Association of CETP Gene Variants with Atherogenic Dyslipidemia Among Thai Patients Treated with Statin.

OBJECTIVE: Patients treated with statins for dyslipidemia may still have a residual risk of atherosclerotic cardiovascular disease (ASCVD). To determine whether genetic variants in the cholesteryl ester transport protein (CETP), rs3764261 (C>A), rs708272 (G>A), and rs12149545 (G>A) affect ASCVD risk, we studied the association of these variants with dyslipidemia in statin-treated patients. PATIENTS AND METHODS: We included 299 adult Thai patients treated with a statin (95 men and 204 women). Genotyping was performed by conducting a TaqMan real-time polymerase chain reaction-based analysis. We used logistic regression models adjusted for potential confounders of age, body mass index, blood pressure, insulin resistance, and statin dosage to analyze the association between CETP variants and atherogenic lipoprotein patterns. RESULTS: CETP polymorphisms of rs3764261 and rs708272, but not rs12149545, were significantly associated with high-density lipoprotein cholesterol (HDL-C), apoA-I, triglycerides, very low-density lipoprotein (VLDL)-C, and large LDL (LDL1-C) levels as well as mean LDL particle size (all p < 0.020). However, no significant difference was observed in total cholesterol, LDL-C, or apoB levels by CETP variants. Regardless of sex, the combination of rs3764261 (CC genotype) and rs708272 (GG or GA genotypes) showed a stronger association with atherogenic dyslipidemia, including features of decreased HDL-C, elevated triglycerides, and LDL subclass pattern B (odds ratio [OR] = 2.99, 95% confidence interval [CI]: 1.78-5.02) compared with the single variant rs3764261 (OR = 2.11, 95% CI: 1.27-3.50) or rs708272 (OR = 2.12, 95% CI: 1.29-3.49). CONCLUSION: The polymorphisms of CETP rs3764261 (CC genotype) and rs708272 (GG and GA genotypes) may have a higher susceptibility to atherogenic dyslipidemia. Testing for CETP rs3764261 and rs708272 may serve as a surrogate marker for lipid management in statin-treated patients, which may help individualize treatment for reducing the residual risk of ASCVD.

Long-term effects of socioeconomic status on the incidence of decreased glomerular filtration rate in a Southeast Asian cohort.

BACKGROUND: There is limited information on the role of low socioeconomic status (SES) in the development of new chronic kidney disease (CKD) in the general population, especially from developing countries. This study will test the hypothesis that low SES increases the risk of incidence of decreased glomerular filtration rate (GFR, used as an estimate for CKD) in a Thai worker cohort. METHOD: In this prospective, longitudinal observational study, we evaluated the association of income and educational attainment on incident decreased GFR (iGFR <60 mL/min/1.73 m2) over a 27-year period in employees of Electricity Generating Authority of Thailand. In 1985, subjects participated in a health survey and were re-examined in 1997, 2002, 2007 and 2012. Education was classified into three categories: low, 0-8th grade; medium, 9-12th grade; and high, >12th grade. Income was categorised as follows: low <10 000 Thai Baht (THB)/month; medium, 10 000-20 000 THB/month; and high, >20 000 THB/month. HRs of iGFR<60 mL/min/1.73 m2 were estimated using Cox interval-censored models with high income or education as the reference groups after adjustments for clinical risk factors. RESULTS: Participants (n=3334) were followed for 23 (15, 27) years. When evaluated separately, both education and income were risk factors for iGFR<60 mL/min/1.73 m2 (adjusted HR education: medium-1.26 (95% CI 1.13 to1.42) and low-1.57 (95% CI 1.36 to 1.81) and adjusted HR income: medium-1.21 (95% CI 0.97 to 1.50) and low-1.47 (95% CI 1.18 to 1.82)). When both income and education were included together, low and medium education remained independently associated with iGFR<60 mL/min/1.73 m2. CONCLUSIONS: Low education was independently associated with increased risk of decreased GFR in a Thai worker population. Strategies to identify risk factors among low SES may be useful to prevent early CKD.

