Raloxifene Lowers Plasma Lipoprotein(a) Concentrations: a Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials

Background and Aims

Lipoprotein(a) (Lp(a)) is a proatherogenic plasma lipoprotein and an independent risk factor for atherosclerotic cardiovascular disease. We investigated the effects of raloxifene, selective estrogen receptor modulator, on circulating Lp(a) levels in postmenopausal women using a systematic review and meta-analysis of randomized controlled trials (RCTs).

Methods

To identify relevant studies, electronic databases (PUBMED, Scopus, Web of Science, and Google Scholar) were searched by up to May 2015 to find controlled trials exploring the effects of oral raloxifene treatment on plasma Lp(a) levels in postmenopausal women. A random-effects model and generic inverse variance method were used for quantitative data synthesis.

Results

Overall, seven eligible RCTs with ten treatment arms were included in this meta-analysis. Meta-analysis suggested a significant reduction of Lp(a) levels after treatment with raloxifene (standardized mean difference (SMD) ?0.42; 95% CI ?0.65, ?0.19; p?<?0.001), which may be considered as a medium effect size. When the studies were categorized according to the administered dose, there was a significant effect in both subsets of studies with administered doses ≤60 mg/day (SMD ?0.43; 95% CI ?0.73, ?0.13; p?=?0.004) and >60 mg/day (SMD ?0.36; 95% CI ?0.68, ?0.05; p?=?0.025). No significant association between the changes in plasma concentrations of Lp(a) with dose and baseline Lp(a) levels was found in the random-effects meta-regression analysis. However, a significant inverse association was observed between the Lp(a)-lowering effect of raloxifene and duration of treatment (p?=?0.001).

Conclusions

Results of the present meta-analysis showed a reduction in plasma Lp(a) concentrations of postmenopausal women with oral raloxifene treatment.

     

Serum zinc and copper status in Iranian patients with pemphigus vulgaris

Background The role of nutritional factors including trace elements has been reported in the pathogenesis of many autoimmune diseases. Objective Regarding the relatively high prevalence of pemphigus vulgaris in Iran, we investigated the serum levels of zinc and copper as two important trace elements, together with the oxidative stress status in patients with pemphigus vulgaris. Materials and methods This case‐control study was performed on 25 patients with newly diagnosed pemphigus vulgaris and 25 age‐ and sex‐matched healthy control subjects. Serum concentrations of zinc, copper, ceruloplasmin as well as copper/zinc ratio were determined for each subject. Oxidative stress was also measured using a novel assay of peroxidant‐antioxidant balance (PAB). Results Mean serum concentrations of zinc and copper as well as copper/zinc ratio were significantly lower in patients (mean age: 47.2 ± 16.2 years; male/female: 14/11) compared with the controls (mean age: 47.3 ± 12.8 years; male/female: 14/11; P < 0.001). In contrast, PAB values were significantly elevated in patients compared with controls (P < 0.01). No significant difference in serum ceruloplasmin concentrations was observed between the groups (P > 0.05). Conclusion Our findings indicate that low serum zinc and copper and increased oxidative stress may be associated with pemphigus vulgaris.     

Cerebral sex dimorphism and sexual orientation

The neurobiology of sexual orientation is frequently discussed in terms of cerebral sex dimorphism (defining both functional and structural sex differences). Yet, the information about possible cerebral differences between sex‐matched homo and heterosexual persons is limited, particularly among women. In this multimodal MRI study, we addressed these issues by investigating possible cerebral differences between homo and heterosexual persons, and by asking whether there is any sex difference in this aspect. Measurements of cortical thickness (Cth), subcortical volumes, and functional and structural resting‐state connections among 40 heterosexual males (HeM) and 40 heterosexual females (HeF) were compared with those of 30 homosexual males (HoM) and 30 homosexual females (HoF). Congruent with previous reports, sex differences were detected in heterosexual controls with regard to fractional anisotropy (FA), Cth, and several subcortical volumes. Homosexual groups did not display any sex differences in FA values. Furthermore, their functional connectivity was significantly less pronounced in the mesial prefrontal and precuneus regions. In these two particular regions, HoM also displayed thicker cerebral cortex than other groups, whereas HoF did not differ from HeF. In addition, in HoM the parietal Cth showed “sex‐reversed” values, not observed in HoF. Homosexual orientation seems associated with a less pronounced sexual differentiation of white matter tracts and a less pronounced functional connectivity of the self‐referential networks compared to heterosexual orientation. Analyses of Cth suggest that male and female homosexuality are not simple analogues of each other and that differences from heterosexual controls are more pronounced in HoM.     

