Serum phosphate levels and the risk of cardiovascular disease and metabolic syndrome: a double-edged sword.

This study was performed to evaluate the relationship between serum phosphate levels and cardiovascular risk factors and metabolic syndrome components in a cross-sectional survey. Plasma phosphate was measured by immunoturbidimetry in 46,798 subjects over 20 years of age with an estimated GFR>or=60 mL/(min 1.73 m(2)) who participated in a health-check survey at the Kangbuk Samsung Hospital in South Korea. The median plasma phosphate level was 3.49+/-0.44 mg/dL and the mean estimated GFR was 77.46+/-8.51 mL/(min 1.73 m(2)). We found that serum phosphate levels had a positive correlation with total cholesterol, HDL-C, lipoprotein a, apolipoprotein A1, calcium, and albumin. In addition, serum phosphate levels had a negative correlation with age, body mass index, uric acid, fasting glucose, insulin, HOMA-IR, HS-CRP, triglyceride levels, systolic blood pressure, diastolic blood pressure, and waist circumference (P<0.001). In conclusion, we found that a high phosphate level is correlated with cardiovascular disease while a lower phosphate level is correlated with metabolic syndrome. Serum phosphate levels that were too high or too low correlated with cardiovascular risk factors and elements of metabolic syndrome, respectively, showing that it may be important to maintain an appropriate level of phosphate for the prevention of cardiovascular events and metabolic syndrome.

Relationship between metabolic syndrome categorized by newly recommended by International Diabetes Federation criteria with plasma homocysteine concentration.

Plasma total homocysteine (tHcy) is an independent risk factor for cardiovascular disease and increased tHcy levels have been reported to be a novel risk factor of atherosclerotic disease. The aim of this study was to assess the association of the metabolic syndrome components with plasma (tHcy) level. Total 722 participants (284 men, 438 women) from the medical checkup program were enrolled in this study. The clinical characteristics and biochemical parameters of the subjects were assessed and the tHcy levels were compared according to the components of metabolic syndrome diagnosed by Adult Treatment Panel (ATP) III guideline and International Diabetes Federation (IDF) criteria. Among the components, groups with larger waist circumference and higher fasting blood glucose levels showed significantly higher tHcy level than the counterparts. Although statistically insignificant, mean concentrations of tHcy was higher in subjects with metabolic syndrome defined by both criteria. In multiple regression analysis, age, sex and systolic blood pressure were the independent determinants of tHcy level. In conclusion, tHcy level was not associated with metabolic syndrome defined by either criteria in Korean subjects.

No association of Pro12Ala polymorphism of PPAR-gamma gene with coronary artery disease in Korean subjects.

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)-gamma, a member of the nuclear hormone receptor family, which is involved in the differentiation of adipose tissue, is reported to be associated with the pathogenesis of type 2 diabetes mellitus, insulin resistance and atherosclerosis. Whether the prevalence of coronary artery disease (CAD) is associated with Pro12Ala polymorphism in exon B of PPAR-gamma was investigated in Korean adults. METHODS AND RESULTS: The study was conducted in 267 subjects (158 males, 109 females, mean age 58 years) who underwent coronary angiography because of chest pain. Cardiovascular risk factors, such as blood pressure, body mass index (BMI), fasting blood sugar and serum lipid profiles, were assessed in all subjects, who were divided into 4 groups according to the number of stenosed coronary arteries: normal, 1-vessel, 2-vessel and 3-vessel disease. Genotyping of Pro12Ala polymorphism was done with real-time polymerase chain reaction. Allelic frequency for proline was 0.955 and 0.045 for alanine, which was in Hardy-Weinberg equilibrium (p=0.74). One hundred and seventeen subjects (43.8%) had normal coronary arteries, 88 (33%) had 1-vessel disease, 39 (14.6%) had 2-vessel disease and 23 (8.6%) had 3-vessel disease. When the cardiovascular risk factors were compared among the 4 groups, there were no meaningful differences except for age and FBG levels, which were significant even after adjustment for age and BMI. There were no significant differences in the prevalence or severity of CAD according to the different genotypes of Pro12Ala, and in logistic regression analysis Pro12Ala polymorphism was not a predictor for CAD. CONCLUSIONS: There was no significant association between Pro12Ala polymorphism in exon B of PPAR-gamma and prevalence or severity of CAD in Korean adults. Further studies on the correlation between Pro12Ala polymorphism and CAD should be carried out in a larger Korean population in the future.

