Usefulness of the Cognitive Composition Test as an Early Discriminator of Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is the preliminary stage of dementia, which is a serious social problem worldwide. This study aimed to investigate whether the Cognitive Composition Test (CCT) is effective for the early diagnosis of MCI. A total of 104 older adults underwent the Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), the Trail Making Test Parts A (TMT-A) and B (TMT-B), and our newly prototyped cognitive composition test (CCT). We created three types of CCT (CCT-A, CCT-B, and CCT-C) with different degrees of difficulty. First, we examined the concurrent validity of CCT-A, CCT-B, and CCT-C with the MoCA, MMSE, TMT-A, and TMT-B. All participants were classified into the healthy control (HC) and MCI groups based on their scores in the Japanese versions of the MoCA and MMSE. The HC and MCI groups were compared using the TMT-A, TMT-B, CCT-A, CCT-B, and CCT-C. Finally, we examined the sensitivity for discrimination of CCT-C. CCT-C had a higher discrimination sensitivity than TMT-A, TMT-B, CCT-A, and CCT-B, with a cut-off value of 65.75 s, a sensitivity level of 0.844, and a specificity of 0.776. It may be a useful screening tool for the early diagnosis of the early-stages of dementia, such as MCI, in asymptomatic older adults.

Association Between Insulin Resistance and Cardinal Rheological Parameters in Young Healthy Japanese Individuals During 75g Oral Glucose Tolerance Test.

BACKGROUND: Insulin resistance is a well-known predictor and risk factor for type 2 diabetes mellitus (T2DM). Higher hematocrit induced by higher insulin resistance affects blood rheology. OBJECTIVE: This study intended to reveal the association between indices of insulin resistance and hemorheological parameters during a 75 g oral glucose tolerance test (75-g OGTT). METHODS: A total of 575 healthy young Japanese participants took 75-g OGTT. We then analyzed the association between insulin resistance indices and hematological parameters. RESULTS: The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was significantly correlated with hematocrit (Ht), hemoglobin (Hb), red blood cell (RBC), white blood cell (WBC), platelet count, lipid parameters and body mass index (BMI). The Matsuda index was negatively correlated with RBC count, WBC count, platelet count, total cholesterol (TC), low-density lipoprotein- cholesterol (LDL-C), triglyceride (TG), and positively correlated with high-density lipoprotein- cholesterol (HDL-C). The disposition index was negatively correlated with Hb, RBC count, LDL-C and BMI, and positively correlated with HDL-C. The Homeostasis Model Assessment of beta cell (HOMA-ß) was positively correlated with WBC count, platelet count, TC, LDL-C and TG. The insulinogenic index was positively correlated with WBC count, platelet count and TC. Multiple regression analysis revealed that HOMA-IR was independently associated with TG, and the Matsuda index was independently associated with TG, WBC count, and platelet count. The insulinogenic index was independently associated with WBC count. CONCLUSION: Cardinal rheological parameters reflected insulin resistance and release even in young healthy Japanese individuals within the physiological range of glycemic control.

Comparison of the Japan Society of Clinical Chemistry reference method and CDC method for HDL and LDL cholesterol measurements using fresh sera.

OBJECTIVES: In 2009, the Japan Society of Clinical Chemistry (JSCC) recommended a reference method for the measurement of serum high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels. This automated method uses cholesterol esterase-cholesterol dehydrogenase to measure cholesterol levels in fractions obtained after ultracentrifugation and dextran sulfate/magnesium chloride precipitation. In the present study, using fresh samples, we compared the LDL-C and HDL-C levels measured using this method with those measured using the traditional Centers for Disease Control and Prevention (CDC)-beta-quantification (BQ) method. DESIGN: and methods: Using both the JSCC and CDC-BQ methods, LDL-C/HDL-C levels were measured in 47 non-diseased and 126 diseased subjects, whose triglyceride levels were lower than 11.29 â€‹mmol/L (1000 â€‹mg/dL). RESULTS: For LDL-C, the equation of the line representing the correlation between the two methods was y â€‹= â€‹0.991x + 0.009 â€‹mmol/L; r â€‹= â€‹0.999; and Sy/x â€‹= â€‹0.025 â€‹mmol/L, where x is the mean LDL-C level measured using the CDC-BQ method. Similarly, for HDL-C, the equation of the line representing the correlation between the two methods was y â€‹= â€‹0.988x + 0.041 â€‹mmol/L, r â€‹= â€‹0.999, and Sy/x â€‹= â€‹0.019 â€‹mmol/L, where x is the mean HDL-C level measured using the CDC-BQ method. CONCLUSIONS: The JSCC method agreed with the CDC-BQ method in cases of both non-diseased and diseased subjects, including those with dyslipidemia.