Association between polymorphisms of LEP, LEPR, DRD2, HTR2A and HTR2C genes and risperidone- or clozapine-induced hyperglycemia.

OBJECTIVE: To determine whether genetic polymorphisms related to pharmacodynamics with metabolic adverse effects, namely leptin promoter (LEP) rs7799039, leptin receptor rs1137101, dopamine D2 rs4436578, serotonin 5-HT2A rs6313, and serotonin 5-HT2C rs518147 and rs12836771, are associated with hyperglycemia induced by risperidone or clozapine in adult Thai patients with psychosis. METHODS: A total of 180 patients treated with risperidone-based (n=130) or clozapine-based (n=50) regimens were included in this study. Blood samples were analyzed for genotyping of the candidate genes and biochemical testing. Genotyping was performed by conducting a TaqMan real-time polymerase chain reaction-based analysis. RESULTS: The prevalence of hyperglycemia was higher in patients receiving clozapine (64.0%) than in those receiving risperidone (30.8%). Among the candidate genes, only the LEP rs7799039 polymorphism demonstrated a significant association with hyperglycemia (χ2=9.879, P=0.008) in patients treated with risperidone; patients with the AA genotype had the highest risk (41.1%), followed by those with AG (20.8%) and GG (0%) genotypes. Using the recessive genetic model (AA vs AG + GG), the odds ratio and 95% CI were 3.28 and 1.44 -7.50, respectively. None of the genes were associated with hyperglycemia in patients treated with clozapine. A binary logistic regression revealed that the LEP rs7799039 polymorphism demonstrated a significant association with hyperglycemia, independent of body-mass index (BMI) in patients receiving risperidone; the odds ratio (95% CI) was 3.188 (1.399-7.262), P=0.006. By contrast, none of the pharmacodynamic genetic factors, except for BMI, were significantly associated with hyperglycemia in patients receiving clozapine. CONCLUSION: The risk of type 2 diabetes mellitus is associated with the LEP rs7799039 polymorphism in Thai adults receiving risperidone but not in those receiving clozapine. Clarifying underlying mechanisms and risk of hyperglycemia provides an opportunity to prevent impaired glucose metabolism in patients receiving risperidone or clozapine.

Performance of body mass index and percentage of body fat in predicting cardiometabolic risk factors in Thai adults.

BACKGROUND: Body mass index (BMI) and percentage of body fat (PBF) are used to measure obesity; however, their performance in identifying cardiometabolic risk in Southeast Asians is unclear. Generally, Asian women have higher PBF and lower BMI than do men and other ethnic populations. This study was conducted to address whether a discord exists between these measures in predicting obesity-related cardiometabolic risk in a Thai population and to test whether associations between the measures and risk factors for cardiovascular disease have a sex-specific inclination. METHODS: A total of 234 (76 men and 158 women) outpatients were recruited. BMI obesity cutoff points were ≥25.0 and ≥27.0 kg/m2 and PBF cutoff points were ≥35.0% and ≥25.0% for women and men, respectively. Blood samples were analyzed for total cholesterol, triglycerides, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, lipoprotein subclasses, apolipoprotein A-I, apolipoprotein B, glucose, hemoglobin A1c, insulin, high-sensitive C-reactive protein (hsCRP), adiponectin, leptin, and 25-hydroxyvitamin D. RESULTS: Twenty-five percent of participants classified as normal-BMI had excessive fat, whereas 9% classified as normal-PBF had excessive BMI. Good relationships were found between BMI and PBF using sex stratification (R2 >0.5). The prevalence of metabolic syndrome was markedly increased in overweight and/or excess body fat groups compared with lean group. Logistic regression analyses showed that BMI was the best predictor of hypertension. BMI was an independent predictor of insulin resistance, hyperglycemia, hypertriglyceridemia, and hyperleptinemia in women, whereas PBF was for men. However, PBF proved to be a good indicator for atherogenic lipoprotein particles in both sexes. Notably, neither index predicted increased hsCRP or 25-hydroxyvitamin D insufficiency. CONCLUSION: Considerable sex-specific variations were observed between BMI and PBF in their associations with and predictability of numerous cardiometabolic biomarkers. No single measure provides a comprehensive risk predication as shown herein with the Thai population, and therefore both should be applied in screening activities.

