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Background Rs4977574 (A > G) and Rs1333045 (C > T) are both single nucleotide polymorphisms (SNPs) related with coronary artery disease, locating on chromosome 9p21.3. The study aimed to identify the correlation between rs4977574 and rs1333045 polymorphism genotypes and coronary heart disease (CHD) in a Chinese population. Methods Blood samples were collected from 855 subjects. A case-control study was used in this experiment, and 598 cases in the CHD group and 257 subjects in the control group were enrolled. Genotyping was identified by the Agena MassARRAY system. Statistical analysis was conducted by SPSS (Ver 16.0) and plink (Ver. 1.07, Shaun Purcell). Haplotype analysis was performed using Haploview software. Results Association analysis by plink indicated a significant difference in the allele distribution for single nucleotide polymorphisms between cases and controls (rs4977574 P = 0.003, rs1333045 P = 0.035). Fisher’s exact test by plink proved that allele G may be associated with a higher risk of CHD (P = 0.003, odds ratio (OR) = 1.371) and the T allele was likely to reduce the risk of coronary events (P = 0.035, OR = 0.798). The serum levels of apolipoprotein A (ApoA) were higher in subjects with the AG + AA genotype of rs4977574 compared to those with the GG genotype (P = 0.028). In the dominant model of rs1333045, the levels of ApoA were higher and LDL levels were lower in the TC + TT genotype than in the CC genotype. Conclusions The present study examined the association between the 9p21 chromosome rs4977574 and rs1333045 polymorphism genotypes and CHD in a population of Chinese patients. The G allele of rs4977574 and the C allele of rs1333045 are the susceptibility sites of CHD.

Subclinical hypothyroidism (SCH) plays a crucial role in the development and progression of coronary heart disease (CAD). Retinol-binding protein 4 (RBP4) is an adipokine correlated with cardiovascular diseases. Recent studies found that RBP4 levels are increased in patients with SCH. However, the relationship of RBP4 with CAD in SCH patients remains unclear. A total of 199 SCH patients (148 with CAD and 51 without CAD) and 102 healthy controls were enrolled in this study. Serum RBP4 was increased in SCH patients than controls. Moreover, serum RBP4 was higher in SCH patients with CAD. Although there was no significant difference of metabolic parameters between SCH patients with and without CAD, serum RBP4 was positively correlated with body mass index, total cholesterol, and low-density lipoprotein cholesterol, as well as thyroid stimulating hormone. Multivariable logistic regression analyses revealed elevated RBP4 was correlated with increased risk for CAD in SCH patients. Serum RBP4 levels were also increased as the number of stenosed vessels increased. Furthermore, increased RBP4 was positively correlated with the severity of CAD quantified by the Gensini score. Our findings demonstrate that serum RBP4 is associated with the presence and severity of CAD in patients with SCH.

Meteorin‐like (Metrnl) is a novel adipokine that is highly expressed in white adipose tissue. Metrnl stimulates energy expenditure and improves glucose tolerance in rodents. However, whether Metrnl plays a role in coronary artery disease (CAD) remains to be elucidated. The present study aimed to investigate the association of serum Metrnl with CAD in Chinese patients. A total of 193 patients with CAD and 156 control subjects were enrolled in this study. Serum Metrnl concentration was measured by enzyme‐linked immunosorbent assay. Anthropometric phenotypes, fasting glucose, serum lipids, and inflammatory cytokines were measured. Serum Metrnl was lower in CAD patients when compared to those controls (132.41 vs 173.17 pg/mL, P < 0.001). Serum Metrnl was negatively correlated with metabolic parameters, including body mass index, total cholesterol, and low‐density lipoprotein cholesterol as well as inflammatory markers including high‐sensitivity C‐reactive protein, IL‐1β, and IL‐11 even after adjustment for potential confounding variables (P < 0.05). In multivariable logistic regression analyses, compared to those in the highest tertile of serum Metrnl levels, subjects in the lowest tertile had the highest risks for CAD (adjusted OR = 2.63, 95% CI = 1.46‐4.27, P = 0.001). After adjustment for potential confounding variables, serum Metrnl was also decreased as the number of stenosed vessels increased (P < 0.001). Furthermore, decreased Metrnl level was negatively correlated with the severity of CAD quantified by the Gensini score. This first case‐control study shows significant associations of serum Metrnl with the presence and severity of CAD, suggesting Metrnl might be a new promising therapeutic target for CAD.

Warfarin is a commonly prescribed and effective oral anticoagulant. Genetic polymorphisms associated with warfarin metabolism and sensitivity have been implicated in the wide inter-individual dose variation that is observed. Several algorithms integrating patients’ clinical characteristics and genetic polymorphism information have been explored to predict warfarin dose. However, most of these algorithms could explain only over half of the variation in a warfarin maintenance dose, suggesting that additional genetic factors may exist and need to be identified. Here, a drug absorption, distribution, metabolism and excretion (ADME) Core Panel Kit-based pharmacogenetic study was performed to screen for warfarin dose-associated SNP sites in Han-Chinese population patients taking warfarin therapy, and the screen was followed by pyrosequencing-based validation. Finally, we confirmed that the common variant rs9923231 in VKORC1 and two novel genes, SLC15A2 (rs1143671 and rs1143672) and SLCO1B3 (rs4149117 and rs7311358), are associated with the warfarin maintenance dose. As has been shown for those carriers with the variant rs9923231 in VKORC1, it was suggested that those subjects with homozygous minor alleles in those four SNPs should take a lower warfarin dose than those carrying the wild type alleles. Together with the established predictor rs9923231 in VKORC1, those four novel variants on SLC15A2 and SLCO1B3 should be considered as useful biomarkers for warfarin dose adjustment in clinical practice in Han-Chinese populations.

Differences in warfarin maintenance dosages based on the presence of polymorphisms in VKORC1, CYP2C9, CYP4F2, and ORM1 can be determined through dosage adjustment according to routine guidelines. Little is known about whether routine therapy could provide consensus anticoagulation control for patients with different genotypes. This study was carried out to compare anticoagulant control in patients with different genotypes. Six hundred seventy patients using warfarin according to Chinese guidelines were enrolled. Warfarin dosages and monitored international normalized ratios (INRs) were recorded. Genotypes of VKORC1 rs9923231, CYP4F2 rs2108622, CYP2C9 rs1057910, and ORM1 rs17650 polymorphisms were determined. Warfarin dosages and INR were compared between genotypes. Patients with the AGCC*F*F*1*1 polymorphism took longer than patients with the AACC*F*F*1*1 polymorphism (20 vs 5 days, P < .001) to achieve the targeted INR range. The INR values of patients with AACC*F*F*1*3 were unstable and did not enter the stable state control phase until after 35 days. The peak INR of patients with the AACC*F*F*1*3 polymorphism was exceedingly high, with some values exceeding the control range limit of 3.0. Patients with the AACC*F*S*1*1 or AACT*F*F*1*1 polymorphisms exhibited similar INR values as the patients with the AACC*F*F*1*1 polymorphism. This study found that routine medication with warfarin provides significantly different levels of anticoagulant control between patients with wild-type genotypes and patients with heterozygous polymorphism genotypes of VKORC1 rs9923231 or CYP2C9 rs1057910. Patients with heterozygous polymorphism genotypes of VKORC1 or CYP2C9 require genotype-directed therapy with warfarin to increase efficacy and safety in anticoagulant treatment.

To explore the association between methylation of antisense non-coding RNA in the INK4 locus (ANRIL) and coronary artery disease (CAD) development. Methylation levels of ANRIL in 100 subjects with CAD and 100 controls were quantitatively analyzed using Sequenom MassARRAY. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify novel pathways. Our analyses indicated that 7 to 8 CpG sites within the 2nd CpG island located upstream of ANRIL, also known as cyclin-dependent kinase inhibitor 2B – antisense 1 (CDKN2B-AS1), are hyper-methylated in CAD subjects compared to controls (p = 0.034). The 40th CpG site within the 2nd CpG island located upstream of CDKN2B-AS1 was methylated to a lesser extent in CAD subjects compared to controls (p = 0.045). Both Pearson and Spearman analyses indicated that methylation levels were significantly associated with total cholesterol (r = 0.204, p = 0.004), fasting high-density lipoprotein cholesterol (r = 0.165, p = 0.020), and fasting low-density lipoprotein cholesterol (r = 0.265, p = 0.000). KEGG pathway analysis revealed a significant enrichment of genes associated with the tumor necrosis factor (TNF) signaling pathway. Among them, CCAAT/enhancer binding protein (C/EBPβ) was identified as a key transcription factor that promotes expression of CDKN2B-AS1 through promotor interaction. DNA methylation of the ANRIL promoter was significantly associated with CAD development in our study. Our analyses suggest that C/EBPβ is a key transcription factor that promotes CDKN2B-AS1 expression by directly interacting with the gene promotor mediated by TNF signaling.

