Gino Iannucci

Left ventricular torsion abnormalities in patients with obstructive sleep apnea syndrome: An early sign of subclinical dysfunction

BACKGROUND Previous echocardiographic studies using tissue Doppler imaging (TDI) and speckle tracking imaging (STI) have demonstrated that obstructive sleep apnea syndrome (OSAS) patients may develop subclinical left ventricular (LV) systolic and diastolic dysfunction. Our purpose was to evaluate the impact of OSAS on LV torsion dynamics and aortic stiffness by using TDI and STI echocardiography. METHODS Forty-two patients with OSAS and no comorbidities were studied. They were classified into mild and severe OSAS according to the apnea-hypopnea index (AHI). Thirty-five healthy subjects were selected as controls. Fifteen patients with severe OSAS underwent chronic nocturnal nasal continuous positive airway pressure (CPAP) therapy. Standard echocardiographic parameters were assessed. Global LV longitudinal strain (LS), radial and circumferential strain were determined by STI. Averaged LV rotation and rotational velocities from the base and apex were obtained and used for calculation of LV torsion (LVtor). Mitral annular velocities and aortic wall velocities and strain (AoS) were also obtained by TDI. RESULTS Severe OSAS had decreased LS compared with control subjects. LVtor increased significantly in severe OSAS compared to normals (p<.001) as a result of a predominant increase in apical rotation and was independently related to AHI and AoS in a multiple stepwise linear regression model. The group treated with CPAP had a significant decrease in LVtor and aortic stiffness index and significant increase in LS and AoS. CONCLUSIONS LVtor, LS and AoS were identified as parameters demonstrating an association between LV dysfunction, aortic stiffness and severity of OSAS independently of other possible factors or comorbidities.

Hepatitis C virus infection and autoimmune diseases

Hepatitis C virus (HCV) infection is associated with a number of extrahepatic disorders. The most studied conditions associated with HCV are type II mixed cryoglobulinemia and B cell lymphoma. However, many reports suggest that HCV might also be associated with a number of autoimmune disorders, both organ-specific and not organ-specific. Although concomitant treatment of HCV infection is a confounding factor when ascertaining the actual role of HCV in inducing autoimmune disease, a considerable amount of experimental data indicates that HCV is able to subvert the immune system and consequently induce autoimmunity. In the present review, we report a series of observations which associate chronic HCV infection with the onset of autoimmune disorders.

Leptin and Adiponectin mRNA Expression From the Adipose Tissue Surrounding the Adrenal Neoplasia

CONTEXT Interplay between adipose tissue and adrenal glands has been recently suggested, without well-founded actions of locally adipose tissue surrounding the adrenal glands. OBJECTIVE We hypothesized that the local expression of leptin and adiponectin can be associated with pathological changes of the adrenal glands. PATIENTS AND MAIN OUTCOME MEASURES We evaluated RT-PCR of leptin and adiponectin mRNA expression from the adipose tissue surrounding adrenal glands in 30 patients, collecting adipose tissue surrounding the adrenal neoplasms, peri-renal and subcutaneous depots. RESULTS Leptin mRNA levels from adrenal neoplasia and peri-renal fat were significantly higher in aldosterone-producing adenoma than in nonfunctioning adenomas (P < 0.001 and P < 0.02, respectively). In patients with Cushings syndrome leptin mRNA levels were significantly higher in adrenal fat than in peri-renal (P < 0.05) and subcutaneous adipose tissue (P < 0.001). Adiponectin mRNA expression from adrenal neoplasia was significantly lower than that from peri-renal and subcutaneous fat depots (P < 0.05). Leptin and adiponectin plasma levels significantly correlated with their mRNA expression from the fat depot surrounding the adrenal neoplasia. CONCLUSIONS Our findings suggest an active role of the fat depot surrounding the adrenal neoplasia, with local secretion of leptin and adiponectin.

Inverse correlation between plasma oxysterol and LDL-cholesterol levels in hepatitis C virus-infected patients

BACKGROUND Hepatitis C virus infection is characterised by enhanced oxidative stress, which can be measured quantitatively by plasma oxysterol concentration. These molecules may affect lipid metabolism through the activation of Liver X Receptors. Hepatitis C virus exploits host lipid metabolism to facilitate its replication and diffusion. In our study we aimed to evaluate and highlight the potential pathogenetic role of oxysterols, 7-ketocholesterol and 7-β-hydroxycholesterol, in hepatitis C virus-related lipid dysmetabolism. METHODS The study was performed in 42 patients with chronic hepatitis C (93% genotype 1b) and 38 non-alcoholic fatty liver disease patients. Plasma oxysterols 7-ketocholesterol and 7-β-hydroxycholesterol were determined by isotope dilution gas chromatography/mass spectrometry. RESULTS Gas chromatography/mass spectrometry revealed higher 7-ketocholesterol (71.2 ± 77.3 vs 30.4 ± 14.5; p<0.005) and 7-β-hydroxycholesterol (23.7 ± 20.6 vs 11.5 ± 4.9; p<0.001) plasma levels in hepatitis C virus patients. Furthermore, multivariate regression analysis highlighted an inverse independent correlation between high oxysterol levels and low low-density lipoprotein cholesterol (p=0.01 for 7-β-hydroxycholesterol; p=0.02 for 7-ketocholesterol) in the hepatitis C virus group; in contrast, the non-alcoholic fatty liver disease group showed a direct correlation between oxysterol levels and low-density lipoprotein-cholesterol (p<0.001 for 7-β-hydroxycholesterol; p=0.002 for 7-ketocholesterol). CONCLUSION These different correlations reveal profound differences in lipid dysmetabolism between chronic hepatitis C and non-alcoholic fatty liver disease patients.

