The cardiovascular consequences of electronic cigarette smoking: a narrative review.

INTRODUCTION: E-cigarettes have emerged as a popular alternative to traditional tobacco smoking in recent years. Despite their growing popularity, concerns have arisen regarding the cardiovascular implications of e-cigarette use. AREAS COVERED: This narrative review aims to highlight the latest evidence on the impact of e-cigarettes on cardiovascular health. EXPERT OPINION: Numerous studies have demonstrated that e-cigarette use can lead to acute adverse cardiovascular effects. Inhalation of e-cigarette aerosols exposes users to a wide range of potentially harmful substances that have been implicated in critical pathophysiologic pathways of cardiovascular disease, namely endothelial dysfunction, oxidative stress, inflammation, sympathetic overdrive, and arterial stiffness. While long-term epidemiological studies specifically focusing on the cardiovascular effects of e-cigarettes are still relatively scarce, early evidence suggests a potential association between e-cigarette use and an increased risk of adverse cardiovascular events. However, it is essential to recognize that e-cigarettes are relatively new products, and the full extent of their long-term cardiovascular impact has not been fully elucidated. In the meantime, promoting tobacco cessation strategies that are evidence-based and regulated, along with rigorous monitoring of e-cigarette use patterns and associated health outcomes, are essential steps in safeguarding cardiovascular health in the face of this emerging public health challenge.

High-Intensity Endurance and Strength Training in Water Polo Olympic Team Players: Impact on Arterial Wall Properties.

INTRODUCTION: Regular physical activity is recommended to minimize health risk. However, the upper intensity threshold associated with the best health outcomes is difficult to be determined. Water polo (WP) Olympic athletes present unique characteristics such as high-intensity exercise, long training sessions, and a combination of endurance and strength training. Therefore, we examined in which way the long-term, intense, mixed endurance and strength training affects the peripheral and central hemodynamics. METHODS: The study population consisted of 20 WP Olympic team players, 20 matched recreationally active (RA) subjects, and 20 sedentary control subjects (Cl). Reflected waves were assessed with the augmentation index (AIx), central aortic stiffness with pulse wave velocity (PWV), and endothelial function with flow-mediated dilation (FMD). RESULTS: Amongst Cl subjects, RA subjects, and WP players, there was no difference in age (p = 0.33) as well as in brachial systolic pressure (p = 0.52), while there was a stepwise decrease in aortic systolic pressure (116 ± 16 mm Hg vs. 107 ± 14 mm Hg vs. 106 ± 6 mm Hg, p = 0.03). There was also a stepwise improvement in AIx (-4.22 ± 9.97% vs. -6.97 ± 11.28% vs. -12.14 ± 6.62%, p = 0.03) and FMD (6.61 ± 1.78% vs. 7.78 ± 1.98% vs. 8.3 ± 2.05%, p = 0.04) according to the intensity of exercise, with WP players having lower AIx and higher FMD compared to RA subjects and Cl subjects. No difference was found in PWV (Cl: 5.88 ± 0.72 m/s vs. RA: 6.04 ± 0.75 m/s vs. WP: 5.97 ± 1.09 m/s, p = 0.82) among the three studied groups. CONCLUSIONS: Young WP Olympic team players depict improved arterial wall properties and endothelial function compared to RA and Cl subjects.

Incidence and cost of bleeding events requiring hospitalization in patients with atrial fibrillation treated with acenocoumarol in Greece.

