Faecalibacterium prausnitzii as a potential Antiatherosclerotic microbe.

BACKGROUND: The gut microbiota plays a crucial role in coronary artery disease (CAD) development, but limited attention has been given to the role of the microbiota in preventing this disease. This study aimed to identify key biomarkers using metagenomics and untargeted metabolomics and verify their associations with atherosclerosis. METHODS: A total of 371 participants, including individuals with various CAD types and CAD-free controls, were enrolled. Subsequently, significant markers were identified in the stool samples through gut metagenomic sequencing and untargeted metabolomics. In vivo and in vitro experiments were performed to investigate the mechanisms underlying the association between these markers and atherosclerosis. RESULTS: Faecal omics sequencing revealed that individuals with a substantial presence of Faecalibacterium prausnitzii had the lowest incidence of CAD across diverse CAD groups and control subjects. A random forest model confirmed the significant relationship between F. prausnitzii and CAD incidence. Notably, F. prausnitzii emerged as a robust, independent CAD predictor. Furthermore, our findings indicated the potential of the gut microbiota and gut metabolites to predict CAD occurrence and progression, potentially impacting amino acid and vitamin metabolism. F. prausnitzii mitigated inflammation and exhibited an antiatherosclerotic effect on ApoE-/- mice after gavage. This effect was attributed to reduced intestinal LPS synthesis and reinforced mechanical and mucosal barriers, leading to decreased plasma LPS levels and an antiatherosclerotic outcome. CONCLUSIONS: Sequencing of the samples revealed a previously unknown link between specific gut microbiota and atherosclerosis. Treatment with F. prausnitzii may help prevent CAD by inhibiting atherosclerosis.

New Loss-of-Function Mutations in PCSK9 Reduce Plasma LDL Cholesterol.

BACKGROUND: Lower plasma levels of LDL (low-density lipoprotein) cholesterol (LDL-C) can reduce the risk of atherosclerotic cardiovascular disease. The loss-of-function mutations in PCSK9 (proprotein convertase subtilisin/kexin type 9) have been known to associate with low LDL-C in many human populations. PCSK9 genetic variants in Chinese Uyghurs who are at high risk of atherosclerotic cardiovascular disease due to their dietary habits have not been reported. METHODS: The study involved the whole-exome and target sequencing of college students from Uyghur and other ethnic groups in Xinjiang, China, for the association of PCSK9 loss-of-function mutations with low plasma levels of LDL-C. The mechanisms by which the identified mutations affect the function of PCSK9 were investigated in cultured cells using biochemical and cell assays. The causal effects of the identified PCSK9 mutations on LDL-C levels were verified in mice injected with adeno-associated virus expressing different forms of PCSK9 and fed a high-cholesterol diet. RESULTS: We identified 2 PCSK9 mutations-E144K and C378W-in Chinese Uyghurs with low plasma levels of LDL-C. The E144K and C378W mutations impaired the maturation and secretion of the PCSK9 protein, respectively. Adeno-associated virus-mediated expression of E144K and C378W mutants in Pcsk9 KO (knockout) mice fed a high-cholesterol diet also hampered PCSK9 secretion into the serum, resulting in elevated levels of LDL receptor in the liver and reduced levels of LDL-C in the serum. CONCLUSIONS: Our study shows that E144K and C378W are PCSK9 loss-of-function mutations causing low LDL-C levels in mice and probably in humans as well.

Impact of Duration of Diabetes Mellitus on Long-Term Outcome in Type 2 Diabetic Patients with Primary Percutaneous Coronary Intervention after the First Myocardial Infarction.

BACKGROUND: Diabetes mellitus (DM) increases the risk of mortality in patients with acute myocardial infarction (AMI). The impact of the diabetes duration on the long-term outcome of those with percutaneous coronary intervention (PCI) after the first AMI is unclear. In this study, we evaluated the predictive value of diabetes duration in the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs). METHODS: A total of 394 type 2 DM patients with PCI after the first AMI were enrolled and were divided into two groups by the diabetes duration: a short-DM group with diabetes duration of <5 years and a long-DM group with a duration of ≥5 years. The clinical endpoint was MACCEs. RESULTS: Multivariate Cox regression analysis found that the diabetes duration was independently associated with increased occurrence of MACCEs (HR: 1.512, 95% CI: 1.033, 2.215, p = 0.034), along with hypertension, Killip class III or IV, creatinine, multivessel disease, and continuous hypoglycemic therapy. After adjusting for the confounding variables, a nested Cox model showed that diabetes duration was still an independent risk factor of MACCEs (HR: 1.963, 95% CI: 1.376, 2.801, p < 0.001). The Kaplan-Meier survival curve illustrated a significantly high risk of MACCEs (HR: 2.045, p < 0.0001) in long-duration DM patients. After propensity score matching, a longer diabetes duration was associated with an increased risk of MACCE occurrence. CONCLUSION: Long-duration diabetes was independently associated with poor clinical outcomes after PCI in patients with their first myocardial infarction. Despite the diabetes duration, continuous hypoglycemic therapy significantly improved long-term clinical outcomes.

