白民富
阜外华中心血管病医院 高血压
Background:Genetic risk factors substantially contributed to the development of coronary atherosclerosis. Genome-wide association study (GWAS) has identified many risk loci for coronary atherosclerosis, but the translation of these loci into therapeutic targets is limited for their location in non-coding regions. Here, we aimed to screen the potential coronary atherosclerosis pathogenic genes expressed though TWAS (transcriptome wide association study) and explore the underlying mechanism association.Methods:Four TWAS approaches (PrediXcan, JTI, UTMOST, and FUSION) were used to screen genes associated with coronary atherosclerosis. Enrichment analysis of TWAS-identified genes was applied through the Metascape website. The summary-data-based Mendelian randomization (SMR) analysis was conducted to provide the evidence of causal relationship between the candidate genes and coronary atherosclerosis. At last, the cell type-specific expression of the intersection genes was examined by using human coronary artery single-cell RNA-seq, interrogating the immune microenvironment of human coronary atherosclerotic plaque at different stages of maturity.Results:We identified 19 genes by at least three approaches and 1 gene (NBEAL1) by four approaches. Enrichment analysis enriching the genes identified at least by two TWAS approaches, suggesting that these genes were markedly enriched in asthma and leukocyte mediated immunity reaction. Further, the summary-data-based Mendelian randomization (SMR) analysis provided the evidence of causal relationship between NBEAL1 gene and coronary atherosclerosis, confirming the protecting effects of NBEAL1 gene and coronary atherosclerosis. At last, the single cell cluster analysis demonstrated that NBEAL1 gene has differential expressions in macrophages, plasma cells and endothelial cells.Conclusion:Our study identified the novel genes associated with coronary atherosclerosis and suggested the potential biological function for these genes, providing insightful guidance for further biological investigation and therapeutic approaches development in atherosclerosis-related diseases.
Frontiers in cardiovascular medicine 2023
Background: The causal direction and magnitude of the associations between blood cell count and coronary heart disease (CHD) remain uncertain due to susceptibility of reverse causation and confounding. This study aimed to investigate the associations between blood cell count and CHD using Mendelian randomization (MR). Methods: In this two-sample MR study, we identified independent blood cell count associated genetic variants from a genome-wide association studies (GWAS) among European ancestry individuals. Summary level data of CHD was obtained from a GWAS consisting of 547261 subjects. Methods of inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), weighted median, and outlier test (MR-PRESSO) were conducted to investigate the associations between blood cell and CHD. Results: Among all cardiovascular outcomes of interest, blood cell counts were only associated with CHD. Our findings indicated that white blood cell count and neutrophil cell count were significantly associated with increased risk of CHD [odds ratio (OR) = 1.07, 95% confidence interval (CI), 1.01-1.14; OR = 1.09, 1.02-1.16). However, there was no significant association between monocyte cell count, basophil cell count, lymphocyte cell count, eosinophil cell count, and CHD (p > 0.05). The results after excluding outliers were consistent with main results and the sensitivity analyses showed no evidence of pleiotropy (MR-Egger intercept, p > 0.05). Conclusion: Our MR study suggested that greater white blood cell count and neutrophil cell count were associated with a higher risk of CHD. Future studies are still warranted to validate the results and investigate the mechanisms underlying these associations.
Frontiers in genetics 2023
Background:Coronary artery disease (CAD) can lead to left ventricular (LV) remodeling, which, in adverse cases, has been associated with heart failure and increased mortality. Here, we aimed to evaluate the predictive value of the noninvasive myocardial work index (NIMWI) for LV reverse remodeling in patients with multivessel CAD after percutaneous coronary intervention (PCI).Methods:A total of 88 consecutive patients with multivessel CAD treated with PCI were identified and categorized according to the presence of LV reverse remodeling 3 months after PCI [≥15% decrease in the LV end diastolic volume (LVEDV)]. With the LV pressure-strain loop (PSL) technique, NIMWIs, including the global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were statistically compared between the reverse LV remodeling group and nonreverse LV remodeling group 1 week before PCI.Results:Significantly lower GWI, GCW, and GWE, and significantly higher GWW were observed in the reverse LV remodeling group compared with the nonreverse LV remodeling group (P<0.05). Left ventricular mass index (LVMI), GCW, and GWE were independently associated with early LV reverse remodeling. Receiver operating characteristic (ROC) curve analysis demonstrated that GCW was the most powerful predictor of early LV reverse remodeling in patients with CAD [area under the curve (AUC) =0.867]. The optimal cutoff GCW value predictive of early LV reverse remodeling was 1,438.5 mmHg% (sensitivity, 85%; specificity, 70%).Conclusions:GCW, among the NIMWIs, may be the major predictor of LV reverse remodeling in patients with multivessel CAD after PCI. NIMWI could potentially provide a new reference index for the quantitative evaluation of LV myocardial work.
Quantitative imaging in medicine and surgery 2022
BACKGROUND:Paroxysmal atrial fibrillation (AF) frequently occurs in patients with Wolff-Parkinson-White (WPW) syndrome. Although successful ablation of the accessory pathway (AP) eliminates paroxysmal AF in some patients, in other patients it can recur.HYPOTHESIS:We investigated the clinical utility of advanced interatrial block (IAB) for predicting the risk of AF recurrence in patients with verified paroxysmal AF and WPW syndrome after successful AP ablation.METHODS:This retrospective study included 103 patients (70 men, 33 women; mean age, 44 ± 16 years) with WPW syndrome who had paroxysmal AF. A resting 12-lead electrocardiogram was performed immediately after successful AP ablation to evaluate the presence of advanced IAB, which was defined as a P-wave duration of >120 ms and biphasic [±] morphology in the inferior leads.RESULTS:During the mean follow-up period of 30.9 ± 20.0 months (range, 2-71 months), 16 patients (15.5%) developed AF recurrence. Patients with advanced IAB had significantly reduced event-free survival from AF (P < .001). Cox regression analysis with adjustment for the left atrial diameter and CHA2 DS2 -VASc score identified advanced IAB (hazard ratio, 9.18; 95% confidence interval [CI], 2.30-36.72; P = .002) and age > 50 years (hazard ratio, 12.64; 95% CI, 1.33-119.75; P = .027) as independent predictors of AF recurrence.CONCLUSIONS:Advanced IAB was an independent predictor of AF recurrence after successful AP ablation in patients with WPW syndrome.
Clinical cardiology 2019
