Yang Ho Kang

The prevalence of low triiodothyronine according to the stage of chronic kidney disease in subjects with a normal thyroid-stimulating hormone

BACKGROUND We hypothesized that the prevalence of low T3 would be increased according to the increase in CKD stage. This study was performed to explore the prevalence in each stage of CKD and relationship with eGFR. METHODS A total of 2284 cases with normal thyroid-stimulating hormone (TSH) level were enrolled and retrospectively analysed during the recent period, from July 2005 to December 2007. RESULTS There was an increasing trend for the population of low T3 according to the increase of a CKD stage (eGFR > or = 90, 8.2%; > or = 60 eGFR < 90, 10.9%; > or = 30 eGFR < 60, 20.8%; > or = 15 eGFR < 30, 60.6%; eGFR < 15, 78.6%). Also, there was positive relationship between eGFR and serum T3 in male, female and total subjects. After adjusting for age and sex, compared with eGFR > or = 60 ml/min/ 1.73 m2, eGFR < 60 ml/min/1.73 m2 was associated with an increased odds of low T3 [odds ratio 2.40 (CI: 1.5315 to 3.1731)]. In multiple regression analysis, eGFR was positively related with T3 (standardized coefficient 0.143, R2 = 0.055, P < 0.001), independent of age and serum albumin. CONCLUSION This study showed that low T3 syndrome was highly prevalent in CKD and was a remarkable finding in early CKD. Furthermore, serum T3 levels were associated with severity of CKD even in the normal TSH level.

Serum Cystatin C Is Related to Pulse Wave Velocity Even in Subjects with Normal Serum Creatinine

We hypothesized that serum cystatin C can be a more predictable marker of arterial stiffness than serum creatinine and creatinine-based glomerular filtration rate (GFR). The aim of this study is to evaluate whether serum cystatin C is related to arterial stiffness independently of serum creatinine in subjects for whom serum creatinine is normal. A total of 2,018 individuals (1,120 males, 898 females) were enrolled. Mean brachial-ankle pulse wave velocity (baPWV) was used as a marker of arterial stiffness and sex-specific analysis was performed. A positive relationship between baPWV and serum cystatin C (Y=1109.0548+329.9102X, r2=0.056, p<0.001) was found in males. Stepwise multivariate regression analysis in males showed that age, waist circumference, heart rate, cystatin C level, triglyceride level, and fasting glucose were independent contributors to baPWV. In females, a positive relationship between baPWV and serum cystatin C (Y=1035.7828+402.2970X, r2=0.090, p<0.001) was found. Stepwise multivariate regression analysis showed that age, heart rate, cystatin C level, fasting glucose and insulin level were independent contributors to baPWV. Age, heart rate, fasting glucose and serum cystatin C were the significant variables in both genders that contributed to baPWV. In conclusion, this study confirmed that serum cystatin C was related to pulse wave velocity even in subjects with normal serum creatinine. This finding suggested that cystatin C could be a more predictable marker of arterial stiffness than serum creatinine and creatinine-based GFR.

Multiple Hypointense Vessels on Susceptibility-Weighted Imaging in Acute Ischemic Stroke: Surrogate Marker of Oxygen Extraction Fraction in Penumbra?