A nomogram to predict ventricular thrombus in dilated cardiomyopathy patients.

BACKGROUND: VT (Ventricular Thrombus) is a serious complication of dilated cardiomyopathy (DCM). Our goal is to develop a nomogram for personalized prediction of incident VT in DCM patients. METHODS: 1267 patients (52.87 ± 11.75 years old, 73.8% male) were analyzed retrospectively from January 01, 2015, to December 31, 2020. A nomogram model for VT risk assessment was established using minimum absolute contraction and selection operator (LASSO) and multivariate logistic regression analysis, and its effectiveness was validated by internal guidance. The model was evaluated by the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). We compared the performance in predicting VT between nomogram and CHA2DS2, CHA2DS2- VASc or ATRIA by AUC, akaike information criterion (AIC), bayesian information criterion (BIC), net reclassification index (NRI), and integrated discrimination index (IDI). RESULTS: 89 patients (7.02%) experienced VT. Multivariate logistic regression analysis revealed that age, left ventricular ejection fraction (LVEF), uric acid (UA), N-terminal precursor B-type diuretic peptide (NT-proBNP), and D-dimer (DD) were important independent predictors of VT. The nomogram model correctly separates patients with and without VT, with an optimistic C score of 0.92 (95%CI: 0.90-0.94) and good calibration (Hosmer-Lemeshow χ2 = 11.51, P = 0.12). Our model showed improved prediction of VT compared to CHA2DS2, CHA2DS2-VASc or ATRIA (all P < 0.05). CONCLUSIONS: The novel nomogram demonstrated better than presenting scores and showed an improvement in predicting VT in DCM patients.

Ablation of Plasma Prekallikrein Decreases Low-Density Lipoprotein Cholesterol by Stabilizing Low-Density Lipoprotein Receptor and Protects Against Atherosclerosis.

BACKGROUND: High blood cholesterol accelerates the progression of atherosclerosis, which is an asymptomatic process lasting for decades. Rupture of atherosclerotic plaques induces thrombosis, which results in myocardial infarction or stroke. Lowering cholesterol levels is beneficial for preventing atherosclerotic cardiovascular disease. METHODS: Low-density lipoprotein (LDL) receptor (LDLR) was used as bait to identify its binding proteins in the plasma, and the coagulation factor prekallikrein (PK; encoded by the KLKB1 gene) was revealed. The correlation between serum PK protein content and lipid levels in young Chinese Han people was then analyzed. To investigate the effects of PK ablation on LDLR and lipid levels in vivo, we genetically deleted Klkb1 in hamsters and heterozygous Ldlr knockout mice and knocked down Klkb1 using adeno-associated virus-mediated shRNA in rats. The additive effect of PK and proprotein convertase subtilisin/kexin 9 inhibition also was evaluated. In addition, we applied the anti-PK neutralizing antibody that blocked the PK and LDLR interaction in mice. Mice lacking both PK and apolipoprotein e (Klkb1-/-Apoe-/-) were generated to assess the role of PK in atherosclerosis. RESULTS: PK directly bound LDLR and induced its lysosomal degradation. The serum PK concentrations positively correlated with LDL cholesterol levels in 198 young Chinese Han adults. Genetic depletion of Klkb1 increased hepatic LDLR and decreased circulating cholesterol in multiple rodent models. Inhibition of proprotein convertase subtilisin/kexin 9 with evolocumab further decreased plasma LDL cholesterol levels in Klkb1-deficient hamsters. The anti-PK neutralizing antibody could similarly lower plasma lipids through upregulating hepatic LDLR. Ablation of Klkb1 slowed the progression of atherosclerosis in mice on Apoe-deficient background. CONCLUSIONS: PK regulates circulating cholesterol levels through binding to LDLR and inducing its lysosomal degradation. Ablation of PK stabilizes LDLR, decreases LDL cholesterol, and prevents atherosclerotic plaque development. This study suggests that PK is a promising therapeutic target to treat atherosclerotic cardiovascular disease.

Audiological Diagnosis of Valvular and Congenital Heart Diseases in the Era of Artificial Intelligence.