BACKGROUND: To estimate the incidence of hemorrhagic events in patients with atrial fibrillation (AF) treated with acenocoumarol, and the management cost of those requiring hospitalization in Greece. METHODS: A nationwide telephone survey was conducted between December 2017 and January 2018, to identify cardiologists who treat AF patients with acenocoumarol. A total of 300 cardiologists were selected and reported the number of AF acenocoumarol-treated patients during the past 12 months and the number of those who experienced a hemorrhagic event. The hospital charges to sickness fund and the cost of resource utilization of AF patients hospitalized between January 2013 and June 2017 at a tertiary hospital in Athens due to acenocoumarol-related bleedings were retrieved. RESULTS: Out of 48,255 AF patients, 12,633 (26.2%) were treated with acenocoumarol. In all, 5.1% of patients experienced a hemorrhagic event with the incidence of bleeding requiring hospitalization being 1.7%. The most common bleeding site was the gastrointestinal system (51.5%). The mean (95% CI) management cost per bleeding event requiring hospitalization was €1,202 (€1,058-€1,420). The higher cost was that of intracranial bleeding €3,887 (€2,700-€5,046). The expected annual economic burden for the management of bleedings related to acenocoumarol and requiring hospitalization was estimated at €1,463,955. CONCLUSIONS: The incidence of bleeding events in AF acenocoumarol-treated patients in Greece as well as the estimated annual economic burden for the management of bleeding events requiring hospitalization, emphasize the need to comply with the current guidelines and to optimize therapeutic strategies for the management of AF side effects with oral anticoagulants, particularly in patients with high bleeding risk.

The influence of resting heart rate on pulse wave velocity measurement is mediated by blood pressure and depends on aortic stiffness levels: insights from the Corinthia study.

OBJECTIVE: Increased resting heart rate as well as increased arterial stiffness are both independent predictors of cardiovascular events and mortality. Results of previous studies have failed to converge concerning the association between heart rate and arterial stiffness, regardless of other potential confounders, such as age, gender and particularly blood pressure (BP). We aimed to investigate: (a) the degree of association (if any) between resting heart rate and carotid-to-femoral pulse wave velocity (PWV), the gold standard index of arterial stiffness, (b) if the relationship between heart rate and PWV is mediated by BP levels and (c) whether their association is affected by the levels of aortic stiffening. APPROACH: Demographic, hemodynamic, laboratory and clinical data of 1566 subjects from the cross-sectional observational 'Corinthia' study were analyzed using univariate and multivariate regression models. Mediation analysis was performed to test whether mean arterial pressure (MAP) is a significant mediator in the heart rate-PWV relationship. The total population was divided in two groups of low and high arterial stiffness according to the median PWV value (8.6 m s-1). MAIN RESULTS: We found that (i) there is a significant association between heart rate and PWV, regardless of other confounding factors. An increase in heart rate by 20 b.p.m. can increase PWV by 0.5 m s-1. However, this association was significant only for subjects with increased aortic stiffness (PWV > 8.6 m s-1) and not for those with PWV ⩽ 8.6 m s-1. Further, (ii) heart rate-PWV association was partially mediated by MAP. SIGNIFICANCE: Increased resting heart rate is related to increased aortic stiffness, only in subjects with stiffer aortas, regardless of BP and other risk factors and subjects' characteristics. The synergistic prognostic effect of increased arterial stiffness and elevated heart rate on target organ damage, cardiovascular events and mortality should be explored in future studies.

Arterial stiffness and subclinical aortic damage of reclassified subjects as stage 1 hypertension according to the new 2017 ACC/AHA blood pressure guidelines.

Background: The 2017 ACC/AHA blood pressure (BP) guidelines generated controversies due to the new proposed BP cut-off values defining hypertension. We aimed to assess aortic stiffness of subjects who are reclassified as stage 1 hypertensive according to the new guidelines and compare them with the subjects of "elevated BP" category. Patients and methods. Data from the "Corinthia" study, an observational, cross-sectional survey of 2,043 participants were analyzed. Subjects were classified into 4 groups: group A: systolic pressure (SBP) 120-129 and diastolic pressure (DBP) < 80 mmHg, group B: SBP 130-139 or DBP 80-89 mmHg, group B1: SBP 130-139 and DBP < 80 mmHg and group B2: SBP 130-139 and DBP 80-89 mmHg. Aortic stiffness was assessed by carotid-to-femoral pulse wave velocity (PWV). A value of PWV > 10m/s was consider indicative of asymptomatic organ damage while values of PWV exceeded the 90 % percentile for each age group were consider as abnormal. Results: Groups B, B1 and B2 have significantly increased PWV compared to group A, independently from age and other risk factors (PWV: 9.2 ± 2.8 vs 9.4 ± 2.7 vs 8.6 ± 2.5 vs 8.1 ± 2.3 m/s, p < 0.01, respectively). The prevalence of PWV > 10 m/s and abnormal PWV values in group A was significantly lower than the corresponding prevalence in randomly selected, age-matched subjects from group B (13.5 % vs 24.4 %, p = 0.027 and 5.6 % vs 14.2 %, p = 0.022, respectively). Conclusions: The reclassified subjects as stage 1 hypertensive by the new guidelines have a significantly increased aortic stiffness and greater prevalence in asymptomatic aortic damage compared to subjects with elevated BP. This finding may indirectly explain the increased cardiovascular risk of this group.