Risk scores to predict decreased glomerular filtration rate at 10 years in an Asian general population.

BACKGROUND: Asians have among the highest prevalence of chronic kidney disease (CKD) or end-stage renal disease in the world. A risk score capable of identifying high risk individuals at the primary care level could allow targeted therapy to prevent future development of CKD. Risk scores for new CKD have been developed in US general populations, but the impact of various risks factors for development of CKD may differ in Asian subjects. In this study, we aimed to develop risk models and simplified risk scores to predict the development of decreased glomerular filtration rate (GFR) at 10 years in an Asian general population using readily obtainable clinical and laboratory parameters. METHODS: Employees of EGAT (The Electric Generating Authority of Thailand) were studied prospectively. Multivariable logistic regression models were used to assess risk factors and used to derive risk models and risk scores for developing decreased GFR at 10 years: Model 1 (Clinical only), Model 2 (Clinical + Limited laboratory tests), and Model 3 (Clinical + Full laboratory tests). The performance of the risk models or risk scores to predict incident cases with decreased GFR were evaluated by tests of calibration and discrimination. RESULTS: Of 3186 subjects with preserved GFR (eGFR ≥60) at baseline, 271 (8.5%) developed decreased GFR (eGFR < 60) at 10 years. Model 1 (Age, sex, systolic blood pressure, history of diabetes, and waist circumference) had good performance (χ2 = 9.02; AUC = 0.72). Model 2 (Age, Sex, systolic blood pressure, diabetes, glomerular filtration rate) had better discrimination (χ2 = 10.87, AUC = 0.79) than Model 1. Model 3 (Model 2+ Uric acid, Hemoglobin) did not provide significant improvement over Model 2. Based on these findings, simplified categorical risk scores were developed for Models 1 and 2. CONCLUSIONS: Clinical or combined clinical and laboratory risk models or risk scores using tests readily available in a resource-limited setting had good accuracy and discrimination power to estimate the 10-year probability of developing decreased GFR in a Thai general population. The benefits of the risk scores in identifying high risk individuals in the Thai or other Asian communities for special intervention requires further studies.

Evaluation of the Framingham Heart Study risk factors and risk score for incident chronic kidney disease at 10 years in a Thai general population.

PURPOSE: Asians have some of the highest rates of end-stage renal disease, but there is limited information on the risk factors for chronic kidney disease (CKD) in the Asian general population. A risk score for incident CKD for the general population has been developed from the US Framingham Heart Study (FHS) Offspring cohort. This score has been validated on Caucasians and African-Americans, but has not been tested on Asians. We aimed to assess the importance of the FHS risk factors and the performance of the FHS risk score in predicting incident CKD at 10 years in a Thai community-based population. METHODS: This is a prospective study to evaluate the risk factors and the performance of the FHS risk score comprising of age, diabetes, hypertension, proteinuria, and GFR in predicting incident CKD at 10 years in employees (n = 2568) of the Electric Generating Authority of Thailand. RESULTS: After excluding subjects with CKD at baseline, 10.4% developed incident CKD defined by the MDRD equation and 10.0% by the CKD-EPI equation. Diabetes, hypertension, and baseline GFR were strong predictors of incident CKD, but proteinuria was not. The agreement between the observed rates and the rates predicted by the FHS risk score was not high (MDRD: χ 2 = 30, P < 0.001; CKD-EPI: χ 2 = 256, P < 0.001), and the discrimination of incident CKD was modest (AUROC (95% CI): MDRD, 0.69 (0.66-0.73); CKD-EPI, 0.63 (0.57-0.65). CONCLUSIONS: Although diabetes, hypertension, and baseline GFR were important risk factors, the FHS risk score might not be sufficiently accurate at estimating incident CKD in an Asian general population.

Impact of risperidone on leptin and insulin in children and adolescents with autistic spectrum disorders.