In recent years, electronic stethoscopes have been combined with artificial intelligence (AI) technology to digitally acquire heart sounds, intelligently identify valvular disease and congenital heart disease, and improve the accuracy of heart disease diagnosis. The research on AI-based intelligent stethoscopy technology mainly focuses on AI algorithms, and the commonly used methods are end-to-end deep learning algorithms and machine learning algorithms based on feature extraction, and the hot spot for future research is to establish a large standardized heart sound database and unify these algorithms for external validation; in addition, different electronic stethoscopes should also be extensively compared so that the algorithms can be compatible with different. In addition, there should be extensive comparison of different electronic stethoscopes so that the algorithms can be compatible with heart sounds collected by different stethoscopes; especially importantly, the deployment of algorithms in the cloud is a major trend in the future development of artificial intelligence. Finally, the research of artificial intelligence based on heart sounds is still in the preliminary stage, although there is great progress in identifying valve disease and congenital heart disease, they are all in the research of algorithm for disease diagnosis, and there is little research on disease severity, remote monitoring, prognosis, etc., which will be a hot spot for future research.

Cystatin C to Left Ventricular Ejection Fraction Ratio as a Novel Predictor of Adverse Outcomes in Patients with Coronary Artery Disease: A Prospective Cohort Study.

Background: While both cystatin C and left ventricular ejection fraction (LVEF) revealed established prognostic efficacy in coronary artery disease (CAD), the relationship between cystatin C/left ventricular ejection fraction ratio (CLR) and adverse clinical outcomes among patients with CAD following percutaneous coronary intervention (PCI) remains obscure, to date. Therefore, we sought to assess the predictive efficacy of CLR among CAD patients who underwent PCI in current study. Methods: A total of 14,733 participants, including 8622 patients with acute coronary syndrome (ACS) and 6111 patients with stable coronary artery disease (SCAD), were enrolled from a prospective cohort of 15,250 CAD patients who underwent PCI and were admitted to the First Affiliated Hospital of Xinjiang Medical University from 2016 to 2021. The primary outcome of this study was mortality, including all-cause mortality (ACM) and cardiac mortality (CM). The secondary outcomes were major adverse cardiovascular events (MACEs), major adverse cardiac and cerebrovascular events (MACCEs) and nonfatal myocardial infarction (NFMI). For CLR, the optimal cut-off value was determined by utilizing receiver operating characteristic curve analysis (ROC). Subsequently, patients were assigned into two groups: a high-CLR group (CLR ≥ 0.019, n = 3877) and a low-CLR group (CLR < 0.019, n = 10,856), based on optimal cut-off value of 0.019. Lastly, the incidence of outcomes between the two groups was compared. Results: The high-CLR group had a higher incidence of ACM (8.8% vs. 0.9%), CM (6.7% vs. 0.6%), MACEs (12.7% vs. 5.9%), MACCEs (13.3% vs. 6.7%), and NFMIs (3.3% vs. 0.9%). After adjusting for confounders, multivariate Cox regression analyses revealed that patients with high-CLR had an 8.163-fold increased risk of ACM (HR = 10.643, 95% CI: 5.525~20.501, p < 0.001), a 10.643-fold increased risk of CM (HR = 10.643, 95% CI: 5.525~20.501, p < 0.001), a 2.352-fold increased risk of MACE (HR = 2.352, 95% CI: 1.754~3.154, p < 0.001), a 2.137-fold increased risk of MACCEs (HR = 2.137, 95% CI: 1.611~2.834, p < 0.001), and a 1.580-fold increased risk of NFMI (HR = 1.580, 95% CI: 1.273~1.960, p < 0.001) compared to patients with low-CLR. Conclusions: The current study indicated that a high CLR is a novel and powerful predictor of adverse long-term outcomes in CAD patients who underwent PCI, and that, it is a better predictor for patients wtih SCAD and ACS. Clinical Trial Registration: NCT05174143, http://Clinicaltrials.gov.

Predictive Value of the Modified GRACE Scoring System for All-Cause Mortality in Patients with Acute Myocardial Infarction.

