Επιστημονικό Έργο και Δημοσιεύσεις Δρ. Ανδρέας Τριανταφύλλης

Acute myocardial infarction-related cardiogenic shock (AMI-CS) is commonly clinically characterised by low blood pressure. Noradrenaline is the guideline-recommended first-line vasopressor therapy in patients in cardiogenic shock to increase blood pressure. Although no strict criteria exist, noradrenaline is commonly titrated to a mean arterial pressure (MAP) of above 65 mmHg. No evidence exists, however, that targeting a pharmacologically induced MAP of above 65 mmHg improves clinical outcome. Furthermore, noradrenaline is associated with unwanted effects such as elevated afterload, increased myocardial oxygen demand, and arrhythmias. Therefore, we sought to investigate whether treatment with a lower noradrenaline-mediated MAP-target regimen in AMI-CS patients leads to improved outcomes. In this international, open-label, multicentre, randomised superiority trial, 776 patients will be allocated in a 1:1 ratio to either the index treatment of a lower noradrenaline-mediated MAP-target regimen (MAP of 55 mmHg) or a standard noradrenaline-mediated MAP-target regimen (MAP of at least 65 mmHg). The NORshock trial tests the hypothesis that a permissive hypotension treatment strategy with reduced use of noradrenaline in patients with AMI-CS is superior to standard care in terms of a combined endpoint of all-cause death and renal replacement therapy within 30 days. The NORshock trial is the first randomised trial investigating a strategy of a lower noradrenaline-mediated MAP-target regimen (MAP of 55 mmHg) compared with a standard noradrenaline-mediated MAP-target regimen (MAP of at least 65 mmHg) on clinical outcomes in AMI-CS patients.

Background/Objectives: Angiographic stenosis severity and functional significance are discordant in up to 65% of intermediate coronary lesions. Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) has shown better clinical outcomes than standard angiography-guided PCI, therefore functional significance defines revascularization. This review evaluates the contemporary evidence for intracoronary physiology assessment tools, such as FFR, non-hyperemic pressure ratios (NHPRs), angiography-derived wire-free indices, and microvascular function testing, and proposes a framework for their implementation into clinical practice. Methods: We conducted a narrative review, synthesizing data from landmark randomized controlled trials (DEFER, FAME I-III, DANAMI-3-PRIMULTI, COMPARE-ACUTE, DEFINE-FLAIR, iFR-SWEDEHEART, iMODERN, FAVOR III China and Europe, FAST III, ALL-RISE, CorMicA), along with pooled analyses, meta-analyses, position papers, and relevant guidelines. Results: FFR-guided revascularization resulted in a 28% reduction in cardiac death or myocardial infarction in pooled analyses (HR 0.72, 95% CI 0.54-0.96). leading to a Class I, Level A indication. NHPRs, including iFR, achieved non-inferiority to the FFR at 1 year; however, a 5-year pooled meta-analysis raised concerns of increased all-cause mortality with iFR guidance compared to the FFR (HR 1.34, 95% CI 1.08-1.67). Approximately 20% of lesions show FFR-iFR discordance, driven by vessel-specific physiology and microvascular factors. Wire-free technologies yielded conflicting results: the FAVOR III China trial favored the QFR over angiography, yet FAVOR III Europe failed non-inferiority versus the FFR, while the recent FAST III and ALL-RISE trials demonstrated the non-inferiority of angiography-derived physiology at 1 year. Up to 40% of patients with angina have non-obstructed coronary arteries, and coronary vasomotor function testing can identify treatable microvascular endotypes improving symptoms and quality of life. Conclusions: Functional invasive coronary angiography is advocated to decipher vessel hemodynamics and to guide treatment. The FFR remains the gold standard for invasive physiological assessments, while NHPRs and wire-free technologies are valuable adjuncts with specific indications and limitations. A thorough microvascular evaluation is essential for differentiating between various INOCA endotypes and is gradually being adopted by the interventional community. While NHPRs and virtual technologies struggle to dethrone the king FFR, a comprehensive intracoronary physiology assessment is essential to guide treatment.

Bleeding remains the most common complication following transcatheter aortic valve implantation (TAVI), despite a decline in its incidence over time. Periprocedural (≤30 days) major or life-threatening bleeding is reported to occur in 2.0-6.6% of patients undergoing TAVI. Major bleeding events carry a significant risk of mortality, with rates of 14.1% at 30 days and 27.8% at one year. The timely identification and management of patients at an elevated risk are therefore essential. Preventive measures include optimizing antithrombotic therapies, utilizing ultrasound-guided femoral access, employing single arterial access or a radial artery for secondary access, and administering unfractionated heparin under close monitoring. Long-term follow-up is essential for recognizing and managing late hemorrhages. In this review, we aimed to provide an in-depth analysis of bleeding events associated with TAVI and the most recent updates regarding the antithrombotic therapy of TAVI patients and its clinical impact.