Acute ST-segment elevation myocardial infarction (STEMI) is the most lethal coronary heart disease with vascular endothelium dysfunction and inflammation in the disease development process. Endothelial cell-specific molecule 1 (ESM-1) and lipoprotein-associated phospholipase A2 (Lp-PLA2) are important for the diagnosis and characterization of STEMI. To date, no studies have reported the correlation between ESM-1 and Lp-PLA2 levels in patients with STEMI, which may be an important predictor of the fatal disease. To measure the level of serum ESM-1 and Lp-PLA2, and to evaluate the relationship and the clinical significance of these two biomarkers in patients with acute STEMI, 37 inpatients with acute STEMI were sequentially enrolled in the research group and 24 study objects with normal coronary artery function were included in the control group. The measurement of the relative parameters was done by enzyme-linked immunosorbent assay using blood samples taken from the median cubital vein while the inpatients were enrolled. The levels of serum SEM-1 and Lp-PLA2 were significantly higher in patients with acute STEMI than in study objects with normal coronary artery function (P

Aims: To investigate the relationship between the miR-130a polymorphism rs731384 and coronary artery disease (CAD) and to further explore the molecular mechanism of the pathogenesis of CAD, an observational single-center study was conducted. Method: A total of 876 subjects were recruited in the present study. Four milliliters of venous blood was drawn after 12 h of fasting to perform biochemical assays. CAD patients and controls were distinguished by coronary angiography. Rs731384 was genotyped on the Agena MassARRAY system according to the manufacturer’s user guide. Statistical analysis was conducted using SPSS 16.0 software. Results: The study found that the plasma levels of total cholesterol (TC) (P=0.006), low-density lipoprotein cholesterol (LDL-C) (P=0.030), apolipoprotein A (ApoA) (P=0.038), and apolipoprotein B (ApoB) (P=0.022) distributed differently in patients with various alleles. Additionally, the AA genotype of rs731384 was found to be a protective factor against CAD in a recessive model (AA:AG+GG, odds ratio (OR) = 0.408, 95% confidence interval (95% CI) = 0.171–0.973, P=0.043). A significant association was found between the gene–environment interaction and CAD risk. The AA genotype along with high-density lipoprotein cholesterol (HDL-C) level ≥ 1.325 mmol/l significantly decreased the CAD risk (AA:AG+GG, OR = 0.117, 95% CI = 0.023–0.588, P=0.009). Conclusion: The mutant AA genotype of rs731384 seems to be a protective factor against CAD, and rs731384 plays an important role in the human metabolism of plasma lipids.

Aims: We evaluated the synergistic effect of lipoprotein-associated phospholipase A2 (Lp-PLA2) in association with classical risk factors in predicting coronary heart disease (CHD) and demonstrated the diagnostic value of Lp-PLA2 for predicting coronary stenotic lesions in subjects with CHD. Methods: Blood samples were acquired from 911 consecutive adult subjects (662 males and 249 females) from 11 ethnic groups. Lp-PLA2 plasma levels were detected using a commercially available turbidimetric immunoassay (TIA). CHD in patients was confirmed using coronary angiography, and the severity of coronary atherosclerosis was assessed using the Gensini scoring system. Results: A binary logistic regression was performed to analyse the relationships between Lp-PLA2 and other risk factors. A multivariate logistic regression analysis revealed that Lp-PLA2 levels were significantly associated with CHD (OR, 1.882; 95% CI, 1.369-2.587, p=0.000).The area under the receiver operating characteristic curve for Lp-PLA2 was 0.589 (95%CI, 0.549-0.629, p=0.000).The synergism between Lp-PLA2 and other risk factors was also investigated. The proportion of CHD attributable to the interaction between Lp-PLA2 and age was as high as 64%. Conclusions: Lp-PLA2 levels in human plasma were positively associated with the severity of CHD, and there was a clear positive interaction between Lp-PLA2 and classical risk factors in predicting CHD.

Objective: The aim of the present study is to investigate the association between the single nucleotide polymorphism (SNP) sites of peroxisome proliferator-activated receptor Δ (PPARD) and the risk of coronary artery disease (CAD). To this end, a prospective observational single-center study of the clinical data from 880 subjects in a Chinese population was conducted. Methods: A total of 880 subjects, including 609 CAD patients and 271 control subjects, were selected for the present study. All inpatients had 4 ml of venous blood drawn after 12 h of fasting, and then clinical tests were conducted to obtain the biochemical parameters. CAD patients and Controls were distinguished by coronary angiography. Statistical analysis was conducted with SPSS software (ver 16.0). Results: A significant association between the G-alleles of PPARD rs3777744 and rs3798343 and a decreased risk for CAD was found. Moreover, we found an interaction between high fasting high-density lipoprotein cholesterol (HDL-C) serum levels, low serum glucose levels and their genotypes, ultimately decreasing the risk of CAD. Haplotype analysis was conducted on the three SNP sites, rs3777744 and rs3798343 to form a block [r2 = 0.79, D′ = 0.99). The A-C haplotypes were associated with an increased risk of CAD (odds ratio (OR), 95% confidence interval (CI): 1.321 (1.060–1.647), P=0.013], and the G-G haplotypes were associated with a decreased risk [OR, 95% CI: 0.714 (0.567–0.849), P=0.004]. Conclusions: Our study indicates a significant association between the G-alleles of PPARD rs3777744 and rs3798343 and a decreased CAD risk. In addition, genotypes interact with high serum HDL-C levels and low serum glucose levels, resulting in decreased prevalence of CAD.

Background Adaptor-related protein complex 2 alpha 2 subunit (AP2A2) gene encodes a protein-a subunit of the AP-2 adaptor protein complex. Evidence has revealed that benzodiazepine receptor-associated protein 1 (BZRAP1) is abundant in the hippocampus with potential effects on brain diseases. Recently, an epidemiological study reported that two variants (rs7396366 and rs2526378) closest to the AP2A2 and BZRAP1 genes are associated with higher plasma lipids and Alzheimer’s disease. Whether the two single nucleotide polymorphisms (SNPs) are actually relevant to coronary artery disease (CAD) and CAD severity remains elusive. Our aim was to assess whether these two SNPs are relevant to CAD and its severity in a Chinese population. Methods Three hundred and thirty-five patients with documented CAD (282 stable CAD, 28 non-ST-segment elevation myocardial infarction, 25 ST-segment elevation myocardial infarction), and 372 non-CAD controls were included in the study. The participants were divided into two groups according to coronary angiography results. CAD patients were further demarcated into subgroups with one-, two-, or three-vessel stenosis. Genotypes at rs7396366 and rs2526378 were examined using polymerase chain reaction-ligase detection reaction. The association between these two SNPs with CAD and its severity were analyzed. Results The frequency of the rs7396366 TT genotype was significantly higher in CAD patients than in controls (13.7% vs. 7.8%, 95% CI: 1.15–3.07, P = 0.014). Subjects with a variant genotype T allele had an increased risk of CAD compared with G allele carriers (additive model: 95% CI: 1.21–3.35, P = 0.008). After adjustment for traditional cardiovascular risk factors, analysis of the dominant models involving rs7396366 also showed that T allele carriers had a significantly higher risk for CAD than G allele carriers had (dominant model: OR 1.48, 95% CI: 1.03–2.14, P = 0.035). Age, sex, type 2 diabetes mellitus, fasting plasma glucose, and the TT genotype in rs7396366 were significantly associated with three-vessel lesions. Despite these significant outcomes of rs7396366, information on rs2526378 showed no significant difference between CAD patients and non-CAD controls. Conclusion Our results show that the T allele and TT genotype in rs7396366, closest to the AP2A2 gene, are linked to an increased risk of CAD and its severity in a Chinese population. Electronic supplementary material The online version of this article (10.1186/s12872-018-0905-2) contains supplementary material, which is available to authorized users.

Objectives We aimed to assess the effect of selective intracoronary hypothermia on outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Background Intracoronary hypothermia, the feasibility and safety of which has been validated in humans, induced by selective trans-coronary infusion of saline at different temperatures can reduce infarct size (IS) prior to reperfusion in animal models of STEMI. Methods Sixty STEMI patients presenting with thrombolysis in myocardial infarction (TIMI) flow grade 0/1 were randomized after coronary artery angiography. Intracoronary hypothermia was induced by selective trans-coronary infusion of saline at 4°C to the endangered myocardium in the 30 patients. The primary endpoint, absolute IS expressed as IS/myocardium at risk (MaR), was assessed by cardiac magnetic resonance imaging at day 7 post-PPCI in 50 patients. Clinical follow-up was undertaken at day 30 after procedure. Results Intracoronary hypothermia was successfully performed in hypothermia group, without increase in arrhythmia or hemodynamic instability. The mean temperature reduction of 5.8 ± 1.1°C in distal coronary artery was achieved before reperfusion. Mean IS/MaR was predominantly reduced in the hypothermia group (44.85 ± 5.89% vs. 50.69 ± 10.75%, P = 0.022), especially in the anterior STEMI subgroup (46.12 ± 7.54% vs. 55.27 ± 11.175%, P = 0.023). The clinical events appeared no statistical difference between the two groups at the 30-day follow-up. Conclusion The statistical difference in IS/MaR by intracoronary hypothermia as adjunctive therapy to PPCI is an important observation and warrants a larger pivotal trial fully powered for efficacy.

Background The single nucleotide polymorphism (SNP) rs12040273, a variant of UDP-N–acetylgalactosamine, polypeptide GalNAc-transferase 2, has recently been reported to be significantly associated with development of carotid artery intima-media thickness (IMT) in a Chinese population based on a genome-wide association study. Because IMT is a potent marker of coronary artery disease (CAD), the aim of this study was to evaluate the relation of rs12040273 to susceptibility and severity of CAD in a Chinese Han population. Methods We performed a hospital-based case-control study. Three hundred and thirty-one individuals (199 CAD patients and 112 non-CAD controls) undergoing coronary angiography were consecutively enrolled in the study. The Gensini score results were used to assess the severity of CAD. The method of polymerase chain reaction-ligase detection reaction (PCR-LDR) was used to distinguish different genotypes at rs12040273. Results The distribution of genotypes at rs12040273 was comparable between CAD patients and non-CAD controls (P > 0.05). The frequencies of the genotypes were also not significantly associated with the risk of CAD and its severity assessed by the Gensini score method, with the OR of 1.38 (95% CI = 0.80–2.40, P = 0.24) and 1.14 (95% CI = 0.69–1.86, P = 0.60) respectively. However, stratified analysis showed that the serum HDL-C levels of subjects with the CC genotype were significantly higher than those with CT/TT genotypes in non-CAD controls (P = 0.002). Conclusion Our results suggest that the rs12040273 variants might not be associated with the susceptibility of CAD or its severity in a Chinese Han population. Moreover, the CC genotype could be associated with elevated serum HDL-C levels.

H19 is an imprinted gene transcribing a long non-coding RNA and is downregulated postnatally. Re-expression of H19 has been observed in patients with atherosclerosis. However, to date, no data has been published on the association of H19 polymorphisms with the risk of coronary artery disease (CAD). In this study, four polymorphisms, rs217727, rs2067051, rs2251375, rs4929984, were analyzed in 701 CAD patients and 873 age- and sex-matched control subjects. Polymorphisms were genotyped by TaqMan technology. Our data showed that the T variant of rs217727 was associated with an increased risk of CAD [additive model: odds ratio (OR) = 2.05, 95%CI = 1.35–3.12; dominant model: OR = 1.46, 95% confidence interval (CI) = 1.12–1.90; recessive model: OR = 1.75, 95%CI = 1.18–2.58], while A variant of rs2067051 was associated with a decreased risk of CAD (additive model: OR = 0.66, 95%CI = 0.45–0.96; recessive model: OR = 0.71, 95%CI = 0.50–0.99). Combined analysis showed that subjects carrying 3 or 4 risk alleles had a significantly increased risk of CAD, relative to those with 0–2 risk alleles (OR = 1.61, 95%CI = 1.20–2.15). Moreover, CAD patients with 3 or 4 risk alleles also had significantly higher Gensini scores than those with 0–2 risk alleles (P = 0.001). Further haplotype-based analysis revealed that individuals with C-G-C-C, T-G-A-A, and T-A-A-A haplotypes indicated a higher prevalence of CAD (OR = 1.88, 95%CI = 1.03–3.43; OR = 2.26, 95%CI = 1.19–4.31; OR = 2.66, 95%CI = 1.34–5.25, respectively), compared to individuals with the most common C-G-A-C haplotype. In conclusion, our study demonstrates for the first time that common polymorphisms of H19 are associated with the risk and severity of CAD in a Chinese population. Future studies are needed to explore the underlying mechanisms of our findings.

The copper transportersitalicCTR1/italic,italicCTR2/italic,italicATP7A/italic, anditalicATP7B/italicregulate intracellular concentration of platinum by mediating its uptake and efflux in cells. We sought to explore the effect of genetic polymorphisms initalicCTR1/italic,italicCTR2/italic,italicATP7A/italic, anditalicATP7B/italicon platinum resistance in patients suffering from epithelial ovarian cancer (EOC). A total of 152 Chinese EOC patients were enrolled in this study, all of whom underwent adjuvant chemotherapy using platinum and taxane after maximal debulking surgery. In total, 11 single-nucleotide polymorphisms (SNPs) initalicCTR1, CTR2, ATP7A/italic, anditalicATP7B/italicwere genotyped in these patients. TheitalicCTR1/italicrs10981694 polymorphism was observed to be associated with carboplatin resistance, while patients with the rs10981694 G allele showed a significantly higher rate of carboplatin resistance (OR = 4.00, 95% CI 1.309 - 12.23, p 0.01). In addition, we found thatitalicATP7A/italicrs2227291 was associated with cisplatin resistance and that carriers of the C allele were more sensitive to cisplatin (OR = 0.40, 95% CI: 0.17 - 0.94, p = 0.03). Our findings suggest that theitalicCTR1/italicanditalicATP7A/italicgenetic polymorphisms could affect platinum resistance. TheitalicCTR1/italicanditalicATP7A/italicgenes might be considered a predictive marker for carboplatin and cisplatin resistance, respectively. .

Recent studies in animal models and humans show that long non-coding RNAs (lncRNAs) are involved in the development of atherosclerosis, which contributes to the pathological foundation of coronary artery disease (CAD). LncRNAs in plasma and serum have been considered as promising novel biomarkers for diagnosis and prognosis of cardiovascular diseases, especially CAD. We here measured the circulating levels of 8 individual lncRNAs which are known to be relevant to atherosclerosis in the plasma samples from 300 patients with CAD and 180 control subjects by using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) methods. We found that the plasma level of H19 and long intergenic non-coding RNA predicting cardiac remodeling (LIPCAR) were significantly increased in patients with CAD. The area under the receiver operating characteristic curve was 0.631 for H19 and 0.722 for LIPCAR. Multivariate logistic regression analyses indicated that plasma H19 and LIPCAR were independent predictors for CAD, even after adjustment for traditional cardiovascular risk factors. Further studies identified that plasma levels of H19 and LIPCAR were also increased in CAD patients with heart failure compared to those with normal cardiac function. Taken together, our results suggest that increased plasma levels of H19 and LIPCAR are associated with increased risk of CAD and may be considered as novel biomarkers for CAD.

Objective To explore the association of working hours and occupational physical activity (OPA) with the occurrence of coronary heart disease (CHD) in a Chinese population. Methods A total of 595 participants (354 and 241 patients with and without CHD, respectively) aged between 24 and 65 were enrolled in our study, which was conducted at the First Affiliated Hospital of Nanjing Medical University between December 2015 and October 2016. Participant characteristics were collected from face-to-face questionnaires, and logistic regression analysis was conducted to examine the association of working hours and OPA with the occurrence of CHD. Results Compared with non-employed people, long working hours (especially ≥55 hours/week) contributed to the occurrence of CHD (adjusted odds ratio[OR] = 2.213, 95% confidence interval [CI]: 1.125, 4.355, P = 0.021) after multivariate adjustment in the Chinese population. With the extension of worktime, the CHD risk increased (P for the dose-response trend = 0.022). Meanwhile, even after adjusting for engagement in physical activity during leisure time, sedentary behavior at work had an adverse effect on CHD risk (adjusted OR = 2.794, 95%CI: 1.526, 5.115, P = 0.001), and a linear relationship was also found between OPA and CHD (P for the trend = 0.005). Conclusions Long working hours and sedentary behavior at work are associated with a high risk of CHD. In addition, prolonged working hours in sedentary occupations increases the risk of CHD, independent of engagement in leisure time physical activity.