Redox State in Atrial Fibrillation Pathogenesis and Relevant Therapeutic Approaches.

BACKGROUND: Myocardial redox state is a critical determinant of atrial biology, regulating cardiomyocyte apoptosis, ion channel function, and cardiac hypertrophy/fibrosis and function. Nevertheless, it remains unclear whether the targeting of atrial redox state is a rational therapeutic strategy for atrial fibrillation prevention. OBJECTIVE: To review the role of atrial redox state and anti-oxidant therapies in atrial fibrillation. METHOD: Published literature in Medline was searched for experimental and clinical evidence linking myocardial redox state with atrial fibrillation pathogenesis as well as studies looking into the role of redoxtargeting therapies in the prevention of atrial fibrillation. RESULTS: Data from animal models have shown that altered myocardial nitroso-redox balance and NADPH oxidases activity are causally involved in the pathogenesis of atrial fibrillation. Similarly experimental animal data supports that increased reactive oxygen / nitrogen species formation in the atrial tissue is associated with altered electrophysiological properties of atrial myocytes and electrical remodeling, favoring atrial fibrillation development. In humans, randomized clinical studies using redox-related therapeutic approaches (e.g. statins or antioxidant agents) have not documented any benefits in the prevention of atrial fibrillation development (mainly post-operative atrial fibrillation risk). CONCLUSION: Despite strong experimental and translational data supporting the role of atrial redox state in atrial fibrillation pathogenesis, such mechanistic evidence has not been translated to clinical benefits in atrial fibrillation risk in randomized clinical studies using redox-related therapies.

The association among biomarkers of renal and heart function in patients with heart failure: the role of NGAL.

AIM: The NGAL is a biomarker of renal injury associated with the progression of heart failure (HF). We examine the association of NGAL with galectin-3 in patients with chronic HF. METHODS: We consecutively enrolled 115 subjects with stable ischemic HF of reduced ejection fraction. Serum levels of galectin-3, b-type natriuretic peptide and NGAL were measured. RESULTS: NGAL levels were positively correlated with galectin-3 (rho = 0.26; p = 0.04) and b-type natriuretic peptide levels (rho = 0.30; p = 0.005) and inversely correlated with ejection fraction (rho = -0.31; p = 0.02) and creatinine clearance levels. The NGAL was independently associated with galectin-3 levels. CONCLUSION: A positive correlation between NGAL and galectin-3 in HF patients was found, revealing a potential association between renal injury and myocardial fibrosis and remodeling in HF.

Coronary Microcirculation and the No-reflow Phenomenon.

The no-reflow phenomenon refers to the post-percutaneous coronary intervention condition in which, despite re-establishing epicardial coronary vessel patency, the flow to the previously ischemic myocardium is markedly reduced. When it does occur, it attenuates the beneficial effect of reperfusion therapy and substantial regions of the myocardium fail to receive adequate perfusion. The pathophysiology of this phenomenon is not completely understood. The possible mechanisms could be related to alterations in the microvascular circulation. Various mechanisms such as activation of inflammatory pathways, vascular damage and hemorrhage, leukocyte infiltration, and cellular edema may be responsible. As the no-reflow phenomenon is associated with adverse clinical consequences, it is of great importance to identify exact responsible mechanisms and apply effective preventive and therapeutic strategies. In this review, we describe an updated overview of the pathophysiological mechanisms and the current preventive tools for no-reflow as well as therapeutic interventions in order to improve coronary blood flow and consequently the prognosis for these patients.