Background: Radiation exposure in the cardiac catheterization laboratory remains a critical occupational hazard for interventional cardiologists and staff, contributing to orthopedic injuries, cataracts, and malignancy. In parallel, procedural complexity continues to increase, demanding both precision and safety. Robotic-assisted percutaneous coronary intervention (R-PCI), alongside advanced shielding systems and imaging integration, has emerged as a transformative strategy to minimize radiation and enhance operator ergonomics. Objective: This state-of-the-art review synthesizes the current clinical evidence and technological advances that support a radiation-reduction paradigm in percutaneous coronary intervention (PCI), with a particular focus on the role of R-PCI platforms, procedural modifications, and emerging shielding technologies. Methods: We reviewed published clinical trials, registries, and experimental studies evaluating robotic PCI platforms, contrast and radiation dose metrics, ergonomic implications, procedural efficiency, and radiation shielding systems. Emphasis was given to the integration of CT-based imaging (coronary computed tomography angiography-CCTA, fractional flow reserve computed tomography-FFR-CT) and low-dose acquisition protocols. Results: R-PCI demonstrated technical success rates of 81-100% and clinical success rates up to 100% in both standard and complex lesions, with significant reductions in operator radiation exposure (up to 95%) and procedural ergonomic burden. Advanced shielding technologies offer radiation dose reductions ranging from 86% to nearly 100%, while integration of (CCTA), (FFR-CT), and Artificial Intelligence (AI) -assisted procedural mapping facilitates further fluoroscopy minimization. Robotic workflows, however, remain limited by lack of device compatibility, absence of haptic feedback, and incomplete integration of physiology and imaging tools. Conclusions: R-PCI, in combination with shielding technologies and imaging integration, marks a shift towards safer, radiation-minimizing interventional strategies. This transition reflects not only a technical evolution but a philosophical redefinition of safety, precision, and sustainability in modern interventional cardiology.

Anxiety disorders are among the most common psychiatric conditions that significantly impair one's quality of life and place a significant burden on healthcare systems. Conventional treatments have certain restraints, such as potential side effects and limited efficacy. Τhe underlying pathophysiological mechanisms of anxiety are not fully understood. A comprehensive literature search was performed in MEDLINE and Scopus databases for original English-language articles published between January 2014 and December 2024. Study selection, data extraction, and screening were independently carried out by multiple investigators using predefined criteria. Our review aimed to help better comprehend the molecular basis of anxiety, focusing on the hypothalamic-pituitary-adrenal (HPA) axis, serotonergic signaling, and gamma-aminobutyric acid (GABA) neurotransmission. In addition, we addressed the role of epigenetics and pharmacogenomics in personalized treatment. Although novel anxiety treatments are promising, they are predominantly preclinical and highly heterogeneous, which poses a challenge to achieving reliable therapeutic efficacy. Our findings could potentially contribute to the development of new therapeutic interventions. Further research is warranted, especially in human subjects, with an aim to combine genetic and epigenetic profiles to refine treatment approaches and develop innovative therapeutics.

BACKGROUND: In psoriasis, damage-associated molecular patterns (DAMPs) released by damaged local tissue act as danger signals and trigger inflammatory responses. Statins, in addition to cholesterol-lowering, have anti-inflammatory effects. We sought to assess the effectiveness of atorvastatin in attenuating plasma DAMPs and inflammatory cytokines in adults with psoriasis.

METHODS: In this prospective 3-month study, we included 21 eligible psoriatic patients who received oral atorvastatin 10 mg/day and 14 non-psoriatic controls. Blood samples for DAMPs measurement were collected at baseline and 3 months. Additionally, efficacy outcomes were estimated using psoriasis severity index and dermatology-specific quality of life index scores at baseline and 3 months.

RESULTS: Compared to control, psoriatic plasma showed a decrease in the decoy of DAMPs, the soluble (s) receptor for advanced glycation end products (sRAGE), and increases in the DAMPs S100B, S100A7, S1100A12, S100A8/A9, DJ-1, the inflammatory cytokines IL-6, IL-1β and TNF-α. Atorvastatin for 3 months improved efficacy scores, increased sRAGE, and decreased DAMPs and inflammatory cytokines toward control levels. Mechanistically, in the immortalized embryonic fibroblast Swiss mouse cell line NIH3T3s, S100A12, and S100A7 induced an inflammatory response and atorvastatin increased sRAGE in the medium.

CONCLUSION: Statin therapy is effective in lowering DAMPs-induced inflammation in psoriasis patients. The main limitation of our study is the small sample size, and the findings should be confirmed in a larger cohort.

