Sabino Carbotta

A multicentre, randomized study of telmisartan versus carvedilol for prevention of atrial fibrillation recurrence in hypertensive patients

Introduction: Atrial remodelling, leading to atrial fibrillation (AF), is mediated by the renin–angiotensin–aldosterone system. Methods: Mild hypertensive outpatients (systolic/diastolic blood pressure 140–159/90–99 mmHg) in sinus rhythm who had experienced ≥ 1 electrocardiogram (ECG)-documented AF episode in the previous six months received randomly telmisartan 80 mg/day or carvedilol 25 mg/day. Blood pressure and 24-hour ECG were monitored monthly for one year; patients were asked to report symptomatic AF episodes and to undergo an ECG as early as possible. Results: One hundred and thirty-two patients completed the study (telmisartan, n=70; carvedilol, n=62). Significantly fewer AF episodes were reported with telmisartan versus carvedilol (14.3% vs. 37.1%; p<0.003). Left atrial diameter, assessed by echocardiography, was similar with telmisartan and carvedilol (3.4±2.3 cm vs. 3.6±2.4 cm). At study end, both regimes significantly reduced mean left ventricular mass index, but the reduction obtained with telmisartan was significantly greater than with carvedilol (117.8±10.7 vs. 124.7±14.5; p<0.0001). Mean blood pressure values were not significantly different between the groups (telmisartan 154/97 to 123/75 mmHg; p<0.001; carvedilol 153/94 to 125/78 mmHg; p<0.001). Conclusions: Telmisartan was significantly more effective than carvedilol in preventing recurrent AF episodes in hypertensive AF patients, despite a similar lowering of blood pressure.

Is Carotid Stenosis in Women a Gender-Related Condition?

BACKGROUND We set out to study, through ultrasound examinations, the carotid bifurcation in men and women with/without carotid stenosis to look for anatomical and electrophysiologic differences. We evaluated other variables to look for differences that might explain the dissimilar behavior of this disease in the two sexes and the presence and impact of risk factors. METHODS We examined 974 subjects aged 25 to 88 years (478 men and 496 women) in whom we considered heart rate, smoking status, and the presence of hypertension, diabetes, hypercholesterolemia, and hypertriglyceridemia. Ultrasound examination of the neck vessels included measurement of intimal medial thickness (IMT), vessel diameter, and outflow area/inflow area ratio. We established plaque location, echogenicity and echostructure, and the percentage of stenosis owing to plaque and measured systolic velocity, flow direction, and the depth of detection of these parameters. We used the apnea and hyperpnea test to assess cerebrovascular reactivity. RESULTS Hypertension and hypercholesterolemia were the most frequent risk factors. Women had a higher heart rate, whereas men had significantly greater IMT. The presence of atheromatous plaque was significantly correlated with age in both sexes, with men having a higher prevalence of carotid plaques. The sexes differed significantly with regard to plaque location, echogenicity, echostructure, and intracranial circulation. Women had a slightly higher blood flow velocity in the intracranial arteries. Risk factors affected plaque formation and extent more in men than in women. CONCLUSIONS These findings suggest that carotid stenosis is a gender-related trait.

Thyroid autoantibodies and breast cancer

We read with great interest the recent article by Shi and colleagues (2014) reporting a meta-analysis on the relationship between thyroid hormones, thyroid autoantibodies and breast cancer. In the paper, the authors analyzed eight different cross-sectional studies, which included more than 4000 participants, and concluded that serum levels of free-triiodothyronine, thyroperoxidase and thyroglobulin autoantibodies are higher in patients affected by breast cancer, compared with the control group. These findings are well in agreement with the meta-analysis reported by Hardefeldt and colleagues, showing an increased risk of breast cancer in patients with autoimmune thyroid disease, and with a recent article by our group in which the prevalence of breast cancer in 3921 female patients affected by both benign and malignant thyroid diseases was evaluated (Hardefeldt et al., 2012; Prinzi et al., 2014). In the latter, we showed that the prevalence of breast cancer in patients affected by thyroid disease, as a whole, was significantly higher, compared to the general population (OR 3.3). Moreover, the agematched analysis showed that the risk of breast cancer was higher in younger patients (0–44 yr, OR 15.2), to decline with the increasing age. In the same study, when patients were dichotomized based on the presence or the absence of thyroglobulin and/or thyroperoxidase autoantibodies, both groups showed a higher risk of breast cancer, compared to the general female population. When the two groups were compared to each other, however, the risk of breast cancer was significantly lower in autoantibody positive patients. Thus, as clearly stated in our article, among patients affected by thyroid diseases, the presence of thyroid autoantibodies may have a protective role against breast cancer (Prinzi et al., 2014). As a consequence, the sentence reported by Shi and colleagues in the Discussion section of their article stating that their findings are in disagreement with our data is not correct and should be, if at all possible, amended.

IRE1α deficiency promotes tumor cell death and eIF2α degradation through PERK dipendent autophagy

Sensors of endoplasmic reticulum (ER) stress function in a co-ordinated manner. In the present study we investigated the relationship between IRE1α and PERK pathways and survival of ER stressed U937 cells and BC3 cells. To this end, we investigated the effects of a subcytotoxic concentration of Tunicamycin in IRE1α-proficient and in IRE1α-deficient cells, by pharmacological inhibition with 4μ8 C or down-regulation by specific siRNA. We show that either type of IRE1α deficiency affects eIF2α expression and causes cell death increase. GSK2606414, a PERK inhibitor, and PERK specific siRNA prevent eIF2α down-regulation and restore cell survival. Degradation of this protein is due to autophagy, as it is prevented by bafilomycin and not by proteasome inhibition. Furthermore, activation of the autophagy flux is PERK dependent. Also the Cathepsin B inhibitor CA074 prevents eIF2α from degradation and reduces cell death. Altogether, these results show that IRE1α deficiency in ER stressed cells leads to an unexpected decrease of eIF2α, an important molecule for protein translation, through PERK dependent autophagy. Thus, IRE1/XBP1 inhibitors may represent a feasible strategy for tumor therapy, while PERK inhibitors may vanish the goal.

Correction to: IRE1α deficiency promotes tumor cell death and eIF2α degradation through PERK-dependent autophagy

Following publication of the article, author Elisabetta Ferretti asked for the following institution to be added to her affiliation: