Background::Genome-wide association studies (GWAS) have identified more than a thousand loci for blood pressure (BP). Functional genes in these loci are cell-type specific. The aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms (RNAm-SNPs).Methods::Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium, we identified associations between RNAm-SNPs and BP. The association between RNAm-SNPs, gene expression, and BP were examined.Results::A total of 355 RNAm-SNPs related to m 6A, m 1A, m 5C, m 7G, and A-to-I modification were associated with BP. The related genes were enriched in the pancreatic secretion pathway and renin secretion pathway. The BP GWAS signals were significantly enriched with m 6A-SNPs, highlighting the potential functional relevance of m 6A in physiological processes influencing BP. Notably, m 6A-SNPs in CYP11B1, PDE3B, HDAC7, ACE, SLC4A7, PDE1A, FRK, MTHFR, NPPA, CACNA1D, and HDAC9 were identified. Differential methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were detected. RNAm-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection (AD) cases and controls. In scRNA-seq study, we identified ARID5A, HLA-DPB1, HLA-DRA, IRF1, LINC01091, MCL1, MLF1, MLXIPL, NAA16, NADK, RERG, SRM, and USP53 as differential expression genes for AD in aortic cells. Conclusion::The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs, gene expression, and BP. The identified BP-associated genes in aortic cells were associated with AD.

Background::Genome-wide association studies (GWAS) have identified more than a thousand loci for blood pressure (BP). Functional genes in these loci are cell-type specific. The aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms (RNAm-SNPs).Methods::Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium, we identified associations between RNAm-SNPs and BP. The association between RNAm-SNPs, gene expression, and BP were examined.Results::A total of 355 RNAm-SNPs related to m 6A, m 1A, m 5C, m 7G, and A-to-I modification were associated with BP. The related genes were enriched in the pancreatic secretion pathway and renin secretion pathway. The BP GWAS signals were significantly enriched with m 6A-SNPs, highlighting the potential functional relevance of m 6A in physiological processes influencing BP. Notably, m 6A-SNPs in CYP11B1, PDE3B, HDAC7, ACE, SLC4A7, PDE1A, FRK, MTHFR, NPPA, CACNA1D, and HDAC9 were identified. Differential methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were detected. RNAm-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection (AD) cases and controls. In scRNA-seq study, we identified ARID5A, HLA-DPB1, HLA-DRA, IRF1, LINC01091, MCL1, MLF1, MLXIPL, NAA16, NADK, RERG, SRM, and USP53 as differential expression genes for AD in aortic cells. Conclusion::The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs, gene expression, and BP. The identified BP-associated genes in aortic cells were associated with AD.

Objective::Regarding the secondary prevention of cardiovascular disease (CVD), there is great interest in preventing recurrent cardiovascular events (RCVEs). The prognostic importance of liver fibrosis scores (LFSs) has previously been reported in various CVDs. We hypothesized that LFSs might also be useful predictors for RCVEs in patients with prior cardiovascular events (CVEs). Herein, we aimed to evaluate the associations of LFSs with RCVEs in a large, real-world cohort of coronary artery disease (CAD) patients with a prior CVE.Methods::In this multicenter prospective study, 6527 consecutive patients with angiography-diagnosed CAD who had experienced a prior CVE (acute coronary syndrome, stroke, percutaneous coronary intervention, or coronary artery bypass grafting) were enrolled. LFSs were computed according to the published formulas: non-alcoholic fatty liver disease fibrosis score (NFS) includes age, body mass index (BMI), impaired fasting glycemia or diabetes mellitus (DM), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, platelets, and albumin; fibrosis-4 (FIB-4) includes age, AST, ALT, and platelets; Forns score includes age, gamma-glutamyltransferase (GGT), and platelets; BARD includes BMI, AST/ALT ratio, and DM; GGT/platelet ratio includes GGT and platelets; AST/ALT ratio includes AST and ALT; and AST/platelet ratio index includes AST and platelets. The originally reported cutoffs were used for the categorization of low-, intermediate-, and high-score subgroups. All patients were followed up for the occurrence of RCVEs (comprising cardiovascular death, non-fatal myocardial infarction, and stroke). Cox and Poisson regression analyses were used to assess the relationship of baseline LFSs with the risk of RCVE.Results::During a mean follow-up of (54.67 ± 18.80) months, 532 (8.2%) RCVEs were recorded. Intermediate and high NFS, FIB-4, Forns, and BARD scores were independently associated with an increased risk of RCVE (hazard ratios ranging from 1.42 to 1.75 for intermediate scores and 1.35 to 2.52 for high scores). In the subgroup analyses of sex, age, BMI, DM, and hypertension status, the increased risk of RCVEs with high LFSs (NFS, FIB-4, Forns, and BARD) was maintained across the different subgroups (all P < 0.05). Conclusion::This study showed that LFSs are indeed independently associated with RCVEs, suggesting that LFSs may be used as novel tools for risk stratification in CAD patients with a prior CVE.

