Surgical and pharmacological reassignment: influence on transsexual cardiovascular risk profile.

BACKGROUND/AIM: To evaluate and stratify early cardiovascular risk of transsexuals who underwent pharmacological and/or surgical gender reassignment. METHODS: Fifty-six transsexuals were divided into two groups: group 1 - underwent gonadectomy (orchiectomy for transwomen and hystero-annessiectomy for transmen); group 2 - hormone replacement therapy alone. All participants underwent carotid artery intima-media thickness (C-IMT) and flow-mediated vasodilation (FMD) of brachial artery evaluations. RESULTS: FMD was lower in patients who had undergone gonadectomy compared with non-surgically treated patients (Group 1: 5.711 vs Group 2: 7.339, P < 0.0001). Mean C-IMT was higher in group 1 than group 2 (group 1: 0.733 vs group 2: 0.582). The duration of hormone therapy correlates positively with mean C-IMT (B = 0.001) and negatively with FMD (%) (B = - 0.007). CONCLUSIONS: Cardiovascular risk, which is expressed in terms of endothelial (FMD) and morphological (C-IMT) dysfunction, increases in subjects undergoing gonadectomy compared with those receiving cross-sex reassignment therapy alone.

Rosuvastatin: Beyond the cholesterol-lowering effect.

Rosuvastatin is a fully synthetic statin wich acts by interfering with the endogenous synthesis of cholesterol through competitively inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A reductase, a liver enzyme responsible of the rate-limiting step in cholesterol synthesis. When compared to other molecules of the same class, it shows high efficacy in the improvement of lipid profile, and, thanks to its non-cholesterol-lowering actions (anti-inflammatory, antioxidant and antithrombotic), represents a crucial tool for cardiovascular primary and secondary prevention. Moreover, recent data highlight rosuvastatin beneficial effects in several other fields. In this manuscript we analyzed literature sources in order to better define rosuvastatin features and discuss some critical issues.

Vascular Function and Myocardial Performance Indices in Children Born Small for Gestational Age.

BACKGROUND: Small-for-gestational-age (SGA) children have increased cardiovascular risk, but the mediating factors are poorly understood. We hypothesized that birth size could affect the cardiovascular system since childhood in the absence of other risk factors. We investigated endothelial and myocardial function in SGA children with regular catch-up growth. METHODS AND RESULTS: Biochemical markers, blood pressure, flow-mediated vasodilation (FMD), common carotid intima-media thickness (cIMT), anteroposterior diameter of the infrarenal abdominal aorta (APAO) and echocardiographic parameters of left and right ventricular (LV and RV) function were studied in 27 SGA and 25 appropriate-for-gestational-age (AGA) subjects. SGA subjects had a higher homeostasis model assessment index than controls (2.61±1.27 vs. 1.56±0.40, P=0.01), higher cIMT (0.51±0.04 mm vs. 0.45±0.07 mm, P=0.007) and APAO (1.31±1.35 cm vs. 1.30±0.16 cm, P=0.005), and lower FMD (10.11±4.17% vs. 12.34±4.28, P=0.04) than controls. On echocardiography SGA had higher Tei index both at LV and RV than controls (P=0.001). Reduced RV systolic function was also observed in SGA subjects. CONCLUSIONS: SGA subjects had vascular morphological and function abnormalities compared with AGA, which increase their cardiovascular risk profile. Furthermore, a subtle cardiac alteration in both RV and LV functions was seen in SGA patients compared with AGA.

Advances in the diagnosis of acute aortic syndromes: Role of imaging techniques.

Aortic diseases include a wide range of pathological conditions: aortic aneurysms, pseudoaneurysms, acute aortic syndromes, atherosclerotic and inflammatory conditions, genetic diseases and congenital anomalies. Acute aortic syndromes have acute onset and may be life-threatening. They include aortic dissection, intramural haematoma, penetrating aortic ulcer and traumatic aortic injury. Pain is the common denominator to all acute aortic syndromes. Pain occurs regardless of age, gender and other associated clinical conditions. In this review, we deal with the main findings in the clinical setting and the most recent indications for diagnostic imaging, which are aimed to start an appropriate treatment and improve the short- and long-term prognosis of these patients.