Background: The diameters of the coronary arteries have been suggested to be a potential predictor of coronary artery disease (CAD). However, whether the diameters of the coronary arteries are associated with the coronary lesion severity on angiography has not been determined. Methods: One hundred sixty-seven consecutive adult patients (109 men and 58 women) aged 31–84 years who underwent coronary angiography for suspected or known CAD were enrolled. The known catheter tip diameter was used as the calibration to measure the diameters of coronary arteries, and the severity of coronary lesions was evaluated with the vessel score and Gensini score. Results: In patients with a higher vessel score and Gensini score, the diameters of the left main (LM), left anterior descending (LAD), left circumflex (LCX), and right coronary arteries (RCA) were smaller (all p

Background: Differences in microRNA (miRNA) profiles between patients with and without coronary heart disease (CHD)have not been fully determined. The purpose of the study was to evaluate in a multi-ethnic population in China the predictive value of miRNAs previously suggested to have a role in CHD. Subject and method: 932 participants were included, and plasma samples obtained. A quantitative reverse-transcription PCR(RT-qPCR) assay was conducted to confirm the concentration of plasma miRNAs. Circulating levels of miRNAs were quantified using the 2-Δct method. The severity of coronary atherosclerosis was evaluated via Gensini Scores. Result: The circulating levels of the nine proposed miRNAs were not different among the five main ethnicities examined (all p > 0.05). The Spearman correlation analyses indicated that miR-221 and miR-130a were negatively associated with the severity of CHD as indicated by Gensini Scores (r = -0.106, p = 0.001;r = -0.073, p = 0.026). Results of the univariate analysis showed that lower circulating miR-221 (OR, 1.663; 95 % CI, 1.255-2.202, p =

Background Early B-cell factor 1 (EBF1) is a transcription factor expressed primarily during early B cell development. Previous studies have shown EBF1 regulates blood glucose and lipid metabolism in mice with diabetes and central adiposity. Recently, a genetic variation (rs36071027) located in an EBF1 gene intron was associated with carotid artery intima-media thickness. However, whether this polymorphism is actually linked with coronary artery disease (CAD) and its severity remains unclear. Methods This study includes 293 CAD cases and 262 controls without CAD. All participants were devided into two groups based on their coronary angiography results. A polymerase chain reaction-ligase detection reaction was used to identify genotypes at rs36071027, and CAD patients were further divided into subgroups with one-, two-, or three-vessel stenosis reflective of CAD severity. Results The frequency of the rs36071027 TT genotype was significantly higher in CAD cases versus controls (4.8% vs. 1.5%, 95% CI: 1.13-10.81 P = 0.029). Subjects with a variant genotype T allele had an increased risk of CAD compared to C allele carriers (additive model: 95% CI: 1.13-2.23, P = 0.008). After adjustment for cardiovascular risk factors, analysis of the additive and dominant models involving rs36071027 also revealed that T allele carriers had a significantly higher risk for CAD than C allele carriers (additive model: OR 1.56, 95% CI 1.10–2.22, P = 0.013; dominant model: OR 1.60, 95% CI 1.07–2.41, P = 0.023). Furthermore, both diabetes and the CT + TT rs36071027 genotype were significantly associated with three-vessel stenosis. Conclusion Our results in a Chinese population suggest that the TT genotype and T alleles in rs36071027 in the EBF1 gene are associated with an increased risk of CAD and its severity. Electronic supplementary material The online version of this article (doi:10.1186/s12872-017-0489-2) contains supplementary material, which is available to authorized users.

To investigate the influence of cytochrome P450 oxidoreductase (POR) polymorphisms (A503V and rs2868177) on warfarin stable dosage (WSD) in Han-Chinese patients with mechanical heart valve replacement (MHVR).Three hundred and seventeen Han-Chinese MHVR patients on stable maintenance dose of warfarin were enrolled. Blood samples were collected for genotyping analyses of VKORC1 -1639GA, CYP2C9 *3, CYP4F2 rs2108622 and POR (A503V and rs2868177). Average WSD of carriers with variant POR genotypes or haplotypes were compared. Association analyses were performed by single and multiple linear regression analysis.The variant allele frequencies of POR polymorphisms (A503V and rs2868177) were 38.8 % and 44.8 %, respectively. D' between POR A503V and rs2868177 was 0.855, r(2) was 0.375, and the frequencies of the four POR haplotypes were 42.3 % for CG, 36.3 % for TA, 18.9 % for CA, and 2.5 % for TG, respectively. There were no significant differences in average WSD among carriers with three variant POR A503V genotypes or among carriers with three variant POR rs2868177 genotypes (both P 0.05). Similarly, there were no significant differences in average WSD among carriers with variant POR haplotypes (all P 0.05). Neither single nor multiple linear regression analyses showed significant effects of POR A503V or POR rs2868177 polymorphisms on WSD.POR polymorphisms (A503V and rs2868177) do not appear to significantly influence WSD in Han-Chinese patients with MHVR.

Slight elevations in cardiac troponin I and T are frequently observed after percutaneous coronary intervention (PCI). Contrast-induced acute kidney injury (CI-AKI) is a complex syndrome induced by exposure to intravascular contrast media (CM). Currently, the relationships between the CM, pre-existing kidney insufficiency, CI-AKI, and myonecrosis after elective PCI are unclear. To investigate the relationship between CI-AKI and post-procedural myonecrosis (PMN) after PCI, we analyzed 327 non-ST-segment elevation acute coronary syndrome subjects undertaking elective PCI. The levels of cardiac troponins (cTns), cTnI and cTnT, at baseline and on at least one occasion 18–24 h after PCI were measured. We also recorded serum levels of creatinine (SCr) and the urine albumin:creatinine ratio (ACR) before coronary angiography, and 24–48 h and 48–72 h after contrast administration. A post-procedure increase in cTns was detected in 16.21% (53/327) of subjects with cTns levels >99th to 5×99th percentile upper reference limit (URL). Twenty-seven patients (8.26%) developed CI-AKI. CI-AKI occurred more often in subjects with PMN than in those without PMN (20.8% versus 5.8%, respectively, P=0.001). Multiple logistic regression analysis revealed that pre-existing microalbuminuria (MA) was an important independent predictor of PMN (OR: 3.31; 95% CI: 1.26–8.65, P=0.01). However, there was no correlation between the incidence of CI-AKI and PMN (OR: 2.38; 95% CI: 0.88–6.46, P=0.09). We conclude that pre-existing MA was not only an important independent predictor of CI-AKI but also of PMN.

ORM1 is a plasma drug binding protein. Its polymorphism rs17650 (SF) has been reported to be an important factor affecting the binding ability and effect of antiretroviral protease inhibitors. The aim of this study was to determine whether the ORM1 rs17650 polymorphism also influences warfarin therapy.A total of 191 Chinese patients with steady-dose warfarin therapy were enrolled in this study. The patients were studied for warfarin maintenance dose, the ORM1 rs17650 polymorphism, and two polymorphisms previously demonstrated to affect warfarin response [CYP2C9 rs1057910 (3) and VKORC1 rs7294 (-1639 GA)].Warfarin dose was partially correlated with the VKORC1 rs7294, CYP2C9 rs1057910 and ORM1 rs17650 polymorphisms. Patients carrying the wild-type of these three genes (n = 96) took a mean dose of 3.0 ± 1.1 mg warfarin, which was significantly higher than that taken by the 52 S patients (2.7 ± 0.7) and 11 S S patients (2.5 ± 0.6 mg) (p = 0.048).We identified ORM1 as another polymorphic gene affecting warfarin dose requirements. ORM1 S carriers require lower maintenance doses to achieve and maintain an optimal level of anticoagulation.

Background Genome-wide association studies have reported that the 9p21.3 locus confers risk for coronary artery disease (CAD). However, it is not known whether rs10811656 is linked with CAD in a Chinese population. Thus, the purpose of this study was to investigate the potential association between rs10811656 and the risk of CAD in a Chinese population. Methods We conducted a hospital-based, case–control study with 251 CAD patients and 304 controls to examine the potential association of rs10811656 with CAD. Results The frequencies of the TT genotypes in CAD cases were significantly different from those in controls (adjusted OR: 1.96, 95 % CI: 1.09–3.505, P = 0.024). Compared to controls, rs10811656 was significantly associated with the stable angina pectoris (adjusted OR: 1.42, 95 % CI: 1.06–1.90, P = 0.017), but not with acute coronary syndrome. There was also a highly significant association of rs10811656 with double-vessel and triple-vessel disease when patients were divided into subgroups based on the number of diseased vessels (adjusted OR: 1.68 and 1.60, 95 % CI: 1.14–2.44 and 1.10–2.33, P = 0.009 and 0.02, respectively). Conclusion Our results suggest that the rs10811656 locus might be associated with CAD in a Chinese Han population.