OBJECTIVE: To evaluate the influence of dose and duration of risperidone treatment on cardiovascular and diabetes risk biomarkers in children and adolescents with autistic spectrum disorders (ASDs). DESIGN AND METHODS: In this cross-sectional analysis, a total of 168 ASDs patients (89% male) treated with a risperidone-based regimen for ≥12months were included. Blood samples were analyzed for glucose and lipid metabolic markers, adiponectin, leptin, prolactin, cortisol and high sensitive C-reactive protein. RESULTS: The mean concentrations of glucose, insulin, prolactin and leptin and HOMA-IR significantly rose with risperidone dosage (all P<0.025), but those of adiponectin and cortisol did not. Using regression analysis, insulin, leptin, prolactin and glucose concentrations and HOMA-IR show significant association with dosage. None of the markers except adiponectin showed dependence on duration of treatment. However, insulin and leptin concentrations and HOMA-IR clearly increased with increasing both dosage and duration. Dosage and duration of treatment had minimal effect on standard lipid profile and lipoprotein subclasses. CONCLUSIONS: Risperidone treatment disturbed glucose homeostasis and endocrine regulation (particularly leptin) in children and adolescents with ASDs, in a dose- and duration-dependent manner, being suggestive of leptin and insulin resistance mechanisms. Metabolic adverse effects, especially development of type 2 diabetes mellitus should be closely monitored, particularly in individuals receiving high doses and/or long-term risperidone treatment.

Effects of Therapy on Urine Neutrophil Gelatinase-Associated Lipocalin in Nondiabetic Glomerular Diseases with Proteinuria.

Urine neutrophil gelatinase-associated lipocalin (NGAL) is widely used as a biomarker for acute kidney injury. Cross-sectional studies have shown that NGAL may be elevated in glomerular diseases, but there is limited information on the value of NGAL in predicting treatment response or on the changes of NGAL levels after therapy. We prospectively evaluated the effects of therapy on NGAL in nondiabetic glomerular diseases. Urine NGAL was collected at biopsy and follow-up at 12 months. At baseline, NGAL in glomerular disease patients (n = 43) correlated with proteinuria, but not with glomerular filtration rate (GFR). After therapy with renin-angiotensin blockers and/or immune modulating agents, change of NGAL correlated with change of proteinuria, but not with change of GFR. NGAL at baseline was not different between patients in complete remission (CR) at follow-up compared to those not in remission (NR). Compared to baseline, NGAL at follow-up decreased in CR (n = 10), but not in NR. Change of NGAL was greater in CR than NR. In conclusion, the change of urine NGAL correlated with the change of proteinuria. Baseline NGAL was not a predictor of complete remission. Future studies will be necessary to determine the role of NGAL as a predictor of long term outcome in proteinuric glomerular diseases.

Independent associations of urine neutrophil gelatinase-associated lipocalin and serum uric acid with interstitial fibrosis and tubular atrophy in primary glomerulonephritis.

The degree of interstitial fibrosis and tubular atrophy (IFTA) is one of the strongest prognostic factors in glomerulonephritis (GN). In experimental models, high serum uric acid (UA) could contribute to IFTA through direct effects on the renal tubules, but the significance of this process has not been evaluated in patients. Urine neutrophil gelatinase-associated lipocalin (NGAL) is produced by renal tubules following acute or chronic damage. We investigated the relationship between UA and NGAL excretion in primary GN and tested whether these biomarkers are independently associated with IFTA. Urine and blood were collected from patients on the day of kidney biopsy. IFTA was assessed semi-quantitatively. Fifty-one patients with primary GN were enrolled. NGAL/creatinine correlated significantly with proteinuria but not with glomerular filtration rate (GFR). By contrast, UA correlated with GFR but not with proteinuria. NGAL/creatinine did not correlate with UA. Both NGAL/creatinine and UA increased with the severity of IFTA. By multivariate analysis, GFR, NGAL/creatinine, and UA were independently associated with moderate-to-severe IFTA. Combining UA and NGAL/creatinine with classical predictors (proteinuria and GFR) tended to improve discrimination for moderate-to-severe IFTA. Findings that UA was unrelated to urinary NGAL excretion suggest that the two biomarkers reflect different pathways related to the development of IFTA in primary GN. Both NGAL/creatinine and UA were independently associated with moderate-to-severe IFTA.