[Possibility of New Circulating Atherosclerosis-Related Lipid Markers Measurement in Medical and Complete Medical Checkups: Small Dense Low-Density Lipoprotein Cholesterol and Lipoprotein Lipase].

Small dense low-density lipoprotein cholesterol (sdLDL-C) concentrations correlate more strongly with cardiovascular disease (CVD) than other LDL-C and large LDL particle concentrations. Lipoprotein lipase (LPL) plays a central role in triglyceride-rich lipoprotein metabolism by catalyzing the hydrolysis of triglycerides in chylomicrons and very low-density lipoprotein particles and is a useful biomarker in diagnosing Type I, Type IV, and Type V hyperlipidemia. Therefore, the measurement of circulating sdLDL-C and LPL concentrations contributes to the assessment of circulating atherosclerosis-related lipid markers. However, the measurement of these lipids has not been fully adopted in medical and complete medical checkups. Recently, novel automated homogenous assay for measuring sdLDL-C and latex particle-enhanced turbidimetric immunoassay (LTIA) for measuring LPL have been developed, respectively. Using these new assays, sdLDL-C values showed excellent agreement with those obtained by isolation of the d = 1.044 - 1.063 g/mL plasma fraction by sequential ultracentrifugation, and LPL values measured with and without heparin injection were highly correlated with the values measured by the LPL-enzyme-linked immunosorbent assay (ELISA). These assays may be superior to the previous assays for the measurement of sdLDL-C and LPL concentrations due their simplicity and reproducibility. The measurements of sdLDL-C and LPL concentrations may be useful as lipid markers in the assessment of the development and progression of atherosclerosis and the detection of pathological conditions and diseases if these markers are measured in medical and complete medical checkups. We have introduced the possibility of the novel measurement of circulating atherosclerosis-related lipid markers such as sdLDL-C and LPL in medical and complete medical checkups. Further studies are needed to clarify whether sdLDL-C and LPL concentrations are related to the development and progression of atherosclerosis and CVD events.

The majority of lipoprotein lipase in plasma is bound to remnant lipoproteins: A new definition of remnant lipoproteins.

BACKGROUND: Lipoprotein lipase (LPL) is a multifunctional protein and a key enzyme involved in the regulation of lipoprotein metabolism. We determined the lipoproteins to which LPL is bound in the pre-heparin and post-heparin plasma. METHODS: Tetrahydrolipstatin (THL), a potent inhibitor of serine lipases, was used to block the lipolytic activity of LPL, thereby preventing changes in the plasma lipoproteins due to ex vivo lipolysis. Gel filtration was performed to obtain the LPL elution profiles in plasma and the isolated remnant lipoproteins (RLP). RESULTS: When ex vivo lipolytic activity was inhibited by THL in the post-heparin plasma, majority of the LPL was found in the VLDL elution range, specifically in the RLP as inactive dimers. However, in the absence of THL, most of the LPL was found in the HDL elution range as active dimers. Furthermore, majority of the LPL in the pre-heparin plasma was found in the RLP as inactive form, with broadly diffused lipoprotein profiles in the presence and absence of THL. CONCLUSIONS: It is suggested that during lipolysis in vivo, the endothelial bound LPL dimers generates RLP, forming circulating RLP-LPL complexes in an inactive form that subsequently binds and initiates receptor-mediated catabolism.

Biological Antioxidant Potential Negatively Correlates With Carotid Artery Intima-Media Thickness.