Objective: The objective of this study was to explore the association between coronary artery disease and genetic polymorphisms of the renin–angiotensin–aldosterone system (RAAS) pathway. In addition, we examined the interactions between demographic and lifestyle risk factors (environmental factors including age, sex, smoking status, alcohol intake) and RAAS polymorphisms on disease risk. Methods: A total of 1089 subjects who underwent coronary angiography were enrolled in this study. Eight RAAS polymorphisms were genotyped in this population: the G2350A (rs4343) polymorphism in exon 17 of the angiotensin converting enzyme (ACE) gene, 1166A→C (rs5186) and 573C/T (rs5182) in the angiotensin II type 1 receptor (AGTR1) gene, the -344C→T transversion (rs1799998) in the aldosterone synthase (CYP11B2) gene, and the G-217A (rs5049), G-6A (rs5051), M235T (rs699; T4072C), and T174M (rs4762; C3889T) polymorphisms in the angiotensinogen (AGT) gene. Subjects with coronary heart disease were defined as those with at least 50% stenosis in at least one major coronary artery, and, the severity of coronary atherosclerosis was defined by the Gensini scoring system. Results: Compared to the subjects with AA genotype, the subjects with AG + GG genotype of rs1799998 had significant lower gensini score (p=0.029). After adjusting for age, gender, cigarette smoking, and alcohol intake status, the AG genotype (OR 0.717 95%CI 0.541–0.950, p=0.021) and the AG + GG genotype (OR 0.730 95%CI 0.559–0.954, p=0.021) distributions of rs1799998 were significantly different between the cases and controls compare to the AA genotype. Subjects with three at-risk loci had increased risk of coronary artery disease compared to subjects carrying 0 or 1 risk-associated polymorphism (OR [95% CI]:1.579 [1.077–2.316], p=0. 019), and the significance of the association was not reduced after adjusting for age, sex, cigarette smoking, or alcohol intake (adjusted OR [95% CI]: 1.673 [1.116–2.507], p=0.013). The results of multifactor-dimensionality reduction analysis revealed an interaction effect of CYP11B2 -344C→T, age, and smoking status on the risk of coronary heart disease (training OR [95% CI]: 3.7685 [2.8463–4.9895], pOR [95% CI]: 2.7583 [1.2038–6.3203], p=0.015). Conclusions: Subjects who carried the G allele of the rs1799998 polymorphism significantly associated with coronary heart disease and severity of coronary atherosclerosis estimated by the Gensini score in the whole population of the study. And, multiple RAAS gene polymorphisms are associated with coronary artery disease. The interaction of the CYP11B2 -344C→T polymorphism (rs1799998), age, and smoking status is also associated with enhanced risk of coronary artery disease.

To investigate the relationship between free triiodothyronine (FT3) and the international normalized ratio (the ratio of the prothrombin time of a patient to the normal sample, INR) in Chinese euthyroid subjects with acute ST-segment elevation myocardial infarction (STEMI).A total of 231 consecutive patients (177 males, 54 females) with STEMI were enrolled. Anthropometric and laboratory measurements, including heart rate, respiratory rate, blood pressure, body temperature, platelet count, INR, prothrombin time, activated partial thromboplastin time, FT3, free thyroxine (FT4), and thyroid-stimulating hormone, were collected from all the patients. The levels of FT3 and FT4 were measured with a full-automatic immune analyzer. The INR was determined using a coagulation analyzer.Patients were classified into 4 groups according to their quartile FT3 and FT4 levels: 0.40-3.09 (n=52), 3.10-3.69 (n=56), 3.70-4.29 (n=64) and 4.30-7.10 (n=59) for FT3; 4.9-14.8 (n=57), 14.9-16.8 (n=58), 16.9-18.7 (n=57) and 18.8-29.0 (n=59) for FT4. Subjects with a high FT3 level had significantly lower values of INR than those with a low FT3 level (P=0.01). Multiple linear regression analysis revealed decreased serum FT3 as an independent risk factor for elevated INR values (β=-0.139, P=0.025). The value of INR was similar among the 4 groups according to the quartile FT4 levels (P=0.36).Free triiodothyronine was negatively associated with INR in the patients with acute STEMI and normal thyroid function.

Background: Epidemiologic studies are inconsistent regarding the association between tea consumption and the risk of coronary artery disease (CAD). Objective: The objective was to perform a meta-analysis to determine whether an association exists between tea consumption and total CAD endpoints in observational studies. Design: We searched PUBMED and EMBASE databases for studies conducted from 1966 through November 2009. Study-specific risk estimates were combined by using a random-effects model. Results: A total of 18 studies were included in the meta-analysis: 13 studies on black tea and 5 studies on green tea. For black tea, no significant association was found through the meta-analysis [highest compared with lowest, summary relative risk (RR): 0.92; 95% CI: 0.82, 1.04; an increment of 1 cup/d, summary RR: 0.98; 95% CI: 0.94, 1.02]. For green tea, the summary RR indicated a significant association between the highest green tea consumption and reduced risk of CAD (summary RR: 0.72; 95% CI: 0.58, 0.89). Furthermore, an increase in green tea consumption of 1 cup/d was associated with a 10% decrease in the risk of developing CAD (summary RR: 0.90; 95% CI: 0.82, 0.99). Conclusions: Our data do not support a protective role of black tea against CAD. The limited data available on green tea support a tentative association of green tea consumption with a reduced risk of CAD. However, additional studies are needed to make a convincing case for this association. Am J Clin Nutr doi: 10.3945/ajcn.110.005363.

To investigate the SLCO1B1 388AG and 521TC polymorphisms in hyperlipidemia patients and evaluate the effect of the two polymorphisms on the lipid-lowering efficacy of pitavastatin.The functional polymorphisms of SLCO1B1 (388AG and 521TC) were genotyped in 140 Chinese patients with essential hyperlipidemia using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and one-step tetra-primers ARMS-PCR. Eighty-five patients were enrolled in the clinical trial and given 2 mg of pitavastatin daily for 8 weeks. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) serum levels were measured at baseline, after 4 weeks and after 8 weeks of treatment.The allele frequencies of SLCO1B1 388AG and 521TC in essential hyperlipidemia patients were 71.1% and 11.1%, respectively. The 4- and 8-week treatment with pitavastatin significantly reduced TC, TG, and LDL levels, but there was no statistical difference among patients with wild type, SLCO1B1 388AG or SLCO1B1 521TC in the lipid-lowering efficacy of pitavastatin.The present study found that the allele frequencies of SLCO1B1 388AG and 521TC in Chinese patients with essential hyperlipidemia are comparable to those in healthy Chinese population. SLCO1B1 388AG and 521TC do not affect the lipid-lowering efficacy of pitavastatin.

Visfatin is a newly identified pro-inflammatory adipokine expressed predominantly in visceral fat. Previous studies have suggested a role for visfatin in low-grade inflammation and regulation of lipid metabolism. Most recently, a genetic polymorphism -1535CT located in the visfatin gene promoter has been identified, and suggested to be associated with the regulation of visfatin expression, lipid levels. However, it is unclear whether this polymorphism has a linkage with CAD.We conducted a hospital-based case-control study with 257 CAD patients and 292 controls to examine the potential association of the Visfatin -1535CT polymorphism with CAD.The frequencies of the CC, CT, and TT genotypes in cases were significantly different from those of controls (chi2=6.223, P=0.045). Subjects with the variant genotypes (CT+TT) had a 40% decreased risk of CAD relative to CC carriers (adjusted OR=0.60, 95%CI=0.40-0.89). Furthermore, the adjusted OR of a TT genotype for CAD was 0.52 (95%CI=0.31-0.87). There was a significant association between Visfatin -1535CT polymorphism and triglyceride levels in both CAD patients and controls (P=0.003, 0.018, respectively). In stratified analyses, the T allele was significantly associated with reduced risk of CAD in males, subjects with age59years, and non-smokers. Moreover, a borderline statistical significance (P=0.058 for trend) was observed between the variant genotypes and severity of CAD.Our results suggested that Visfatin -1535CT polymorphism might be associated with reduced risk of CAD in a Chinese population.

The aim of this study was to test the hypothesis that lower serum sodium may be associated with increased cardiovascular events and all-cause mortality by means of long-term follow-up of subjects with coronary atherosclerosis in a prospective, hospital-based epidemiological study in China. A prospective, hospital-based epidemiological design was used. The study population consisted of 1069 consecutive patients who were scheduled to undergo coronary angiography for suspected or known coronary atherosclerosis. The severity of coronary atherosclerosis was defined using Gensini's score system. Age, sex-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the quartiles of serum sodium concentration were estimated with Cox proportional hazard models, using quartile 1 as the reference. Cox proportional hazard models were also constructed to estimate the hazard ratios and 95% confidence intervals for all-cause mortality and final end-point events by serum sodium quartile and to adjust for potentially confounding variables. Multivariate models were adjusted for the following variables: age, sex, smoking status, alcohol consumption, body mass index, blood pressure, potassium, chloride, total cholesterol, triglycerides, fasting blood glucose, urea, creatinine, uric acid, and Gensini's score. During the median 2.86 years (3011.66 person-years) of follow-up, 176 final end-point events were documented. These events included 79 deaths and 97 readmissions for coronary heart disease. There was a statistically significant inverse association of serum sodium with all-cause mortality (P

Objective Therapeutic angiogenesis is a new strategy for treatment of vascular insufficiency. Hepatocyte growth factor (HGF)-induced angiogenesis has been applied to induce the neovascularization of ischemic adult tissues in preclinical studies. This report summarizes a phase I clinical trial on the safety of adenovirus-mediated human HGF (Ad-HGF) gene transfer to treat clinically significant coronary artery disease. Methods The 18 patients with severe and diffused triple vessel disease determined by coronary angiography, 1–3 of the main coronary arteries not amenable to bypassing grafting and to catheter-based revascularization were assigned to 3 study groups according to the dose of Ad-HGF (from low to high), and the total dose as follows: 5 × 109 pfu (group A, n = 6); 1 × 1010 pfu (group B, n = 6); 2 × 1010 pfu (group C, n = 6). Arterial gene transfer was performed by over-the wire balloon to the distal of the accessible artery or otherwise the ostium of the target vessels by diagnostic coronary catheter. General safety parameters and cardiac-specific parameters were measured through the preoperative period and on day 7, 21, and 35 postoperatively. The safety and tolerance of Ad-HGF for patients were evaluated according to functional and cytological assessments. Results During the acute phase up to day 35 and at 11–14 months of follow-up there were no serious adverse events. A mild fever during the first 3 days was not present at day 4, and no long term or paroxysmal fever was found. There were no acute alterations in hemodynamic parameters and the electrocardiogram remained normal. No serious pericardial effusion was reported and there were no arrhythmia on Holter registrations. Moreover, the serum levels of HGF were not changed and the serum anti-adenovirus in the patients was not detected up to day 35. Conclusions The present study demonstrates that it is feasible to safely use an adenovirus gene-transfer vector to deliver the human hepatocyte growth factor gene to individuals with clinically significant coronary artery disease by direct intracoronary injection. However, a great deal of additional work must be done before administration of Ad-HGF can be recommended for clinical practice.

