RAGE gene polymorphism in heart failure patients with and without angiographic evidence of significant coronary atherosclerosis.

Heart failure (HF) is a multifactorial disorder in which clinical, environmental and genetic components take part. For this reason it is possible that common gene variants could affect development, progression and response to pharmacological therapy. In recent years the role of AGEs in the pathogenesis of cardiovascular diseases has become recognized but little is known about the role of the AGE-RAGE system in heart failure. The aim of the present study was to identify possible relationship between -374 T/A RAGE gene polymorphism with heart failure. The population in this study consists of 386 subjects with HF, selected according to the presence of depressed Left Ventricular Ejection Fraction (LVEF) <45%, and 639 patients with CAD documented at coronary angiography. Within the population with HF there are 228 patients with disease secondary to not ischemic cause and 158 with post-ischemic condition. The sample of AA genotype was significantly lower in patients with post-ischemic HF in respect to HF secondary to non-ischemic causes (p<0.001). A significant difference between the two groups was also observed regarding the allele frequency. In addition, differences in the allelic and the genotypic frequencies of homozygous genotypes were found between the HF patients free from evidence of coronary significant lesions and patients with at least one hemodynamically significant coronary lesion, both HF and CAD. In patients with at least one vessel compromised the presence of A allele and the homozygous AA genotype were significantly lower than in patients with lesion-free coronary. In conclusion, our research reveals that the -374 T/A polymorphism is related to the genesis of atherosclerotic coronary artery disease but not to its evolution. The protective role of AA genotype in respect to atheromatous disease is therefore confirmed also in the HF population with non-ischemic origin

Disease Severity in Treatment Resistant Schizophrenia Patients Is Mainly Affected by Negative Symptoms, Which Mediate the Effects of Cognitive Dysfunctions and Neurological Soft Signs

This post-hoc study was aimed at assessing whether disease severity was higher in a sample of Treatment Resistant Schizophrenia patients (TRS) compared to schizophrenia patients responsive to antipsychotics (non-TRS). Determinants of disease severity were also investigated in these groups. Eligible patients were screened by standardized diagnostic algorithm to categorize them as TRS or non-TRS. All patients underwent the following assessments: CGI-S; PANSS; DAI; NES; a battery of cognitive tests. Socio-demographic and clinical variables were also recorded. TRS patients exhibited significantly higher disease severity and psychotic symptoms, either as PANSS total score or subscales' scores. A preliminary correlation analysis ruled out clinical and cognitive variables not associated with disease severity in the two groups. Hierarchical linear regression showed that negative symptoms were the clinical variable explaining the highest part of variation in disease severity in TRS, while in non-TRS patients PANSS-General Psychopathology was the variable explaining the highest variation. Mediation analysis showed that negative symptoms mediate the effects of verbal fluency dysfunctions and high-level neurological soft signs (NSS) on TRS' disease severity. These results show that determinants of disease severity sharply differ in TRS and non-TRS patients, and let hypothesize that TRS may stem from cognitive disfunctions and putatively neurodevelopmental aberrations

Esmolol for the treatment of recurrent ventricular tachycardia

Cardiac arrest and electrical storm are two major emergencies. The use of beta blockers in these clinical conditions has been proposed; however, definite data about the emergency use of beta blockers in recurrent ventricular tachycardia with pulse have never been published. We report two cases of recurrent ventricular tachycardia, which were unresponsive to the standard pharmacological treatment but successfully responsive to esmolol infusion. Both cases showed a reduced left ventricle ejection fraction due to an acute myocardial infarction and to an idiopathic dilated cardiomyopathy respectively. Nevertheless, the use of esmolol was shown to be both safe and effective without inducing low output syndrome

Possible Role of −374T/A Polymorphism of RAGE Gene in Longevity

Demographic and social changes in the last decades have resulted in improvements in health and longevity. The survival of elderly people has improved significantly and thus centenarians are becoming the fastest growing population group. Environmental, genetic, and accidental factors have influenced the human life span. Researchers have gained substantial evidence that advanced glycation end products may play an important role in the processes of physiological aging. The aim of the present study was to investigate any differences in the frequencies of −374T/A polymorphism in subjects aged &gt;90 years and in middle-aged individuals. We observed association between the A allele and genotype homozygous for this allele (AA) with a longer life expectancy in the male population. In particular, there was a prevalence of AA genotype and A allele in long-living subjects and a prevalence of the allele T in middle-aged subjects, indicating a possible protective role of the allele A to aging. In conclusion, our results support the hypothesis that longevity is the result of a good functioning of the immune system and a presumable hyper-expression of variants of anti-inflammatory genes of immunity. The differences in the genetic regulation of inflammatory processes may influence the presence of age-related disorders

Cardiovascular risk factors and Sympatho-Vagal balance: Importance of time-domain heart rate variability

bjective: Cardiovascular Disease (CVD) is the leading cause of death and disability worldwide. Dysregulation of the autonomic nervous system associated with various pathological conditions often occurs in presence of cardiovascular risk factors. Heart Rate Variability (HRV) may be used to assess autonomic imbalances. The aim of our study is to evaluate the correlation between HRV and the main cardiovascular risk factors in subject who underwent digital ambulatory 24 hours Holter ECG monitoring for clinical investigations. Methods: We evaluated time domain parameters of HRV by Holter ECG monitoring in a large population categorized based on the presence or absence of the major cardiovascular risk factors. Results: We found significant differences in time domain parameters of HRV in patients with and without common risk factor for CVD such as diabetes, family history for Coronary Artery Disease and dyslipidemia. We also analyzed our study population based on age and we found a positive correlation with the standard deviation of all NN intervals (SDNN), square root of the mean of the sum of the square of the differences between adjacent NN intervals (RMSSD), mean R-R intervals and by the number of adjacent NN intervals differing by more than 50 ms divided by the total number of all NN intervals (pNN50) and an inverse correlation for the others parameters. Conclusion: Non-modifiable risk factors (age, gender, family history) along with dyslipidemia and diabetes, are related to a change in HRV, while modifiable risk factors (smoking, hypertension, overweight, hyperhomocysteinemia) showed no correlation. This would seem to indicate that the genetic components more than lifestyle habits and behavior act on the nervous control of the heart. Our study shows the possibility to find interesting clinical-prognostic data, analyzing simple parameters obtained from instrumental methods of investigation performed for other clinical reasons