Objective::Regarding the secondary prevention of cardiovascular disease (CVD), there is great interest in preventing recurrent cardiovascular events (RCVEs). The prognostic importance of liver fibrosis scores (LFSs) has previously been reported in various CVDs. We hypothesized that LFSs might also be useful predictors for RCVEs in patients with prior cardiovascular events (CVEs). Herein, we aimed to evaluate the associations of LFSs with RCVEs in a large, real-world cohort of coronary artery disease (CAD) patients with a prior CVE.Methods::In this multicenter prospective study, 6527 consecutive patients with angiography-diagnosed CAD who had experienced a prior CVE (acute coronary syndrome, stroke, percutaneous coronary intervention, or coronary artery bypass grafting) were enrolled. LFSs were computed according to the published formulas: non-alcoholic fatty liver disease fibrosis score (NFS) includes age, body mass index (BMI), impaired fasting glycemia or diabetes mellitus (DM), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, platelets, and albumin; fibrosis-4 (FIB-4) includes age, AST, ALT, and platelets; Forns score includes age, gamma-glutamyltransferase (GGT), and platelets; BARD includes BMI, AST/ALT ratio, and DM; GGT/platelet ratio includes GGT and platelets; AST/ALT ratio includes AST and ALT; and AST/platelet ratio index includes AST and platelets. The originally reported cutoffs were used for the categorization of low-, intermediate-, and high-score subgroups. All patients were followed up for the occurrence of RCVEs (comprising cardiovascular death, non-fatal myocardial infarction, and stroke). Cox and Poisson regression analyses were used to assess the relationship of baseline LFSs with the risk of RCVE.Results::During a mean follow-up of (54.67 ± 18.80) months, 532 (8.2%) RCVEs were recorded. Intermediate and high NFS, FIB-4, Forns, and BARD scores were independently associated with an increased risk of RCVE (hazard ratios ranging from 1.42 to 1.75 for intermediate scores and 1.35 to 2.52 for high scores). In the subgroup analyses of sex, age, BMI, DM, and hypertension status, the increased risk of RCVEs with high LFSs (NFS, FIB-4, Forns, and BARD) was maintained across the different subgroups (all P < 0.05). Conclusion::This study showed that LFSs are indeed independently associated with RCVEs, suggesting that LFSs may be used as novel tools for risk stratification in CAD patients with a prior CVE.

