Current Vascular Pharmacology - Volume 16, Issue 6, 2018

Introduction: Cardiac arrhythmias are challenging diseases in childhood. Most of them in pediatric subjects (90.2%) are atrioventricular reentrant tachycardias and atrioventricular nodal reentrant tachycardias. The standard 12-lead ECG is a highly accurate diagnostic tool but an invasive electrophysiological study is often required. The main concern about this kind of procedures is their invasive nature and the need of radiations, so antiarrhythmic agents are currently the first line therapy. However, they often show side effects and can be insufficient for the rate control. Materials and Methods: We performed a systematic research on Embase and PubMed. We found 563 articles and selected the most representative 50. Discussion: Management of cardiac arrhythmias could be very difficult in several scenarios, especially in children with body weight <15 kg and age <4 years. In general, pediatric subjects show a cumulative risk of malignancy greater than adults, having greater life expectancy. On this basis the guiding principle during radiation delivery in electrophysiological procedures is “as low as reasonably achievable” (acronym: ALARA). The development of 3-dimensional (3D) electroanatomical mapping systems allowed significant reduction of exposure. The most recently reported experiences demonstrate safety and feasibility of fluoroless ablation in the most common arrhythmias in children, even in challenging conditions. Conclusion: The first reasonable approach in cardiac arrhythmias involving younger patients seems to be pharmacological. However antiarrhythmic drugs pose problems both in terms of side effects and often have poor efficacy. Expertise in electrophysiological techniques is constantly increasing and the development of new technologies allow us to encourage the use of electroanatomical mapping systems in order to reduce the radiation exposure in children undergoing to catheter ablation, especially for accessory pathways.

Background: Ischaemic stroke is often complicated with haemorrhage within the infarct zone or in a remote location especially when treated with intravenous thrombolysis and/or thrombectomy. While these early recanalisation treatments are highly effective, some of the benefit is lost because of haemorrhagic complications and consequential neurological deterioration of the patients. A number of mechanisms have been described that mediate the haemorrhagic changes and several agents have been tested in experimental models for inhibiting post-stroke haemorrhage. Methods: Here, we review and discuss the small animal models of focal cerebral ischaemia and postischaemic stroke haemorrhagic transformation and how these models can best be utilised for developing further insights as well as potential treatment approaches for this serious clinical complication. Results: The need to use appropriate animal models with relevant stroke risk factors to improve the clinical relevance and applicability of findings is becoming ever more apparent. Current focal ischaemia models can be adapted for the study of haemorrhagic transformation post-stroke. Conclusion: A number of factors can be added to the animal model design to increase the incidence and/or severity of haemorrhagic transformation post-ischaemic stroke, which can improve clinical relevance, aid the study of the pathophysiology and the future development of novel interventions.

Peripheral Artery Disease (PAD), a common vascular disease, has been associated with increased Cardiovascular (CV) morbidity and mortality as well as all-cause death. Type 2 Diabetes Mellitus (T2DM) predisposes to PAD development. In T2DM patients, PAD further increases the risk for CV disease and death as well as foot morbidity and microvascular complications. The present narrative review discusses the role of oxidative stress and inflammation in the pathophysiology of PAD with or without the presence of T2DM. The effects of lifestyle measures (i.e. diet, physical activity and smoking cessation) and drug treatment on markers of oxidative stress and inflammation are also considered. Further research should establish the clinical implications of such effects as well as the clinical use of antioxidants and anti-inflammatory drugs in PAD.

Pulmonary Hypertension (PH) related to Left Heart Disease (LHD) is the most common form of PH, accounting for more than two third of all PH cases. The hemodynamic abnormalities seen in PHLHD are complex, and there are currently minimal evidence-based recommendations for the management of PH-LHD. While it is accepted that PH in the context of left heart disease is a marker of worse prognosis, it remains unclear whether its primary treatment is beneficial or harmful. In this article, we discuss the prevalence and significance of PH in patients with Heart Failure (HF) with Reduced Ejection Fraction (HFrEF) as well as HF with Preserved Ejection Fraction (HFpEF), and those with valvular heart disease and provide insights into the complex pathophysiology of cardiopulmonary interrelationship in individuals with PH due to left heart disease. Furthermore, we provide a framework for diagnostic testing and an approach to optimal management of these complex patients based on current European Society of Cardiology (ESC) guidelines.