Background: Multiple hypointense vessels (MHV) on susceptibility-weighted imaging (SWI) are frequently observed in patients with acute cerebral ischemia, but their implication has not been clearly established. To elucidate the clinical significance of MHV on SWI, we investigated the association of MHV on SWI with clinical data and other MR markers in patients with acute ischemic stroke. Methods: We enrolled acute stroke patients with internal carotid or proximal middle cerebral artery occlusion who underwent MRI including SWI within 3 days from stroke onset. Baseline clinical data were reviewed. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS). We graded the degree of MHV on SWI as four groups of none, subtle, relative, or extensive by the modified Alberta Stroke Program Early CT Scan (ASPECTS) system. To evaluate the degree of collateral flow, distal hyperintense vessels (DHV) on FLAIR and vessels on post-contrast time-of-flight MR angiography (TOF MRA) source images were graded respectively as 3 groups: none/subtle/prominent and poor/moderate/good. Diffusion and perfusion lesion volume and diffusion-perfusion mismatch (DPM) ratio were measured in all patients. We analyzed the association of the degree of MHV on SWI with clinical data and MR markers. Results: Eighty patients were included in the study. The mean MR time from stroke onset was 12.4 h (range 0.5-63.0). There is no difference in MR time from stroke onset between groups of MHV on SWI. MHV were observed in 68 (85%) of 80 patients: none in 12, subtle in 11, relative in 13, and extensive in 44. There were no statistically significant associations between MHV on SWI and vascular risk factors. Patients with more extensive MHV on SWI had a smaller diffusion volume (p < 0.001), larger DPM (p < 0.001), and lower initial NIHSS scores (p = 0.022). Prominent DHV was presented in 29 of 44 patients with extensive MHV (p < 0.001). Good collateral flow on TOF MRA source images was presented in 37 of 44 patients with extensive MHV (p < 0.001). Conclusions: More extensive MHV on SWI in acute ischemic stroke is associated with lower initial NIHSS scores, smaller diffusion lesion volume, better collateral flow, and larger DPM. Our results show the possibility that MHV on SWI may be a useful surrogate marker for predicting increased oxygen extraction fraction and diffusion-perfusion mismatch in acute ischemic hemisphere.

The Association of Serum Cystatin C with Glycosylated Hemoglobin in Korean Adults

Background Cystatin C has been known to be associated not only with early renal impairment but also with the incidence of diabetic conditions (prediabetes plus diabetes). However, it is not clear whether cystatin C levels are associated with the prevalence of diabetic conditions in Asian populations. We evaluated this association using glycosylated hemoglobin (HbA1c) levels as the definition of diabetes in Korean adults. Methods We analyzed data from 1,559 Korean adults (937 men and 622 women) with available serum cystatin C and HbA1c values. Results The serum cystatin C levels in subjects with prediabetes and diabetes were significantly increased (0.91±0.14 mg/L in prediabetes and 0.91±0.17 mg/L in diabetes vs. 0.88±0.13 mg/L in patients with normal glucose levels, P=0.001). At increasing cystatin C levels, the prevalence of subjects with prediabetes (30.2% vs. 14.6%, P<0.001) and those with diabetes (10.6% vs. 8.0%, P<0.001) significantly increased in the group with the highest cystatin C levels. The group with the highest cystatin C levels had a significantly increased odds ratio (OR) for the presence of diabetic conditions compared to the group with the lowest values in total subjects (OR, 2.35; 95% confidence interval [CI], 1.54 to 3.58; P<0.001) and in women (OR, 4.13; 95% CI, 1.97 to 8.65; P<0.001), though there was no significant increase after adjusting for multiple variables. Conclusions Higher levels of serum cystatin C are associated with an increased prevalence of diabetic conditions in Korean adults. Our findings may extend the positive association of cystatin C with diabetes incidence to an Asian population.

Long Term Effect of High Glucose and Phosphate Levels on the OPG/RANK/RANKL/TRAIL System in the Progression of Vascular Calcification in rat Aortic Smooth Muscle Cells

Osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL)/receptor activator of NF-κB (RANK) axis, and TNF-related apoptosis-inducing ligand (TRAIL) participate in vascular calcification process including atherosclerosis, but their contributions under high glucose (HG) and phosphate (HP) condition for a long-term period (more than 2 weeks) have not been fully determined. In this study, we evaluated the effects of HG and HP levels over 2 or 4 weeks on the progression of vascular calcification in rat vascular smooth muscle cells (VSMCs). Calcium deposition in VSMCs was increased in medium containing HG (30 mmol/L D-glucose) with β-glycerophosphate (β-GP, 12 mmol/L) after 2 weeks and increased further after 4 weeks. OPG mRNA and protein expressions were unchanged in HG group with or without β-GP after 2 weeks. However, after 4 weeks, OPG mRNA and protein expressions were significantly lower in HG group with β-GP. No significant expression changes were observed in RANKL, RANK, or TRAIL during the experiment. After 4 weeks of treatment in HG group containing β-GP and rhBMP-7, an inhibitor of vascular calcification, OPG expressions were maintained. Furthermore, mRNA expression of alkaline phosphatase (ALP), a marker of vascular mineralization, was lower in the presence of rhBMP-7. These results suggest that low OPG levels after long term HG and phosphate stimulation might reduce the binding of OPG to RANKL and TRAIL, and these changes could increase osteo-inductive VSMC differentiation, especially vascular mineralization reflected by increased ALP activity during vascular calcification.

Low serum TNF-related apoptosis-inducing ligand (TRAIL) levels are associated with acute ischemic stroke severity

BACKGROUND TNF-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor receptor superfamily and its serum level is known to be closely associated with future cardiovascular events and prognosis of various cardiovascular diseases. We investigated whether serum TRAIL levels are associated with the severity of acute ischemic stroke and specific stroke subtype. METHODS We used an enzyme-linked immunosorbent assay to measure the serum TRAIL levels of 293 patients with acute ischemic stroke within 7 days of onset. Stroke subtype was classified as large artery atherosclerosis, cardioembolism, small vessel occlusion and other determined etiology. We used National Institute of Health Stroke Scale (NIHSS) score of first hospital day and stroke volume on diffusion-weighted imaging within 7 days of stroke onset for measuring the severity of acute ischemic stroke. RESULTS The level of serum TRAIL showed significant negative correlations with NIHSS score and stroke volume. Serum TRAIL levels significantly decreased as the tertile of NIHSS score and stroke volume increased. The relative risk of patients with serum TRAIL<64.0 pg/mL for the presence of highest tertile of NIHSS score was significantly increased (adjusted OR [95%CI]; 7.07 [3.64-13.74]). Regarding stroke volume, the relative risk of patients with serum TRAIL<71.5 pg/mL for the presence of highest tertile of stroke volume was also significantly increased (adjusted OR [95%CI]; 2.81 [1.61-4.92]). There are no significant differences of serum TRAIL level among stroke subtypes. CONCLUSIONS Low serum TRAIL levels were significantly associated with the acute ischemic stroke severity. This finding suggests that serum TRAIL might also have a role in acute ischemic stroke as well as other cardiovascular diseases.

Comparison of Serum Ferritin and Vitamin D in Association with the Severity of Nonalcoholic Fatty Liver Disease in Korean Adults

Background Increased serum ferritin and decreased vitamin D levels associated with nonalcoholic fatty liver disease (NAFLD). However, their association with the severity of NAFLD has not been fully evaluated. The aim of this study was to compare the association of serum ferritin and 25(OH)D3 levels with the severity of ultrasonographically detected NAFLD (US-NAFLD) and hepatic steatosis defined by fatty liver index (FLI) in Korean adults. Methods A cross-sectional analysis of clinical and anthropometric data, including serum ferritin and 25(OH)D3, from men (n=295) and women (n=263) who underwent a routine health check-up in 2012. Results In men, with an increase in the quartile of serum ferritin level, the incidences of subjects with metabolic syndrome (P=0.002), US-NAFLD (P=0.041), and FLI ≥60 (P=0.010) were significantly elevated. In women, the incidence of subjects with US-NAFLD was also significantly elevated with increases in the serum ferritin quartile (P=0.012). Regarding 25(OH)D3, no statistical differences were observed among the different quartiles in either gender. Serum ferritin level significantly increased as the severity of US-NAFLD increased (P<0.001); however, no significant differences in 25(OH)D3 level were observed in men. No significant differences in either serum ferritin or 25(OH)D3 level were observed among women with different levels of severity of US-NAFLD. Conclusion Increased serum ferritin level showed a closer association with severity of NAFLD compared with level of serum vitamin D, suggesting that serum ferritin level may be a better marker than vitamin D level for predicting the severity of US-NAFLD and hepatic steatosis in a clinical setting.