Background: To establish a modified Global Registry of Acute Coronary Events (GRACE) scoring system with an improved predictive performance compared with the traditional GRACE scoring system. Methods: We identified 5512 patients who were hospitalized with a definite diagnosis of acute myocardial infarction (AMI) from January 1, 2015, to December 31, 2020, at the Heart Center of the First Affiliated Hospital of Xinjiang Medical University through the hospital's electronic medical record system. A total of 4561 patients were enrolled after the inclusion and exclusion criteria were applied. The mean follow-up was 51.8 ± 23.4 months. The patients were divided into dead and alive groups by endpoint events. The differences between the two groups were compared using the two-sample t test and chi-square test. Adjusted traditional risk factors as well as LogBNP (B-type natriuretic peptide precursor, BNP) and the modified GRACE scoring system were included in a multifactorial COX regression model. The predictive performance of the traditional and modified GRACE scoring systems was compared by (Receiver Operating Characteristic) ROC curves. Results: Significant differences in age, heart rate, creatinine, uric acid, LogBNP, traditional GRACE score, and modified GRACE score were found between the dead and alive groups by the two-sample t test. Comparison of the two groups by the chi-square test revealed that the dead group had a higher incidence of males; higher cardiac function class; a previous history of hypertension, diabetes, coronary artery disease (CAD), or cerebrovascular disease; a history of smoking; the need for intra-aortic balloon pump (IABP) support; and more patients taking aspirin, clopidogrel, ticagrelor, and ß -blockers. The results were analyzed by a multifactorial COX regression model, and after adjusting for confounders, age, cardiac function class, history of CAD, use of aspirin and ß -blockers, and the modified GRACE scoring system were found to be associated with all-cause mortality (ACM) in patients with AMI. The ROC curve was used to compare the predictive performance of the conventional GRACE scoring system with that of the modified GRACE scoring system, and it was found that the modified GRACE scoring system (Area Under Curve (AUC) = 0.809, p < 0.001, 95% (Confidence Interval) CI (0.789-0.829)) was significantly better than the traditional GRACE scoring system (AUC = 0.786, p < 0.001, 95% CI (0.764-0.808)), the comparison between the two scores was statistically significant (p < 0.001). The change in the C statistic after 10-fold crossover internal validation of the modified GRACE score was not significant, and the integrated discrimination improvement (IDI) between the old and new models was calculated with IDI = 0.019 > 0, suggesting that the modified GRACE score has a positive improvement on the traditional GRACE score. Conclusions: The modified GRACE scoring system, established by combining B-type natriuretic peptide precursor (BNP) and the traditional GRACE scoring system, was independently associated with ACM in patients with AMI, with a larger AUC and higher predictive value than the traditional GRACE scoring system. Clinical Trial Registration: NCT02737956.

Predictive Value of the Fibrinogen to Gamma-Glutamine Transferase Ratio in the Long-Term Outcome in Patients with Coronary Heart Disease: A Retrospective Cohort Study.

Background: The ratio of fibrinogen to γ -glutamine transferase (FGR) was used to predict long-term prognosis in patients with coronary heart disease (CHD). Methods: A total of 5638 patients with CHD who were hospitalized from January 2008 to December 2016 were retrospectively enrolled in the study. The mean follow-up time was 35.9 ± 22.5 months. The follow-up endpoints were major cardiac and cerebrovascular adverse events (MACCE). The optimal FGR cut-off value was determined and divided into high- and low-FGR groups according to the receiver operating characteristic (ROC) curve. Statistical methods were used to compare the differences between the two groups and their prognoses to determine whether FGR can predict prognosis in patients with CHD. The traditional predictors were incorporated into the logistic regression model to observe the correlation between these indicators and all-cause mortality (ACM) events. We compared the prediction performance of FGR and traditional predictors on the occurrence of ACM events by ROC curves. Results: The optimal cut-off value was determined via a ROC analysis (FGR = 1.22, p = 0.002), and subjects were classified into high and low FGR groups. The follow-up found that the incidence of MACCE in the high FGR group was higher than that in the low FGR group. The COX multivariate regression model showed that high FGR was independently correlated with the occurrence of MACCE. In addition, the Kaplan-Meier survival curve showed that the risk of events was significantly increased in the group with high FGR. With increases in the FGR ratio, the risk of MACCE was increased. The ROC curve revealed that the risk of ACM was statistically different between the FGR and the traditional risk factor model (p = 0.002), (Fibrinogen (p = 0.008), γ -glutamine transferase (GGT) (p = 0.004), and N-terminal pro brain natriuretic peptide (NT-ProBNP) (p = 0.024)). The comparison between other different models were not statistically significant (p > 0.05). The area under the FGR model curve was larger than that of the traditional risk factors, fibrinogen, GGT and NT-ProBNP models. Conclusions: High FGR can increase the risk of MACCE in patients with CHD; additionally, it can be used as a new biomarker for long-term prognosis in CHD patients. Clinical Trial Registration: All details of this study are registered on the website (http://www.chictr.org.cn), registration number: ChiCTR-ORC-16010153.

Mutated CYP17A1 promotes atherosclerosis and early-onset coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is a multi-factor complex trait and is heritable, especially in early-onset families. However, the genetic factors affecting the susceptibility of early-onset CAD are not fully characterized. METHODS: In the present study, we identified a rare nonsense variant in the CYP17A1 gene from a Chinese Han family with CAD. To validate the effect of this variation on atherosclerosis and early-onset coronary artery disease, we conducted studies on population, cells, and mice. RESULTS: The mutation precisely congregated with the clinical syndrome in all the affected family members and was absent in unaffected family members and unrelated controls. Similar to the human phenotype, the CYP17A1-deficient mice present the phenotype of metabolic syndrome with hypertension, increased serum glucose concentration, and presentation of central obesity and fatty liver. Furthermore, CYP17A1 knockout mice or CYP17A1 + ApoE double knockout mice developed more atherosclerotic lesions than wild type (WT) with high fat diary. In cell models, CYP17A1 was found to be involved in glucose metabolism by increasing glucose intake and utilization, through activating IGF1/mTOR/HIF1-α signaling way, which was consistent in CYP17A1 knockout mice with impaired glucose tolerance and insulin resistance. CONCLUSIONS: Through our study of cells, mice and humans, we identified CYP17A1 as a key protein participating in the pathophysiology of the atherosclerotic process and the possible mechanism of CYP17A1 C987X mutation induced atherosclerosis and early-onset CAD involving glucose homeostasis regulation was revealed. Video Abstract.

