Higher Circulating Lymphocytes and the Incidence of Pre-eclampsia and Eclampsia.

Excessive immune activation contributes to the onset of early dysfunction of the maternal-fetal interface, and it is closely linked to the development of pre-eclampsia. However, the effect of specific immune cells on the risk of pre-eclampsia and eclampsia remains controversial. We investigated the causal relationship between immune cells and pre-eclampsia and eclampsia. For exposure, we extracted genetic variants associated with immune cell-related traits, and for outcomes, we used summary genetic data of pre-eclampsia/eclampsia. A two-sample Mendelian randomization (MR) analysis was then performed to assess the causal relationship. Robustness of the MR results was then evaluated through colocalization analysis. We found that genetically proxied circulating lymphocyte absolute count was causally associated with total eclampsia (odds ratio (OR) = 1.53, 95% confidence interval (CI) (1.31-1.79), p = 1.15E - 07) and pre-eclampsia (OR = 1.50, 95% CI (1.28-1.77), p = 9.18E - 07); T cell absolute count was causally associated with total eclampsia (OR = 1.49, 95% CI (1.28-1.73), p = 2.73E - 07) and pre-eclampsia (OR = 1.47, 95% CI (1.25-1.72), p = 1.76E - 06). And CD28- CD25+ CD8+ T cell absolute count was causally associated with total eclampsia (OR = 1.83, 95% CI (1.44-2.32), p = 7.11E - 07) and pre-eclampsia (OR = 1.77, 95% CI (1.38-2.26), p = 6.55E - 06). Colocalization analysis revealed that immune cell-related traits shared the same variant with pre-eclampsia/eclampsia. Our study suggested causal effects of genetic predisposition to high lymphocyte absolute count levels, T cell absolute count, and CD28- CD25+ CD8+ T cell absolute count on eclampsia, particularly pre-eclampsia risk, providing crucial new insights into the potential prevention target for eclampsia and pre-eclampsia.

Transcriptome-wide association study reveals novel susceptibility genes for coronary atherosclerosis.

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.

White blood cells and coronary heart disease: A mendelian randomization study.

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.

Predictive value of the echocardiographic noninvasive myocardial work index for left ventricular reverse remodeling in patients with multivessel coronary artery disease after percutaneous coronary intervention.

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.

Research on the Damage of Adrenal Pheochromocytoma to Patients' Cardiovascular Vessels and Its Correlation with Hypertension.

Chromaffin cell-centered pheochromocytoma (Pheo) is a rare tumour. Pheochromocytoma and how it affects the heart will be the topic of this article. Due to the comparable symptoms and indications of the sympathetic nervous system, a pheochromocytoma might be difficult to detect early. There are also other frequent differential diagnoses that might delay the detection of a pheochromocytoma. One of the most common side effects of pheochromocytoma is unmanageable hypertension. Hypertensive crisis (extreme increases in blood pressure) can develop, which is a life-threatening condition that leads to strokes or arrhythmia. Estimated to affect African Americans significantly, they frequently go undetected due to a lack of resources or accessibility of services. Because this tumour is difficult to identify and its symptoms often resemble those of other diseases, it is frequently overlooked. A pheochromocytoma's long-term consequences can include cardiac muscle deterioration, congestive heart failure (CHF), a higher diabetes risk and possibly death. Masked hypertension (MH) is more common in people with adrenal pheochromocytoma, which has been related to an increased risk of heart disease. With the use of ambulatory blood pressure monitoring, this research set out to find out how common mental health issues are among people with APs. There were 85 participants in all, 43 of whom had APs and 42 of whom had the same age, gender, BMI, smoking and diabetes as the AP patients. Measurements were made of the BP and AP in both the diseased and control groups. Retrospective data collection was used to gather biochemical, hormonal and radiological information on the patients. The Pearson-Boltzmann CNN method was then used to assess risk based on the diagnosis results. Furthermore, depending on the risk score, more nonselective blockers (e.g., prazosin, doxazosin, terazosin, and metyrosine) have been used to lower perioperative catecholamine levels, hence reducing illness risk. After a successful surgical excision of the tumour, the recommended therapy can usually be stopped quickly.

Advanced interatrial block predicts recurrence of atrial fibrillation after accessory pathway ablation in patients with Wolff-Parkinson-White syndrome.

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.

Effects of Renal Denervation from the Intima and the Adventitia of Renal Arteries on Renal Sympathetic Nerve Activity in Dogs: A Comparative Study.

OBJECTIVES: This study was designed to observe the efficacy and safety of renal denervation from the inside and outside of renal arteries. METHODS: Fourteen beagles were randomly divided into a control group (n = 4) and treatment group (n = 10). One renal artery in every beagle of the treatment group was randomly assigned to an intimal group (10 renal arteries) which underwent percutaneous renal denervation from the inside, and another renal artery was assigned to an adventitial group (10 renal arteries) which underwent renal denervation from the outside by laparotomy. RESULTS: Compared with the intimal group, the renal norepinephrine (NE) concentration in the adventitial group had significantly decreased (p = 0.003) at 3 months postsurgery. Renal artery HE staining showed that the perineurium from the adventitial group appeared thickened. Western blotting showed that renal tissue tyrosine hydroxylase (TH) protein expression in the adventitial group was significantly lower than that in the intimal group (p < 0.01) at 3 months postsurgery. There was a renal artery stenosis and a renal atrophy in the intimal group after 1 month of follow-up. CONCLUSION: The inhibitory effect on renal sympathetic nerve activity was more effective in the adventitial group than the intimal group, and renal denervation in the former group was safe.

Effects of thyroid dysfunction on the severity of coronary artery lesions and its prognosis.

BACKGROUND: Abnormal thyroid hormone metabolism influences the occurrence and progress of coronary heart disease (CHD). The aim of the present study was to analyze the severity of coronary artery lesions and the prognosis of thyroid dysfunction patients admitted for coronary angiography (CAG). METHODS: From July 2011 to July 2012, 605 consecutive patients with suspected coronary heart disease admitted for CAG were selected. The patients were divided into three groups, based on their thyroid function prior to CAG: euthyroid group (n=455 patients), low T3 syndrome group (n=96 patients), and hypothyroidism group (n=54 patients). All patients underwent CAG. Then the severity of coronary artery lesions was assessed by Gensini scores. All patients were followed up for major adverse cardiac events. RESULTS: The prevalence of CHD in low T3 syndrome group and hypothyroidism group was significantly higher than that in the euthyroid group (p<0.001 and p=0.004, respectively). Moreover, the severity of coronary artery lesions in low T3 syndrome group and hypothyroidism group was significantly greater than that in the euthyroid group (all p<0.001). Multinomial logistic regression analysis demonstrated that low T3 syndrome was an independent risk factor of coronary artery moderate [odds ratio (OR)=4.268, 95% CI: 3.294-7.450, p=0.016] and severe (OR=4.294, 95% CI: 2.259-9.703, p<0.001) lesions. The mean duration of follow-up was 15.3±3.8 months; patients with thyroid dysfunction had a significantly worse prognosis as compared to those in the euthyroid group for the composite end-point (p<0.01). Moreover, the incidence of the composite end-point (all-cause death, non-fatal myocardial infarction, and coronary revascularization) was significantly higher in low T3 syndrome group and hypothyroidism group compared with that of in the euthyroid group (all p<0.001). CONCLUSIONS: The patients with hypothyroidism and low T3 syndrome had a high prevalence of CHD, increased severity of coronary artery lesions and poor prognosis.