National Cholesterol Education Panel ΙΙΙ Guidelines Performance Role in Preventing Myocardial Infarction in a Large Cohort Without a History of Coronary Artery Disease: Korea Acute Myocardial Infarction Registry Study

The Third Report of the Adult Treatment Panel National Cholesterol Education Program (NCEP-ATPIII) guidelines are widely used for the primary prevention of a coronary event. These guidelines were developed using experimental data from studies that enrolled mostly Caucasian patients. The pathogenesis of atherosclerosis varies with ethnicity. Given these two circumstances, the authors sought to investigate the performance of the guidelines in a large Asian cohort. The Korea Acute Myocardial Infarction Registry (KAMIR) includes data collected between November 2005 and December 2006 from 41 referral centers in South Korea. A retrospective review of the clinical data was performed. After patients with a history of coronary heart disease (CHD), CHD equivalent, and those taking lipid-lowering medications were excluded, 2969 individuals (76% men; 61±12 years) were enrolled. The recommendations for lipid-lowering treatments according to the NCEP-ATPΙΙΙ were examined in the context of the cohort. A total of 38%, 66%, and 8% of the study participants had hypertension, were smokers, and had a family history of premature CHD, respectively. When patients were stratified by the number of risk factors present and their 10-year CHD risk, 69% diagnosed with an acute myocardial infarction did not qualify for drug therapy. Irrespective of the age group examined (young, intermediate, and old), the percentage of patients who did not qualify for a lipid-lowering pharmacologic intervention was higher than 60%. NCEP-ATPIII underestimates CHD risk in individuals of Asian descent. Further studies are needed to improve primary CHD prevention in this patient population.     

Caspases‐2 and ‐8 are involved in the presenilin1/γ‐secretase‐dependent cleavage of amyloid precursor protein after the induction of apoptosis

The presenilin/γ‐secretase protease cleaves many type‐I membrane proteins, including the amyloid β‐protein (Aβ) precursor (APP). Previous studies have shown that apoptosis induces alterations in Aβ production in a caspase‐dependent manner. Here, we report that staurosporine (STS)‐induced apoptosis induces caspase‐8 and/or‐2‐dependent γ‐secretase activation. Blocking of caspase activity with caspase‐8 inhibitor z‐IETD‐fmk, and caspase‐2 inhibitor z‐VDVAD‐fmk reduced Aβ production by STS in H4 cells expressing the Swedish mutant of APP (HSW) or APP‐C99 (H4‐C99). There was no inhibitory effect of other caspases (‐1, ‐3, ‐5, ‐6, ‐9) on Aβ production by STS. This finding was further supported by evidence that siRNA transfection, depleting caspase‐2 or ‐8 levels, lowered Aβ production in HSW and H4‐C99 cells without affecting expression of APP or γ‐secretase complex. In addition, Aβ production by STS was decreased by JNK inhibitors, SP600125. These results suggest that caspase‐2 and/or ‐8 is involved in presenilin/γ‐secretase activation and Aβ production in apoptosis. © 2010 Wiley‐Liss, Inc.     

Treatment with Selective Serotonin Reuptake Inhibitors and Mirtapazine Results in Differential Brain Activation by Visual Erotic Stimuli in Patients with Major Depressive Disorder

Objective

The objective of this study was to identify patterns of brain activation elicited by erotic visual stimuli in patients treated with either Selective Serotonin Reuptake Inhibitors (SSRIs) or mirtazipine.

Methods

Nine middle-aged men with major depressive disorder treated with an SSRI and ten middle-aged men with major depressive disorder treated with mirtazapine completed the trial. Ten subjects with no psychiatric illness were included as a control group. We conducted functional brain magnetic resonance imaging (fMRI) while a film alternatively played erotic and non-erotic contents for 14 minutes and 9 seconds.

Results

The control group showed activation in the occipitotemporal area, anterior cingulate gyrus, insula, orbitofrontal cortex, and caudate nucleus. For subjects treated with SSRIs, the intensity of activity in these regions was much lower compared to the control group. Intensity of activation in the group treated with mirtazapine was less than the control group but grea-ter than those treated with SSRIs. Using subtraction analysis, the SSRI group showed significantly lower activation than the mirtazapine group in the anterior cingulate gyrus and the caudate nucleus.

