Causal effect between total cholesterol and HDL cholesterol as risk factors for chronic kidney disease: a mendelian randomization study.

BACKGROUND: While observational studies show an association between serum lipid levels and cardiovascular disease (CVD), intervention studies that examine the preventive effects of serum lipid levels on the development of CKD are lacking. METHODS: To estimate the role of serum lipid levels in the etiology of CKD, we conducted a two-sample mendelian randomization (MR) study on serum lipid levels. Single nucleotide polymorphisms (SNPs), which were significantly associated genome-wide with serum lipid levels from the GLGC and CKDGen consortium genome-wide association study (GWAS), including total cholesterol (TC, n = 187,365), triglyceride (TG, n = 177,861), HDL cholesterol (HDL-C, n = 187,167), LDL cholesterol (LDL-C, n = 173,082), apolipoprotein A1 (ApoA1, n = 20,687), apolipoprotein B (ApoB, n = 20,690) and CKD (n = 117,165), were used as instrumental variables. None of the lipid-related SNPs was associated with CKD (all P > 0.05). RESULTS: MR analysis genetically predicted the causal effect between TC/HDL-C and CKD. The odds ratio (OR) and 95% confidence interval (CI) of TC within CKD was 0.756 (0.579 to 0.933) (P = 0.002), and HDL-C was 0.85 (0.687 to 1.012) (P = 0.049). No causal effects between TG, LDL-C- ApoA1, ApoB and CKD were observed. Sensitivity analyses confirmed that TC and HDL-C were significantly associated with CKD. CONCLUSIONS: The findings from this MR study indicate causal effects between TC, HDL-C and CKD. Decreased TC and elevated HDL-C may reduce the incidence of CKD but need to be further confirmed by using a genetic and environmental approach.

Weighted gene coexpression network analysis identifies the key role associated with acute coronary syndrome.

The present study sought to identify potential hub genes and pathways of acute coronary syndrome (ACS). We downloaded the dataset (GSE56045) from the Gene Expression Omnibus (GEO) database and analyzed weighted gene coexpression networks (WGCNA). Gene Ontology annotation, Disease Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using R software. The protein-protein interaction (PPI) network was constructed using Cytoscape, and the Molecular Complex Detection app was employed to identify significant modules and hub genes. The hub genes were then validated in other microarrays and patients by RT-PCR. Two modules were identified and associated with coronary artery disease (CAD) and included 219 genes. After function and PPI analyses, 24 genes were identified to be potentially associated with CAD. Linear correlation was performed to calculate the relationship between the gene expression levels and coronary artery calcification score and found that CCR7 (R = -0.081, P = 0.0065), CD2 (R = -0.075, P = 0.0012), CXCR5 (R = -0.065, P = 0.029) and IL7R (R = -0.06, P = 0.043) should be validated in other dataset. By comparing the gene expression levels in different groups in GSE23561, GSE34822, GSE59867, GSE60993 and GSE129935, only two genes (CCR7 and CXCR5) showed significance. The nomogram showed that CXCR5 showed the risk of ACS. Further analysis in chest patients found CXCR5 played a key role resulting in ACS. Our WGCNA analysis identified CXCR5 as a risk factor for ACS, and the potential pathogenesis may be associated with immune inflammation.

Integrated Weighted Gene Co-expression Network Analysis Identified That TLR2 and CD40 Are Related to Coronary Artery Disease.

The current research attempted to identify possible hub genes and pathways of coronary artery disease (CAD) and to detect the possible mechanisms. Array data from GSE90074 were downloaded from the Gene Expression Omnibus (GEO) database. Integrated weighted gene co-expression network analysis (WGCNA) was performed to analyze the gene module and clinical characteristics. Gene Ontology annotation (GO), Disease Ontology (DO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by clusterProfiler and the DOSE package in R. A protein-protein interaction (PPI) network was established using Cytoscape software, and significant modules were analyzed using Molecular Complex Detection (MCODE) to identify hub genes. Then, further functional validation of hub genes in other microarrays and population samples was performed, and survival analysis was performed to investigate the prognosis. A total of 660 genes were located in three modules and associated with CAD. GO functions identified 484 biological processes, 39 cellular components, and 22 molecular functions with an adjusted P < 0.05. In total, 38 pathways were enriched in KEGG pathway analysis, and 147 DO items were identified with an adjusted P < 0.05 (false discovery rate, FDR set at < 0.05). There was a total of four modules with a score > 10 after PPI network analysis using the MCODE app, and two hub genes (TLR2 and CD14) were identified. Then, we validated the information from the GSE60993 dataset using the GSE59867 dataset and population samples, and we found that these two genes were associated with plaque vulnerability. These two genes varied at different time points after myocardial infarction, and both of them had the lowest prognosis of heart failure when they were expressed at low levels. We performed an integrated WGCNA and validated that TLR2 and CD14 were closely associated with the severity of coronary artery disease, plaque instability and the prognosis of heart failure after myocardial infarction.

Dilator method and needle method for atrial transseptal puncture: a retrospective study from a cohort of 4443 patients.

AIMS: To compare the safety and efficacy of a new dilator method vs the traditional needle method for transseptal puncture (TSP) in a large cohort study. METHODS AND RESULTS: From February 1995 to December 2010, 4443 consecutive patients undergoing TSP done either by a needle method or by a new dilator method were reviewed retrospectively. Data as procedure-related time and complications were evaluated. For the standard needle method, TSP was performed by extending out the needle. In comparison, for the new dilator technique, TSP was performed without an outer sheath and with the needle kept within the dilator; the blunt tip of the dilator was used to help locating the position of the fossa ovalis on purpose. Transseptal puncture was performed by the new dilator method in 2151 patients (48.4%) and by the traditional needle method in 2292 patients (51.6%). The average TSP time needed by the dilator method was longer than that needed by the needle method (5.6 ± 3.9 vs. 3.8 ± 2.9 min, P< 0.05). Additional left atrial angiography was required in seven (0.33%) patients for the dilator and in 39 patients (1.70%) for the needle method (P< 0.05). The total rate of severe complications and obvious TSP-related complications was significantly lower in patients who underwent the dilator method than in those who underwent the needle method (0.33 vs. 1.18%, and 0.20 vs. 1.00%, respectively, P < 0.05). CONCLUSION: Our data suggest that the new dilator technique is much safer than that of the standard needle method. It needs relatively longer procedure time but results in significantly fewer episodes of severe complications. Particularly, the blunt tip of the dilator can be used to help locate the fossa ovalis. Therefore, the new dilator technique might be a better choice for relatively less-experienced operators.