Background: Volatile Anaesthetics (VA) are commonly used worldwide for induction and/or maintenance of general anaesthesia. They act in the central nervous system to reduce sensation and motor response during surgical and invasive diagnostic procedures. VAs also have some non-anaesthetic properties in the brain when administrated to patients at the extremes of age. Their biological impact on other organs should be taken into account during administration of anaesthesia. Objective: In this review we summarize the recent knowledge on the non-anaesthetic effects of inhaled halogenic ethers on cells and tissues. Results and Conclusion: Exposure to VAs may promote lasting neuro-behavioural deficits in the brains of developing children and deterioration in cognitive performance in elderly individuals. Preconditioning with VAs can prevent or minimise tissue ischaemia in the heart and brain. VAs act as an antiinflammatory in response to tissue damage during surgery and may attenuate both local and systemic inflammatory response. Further research is needed to elucidate a link between laboratory findings and their possible effects in humans. Because many questions remain unanswered in this field, translational medicine should be more focused on safety in anaesthesia for the improvement public health.

Background: Atherosclerosis is a multifactorial inflammatory disease of the cardiovascular system. It has been suggested that periodontitis, an infectious disease of oral cavity caused by gramnegative anaerobic bacteria, could be linked to atherosclerosis. Objective: The objective of this systematic review was to assess the evidence between the association of periodontitis and atherosclerosis in adults. Methods: A systematic literature search was conducted in 7 databases up to January 2017, according to the Preferential Reports for Systematic Review and Meta-analysis (PRISMA) guidelines. Studies in humans with atherosclerosis were considered eligible when considering a group exposed to periodontitis and a control group (absence of periodontitis), in which the primary outcome was the association between the 2 diseases (atherosclerosis and periodontitis). The synthesis of the qualitative studies included was evaluated using previously validated checklist for assessing the risk of bias. Results: Among the 2138 studies found, 4 observational studies met the eligibility criteria and were included in the qualitative synthesis. All articles were considered adequate, presenting consistent and valid information. The results of the selected studies show the expected effects, being considered as low risk of bias. Conclusion: The available evidence indicates an association between the 2 diseases, with elevated levels of inflammatory markers, mainly C-reactive protein and interleukin 6.

Background: Xanthine oxidase inhibitors are commonly used to lower uric acid levels in patients with gout. Due to their effects on endothelial function, they have also been investigated for possible benefits for patients with cardiovascular disease. Objective: To assess the efficacy and safety of xanthine oxidase inhibitors in the treatment of patients with history of stroke. Methods: MEDLINE (1946-June 2017) and EMBASE (1947-June 2017) were queried using the search terms: “allopurinol” OR “febuxostat” OR “xanthine oxidase inhibitor” OR “xanthine oxidase/ antagonists and inhibitors” AND “stroke” OR “cerebral infarction” OR “cerebrovascular accident”. Studies appropriate to the objective were evaluated, including five randomized, placebo-controlled, double-blind trials investigating the effect of allopurinol in patients with history of stroke. No articles evaluating the use of febuxostat in this setting were identified. Results: In patients with history of stroke, treatment with allopurinol resulted in improvements in several markers of endothelial function, inflammatory markers, and scores on the Modified Rankin Scale. Study durations ranged from 6 weeks to 1 year, and studies used varying doses of allopurinol. Allopurinol was well tolerated in most studies, with some reports of gastrointestinal adverse effects, headache and rash. Conclusion: Based on the reviewed literature, allopurinol appears to be a promising therapy to improve vascular function and reduce disability in patients who have had a stroke. The benefits seen are in combination with current standard of care treatments with aspirin and lipid-lowering therapy. Larger trials are necessary to better understand the role of allopurinol in patients with history of stroke.