A prediction model to predict in-hospital mortality in patients with acute type B aortic dissection.

BACKGROUND: Acute type B aortic dissection (ABAD) is a life-threatening cardiovascular disease. A practicable and effective prediction model to predict and evaluate the risk of in-hospital death for ABAD is required. The present study aimed to construct a prediction model to predict the risk of in-hospital death in ABAD patients. METHODS: A total of 715 patients with ABAD were recruited in the first affiliated hospital of Xinjiang medical university from April 2012 to May 2021. The information on the demographic and clinical characteristics of all subjects was collected. The logistic regression analysis, receiver operating characteristic (ROC) curve analysis, and nomogram were applied to screen the appropriate predictors and to establish a prediction model for the risk of in-hospital mortality in ABAD. The receiver operator characteristic curve and calibration plot were applied to validate the performance of the prediction model. RESULTS: Of 53 (7.41%) subjects occurred in-hospital death in 715 ABAD patients. The variables including diastolic blood pressure (DBP), platelets, heart rate, neutrophil-lymphocyte ratio, D-dimer, C-reactive protein (CRP), white blood cell (WBC), hemoglobin, lactate dehydrogenase (LDH), procalcitonin, and left ventricular ejection fraction (LVEF) were shown a significant difference between the in-hospital death group and the in-hospital survival group (all P < 0.05). Furthermore, all these factors which existed differences, except CRP, were associated with in-hospital deaths in ABAD patients (all P < 0.05). Then, parameters containing LVEF, WBC, hemoglobin, LDH, and procalcitonin were identified as independent risk factors for in-hospital deaths in ABAD patients by adjusting compound variables (all P < 0.05). In addition, these independent factors were qualified as predictors to build a prediction model (AUC > 0.5, P < 0.05). The prediction model was shown a favorable discriminative ability (C index = 0.745) and demonstrated good consistency. CONCLUSIONS: The novel prediction model combined with WBC, hemoglobin, LDH, procalcitonin, and LVEF, was a practicable and valuable tool to predict in-hospital deaths in ABAD patients.

Effects of Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting on Clinical Outcomes in Patients with Reduced Ejection Fraction Heart Failure and Coronary Heart Disease: A Meta-Analysis.

OBJECTIVE: To clarify the effects of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on the clinical outcomes of patients with coronary heart disease (CHD) complicated with reduced ejection fraction heart failure (HFrEF) through meta-analysis. METHODS: Three major literature databases - PubMed, Web of Science, and Cochrane - were searched by search terms and the literature retrieval time was publications dating from January 2007 to December 2021. To search for observational studies and randomized controlled trials (RCT) comparing the efficacy of PCI and CABG in patients with CHD and HFrEF, the abstract or full text of the literature was read and the final included literature was determined, according to inclusion and exclusion criteria. The quality of the included literature was evaluated using the Ottawa scale and data extraction was further completed. Data analysis was made using RevMan5.4 and R4.1 software; relevant forest plots and funnel plots were made, according to the extracted data. Egger's test was used to evaluate whether the data had publication bias. Outcomes were the major adverse cardiovascular events (MACE). RESULTS: A total of 10 studies were included and 11,032 subjects were included, made up of 5,521 cases of PCI and 5,511 cases of CABG. The results showed no significant difference between the two groups in cardiac mortality (CM) (RR=1.13, 95% CI 0.98-1.30, P = 0.10) and in overall all-cause mortality (ACM) (RR=1.12, 95% CI 0.92-1.37, P = 0.25). In the subgroup analysis of ACM, in the subgroups with left ventricular ejection fraction (LVEF) less than 35% and exceeding 35% and less than 50% (RR=1.12, 95% CI 0.92-1.37, P = 0.25) between the two groups, there was no statistical difference. However, among other MACE, compared with the PCI group, the CABG group had a lower risk of MACE (RR=1.58, 95%CI 1.49-1.70, P < 0.00001), myocardial infarction (MI) (RR=1.99, 95% CI 1.02-3.88, P = 0.04), heart failure (HF) (RR=1.29, 95% CI 1.17-1.43, P < 0.00001) and revascularization (RR=2.74, 95% CI 1.93-3.90, P < 0.00001). Finally in the CABG group, the risk of stroke or transient ischemic attack (TIA) was higher (RR=0.71, 95% CI 0.58-0.86, P = 0.0006) than the PCI group. CONCLUSIONS: The mortality rates of PCI and CABG were similar in patients with CHD complicated with HFrEF. Compared with PCI, CABG had a lower incidence of MACE, MI, HF, and revascularization, and a higher incidence of stroke or TIA.