Oxidative stress is a crucial factor in the pathogenesis and development of cardiovascular disease. Recently, simplified methods for the detection of reactive oxygen species (ROS) using the derivatives of reactive oxygen metabolites (d-ROMs) test as an index of ROS products and the biological antioxidant potential (BAP) test as an index of antioxidant potential have been utilized. These methods are easy to perform, quick, inexpensive since they use small equipment, and provide reliable results compared with established oxidative stress and antioxidant markers. Because oxidative stress has been shown to represent the balance of production of ROS and antioxidant capacity, it is more appropriate to evaluate ROS and antioxidant capacity simultaneously. However, no study has examined the associations among d-ROMs, BAP values, and carotid artery intima-media thickness (IMT) concurrently. Therefore, we studied the associations among d-ROMs, BAP values, and the carotid artery IMT. Carotid artery IMT, blood pressure (BP), fasting circulating d-ROMs, BAP, glucose metabolism, lipid, and C-reactive protein levels were measured in 95 subjects (age: 49.5 ± 13.8 years; men: 41; women: 54), including 42 healthy subjects and 53 patients with hypertension, dyslipidemia, and diabetes mellitus who were not on medication. The results of multiple regression analysis revealed that dependent carotid artery IMT determinants remained significantly associated with age, systolic BP, total cholesterol, and BAP, whereas dependent BAP determinants remained significantly associated with body mass index and carotid artery IMT. BAP was strongly correlated with carotid artery IMT in our cohort. Our results suggest that BAP may be a useful risk marker for carotid atherosclerosis.

Fasting serum insulin levels and insulin resistance are associated with blood rheology in Japanese young adults without diabetes.

OBJECTIVES: To evaluate fasting serum insulin levels and insulin resistance, and their association with blood rheology, in Japanese young adults without diabetes. METHODS: Blood samples were analysed and blood rheology was estimated using haematological parameters. Whole blood passage time was measured using a Hitachi MC-FAN(©) microchannel array flow analyser. RESULTS: Out of 151 subjects (mean age, 24.1 ± 1.5 years), fasting serum insulin levels and insulin resistance (using homeostasis model assessment-estimated insulin resistance [HOMA-IR]), were positively correlated with longer whole blood passage times and higher values for haematocrit (Hct), haemoglobin (Hb), fibrinogen, body weight, body mass index (BMI), triglycerides, and low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio, and were negatively correlated with HDL-C. Whole blood passage time correlated with body weight, BMI, LDL-C/HDL-C ratio, Hct, Hb, white blood cell (WBC) count, platelet count, fibrinogen, fasting serum insulin levels, and HOMA-IR. Multiple regression analysis revealed that whole blood passage time was independently associated with Hct, fibrinogen levels, and WBC count. CONCLUSIONS: Fasting serum insulin levels and insulin resistance were associated with blood rheology, and may influence blood rheology by modulating haematological parameters and lipid parameters in young adults without diabetes.

Use of capillary electrophoresis with dual-opposite end injection for simultaneous analysis of small ions in saliva samples from wrestlers undergoing a weight training program.

Capillary electrophoresis-capacitively coupled contactless conductivity detection (CE-C4D), conducted using an in-house-developed polyvinyl alcohol (PVA)-coated capillary system, was applied for the simultaneous analysis of small anions and cations in saliva samples from wrestlers undergoing a weight training program. Use of the PVA capillary for CE provided good reproducible ion separation with minimization of the electroosmotic flow and suppression of protein adsorption onto the capillary wall. Four cations and eight anions were separated in 12min, using a background electrolyte of 20mM MES/20mM histidine and 18-crown-6 ether (pH 6) at 20kV. The relative standard deviations (n=5) of the migration times and peak areas were <1% and <8%, respectively. The detection limit at a signal-to-noise ratio of 3 ranged from 1.6 to 10µM. Using the optimized CE-C4D system, we investigated the correlations between the concentrations of salivary ions and cortisol, which is commonly used as a stress marker. Analysis of saliva samples from ten wrestlers, who were attempting rapid weight loss before a competition, showed the following trends: (1) all ion concentrations, except for Ca(2+), Na(+), and Cl(-), increased between the first and last days of weight loss; (2) Mg(2+) increased to 166% (from 0.50mM to 1.4mM) between the first and last days of weight loss, being the highest increase of all the ions; and (3) K(+), Mg(2+), NO3(-), and SCN(-) levels were strongly correlated (P<0.05) with cortisol. The CE-C4D rapidly produced useful data on saliva ion contents, with good ion recovery as determined by the standard addition method (89-110%).

Impaired blood rheology is associated with endothelial dysfunction in patients with coronary risk factors.