Focus on alirocumab: A PCSK9 antibody to treat hypercholesterolemia.

Statin treatment represents the gold standard in the reduction of low-density lipoprotein cholesterol and cardiovascular risk. Although statin therapy is generally well tolerated, some patients fail to achieve the target level of low-density lipoprotein cholesterol or discontinue the treatment for the occurrence of adverse events. In recent years new lipid-modifying agents have been studied to overcome these limitations and to reduce low-density lipoprotein cholesterol plasma levels. Alirocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, thereby preventing its interaction with low density lipoprotein receptors. Several trials have been conducted in the last few years to evaluate long-term effects of this new molecule on low-density lipoprotein cholesterol levels and cardiovascular risk.

Dietary intake of carotenoids and their antioxidant and anti-inflammatory effects in cardiovascular care.

Cardiovascular disease related to atherosclerosis represents nowadays the largest cause of morbidity and mortality in developed countries. Due to inflammatory nature of atherosclerosis, several studies had been conducted in order to search for substances with anti-inflammatory activity on arterial walls, able to exert beneficial roles on health. Researches investigated the role of dietary carotenoids supplementation on cardiovascular disease, due to their free radicals scavenger properties and their skills in improving low-density lipoprotein cholesterol resistance to oxidation. Nevertheless, literature data are conflicting: although some studies found a positive relationship between carotenoids supplementation and cardiovascular risk reduction, others did not find any positive effects or even prooxidant actions. This paper aimed at defining the role of carotenoids supplementation on cardiovascular risk profile by reviewing literature data, paying attention to those carotenoids more present in our diet (ß-carotene, α-carotene, ß-cryptoxanthin, lycopene, lutein, zeaxanthin, and astaxanthin).

HCN channels and heart rate.

Hyperpolarization and Cyclic Nucleotide (HCN) -gated channels represent the molecular correlates of the "funny" pacemaker current (I(f)), a current activated by hyperpolarization and considered able to influence the sinus node function in generating cardiac impulses. HCN channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. This channel family comprises four members: HCN1-4, but there is a general agreement to consider HCN4 as the main isoform able to control heart rate. This review aims to summarize advanced insights into the structure, function and cellular regulation of HCN channels in order to better understand the role of such channels in regulating heart rate and heart function in normal and pathological conditions. Therefore, we evaluated the possible therapeutic application of the selective HCN channels blockers in heart rate control.

Morphological and functional vascular changes induced by childhood obesity.

BACKGROUND: To investigate endothelial dysfunction and morphological vascular changes in childhood obesity. METHODS: 93 overweight/obese children (body mass index 26 ± 5 kg/m(2); median 26 kg/m(2); interquartile range 22-28 kg/m(2)), mean age 10.9 ± 2.7 years, underwent a check-up of total, high-density lipoprotein- and low-density lipoprotein-cholesterol, triglycerides, C-reactive protein, erythrocyte sedimentation rate, and white blood cell count, together with ultrasound measures of flow-mediated dilatation, carotid intima-media thickness, and anterior-posterior diameter of the abdominal aorta. RESULTS: The body mass index of overweight/obese children had a statistically significant linear relationship (p < 0.05) with triglycerides, erythrocyte sedimentation rate, carotid intima-media thickness, anterior-posterior diameter of the abdominal aorta, and flow-mediated dilatation values. CONCLUSIONS: Overweight/obese children have an initial endothelial dysfunction and vascular damage, i.e., the first stage in the development of atherosclerosis.

Can carotid plaque histology selectively predict the risk of an acute coronary syndrome?