Patients with SARS-CoV-2 infection carry an increased risk of cardiovascular disease encompassing various implications, including acute myocardial injury or infarction, myocarditis, heart failure, and arrhythmias. A growing volume of evidence correlates SARS-CoV-2 infection with myocardial injury, exposing patients to higher mortality risk. SARS-CoV-2 attacks the coronary arterial bed with various mechanisms including thrombosis/rupture of preexisting atherosclerotic plaque, de novo coronary thrombosis, endotheliitis, microvascular dysfunction, vasculitis, vasospasm, and ectasia/aneurysm formation. The angiotensin-converting enzyme 2 receptor plays pivotal role on the cardiovascular homeostasis and the unfolding of COVID-19. The activation of immune system, mediated by proinflammatory cytokines along with the dysregulation of the coagulation system, can pose an insult on the coronary artery, which usually manifests as an acute coronary syndrome (ACS). Electrocardiogram, echocardiography, cardiac biomarkers, and coronary angiography are essential tools to set the diagnosis. Revascularization is the first-line treatment in all patients with ACS and obstructed coronary arteries, whereas in type 2 myocardial infarction treatment of hypoxia, anemia and systemic inflammation are indicated. In patients presenting with coronary vasospasm, nitrates and calcium channel blockers are preferred, while treatment of coronary ectasia/aneurysm mandates the use of antiplatelets/anticoagulants, corticosteroids, immunoglobulin, and biologic agents. It is crucial to untangle the exact mechanisms of coronary involvement in COVID-19 in order to ensure timely diagnosis and appropriate treatment. We have reviewed the current literature and provide a detailed overview of the pathophysiology and clinical spectrum associated with coronary implications of SARS-COV-2 infection. Patients with SARS-CoV-2 infection carry an increased risk of cardiovascular disease encompassing various implications, including acute myocardial injury or infarction, myocarditis, heart failure, and arrhythmias. A growing volume of evidence correlates SARS-CoV-2 infection with myocardial injury, exposing patients to higher mortality risk. SARS-CoV-2 attacks the coronary arterial bed with various mechanisms including thrombosis/rupture of preexisting atherosclerotic plaque, de novo coronary thrombosis, endotheliitis, microvascular dysfunction, vasculitis, vasospasm, and ectasia/aneurysm formation. The angiotensin-converting enzyme 2 receptor plays pivotal role on the cardiovascular homeostasis and the unfolding of COVID-19. The activation of immune system, mediated by proinflammatory cytokines along with the dysregulation of the coagulation system, can pose an insult on the coronary artery, which usually manifests as an acute coronary syndrome (ACS). Electrocardiogram, echocardiography, cardiac biomarkers, and coronary angiography are essential tools to set the diagnosis. Revascularization is the first-line treatment in all patients with ACS and obstructed coronary arteries, whereas in type 2 myocardial infarction treatment of hypoxia, anemia and systemic inflammation are indicated. In patients presenting with coronary vasospasm, nitrates and calcium channel blockers are preferred, while treatment of coronary ectasia/aneurysm mandates the use of antiplatelets/anticoagulants, corticosteroids, immunoglobulin, and biologic agents. It is crucial to untangle the exact mechanisms of coronary involvement in COVID-19 in order to ensure timely diagnosis and appropriate treatment. We have reviewed the current literature and provide a detailed overview of the pathophysiology and clinical spectrum associated with coronary implications of SARS-COV-2 infection.

A 59-year-old diabetic man with a history of numerous coronary angiographies (CAs) and peripheral artery disease underwent CA due to a non-ST elevation myocardial infarction. Femoral, radial, and ulnar arteries were unpalpable.

Coronary artery ectasia (CAE) is defined as abnormal dilation of a coronary artery with a diameter exceeding that of adjacent normal arterial segment by >1.5 times. CAE is a pathological entity of the coronary arteries and characterized as a variant of coronary atherosclerosis. CAE frequently coexists with coronary artery disease (CAD). While inflammation appears to be involved, the pathophysiology of CAE remains unclear. Damage-associated molecular patterns (DAMPs), defined as endogenous molecules released from stressed or damaged tissue, are deemed as alarm signals by the innate immune system. Inflammatory agents can generate DAMPs and DAMPs can create a pro-inflammatory state. In a prospective cross-sectional study, we enrolled 29 patients with CAE and non-obstructive CAD, 19 patients with obstructive CAD without CAE, and 14 control subjects with normal (control) coronary arteries age- and sex-matched with the CAE patients, to investigate the differential expression of plasma DAMPs. Patients with CAE and non-obstructive CAD had increased plasma levels of the DAMPs S100B, S100A12, HMGB1, and HSP70, the DAMPs receptor TLR4, and miR328a-3p compared to CAD and controls. Plasma levels of the mir328a-3p target the protective soluble form of the DAMPs receptor for advanced glycation end products (sRAGE), and the antioxidant DJ-1 was decreased in both CAE and CAD compared to controls. In an in vitro human umbilical vein endothelial cells model, circulating levels of S100B, HMGB1, HSP70 as well as CAE patient plasma induced inflammatory responses. The differential expression of the DAMPs S100B, HSP70, HMGB1, and their receptors TLR4 and sRAGE in CAE versus CAD makes them attractive novel biomarkers as therapeutic targets and therapeutics.

Chronic total occlusions (CTOs) represent the most complex subset of coronary artery disease and therefore careful planning of CTO percutaneous coronary recanalization (PCI) strategy is of paramount importance aiming to achieve procedural success, and improve patient's safety and post CTO PCI outcomes. Intravascular imaging has an essential role in facilitating CTO PCΙ. First, intravascular ultrasound (IVUS), due to its higher penetration depth compared to optical coherence tomography (OCT), and the additional capacity of real-time imaging without need for contrast injection is considered the preferred imaging modality for CTO PCI. Secondly, IVUS can be used to resolve proximal cap ambiguity, facilitate wire re-entry when dissection and re-entry strategies are applied and most importantly to guide stent deployment and optimization post implantation. The role of OCT during CTO PCI is currently limited to stent sizing and optimization, however, due to its high spatial resolution, OCT is ideal for detecting stent edge dissections and strut malapposition. In this review, we describe the use of intravascular imaging for lesion crossing, plaque characterization and wire tracking, extra- or intra-plaque, and stent sizing and optimization during CTO PCI and summarize the findings of the major studies in this field.