The aim of the present study was to assess the influence of the endothelial lipase (EL) gene 584C/T variant, which results in a change at codon 111 of the EL gene from threonine to isoleucine, on the risk of coronary artery disease (CAD) in a Chinese population. The study population consisted of 265 CAD patients and 265 age- and sex-matched control subjects. The T allele frequency was significantly lower among CAD patients than among control subjects (18.3% vs. 29.8%; P < 0.001). In both the CAD and control groups, the T allele carriers had higher high density lipoprotein cholesterol (HDL-C) levels than homozygote C allele carriers. In a multiple logistic regression model adjusted for age, sex, body mass index, smoking, hypertension, diabetes, hyperlipidemia, and low density lipoprotein cholesterol, a significantly decreased risk of developing CAD was found in subjects carrying a variant CT or TT genotype (odds ratio = 0.496, 95% confidence interval = 0.341–0.723; P < 0.001), and the significance persisted after further adjustment for HDL-C. In conclusion, our observation that the EL 584T allele was associated with protection from CAD in this Chinese population replicates the findings in a Japanese study, which found a similar association of this allele with acute myocardial infarction, independent of HDL-C levels.

Background Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor, is considered to exert a protective effect against atherosclerosis. The Leu72Met (+ 408C > A) polymorphic variant of the preproghrelin, the gene for the ghrelin precursor, has been linked to obesity, diabetes and metabolic syndrome. However, it is unclear whether this polymorphism is associated with coronary artery disease (CAD). Methods We conducted a case-control study with 317 CAD patients and 323 controls to investigate the potential association of the Leu72Met polymorphism with the occurrence of CAD and CAD-related phenotypes in Chinese population. Results No significant difference in the Leu72Met genotype frequency was observed between CAD patients and controls (P = NS). The Leu72Met polymorphism was not associated with hypertension, diabetes, dyslipidemia, the number of diseased vessels, plasma total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol or fasting glucose levels in CAD patients. However, among CAD patients, those with variant genotypes (Leu72Met and Met72Met) had lower BMI (24.4 ± 0.3 kg/m2) than Leu72Leu carriers (25.4 ± 0.2 kg/m2, adjusted P = 0.033). Conclusion Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with CAD in Chinese population. However, the Leu72Met variant is associated with BMI among CAD patients.

Objective To test the hypothesis that the identification of mutation in the carboxypeptidase E (CPE) gene which leads to marked hyperproinsulinaemia is consistent with a possible role for mutations in CPE in the development of coronary heart disease. Methods The study subjects consisted of 51 consecutive patients (34 males and 17 females) who will undergo coronary angiography for suspected or known coronary atherosclerosis. Coronary heart disease (CHD) was defined as having a luminal diameter stenosis ≥50% in at least one of three major coronary arteries by coronary angiography or based on the Rose Questionnaire. The insulin and proinsulin level were measured using highly sensitive two-site sandwich ELISA methods. Screening for mutations of the eight exons of the CPE gene was performed by polymerase chain reaction followed by bidirectional sequencing. Results We scanned eight exons and exon–intron junctional region. Overall, we found 12 distinct variants in the intron region and three variants in the exon region. Among the 15 variants, 10 mutations were rare. The further explored study reveal that the above five non-rare variants would not affect the level of glucose, insulin, and proinsulin. However, the results suggest that the prevalence of the coronary heart disease was significant difference between the wild type group and mutant type group according to the A4545G (P = 0.020). The results from the logistic regression reveal that the subjects with the CPE mutation of A4545G, the odds ratio for the coronary heart disease was 0.196 (95% CI: 0.046 to 0.830, P = 0.027). Conclusions In the present study, the mutation of CPE gene would not affect the level of glucose, insulin, and proinsulin. The hypothesis of a possible role for mutations in CPE in the development of coronary heart disease needs further study.

Aim: To explore the relationship between serum sodium concentration and coronary atherosclerosis. Methods: The study population consisted of 896 consecutive patients (684 males and 212 females) who underwent coronary angiography for suspected or known coronary atherosclerosis. Smoking and drinking were investigated. The anthropometric measurements, including body mass index, systolic blood pressure and diastolic blood pressure, and the serum measurements, including sodium, potassium, chlorine, lipids, blood glucose, urea, creatinine, and uric acid for every patient were conducted. The severity of coronary atherosclerosis was defined by the Gensini score system. The statistical methods, including one-way ANOVA, Kruskal-Wallis test, Spearman correlation analysis, partial correlation analysis, multivariate stepwise linear regression analysis, and multinomial logistic regression analysis were employed to explore the relationship between serum sodium concentration and the Gensini score. Results: The analysis of the Kruskal-Wallis test indicated that the distribution of the Gensini score ( P =0.000) differed among the groups according to serum sodium concentration, quartile values of which were used as cut-off points. The Spearman correlation and partial correlation analysis controlling for gender, smoking status, and drinking status indicated that the Gensini score significantly correlated with the sodium concentration ( r =-0.241, P =0.000 for the Spearman correlation, r =-0.114, P =0.000 for the partial correlation). The results from the multivariate stepwise linear regression analysis showed that the left ventricular ejection fraction (β=-0.228, P =0.000), age (β=0.137, P =0.010), glucose level (β=0.129, P =0.000), and sodium level (β=-0.106, P = 0.004) were significantly and independently associated with the Gensini score. The results of the multinomial logistic regression analysis suggested that the hyponatremia was the risk factor for the higher Gensini score. Conclusion: The serum sodium concentration was significantly and negatively associated with the Gensini score; and the actual mechanism underlying the association needs further study.

The aim of this study was to identify the synergistic effect of microRNA expression with classical risk factors of coronary heart disease (CHD) and to explore their diagnostic value for coronary stenotic lesions in subjects with CHD. Plasma samples were obtained from 66 subjects with CHD and from 58 control individuals. A quantitative reverse-transcription PCR (RT-qPCR) assay was conducted to confirm the relative expressions of the known CHD-related miRNAs. The severity of coronary atherosclerosis was based on the Gensini scoring system. The expression of miR-125b in plasma of the CHD group was lower than that of the non-CHD group (0.14 ± 0.09 vs. 0.18 ± 0.10, p = 0.055) and the miR-125b levels significantly decreased following an increasing Gensini score (P = 0.037). Spearman correlation analyses indicated the Gensini score was negatively associated with miR-125b (r = −0.215, p = 0.017). Of all the miRNAs, miR-125b showed the lowest AUC (0.405; 95% CI: 0.305 ~ 0.506, p = 0.070). We found several synergistic effects between miR-125b and classical risk factors, such as age, sex, CR, FBG and HDL-C; the proportion of CHD attributable to the interaction of miR-125b and age was as high as 80%. Therefore, miR-125b was shown to play an important role in individual’s susceptibility to developing CHD.