To investigate the relationship between blood rheology and endothelial function in patients with coronary risk factors, brachial arterial flow-mediated vasodilatation (FMD), an index of endothelial function and blood passage time (BPT), an index of blood rheology, and fasting blood cell count, glucose metabolism, and plasma fibrinogen, lipid, C-reactive protein, and whole blood viscosity levels were measured in 95 patients with coronary risk factors and 37 healthy controls. Brachial arterial FMD after reactive hyperemia was assessed by ultrasonography. BPT was assessed using the microchannel method. In healthy controls, BPT significantly correlated with FMD (r = - 0.325, p <  0.05), HDL cholesterol (r = - 0.393, p <  0.05), body mass index (BMI; r = 0.530, p <  0.01), and plasma fibrinogen concentration (r = 0.335, p <  0.05). In a multivariate regression analysis adjusted for all clinical variables, BPT remained significantly associated with BMI and fibrinogen, but not with FMD, in healthy controls. In patients with coronary risk factors, BPT significantly correlated with FMD (r = - 0.331, p <  0.01), HDL cholesterol (r = - 0.241, p <  0.05), BMI (r = 0.290, p <  0.01), hematocrit (r = 0.422, p <  0.001), white blood cell count (r = 0.295, p <  0.01), platelet count (r = 0.204, p <  0.05), and insulin (r = 0.210, p <  0.05). In a multivariate regression analysis adjusted for all clinical variables, BPT remained strongly associated with FMD and hematocrit in patients with coronary risk factors. These data indicate that BPT is closely associated with FMD in patients with coronary risk factors and suggest that the measurement of blood rheology using the microchannel method may be useful in evaluating brachial arterial endothelial function as a marker of atherosclerosis in these patients.

[Causes and Abnormal Lipid Laboratory Values of Secondary Hyperlipidemia: Endocrine Disease].

Secondary hyperlipidemia is common and occurs frequently in patients with endocrine disease such as hy- pothyroidism, Cushing's syndrome, and acromegaly, metabolic disease such as diabetes mellitus, renal dis- ease such as nephrotic syndrome and chronic renal failure, liver disease such as obstructive liver disease, and as a side-effect of glucocorticoids and estrogens. The underlying cause of high serum lipid levels will often be missed if it is not actively sought. We describe. the causes and abnormal lipid laboratory values of sec- ondary hyperlipidemia in endocrine disease patients such as those with hypothyroidism, Cushing's syndrome, and acromegaly. Hypothyroidism is associated with elevated serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), and normal or elevated high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), respectively. The lipid abnormalities are due to the reductions in hepatic LDL receptor function and hepatic TG lipase (HTGL) activity. Cushing's syndrome is associated with elevated serum TC, LDL-C, and TG and elevated or normal HDL-C. The lipid abnormalities are due to the glucocorticoid- induced increase in very low-density lipoprotein (VLDL) and elevation in lipoprotein lipase (LPL) activity. Acromegaly is associated with normal serum TC, reduced LDL-C and HDL-C, and elevated TG. The lipid abnormalities are due to the growth hormone-induced reductions in LPL and HTGL activity and increase in hepatic LDL receptors. When we examine hyperlipidemic patients, it is important to diagnose the true name of the disease, usually in consideration of the possibility of the cause of secondary hyperlipidemia. [Review].

Type 2 Iodothyronine Deiodinase Activity Is Required for Rapid Stimulation of PI3K by Thyroxine in Human Umbilical Vein Endothelial Cells.

Thyroid hormones (THs) exert a number of physiological effects on the cardiovascular system. Some of the nongenomic actions of T3 are achieved by cross coupling the TH receptor (TR) with the phosphatidylinositol 3-kinase (PI3K)/protein kinase Akt (Akt) pathway. We observed that both T3 and T4 rapidly stimulated Akt phosphorylation and Ras-related C3 botulinum toxin substrate 1 (Rac1) activation, which resulted in cell migration, in a PI3K-dependent manner in human umbilical vein endothelial cells (HUVECs). We identified the expression of type 2 iodothyronine deiodinase (D2), which converts T4 to T3, and TRα1 in HUVECs. D2 activity was significantly stimulated by (Bu)2cAMP in HUVECs. The blockade of D2 activity through transfection of small interfering RNA (siRNA) specific to D2 as well as by addition of iopanoic acid, a potent D2 inhibitor, abolished Akt phosphorylation, Rac activation, and cell migration induced by T4 but not by T3. The inhibition of TRα1 expression by the transfection of siRNA for TRα1 canceled Akt phosphorylation, Rac activation, and cell migration induced by T3 and T4. These findings suggest that conversion of T4 to T3 by D2 is required for TRα1/PI3K-mediated nongenomic actions of T4 in HUVECs, including stimulation of Akt phosphorylation and Rac activation, which result in cell migration.

