Zi-Xiang Yu

Personalized antiplatelet therapy according to CYP2C19 genotype after percutaneous coronary intervention: A randomized control trial

OBJECTIVE The objective of this study is to compare personalized antiplatelet therapy according to CYP2C19 phenotype with conventional antiplatelet therapy in patients after percutaneous coronary intervention (PCI). METHODS A total of 600 patients with coronary artery disease (CAD) undergoing PCI randomly received a personalized antiplatelet therapy (group A; n=301) or conventional antiplatelet treatment (group B; n=299). For group A, antiplatelet therapy was performed according to CYP2C19 phenotype. For group B, the patients received conventional antiplatelet treatment without detected CYP2C19 genotype. The primary end point was compared between these two groups. This study is registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-11001807). RESULTS The primary end point occurred in 27 patients assigned to conventional treatment as compared with 8 patients assigned to personalized therapy (cumulative event rate, 9.03% vs. 2.66%; P<0.01). The composite rate of death, myocardial infarction, or stroke at 180 days occurred in 3 and 18 patients in the two groups, respectively (cumulative event rate, 1.0% and 6.2%, P<0.01). The cumulative 180-day incidence of ST was significantly lower in group A than in group B (0.66% vs. 3.01%, P=0.032). The 180-day incidence of MI (0.33% vs. 3.01%, P=0.011) and death (0.33% vs. 2.34%, P=0.011) was fewer than that in control, respectively. We did not find the significant difference in bleeding events between the 2 groups. CONCLUSION Personalized antiplatelet therapy according to CYP2C19 genotype after PCI can significantly decrease the incidence of major adverse cardiovascular events and the risk of 180-day ST in Chinese population.

Prevalence, awareness, treatment and control of dyslipidemia among adults in Northwestern China: the cardiovascular risk survey

AimThe aim of this study was to estimate the prevalence, awareness, treatment, and control of dyslipidemia in Xinjiang, China.MethodStratified sampling method was used to select a representative sample of the general population including Chinese Han, Uygur, and Kazak in this geographic area. Seven cities were chosen. Based on the government records of registered residences, one participant was randomly selected from each household. The eligibility criterion for the study was ≥ 35 years of age.ResultsA total of 14,618 participants (5,757 Han, 4,767 Uygur, and 4,094 Kazak), were randomly selected from 26 villages in 7 cities. The prevalence of dyslipidemia was 52.72% in the all participants. The prevalence of dyslipidemia was higher in Han than that in the other two ethnic (58.58% in Han, 48.27% in Uygur, and 49.60% in Kazak, P < 0.000). The prevalence of dyslipidemia was higher in men than that in women (56.4% vs. 49.3%, P < 0.000). Among the participants with dyslipidemia, the proportion of those who aware, treat, control of dyslipidemia were 53.67%, 22.51%, 17.09% in Han, 42.19%, 27.78%, 16.20% in Uygur, 37.02%, 21.11%, 17.77% in Kazak.ConclusionDyslipidemia is highly prevalent in Xinjiang. The proportion of participants with dyslipidemia who were aware, treated, and controlled is unacceptably low. These results underscore the urgent need to develop national strategies to improve the prevention, detection, and treatment of dyslipidemia in Xinjiang.

Appropriate Body Mass Index and Waist Circumference Cutoffs for Categorization of Overweight and Central Adiposity among Uighur Adults in Xinjiang