Non-natriuretic peptide biomarkers in heart failure with preserved and reduced ejection fraction.

Heart failure (HF) with reduced and preserved ejection fraction constitutes two entities with distinct pathogenetic backgrounds sharing common features. Beyond natriuretic peptides, several novel biomarkers have been proven useful in the diagnosis, prognosis and treatment of HF. Biomarkers of myocardial fibrosis have a low diagnostic yield in subjects with acute HF but may add prognostic information, especially in patients with HF and preserved ejection fraction. Biomarkers of renal impairment identify subjects with worse prognosis independently of left ventricle ejection fraction while inflammatory markers have not been proven useful in patients with systolic or diastolic impairment. In this review article, we summarize the main differences and application of non-natriuretic peptide biomarkers in HF patients with preserved and reduced ejection fraction.

Statins and inflammation in cardiovascular disease.

BACKGROUND: Chronic inflammation and immune system activation underlie a variety of seemingly unrelated cardiac conditions including not only atherosclerosis and the subsequent coronary artery disease but also peripheral artery disease, hypertension with target organ damage and heart failure. The beneficial effects of HMG-CoA reductase inhibitors or statins are mainly attributed to their ability to inhibit hepatic cholesterol biosynthesis. Beyond their lipid lowering activity, ample evidence exists in support of their potent anti-inflammatory properties which initiate from the inhibition of GTPase isoprenylation, activating a cataract of secondary pathways and extend to the inhibition and blocking of immune cell activation and interaction. OBJECTIVE: To summarize the anti-inflammatory mechanisms of statins in clinical and experimental settings in cardiovascular disease. METHODS: A systematic search of PubMed and the Cochrane Database was conducted in order to identify the majority of trials, studies, current guidelines and novel articles related to the subject. RESULTS: In vitro, statins have immuno-modulatory and anti-inflammatory effects, and they can exert anti-atherosclerotic effects independently of their hypolipidemic actions. In addition, positive results have emerged from mechanistic and experimental studies on the active role of HMG-CoA reductase inhibitors in HF. By extrapolating those data in clinical setting, we further understand how HMG-CoA reductase inhibitors can beneficially affect not only systolic but also diastolic HF. CONCLUSION: In this review article, we present the basic pathophysiologic data supporting the anti-inflammatory actions of statins in clinical and experimental settings and we link these mechanisms with confirmatory clinical data on the potent non lipid lowering effects of HMG-CoA reductase inhibitors.

Statins and left ventricular function.

BACKGROUND: Statins are a well-established class of drugs in both preventing coronary events and treating cardiovascular atherosclerotic disease, however their use in heart failure is still in debate. OBJECTIVES: To establish whether statins' pleiotropic actions in endothelium, inflammation, remodeling of the heart and anti-arrhythmic potential may be in favorable of heart failure patients. METHODS: We proceed to literature search of English bibliography under the terms heart failure, statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. RESULTS: Various experimental and clinical trials on the use of statins in the different subtypes of heart failure according to the ejection fraction of the left ventricle have been conducted to conclude whether statins should be part of their patients' treatment. The evidence shows that the subgroup of patients with ischemic heart disease and those with preserved ejection fraction seems to have better results from the use of statins although randomized control trial in the total heart failure population did not show any benefit in mortality, Conclusion: Statins may be beneficial act to left ventricle systolic and diastolic performance of heart failure patients however their result in mortality cannot be established based on current evidence.

Genotyping, Platelet Activation, and Cardiovascular Outcome in Patients after Percutaneous Coronary Intervention: Two Pieces of the Puzzle of Clopidogrel Resistance.