Relationship between carotid artery intima-media thickness and small dense low-density lipoprotein cholesterol concentrations measured by homogenous assay in Japanese subjects.

BACKGROUND: Small dense low-density lipoprotein cholesterol (sdLDL-C) concentrations correlate more strongly with coronary heart disease than other LDL-C and large LDL particle concentrations. We investigated the association between carotid artery intima-media thickness (IMT) and sdLDL-C concentrations in Japanese subjects. METHODS: Carotid artery IMT, blood pressure (BP), fasting plasma sdLDL-C, glucose metabolism, lipid, and C-reactive protein concentrations were measured in 97 native Japanese subjects. Carotid artery IMT was assessed by ultrasonography, and sdLDL-C concentrations were measured by a homogenous assay. Pearson's correlation coefficient analyses and multiple regression analyses were used to examine the relationships between carotid artery IMT values, sdLDL-C values, and other clinical variables. RESULTS: After multiple regression analysis, including age, sex, body mass index, systolic BP, diastolic BP, fasting plasma glucose, HbA1c, estimated glomerular filtration rate (eGFR), total-C, high-density lipoprotein (HDL)-C, triglyceride, LDL-C, non-HDL-C, large buoyant LDL-C, and sdLDL-C, carotid artery IMT remained significantly associated with age, systolic BP, diastolic BP, and sdLDL-C, whereas sdLDL-C remained significantly associated with age, total-C, HDL-C, triglycerides, and carotid artery IMT. CONCLUSIONS: When measured by a homogenous assay, carotid artery IMT may have a closer relationship with sdLDL-C concentrations than other lipid parameters in Japanese subjects. sdLDL-C may be a potentially useful risk marker when assessing carotid artery IMT in Japanese subjects.

Determination of serum lipoprotein lipase using a latex particle-enhanced turbidimetric immunoassay with an automated analyzer.

BACKGROUND: Lipoprotein lipase (LPL) plays a central role in triglyceride-rich lipoprotein metabolism by catalyzing the hydrolysis of triglycerides. Quantification of serum LPL is useful for diagnosing lipid disorders, but there is no rapid method of measuring LPL for clinical use. METHODS: We developed a rapid and sensitive latex particle-enhanced turbidimetric immunoassay (LTIA) serum LPL using latex bead-immobilized anti-LPL monoclonal antibodies. The assay was performed on a Hitachi 7700 P analyzer and evaluated for its validity as a method of quantitating the serum LPL concentration in parallel with ELISA. RESULTS: Dilution tests using LTIA produced a calibration curve from 0.5 to 800ng/ml. Within-run CV was obtained in the range of 2.2-5.5%. No interference was observed in the testing of specimens containing potentially interfering substances such as bilirubin-F and C, hemoglobin, triglycerides and rheumatoid factor. A strong correlation between LTIA and ELISA was confirmed (n=40, r=0.967, y=0.99x-1.86). The normal range of LPL in pre-heparin serum was 50-77ng/ml and in post-heparin plasma 354-410ng/ml, respectively. CONCLUSION: The LTIA assay is applicable in quantitating the concentration of LPL in both pre-heparin serum and post-heparin plasma. This assay is more convenient and faster than ELISA and highly suitable for clinical routine analysis.

The role of circulating lipoprotein lipase and adiponectin on the particle size of remnant lipoproteins in patients with diabetes mellitus and metabolic syndrome.

BACKGROUND: The factors regulating particle size of remnant lipoproteins (RLPs) in type 2 diabetes (T2DM) and metabolic syndrome (MetS) cases have not been well elucidated. METHODS: T2DM, MetS and healthy controls with and without a fatty liver were studied. Remnant lipoprotein (RLP)-cholesterol (RLP-C) and RLP-triglyceride (RLP-TG), small dense LDL-cholesterol (sdLDL-C), lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL) and adiponectin concentrations were measured in the fasting pre-heparin plasma. The RLP particle size was estimated by the RLP-TG/RLP-C ratio. RESULTS: The serum TG, RLP-C, RLP-TG, RLP-TG/RLP-C ratio and sdLDL-C were significantly greater in T2DM and MetS than in controls. Fatty liver and high serum TG were significantly associated with an increased RLP-TG/RLP-C ratio which was used to estimate the particle size of RLP in controls, T2DM and MetS. LPL and adiponectin in the pre-heparin plasma were inversely correlated with RLP-TG/RLP-C ratio in normal, T2DM and MetS. LPL was also positively correlated with adiponectin in all three cases. CONCLUSIONS: RLP particle size in T2DM and MetS was significantly larger than in controls and was regulated by circulating LPL and adiponectin, but not HTGL. Fatty liver and high TG were significantly associated with the prevalence of the large RLP particle size.