OBJECTIVE To predict the acute response to cardiac resynchronization therapy (CRT) in patients with left ventricular mechanical dyssynchrony using equilibrium radionuclide angiography (ERNA). PATIENTS AND METHODS A total of 24 consecutive heart failure patients scheduled for CRT were included. ERNA was performed before and within 48 h after pacemaker implantation to calculate both left ventricular (LV) volumes and LV dyssynchrony. LV dyssynchrony was defined as the standard left ventricular phase shift and left ventricular phase standard deviation (LVPS% and LVPSD%). Patients were subsequently divided into acute responders or nonresponders, based on a reduction of at least 15% in LV end-systolic volume immediately after CRT. RESULTS Fifteen patients (63%) were classified as acute responders. Baseline characteristics were similar between responders and nonresponders except for the LVPS% and LVPSD%, which were larger in responders. Moreover, responders demonstrated a significant reduction of LVPS% and LVPSD% immediately after CRT (from 28.00±2.88 to 17.53±4.94 and 11.20±2.54 to 5.60±1.80, P

Oxidative stress may play a role in the development of atherosclerosis. The purpose of the present study was to explore the relationship between 8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)) levels and the presence of coronary artery disease (CAD) and to also clarify whether 8-iso-PGF(2alpha) might add independently to measures of CAD extent. The study group consisted of 241 consecutive patients who were undergoing coronary angiography for suspected CAD. 8-iso-PGF(2alpha) levels were recorded for all participants. The analysis revealed a significant difference in 8-iso-PGF(2alpha) levels in patients with and without hypertension (P0.001), in patients with diabetes relative to nondiabetic patients (P0.05), and in males respect to females (P0.001). A significant positive correlation was found between age and 8-iso-PGF(2alpha) levels (P0.001). 8-iso-PGF(2alpha) levels correlated with the number of cardiovascular risk factors (P0.001). 8-iso-PGF(2alpha) levels were higher in the CAD(+) respect to the CAD(-) groups (337.7+/-80.2 and 263.8+/-74.2 pg/ml and P0.001). A stepwise elevation in the 8-iso-PGF(2alpha) levels was found depending on the number of affected vessels (P0.001). The 8-iso-PGF(2alpha) levels showed a significant positive correlation with the numbers of50 and25% stenotic segments (P0.001) and the extent score of coronary stenosis (P0.001). The multivariate logistic regression analysis indicated 8-iso-PGF(2alpha) as an independent factor associated with CAD (odds ratio, 2.47 and P=0.001). The results suggested that 8-iso-PGF(2alpha) is associated with the presence of CAD in patients undergoing coronary angiography and is also related to the extent of coronary stenosis in Chinese population.

Background: Reports about the relationships between specific insulin concentration and coronary heart disease risk are controversial. Hypothesis: The objective of this study was to examine the association between insulin level and the severity of coronary atherosclerosis. Methods: The study population consisted of 507 consecutive patients (376 men and 131 women) who underwent coronary angiography for suspected or known coronary atherosclerosis. The patients' habits of smoking and drinking were investigated, and anthropometric measurements including body mass index, systolic and diastolic blood pressures, as well as plasma measurements including lipids and blood glucose were taken. The true insulin level was measured using a highly sensitive two-site sandwich ELISA. The severity of coronary atherosclerosis was defined by the Gensini score system. The statistical methods including Kruskal-Wallis test, chi-square analysis, Spearman correlation analysis, and multivariate stepwise linear regression analysis were employed to explore the relationship between specific insulin level and coronary atherosclerosis. Results: When the Gensini score was examined as a categorical variable classified by tertile values, subjects with a high Gensini score had significantly higher values of fasting plasma specific insulin level (p = 0.022). The Spearman correlation analysis suggest that the Gensini score correlated significantly with true insulin (mIU/l) (r = 0.095, p = 0.033). However, the results from the multivariate stepwise linear regression analysis show that the association between specific insulin level and severity of coronary atherosclerosis lost its significance. Conclusions: The level of plasma fasting specific insulin was associated significantly with the severity of coronary atherosclerosis, as measured by Gensini score, but hyperinsulinemia showed no association with the severity of coronary atherosclerosis in multivariate analyses.

To determine the frequencies of CYP3A4 alleles (CYP3A4*4,*5 and *6) in Chinese hyperlipidemic patients and to observe the impact of CYP3A4*4 (Ile118Val) genetic polymorphism on the lipid-lowering effects of simvastatin and on the activity of CYP3A4.From hospitalized and non-hospitalized patients, 211 unrelated hyperlipidemic patients were recruited for genotyping. CYP3A4 genotypes were determined by means of polymerase chain reaction and restriction fragment length polymorphism analysis. Of the non-hospitalized hyperlipidemic patients, 8 with CYP3A4*1/*1 and 8 with CYP3A4*1/*4 genotypes were selected to be treated with 20 mg simvastatin daily for 4 weeks. Serum triglycerides (TG), cholesterol (CHO) and low-density lipoprotein (LDL) levels were determined using an automated analyzer (Hitachi 747, Boehringer Mannheim, Mannheim, Germany). CYP3A4 activity was determined by the ratio of 6-hydroxycortisol to free cortisol (6-OHC/FC) in the morning spot urine with a high-throughput liquid chromatography-tandem mass spectrometry method.Of 211 subjects, 14 (allele frequency 3.32%) were heterozygous for CYP3A4*4 (Ile118Val). Nevertheless, no subjects with a CYP3A4*5 or CYP3A4*6 allele or homozygous for CYP3A4*4 were identified. The ratio of 6beta-OHC/FC was 9.9 +/- 13.7 and 56.6 +/- 35.7 in subjects with the Ile118Val variant (n = 8) and in CYP3A4 wild-type subjects (n = 8), respectively (P = 0.0039). After oral intake of simvastatin 20 mg daily for 4 weeks, the change of serum lipids in CYP3A4*1/*1 and CYP3A4*1/*4 groups showed a significant difference, with a mean decrease in triglycerides and total cholesterol of 38.1 +/- 7.6% versus 25.1 +/- 8.3% (P = 0.034) and of 35.8 +/- 9.6% versus 22.0 +/-20.4% (P = 0.0015) (means +/- SD), respectively. We found no statistically significant difference in the reductions of LDL between subjects carrying the *1 and *4 genotypes (29.0 +/- 7.4% versus 36.8 +/- 8.8%, P = 0.0721).The allele frequency of CYP3A4*4 was 3.32% among the hyperlipidemic patients from the Chinese mainland. CYP3A4*4 was an allelic variant related to a functional decrease of CYP3A4 activity, and *4 expression seemed to increase the lipid-lowering effects of simvastatin.

Background: Breast cancer is the most frequent type of tumor in women. The main cause of breast cancer remains unknown. Extensive studies have shown that endogenous steroid hormones, especially estrogens, are important in the development and the progression of breast cancer, and the carcinogenesis of estrogens is related to their major oxidative metabolites, 16a- hydroxyestrogens and 4-hydroxyestrogens. CYP3A plays a major role in the 4- and 16a-hydroxylation of estrogens. Furthermore, CYP3A is present in human mammary epithelial cells and expressed higher and more frequently in malignant breast cells than in the adjacent normal breast tissue. Hence, it will be significant to perform more work to determine the association between CYP3A activity and breast cancer susceptibility. Aims: To evaluate the relationship of CYP3A activity to breast cancer susceptibility in Chinese Han women using the plasma 1-hydroxymidazolam (1-OHMDZ) to midazolam (MDZ) ratio as the marker of CYP3A activity. Methods: One hundred and twenty-nine Chinese Han female breast tumor patients and 121 healthy unrelated female volunteers were enrolled in the current study. After an overnight fast, each subject was administered a single oral dose (7.5 mg) of midazolam. Blood samples (5 ml) were drawn at 1 h after the drug administration. The concentration of parent MDZ and its major metabolite 1-OH-MDZ was measured in all the plasma samples using high-performance liquid chromatography. Results: Complete chromatographic data on plasma ratios of 1-OHMDZ to MDZ for 103 cases of breast cancer and 114 controls were available. The plasma concentration ratios of 1-OHMDZ to MDZ were 0.4520±0.2318 and 0.3298±0.1610 for the malignant cases and the controls, respectively. A higher CYP3A activity was found in the breast cancer cases than in the controls (P

Two potential single-nucleotide polymorphisms (SNP) (C314T and A595G) exist in the gene for human histamine N-methyltransferase (HNMT).A radiochemical microassay was used to measure the erythrocyte HNMT activities, whereas the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed to perform the genetic analysis in 247 unrelated Chinese Han subjects.All subjects had detectable HNMT activity. The activity of HNMT was gender related (malesfemales, p0.0001), with a 5.5-fold individual variation. The distribution of HNMT activity was compatible with a normal distribution. There were 28 heterozygotes for the variant T314 allele among the 247 subjects, whereas no A595G transition was observed. All heterozygotes for the T314 allele displayed an intermediate or low HNMT activity, with an average HNMT activity being 34.0% lower than those with wild-type genotype (623.1+/-136.0 vs. 944.8+/-249.3 U/ml red blood cells [RBC], p0.0001).The C314T polymorphism was functionally important and contributes in part to phenotypic variance of HNMT activity in Chinese Han population. Additional unknown genetic or epigenetic factors should also play important roles in the regulation of HNMT activity.

A number of studies have suggested the benefits of pet ownership to human health, including cardiovascular disease (CVD). However, there are few findings regarding pet ownership and coronary artery disease (CAD). The objective of this study is to investigate the association between pet ownership and CAD in a Chinese population. From October 2015 to May 2016, a survey consisting of 561 consecutive patients was done in Nanjing, China. Based on the results of coronary arteriography for the first time, participants were divided into 2 groups (non-CAD and CAD groups). Pet ownership information was collected by using a questionnaire. After multivariate adjustments, pet ownership was associated with a decreased CAD risk (odds ratios [OR]: 0.504, 95% confidence intervals [CIs]: 0.310–0.819). There was a reduced CAD risk among dog owners (OR: 0.420, 95% CI: 0.242–0.728) when compared with the cat group (OR: 0.738, 95% CI: 0.240–2.266) and the cat and dog group (OR: 1.052, 95% CI: 0.330–3.355). With the increase of pet ownership duration, there was a decreased tendency of CAD risk, including years of keeping pets (P for trend = 0.008) and time of playing with pets per day (P for trend = 0.001). In addition, similar dose–response relationship was observed for starting age of keeping pets (P for trend = 0.002). Pet ownership, especially dog ownership, can be a protective factor for CAD in Chinese patients.