Effects of glomerular filtration rate estimating equations derived from different reference methods on staging and long term mortality risks of chronic kidney disease in a Southeast Asian cohort.

AIM: There are limited data on the risks of chronic kidney disease (CKD) in Southeast Asian populations. Several GFR estimating equations have been developed in diverse Asian populations, but they produce markedly discrepant results. We investigated the impact of Asian equations on the mortality risk of CKD in a Thai cohort during long term follow-up, and explored the differences between equations grouped according to the reference GFR methods used to develop them. METHODS: Employees of the Electricity Generating Authority of Thailand (n = 3430) were enrolled in a health survey and followed up for 22 years. The risks for all-cause mortality for each GFR stage classified by CKD-EPI or different Asian equations were assessed by using Cox proportional hazard models. RESULTS: Equations derived from DTPA clearance (Chinese MDRD, Thai GFR, Singapore CKD-EPI) produced higher GFR, whereas equations from inulin clearance (Japanese CKD-EPI, Taiwan MDRD or Taiwan CKD-EPI) produced lower GFR compared to CKD-EPI. (Average ΔGFR: inulin, -14.9 vs. DTPA +5.80 mL/min per 1.73 m(2) , P < 0.001). CKD prevalence varied widely (0.7 to 24 %) with inulin-based equations being higher than DTPA-based. GFR stage concordance was over 80% for equations using similar reference method compared to less than 40% between inulin and DTPA-based equations. Low GFR (<45) was an independent mortality risk factor when DTPA-based equations were used, but not when inulin-based equations were used. CONCLUSION: Chronic kidney disease prevalence and prognosis in Thais varied widely depending on the equation used. Differences in the reference GFR methods could be an important cause for the discrepancies between Asian equations.

Small-dense LDL/large-buoyant LDL ratio associates with the metabolic syndrome.

OBJECTIVE: Heterogeneous particles of intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) vary in atherogenesis. We investigated the association between the metabolic syndrome (MetS) score and lipoprotein subclasses. DESIGN AND METHODS: A total of 260 outpatients were scored into six groups, based on their number of MetS components. Lipoprotein subclass determined by polyacrylamide tube gel electrophoresis separates IDL particles into three midbands (MID-A to C) and LDL into larger-buoyant (LDL1 and LDL2) and small-dense LDL (LDL3 to LDL6). RESULTS: Mean concentrations of VLDL, MIDC, LDL2, and LDL3 to LDL6 positively correlated with increasing MetS score, but those of MIDA, LDL1 and HDL-C inversely correlated. LDL2 and LDL3 to LDL6 increased while MIDA and LDL1 decreased with increasing visceral fat, HOMA-IR, and triglycerides, with a reverse pattern for HDL-C. MIDB and MIDC were unchanged. By logistic regression, LDL1 and LDL3 to LDL6 significantly associates with the MetS score (odds ratio=0.957 and 1.077, respectively). The ratio of (LDL3 to LDL6)/LDL1 in the presence of HDL-C, showed the strongest association with MetS. CONCLUSIONS: Respective subpopulations of IDL and LDL particles can vary in their ability to identify MetS. Because of the most strongly associated with MetS, (LDL3 to LDL6)/LDL1 ratio is proposed as an excellent marker for evaluating lipid metabolic status in patient with MetS.

Comparison of a direct enzymatic assay and polyacrylamide tube gel electrophoresis for measurement of small, dense low-density lipoprotein cholesterol.