Association of genetic polymorphisms of PCSK9 with type 2 diabetes in Uygur Chinese population.

BACKGROUND: PCSK9 gene expression is associated with biological processes such as lipid metabolism, glucose metabolism, and inflammation. In the present study, our primary objective was to assess the association between the single-nucleotide polymorphisms in the PCSK9 gene and type 2 diabetes in Uygur subjects, in Xinjiang, China. METHODS: We designed a case-control study including 662 patients diagnosed with T2DM and 1220 control subjects. Four single-nucleotide polymorphisms (rs11583680, rs2483205, rs2495477 and rs562556) of PCSK9 gene were genotyped using the improved multiplex ligation detection reaction technique. RESULTS: For rs2483205, the distribution of genotypes, dominant model (CC vs CT + TT), overdominant model (CC + TT vs CT) showed significant differences between T2DM patients and the controls (P = 0.011 and P = 0.041 respectively). For rs2495477, the distribution of genotypes, the dominant model (AA vs GA + GG) showed significant differences between T2DM patients and the controls (P = 0.024). Logistic regression analysis suggested after adjustment of other confounders, the differences remained significant between the two groups [for rs2483205 CC vs CT + TT: odds ratio (OR) = 1.321, 95% confidence interval (CI) 1.078-1.617, P = 0.007; CC + TT vs CT: OR = 1.255, 95% CI 1.021-1.542, P = 0.03; for rs2495477 AA vs GA + GG: OR = 1.297, 95% CI 1.060-1.588, P = 0.012]. CONCLUSION: The present study indicated that CT + TT genotype and CT genotype of rs2483205, as well as GA + GG genotype of rs2495477 in PCSK9 gene were associated with an increased risk of type 2 diabetes in the Uygur population in Xinjiang.

Initial Invasive Versus Conservative Management of Stable Ischemic Heart Disease in Patients With a History of Heart Failure or Left Ventricular Dysfunction: Insights From the ISCHEMIA Trial.

BACKGROUND: Whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in the setting of a history of heart failure (HF) or left ventricular dysfunction (LVD) when ejection fraction is ≥35% but <45% is unknown. METHODS: Among 5179 participants randomized into ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), all of whom had left ventricular ejection fraction (LVEF) ≥35%, we compared cardiovascular outcomes by treatment strategy in participants with a history of HF/LVD at baseline versus those without HF/LVD. Median follow-up was 3.2 years. RESULTS: There were 398 (7.7%) participants with HF/LVD at baseline, of whom 177 had HF/LVEF >45%, 28 HF/LVEF 35% to 45%, and 193 LVEF 35% to 45% but no history of HF. HF/LVD was associated with more comorbidities at baseline, particularly previous myocardial infarction, stroke, and hypertension. Compared with patients without HF/LVD, participants with HF/LVD were more likely to experience a primary outcome composite of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest (4-year cumulative incidence rate, 22.7% versus 13.8%; cardiovascular death or myocardial infarction, 19.7% versus 12.3%; and all-cause death or HF, 15.0% versus 6.9%). Participants with HF/LVD randomized to the invasive versus conservative strategy had a lower rate of the primary outcome (17.2% versus 29.3%; difference in 4-year event rate, -12.1% [95% CI, -22.6 to -1.6%]), whereas those without HF/LVD did not (13.0% versus 14.6%; difference in 4-year event rate, -1.6% [95% CI, -3.8% to 0.7%]; P interaction = 0.055). A similar differential effect was seen for the primary outcome, all-cause mortality, and cardiovascular mortality when invasive versus conservative strategy-associated outcomes were analyzed with LVEF as a continuous variable for patients with and without previous HF. CONCLUSIONS: ISCHEMIA participants with stable ischemic heart disease and at least moderate ischemia with a history of HF or LVD were at increased risk for the primary outcome. In the small, high-risk subgroup with HF and LVEF 35% to 45%, an initial invasive approach was associated with better event-free survival. This result should be considered hypothesis-generating. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

A prediction model based on platelet parameters, lipid levels, and angiographic characteristics to predict in-stent restenosis in coronary artery disease patients implanted with drug-eluting stents.