Conclusion

Our study suggests that the different rates of sexual side effects between the patients in the SSRI-treated group and the mirtazapine-treated group may be due to different effects on brain activation.     

Associations of dialysis modality and infectious mortality in incident dialysis patients in Australia and New Zealand

BACKGROUND: The aim of the present investigation is to compare rates, types, causes, and timing of infectious death in incident peritoneal dialysis (PD) and hemodialysis (HD) patients in Australia and New Zealand. STUDY DESIGN: Observational cohort study using the Australian and New Zealand Dialysis and Transplant Registry data. SETTING & PARTICIPANTS: The study included all patients starting dialysis therapy between April 1, 1995, and December 31, 2005. PREDICTOR: Dialysis modality. OUTCOMES & MEASUREMENTS: Rates of and time to infectious death were compared by using Poisson regression, Kaplan-Meier, and competing risks multivariate Cox proportional hazards model analyses. RESULTS: 21,935 patients started dialysis therapy (first treatment PD, n = 6,020; HD, n = 15,915) during the study period, and 1,163 patients (5.1%) died of infectious causes (PD, 529 patients; 7.6% versus HD, 634 patients; 4.2%). Incidence rates of infectious mortality in PD and HD patients were 2.8 and 1.7/100 patient-years, respectively (incidence rate ratio PD versus HD, 1.66; 95% confidence interval [CI], 1.47 to 1.86). After performing competing risks multivariate Cox analyses allowing for an interaction between time on study and modality because of identified nonproportionality of hazards, PD consistently was associated with increased hazard of death from infection compared with HD after 6 months of treatment (<6 months hazard ratio [HR], 1.08; 95% CI, 0.76 to 1.54; 6 months to 2 years HR, 1.31; 95% CI, 1.09 to 1.59; 2 to 6 years HR, 1.51; 95% CI, 1.26 to 1.80; >6 years HR, 2.76; 95% CI, 1.76 to 4.33). This increased risk of infectious death in PD patients was largely accounted for by an increased risk of death caused by bacterial or fungal peritonitis. LIMITATIONS: Patients were not randomly assigned to their initial dialysis modality. Residual confounding and coding bias could not be excluded. CONCLUSIONS: Dialysis modality selection significantly influences risks, types, causes, and timing of fatal infections experienced by patients with end-stage kidney disease in Australia and New Zealand.     

Influence of age and visceral fat area on plasma adiponectin concentrations in women with normal glucose tolerance

BACKGROUND: Age-related adiponectin concentration has been discrepantly reported. We investigated the distribution of adiponectin by age in healthy women with normal glucose tolerance (NGT) and the relationship of adiponectin with visceral fat area (VFA). METHODS: Three-hundred fifty-nine women (age: 38+/-0.6 years, BMI: 26.5+/-0.2 kg/m(2)) were categorized into 4 age-groups: 20-29, 30-39, 40-49, and 50-64 years. Computed tomography was performed to measure abdominal fat area and adiponectin, TNF-alpha, interleukin-6 (IL-6), CRP, insulin, free fatty acid (FFA), and blood urea nitrogen (BUN) were determined. RESULTS: No significant differences were observed in BMI, total body fat percent and concentrations of insulin, IL-6 and CRP among age-groups. Waist circumference, total fat area at L4, and FFA were significantly higher only in postmenopausal women than in previous decades of premenopausal women. VFA, adiponectin and TNF-alpha concentrations are significantly higher in older women than in younger women. Higher adiponectin concentration in older women was clearly shown even after adjustment for VFA (P<0.05). Age per se was positively correlated with plasma adiponectin concentrations (r=0.21, P<0.001) and these relationship became stronger (r=0.36, P<0.001) after controlled for VFA. VFA was negatively correlated with adiponectin (r=-0.16, P<0.01) in total studied population. However, when analyzed subgroups separately, a strong negative correlation (r=-0.37, P<0.001) was found in younger women (<40 years), while a weak significant relationship (r=-0.18, P<0.05) was found in older women (> or =40 years). In a multiple stepwise regression model to predict adiponectin, only age and VFA remained in the model at P<0.001. CONCLUSIONS: We observed a significant positive relationship between plasma adiponectin and age, even after adjustment for visceral adiposity. These associations suggest that adiponectin concentrations are affected by visceral adiposity, with additional independent effects of age.