Comparison of the effect of post-heparin and pre-heparin lipoprotein lipase and hepatic triglyceride lipase on remnant lipoprotein metabolism.

BACKGROUND: A comparison of post-heparin and pre-heparin plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) on the metabolism of remnant lipoproteins (RLPs) has not been reported yet. METHODS: Healthy volunteers were injected with heparin for LPL and HTGL determination in the fasting (8:00) and postprandial (20:00) plasma on the same day. Plasma total cholesterol (TC), triglycerides (TG), LDL-C, HDL-C, small dense LDL (sdLDL)-C, remnant lipoprotein (RLP)-C, RLP-TG, the RLP-TG/RLP-C ratio, adiponectin and apoCIII were measured. RESULTS: LPL activity and concentration in the post-heparin plasma exhibited a significant inverse correlation with TG, RLP-C, RLP-TG, and RLP particle size estimated as RLP-TG/RLP-C ratio and sdLDL-C, and positively correlated with HDL-C. HTGL was only inversely correlated with HDL-C. LPL concentration in the pre-heparin plasma was also inversely correlated with the RLP-TG/RLP-C ratio and other lipoprotein parameters. Adiponectin was inversely correlated with RLP-TG/RLP-C ratio and apoC III was positively correlated with RLP-TG/RLP-C ratio, but not correlated with LPL activity. CONCLUSION: LPL activity and concentration were inversely and significantly correlated with the particle size of RLP in both the post-heparin and pre-heparin plasma. Those results suggest that LPL concentration in pre-heparin plasma can take the place of LPL activity in the post-heparin plasma.

Small dense LDL cholesterol measured by homogeneous assay in Japanese healthy controls, metabolic syndrome and diabetes patients with or without a fatty liver.

BACKGROUND: Serum small dense LDL-cholesterol (sdLDL-C) levels in healthy controls and the cases with diabetes (T2DM) and metabolic syndrome (MetS) with or without a fatty liver in a large, typical Japanese population was determined. METHODS: The plasma lipids and lipoproteins, including sdLDL-C by homogeneous assay, were determined in controls, MetS and T2DM patients (n=5255). The cases with MetS and preliminary MetS (pre-MetS) as well as T2DM and preliminary T2DM (pre-DM) were selected based on the Japanese criteria for MetS and T2DM. Fatty liver was diagnosed using the ultrasonography. RESULTS: The 75th percentile values for sdLDL-C were 27.5mg/dl for men and 23.3mg/dl for women and increased with age. The concentrations of sdLDL-C and sdLDL-C/LDL-C were significantly higher in pre-MetS and pre-T2DM patients than healthy controls as well as in MetS and T2DM patients. Significantly higher sdLDL-C was found in cases with a fatty liver than without a fatty liver in all five groups. CONCLUSIONS: Significantly elevated sdLDL-C levels were found in pre-MetS, MetS and pre-T2DM, T2DM patients compared to the healthy controls. Fatty liver significantly enhanced serum sdLDL-C levels and the multiple regression analyses ascertained that fatty liver was an independent determinant for sdLDL-C.

Evaluation of cardiac sympathetic nerve activity and aldosterone suppression in patients with acute decompensated heart failure on treatment containing intravenous atrial natriuretic peptide.

PURPOSE: Aldosterone prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, inhibits aldosterone synthase gene expression in cultured cardiocytes. We evaluated the effects of intravenous ANP on cardiac sympathetic nerve activity (CSNA) and aldosterone suppression in patients with acute decompensated heart failure (ADHF). METHODS: We studied 182 patients with moderate nonischemic ADHF requiring hospitalization and treated with standard therapy containing intravenous ANP and 10 age-matched normal control subjects. ANP was continuously infused for >96 h. In all subjects, delayed total defect score (TDS), heart to mediastinum ratio, and washout rate were determined by 123I-metaiodobenzylguanidine (MIBG) scintigraphy. Left ventricular (LV) end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography. All patients with acute heart failure (AHF) were examined once within 3 days and then 4 weeks after admission, while the control subjects were examined only once (when their hemodynamics were normal). Moreover, for 62 AHF patients, plasma aldosterone concentrations were measured at admission and 1 h before stopping ANP infusion. RESULTS: 123I-MIBG scintigraphic and echocardiographic parameters in normal subjects were more favorable than those in patients with AHF (all p < 0.001). After treatment, all these parameters improved significantly in AHF patients (all p < 0.001). We also found significant correlation between percent changes of TDS and aldosterone concentrations (r = 0.539, p < 0.001) in 62 AHF patients. CONCLUSION: The CSNA and LV performance were all improved in AHF patients. Furthermore, norepinephrine uptake of myocardium may be ameliorated by suppressing aldosterone production after standard treatment containing intravenous ANP.