Objective The current overweight and central adiposity guidelines based on Western populations were not consistent with many studied based on the Asian populations. Uighur people live in Xinjiang Uighur Autonomous Region which is located in the center of Asia. Their overweight and central cutoffs were largely unknown. We aimed to identify cutoffs for body mass index (BMI; in kg/m2) and waist circumference (WC; in cm) for categorization of overweight and central adiposity among Uighur adults in Xinjiang. Methods 4767 Uighur participants were selected from the Cardiovascular Risk Survey (CRS) which was carried out from October 2007 to March 2010. The age of the participants were from 35 to 101 years old with the mean age of 50.09 years. Anthropometric data, blood pressure, serum concentration of serum total cholesterol, triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL) and fasting glucose were documented. The prevalence, sensitivity, specificity and distance on the receiver operating characteristic (ROC) curve of each BMI and waist circumference values were calculated. Results The prevalence of hypertension, hypercholesterolemia and hypertriglyceridemia were higher with higher BMI for both men and women. The prevalence of hypertension and hypercholesterolemia were higher with higher waist circumference for both men and women. In women, the prevalence of hypertriglyceridemia was noticed to increase as the waist circumference increased. The shortest distance in the receiver operating characteristic curves for hypertension, dyslipidemia, diabetes, or ≥ 2 of these risk factors suggested a BMI cutoff of 26 and a waist circumference cutoff of 90 cm for both men and women. Conclusions Higher cutoffs for BMI and waist circumference are needed in the identification of Uighur patients at high risk of cardiovascular disease.

Prevalence of major cardiovascular risk factors and adverse risk profiles among three ethnic groups in the Xinjiang Uygur Autonomous Region, China.

BackgroundPrevalence of cardiovascular disease (CVD) risk factors have been scarcely studied in Xinjiang, a multi-ethnic region.MethodsMulti-ethnic, cross-sectional cardiovascular risk survey study in Xinjiang, including individuals of Uygur (n = 4695), Han (n = 3717) and Kazakh (n = 3196) ethnicities, aged 35-74 years. Analyses involved 11,608 participants with complete data enrolled between October 2007 and March 2010.ResultsThere were differences in age-standardized prevalence of CVD risk factors between the three groups (all P < 0.001). Hypertension, obesity and smoking rates were higher among Kazakh (54.6%, 24.5%, and 35.8%, respectively). Dyslipidemia prevalence was higher among Uygur (54.3%), and diabetes prevalence was higher among Hans (7.1%). Age-standardized prevalence of adverse CVD risk profiles was different across different ethnicities. Compared with the Han participants, the Uygur and Kazakh had more CVD risk factors (P < 0.001). Compared with the Han participants, the adjusted odds ratios of 1, 2, and ≥3 risk factors profiles for Kazakh and Uygur participants were higher (all P < 0.001).ConclusionsThe present study showed the pervasive burden of CVD risk factors in all participant groups in the Xinjiang region. Three major ethnic groups living in Xinjiang had striking differences in the prevalence of major CVD risk factors and adverse risk profiles. Ethnic-specific strategies should be developed to prevent CVD in different ethnic groups, as well as to develop strategies to prevent future development of adverse CVD risk factors at a younger age.

Serum uric acid levels are associated with polymorphism in the SAA1 gene in Chinese subjects.

Objective Serum uric acid (SUA) is a cardiovascular risk marker associated with inflammation. The serum amyloid A protein (SAA) is an inflammatory factor and is associated with cardiovascular disease (CVD). However, the relationship between genetic polymorphisms of SAA and SUA levels has not been studied. The objective of this study was to investigate the association between SUA levels and SAA genetic polymorphisms. Methods All participants were selected from subjects participating in the Cardiovascular Risk Survey (CRS) study. The single nucleotide polymorphism (SNP) rs12218 of the SAA1 gene was genotyped by using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. The association of SUA levels with genotypes was assessed by using the general liner mode. Results The SNP rs12218 was associated with SUA levels by analyses of a dominate model (P = 0.002) and additive model (P = 0.005), and the difference remained significant after adjustment of sex, age, obesity, ethnicity, HDL-C, alcohol intake, smoking, and creatinine (P = 0.006 and P = 0.023, respectively). The TT genotype was associated with an increased SUA concentration of 39.34 mmol/L (95% confidence interval [CI], 3.61–75.06, P = 0.031) compared with the CC genotype, and the TT genotype was associated with an increased SUA concentration of 2.48 mmol/L (95% CI, 6.86–38.10; P = 0.005) compared with the CT genotype. Conclusions The rs12218 SNP in the SAA1 gene was associated with SUA levels in Chinese subjects, indicating that carriers of the T allele of rs12218 have a high risk of hyperuricemia.