OBJECTIVES: Individual platelet responses to antiplatelet therapy depend on genetic, cellular, and clinical factors. CYP2C19 and P2Y12 receptor polymorphisms are implicated in platelet responses to antiplatelet treatment. We aimed to evaluate the impact of CYP2C19 and C34T P2Y12 genotyping on platelet reactivity and cardiovascular outcome in patients after percutaneous coronary intervention (PCI) on clopidogrel treatment. METHODS: We enrolled 408 patients with stable coronary artery disease (CAD) receiving aspirin and clopidogrel (75 mg/day) 1 month after PCI. High on-treatment platelet reactivity was evaluated using the VerifyNow Assay in a subset of patients. CYP2C19*2 and C34T P2Y12 genotyping was performed by real-time polymerase chain reaction. The primary end point was the composite of death or hospitalization for cardiovascular causes, and patients were followed for a median time of 13 months. RESULTS: In the total study population, 37% were carriers of at least 1 CYP2C19*2 loss-of-function allele, and 53% were carriers of at least 1 C34T loss-of-function allele. Interestingly, homozygotes of the CYP2C19*2 loss-of-function allele had significantly increased P2Y12 reaction units (PRU) (p = 0.007). However, PRU did not differ between carriers and noncarriers of the C34T loss-of-function allele (p = 0.41). Moreover, carriers of CYP2C19*2 had an increased hazard ratio (HR) for the occurrence of the primary end point (for carriers HR = 1.96, 95% CI 1.05-3.66, p = 0.03), whereas the C34T polymorphism had no impact on the cardiovascular outcome (p = 0.17). Finally, PRU was associated with cardiovascular outcome even after adjustment for the presence of any reduced function allele polymorphism. CONCLUSIONS: We documented a different effect of CYP2C19 and P2Y12 receptor polymorphisms on platelet reactivity and cardiovascular outcome in CAD patients after PCI on clopidogrel treatment. Importantly, increased platelet reactivity adversely affects the cardiovascular outcome independently of the studied polymorphisms.

Usefulness of C-Reactive Protein as a Predictor of Contrast-Induced Nephropathy After Percutaneous Coronary Interventions in Patients With Acute Myocardial Infarction and Presentation of a New Risk Score (Athens CIN Score).

Contrast-induced nephropathy (CIN) after percutaneous coronary interventions (PCI) in patients with acute myocardial infarction (AMI) is associated with high morbidity and mortality, whereas there are no reliable predictive tools easy to use. We evaluated the association of pre-procedural high-sensitivity C-reactive protein (hsCRP) with the development of CIN and integrated this variable in a new risk CIN prediction model. Consecutive patients (348 AMI subjects) who underwent PCI were recruited. Creatinine levels were detected on admission, at 24, 48, and 72 hours after PCI. CIN was defined using the Kidney Disease: Improving Global Outcomes criteria. In our study population (348 subjects), CIN developed in 54 patients (15.5%). Patients with CIN were older and had higher hsCRP at admission, whereas their ejection fraction (EF) and glomerular filtration rate (GFR) were lower. In multivariate analysis after incorporating potential confounders, hsCRP at admission was an independent predictor of CIN (OR for logCRP 2.00, p = 0.01). In receiver-operating characteristic curve analysis, a model incorporating hsCRP, age, GFR, and EF showed good accuracy in predicting the development of CIN (c statistic 0.84, 95% confidence interval 0.793 to 0.879). A total risk score derived from the proposed model yielded significant positive and negative predictive values and classified 85.8% of our patients correctly for CIN. In conclusion, measuring hsCRP levels at admission in patients who underwent PCI for AMI may offer additional assistance in predicting the development of CIN. A model incorporating age and admission hsCRP, EF, and GFR emerged as an accurate tool for predicting CIN in this context.

Effects of CYP2C19 Polymorphism on Endothelial Function, Arterial Stiffness and Inflammation in Coronary Artery Disease Patients Under Clopidogrel Treatment.