The aim of this study was to assess whether carotid plaque morphology is an independent predictive factor of stroke and, innovatively, of acute coronary syndrome (ACS). We analyzed morphological aspects of carotid atherosclerotic plaque associated with an increased risk of ACS and stroke. We examined 72 carotid endarterectomy (CEA) specimens obtained between January 2005 and February 2009. All patients underwent follow-up for 12 months after the revascularization treatment to assess the occurrence of ACS and stroke. Data obtained showed that in patients with a previous ACS and in those who had developed an ACS during follow-up after CEA, the degree of carotid plaque calcification was more severe than in patients who did not develop an ACS, either before CEA or during follow-up. However, plaques of patients with ACS were mostly devoid of a significant inflammatory component, whereas a rich infiltrate, mainly consisting of monocytes-macrophages and lymphocytes, was present in plaques of subjects who did not develop an ACS. This element was particularly important since strokes occurred only in the latter group of patients (62% versus 0%). Therefore, we deduced that inflammation, from the histological point of view, is more correlated with cerebral circulation disorders than with coronary disease. In conclusion, while the finding of a soft plaque with a large necrotic core and a marked inflammatory component, often characterized by acute complications, may be predictive of an increased risk of cerebro-vascular events, a heavily calcified plaque may be indicative of a high risk of coronary events.

Statins: Pharmacokinetics, Pharmacodynamics and Cost-Effectiveness Analysis.

Cardiovascular diseases secondary to atherosclerosis are the primary causes of early death and disability worldwide and dyslipidaemia represents one of the most important modifiable risk factors. Among lipid abnormalities that define it, low-density lipoprotein cholesterol (LDL-C) is the primary target of therapy, since multiple randomized controlled trials have shown the positive impact of its reduction on atherosclerosis development. For their ability to lower LDL-C levels, statins are the most studied drugs in cardiovascular disease prevention, of proven utility in slowing the progression or even determining regression of atherosclerosis. In addition, they have ancillary proprieties, with positive effects on the mechanisms involved in the development of atherosclerosis and cardiovascular morbidity and mortality, the so-called "pleiotropic mechanisms". Although sharing the same mechanism of action, the different chemical and pharmacological characteristics of each kind of statins affect their absorption, bioavailability, plasma protein binding properties, excretion and solubility. In this overview, we analysed pharmacokinetic and pharmacodynamic mechanisms of this class of drugs, specifying the differences among the molecules, along with the economic aspects. Detailed knowledge of characteristics and differences of each kind of available statin could help the physician in the correct choice, based also on patient's clinical profile, of this essential tool with a demonstrated high cost-effectiveness both in primary than in the secondary prevention of cardiovascular disease.

Apixaban: Effective and Safe in Preventing Thromboembolic Events in Patients with Atrial Fibrillation and Renal Failure.

BACKGROUND: Thromboembolic events, principally stroke, represent one of the leading causes of morbidity and mortality among subjects with atrial fibrillation. Chronic kidney disease determines a further increase of thromboembolic events, bleeding and mortality and complicates the pharmacological management of patients with atrial fibrillation, mainly due to the side effects of antiarrhythmic and anticoagulant drugs with renal excretion. Apixaban is a new oral anticoagulant characterized by good bioavailability and renal elimination accounting for only 25%, showing a safety profile and effectiveness in patients with renal impairment. OBJECTIVE: In this manuscript, we reviewed literature data on the use of apixaban in the management of non-valvular atrial fibrillation in patients with renal failure, in order to clarify an often-debated topic in clinical practice. METHOD: A PubMed search was performed on the terms atrial fibrillation, apixaban and renal failure with the aim of identifying relevant manuscripts, large randomized clinical trials, meta-analyses, and current guidelines. RESULTS: Literature data show that apixaban could represent an interesting alternative to warfarin and other selective antagonists of coagulation factors in patients with impaired renal function. About the risk of major bleeding, apixaban appears to be safer than warfarin in the presence of any degree of renal failure. CONCLUSION: Apixaban show to be an effective anticoagulant in patients with atrial fibrillation, even superior to warfarin in reducing the risk of stroke and systemic embolism regardless of the presence of renal insufficiency. Moreover, Food and Drug Administration allows the use of apixaban in patients with end stage renal disease on hemodialysis.

Endothelial dysfunction and cardiovascular risk factors in childhood acute lymphoblastic leukemia survivors.