Objective To study the relationship of different ABO blood types with the risk of cardiovascular events and the severity of CHD.Methods A total of coronary arteriography-confirmed 3823 Chinese Han CHD patients were divided into O blood type group (n=1140) and non-O blood type group (n=2683).A total of 3654 patients who were followed up by telephone for a median period of 24.6 months were divided into cardiovascular events group (n=348) and cardiovascular events-free group (n =3306).The risk of cardiovascular events in CHD patients with different ABO blood types was assessed according to the Cox proportional hazards model.Results The incidence of left main branch lesion or 3-branch lesions was significantly higher in cardiovascular events group than in cardiovascular events-free group (15.2％ vs 8.1％,47.7％ vs 30.5％,P＜0.01).The Gensini score was significantly higher in non-O blood type group than in O blood type group (20 vs 18,P＜0.05).The incidence of cardiovascular events was higher in non-O blood type group than in O blood type group (10.3％ vs 7.8％,P=0.019).Cox proportional hazards model showed that non-O blood type was an risk factor for cardiovascular events (HR =1.318,95 ％CI:1.030-1.685).The risk of cardiovascular events was still higher in non-O blood type group than in O blood type group after adjustment for confounders (HR=1.291,95％CI:1.008-1.657,P=0.046).Conclusion Non-O blood type is closely related with cardiovascular events in Chinese Han CHD patients.

Objective To study the value of endothelin-1 (ET-1) in predicting the outcome of stable coronary artery disease (SCAD) patients.Methods A total of 3154 SCAD patients who were followed up for 24 months were divided into cardiocerebral vascular events group (n=189) and cardiocerebral vascular events-free group (n =2965).Their serum ET-1 level was measured by ELISA.The patients were further divided into ET-1 ＜0.3 pmol/L group (n=1588) and ET-1≥0.3 pmol/L group (n=1566).The value of ET-1 in predicting the end events was assessed by Cox regression analysis.The survival curve was plotted by Kaplan-Meier analysis.Results The serum ET-1 level was signify-cantly higher in cardiocerebral vascular events group than in cardiocerebral vascular events-free group (0.33 pmol/L vs 0.30 pmol/L,P=0.004).The incidence of clinical end events was significantly lower in ET-1 ≥0.3 pmol/L group than in ET-1 ＜0.3 pmol/L group (7.02％ vs 4.97％,P=0.015).Multivariable Cox regression analysis showed that ET-1 was a predictor of clinical end events (HR=1.656,95％CI:1.099-2.496,P=0.016).Kaplan-Meier analysis showed that the events-free survival rate was lower in patients with a higher serum ET-1 level than in those with a lower serum ET-1 level (P=0.016).Conclusion ET-1 is an important risk factor for the outcome of SCAD patients.Further studies are needed to confirm its long-term value in predicting the outcome of SCAD patients.

Objective: To investigate the current status of application of intra-aortic balloon pump(IABP) and analyze the factors which might impact the application of IABP in patients with acute myocardial infarction complicated with cardiac shock in China. Methods: In China Acute Myocardial Infarction (CAMI) Registry,a nationwide, multicenter(107 hospitals), prospective study, 26 592 patients with acute myocardial infarction were enrolled consecutively between January 1, 2013 and September 30, 2014. After excluding of 30 cases due to missing important data,26 562 cases were analyzed.The application status of IABP was analyzed and multivariate logistic regression analysis was performed to determine the factors related to IABP application. Results: A total of 785(3.0%) patients with acute myocardial infarction received IABP implantation, and 381(49.9%) patients belonged to preventive application of IABP before primary percutaneous coronary intervention,and 6(0.8%) patients were complicated with mechanical complications.There were 118(15.0%) patients with cardiac shock received IABP implantation, which accounted for 12.0%(118/984) of all patients with cardiac shock.Multivariate logistic regression analysis showed that the clinical independent factors of the decision of IABP insertion included dyslipidemia (OR=2.858, 95%CI 1.397-5.846, P=0.004),left ventricular ejection fraction (OR=0.977, 95%CI 0.961-0.994, P=0.009),usage of dopamine (OR=2.817, 95%CI 1.495-5.308, P=0.001), left main disease (OR=2.817, 95%CI 1.495-5.308, P=0.001), GRACE score (OR=1.006, 95%CI 1.000-1.011, P=0.034), receiving primary percutaneous coronary intervention (OR=4.508, 95%CI 1.673-12.146, P=0.003), teritiary hospitals (OR=2.562, 95%CI 1.498-4.384, P=0.001), and higher education of the patients (OR=2.183, 95%CI 1.056-4.509, P=0.016). Conclusions Among the Chinese acute myocardial infarction patients who received IABP implantation, nearly half application of IABP are preventive implantation before primary percutaneous coronary intervention. Only a few patients complicated with cardiac shock received IABP insertion. The clinical conditions, grade of hospitals, degree of education impact the decision of IABP insertion for the patients with acute myocardial infarction. Clinical Trial Registry National Institutes of Health, NCT018746.