BACKGROUND: The present study was aimed to establish a prediction model for in-stent restenosis (ISR) in subjects who had undergone percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). MATERIALS AND METHODS: A retrospective cohort study was conducted. From September 2010 to September 2013, we included 968 subjects who had received coronary follow-up angiography after primary PCI. The logistic regression analysis, receiver operator characteristic (ROC) analysis, nomogram analysis, Hosmer-Lemeshow χ2 statistic, and calibration curve were applied to build and evaluate the prediction model. RESULTS: Fifty-six patients (5.79%) occurred ISR. The platelet distribution width (PDW), total cholesterol (TC), systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and lesion vessels had significant differences between ISR and non-ISR groups (all P < 0.05). And these variables were independently associated with ISR (all P < 0.05). Furthermore, they were identified as predictors (all AUC > 0.5 and P < 0.05) to establish a prediction model. The prediction model showed a good value of area under curve (AUC) (95%CI): 0.72 (0.64-0.80), and its optimized cut-off was 6.39 with 71% sensitivity and 65% specificity to predict ISR. CONCLUSION: The incidence of ISR is 5.79% in CAD patients with DES implantation in the Xinjiang population, China. The prediction model based on PDW, SBP, TC, LDL-C, and lesion vessels was an effective model to predict ISR in CAD patients with DESs implantation.

Genetic polymorphism of IDOL gene was associated with the susceptibility of coronary artery disease in Han population in Xinjiang, China.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of death worldwide. In this study, we aimed to explore whether some genetic variants of the human IDOL gene were associated with CAD among Chinese population in Xinjiang. METHODS: We designed two independent case-control studies. The first one included in the Han population (448 CAD patients and 343 controls), and the second one is the Uygur population (304 CAD patients and 318 controls). We genotyped three SNPs (rs2072783, rs2205796, and rs909562) of the IDOL gene. RESULTS: Our results revealed that, in the Han female subjects, for rs2205796, the distribution of alleles, dominant model (TT vs. GG + GT) and the additive model (GG + TT vs. GT) showed significant differences between CAD patients and the control subjects (P = 0.048, P = 0.014, and P = 0.032, respectively). CONCLUSIONS: The rs2205796 polymorphism of the IDOL gene is associated with CAD in the Chinese Han female population in Xinjiang, China.

FBXW7 gene polymorphism is associated with type 2 diabetes in the Uygur population in Xinjiang, China.

BACKGROUND: FBXW7 gene expression is positively correlated with glycolipid metabolism and is associated with diabetes in animal models. In the current study, we focused on exploring whether genetic variants of the FBXW7 gene were associated with type 2 diabetes (T2DM) and the risk factors for T2DM in Uygur people in Xinjiang, China. METHODS: A total of 2164 Chinese Uygur subjects (673 T2DM patients and 1491 controls) were recruited for our case-control study, and four SNPs (rs10033601, rs2255137, rs2292743 and rs35311955) of the FBXW7 gene were genotyped using the improved multiplex ligation detection reaction (iMLDR) technique. RESULTS: Our study showed that the genotypes using the overdominant model (GA vs AA + GG) of rs10033601 and using the overdominant model (TA vs TT + AA) of rs2292743 were significantly different between T2DM patients and the controls (P = 0.005 and P = 0.012, respectively). After multivariate adjustments for confounders, the rs10033601 and rs2292743 SNPs were still independent risk factors for T2DM [GA vs AA + GG: odds ratio = 1.35, 95% confidence interval (CI) = 1.12-1.64, P = 0.002; TA vs TT + AA: OR = 1.28, 95% CI = 1.06-1.55, P = 0.011]. Participants within the Chinese Uygur populations and who with the GA genotype of rs10033601 and the TA genotype of rs2292743 were associated with significantly elevated glucose levels. CONCLUSIONS: Our study revealed that both rs10033601 and rs2292743 of the FBXW7 gene were associated with T2DM in the Uygur populations in Xinjiang.

Gamma-glutamyl transferase to albumin ratio as a novel predictor of bleeding events and mortality in patients after percutaneous coronary intervention: A retrospective cohort study.

OBJECTIVES: To determine whether gamma-glutamyl transferase (GGT) to albumin ratio (GAR) independently predicts mortality and bleeding events in coronary artery disease (CAD) patients who undergo percutaneous coronary intervention (PCI). BACKGROUND: Serum GGT and albumin levels have been associated with CAD risk and mortality. However, more analysis is needed to determine their predictive relationship with adverse outcomes. METHODS: In total, 5,638 patients from a large retrospective cohort study were enrolled from January 2008 to December 2016 and divided into two groups (GAR <0.62, n = 2,712 and GAR ≥0.62, n = 2,926). The average follow-up time was 35.9 ± 22.6 months. Multivariate Cox regression analyses were performed to determine the risk of all-cause mortality and bleeding events associated with GAR. RESULTS: The low-GAR group had a significantly higher number of all-cause mortality (p = .016) and bleeding events (p = .010) than the high-GAR group. Multivariate Cox regression analyses showed that the risk of all-cause death and bleeding events decreased by 23.8% (hazard risk [HR] = 0.762 95% confidence interval [CI]: 0.601-0.966, p = .025) and 39.4% (HR = 00.616, 95% CI: 0.446-0.852, p = .003), respectively, in the high-GAR group. In patients with acute coronary syndrome, the risk of bleeding events decreased by 57.3% in the high-GAR group (HR = 0.427, 95% CI: 0.234-0.781, p = .006). In patients with stable coronary heart disease, the risk of all-cause death decreased 28.6% (HR = 0.714, 95% CI: 0.540-0.944, p = .018) in the high-GAR group. CONCLUSION: GAR was an independent and novel predictor of mortality and bleeding events in CAD patients who underwent PCI.