Serum uric acid levels are associated with high blood pressure in Chinese children and adolescents aged 10-15 years.

Objective: The present study examined the association between uric acid levels and high blood pressure in a multiethnic study of Chinese children and adolescents. Methods: The participants were divided into four different groups according to the uric acid quartiles. Three logistic regression models were conducted to investigate the relationship between the high blood pressure and uric acid levels. Model 1 adjusted age, sex and ethnicity. Model 2 adjusted age, sex, ethnicity, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, estimated glomerular filtration rate, fasting glucose and waist circumference. Model 3 adjusted all the confounding factors in model 2 except the waist circumference and BMI. The concentrations of uric acid in high blood pressure participants and normotensive participants were compared with or without adjustment for confounding factors. Results: A total of 3778 participants aged 10–15 years from the Xinjiang Congenital Heart Disease Survey were included in the present study. The percentages of the high blood pressure in the four different uric acid quartiles were 7.4, 8.6, 9.6 and 11.8%, respectively. In model 1, 2 and 3 of the logistic regression, the participants in the third and fourth uric acid quartiles had significantly higher chance of suffering the high blood pressure when compared with the participants in the first uric acid quartile [odds ratio 1.608, 1.587, 1.597, P = 0.005, 0.015, 0.015, respectively, between participants in the first quartile and the third quartile; odds ratio 1.981, 1.945, 1.810, P = 0.001, 0.002, 0.007, respectively, between participants in the first quartile and the fourth quartile). The concentrations of serum uric acid were 220.7 &mgr;mol/l in high blood pressure participants and 204.1 &mgr;mol/l in normotensive participants (P = 0.024). After adjustment for confounding factors, the concentrations of serum uric acid were 219.7 vs. 204.5 &mgr;mol/l in one model (P < 0.001) and 219.3 vs. 204.5 &mgr;mol/l in the other model (P < 0.001). Conclusions: Among Chinese children and adolescents, increasing levels of serum uric acid are associated with high blood pressure.

FrzA gene protects cardiomyocytes from H2O2-induced oxidative stress through restraining the Wnt/Frizzled pathway.

BackgroundLately, there is accumulating evidence that the Wnt/Frizzled pathway is reactivated after myocardial infarction, the inhibition of the pathway is beneficial since it reduce of myocardial apoptosis and prevents heart failure. FrzA/Sfrp-1, a secreted frizzled-related protein and antagonist for the wnt/frizzled pathway. We assessed the hypothesis that FrzA protects cardiomyocytes from H2O2-Induced Oxidative damage through the inhibition of Wnt/Frizzled pathway activity.MethodsWe used a recombinant AAV9 vector to deliver FrzA gene into neonatal rat ventricle myocytes and developed an oxidative stress model using H2O2. The cell vitality was measured by MTT colorimetric assay. Western blot and RT-PCR were used to evaluate the expressions of Dvl-1, β-catenin, c-Myc, Bax and Bcl-2. Flow cytometry analysis of cardiomyocytes apoptosis.ResultsWe confirmed that Wnt/frizzled pathway is involved in H2O2-induced apoptosis in cardiomyocytes. Compared with controls, H2O2 induced the upregulation of Dvl-1, β-catenin, and c-Myc. FrzA suppressed the expression of Dvl-1, β-catenin, c-Myc and the activity of the Wnt/frizzled pathway. Furthermore, FrzA over-expression decreased the apoptotic rate, and the Bax/Bcl-2 ratio in cardiomyocytes treated with H2O2.ConclusionsFrzA, through the inhibition of Wnt/Frizzled pathway activity reduced H2O2-induced cardiomyocytes apoptosis and could be a potential therapeutic target for prevention of cardiac oxidative damage.