Asthma is a heterogeneous disease, characterized by chronic inflammation and oxidative stress of the airways. Several inflammatory pathways including activation of the receptor for advanced glycation end products (RAGE) have been described in the course of the disease. DJ-1 is a redox-sensitive protein with multifaceted roles in mast cell homeostasis and an emerging role in the pathogenesis of asthma. Moreover, cardiac function abnormalities have been described via echocardiography in patients with asthma. The main aim of this study was to investigate the plasma levels of RAGE, its ligands and DJ-1 in asthmatic patients pre- and post-treatment along with echocardiographic indices of cardiovascular function. The study population was divided into two groups. Group A included 13 patients with newly diagnosed bronchial asthma who were free of treatment for at least two weeks and Group B included 12 patients without asthma. An echocardiography examination was performed on all patients. The plasma levels of RAGE, its ligands (AGEs, S100A12, S100B, S100A8/A9), the interleukins (IL-6, IL-1β) and DJ-1 were measured. No differences were noted among the two groups for baseline characteristics and echocardiographic indices of cardiac function. In Group A, 31% suffered from mild asthma, 54% from moderate asthma and 15% from severe asthma. Plasma levels of IL-6, AGEs and AGE/RAGE ratio were increased and those of S100A12 and DJ-1 were decreased in asthmatics. Pharmacotherapy with corticosteroids/β2-agonists decreased IL-6, and AGEs, and increased DJ-1. In search of novel approaches in diagnosing and treating patients with asthma, S100A12, ratio AGE/sRAGE, and DJ-1 in addition to IL-6 may prove to be useful tools.

BACKGROUND AND AIMS: The multi-ligand receptor for advanced glycation end products (RAGE) and its ligands AGEs and S100/calgranulin proteins are important mediators of inflammation and oxidative stress whereas the soluble form of RAGE (sRAGE) by acting as a decoy and the antioxidant PARK7/DJ-1 exert antiatherogenic effects. We examined whether sRAGE and its ligands AGEs, S100A8/A9, S100B, S100A12 and DJ-1 are associated with the presence of angiographic coronary artery disease (CAD) in asymptomatic patients with and without diabetes.

METHODS AND RESULTS: Plasma levels of RAGE ligands, sRAGE and DJ-1 were determined in 50 patients with angiographically proven CAD and in 50 age-matched healthy controls. In the whole cohort, lower levels of sRAGE and higher levels of interleukin-6 (IL-6), the RAGE ligands S100B, S100A12 and the AGEs/sRAGE ratio were associated with CAD. In patients without diabetes (n = 72), lower levels of sRAGE and DJ-1 and higher levels of IL-6 and AGEs/sRAGE ratio were associated with CAD. In multivariable analysis, AGEs/sRAGE ratio was an independent predictor of CAD both in the whole cohort (p = 0.034, OR = 1.247, [95%CI: 1.024, 1.0519]) and in the subgroup of patients without diabetes (p = 0.021, OR = 1.363, 95%CI [1.048, 1.771]) on top of established cardiovascular risk factors.

CONCLUSION: Alterations in plasma RAGE axis inflammatory mediators are associated with atherosclerosis, and higher levels of AGEs/sRAGE ratio are independently associated with CAD in asymptomatic patients and may act as a novel biomarker for predicting CAD. DJ-1 emerges as promising marker of oxidative stress in CAD patients without diabetes, a finding that deserves further study.

Conspiracy theories can have particularly harmful effects by negatively shaping health-related behaviours. A significant number of COVID-19 specific conspiracy theories emerged in the immediate aftermath of the pandemic outbreak. The aim of this study was to systematically review the literature on conspiracy theories related to COVID-19 during the first year of the pandemic (2020), to identify their prevalence, their determinants and their public health consequences. A comprehensive literature search was carried out in PubMed and PsycINFO to detect all studies examining any conspiracy theory related to COVID-19 between January 1st 2020, and January 10th 2021. Forty-three studies were included with a total of 61,809 participants. Between 0.4 and 82.7% of participants agreed with at least one conspiracy belief. Certain sociodemographic factors (young age, female gender, being non-white, lower socioeconomic status), psychological aspects (pessimism, blaming others, anger) and other qualities (political conservatism, religiosity, mistrust in science and using social media as source of information) were associated with increased acceptance of conspiracy theories. Conspiracy beliefs led to harmful health-related behaviours and posed a serious public health threat. Large-scale collaborations between governments and healthcare organizations are needed to curb the spread of conspiracy theories and their adverse consequences.

OBJECTIVE: To explore the association of sleep characteristics with cardiovascular disease (CVD) using self-reported questionnaires.