Objective: To develop a risk score by incorporating Hemoglobin A1c(HbA1c) with traditional risk factors for the prediction of coronary artery disease (CAD) in Chinese subjects. Methods: A total of 196 consecutive subjects (131 males and 65 females) aged 38-89 years who underwent coronary angiography were enrolled in this study. HbA1c risk score sheets for the prediction of CAD were developed using age, gender and HbA1c. A receiver-operating characteristic curve analysis was used to determine the optimum cut-off levels of the HbA1c risk score for predicting CAD. Results: In the ROC curve analysis, the optimal cut-off value of the HbA1c score for predicting CAD was 5.1, with a sensitivity of 72.0% and a specificity of 75.5% (area under the curve 0.781, 95% confidence interval 0.709 to 0.854, p=0.000). Conclusions: The HbA1c score system is a simple and feasible method that can be used for the prediction of CAD. Large-scale studies are needed to further substantiate these results.

Objective The relationship between admission serum calcium levels and in-hospital mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) has not been well definitively explored. The objective was to assess the predictive value of serum calcium levels on in-hospital mortality in STEMI patients. Methods From 2003 to 2010, 1431 consecutive STEMI patients admitted to the First Affiliated Hospital of Nanjing Medical University were enrolled in the present study. Patients were stratified according to quartiles of serum calcium from the blood samples collected in the emergency room after admission. Between the aforementioned groups,the baseline characteristics, in-hospital management, and in-hospital mortality were analyzed. The association of serum calcium level with in-hospital mortality was calculated by a multivariable Cox regression analysis. Results Among 1431 included patients, 79% were male and the median age was 65 years (range, 55–74). Patients in the lower quartiles of serum calcium, as compared to the upper quartiles of serum calcium, were older, had more cardiovascular risk factors, lower rate of emergency revascularization,and higher in-hospital mortality. According to univariate Cox proportional analysis, patients with lower serum calcium level (hazard ratio 0.267, 95% confidence interval 0.164–0.433, p

We performed a large, long-term cohort study to evaluate the association of renin-angiotensin-aldosterone system gene polymorphisms and baseline phenotypes to all-cause mortality among patients with angiographically confirmed coronary atherosclerosis. The study included 1075 subjects who underwent coronary angiography. Patients were genotyped for eight polymorphisms (rs4343, rs5186, rs5182, rs5049, rs5051, rs699, rs4762, and rs1799998), and their baseline plasma angiotensin II and aldosterone levels were measured. The interval between baseline and follow-up time-points ranged from 6.39 to 9.59 years. The results of multivariate regression analysis further indicated that high baseline angiotensin II levels (1.226 (1.024–1.468), p = 0.027) were independently associated with all-cause death. Therefore, we found that an increased baseline plasma angiotensin II level was associated with higher long-term all-cause mortality, even after correcting for established cardiovascular risk factors.

Objective Epidemiologic findings are inconsistent regarding the association between flavonol intake and the risk for stroke. The aim of this study was to determine whether an association exists between them in observational studies. Methods We searched the PubMed and EMBASE databases for studies conducted from 1966 to August 2013. Prospective cohort studies that provided relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between flavonol intake and risk for stroke were included. A random effects model was used to combine study-specific risk estimates. Results The meta-analysis included eight studies, with 5228 stroke cases among 280 174 participants. The summary RR indicated a significant association between highest flavonol intake and reduced risk for stroke (summary RR, 0.86; 95% CI, 0.75–0.99). Furthermore, an increase in flavonol intake of 20 mg/d was associated with a 14% decrease in the risk for developing stroke (summary RR, 0.86; 95% CI, 0.77–0.96). Subgroup analyses suggested a significant inverse association between highest flavonol intake and stroke risk among men (summary RR, 0.74; 95% CI, 0.56–0.97) but not women (summary RR, 0.99; 95% CI, 0.85–1.16). Conclusions Higher dietary flavonol intake is associated with a reduced risk for stroke, especially among men. Our results support recommendations for higher consumption of flavonol-rich foods to prevent stroke.

To examine the influence of walking at different times of day on lipids and inflammatory markers in sedentary patients with coronary artery disease (CAD).A total of 330 patients recruited from Nanjing between September 2011 and November 2012 were randomly assigned to a control group (n=110), morning (n=110) or evening walking group (n=110). Both the walking groups were asked to walk 30 min/day or more on at least 5 days/week either in the morning or evening for 12 weeks. Lipids and inflammatory markers were measured before and after exercise intervention.Compared with baseline, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were improved in all groups. Significances were shown in the changes of fibrinogen, high sensitivity C-reactive protein (hsCRP), white blood cell (WBC) count, TC, triglycerides, LDL-C, lipoprotein(a) between groups. The evening walking group had a larger decrease in fibrinogen (0.16 ± 0.19 g/L, P0.001), hsCRP (1.16 ± 1.07 mg/L, P0.001), WBC count (0.76 ± 1.53·10(9)/L, P=0.004) and LDL-C (0.34 ± 0.31 mmol/L, P0.001) than the other two groups.Our walking program successfully resulted in a favorable change in lipids and inflammatory markers. Patients in the evening walking group gained more benefits than those walking in the morning walking group. NCT01887093.

Aims: To explore the association between six single-nucleotide polymorphisms in OLR1, PON1, MTHFR gene and the angiographical characteristics of coronary atherosclerosis to determine if any of the conventional factors correlate with genetic polymorphisms in the advent of the disease. Methods: We examined rs1801131, rs1801133, rs3736232, rs3736234, rs854563 and rs662 by TaqMan® SNP Genotyping Assays in 1075 subjects that underwent angiography. The angiographical characteristics of coronary atherosclerosis were defined by the Gensini Score system. Results: The T allele of rs1801133 was associated with coronary atherosclerosis severity with the OR = 1.49, 95% CI = 1.04-2.14. In MTHFR gene, haplotype T-A was a susceptibility haplotype to coronary atherosclerosis (OR = 1.27, 95% CI = 1.06-1.51) whereas haplotype C-A had a protective effect (OR = 0.83, 95% CI = 0.70-0.99). In addition, several synergistic effects between rs1801133 and conventional risk factors such as diabetes and smoking were found. Conclusions: Collectively, the results demonstrate that the T allele of rs1801133 conferred an increased risk for coronary atherosclerosis. The MTHFR C-A haplotype was a protective haplotype, while T-A haplotype was a susceptibility haplotype. The presence of the T allele of rs1801133 increases the odds of coronary atherosclerosis severity when associated with conventional risk factors.

Objective This study was designed to examine the prevalence of unilateral and bilateral diagonal earlobe creases (DELCs) with respect to the diagnosis of coronary heart disease (CHD). Methods A total of 558 consecutive participants (402 males and 156 females) aged 36–91 years who underwent coronary angiography were enrolled in this study. The participants were classified as being without a DELC, having a unilateral DELC and having bilateral DELCs; participants with either a unilateral DELC or bilateral DELCs were defined as participants with DELCs. Significant CHD was defined as at least one major vessel with >50% stenosis, and coronary atherosclerosis severity was defined using the Gensini scoring system. Results In the present study, bilateral DELCs were more frequently among male (p=0.001), CHD (p=0.000), older people (p=0.000) and those with more severe coronary artery atherosclerosis (p=0.000). The results of the multiple regression analyses indicated that DELCs (OR, 4.861; 95% CI 3.093 to 7.642, p=0.000) remained independently associated with a risk of CHD. It was assumed that participants without a DELC have a certain background risk for CHD (OR is assumed to be 1); the results of the multivariate logistic regression indicated that the relative risk of CHD among participants with bilateral DELCs was 5.690 among all participants (OR, 5.690; 95% CI 3.450 to 9.384, p=0.000), 5.436 among male participants (OR, 5.436; 95% CI 2.808 to 10.523, p=0.000) and 7.148 among female participants (OR, 7.148; 95% CI 3.184 to 16.049, p=0.000). Moreover, a positive association between DELC and age (SI=1.21, SIM=1.65, AP =0.132), gender (SI=2.09, SIM=0.81, AP=0.49) and smoking status (SI=1.49, SIM=0.73, AP=0.29) was found, respectively. Conclusions The results of the present study indicated that DELCs are a simple and a feasible means of identifying CHD. However, the exact mechanism underlying the relationship between DELCs and CHD warrants further study.