Genetic polymorphisms of serum amyloid A1 and coronary artery disease risk

Serum amyloid A (SAA) protein is not only an inflammatory factor but also an apolipoprotein that can replace apolipoprotein A1 (apoA1) as the major apolipoprotein of high-density lipoprotein cholesterol (HDL-C). However, the relationship between genetic polymorphisms of SAA and coronary artery disease (CAD) remains unclear. A total of four single nucleotide polymorphisms (rs12218, rs4638289, rs7131332, and rs11603089) of the SAA gene were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in two independent case-control studies, one of the Han population (1416 CAD patients and 1373 control subjects) and the other of the Uygur population (588 CAD patients and 529 control subjects). We found that the rs12218 CC genotype was more frequent among the CAD patients than among the controls in both the Han (8.3% vs. 4.8%, P < 0.001) and Uygur populations (15.5% vs. 11.3%, P < 0.05). After adjustments for confounding factors, such as sex, age, smoking, drinking, hypertension, diabetes, and serum levels of triglycerides, total cholesterol, HDL, and plasma SAA, the differences remained significant in the Han (CC vs. CT+TT, P < 0.001, OR = 3.863, 95% CI: 1.755-12.477) and Uygur groups (CC vs. CT+TT, P = 0.031, OR = 3.022, 95% CI: 1.033-8.840). Genetic polymorphisms in SAA1 are associated with CAD in the Han and Uygur populations in western China.

Association of intercellular adhesion molecule‑1 gene polymorphism with coronary heart disease.

Intercellular adhesion molecule‑1 (ICAM‑1) is an important adhesion molecule that has a crucial role in lymphocyte migration and atherosclerosis pathogenesis activation. The aim of the present study was to explore the association between the rs5498 polymorphism of the ICAM‑1 gene and coronary heart disease (CHD). The rs5498 polymorphism of the ICAM‑1 gene was detected using polymerase chain reaction‑restriction fragment length polymorphism in 674 patients with CHD and 779 control subjects. The results showed that the frequency of the G allele was significantly higher in patients with CHD than that in controls (29.1 vs. 23.3%; P<0.001). The frequency of the AG+GG genotypes was higher in patients with CHD than that in controls (49.7 vs. 40.8%; P=0.001). Multiple logistic regression analysis showed that AG+GG was an independent risk factor for CHD (odds ratio, 1.919; 95% confidence intervals, 1.471‑2.503; P<0.001). For males, the frequencies of the G allele and AG+GG genotype were also higher in patients with CHD than those in control subjects (frequency of G allele, 29.9 vs. 22.7%; P<0.001; frequency of AG+GG genotype, 50.6 vs. 40.3%; P=0.001). For females, no significant differences in genotype or allele distribution were observed between the two groups. In conclusion, it was demonstrated in the present study that the rs5498 polymorphism of the ICAM‑1 gene was associated with CHD in males. Males with the G allele (AG and GG genotype) may therefore have a higher risk for CHD than those with the AA genotype.

Exome Sequencing in a Family Identifies RECQL5 Mutation Resulting in Early Myocardial Infarction.

Abstract Coronary artery disease (CAD) including myocardial infarction (MI) is the leading cause of death worldwide and is commonly caused by the interaction between genetic factors and environmental risks. Despite intensive efforts using linkage and candidate gene approaches, the genetic etiology for the majority of families with a multigenerational early CAD /MI predisposition is unknown. In this study, we used whole-exome sequencing of 10 individuals from 1 early MI family, in which 4 siblings were diagnosed with MI before the age of 55, to identify potential predisposing genes. We identified a mutation in the RECQL5 gene, 1 of the 5 members of the RECQ family which are involved in the maintenance of genomic stability. This novel mutation, which is a TG insert at position 73,626,918 on the 13 chromosome and occurs before the last nucleotide of the introns 11 acceptor splice site affecting splicing of RECQL5. RT-PCR suggested the control subject had a full-length mRNA including exon 12, but the patients with RECQL5 mutation had a shorter mRNA form involving splicing of exons 11 to 13 directly, with skipping of exon 12. Quantitative RT-PCR analysis of RECQL5 exon 12 demonstrated that individuals whose genotype is mutant homozygote had only trace amounts of mRNA containing this exon and the family members who carry the heterozygous genotype had a level at 48% to 55% of the controls level. These findings provide insight into both the pathogenesis of MI and the role of RECQL5 gene in human disease.