MATERIAL AND METHODS: 957 adults between 19 and 86 years old were enrolled in this cross-sectional study. The participants were classified into three groups [short (<6h), normal (6-8h), and long (>8h) sleepers] by using multistage stratified cluster sampling. CVD was defined by a positive response to the questions: "Have you been told by a doctor that you have had a heart attack or angina or stroke or have you undergone bypass surgery?". Sleep quality, utilizing Epworth sleepiness scale, Athens insomnia scale, Pittsburgh sleep quality index and Berlin questionnaire, was also examined.

RESULTS: Prevalence of CVD was 9.5%. Individuals with CVD exhibited reduced sleep duration by 33 min (p<0.001) and sleep efficiency by 10% (p<0.001). In multivariable logistic regression analysis, adjusting for subjects' sociodemographic, lifestyle habits and health related characteristics, short sleep duration was almost three times more frequent in patients with CVD (aOR=2.86, p<0.001 in the entire sample; aOR=2.68, p=0.019 in women and aOR=2.57, p=0.009 in men). Furthermore, CVD was significantly associated with excessive daytime sleepiness (aOR=2.02, p=0.026), insomnia (aOR=1.93, p=0.010), poor sleep quality (aOR=1.90, p=0.006) and increased risk of obstructive sleep apnea (aOR=2.08, p=0.003).

CONCLUSION: Our study highlights a strong correlation of sleep insufficiency with CVD and promotes early pharmacological or cognitive behavioral interventions in order to protect cardiovascular health.

OBJECTIVES: To identify angiographic predictors of aberrant left circumflex artery (LCx) by comparing left main (LM) length and bifurcation angle between patients with aberrant LCx and normal anatomy.

BACKGROUND: Failure to recognize aberrant LCx during a cardiac catheterization may hamper correct diagnosis, delay intervention in acute coronary syndromes, and result in increased contrast volume, radiation exposure, and infarct size.

METHODS: We retrospectively analyzed angiograms of aberrant LCx patients and normal anatomy matched controls, in three-participating centers. LM-length, bifurcation angle between the left anterior descending (LAD) and the first non-LAD branch of the LM, and procedural data were compared.

RESULTS: Between 2003 and 2020, 136 patients with aberrant LCx and 135 controls were identified. More catheters (2.4 ± 0.6 vs. 2.2 ± 0.9, p = 0.009), larger contrast volumes (169 ± 94 ml vs. 129 ± 68 ml, p < 0.0005), and prolonged fluoroscopy time (652.9 ± 623.7 s vs. 393.1 ± 332.1 s, p < 0.0005), were required in the aberrant LCx-group compared with controls. Patients with aberrant LCx had a longer LM-length and a more acute bifurcation angle, both in caudal and cranial views, compared with controls (24.7 ± 8.1 vs. 10.8 ± 4.5 mm, p < 0.0005 and 26.7 ± 7.4 vs. 12 ± 5.5 mm, p < 0.0005, respectively, and 45.2° ± 12° vs. 88.8° ± 23°, p < 0.0005 and 51.9° ± 21° vs. 68.2° ± 28.3°, p < 0.0005, respectively). In ROC analysis, LM-length showed the best diagnostic accuracy for detecting aberrant LCx. In multiple logistic regression analysis, a cranially measured LM-length > 17.7 mm was associated with a 5.3 times greater probability of predicting aberrant LCx [95% CI (3.4-8.1), p < 0.0001].

CONCLUSIONS: Our study suggests that a long LM-length and an acute bifurcation angle can indicate the presence of aberrant LCx. We present a practical algorithm for its rapid identification.

With combined antiretroviral therapy, people living with HIV (PLWH) survive longer and are now more likely to die from cardiovascular diseases. PLWH presenting with a ST-segment elevation myocardial infarction are likely to have a high thrombus burden and are at high risk for in-hospital and long-term adverse events. An increasing number of PLWH are presenting with stable coronary artery disease related to atherosclerosis. Revascularization in these patients is associated with higher in-hospital and long-term major adverse cardiovascular events, including stent thrombosis and in-stent restenosis. However, data in this expanding population concerning optimal revascularization strategy are still lacking. In particular, data comparing percutaneous versus surgical revascularization in PLWH are needed. In this review we highlight the currently available data related to coronary revascularization in PLWH.

OBJECTIVE: To investigate the potential association between sleep insufficiency and dyslipidemia (DL) in the primary care setting using self-reported questionnaires.

MATERIAL AND METHODS: 957 adults aged between 19 and 86 years old from the rural area of Thrace, Greece were enrolled in this cross-sectional study. Multistage stratifed cluster sampling was used and the subjects were classifed into three groups according to sleep duration [short (<6h), normal (6-8h), and long (>8h) sleep duration]. DL was defined by a positive response to the question "Have you ever been told by a doctor or health professional that your blood cholesterol or triglyceride levels were high?", or if they were currently taking antilipidemic agents. Sleep quality, utilizing Epworth sleepiness scale, Athens insomnia scale, Pittsburgh sleep quality index and Berlin questionnaire, was also examined.

RESULTS: DL prevalence was significantly associated with short sleep duration (aOR=2.18, p<0.001) and insomnia (aOR=1.43, p=0.050), while its relation with poor sleep quality (aOR=1.31, p=0.094) and risk for obstructive sleep apnea (aOR=1.32, p=0.097) were of marginal statistical significance. Concerning insomnia subtypes, DL was significantly associated with difficulties maintaining sleep (aOR=2.99, p<0.001) and early morning awakenings (aOR=1.38, p=0.050), but not difficulties initiating sleep (aOR=1.18, p=0.328).