BACKGROUND: Small, dense low-density lipoprotein cholesterol (sdLDL-C) has been linked to the progression of cardiovascular disease. We compared two methods for determination of sdLDL-C, a direct enzymatic (ENZ) method and a polyacrylamide tube gel electrophoresis (PGE) assay, and investigated the associations of both sdLDL-C measurements with metabolic syndrome. METHODS: We analyzed 242 patient sera for sdLDL and atherosclerosis-related markers. The PGE method separates the intermediate-density lipoprotein particles into three midbands (MID-A to MID-C) and the LDL particles into seven subfractions (LDL1 to LDL7); the sdLDL-PGE result is calculated as the sum of cholesterol concentrations from LDL3 to LDL7. RESULTS: The regression equation for sdLDL-C was [ENZmmol/L]=0.779[PGE]+0.67, r=0.713. ENZ showed higher sdLDL-C concentrations than PGE (0.86±0.33 vs. 0.24±0.32 mmol/L); however, the difference was not associated with sdLDL-C concentration (p=0.290). sdLDL-C, as measured with the enzymatic assay, exhibited significant positive correlations with very-low-density lipoprotein, MID-C, MID-B, and LDL2 (all p<0.001), considered atherogenic lipoproteins, but did not correlate with the less atherogenic lipoproteins MID-A and LDL1 (all p>0.600). The ENZ and PGE methods yielded similar patterns of correlation between sdLDL-C, and atherosclerosis-related markers. Using logistic regression, sdLDL-ENZ and apolipoprotein B were identified as significant predictors of metabolic syndrome (p<0.03). CONCLUSIONS: The ENZ assay for sdLDL-C correlated well with the PGE method. The ENZ method measures a broader range of atherogenic lipoprotein particles than PGE and has the potential to identify subjects with vascular risk, thus contributing in directing specific interventions for cardiovascular prevention.

Small-dense LDL cholesterol/large-buoyant LDL cholesterol ratio as an excellent marker for indicating lipodystrophy in HIV-infected patients.

OBJECTIVES: To examine whether the lipid parameters are predicting factors for human immunodeficiency virus (HIV)-associated lipodystrophy. METHODS: Whole-body fat compositions of HIV-positive patients receiving stavudine-containing antiretroviral regimens (n = 79) were determined. Lipodystrophy was defined as a ratio of trunk fat mass/lower limb fat mass greater than 2.28. Blood samples were analyzed for total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), small-dense LDL-C (sdLDL-C), apoAI, apoB, lipoprotein(a), and CD4 cell counts. Large-buoyant LDL-C (lbLDL-C) was calculated (LDL-C minus sdLDL-C). RESULTS: Twenty-six patients were classified as having lipodystrophy. The mean values of triglycerides, HDL-C, sdLDL-C, apoB, TC/HDL-C, apolipoprotein (apo) B/apoAI, and sdLDL-C/lbLDL-C showed significant differences between patients with and without lipodystrophy (P < .02). Using logistic regression analysis, sdLDL-C/lbLDL-C was identified as a significant predictor of lipodystrophy (P < .001). At a ratio of 0.554, the odds ratio was 17.8 with a likelihood ratio of 5.5. CONCLUSIONS: The sdLDL-C/lbLDL-C ratio is an excellent marker for indicating lipodystrophy in HIV-infected patients.

Effect of enhanced external counterpulsation treatment on renal function in cardiac patients.

BACKGROUND: Enhanced external counterpulsation (EECP) enhances coronary perfusion and reduces left ventricular afterload. However, the role of EECP on renal function in cardiac patients is unknown. Our aim was to assess renal function determined by serum cystatin C in cardiac patients before and after EECP treatment. METHODS: A prospective observational longitudinal study was conducted in order to evaluate renal function using serum cystatin C (Cys C) and estimated glomerular filtration rate (GFR) after 35 sessions of EECP treatment in 30 patients with chronic stable angina and/or heart failure. The median (IQR) time for follow-up period after starting EECP treatment was 16 (10-24) months. RESULTS: Cys C significantly declined from 1.00 (0.78-1.31) to 0.94 (0.77-1.27) mg/L (p < 0.001) and estimated GFR increased from 70.47 (43.88-89.41) to 76.27 (49.02-91.46) mL/min/1.73 m(2) (p = 0.006) after EECP treatment. Subgroup analysis showed that patients with baseline GFR <60 mL/min/1.73 m(2) or NT-proBNP >125 pg/mL had a significant decrease in Cys C when compared to other groups (p < 0.01). CONCLUSIONS: The study demonstrated that EECP could improve long-term renal function in cardiac patients especially in cases with declined renal function or with high NT-proBNP. TRIAL REGISTRATION: The study was registered in the clinical trial as International Standard Randomized Controlled Trial Number ISRCTN11560035.