The differential effects of age on the association of KLOTHO gene polymorphisms with coronary artery disease.

The Klotho knockout mouse is thought to be a good animal model for human aging. Recent studies have reported on the association of KLOTHO gene mutation with cardiovascular disease in humans. We observed the frequencies of single nucleotide polymorphisms, that is, G-395A in the promoter region, C1818T in exon 4, and a functional variant, KL-VS, of KLOTHO gene in Koreans, and we investigated their relationships with the presence of coronary artery disease (CAD) in patients who had undergone coronary angiograms. A total of 274 subjects who underwent coronary angiograms because of chest pain were enrolled, and their blood pressure, body mass index, fasting blood glucose level, and lipid profiles were measured. Genotypings were performed on samples of their blood with real-time polymerase chain reaction. Two single nucleotide polymorphisms, G-395A and C1818T, complied with Hardy-Weinberg equilibrium. For the KL-VS genotype, 1 homozygote subject for the adverse allele was detected among the entire population (GG for F352V and CC for C370S). When the subjects were classified into 4 groups according to the number of stenotic vessels, there were no differences among the mean values of the cardiovascular risk factors, except for age and the fasting blood glucose levels, which showed a significant difference between that of the normal and the diseased vessel groups. There were no differences in the prevalence of CAD according to the genotypes of the G-395A polymorphism; however, for the C1818T polymorphism, those subjects with the T allele showed a lower prevalence of CAD than those with the CC genotype. When the subjects were divided into 2 groups according to age, in the group younger than 60 years, T allele carriers of the C1818T polymorphism showed a lower prevalence of CAD than did the noncarriers. In the group older than 60 years, A allele carriers of the G-395A polymorphism showed a lower prevalence of CAD than did the noncarriers. On the haplotype analysis, the GG-CC haplotype showed an increased risk for CAD with an odds ratio of 2.594 (95% confidence interval, 1.385-4.858; P = 0.003). Differential effects of age were observed in the association of KLOTHO G-395A and C1818T polymorphisms with CAD in Koreans. The KL-VS variant seems to be rarely found in the Korean population. These results infer the possibility of the KLOTHO gene being a candidate gene of atherosclerosis in humans, and further research on this topic needs to be done.

Associations between two single nucleotide polymorphisms of adiponectin gene and coronary artery diseases.

Adiponectin, an adipocyte-secreted protein, is known to have anti-atherogenic, anti-inflammatory and anti-diabetic properties and its serum levels are decreased in obesity, type 2 diabetes, and coronary artery disease. Several studies have been performed to investigate the association of genetic variations in the adiponectin with obesity, insulin resistance, and type 2 diabetes, but few studies were performed in association with coronary artery disease. Therefore we examined the associations between two single nucleotide polymorphisms (SNPs), +45T>G and +276G>T of the adiponectin gene, and coronary artery diseases (CAD). One hundred and fifty six subjects (mean age 57.4 yrs) were enrolled in which coronary angiograms were performed due to chest pain. Genotypings were done for two SNPs in the adiponectin gene by Taqman polymerase chain reaction (PCR) method. The presence of CAD was defined as a >50% reduction of coronary artery diameter. Among 156 subjects, the allele frequencies were 0.683 for G allele and 0.317 for T allele in SNP +276G>T and 0.705 for T allele and 0.295 for G allele in SNP +45T>G. Both genotypes were in compliance with Hardy-Weinberg equilibrium. No association with the presence of CAD was observed for adiponectin gene SNP276 and SNP45 (p = 0.954, p = 0.843). Also, no significant association was observed between the severity of CAD and either SNPs (p = 0.571, p = 0.955). Our study showed that SNP +276G>T and +45T>G in adiponectin gene were not associated with the presence of CAD. Further studies will be necessary to confirm the role of SNP 276G>T and 45T>G in the development of CAD.