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) survivors have increased risk of obesity, metabolic alterations and cardiovascular disease (CVD). Vascular endothelial function has been studied in adult cancers. Limited data exist regarding CVD risk factors among childhood ALL survivors. We aimed to assess endothelial function, metabolic and cardiovascular risk factors in young survivors of childhood ALL. METHODS: Auxological parameters, blood pressure, glucose, lipid profile, hemostatic markers (total adiponectin and high-molecular-weight subfraction, endothelin-1, von Willebrand factor antigen, thrombin-antithrombin complex, D-dimers, fibrinogen), high sensitive C-reactive protein and ultrasound parameters of endothelial function (flow-mediated dilation-FMD, common carotid intima-media thickness-C-IMT, and antero-posterior diameter of infra-renal abdominal aorta-APAO) were assessed in 52 ALL survivors and 34 sex and age-matched controls. RESULTS: ALL patients and controls were not statistically different as regards body mass index and waist circumference. Blood pressure, glucose, total and LDL-cholesterol, triglycerides, high sensitive C-reactive protein were statistically higher in ALL than in controls, while HDL-cholesterol was lower in ALL than in controls. Patients showed statistically lower high-molecular-weight adiponectin and thrombin-antithrombin complex (p=0.003 and p<0.001, respectively) and higher vonWillebrand factor antigen (p=0.002) than controls. FMD was lower in patients than in controls (p<0.001). Biomarkers of endothelial function, systolic blood pressure and waist circumference were correlated to FMD. CONCLUSIONS: ALL survivors showed derangement of endothelial function, which likely occurs during chemotherapy and lasts till follow up. They showed metabolic alterations even though obesity was not documented. Endothelial vascular parameters should be evaluated earlier during follow-up to detect preclinical onset of CVD.

Fulminant Peripartum myocarditis associated with sudden cardiac death: a case report.

Myocarditis is an inflammatory disease of myocardium, associated with nonischemic necrosis and degeneration of myocytes. Although the clinical course is rapid, myocarditis can lead to dilated cardiomyopathy with chambers dilatation and ventricular dysfunction. The pathophysiology of myocarditis in humans is not completely understood. There are several etiological agents implicated, mainly viral agents. The clinical presentation is extremely various, with nonspecific systemic symptoms until sudden death. The great variability of symptoms makes the diagnosis, therefore, extremely difficult. We report the case of a 40-year-old woman who developed, after childbirth, hyperthermia associated with neck and left arm pain; initially treated with acetaminophen, without any benefit, the young woman, after few days, died suddenly. The autopsy documented the presence of edematous lungs and enlarged and congested liver. The microbiological tests performed 4 days after death were negative. The heart was normal in shape and volume; a section of the left ventricle wall showed subendocardial discromic areas histologically characterized by multifocal perivascular and interstitial inflammatory infiltrates. These infiltrates consisted mainly of neutrophils with eosinophil component associated with myocyte necrosis and hemorrhagic interstitial infiltration.

Pulmonary hypertension in thyroid diseases.

The influence of thyroid hormones on cardiovascular system is well established. Thyroid diseases can effectively enhance the alteration on cardiovascular system by influencing chronotropic and inotropic actions of the heart; altering the strength and the speed of contraction, the speed of relaxation, the duration of the potential of action, and the duration of the refractory period and atrio-ventricular conduction time; modulating circulation and peripheral vascular beds. One of the more intriguing insights in the connection between thyroid diseases and cardiovascular alterations is related to the evaluation of the influence of thyroid hormones on pulmonary vascular beds. Literature reported several studies regarding the association between both hypothyroidism and hyperthyroidism and the occurrence of increased vascular pulmonary arterial pressure. Nevertheless, the pathogenetic mechanisms able to explain such relationship are not fully understood. Many doubts still persist in the comprehension of the mechanisms of pulmonary hypertension in thyroid diseases. The aim of this review was to provide possible explanation about the possible interaction between pulmonary vascular beds and thyroid function in order to evaluate the possibility of novel perspectives in the general management of patients suffering from thyroid and cardiovascular diseases.

The association between cardiac and gastrointestinal disorders: causal or casual link?

Cardiovascular diseases are the leading cause of death worldwide: among them, coronary artery disease and arrhythmias represent the most frequent pathological conditions. Similarly, the gastrointestinal disorders, that is, gastroesophageal reflux and inflammatory bowel diseases, have a high incidence in the general population. Several pieces of evidence have documented a link between cardiac and gastrointestinal disorders as they often share similar risk factors and symptoms. Furthermore, both can simultaneously occur in the same patient, thus creating problems in the correct clinical diagnosis. It is well known that gastrointestinal disorders may present with chest pain and mimic angina pectoris. In contrast, they can also unmask heart disease, such as in the case of the angina-linked ischemia. The aim of this review was to elucidate the mechanisms underlying the relationship between cardiac and gastrointestinal diseases to better understand the causal or casual character of such a linkage.