Heterogeneous properties of intermediate- and low-density lipoprotein subpopulations.

OBJECTIVE: Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) consist of heterogeneous particles whose subpopulations may have different atherogenic characteristics. This study investigated the associations between these subpopulations and other lipids, lipoproteins and atherosclerosis-related markers. DESIGN AND METHODS: A total of 416 subjects (124 males and 292 females, mean age: 50.8 years) were enrolled in this study. Using polyacrylamide gel electrophoresis, serum lipoproteins were separated according to their specific electrophoretic mobility based on particle size. The IDL particles were separated into three midbands (MID-A to C), and the LDL particles were separated into seven subfractions (LDL1 to 7). RESULTS: MID-B, MID-C, LDL2 and LDL3 to 6 (as a small LDL fraction) were significantly and positively correlated with very LDL (VLDL), while MID-A and LDL1 were significantly and inversely correlated with VLDL. MID-A and LDL1 were significantly and positively correlated with high-density lipoprotein (HDL). The correlation patterns between MID-A or LDL1 and triglycerides, apolipoprotein A-I, glucose, the insulin resistance index, creatinine and the mean LDL particle size had similar trends to those between HDL and these parameters. CONCLUSIONS: The respective subpopulations of IDL and LDL particles can vary in their ability to predict cardiovascular disease risks. These variations may partially explain why quantitative assessments using LDL-cholesterol concentrations, as typically performed in conventional practice, are not perfect predictors of cardiovascular disease. Further studies are required to determine the clinical relevance of analyzing the IDL and LDL subpopulations.

The impact of different GFR estimating equations on the prevalence of CKD and risk groups in a Southeast Asian cohort using the new KDIGO guidelines.

BACKGROUND: Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group recommended that patients with CKD should be assigned to stages and composite relative risk groups according to GFR (G) and proteinuria (A) criteria. Asians have among the highest rates of ESRD in the world, but establishing the prevalence and prognosis CKD is a problem for Asian populations since there is no consensus on the best GFR estimating (eGFR) equation. We studied the effects of the choice of new Asian and Caucasian eGFR equations on CKD prevalence, stage distribution, and risk categorization using the new KDIGO classification. METHODS: The prevalence of CKD and composite relative risk groups defined by eGFR from with Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI); standard (S) or Chinese(C) MDRD; Japanese CKD-EPI (J-EPI), Thai GFR (T-GFR) equations were compared in a Thai cohort (n = 5526) RESULTS: There was a 7 fold difference in CKD3-5 prevalence between J-EPI and the other Asian eGFR formulae. CKD3-5 prevalence with S-MDRD and CKD-EPI were 2 - 3 folds higher than T-GFR or C-MDRD. The concordance with CKD-EPI to diagnose CKD3-5 was over 90% for T-GFR or C-MDRD, but they only assigned the same CKD stage in 50% of the time. The choice of equation also caused large variations in each composite risk groups especially those with mildly increased risks. Different equations can lead to a reversal of male: female ratios. The variability of different equations is most apparent in older subjects. Stage G3aA1 increased with age and accounted for a large proportion of the differences in CKD3-5 between CKD-EPI, S-MDRD and C-MDRD. CONCLUSIONS: CKD prevalence, sex ratios, and KDIGO composite risk groupings varied widely depending on the equation used. More studies are needed to define the best equation for Asian populations.

Estimation of plasma small dense LDL cholesterol from classic lipid measures.

