Administration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death but not increased all-cause mortality.

Background and Purpose-Chronic kidney disease may increase the risk for ischemic stroke or systemic embolism in patients with nonvalular atrial fibrillation (AF). We conducted a meta-analysis to summarize all published studies to investigate the link between chronic kidney disease and risk of thromboembolic events in AF. Methods-We performed a literature search using MEDLINE (source PubMed, 1966 and EMBASE (1980 to July 2014) with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. Results-Eighteen studies involving 538 479 patients and 41 719 incident thromboembolic events were identified. From the pooled analysis, AF patients with estimated glomerular filtration rate <60 mL/min compared with those with estimated glomerular filtration rate ≥60 mL/min experienced a significantly increased risk for developing thromboembolic events (relative risk, 1.62 [95% confidence interval, 1.40-1.87; P<0.001]). The annual rate of thromboembolic events increased by 0.41% (95% confidence interval, 0.17%-0.65%) for a 10 mL/min decrease in renal function. Addition of renal impairment to CHADS 2 slightly improved the stroke risk stratification. Conclusions-Impaired renal function is an independent predictor of stroke or systemic embolism in patients with nonvalvular AF. Consideration of renal function may improve stroke risk stratification in patients with AF. (Stroke.

1. Increasing evidence indicates that hydrogen sulphide (H₂S) may serve as an important biological cytoprotective agent. Heat shock protein (Hsp) 90 can attenuate stress-induced injury. However, whether Hsp90 mediates the cytoprotective effect of H₂S against chemical hypoxia-induced injury in PC12 cells is not known. 2. In the present study, CoCl₂ (a chemical hypoxia mimetic) was used to treat PC12 cells to create a model of chemical hypoxia. To explore the role of Hsp90 in the cytoprotection afforded by H₂S against chemical hypoxia-induced injury, 2 μmol/L 17-allylaminogeldanamycin (17-AAG), a selective inhibitor of Hsp90, was administered for 30 min prior to preconditioning with 400 μmol/L NaHS, followed by chemical hypoxia. 3. Cobalt chloride reduced cell viability (by 52.7 ± 1.5%), increased PC12 cell apoptosis (by 42.1 ± 1.5%), induced reactive oxygen species (ROS) by 3.79% compared with control and induced the dissipation of mitochondrial membrane potential (MMP) by 2.56% compared with control. 4. Pretreatment of PC12 cells with 100-400 μmol/L sodium hydrosulphide (NaHS), an H₂S donor, for 3 h prior to exposure to 600 μmol/L CoCl₂ provided significant, concentration-dependant protection to PC12 cells against CoCl₂-induced cytotoxicity. Specifically, pretreatment of PC12 cells with 400 μmol/L NaHS decreased apoptosis to 16.77 ± 1.77% and blocked the CoCl₂-induced increase in ROS production and loss of MMP. 5. At 400 μmol/L, NaHS upregulated Hsp90 in a time-dependant manner (over the period 0-180 min). In addition to its effects on Hsp90 expression, NaHS pretreatment of PC12 cells augmented the overexpression of Hsp90 induced by 600 μmol/L CoCl₂ by 1.38-fold (P < 0.01). 6. Treatment of PC12 cells with 2 μmol/L 17-AAG for 30 min prior to NaHS pretreatment blocked the overexpression of Hsp90 induced by NaHS preconditioning, as evidenced by decreased cell viability (by 54.2 + 1.2%; P < 0.01), increased PC12 cell apoptosis (by 36.6 ± 1.2%; P < 0.01) and increasing ROS production. 7. The findings of the present study provide novel evidence that Hsp90 mediates H₂S-induced neuroprotection against chemical hypoxia-induced injury via anti-oxidant and anti-apoptotic effects.

Background Our understanding of the weight-outcome association mainly comes from single-time body mass index (BMI) measurement. However, data on long-term trajectories of within-person changes in BMI on diverse study outcomes are sparse. Therefore, t his study is to determine the associations of individual BMI trajectories and cardiovascular outcomes. Methods The present analysis was based on data from 4 large prospective cohorts and restricted to participants aged ≥45 years with at least two BMI measurements. Hazard ratios (HR) and 95% confidence intervals(95%CI) for each outcome according to different BMI trajectories were calculated in Cox regression models. Findings The final sample comprised 29,311 individuals (mean age 58.31 years, and 77.31% were white), with a median 4 BMI measurements used in this study. During a median follow-up of 21.16 years, there were a total of 10,192 major adverse cardiovascular events (MACE) and 11,589 deaths. A U-shaped relation was seen with all study outcomes. Compared with maintaining stable weight, the multivariate adjusted HR for MACE were 1.53 (95%CI 1.40–1.66), 1.26 (95%CI 1.16–1.37) and 1.08 (95%CI 1.02–1.15) respectively for rapid, moderate and slow weight loss; 1.01 (95%CI 0.95–1.07), 1.13 (95%CI 1.05–1.21) and 1.29 (95%CI 1.20–1.40) respectively for slow, moderate and rapid weight gain. Identical patterns of association were observed for all other outcomes. The development of BMI differed markedly between the outcome-free individuals and those who went on to experience adverse events, generally beginning to diverge 10 years before the occurrence of the events. Interpretation Our findings may signal an underlying high-risk population and inspire future studies on weight management. Funding National Natural Science Foundation of China, Guangdong Natural Science Foundation.

Aims/IntroductionAngiotensin‐(1–7) (Ang‐[1–7]), recognized as a new bioactive peptide in the renin–angiotensin system, shows biological and pharmacological properties in diabetic cardiovascular diseases. The leptin‐induced p38 mitogen‐activated protein kinase (MAPK) pathway has been reported to contribute to high glucose (HG)‐induced injury. In the present study, we showed the mechanism of how Ang‐(1–7) can protect against HG‐stimulated injuries in H9c2 cells.Materials and MethodsH9c2 cells were treated with 35 mmol/L glucose (HG) for 24 h to establish a model of HG‐induced damage. Apoptotic cells were observed by Hoechst 33258 staining. Cell viability was analyzed by cell counter kit‐8. The expression of protein was detected by western blot. Reactive oxygen species was tested by 2′,7′‐dichlorodihydrofluorescein diacetate staining. Mitochondrial membrane potential was measured by 5,5′,6,6′‐Tetrachloro‐1,1′,3,3′‐tetraethyl‐imidacarbocyanine iodide staining.ResultsThe present results showed that treating H9c2 cells with HG obviously enhanced the expressions of both the leptin and phosphorylated (p)‐MAPK pathway. However, the overexpression levels of leptin and p‐p38 MAPK/p‐extracellular signal‐regulated protein kinase 1/2 (ERK1/2), but not p‐c‐Jun N‐terminal kinase, were significantly suppressed by treatment of the cells with Ang‐(1–7). Additionally, leptin antagonist also markedly suppressed the overexpressions of p38 and ERK1/2 induced by HG, whereas leptin antagonist had no influence on the overexpression of c‐Jun N‐terminal kinase. More remarkable, Ang‐(1–7), leptin antagonist, SB203580 or SP600125, respectively, significantly inhibited the injuries induced by HG, such as the increased cell viability, decreased apoptotic rate, reduction of ROS production and increased mitochondrial membrane potential. Furthermore, the overexpressions of p38 MAPK, ERK1/2 and leptin were suppressed by N‐actyl‐L‐cystine.ConclusionsThe present findings show that Ang‐(1–7) protects from HG‐stimulated damage as an inhibitor of the reactive oxygen species–leptin–p38 MAPK/ERK1/2 pathways, but not the leptin–c‐Jun N‐terminal kinase pathway in vitro.