Inflammatory bowel disease, liver diseases and endothelial function: is there a linkage?

Atherosclerosis is a systemic inflammatory disease able to deeply worsen the outcome of patients because of its serious clinical consequences. The complex inflammatory background underlining such a disease makes atherosclerosis linked to several systemic inflammatory conditions able to impair endothelial function and morphology. Inflammatory bowel diseases are a group of gastrointestinal diseases including Crohn's disease and ulcerative colitis, that is, syndromes characterized by changes in mucosal immunity and gastrointestinal physiology, which could negatively influence the vascular endothelial function and structure. Hepatitis (i.e. inflammatory diseases of the liver mainly due to viral infections) and nonalcoholic fatty liver disease could be aligned to inflammatory bowel disease in such an induction of atherosclerosis disease.Many studies tried to point out the relationship between bowel and liver inflammatory diseases and early vascular changes, considered the first step for atherosclerosis development.The aim of such a narrative review is to explain the relationship between inflammatory bowel disease, hepatitis and nonalcoholic fatty liver disease and their role in increasing cardiovascular risk profile due to early impairment in vascular function and morphology.

Ivabradine, coronary artery disease, and heart failure: beyond rhythm control.

Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, ß-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies.

The role of omega-3 polyunsaturated fatty acids supplementation in childhood: a review.

Dietary omega-3 polyunsaturated fatty acids (ω-3 PUFAs) benefits are not clearly defined in childhood although already well-defined in adults. Recent studies have demonstrated their positive effects on bronchial asthma, neuropsychiatric disorders and cognitive brain function in childhood. Furthermore, it has been demonstrated as a relationship between the increased incidence of childhood obesity and the role of ω-3 PUFAs in reducing the metabolic and vascular alterations induced by the fat accumulation since young age. Such relationship could be more important in prevention of future cardiovascular events. In fact, ω-3 PUFAs could improve endothelial function and structure since childhood. By considering endothelial dysfunction as a well-known early marker of atherosclerosis, its amelioration in the beginning years of individuals' life will certainly reduce the cardiovascular risk profile in adulthood. Nevertheless, their use is limited by several factors, such as the lack of studies in children and the awful taste of the products enriched with ω-3 PUFAs, although several patents have managed to overcome such defects and developed the use of these molecules. This paper is a literature study and patents analysis aiming to explore key issues regarding ω-3 PUFAs administration in childhood in order to take into account its routine intake daily. However, it is well-established that further studies are needed to endorse the promising results outlined by literature analysis.

Carotenoids and cardiovascular risk.

Fruits and vegetables (typically associated with the Mediterranean diet) are very rich in carotenoids, i.e. fat-soluble pigments really important in human life. Structurally, carotenoids consists of eleven (beta-carotene, zeaxanthin, lycopene) or ten (alpha-carotene, lutein) conjugated double bonds, responsible for their antioxidant capability in agreement with their substituents. Low-Density Lipoprotein (LDL) particles oxidation process is the one of the most important first steps of atherosclerotic disease and, consequentially, the first pathogenetical step of cerebro- and cardiovascular events like myocardial infarction and stroke, which are the first cause of death in industrialized countries. Reactive oxygen species (ROS) also seem to be the target of Carotenoids main action, by scavenging singlet oxygen (1O2) and free radicals. Literature data showed that ROS increase atherosclerotic individual burden. The carotenoids scavenging action could reduce atherosclerosis progression partly due to such a decrease in ROS concentrations. Many studied demonstrated such a reduction by analyzing the relationship between carotenoids and Intima-Media Thickness of common carotid artery wall (CCA-IMT), [a well established marker of atherosclerosis evolution] reduction. Aim of this review is to evaluate actual knowledge about the importance of carotenoids molecules in slowing down the starting and the progression of atherosclerotic plaque, and to consider their implementation in everyone's diet as a tool to obtain a sharp decrease of LDL oxidation and their possible effect on endothelial function.