CONCLUSION: This study reveals an association between sleep pathology and DL. Thus, early pharmacological and cognitive or behavioral interventions that improve sleep are deemed necessary in order to decrease DL burden.

Background: We aimed to investigate the relationship between sleep characteristics with hypertension using self-reported questionnaires. Material & methods: A total of 957 adults were classified into three groups (short [<6 h], normal [6-8 h] and long [>8 h] sleepers). Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or use of antihypertensive medication at the time of interview. Results: Overall prevalence of hypertension was 34.3%. Association between short sleep duration and hypertension that was age-specific, present only among younger and middle aged individuals and sparing the elderly, but not gender-specific, as no discrepancies existed between males and females in all age groups, was evident. Conclusion: This study promotes early pharmacological or cognitive behavioral interventions on sleep disturbances in order to reduce hypertension burden.

Apart from its beneficial effects on cardiovascular risk factors, an anti-inflammatory effect of exercise is strongly implicated. Yet, data regarding the effect of an exercise intervention on healthy individuals are limited and contradictory. The present study aimed to investigate the effects of a physical activity intervention on the soluble form of the receptor for advanced glycation end products (sRAGEs) and its ligands S100A8/A9. A total of 332 young army recruits volunteered and 169 completed the study. The participants underwent the standard basic training of Greek army recruits. IL-6, IL-1β, S100A8/A9, and sRAGEs were measured at the beginning and at the end of the training period. Primary rodent adult aortic smooth muscle cells (ASMCs) were analyzed for responsiveness to direct stimulation with S100A8/A9 alone or in combination with sRAGEs. At the end of the training period, we observed a statistically significant reduction in S100A8/A9 (630.98 vs. 472.12 ng/mL, p = 0.001), IL-1β (9.39 [3.8, 44.14] vs. 5.03 [2.44, 27.3] vs. pg/mL, p = 0.001), and sRAGEs (398.38 vs. 220.1 pg/mL, p = 0.001). IL-6 values did not change significantly after exercise. S100A8/A9 reduction was positively correlated with body weight (r = 0.236 [0.095, 0.370], p = 0.002) and BMI (r = 0.221 [0.092, 0.346], p = 0.004). Direct stimulation of ASMCs with S100A8/A9 increased the expression of IL-6, IL-1β, and TNF-α and, in the presence of sRAGEs, demonstrated a dose-dependent inhibition. A 4-week military training resulted in significant reduction in the pro-inflammatory cytokines IL-1β and S100A8/A9 complex. The observed reduction in sRAGEs may possibly reflect diminished RAGE axis activation. Altogether, our findings support the anti-inflammatory properties of physical activity.

OBJECTIVES: Performing percutaneous coronary intervention (PCI) for fractional flow reserve (FFR) positive coronary lesions improves clinical outcomes and is recommended by international guidelines. It has been hypothesized that lesions with a positive FFR but a preserved coronary flow reserve (CFR) are less likely to be flow limiting and might best be treated medically. We investigated the association of CFR in FFR-positive lesions with clinical outcomes when treated medically, as well as the treatment effect of PCI vs medical therapy in FFR-positive lesions and a preserved CFR.

METHODS: We performed a substudy of the randomized, multicenter Compare-Acute trial, in which stabilized ST-segment elevation myocardial infarction (STEMI) patients with non-culprit lesions were randomized to either FFR-guided PCI or medical therapy. Based on baseline and hyperemic pressure gradients, we computed physiologic limits of CFR, the so-called pressure-bounded CFR (pb-CFR), and classified lesions as low (<2) or preserved (≥2). The primary endpoint was 12-month major adverse cardiac and cerebrovascular event (MACCE) rate, defined as a composite of death from any cause, non-fatal myocardial infarction, revascularization, or cerebrovascular events.

RESULTS: A total of 980 lesions from 885 patients were included in this substudy. In lesions with FFR ≤0.80, a total of 249 patients had a pb-CFR <2 and 29 patients had a preserved CFR (pb-CFR ≥2). The rate of MACCE at 1 year was not significantly different between patients with FFR ≤0.80 and pb-CFR <2 vs patients with FFR ≤0.80 and pb-CFR ≥2 (25% vs 17%, respectively; P=.39). Because of randomization, baseline characteristics were well balanced between patients with FFR ≤0.80 and pb-CFR ≥2 treated by either by PCI or medical therapy. Importantly, in patients with FFR ≤0.80 and pb-CFR ≥2, MACCE occurred more frequently in patients treated medically vs patients treated by PCI (44% vs 0%, respectively; P=.01).

CONCLUSIONS: Preserved or low pb-CFR did not alter clinical outcomes in patients with a positive FFR. Patients with FFR-positive coronary lesions but a preserved CFR had more clinical events when treated medically vs those treated with PCI.