Situational syncope induced by belching.

We describe a case of situational syncope induced by belching. The patient showed severe syncope with a high-degree atrioventricular block just after belching, but has not experienced syncope or dizziness over a 3-month follow-up after permanent pacemaker implantation.

Relationship of serum osteoprotegerin levels with coronary artery disease severity, left ventricular hypertrophy and C-reactive protein.

OPG (osteoprotegerin) is an inhibitor of osteoclastogenesis and recent work suggests it has a role in atherosclerosis. Therefore we measured serum OPG levels in patients with coronary artery disease, compared the serum OPG levels among the different groups according to the number of stenotic vessels and determined whether there was any correlation with aortic calcification, LV (left ventricular) mass index and serum CRP (C-reactive protein) levels. Subjects (n=100; mean age, 57 years) who underwent coronary angiograms were enrolled. Blood pressure, body mass index, fasting blood glucose, lipid profiles and CRP levels were measured and the LV mass indices were calculated using ECGs. Serum OPG levels were measured by ELISA. The presence of calcification in the aortic notch was checked by a chest X-ray. The subjects were divided into four groups according to the number of stenotic vessels. The mean serum OPG levels increased significantly as the number of stenotic vessels increased, and the mean serum OPG levels were higher in the group with three-vessel disease compared with the groups with no- or one-vessel disease. The mean serum CRP level was significantly higher in the group with three-vessel disease compared with the groups with no-, one- and two-vessel disease. Age and LV mass index showed significant positive correlations with serum OPG levels, although significance was lost after an adjustment for age. Serum CRP levels were positively correlated with serum OPG levels even after an adjustment for age. There were no differences in serum OPG levels according to the presence of fasting hyperglycaemia or aortic calcification. In conclusion, serum OPG level was related to the severity of stenotic coronary arteries and serum CRP levels. LV mass indices showed no significant correlation with OPG levels. The precise mechanism for the role of OPG in atherosclerosis needs to be investigated further.

In normoglycemic Koreans, insulin resistance and adipocity are independently correlated with high blood pressure.

BACKGROUND: There is some controversy about the role of insulin resistance (IR) in the regulation of blood pressure (BP). Moreover, a large study of the association between BP and IR has not been conducted in normal glucose tolerance Asians. The present study investigated the relationships between IR, body mass index (BMI) and waist circumference and BP in normoglycemic Koreans. METHODS AND RESULTS: Anthropometric indices of adiposity, metabolic variables (fasting serum insulin and a homeostasis model assessment (HOMA) index of insulin sensitivity), BP and several cardiovascular risk factors were measured during a cross-sectional survey of 49,076 normoglycemic Korean subjects. A high BP was defined as a systolic BP >/=140 mmHg or a diastolic BP >/=90 mmHg. The prevalence of high BP by HOMA grading was 0.985 (95% confidence interval (CI) 0.857-1.132, p=0.835), 1.180 (95% CI 1.032-1.350, p=0.016), 1.289 (95% CI 1.129-1.472, p<0.001), and 1.540 (95% CI 1.341-1.768, p<0.001) times higher in subjects in the second, third, fourth, and fifth quintiles, respectively, compared with those in the first quintile. In addition, age, sex, waist circumference and BMI were found to be significantly associated with a high BP. CONCLUSION: IR, BMI and waist circumference are independently correlated with high BP in normoglycemic Koreans.