IDOL G51S Variant Is Associated With High Blood Cholesterol and Increases Low-Density Lipoprotein Receptor Degradation.

OBJECTIVE: A high level of LDL-C (low-density lipoprotein cholesterol) is a major risk factor for cardiovascular disease. The E3 ubiquitin ligase named IDOL (inducible degrader of the LDLR [LDL receptor]; also known as MYLIP [myosin regulatory light chain interacting protein]) mediates degradation of LDLR through ubiquitinating its C-terminal tail. But the expression profile of IDOL differs greatly in the livers of mice and humans. Whether IDOL is able to regulate LDL-C levels in humans remains to be determined. Approach and Results: By using whole-exome sequencing, we identified a nonsynonymous variant rs149696224 in the IDOL gene that causes a G51S (Gly-to-Ser substitution at the amino acid site 51) from a Chinese Uygur family. Large cohort analysis revealed IDOL G51S carriers (+/G51S) displayed significantly higher LDL-C levels. Mechanistically, the G51S mutation stabilized IDOL protein by inhibiting its dimerization and preventing self-ubiquitination and subsequent proteasomal degradation. IDOL(G51S) exhibited a stronger ability to promote ubiquitination and degradation of LDLR. Adeno-associated virus-mediated expression of IDOL(G51S) in mouse liver decreased hepatic LDLR and increased serum levels of LDL-C, total cholesterol, and triglyceride. CONCLUSIONS: Our study demonstrates that IDOL(G51S) is a gain-of-function variant responsible for high LDL-C in both humans and mice. These results suggest that IDOL is a key player regulating cholesterol level in humans.

Case-Control Study on the Interaction Effects of rs10757278 Polymorphisms at 9p21 Locus and Traditional Risk Factors on Coronary Heart Disease in Xinjiang, China.

OBJECTIVE: To study the interaction effects of rs10757278 polymorphisms at 9p21 locus and traditional risk factors on coronary heart disease (CHD) in Xinjiang, China. METHODS: This case-control study consecutively enrolled 310 unrelated consecutive CHD patients aged 18-70 years old. All study participants were recruited between January and December 2017 from The Heart Center of The First Affiliated Hospital of Xinjiang Medical University. CHD patients were confirmed by coronary angiography (≥50% diameter stenosis in at least one of the major coronary arteries) according to the American Heart Association criteria for the confirmation of CHD. Healthy subjects were randomly selected from the occupational population, who received physical examination in our hospital and matched to cases on the basis of age (±3 years) and sex, those without medical history of cardiovascular diseases, and 536 subjects were selected as the control group after medical history inquiry, physical examination, cardiac ultrasound, electrocardiogram, and other blood biochemical examinations in the hospital. The occupational stress was evaluated by an effort-reward imbalance questionnaire. An epidemiological survey was conducted to collect clinical data. Chi-squared test, analysis of variance, and binary logistic regression analysis were adopted. RESULTS: Both the case and the control groups showed significant difference in smoking, drinking, physical activity, hypertension, diabetes mellitus, family history of CHD, and body mass index (BMI) (all P < 0.05); prevalence of CHD was not related to occupational stress. There was no significant difference in occupational stress level between the 2 groups (P > 0.05); Differences in rs10757278 genotype between the case group and the control groups were statistically significant; binary logistic regression analysis was used to evaluate the risk factors of CHD. After adjustment for age and sex, significant increased risk effects for CHD were found to be associated with smoking [odds ratio (OR) = 2.311; 95% confidence interval (CI): 1.04-2.499; P < 0.001], physical exercise (OR = 1.365; 95% CI: 1.137-1.639; P < 0.001), hypertension (OR = 4.627; 95% CI: 2.165-10.764; P < 0.001), family history of CHD (OR = 4.103; 95% CI: 3.169-6.892; P < 0.001), BMI (OR = 2.484; 95% CI: 2.036-3.03; P < 0.001), and GG genotype at rs10757278 (OR = 1.978; 95% CI: 1.413-2.769; P < 0.001); We noted that a significant interaction association between GG genotype at rs10757278 and CHD differs across categories of smoking, hypertension, family history of CHD, and BMI. CONCLUSION: GG genotype at rs10757278 may be a risk factor for CHD. And there are interaction effects between GG genotype of rs10757278 in region 9p21 gene and traditional risk factors.