DJ-1 was originally identified as an oncogene product while mutations of the gene encoding DJ-1/PARK7 were later associated with a recessive form of Parkinson's disease. Its ubiquitous expression and diversity of function suggest that DJ-1 is also involved in mechanisms outside the central nervous system. In the last decade, the contribution of DJ-1 to the protection from ischemia-reperfusion injury has been recognized and its involvement in the pathophysiology of cardiovascular disease is attracting increasing attention. This review describes the current and gaps in our knowledge of DJ-1, focusing on its role in regulating cardiovascular function. In parallel, we present original data showing an association between increased DJ-1 expression and antiapoptotic and anti-inflammatory markers following cardiac and vascular surgical procedures. Future studies should address DJ-1's role as a plausible novel therapeutic target for cardiovascular disease.

OBJECTIVE: To investigate the potential association between sleep pathology and diabetes mellitus (DM) using self-reported questionnaires.

MATERIAL AND METHODS: 957 adults aged between 19 and 86 years old were enrolled in this cross-sectional study. Multistage stratified cluster sampling was used and subjects were classified into three groups [short (<6h), normal (6-8h) and long (>8h) sleep duration]. Individuals were classified as diabetics if they responded positively to the questions: "Have you ever been told that you are diabetic or have high blood sugar by a health professional?" or "Are you on antidiabetic medication?". Sleep quality, utilizing Epworth sleepiness scale, Athens insomnia scale, Pittsburgh sleep quality index and Berlin questionnaire, was also examined.

RESULTS: DM prevalence was higher among expatriated and Muslim Greeks (23.1% and 18.7%, respectively) compared to indigenous Greek Christians (4.4%). DM prevalence was significantly associated with short sleep duration (aOR=2.82, p<0.001), excessive daytime sleepiness (aOR=2.09, p=0.019) and poor sleep quality (aOR=2.56, p<0.001), while its relation with insomnia (aOR=1.63, p=0.065) and risk for obstructive sleep apnea (aOR=1.53, p=0.080) were of marginal statistical significance.

CONCLUSION: This study indicates an association between sleep quantity, quality and DM and supports early pharmacological and cognitive behavioral interventions on sleep disturbances in order to reduce the burden of DM with increased focus on minority population needs.

Introduction:Ambulatory blood pressure monitoring (ABPM) is a non-invasive method of obtaining brachial artery pressure assessment over 24 hours while patients undergo normal daily activities. Side effects, such as peripheral petechiae, limb edema, and sleep disturbance, are usually mild and reversible. Case report:A 67-year-old male presented with excruciating left hand pain and weakness on waking up from night sleep, having worn a cuff on his left arm for a whole day in the context of 24-hour ABPM. Clinical extremeexamination confirmed hypoesthesia in the left median and ulnar nerve distribution and weakness solely affecting ulnar and sparing median innervated hand muscles. Neurophysiological testing was performed. Interestingly, although median and ulnar motor responses were abnormal the respective sensory responses were unremarkable. Conclusion:To our knowledge, this is the first reported case of simultaneous proximal median and ulnar neuropathy complicating 24-hour ABPM. From a neurophysiological standpoint, it is also intriguing as this is a rare case of peripheral neuropathy with prominent motor fibre involvement, but normal sensory responses.

Accumulating evidence indicates that heat shock proteins (HSPs) may represent a suitable biomarker to predict atrial fibrillation (AF). We investigated the relation of circulating serum HSP70 (sHSP70) with inflammatory cytokines and recurrence of symptomatic recent onset AF (ROAF). We enrolled 90 patients with ROAF (the duration from onset of symptoms ≤24 hours) and 30 controls. Patients received amiodarone for cardioversion and rhythm control. The association of serum HSP70, serum interleukin-2 (sIL-2), and serum interleukin-4 (sIL-4) with the presence of cardioversion and AF recurrence within a year was investigated. Toll-like receptor 4 (TLR4) signaling dependence for IL-2 and IL-4 induction in response to stimulation with HSP70 was tested in rat aortic vascular smooth muscle cell cultures. Patients had higher sHSP70 and sIL-2 and lower sIL-4 compared with controls. Serum HSP70 was independently associated with ROAF (P = 0.005) and correlated with sIL-2 (r = 0.494, P < 0.001) and sIL-4 (r = -0.550, P < 0.001). By 48 hours, 71 of the 90 patients were cardioverted, with noncardioverted patients having higher sHSP70 and sIL-2 and lower sIL-4, which were the only independent factors associated with cardioversion. AF recurred in 38 of the 71 cardioverted patients in 1 year. A cutoff value of sHSP70 ≥0.65 ng/mL and sIL-2 ≥0.21 pg/mL was the only independent factor associated with AF recurrence (hazard ratio: 3.311, 95% confidence interval: 1.503-7.293, P = 0.003 and hazard ratio: 3.144, 95% confidence interval: 1.341-7.374, P = 0.008, respectively). The exposure of smooth muscle cell to HSP70 in vitro increased the expression of IL-2 (5×) and IL-4 (1.5×) through TLR4-dependent and receptor-independent mechanisms. In conclusion, sHSP70 and sIL-2 might constitute a prognostic tool for determining the cardioversion and recurrence likelihood in ROAF.