Validation of homogeneous assays for HDL-cholesterol using fresh samples from healthy and diseased subjects.

BACKGROUND: High-density lipoprotein-cholesterol (HDL-C) is a negative risk factor for cardiovascular events. Although several homogeneous HDL-C assays are available, their accuracy has not been validated, particularly in subjects with disease. We aimed to clarify whether HDL-C concentrations measured by homogeneous assays [HDL-C (H)] agree with those determined by the reference measurement procedures [HDL-C (RMP)] using ultracentrifugation and precipitation with heparin-manganese reagent in fresh clinical samples. METHODS: HDL-C concentrations in samples from 48 healthy subjects and 119 subjects with disease were determined using 12 homogeneous assays and RMPs. RESULTS: All reagents showed excellent intra- and inter-assay CVs (<2.23%) for two pooled sera. Furthermore, the mean bias was within ± 1.0% in nine reagents using samples from healthy subjects and in eight reagents using samples from subjects with disease. In a single HDL-C (H) determination, the total error requirement of the National Cholesterol Education Program (95% of results < 13%) was fulfilled in nine reagents using samples from healthy subjects and six reagents in those from subjects with disease. Error component analysis revealed that only one reagent exceeded ± 10% total error in samples from healthy subjects, whereas four reagents exceeded this error in samples from subjects with disease. Correlations between HDL-C (H) and HDL-C (RMP) revealed that the slopes were within 1.00 ± 0.06 in six reagents in healthy subjects, and eight reagents in subjects with disease. CONCLUSIONS: Except for three reagents, HDL-C (H) agrees well with HDL-C (RMP) in subjects with common disease, but not in those with extremely low HDL-C or abnormal HDL composition.

Effects of oral nicorandil therapy on sympathetic nerve activity and cardiac events in patients with chronic heart failure: subanalysis of our previous report using propensity score matching.

PURPOSE: Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, improves cardiac sympathetic nerve activity (CSNA) in patients with ischaemic heart disease. However, the long-term effects on both CSNA, as evaluated by (123)I-metaiodobenzylguanidine (MIBG) scintigraphy, and prognosis have not been determined in patients with chronic heart failure (CHF). METHODS: This study was a subanalysis of our previous results that serial (123)I-MIBG scintigraphic studies are the most useful prognostic indicator in CHF patients. The study group comprised 208 patients with CHF (left ventricular ejection fraction <45 %) but no cardiac events for at least 5 months identified on the basis of a history of decompensated acute heart failure requiring hospitalization. These patients underwent (123)I-MIBG scintigraphy and echocardiography just before leaving the hospital and again 6 months later. We selected 170 patients and used propensity propensity score matching to compare patients who received oral nicorandil (85 patients) and those who did not (85 patients). The patients were followed up for a median of 5.03 years, with the primary and secondary study end-points defined as the occurrence of a fatal cardiac event and a major adverse cardiac event (MACE), respectively. RESULTS: After treatment, the extent of changes in (123)I-MIBG scintigraphic and echocardiographic parameters in the nicorandil group were more favourable than in those not receiving nicorandil. Of the 170 patients, a fatal cardiac event occurred in 42, and a MACE in 68 during the study. Multivariate Cox regression analyses revealed that no nicorandil treatment was a significant predictor of both cardiac death and MACE in our patients with CHF. On Kaplan-Meier analysis, the rates of freedom from cardiac death or from MACE in the nicorandil group were significantly higher than in those not receiving nicorandil (all p<0.05). CONCLUSION: Long-term nicorandil treatment improves CSNA and left ventricular parameters in patients with CHF. Furthermore, this agent is potentially effective for reducing the incidence of cardiac events in patients with CHF.