Annapaola Zito

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 (β-carotene, α-carotene, β-cryptoxanthin, lycopene, lutein, zeaxanthin, and astaxanthin).

Correlation between Inflammatory Markers of Atherosclerosis and Carotid Intima-Media Thickness in Obstructive Sleep Apnea

Obstructive Sleep Apnea (OSA) is a sleep-related breathing disorder associated with the development of cardiovascular diseases and atherosclerosis. Systemic inflammation plays an important role in the development of cardiovascular complications in OSA patients. The aim of the study was to evaluate the relationship between carotid intima-media thickness (cIMT) and inflammatory markers plasma levels in OSA patients. We enrolled 80 OSA patients and 40 controls matched for age and body mass index (BMI). The presence and severity of sleep apnea was determined by in-laboratory portable monitoring (PM). Demographic data, blood pressure, heart rate, and cIMT were measured. High-sensitive C-Reactive Protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α and pentraxin (PTX)-3 serum concentrations were detected. cIMT was higher in OSA patients than controls (0.89 ± 0.13 mm vs. 0.65 ± 0.1 mm, p < 0.01). Moderate-severe OSA patients (0.95 ± 0.09 mm) had significantly increased cIMT than mild OSA (0.76 ± 0.1 mm; p < 0.01) and control (0.65 ± 0.1 mm; p < 0.01). hsCRP, IL-6, TNF-α, and PTX-3 in patients with OSA (1.67 ± 0.66 mg/L, 2.86 ± 1.39 pg/mL, 20.09 ± 5.39 pg/mL, 2.1 ± 0.59 ng/mL, respectively) were significantly higher than in controls (1.08 ± 0.53 mg/L, p < 0.01; 1.5 ± 0.67 pg/mL, p < 0.01; 12.53 ± 3.48 pg/mL, p < 0.01; 1.45 ± 0.41 ng/mL, p < 0.01, respectively). Carotid IMT was significantly correlated to CRP (r = 0.44; p < 0.01), IL-6 (r = 0.42; p < 0.01), TNF-α (r = 0.53; p < 0.01), and PTX-3 (r = 0.49; p < 0.01). OSA patients showed increased cIMT, CRP, IL-6, TNF-α, and PTX-3 levels. Inflammatory markers levels are correlated to cIMT in OSA patients.

Endothelial Function in Pre-diabetes, Diabetes and Diabetic Cardiomyopathy: A Review

Diabetes mellitus worsens cardiovascular risk profile of affected individuals. Its worldwide increasing prevalence and its negative influences on vascular walls morphology and function are able to induce the expression of several morbidities which worsen the clinical conditions of the patients getting them running towards a reduced survival curve. Although overt diabetes increases the mortality rate of individuals due to its pathogenesis, poor information are in literature about the role of pre-diabetes and family history of diabetes mellitus in the outcome of general population. This emphasizes the importance of early detection of vascular impairment in subjects at risk of developing diabetes. The identification of early stages of atherosclerotic diseases in diabetic persons is a fundamental step in the risk stratification protocols followed-up by physicians in order to have a complete overview about the clinical status of such individuals. Common carotid intima-media thickness, flow-mediated vasodilatation, pulse wave velocity are instrumental tools able to detect the early impairment in cardiovascular system and stratify cardiovascular risk of individuals. The aim of this review is to get a general perspective on the complex relationship between cardiovascular diseases onset, pre-diabetes and family history of diabetes. Furthermore, it points out the influence of diabetes on heart function till the expression of the so-called diabetic cardiomyopathy.

Task force on: 'Early markers of atherosclerosis: influence of age and sex'.

Atherosclerosis and its complications are the most important causes of death all over the world, especially in Western countries. Diet habits, modern stress life, smoking, sedentary way of life and an involvement of genetic pattern of individuals lead to a sure degeneration of quality of life increasing the risk of atherosclerosis development. For this reason, the main purpose of actual medicine is to identify all the markers that could allow the physicians to evaluate the first moments of the development of this dangerous pathological process. The aim is to reduce the speed of its evolution, trying to delay indefinitely the risk coming from the morphological alterations of the vessels. ‘Endothelium function’ could allow physicians to detect the first moment of the natural history of atherosclerosis process. Its impairment is the first step in the degeneration of vascular structures. Many methods [flow-mediated vasodilatation (FMD); antero-posterior abdominal aorta diameter (APAO); intima-media thickness of the common carotid artery (CCA-IMT); arterial stiffness; and so on] try to evaluate its function, but many limitations come from general population characteristics. A standardization of the methods should take into account individuals’ peculiarities. Two elements, not modifiable, should be taken into account for vascular evaluation: age and sex. The aim of this review is to outline the linkage among age, sex and instrumental evaluation of patients considered for a noninvasive assessment of their cardiovascular risk profile.

Endothelial function and cardiovascular risk in active inflammatory bowel diseases

BACKGROUND Endothelial dysfunction has been already reported in inflammatory bowel diseases (IBD). However, case series so far examined were rather heterogeneous as for disease severity and subsets investigated. OBJECTIVE We evaluated endothelial dysfunction by brachial artery flow-mediated vasodilatation (FMD), and subclinical atherosclerosis by assessment of common carotid intima-media thickness (CCA-IMT) in a cohort of patients with Crohns disease (CD) or Ulcerative colitis (UC) in active phase compared to healthy control subjects. METHODS Forty-nine patients (mean age 41±16 years), 25 with CD and 23 with UC, and forty controls (mean age 45±15 years) were enrolled. Diagnosis was based on the standard clinical, endoscopic and histological criteria. Disease activity was assessed by Crohns Disease Activity Index or Disease Activity Index. All patients, were under medical treatment as appropriate. RESULTS FMD values were lower in IBD patients than controls (6.1±3.0 vs 8.2±3.4. p=0.003); no difference was seen between UC/CD groups (5.9±3.5 vs 6.3±2.6, p=0.67). No changes in statistical differences occurred after adjustment for age, gender, body mass index and family history of cardiovascular disease. Finally, no differences in IMT values were seen between IBD patients and controls. Disease duration and medical treatment did not affect endothelial function. CONCLUSIONS Our study showed a lower FMD in IBD patients. Inflammation and immune response could explain endothelial dysfunction, which is the earliest stage of atherosclerotic process. IBD patients in active phase might therefore be at higher risk for atherosclerosis progression.