Curcuminoids Modulate Pro‐Oxidant–Antioxidant Balance but not the Immune Response to Heat Shock Protein 27 and Oxidized LDL in Obese Individuals

Curcuminoids have potentially important functional qualities including anti‐inflammatory and antioxidant properties. In this randomized double‐blind placebo‐controlled cross‐over trial, the effects of a curcuminoid supplement on serum pro‐oxidant–antioxidant balance (PAB) and antibody titres to Hsp27 (anti‐Hsp27) and oxLDL (anti‐oxLDL) were investigated. Thirty obese individuals were randomized to receive either curcuminoids (1 g/day) or placebo for a period of 30 days. After a wash‐out period of 2 weeks, subjects were crossed over to the alternate regimen for another 30 days. Serum PAB along with anti‐Hsp27 and anti‐oxLDL titres was measured at the beginning and at the end of each study period. There was no significant carry‐over effect for any of the assessed parameters. Curcuminoid supplementation was associated with a significant decrease in PAB (p = 0.044). However, no significant change was observed in serum concentrations of anti‐Hsp27 or anti‐oxLDL (p > 0.05). These findings suggest that oral curcuminoids supplementation (1g/day) is effective in reducing oxidative stress burden, though this needs to be validated in larger study populations. Copyright © 2013 John Wiley & Sons, Ltd.     

Changes in plasma level of heat shock protein 27 after acute coronary syndrome

We assessed the association between serum heat shock protein 27 (Hsp-27)concentrations in patients with acute coronary syndrome (ACS) and compared them with healthy participants. Patients with ACS (n = 75) were recruited and their biochemical parameters were compared with 75 healthy participants. Heat shock protein 27 concentrations were measured from blood samples taken on admission and 12 hours after the onset of chest pain. In the patient group, Hsp-27 concentrations (31.62 [20.12-38.51] ng/mL) in the first blood samples were significantly (P < .001) higher than in control samples (20.12 [16.67-28.17] ng/mL). In patients, serum Hsp-27 levels on admission were significantly (P < .001) higher than for the samples collected 12 hours after the onset of chest pain (25.87 [15.52-31.62]); the latter did not differ significantly from samples of healthy controls. In conclusion, serum Hsp-27 concentrations are elevated in the early hours following ACS, but fall to levels near to those in healthy individuals after about 12 hours from the onset of chest pain.     

Malondialdehyde-Modified LDL IgG Antibody Levels and Indices of Cardiac Function in Valvular Heart and Coronary Artery Disease Patients

Objective

To compare the changes in anti-malondialdehyde-modified low-density lipoprotein (MDA-LDL) IgG levels among patients undergoing off-pump and on-pump coronary artery bypass grafting (CABG) or valvuloplasty.

Subjects and Methods

A total of 38, 39 and 34 patients who underwent off-pump CABG, on-pump CABG and valvuloplasty, respectively, were enrolled in this study. Serum anti-MDA-LDL IgG values were measured 24 h before and after the operative procedures and at discharge. Echocardiography was also done before surgery and before discharge. The results were compared with values from 50 healthy controls.

Results

In all patients, a reduction in antibody titers was observed post-operatively. However, the decrease was significant only in the off-pump CABG–before surgery: 42.33 (25.83–58.51), after surgery: 30.86 (16.36–51.33) and at discharge: 10.96 (6.82–23.57; p = 0.027). There was a significant positive association between anti-MDA-LDL IgG levels and ejection fraction (r = 0.248, p = 0.036) and a negative association with E/E'', a marker of pulmonary capillary wedge pressure, in the coronary patients (r = −0.345, p = 0.012), but no significant associations were found in patients with valvular heart disease.

Conclusions

Serum anti-MDA-LDL IgG levels were associated with cardiac function indices in coronary patients undergoing CABG.Key Words: Anti-malondialdehyde-modified low-density lipoprotein, Valvular heart disease, Coronary artery bypass grafting, Cardiac function     

A cross-sectional study of the association between heat shock protein 27 antibody titers, pro-oxidant-antioxidant balance and metabolic syndrome in patients with angiographically-defined coronary artery disease

ObjectiveTo investigate the association between serum antibody titers to Hsp27 (anti-Hsp27) and pro-oxidant–antioxidant balance (PAB) in patients with angiographically-defined coronary artery disease (CAD) with or without the metabolic syndrome (MS).DesignSubjects (n = 243) were classified into MS+ (n = 161) and MS? (n = 82) subgroups, based on the AHA/NHBLI criteria.ResultsSerum anti-Hsp27 titers were found to be significantly higher in the MS+ vs. MS? group. However, no significant difference was observed in serum PAB values. When assessed for individual components of MS, increased serum anti-Hsp27 was found to be higher in subgroups with elevated triglycerides, elevated blood pressure and reduced high-density lipoprotein cholesterol (HDL-C). Subgroups of patients with elevated triglycerides had higher PAB values. HDL-C was the only significant predictor of anti-Hsp27 in the population as a whole.ConclusionThe evidence from this investigation indicates the presence of elevated anti-Hsp27 in patients with concurrent CAD and MS compared to those with CAD alone.