OLR1, PON1 and MTHFR gene polymorphisms, conventional risk factors and the severity of coronary atherosclerosis in a Chinese Han population.

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.

Renin-angiotensin-aldosterone system gene polymorphisms and coronary artery disease: detection of gene-gene and gene-environment interactions.

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], p<0.0001; testing OR [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.

Negative association between free triiodothyronine level and international normalized ratio in euthyroid subjects with acute myocardial infarction.

AIM: 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). METHODS: 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. RESULTS: 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 (ß=-0.139, P=0.025). The value of INR was similar among the 4 groups according to the quartile FT4 levels (P=0.36). CONCLUSION: Free triiodothyronine was negatively associated with INR in the patients with acute STEMI and normal thyroid function.

Combined effects of admission serum creatinine concentration with age and gender on the prognostic significance of subjects with acute ST-elevation myocardial infarction in China.

OBJECTIVE: to explore the impact of admission serum creatinine concentration on the in-hospital mortality and its interaction with age and gender in patients with acute ST-segment elevation myocardial infarction (STEMI) in China. METHODS: 1424 acute STEMI patients were enrolled in the study. Anthropometric and laboratory measurements were collected from every patient. A Cox proportional hazards regression model was used to determine the relationships between the admission serum creatinine level (Cr level), age, sex and the in-hospital mortality. A crossover analysis and a stratified analysis were used to determine the combined impact of Cr levels with age and gender. RESULTS: Female (HR 1.687, 95%CI 1.051 ∼ 2.708), elevated Cr level (HR 5.922, 95%CI 3.780 ∼ 9,279) and old age (1.692, 95%CI 1.402 ∼ 2.403) were associated with a high risk of death respectively. After adjusting for other confounders, the renal dysfunction was still independently associated with a higher risk of death (HR 2.48, 95% CI 1.32 ∼ 4.63), while female gender (HR 1.19, 95%CI 0.62 ∼ 2.29) and old age (HR 1.77, 95%CI 0.92 ∼ 3.37) was not. In addition, crossover analysis revealed synergistic effects between elevated Cr level and female gender (SI = 3.01, SIM = 2.10, AP = 0.55). Stratified analysis showed that the impact of renal dysfunction on in-hospital mortality was more pronounced in patients <60 years old (odds ratios 11.10, 95% CI 3.72 to 33.14) compared with patients 60 to 74 years old (odds ratios 5.18, 95% CI 2.48 ∼ 10.83) and patients ≥ 75 years old (odds ratios 3.99, 95% CI 1.89 to 8.42). CONCLUSION: Serum Cr concentration on admission was a strong predictor for in-hospital mortality among Chinese acute STEMI patients especially in the young and the female.

Relationship of renin-angiotensin-aldosterone system polymorphisms and phenotypes to mortality in Chinese coronary atherosclerosis patients.

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.

Time distribution of the onset of chest pain in subjects with acute ST-elevation myocardial infarction: an eight-year, single-center study in China.

OBJECTIVE: The objective of this study was to explore the time distribution patterns of the onset of chest pain in subjects with acute ST-elevation myocardial infarction in a Chinese population. METHODS: A total of 1467 patients with acute ST-elevation myocardial infarction were enrolled from 2003 to 2010. The hourly, daily, monthly, seasonal and day-of-week fluctuations in the prevalence of acute ST-elevation myocardial infarction were analyzed. RESULTS: A peak was found between the morning hours of 07:31 and 08:30. A second peak was observed between 14:31 and 15:30, and a third peak was found between 23:31 and 00:30 (p<0.001). The monthly maximum was recorded in November and the minimum was in April (p<0.001). The number of daily cases was greatest in autumn and lowest in the spring (p = 0.001). Day-of-the-week variations of ST-elevation acute myocardial infarction were not found, except in patients more than 75-years-old. CONCLUSIONS: Periodic variations in the frequency of ST-elevation acute myocardial infarction in Chinese patients showed significant differences with regard to diurnal, monthly and seasonal patterns. The exact mechanisms underlying these circadian variations require further study.

Association of SNP rs6903956 on chromosome 6p24.1 with angiographical characteristics of coronary atherosclerosis in a Chinese population.

OBJECTIVE: To explore the association between rs6903956 and severity of coronary artery disease (CAD) in a Chinese population. METHODS: A cohort of 1075 consecutive patients who underwent coronary arteriography for suspected or known coronary atherosclerosis was enrolled in our study. Coronary atherosclerosis severity was defined by Gensini's Score System and counts of diseased vessels. RESULTS: Gensini score frequencies and counts of diseased vessels differed among GG, AG, AA genotype groups at the rs6903956 locus (p = 0.025 for Gensini score frequencies vs. p = 0.024 for counts of diseased vessels, respectively). A univariate logistic regression analysis revealed that the genotype distribution of this SNP was associated significantly with angiographical characteristics of coronary atherosclerosis risk (p = 0.030, odds ratio (OR) = 1.444, 95% confidence interval (CI) = 1.036∼2.013 for AG vs. GG; p = 0.021, OR = 5.896, 95% CI = 1.299∼26.750 for AA vs. GG and p = 0.007, OR = 1.564, 95% CI = 1.132∼2.162 for combined (AG+AA) vs. GG). A multivariate logistic regression analysis indicated that the genotype distribution of the rs6903956 polymorphism be associated significantly with the angiographical characteristics of coronary atherosclerosis risk (p = 0.004, OR = 1.578, 95% CI = 1.155∼2.154 for GG vs. AG vs. AA; p = 0.013, OR = 1.541, 95% CI = 1.097∼2.163 for GG vs. GA+ AA). A stratification analysis revealed that male subjects and smoking subjects had a higher frequency of the rs6903956 heterozygous mutant among higher Gensini score subjects than among lower Gensini score subjects (p = 0.023, OR = 1.579, 95% CI = 1.064∼2.344 for male subgroup; p = 0.005, OR = 2.075, 95% CI = 1.249∼3.448 for smoking subgroup). CONCLUSIONS: Allele A is a risk factor for CAD and the G-to-A allele substitution may underlie the association between rs6903956 and CAD.

Testosterone is negatively associated with the severity of coronary atherosclerosis in men.

This study aimed to determine whether plasma testosterone is associated with the severity of coronary atherosclerosis in a group of 803 men who underwent elective coronary angiography. Testosterone levels were measured in 803 male patients who were categorized into three groups according to testosterone level tertiles. All patients underwent elective coronary angiography, and the severity of coronary artery disease (CAD) was determined by the Gensini score. Moreover, patients were classified into two groups according to Gensini scores (score ≤26 and score >26) using the median values as cutoff points. The plasma testosterone levels were measured by an ELISA kit. The level of testosterone was negatively associated with the Gensini score (r=-0.188; P=0.000). A multiple linear regression analysis revealed that testosterone was an independent risk factor for the Gensini score (ß=-0.110; P=0.002) after adjusting for confounding covariates. In a multivariate logistic regression model, the severity of CAD was shown to be significantly lower in the third tertile (highest) of testosterone compared to the first tertile (lowest) of testosterone (odds ratio (OR)=0.465; 95% confidence interval (CI): 0.327-0.662; P=0.000). In this study, patients with lower testosterone levels had higher Gensini scores in a group of 803 men who underwent elective coronary angiography. Additional studies are needed to clarify the direction of causality and possible underlying mechanisms.