Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated.

The chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) have been recently much focused as independent risks for cardiovascular disease. Furthermore, the complication of both has a worse prognosis compared with patients with only one of these diseases. However, the details of the underlying mechanisms of this worsened prognosis have not been clear. The cross-sectional study was conducted to examine whether the overlap of COPD augment the increase in arterial stiffness in subjects with OSA. If so, we examined the exaggeration of nocturnal hypoxemia and its related inflammation are related to this augmentation of increased arterial stiffness. In 524 male subjects with OSA diagnosed by polysomnography (apnea-hypopnea index >5/h) (52 ± 14 years old), the forced expiratory volume at 1 s/the forced vital capacity (FEV(1)/FVC) ratio, brachial-ankle pulse wave velocity (baPWV), blood C-reactive protein (CRP) and B-natriuretic peptide (BNP) levels were measured. The prevalence rate of COPD was 12% in this study subjects. Plasma BNP levels and the crude (median value, 17.2 vs. 14.1 m/s, p < 0.01) and adjusted value of baPWV were significantly higher in subjects with overlap syndrome than in those with OSA alone. However, parameters of nocturnal hypoxemia and serum CRP levels were similar between both groups. Thus, the overlap of COPD in patients with OSA augments increase in arterial stiffness without the exaggeration of nocturnal hypoxemia and inflammation. Even so, this augmentation may partially contribute to the increased cardiovascular risk in the overlap syndrome.

Background Although 30‐day readmission is thought to be an important quality indicator in patients with hospitalized heart failure, its prognostic impact and comparison of patients who were readmitted beyond 30 days has not been investigated. We assessed early (0–30 days) versus midrange (31–90 days) readmission in terms of incidence and distribution, and elucidated whether the timing of readmission could have a different prognostic significance. Methods and Results We examined patients with hospitalized heart failure registered in the WET ‐ HF (West Tokyo Heart Failure) registry. The primary outcomes analyzed were all‐cause death and HF readmission. Data of 3592 consecutive patients with hospitalized heart failure (median follow‐up, 2.0 years [interquartile range, 0.8–3.1 years]; 39.6% women, mean age 73.9±13.3 years) were analyzed. Within 90 days after discharge, HF readmissions occurred in 11.1% patients. Of them, patients readmitted within 30 and 31 to 90 days after discharge accounted for 43.1% and 56.9%, respectively. Independent predictors of 30‐ and 90‐day readmission were almost identical, and after adjustment, readmission for HF within 90 days (including both early and midrange readmission) was an independent predictor of subsequent all‐cause death (hazard ratio, 2.36; P <0.001). Among 90‐day readmitted patients, the time interval from discharge to readmission was not significantly associated with subsequent all‐cause death. Conclusions Among patients readmitted within 90 days after index hospitalization discharge, ≈60% of readmission events occurred beyond 30 days. Patients readmitted within 90 days had a higher risk of long‐term mortality, regardless of the temporal proximity of readmission to the index hospitalization.

This study indicates that severe OSA independently increases serum cystatin C levels in patients without CKD. Cystatin C is considered to be a biomarker that reflects both clinically latent renal dysfunction and cardiovascular risk that are influenced by OSA.

Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular disease (CVD), particularly in the middle-aged population. However, the clinical importance of OSA as a risk for CVD in the elderly population remains controversial. Moreover, evidence for the effectiveness of continuous positive airway pressure (CPAP) treatment for the secondary prevention of CVD in elderly patients is lacking. We assessed whether CPAP treatment improves cardiovascular outcomes in elderly patients with OSA and CVD. In this retrospective cohort study, we enrolled 130 elderly patients aged 65-86 years with moderate to severe OSA (apnea-hypopnea index ≥15/h) and a history of hospitalization due to CVD, who underwent polysomnography between November 2004 and July 2011. Patients were divided into the CPAP group (n = 64) or untreated OSA group (n = 66). The main outcome measures were cardiovascular death and hospitalization due to CVD. During the mean follow-up period of 32.9 ± 23.8 (standard deviation) months, 28 (21.5 %) patients either died or were hospitalized. The Kaplan-Meier curves indicated that event-free survival was significantly lower in the untreated OSA group than in the CPAP group (P < 0.005). A multivariate analysis showed that the risk was significantly increased in the untreated OSA group (hazard ratio 5.13; 95 % confidence interval 1.01-42.0; P < 0.05). Moderate to severe OSA not treated with CPAP was an independent risk factor for relapse of a CVD event, and adequate CPAP treatment improved cardiovascular outcomes in elderly patients.

No abstract

Coexistent severe OSA and MS can exacerbate LV concentric hypertrophy. However, not only the coexistence of these two disorders, but also either severe OSA or MS can impair LV diastolic function.

During brain development, the design of primary neural networks is primarily determined by environmental stimuli after their formation. In particular, the juvenile period is critical, during which neuronal circuits that consist of both excitatory and inhibitory neurons are remodeled by experience. Social isolation during the juvenile period profoundly affects brain development and contributes to the development of psychiatric disorders. We previously reported that 2 weeks of social isolation after weaning reduced excitatory synaptic inputs and intrinsic excitability in a subtype of layer 5 pyramidal cells, which we defined as prominent h-current (PH) cells, in the medial prefrontal cortex (mPFC) in mice. However, it remains unclear how juvenile social isolation affects inhibitory neuronal circuits that consist of pyramidal cells and interneurons. We found that 2 weeks of social isolation after weaning increased inhibitory synaptic inputs exclusively onto PH cells with a concomitant deterioration of action potential properties. Although social isolation did not alter the inhibitory synaptic release mechanisms or the number of inhibitory functional synapses on PH cells, we found that it increased the intrinsic excitability of fast-spiking (FS) interneurons with less excitatory synaptic inputs and more h-current. Our findings indicate that juvenile social isolation enhances the activity of inhibitory neuronal circuits in the mPFC.