Epicardial Fat Thickness and Primary Aldosteronism.

Primary aldosteronism (PA) is associated with increased cardiovascular risk and left ventricle (LV) changes. Given its peculiar biomolecular and anatomic properties, excessive epicardial fat, the heart-specific visceral fat depot, can affect LV morphology. Whether epicardial fat can be associated with aldosterone and LV mass (LVM) in patients with PA is unknown. We performed ultrasound measurement of the epicardial fat thickness (EAT) in 79 consecutive newly diagnosed patients with PA, 59 affected by bilateral adrenal hyperplasia (IHA), 20 aldosterone-producing adenoma (APA), and 30 patients with essential hypertension (low renin hypertension) (EH). The 3 groups did not differ by age, sex distribution, body mass index (BMI), waist circumference (WC), or blood pressure values. EAT showed a trend of increase in both APA and IHA groups when compared to patients with EH (8.3±1.8 vs. 7.9±1.3 vs. 7.8±2 mm, respectively). EAT was significantly correlated with indexed LVM in the IHA group (r=0.35, p<005), better than BMI or WC were. Interestingly, EAT was highly associated with plasma aldosterone concentrations (PAC) and PAC/plasma renin activity (PRA) (PAC/PRA) in the APA group (p=0.58, p=0.37, p<0.01, for both), whereas BMI and WC were not. EAT was also correlated with PRA in the IHA group (p=-0.28, p<0.05). Our study indicates a novel and interesting interaction of EAT with PA, independent of obesity, abdominal fat and blood pressure control. EAT can locally affect LVM, at least in patients with IHA. Further studies in larger population will be required to confirm these findings.

Cardiovascular reactivity of mitral valve prolapse patients during experimental stress exposure: evidence for a functional nature of cardiovascular symptoms

We studied a group of 18 patients with mitral valve prolapse (MVP) and a group of 20 healthy controls. Subjects in both groups were subjected to a 1–h experimental stress exposure during which Holter‐ECG monitoring was performed and was then continued for the following 24 h. MVP patients complained of significant cardiac palpitation during the stress session, but ECG examination did not reveal significant inter‐group differences. However, the two groups did show statistically significant differences in some psychometric measurements (Toronto Alexithymia Scale, Anxiety Sensitivity Index, Fear Questionnaire, Beck Depression Inventory, and Harm Avoidance subscale of Tridimensional Personality Questionnaire) that underlie personality traits known to be important in the process fostering functional somatic symptoms, according to the somatosensory amplification model. As no objective signs of cardiac rhythm modification were found in MVP patients under stress, we postulate that the symptoms for which these patients were referred have a functional nature, and that there is no pathogenetic link with the underlying valvular defect.

Non-Alcoholic Fatty Liver Disease and Nutritional Implications: Special Focus on Copper

Non-alcoholic fatty liver disease (NAFLD) is characterized by excess lipids in hepatocytes, due to excessive fatty acid influx from adipose tissue, de novo hepatic lipogenesis, in addition to excessive dietary fat and carbohydrate intake. Chronic hepatic lipid overload induces mitochondrial oxidative stress and cellular damage leading the development of NAFLD into a more severe liver disease condition, non-alcoholic steato-hepatitis (NASH). In turn, this can progress to cirrhosis and hepatocellular carcinoma (HCC). Among others, copper is one of the main bio-metals required for the preponderance of the enzymes involved in physiological redox reactions, which primarily occurs during mitochondrial respiration. Thus, copper homeostasis could be considered a target point for counteracting the progression of NAFLD. Accordingly, many diseases are correlated to unbalanced copper levels and, actually, some clinical trials are examining the use of copper chelating agents. Currently, no pharmacological interventions are approved for NAFLD, but nutritional and lifestyle modifications are always recommended. Fittingly, antioxidant food agents recognized to improve NAFLD and its complications have been described in the literature to bind copper. Therefore, this review describes the role of nutrition in the development and progression of NAFLD with a particular focus on copper and copper-binding antioxidant compounds against NAFLD.

Automatic analysis of high resolution atrial activation in mitral valve stenosis

High resolution P-waves of 28 patients having a mean age of 45 years and affected by isolated mitral valve stenosis (nine of whom showed paroxysmal atrial fibrillation) have been compared with those obtained from 30 healthy subjects about 35 years old. Our primary aim was to characterize the signal-averaged P-wave in mitral valve stenosis. Parameters which differed between the two groups in time domain analysis were the P-wave duration, the abscissa of the maximum positive voltage amplitude, the peak-to-peak amplitude and the integrated voltage-time product, which turned out to be greater in the patient class than in the healthy set; furthermore, in the frequency domain analysis, amplitudes in the range from 37 to 60 Hz were greater in healthy subjects than in patients. A successive analysis carried out to predict those patients with mitral valve stenosis who are at risk of developing paroxysmal atrial fibrillation showed that the P-wave duration and the amplitudes (in the range 60-106 Hz) were the most distinctive parameters, but, unfortunately, without any significant difference with respect to those of patients with mitral valve stenosis alone. Finally, some correlations between the age, the P-wave duration and the left atrial diameter of patients, were revealed to exist only in patients affected by episodes of atrial fibrillation.

Enhanced Soluble Serum CD40L and Serum P-Selectin Levels in Primary Aldosteronism

Primary aldosteronism (PA) is one of the most frequent forms of secondary hypertension, associated with atherosclerosis and higher risk of cardiovascular events. Platelets play a key role in the atherosclerotic process. The aim of the study was to evaluate the platelet activation by measuring serum levels of soluble CD40L (sCD40L) and P-selectin (sP-selectin) in consecutive PA patients [subgroup: aldosterone-secreting adrenal adenoma (APA) and bilateral adrenal hyperplasia (IHA)], matched with essential hypertensive (EH) patients. The subgroup of APA patients was revaluated 6-months after unilateral adrenalectomy. In all PA group, we measured higher serum levels of both sP-selectin (14.29±9.33 pg/ml) and sCD40L (9.53±4.2 ng/ml) compared to EH patients (9.39±5.3 pg/ml and 3.54±0.94 ng/ml, respectively; p<0.001). After removal of APA, PA patients showed significant reduction of blood pressure (BP) values, plasma aldosterone (PAC) levels and ARR-ratio, associated with a significant reduction of sP-selectin (16.74±8.9 pg/ml vs. 8.1±3.8 pg/ml; p<0.01) and sCD40L (8.6±1 ng/ml vs. 5.24±0.94 ng/ml; p<0.001). In PA patients, we found a significant correlation between sP-selectin and sCD40L with PAC (r=0.52, p<0.01; r=0.50, p<0.01, respectively); this correlation was stronger in APA patients (r=0.54; p<0.01 r=0.63; p<0.01, respectively). Our results showed that PA is related to platelet activation, expressed as higher plasma values of sCD40L and sP-selectin values. Surgical treatment and consequent normalization of aldosterone secretion was associated with significant reduction of sCD40L and sP-selectin values in APA patients.

Plasma endothelin-1 levels in patients with resistant hypertension: effects of renal sympathetic denervation

Abstract Introduction: Resistant arterial hypertension (RHT) is defined as poor controlled blood pressure (BP) despite optimal doses of three or more antihypertensive agents, including a diuretic. In the development of RHT, hyperactivity of sympathetic (SNS) and renin–angiotensin–aldosterone (SRAA) systems are involved, and SNS is a potent stimulator of vasoactive endothelin-1 (ET-1) peptide. Renal sympathetic denervation (RSD) through disrupting renal afferent and efferent nerves attenuates SNS activity. Material and methods: We carried out pilot study investigating the effect of RSD on BP and plasma ET-1 levels in consecutive 9 RHT patients (7 male and 2 female, mean age of 56 ± 13.3). Results: After 12 months of the RSD, we observed a significant reduction of BP office, 24-h ambulatory BP monitoring (ABPM) (p < 0.05, respectively), and “non-dipping” pattern (from 55% to 35%) (p < 0.05). Moreover, RSD significantly decreased plasma ET-1 levels in both renal artery (at right from 21.8 ± 4.1 to 16.8 ± 2.9 pg/ml; p = 0.004; at left from 22.1 ± 3.7 to 18.9 ± 3.3 pg/ml; p = 0.02). We observed positive correlations between plasma renal arteries ET-1 levels and systolic BP values at ABPM [Global-SBP (r = 0.58; p < 0.01), Diurnal-SBP (r = 0.51; p < 0.03) and Nocturnal-SBP (r = 0.58; p < 0.01), respectively]. Discussion: Our data confirmed the positive effects of RSD on BP values in patients with RHT, and showed a possible physio-pathological role of ET-1. KEY MESSAGES RSD is associated to a significant reduction of plasma ET-1 levels, representing an useful tool into reduction of BP in RHT patients.