Objective: To investigate the characteristics of body fat distribution and the relationship between body fat index and Atherogenic Index of Plasma (AIP) in Type 2 Diabetes Mellitus (T2DM) patients. Methods: A total of 316 participants were divided into a T2DM group and a non-diabetes group (controls). According to the Visceral Fat Area (VFA), all participants were further divided into VFA ≥100 cm2 and VFA <100 cm2 groups. To compare the differences of blood lipid, blood glucose, body fat index and AIP between the 2 groups, single factor correlation analysis was used to determine the correlation between the indexes and AIP, and multiple linear regression was used to analyse the correlation between the related factors and AIP. Results: The body fat index (including body fat content, Percentage of Body Fat (PBF), Waist to Hip Fat Ratio (WHR) and VFA), Triglyceride (TG), Fasting Insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and AIP in T2DM group were significantly higher than in the control group, while High Density Lipoprotein Cholesterol (HDL-C) level was significantly higher in the control group. In the VFA ≥ 100 cm2 group, TG, Low Density Lipoprotein Cholesterol (LDL-C), FINS, HOMAIR and AIP were all higher than that in the VFA <100 cm2 group. There was a positive correlation between AIP and VFA, body fat content, percentage of body fat, and WHR, respectively. There was also a negative correlation between AIP and HDL-C, which was not related to age, sex, Fasting Glucose (FPG), glycosylated haemoglobin (HbA1c), Total Cholesterol (TC), LDL-C and course of disease. Compared with the VFA <100 cm2 group, the VFA ≥100 cm2 group had higher blood Uric Acid (UA) levels and UA was positively correlated with VFA. After correcting the effect of UA on AIP, VFA was still an independent related factor of AIP, and VFA increased the risk of atherosclerosis by increased UA. Conclusion: T2DM patients have the abnormal distribution of body fat and a high VFA, which was associated with AIP.

Aims: To evaluate the impact of Angiotensin-Converting Enzyme Inhibitors (ACEIs)/ Angiotensin Receptors Blockers (ARBs) on in-hospital, 3- and 12-month all-cause mortality in Acute Heart Failure (AHF) patients with left ventricular systolic dysfunction in 7 countries of the Middle East. Methods and Results: Data was analysed from 2,683 consecutive patients admitted with AHF and Left Ventricular Ejection Fraction (LVEF) (<40%) from 47 hospitals from February to November 2012. Analyses were evaluated using univariate and multivariate statistics. The overall mean age of the cohort was 58±15, 72% (n=1,937) were males, 62% (n=1,651) had coronary artery disease, 57% (n=1,539) were hypertensives and 47% (n=1,268) had diabetes. Overall cumulative mortality at inhospital, 3- and 12-month follow-up was 5.8% (n=155), 12.6% (n=338) and 20.4% (n=548), respectively. Adjusting for demographic and clinical characteristics as well as medication in a multivariate logistic regression model, ACEIs were associated with lower risk of in-hospital mortality (adjusted odds ratio (aOR), 0.48; 95% Confidence Interval (CI): 0.25 to 0.94; p=0.031). At 3-month follow-up, both ACEIs (aOR, 0.64; 95% CI: 0.43 to 0.95; p=0.025) and ARBs (aOR, 0.34; 95% CI: 0.18 to 0.62; p<0.001) were associated with lower risk of mortality. Additionally, at 12-month follow-up, those prescribed ACEIs (aOR, 0.71; 95% CI: 0.53 to 0.96; p=0.027) and ARBs (aOR, 0.47; 95% CI: 0.31 to 0.71; p<0.001) were still associated with lower risk of mortality. Conclusion: ACEIs and ARBs treatments were associated with lower mortality risk during admission and up to 12-month of follow-up in Middle East AHF patients with left ventricular systolic dysfunction.

