Physiol Endocrinol Metab 2020 07 27;319(1):E105-E109. Epub 2020 May 27.

Second Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Recent reports have shown a strong association between obesity and the severity of COVID-19 infection, even in the absence of other comorbidities. After infecting the host cells, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause a hyperinflammatory reaction through the excessive release of cytokines, a condition known as "cytokine storm," while inducing lymphopenia and a disrupted immune response. Obesity is associated with chronic low-grade inflammation and immune dysregulation, but the exact mechanisms through which it exacerbates COVID-19 infection are not fully clarified. The production of increased amounts of cytokines such as TNFα, IL-1, IL-6, and monocyte chemoattractant protein (MCP-1) lead to oxidative stress and defective function of innate and adaptive immunity, whereas the activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome seems to play a crucial role in the pathogenesis of the infection. Endothelial dysfunction and arterial stiffness could favor the recently discovered infection of the endothelium by SARS-CoV-2, whereas alterations in cardiac structure and function and the prothrombotic microenvironment in obesity could provide a link for the increased cardiovascular events in these patients. The successful use of anti-inflammatory agents such as IL-1 and IL-6 blockers in similar hyperinflammatory settings, like that of rheumatoid arthritis, has triggered the discussion of whether such agents could be administrated in selected patients with COVID-19 disease.
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http://dx.doi.org/10.1152/ajpendo.00198.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322508PMC
July 2020
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