Time-domain heart rate variability in coronary artery disease patients affected by thyroid dysfunction

Subclinical hypothyroidism and hyperthyroidism have been recognized as clinical entities with negative effects on the cardiovascular system. Moreover, the effect of treated thyroid dysfunction on parameters associated with the cardiovascular control system has been poorly investigated. In the present study we analyzed time-domain heart rate variability in coronary artery disease (CAD) patients with known thyroid diseases. Twenty-four hour ECG monitoring was performed in 344 patients with coronary artery disease (174 with thyroid dysfunction and 170 without thyroid dysfunction used as a control group), using a 3-channel tape recorder. Time domain parameters of heart rate variability (HRV) were definitely lower both in patients with subclinical hypothyroidism and subclinical hyperthyroidism than in the control group, with statistically significant differences in SDNN, RMSSD, TINN, and mean RR for both subgroups. Furthermore, patients on L-thyroxine treatment and restored euthyroidism had generally higher HRV values than patients with subclinical hypothyroidism, nevertheless SDNN, RMSSD, SDNN index, TINN, and mean RR were significantly lower when compared to those of the control group. Significant differences in HRV were also found between hyperthyroid patients under treatment and control group subjects with respect to RMSSD, TINN, and mean RR values. In conclusion, patients with cardiac disease and known thyroid disease, even when the disease is in the subclinical range or despite treatment, should be regarded as patients at additional risk conveyed by thyroid hormone disturbances

Plasma Levels of Soluble Receptor for Advanced Glycation End Products and Coronary Atherosclerosis: Possible Correlation with Clinical Presentation

Receptor for Advanced Glycation End-products (RAGE) is a multi-ligand receptor ubiquitous present on epithelial, neuronal, vascular and inflammatory cells, usually expressed at low levels in homeostasis and to increased degrees at sites of stress or injury. The aim of the present study was to evaluate sRAGE plasma levels in patients with Acute Coronary Syndrome (ACS) and to assess its diagnostic efficacy in identification of patients with acute events. Plasma levels of sRAGE were determined in 860 patients with Coronary Artery Disease (CAD): 530 patients presented stable angina and 330 were observed during acute ischemic event (147 with unstable angina and 183 with myocardial infarction). sRAGE plasma levels were significantly lower in patients with ACS than in patients with stable angina: [median 584 pg/mL (IQR: 266–851 pg/mL) in MI patients, median 769 pg/mL (IQR: 394–987 pg/mL) in patients with unstable angina, median 834 pg/mL (IQR 630–1005 pg/mL) in patients with stable angina; P<0.001]. sRAGE levels did not differ among ACS patients stratified by the extent of coronary artery disease. In conclusion, this study confirm the role of sRAGE in activation and progression of inflammatory process and suggests the possibility that sRAGE can be considered an indicator of destabilization of vulnerable plaque

Studio dei polimorfismi nel gene del recettore dell’apelina in pazienti con e senza ipertensione arteriosa

Apelina è un peptide endogeno che aumenta l’inotropismo cardiaco attraverso l’interazione con il suo recettore APJ. Alcuni risultati indicano che il sistema apelinergico possa avere un ruolo fisiopatologico nell’ambito delle malattie cardiovascolari e ci sono prove che mostrano il ruolo del sistema apelinergico nella regolazione della pressione sanguigna in vitro e in modelli animali. Il ruolo di apelina-APJ nella fisiologia del sistema cardiovascolare e la sua interazione con altri processi neuroendocrini non è stato completamente chiarito. Tuttavia, gli studi riportati indicano che la trasmissione del segnale mediata da apelina possa essere coinvolta nella regolazione della pressione arteriosa, funzione contrattile cardiaca, bilancio idrico, l’angiogenesi e l’inibizione dell’apoptosi. Abbiamo valutato la possibile relazione tra i polimorfismi G212A e A445C di APJ e la presenza di malattia coronarica (CAD) in pazienti italiani e nei controlli sani mediante RFLP-PCR. Abbiamo analizzato le frequenze alleliche e genotipiche dei polimorfismi APJ in 664 pazienti (378 con ipertensione) e 143 controlli. Non c’erano differenze tra le frequenze alleliche e genotipiche nei pazienti rispetto ai controlli per entrambi i polimorfismi analizzati. Nella popolazione CAD abbiamo osservato un aumento della frequenza dell’allele G212 nei pazienti con ipertensione rispetto ai pazienti senza ipertensione. Nessuna differenza è stata invece evidenziata nei due sottogruppi per il polimorfismo A445C. Anche se il ruolo funzionale del polimorfismo G212A non è stato ancora identificato, è possibile ipotizzare che la presenza dell’allele A sia in grado di causare un aumento nella funzione del sistema apelina/APJ associato ad un minor rischio di ipertensione arteriosa (IA)