Objectives: To investigate the prevalence rate and clinical characteristics of familial hypercholesterolemia (FH) in Chinese patients undergoing coronary angiography due to angina-like chest pain. Methods: From March 2011 to December 2016, a total of 9 908 consecutive patients undergoing coronary angiography in Fuwai Hospital due to angina-like chest pain were enrolled. The age of enrolled patients was (56.6±11.1) years old, and 6 782 cases (68.4%) were male. The patients were divided into two groups: FH group (n=271) and non-FH group (n=9 637) according to the Dutch Lipid Clinic Network diagnostic criteria. A retrospective analyze was performed on the baseline features between the two groups including lipids levels, coronary artery disease (CAD) characteristics, and lipids-lowering treatments. Results: In the total cohort, the prevalence of definite/probable FH was 2.7% (271/9 908). The incidence of premature coronary artery disease (PCAD) (women < 60 years old, or men < 55 years old) was higher in patients with FH than that in patients without FH (70.2%(201/271) vs. 44.5% (4 287/9 637); χ²=93.738, P<0.001). Patients with FH had higher level of TC and LDL-C when compared with patients without FH ((6.74±2.48) mmol/L vs. (4.15±1.10) mmol/L; (4.53±2.39) mmol/L vs. (2.52±0.97) mmol/L; t=19.403, 22.233, P<0.001, respectively). Additionally, 84.9% (230/271) of FH patients were treated with statin at different intensities, but none of them achieved the LDL-C<2.6 mmol/L. Conclusions Chinese patients with familial hypercholesterolemia not only showed a high presence of PCAD and higher lipids levels, but also exhibited a low rate of achievement of low-density lipoprotein cholesterol targets despite statin therapy. Our results thus highlight the importance of early diagnosis and intensive treatment of FH patients.

Objective: To analyze the prevalence and clinical features of familial hypercholesterolemia (FH) in Chinese patients with myocardial infarction (MI). Method: This retrospective study recruited a total of 2 119 consecutive patients (age (56.7±10.9) years old) undergoing coronary angiography with first MI from April 2011 to December 2016. Patients were divided into 2 groups: premature MI (male<55 years old, female<60 years old) and non-premature MI. The diagnosis of FH was established according to Dutch Lipid Clinic Network (DLCN) diagnostic criteria and referred as definite/probable FH in our study. The prevalence and clinical features of FH, including lipid level, MI characteristics and stain therapy, were explored. Multivariable logistic regression analysis was used to assess the predictive value of FH for the presence of premature MI. Results: The prevalence of definite/probable FH was 3.68% (78/2 119) in MI patients and 7.28% (68/934) in premature MI patients. Onset of MI occurred 10 years earlier in patients with definite/probable FH than those without FH ((47.9±9.4) years vs. (58.8±10.7) years, P<0.01). Additionally, we found that the risk of premature MI was significantly and independently increased in definite/probable FH patients (OR=5.32, 95%CI 2.77-10.22, P<0.01). None of FH patients reached the target of LDL-C<1.8 mmol/L under statin therapy. Conclusions The prevalence of FH in Chinese patients with MI is not rare. Clinically, FH is linked with the early onset of MI.