Multigate Quality Doppler Profiles and Morphological/Hemodynamic Alterations in Multiple Sclerosis Patients

Venous echo-color-Doppler (ECD) showed that chronic cerebrospinal venous insufficiency (CCSVI) syndrome is related to multiple sclerosis (MS). Study aims were to assess interobserver variability in ultrasound evaluation of MS patients and to relate echo-markers to MS clinical symptoms and the disability degree. 277 MS patients (117 men, mean age 43.05+10.04 years) admitted to the Neurology Department of Bari University General Hospital, underwent clinical, Expanded Disability Status Scale (EDSS) evaluation, and a cerebro-venous system ECD evaluation. Two operators reevaluated 32 patients to calculate interobserver variability. McNemar test confirmed the procedure reproducibility between two operators (p=ns). Septa/membranes correlated with deep cerebral veins reflux [right: 16% absence vs. 58% presence, p < 0.0001; left: 26% vs. 50%, p < 0.0001]; their absence in Primary Progressive (PP) MS form [right: 11% vs. 2%, p < 0.001; left: 12% vs. 2%, p < 0.001]. Internal jugular veins (IJVs) reflux absence was in Relapsing-remitting (RR) form [right: 60% vs. 74%, p=0.036; left: 56% vs. 85%, p < 0.0001] like hemodynamically significant stenosis [right: 57% vs. 69%, p=0.033; left: 49% vs. 73%, p < 0.001] not present in PP [right: 11% vs. 2%, p < 0.001; left: 10% vs. 3%, p=0.009]. A supine IJVs blocked flow was related to the EDSS class [right: 4.8±1.5 vs. 5.4±1.4, p=0.006; left: 4.7±1.6 vs. 5.5±1.2, p < 0.0001]; its absence was linked to RR [right: 60% vs. 76%, p=0.016; left: 58% vs. 79%, p < 0.001]. ECD has an important value in MS patients with IJV anomalies detection and a good interobserver procedure reproducibility. MS is associated with CCSVI, although further studies are needed.

HCN Channels and Heart Rate

Hyperpolarization and Cyclic Nucleotide (HCN) -gated channels represent the molecular correlates of the “funny” pacemaker current (If), 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.

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 everyones diet as a tool to obtain a sharp decrease of LDL oxidation and their possible effect on endothelial function.

Correlation between coronary artery disease severity, left ventricular mass index and carotid intima media thickness, assessed by radio-frequency

BackgroundIntima-media thickness of the common carotid artery (CCA-IMT) is a validated marker of systemic atherosclerosis process. The aim of this study was to evaluate the association between coronary artery disease (CAD), left ventricular hypertrophy (LVH) and CCA-IMT, assessed by Radio Frequency-Quality Intima Media Thickness (RFQIMT) method, the next generation of IMT real-time measurement, based on the direct analysis of the radiofrequency signal and endowed with high accuracy and reproducibility in early detection of arterial wall thickness.Methods115 patients (76 men, mean age: 65.1 ± 12 years) referred to our department and shown significant (≥ 70% luminal obstruction) stenosis at least in one major epicardial coronary artery were studied. Coronary angiograms were divided for severity and extent of the disease: 79 patients (69%) had one, 24 patients (21%) two, 12 patients (10%) three major epicardial coronary arteries with ≥ 70% stenosis. All patients underwent echocardiography and carotid ultrasound examination, assessed by RF.ResultsDividing RFQIMT data in tertiles, dyslipidaemia (31 patients with IMT ≥ 1.20 mm vs 16 with IMT = 0.91-1.19 vs 25 with IMT ≤ 0.9, p = 0.004), LVMI (153.5 ± 20.6 g/m2 in IMT ≥ 1.20 mm vs 131.2 ± 8.4 g/m2 in IMT = 0.91-1.19 mm vs 114.3 ± 11.1 g/m2 in IMT ≤ 0.9 mm, P < 0.001) and number of high stenosed coronary arteries (IMT ≥ 1.20 mm population more often showed three vessel diseases than IMT ≤ 0.90 mm one, P < 0.001) seemed to be significantly related to CCA-IMT increases. Furthermore, LVMI is positively related to IMT (r = 0.91; P < 0.001). In a multivariate regression model (R2 = 0.88), RFQIMT remained significantly associated with the dyslipidemia (regression coefficient ± standard error [SE]: 0.057 ± 0.023; p = 0.017), LVMI (regression coefficient ± SE: 0.01 ± 0.001; P < 0.0001) and number of damaged coronaries (regression coefficient ± SE: 0.0174 ± 0.028; P < 0.0001).ConclusionsRFQIMT is a sophisticated method for carotid ultrasound evaluation. Its evaluation in patients with at least one important major epicardial coronary vessel stenosis would help the accuracy in the general assessment of the number of coronary lesions in these patients.

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, β-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.