Background: Bone Gamma-carboxyglutamic acid (Gla)-protein (BGP or osteocalcin) is a vitamin K-dependent protein involved in the regulation of bone mineralization. Smoking is a risk factor for osteoporosis. Methods: We carried out a secondary analysis of the Vitamin K Italian (VIKI) study to investigate the association between cigarette smoking and BGP levels in patients with end stage renal disease. Data were collected in 370 haemodialysis patients, 37% (136) smokers (or ex-smokers) and 63% (234) nonsmokers. Vascular calcifications and vertebral fractures (quantitative morphometry) were identified on spine radiographs. Results: Smokers had significantly lower BGP levels (152 vs. 204 μg/L, p=0.003). Smokers had lower plasma phosphate levels (4.2 vs. 4.7 mg/dl, p<0.01). Lower BGP levels were associated with aortic calcification (p<0.001), iliac calcification (p=0.042) and vertebral fractures (p=0.023). In addition, the regression model showed that smoking is associated with a significant reduction of total BGP levels by about 18% (p=0.01). Conclusion: This is the first clinical study in a haemodialysis population, which identifies cigarette smoking as a potential factor that can lower BGP levels, a protective agent in bone and vascular health.

Background: Obesity and micronutrient deficiencies contribute to the risk of cardiometabolic diseases such are type 2 diabetes mellitus and Cardiovascular Disease (CVD). Objective: We examined the frequency of concomitant deficit of Magnesium (Mg) and vitamin D in obese patients and evaluated the connection of these combined deficiencies with indicators of cardiometabolic risk in non-diabetic subjects. Methods: Non-diabetic middle aged adults (n = 80; mean age 36 ± 4 years, 52% women) were recruited based on weight/adiposity parameters [i.e. Body Mass Index (BMI) and body fat percentage (FAT%)]. Cardiometabolic risk indicators [insulin resistance (Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)) and CVD risk (Framingham risk score for predicting 10-year CVD)], Mg status (i.e. total serum Mg concentration (TMg), Chronic Latent Mg Deficiency (CLMD) - 0.75-0.85 mmol/L), vitamin D status (i.e. serum concentration of 25-hydroxyvitamin D (25(OH)D), vitamin D deficiency <50 nmol/l) were assessed. Results: Among obese subjects 36% presented a combination of vitamin D deficiency and CLMD. In all studied patients, 25(OH)D and TMg levels both, individually and combined, showed a negative linear correlation with HOMA-IR and CVD risk. In subjects with CLMD (TMg <0.85 mmol/L), a negative linear coefficient was found between 25(OH)D and, HOMA-IR and CVD risk, compared with subjects with normal TMg status (TMg ≥0.85 mmol/L). Conclusion: CLMD and vitamin D deficiency may commonly be present in obese non-diabetic subjects. Individually and combined, both deficiencies predispose non-diabetic patients to increased risk of cardiometabolic diseases. Maintaining normal Mg status may improve the beneficial effects of vitamin D on cardiometabolic risk indicators.

Background: Polymorphisms of the Adrenergic Receptors (ARs) might affect the development and progression of Heart Failure (HF) and the response to treatment with β-blockade therapy. Objective: To examine the role of the Gln27Glu polymorphism of β2-AR in HF development and to assess the hypothesis that Gln27Glu is associated with coronary artery disease in patients with ischaemic HF. Methods: In this case control study we enrolled 155 consecutive patients with symptomatic HF of ischaemic aetiology with impaired Left Ventricular Ejection Fraction (LVEF) ≤35%. The control group consisted of 133 patients with no obstructive coronary artery disease and or evidence of HF. Results: Concerning HF and control subjects there was no significant differences in the prevalence of Gln27Gln homozygotes (46 vs. 44%, p=0.82). In HF patients concerning the differences in patient characteristics between allele categories (Gln27Gln vs. Gln27Glu/Glu27Glu) there was no difference in risk factors, LVEF, treatment, the clinical status and NYHA categorization of patients, and in the prevalence of multi-vessel coronary artery disease. Interestingly, participants homozygous for Gln had significant higher prevalence of previous myocardial infarction (Gln27Gln vs. Gln27Glu/Glu27Glu: 77 vs. 23%, p=0.02). Conclusion: The present study shows that the Gln27Gln genotype of β2-AR is the most predominant while the Glu27Glu is the least prevalent in our HF population. There was no difference in the prevalence of polymorphism Gln27Glu between HF patients and control subjects. However, the presence of Glu allele was associated with lower myocardial infarction rate.