BACKGROUND: Clopidogrel's ability to inhibit platelet function determined its clinical usefulness. The role of CYP2C19*2 genotype on antiplatelet treatment is recently under question. Arterial wall properties and inflammation are key players in atherosclerosis development. Hence, we evaluated the impact of CYP2C19*2 genetic polymorphism on endothelial function, arterial stiffness and inflammation in coronary artery disease (CAD) patients receiving clopidogrel treatment. METHODS AND RESULTS: In this study we enrolled 408 consecutive patients with stable CAD under dual antiplatelet therapy (clopidogrel 75mg/day, aspirin 100mg/day), 30 days after percutaneous coronary intervention. Measurement of flow-mediated dilation (FMD) of the brachial artery was used to evaluate endothelial function. Carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) was measured to estimate arterial stiffness. Real time polymerase chain reaction was used for the genotyping of CYP2C19*2. Levels of tumor necrosis factor alpha (TNF-a) and interleukin 6 (IL-6) were measured with ELISA. We found no difference in basic clinical and demographic characteristics nor in FMD, PWV, AIx and inflammatory status (p=NS for all) between CYP2C19 homozygotes for the wild type; carriers of reduced function allele and homozygotes for the reduced function allele. CONCLUSION: CYP2C19*2 loss of action polymorphism causes no impact on vascular function and inflammatory status in stable CAD patients receiving clopidogrel treatment.

The role of microRNAs in coronary artery disease: From pathophysiology to diagnosis and treatment.

MicroRNAs (miRNAs) are tiny non-coding RNA molecules that regulate gene expression predominantly at the post-transcriptional level. Far from being simple intracellular regulators, miRNAs have recently been involved in intercellular communication and have been shown to circulate in the bloodstream in stable forms. In the past years specific miRNA expression patterns have been linked to the development of atherosclerosis and coronary artery disease, two closely related conditions. The study of miRNAs has promoted our understanding of the processes involved in the pathogenesis of atherosclerosis and innovative diagnostic and therapeutic approaches have emerged. In this review, we present the role of miRNAs in the development of atherosclerosis, on coronary artery disease progression and we assess their role as diagnostic biomarkers. Finally we evaluate the therapeutic and preventive opportunities that arise from the study of miRNAs in coronary artery disease and especially in myocardial infarction.

Vascular function and ocular involvement in sarcoidosis.

Ocular involvement occurs in sarcoidosis (Sar) patients mainly in the form of uveitis. This study was designed to determine if uveitis in Sar patients is associated with vascular impairment. We enrolled 82 Sar patients and 77, age and sex matched, control subjects (Cl). Sar patients were divided into those with ocular sarcoidosis (OS) and those without ocular sarcoidosis (WOS). Endothelial function was evaluated by flow-mediated dilation (FMD). Pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as a measure of arterial wave reflections. Although there was no significant difference in sex, age and mean arterial pressure, patients with OS compared to WOS patients and Cl subjects had impaired FMD (p<0.001), increased AIx (p=0.02) and increased PWV (p=0.001). Interestingly, impaired FMD in Sar patients was independently, from possible covariates (age, sex, smoking habits, arterial hypertension, dyslipidemia), associated with increased odds of ocular involvement (odds ratio=1.69, p=0.001). More precisely ROC curve analysis revealed that FMD had a significant diagnostic ability for the detection of OS (AUC=0.77, p<0.001) with a sensitivity of 79% and a specificity of 68% for an FMD value below 6.00%. To conclude in the present study we have shown that ocular involvement in Sar patients is associated with impaired endothelial function and increased arterial stiffness. These results strengthen the vascular theory which considers uveitis a consequence of vascular dysfunction in Sar patients and reveals a possible clinical importance of the use of endothelial function tests.

Circulating Biomarkers Determining Inflammation in Atherosclerosis Progression.

Atherosclerosis is the main underlying pathology of cardiovascular disease and is precipitated by various hereditary and non-hereditary risk factors. Inflammation is considered an important step in the progression of atherosclerosis and involves numerous cells, mediators and cellular procedures. Therefore, a biomarker able to determine the vascular inflammatory status is imperative as the combination of inflammatory biomarkers with the classic risk factors might provide further information about atherosclerosis progression and cardiovascular risk. The identification of novel inflammatory molecules and the improvement in analytical methods allows the potential implementation of these tests in every day clinical practice. In the current article, we focus on the role of established and novel biomarkers in atherosclerosis progression and in the determination of cardiovascular risk. We also present recent data concerning the risk stratification of patients according to their inflammatory status and the possible anti-inflammatory treatment strategies.