The Association between Apolipoprotein A-II and Metabolic Syndrome in Korean Adults: A Comparison Study of Apolipoprotein A-I and Apolipoprotein B.

Background Apolipoprotein A-II (apoA-II) is the second-most abundant apolipoprotein in human high-density lipoprotein and its role in cardio metabolic risk is not entirely clear. It has been suggested to have poor anti-atherogenic or even pro-atherogenic properties, but there are few studies on the possible role of apoA-II in Asian populations. The aim of this study is to evaluate the role of apoA-II in metabolic syndrome (MetS) compared with apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) in Korean adults. Methods We analyzed data from 244 adults who visited the Center for Health Promotion in Pusan National University Yangsan Hospital for routine health examinations. Results The mean apoB level was significantly higher, and the mean apoA-I level was significantly lower, in MetS; however, there was no significant difference in apoA-II levels (30.5±4.6 mg/dL vs. 31.2±4.6 mg/dL, P=0.261). ApoA-II levels were more positively correlated with apoA-I levels than apoB levels. ApoA-II levels were less negatively correlated with homocysteine and high sensitivity C-reactive protein levels than apoA-I levels. The differences in MetS prevalence from the lowest to highest quartile of apoA-II were not significant (9.0%, 5.7%, 4.9%, and 6.6%, P=0.279). The relative risk of the highest quartile of apoA-II compared with the lowest quartile also was not significantly different (odds ratio, 0.96; 95% confidence interval, 0.95 to 1.04; P=0.956). Conclusion Compared with apoA-I (negative association with MetS) and apoB (positive association with MetS) levels, apoA-II levels did not show any association with MetS in this study involving Korean adults. However, apoA-II may have both anti-atherogenic and pro-atherogenic properties.

Prevalent Rate of Nonalbuminuric Renal Insufficiency and Its Association with Cardiovascular Disease Event in Korean Type 2 Diabetes

Background Nonalbuminuric renal insufficiency is a unique category of diabetic kidney diseases. The objectives of the study were to evaluate prevalent rate of nonalbuminuric renal insufficiency and to investigate its relationship with previous cardiovascular disease (CVD) event in Korean patients with type 2 diabetes mellitus (T2DM). Methods Laboratory and clinical data of 1,067 subjects with T2DM were obtained and reviewed. Study subjects were allocated into four subgroups according to the CKD classification. Major CVD events were included with coronary, cerebrovascular, and peripheral vascular events. Results Nonalbuminuric stage ≥3 CKD group, when compared with albuminuric stage ≥3 CKD group, had shorter diabetic duration, lower concentrations of glycated hemoglobin, high density lipoprotein cholesterol, and high-sensitivity C-reactive protein, lower prevalent rates of retinopathy and previous CVD, and higher rate of treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Nonalbuminuric stage ≥3 CKD group showed a greater association with prior CVD events than no CKD group; however, albuminuric stage ≥3 CKD group made addition to increase prevalence of prior CVD events significantly when CKD categories were applied as covariates. Association of prior CVD events, when compared with normal estimated glomerular filtration rate (eGFR) and nonalbuminuria categories, became significant for declined eGFR, which was higher for eGFR of <30 mL/min/1.73 m2, and albuminuria. Conclusion The results show that subjects with nonalbuminuric stage ≥3 CKD is significantly interrelated with occurrence of prior CVD events than those with normal eGFR with or without albuminuria. Comparing with normal eGFR and nonalbuminuria categories, the combination of increased degree of albuminuria and declined eGFR is becoming significant for the association of prior CVD events.

Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with abnormal cortisol secretion mediated by catecholamines.

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