Calculated low-density lipoprotein cholesterol (cLDL-C) may differ from direct measurement (dLDL-C), and this difference may depend on presence of small, dense LDL (sdLDL) particles in addition to variation in triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations. The presence of such dependence would offer a simple means to estimate sdLDL. We studied dependence of sdLDL on cLDL-C, dLDL-C, and other variables. We measured the levels of glucose, creatinine, total cholesterol, TG, HDL-C, and dLDL-C using standardized methods in 297 samples. For sdLDL cholesterol (sdLDL-C), a novel homogeneous assay was used. The cLDL-C was calculated using the Friedewald formula for 220 subjects after excluding for liver or renal disease. Using stepwise regression analysis identified non-HDL-C, cLDL-C, and dLDL-C as significant variables (P < .001; R(2) = 0.88). The regression equation was as follows: sdLDL-C (mg/dL) = 0.580 (non-HDL-C) + 0.407 (dLDL-C) - 0.719 (cLDL-C) - 12.05. The sdLDL-C concentration can be estimated from non-HDL-C, dLDL-C, and cLDL-C values. Identification of a simple, inexpensive marker for sdLDL particles provides a cost-effective method for screening cardiovascular disease risk.

Hypothalamic-pituitary dysfunction in survivors of childhood brain tumors in Prasat Neurological Institute.

OBJECTIVE: To assess hypothalamic-pituitary dysfunction in childhood brain tumor survivors in Prasat Neurological Institute. MATERIAL AND METHOD: Between October 2007 and September 2008, 19 brain tumor survivor children in Prasat Neurological Institute without recurrence at least 2 years after complete treatment were included in the present study. The patients were categorized according to brain tumor location into directly (DHPA) (9 cases) and indirectly (IDHPA) (10 cases) involving hypothalamic-pituitary axis. All patients were treated by surgery. Furthermore, six cases were combined with radiation and chemotherapy and 10 cases were combined with radiation therapy only. Growth Hormone (GH) stimulation test by clonidine and/or L-Dopa, ACTH stimulation test and thyroid function test (TFT) were done. RESULTS: The mean age at diagnosis was 9.9 +/- 4.6 years old and the interval from diagnosis to study was 5.8 +/- 2.2 years. Seven DHPA (77%) and seven IDHPA patients (70%) had low peak GH with significant lower level in the former group (p < 0.05). Six of seven DHPA (85%) and one IDHPA patients (10%) had low response to ACTH stimulation test. All DHPA (100%) and 10% IDHPA patients had central hypothyroidism. By ACTH stimulation test in DHPA patients, hypocortisolism was detected in five and excluded in one who later stopped prednisolone after prolonged continuation. The central hypothyroidism was newly detected in two DHPA patients and replacement therapy was initiated GH deficiency (GHD) was detected by GH stimulation test in 73% of overall brain tumors. Growth hormone therapy would be considered in the appropriate GHD patients. CONCLUSION: With effective therapy and improving survival rates of brain tumor children, hypothalamic-pituitary dysfunction in either DHPA or IDHPA group should be regularly monitored to prevent further morbidity and improve quality of life.

Performance of a new interference-resistant glucose meter.

OBJECTIVES: Glucose meters are widely used in self and hospital monitoring of blood glucose. We examined the analytical performance of a StatStrip glucose monitoring system. DESIGN AND METHODS: Linearity, % recovery and within-run imprecision were studied using glucose-spiked whole blood. A total of 120 heparinized samples were used in method comparison using a plasma hexokinase on the Dimension RxL MAX analyzer as the comparison method. Common interferences were tested on the StatStrip, Accu-Chek Advantage and the MediSense Optium glucose meters at low, middle and high glucose levels. RESULTS: The StatStrip assay showed excellent linearity and recovery. The coefficient of variations for imprecision were <5%. This meter correlated well with the comparison method (y=0.994X+0.03; r=0.995, S(y/x)=0.05 mmol/L, bias=-0.01 mmol/L). Of the three meters tested, only the StatStrip showed interference <10% for all spiked levels of acetaminophen, ascorbic acid, maltose and hematocrit at three levels of glucose tested. CONCLUSIONS: The StatStrip meter showed good performance and is suitable for point-of-care hospital glucose testing.