We determined whether plasma concentrations of the receptor for advanced glycation end products (RAGE) and the soluble (s) form of RAGE (sRAGE) in healthy individuals and patients with type 2 diabetes (T2D) modulate vascular remodeling. Healthy individuals and patients with T2D were divided into two age groups: young = <35 years old or middle-aged (36-64 years old) and stratified based on normal glucose tolerance (NGT), impaired (IGT), and T2D. Plasma titers of sRAGE, the RAGE ligands, AGEs, S100B, S100A1, S100A6, and the apoptotic marker Fas ligand Fas(L) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic potential of the above RAGE ligands and sRAGE were assessed in cultured adult rat aortic smooth muscle cells (ASMC). In NGT individuals, aging increased the circulating levels of AGEs and S100B and decreased sRAGE, S100A1 and S100A6. Middle-aged patients with T2D presented higher levels of circulating S100B, AGEs and FasL, but lower levels of sRAGE, S100A1 and S100A6 than individuals with NGT or IGT. Treatment of ASMC with either AGEs or S100B at concentrations detected in T2D patients increased markers of inflammation and apoptosis. Responses attenuated by concomitant administration of sRAGE. In middle-aged patients with T2D, lower circulating plasma levels of sRAGE may limit decoy and exogenous trapping of deleterious pro-apoptotic/pro-inflammatory RAGE ligands AGEs and S100B, increasing the risk for diabetic complications.

STUDY OBJECTIVES: Lifestyle changes decrease blood pressure (BP) levels by 3-5 mmHg in hypertensive patients. We assessed the effect of mid-day sleep on BP levels in hypertensive patients.

METHODS: We prospectively studied two hundred and twelve hypertensive patients. Mid-day sleep duration, lifestyle habits, anthropometric characteristics, office BP, ambulatory BP monitoring, pulse wave velocity (PWV), augmentation index (AI) were recorded. A standard echocardiographic evaluation was performed.

RESULTS: 53.8% were females, mean age was 62.5±11.0 years and mean body mass index was 28.9±5.4kg/m². Mean average 24h systolic and diastolic BP (SBP & DBP) was 129.9±13.2/76.7±7.9 mmHg respectively. The majority was non-smokers (70.3%) and did not have diabetes (74.7%). The mean midday sleep duration was 48.7±54.3 min. Average 24h SBP (127.6±12.9 mmHg vs 132.9±13.1 mmHg), average daytime SBP & DBP were lower in patients who sleep at midday, compared to those who do not (128.7±13/76.2±11.5 vs 134.5±13.4/79.5±10.4 mmHg) (p<0.005). The effect was not correlated to the dipping status. Midday sleep duration was negatively correlated with average 24h SBP & daytime SBP. In a linear regression model, for every 60 min of midday sleep, 24h average SBP decreases by 3 mmHg (p<0.001). There were no differences in the number of antihypertensive medications, PWV, AI or echocardiographic indices between study groups.

CONCLUSIONS: Mid-day sleep significantly decreases average 24h and daytime SBP/DBP in hypertensives. Its effect seems to be as potent as other well-established lifestyle changes and is independent of dipping status.

Stress induced (Takotsubo) cardiomyopathy (TC) represents an acute heart failure syndrome triggered by physical or emotional stressors. COVID-19 pandemic has caused an unprecedented health crisis resulting in fear, distress and anxiety, with emerging cardiovascular implications. COVID-19 related stress can act as potential trigger for TC. We present a case of an elderly female who developed TC due to stress surrounding COVID-19.

COVID-19 pandemic has caused a global public health emergency resulting in unprecedented individual and societal fear and anxiety. The stress surrounding this biothreat appears to have clinical implications in all aspects of medicine, both in mental and physical health spheres. The impact of COVID-19 related anxiety in Cardiology, Paediatrics, Oncology, Dermatology, Neurology and Mental Health and how it affects treatments is discussed. Moreover, the need for introducing novel communication and therapeutic approaches is highlighted in the new landscape of the COVID-19 era.

In light of the unprecedented public health crisis of the COVID-19 pandemic, it is highly important to acknowledge the psychological impact of this mounting threat on healthcare professionals. Previous experience from smaller scale epidemics and emerging literature around COVID-19 show that the unparalleled amount of stress that healthcare workers are dealing with, is associated with increased psychological morbidities. We have depicted the psychological burden that the COVID-19 pandemic has posed on healthcare professionals in Greece and have reviewed the literature around the effect of previous epidemics on frontline healthcare staff. Moreover, we discuss potential triggers and the need for measures to minimise the psychological pressure on those at the frontline against this biothreat.

Systemic lupus erythematosus (SLE) is a heterogeneous disease with a broad spectrum of clinical manifestations. Periaortitis is a rare disorder which may manifest isolated or in association with other autoimmune diseases, including SLE. Another rare, yet severe cardiovascular manifestation of lupus is diffuse subendocardial vasculitis (DSV), which should be suspected in patients presenting with myocardial hypokinesis, impaired ejection fraction and normal coronary angiography. Cardiovascular Magnetic Resonance (CMR) imaging is crucial to distinguish between DSV and lupus myocarditis, which should also be included in the differential diagnosis. Herein, we describe a case of a female patient with pre-existing SLE, who presented with both periaortitis and DSV, and discuss the diagnostic challenges associated with these rare manifestations.