Yutaka Shiina

Regional sympathetic denervation detected by iodine 123 metaiodobenzylguanidine in non-Q-wave myocardial infarction and unstable angina.

Previous studies have revealed that the sympathetic nervous system is more vulnerable to ischemia than the myocardium itself. Thus our study was undertaken to detect denervated myocardium in non-Q-wave myocardial infarction (MI) and unstable angina with iodine 123 metaiodobenzylguanidine (123I-MIBG), which can delineate myocardial sympathetic innervation. Eight patients with non-Q-wave MI and 12 with unstable angina were studied. Sequential 123I-MIBG and thallium-201 chloride (201TlCl) imaging and single-photon emission computed tomography (SPECT) were performed at rest 24 +/- 12 days after the last ischemic attack. Myocardial perfusion defect was not detected by 201TlCl in 4 of 8 patients with non-Q-wave MI, whereas 123I-MIBG SPECT imaging revealed defects corresponding to myocardial ischemic areas predicted by coronary angiography in all 8 patients. 123I-MIBG imaging revealed defects in 7 of 12 patients with unstable angina corresponding to coronary angiographic findings, whereas no myocardial perfusion defect was detected by 201TlCl imaging in any of them. In conclusion, 123I-MIBG SPECT is a sensitive method for detecting myocardium exposed to transient ischemia that cannot be detected by 201TlCl imaging.

Skew of plasma low- and high-density lipoprotein distributions to less dense subfractions in normotriglyceridemic chronic kidney disease patients on maintenance hemodialysis treatment.

Background: Plasma levels of small, dense low-density lipoprotein (LDL) were reported to increase in chronic kidney disease (CKD) patients on hemodialysis (HD), but most of these patients were hypertriglyceridemic. Plasma levels of small, dense LDL are known to increase in hypertriglyceridemic subjects. Therefore, to investigate the direct effect of CKD on the distribution of LDL subfractions, we investigated the distribution of LDL subfractions in normotriglyceridemic CKD patients on HD. Methods: The levels of plasma lipoprotein subfractions and lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP), which markedly influence the distributions of plasma LDL and high-density lipoprotein (HDL) subfractions, were compared between 40 HD patients and 40 normolipidemic controls. Plasma lipoproteins were subfractionated into seven subfractions by ultracentrifugation. Results: Plasma levels of cholesterol (C) in remnant-like particle, which is equivalent to the triglyceride (TG)-rich lipoprotein remnant, were twice as high in HD patients as those in controls with matched TG levels. Plasma levels of C and TG in VLDL and IDL (intermediate density lipoprotein) were slightly higher in HD patients than in controls. The C/TG ratio of VLDL was significantly higher in HD patients than in controls. In comparison with the corresponding values in controls, the C and TG levels in low-density LDL and HDL2 in HD patients were high, whereas those in medium-density LDL, high-density LDL, and HDL3 were low. Plasma LCAT activity and CETP mass were lower in HD patients than in controls. Conclusion: Distribution of LDL and HDL skewed toward less dense fractions in normotriglyceridemic CKD patients on HD. A decrease in reverse C transport likely played an important role in these changes in the patients.

Triglyceride‐rich lipoproteins in chronic kidney disease patients undergoing maintenance haemodialysis treatment

Objective:  Plasma triglyceride (TG) levels were reported to be high in chronic kidney disease (CKD) patients undergoing haemodialysis (HD) treatment. One of the atherogenic causes of hypertriglyceridemia is the increase in TG‐rich lipoprotein remnants, which are equivalent to remnant‐like particle cholesterol (RLP‐C). Here, we compared the plasma levels of TG, a representative indicator of TG‐rich lipoproteins and RLP‐C, as well as the TG/RLP‐C ratio between CKD patients undergoing HD and controls, in an effort to elucidate the atherogenicity of TG‐rich lipoproteins in CKD patients on HD.

Comparison of the effects of low-dose rosuvastatin on plasma levels of cholesterol and oxidized low-density lipoprotein in 3 ultracentrifugally separated low-density lipoprotein subfractions

BACKGROUND Plasma-oxidized (ox) low-density lipoprotein (LDL) is an atherogenic lipoprotein. The distribution of ox-LDL in plasma LDL subfractions and the effect of statins on this distribution have not been investigated in detail. OBJECTIVE We examined the distribution of cholesterol and ox-LDL in 3 ultracentrifugally separated plasma LDL subfractions and investigated the effects of a statin, rosuvastatin, on the levels of these lipoproteins. MATERIALS AND METHODS Thirty-one polygenic hypercholesterolemic subjects were included in this study. Levels of cholesterol and ox-LDL in 3 plasma LDL subfractions and plasma levels of remnant-like particle cholesterol, ox-LDL, and adiponectin were measured after 0, 3, 6, and 12 months of treatment with rosuvastatin. Sequential ultracentrifugation was performed to subfractionate plasma lipoproteins. RESULTS The mean daily dose of rosuvastatin over the 12 months of treatment was 2.9 ± 1.0 mg (mean ± standard deviation). The cholesterol subfraction distribution was 43 ± 10% as low-density LDL, 46 ± 8% as medium-density LDL, and 13 ± 5% as high-density LDL. Similarly, the distribution of ox-LDL was 31 ± 10% as low-density LDL, 48 ± 7% as medium-density LDL, and 22 ± 8% as high-density LDL. After 12 months of treatment with rosuvastatin, the level of cholesterol was significantly reduced in all 3 subfractions (P < .0001), as was the level of ox-LDL (P < .0001). Furthermore, the plasma cholesterol level in high-density lipoprotein2 increased significantly. CONCLUSIONS The distribution of ox-LDL in plasma LDL subfractions was more skewed toward the denser subfractions, compared with cholesterol. Rosuvastatin treatment significantly reduced plasma levels of cholesterol and ox-LDL in all LDL subfractions.

Particular human leukocyte antigen alleles are associated with biochemical traits in the Japanese population

We analyzed genetic associations among 7 biochemical traits (fasting plasma glucose, HbA1c, total cholesterol, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein cholesterol, triglyceride, and uric acid) and 6 HLA loci using 1,616 individuals who visited the Health Evaluation and Promotion Center at Tokai University Hospital. Significant differences between the individuals carrying particular HLA alleles and those not carrying the alleles in certain biochemical traits were observed by Mann-Whitney U test. In female subjects, DPB1*03:01 was significantly associated with HbA1c (p = 0.0000665), and DRB1*14:03 was associated with total cholesterol concentration (p = 0.0015). In male subjects, C*14:02 demonstrated significant associations with fasting plasma glucose with p values of 0.0041. By contrast, Fishers exact test indicated that female DRB1*14:03 was associated with a high concentration of total cholesterol (p = 000323, odds ratio [OR] = 4.32, 95% confidence interval [95% CI] = 1.83-10.36), whereas female DPB1*02:01 had a protective effect against a high concentration of LDL cholesterol (p =0.0043, OR = 0.41, 95% CI = 0.19-0.79). These associations have a statistical power of more than 0.8 and still retain significance after Bonferroni correction.

Decrease in glomerular filtration rate by plasma low-density lipoprotein cholesterol in subjects with normal kidney function assessed by urinalysis and plasma creatinine

OBJECTIVE It has not been well defined whether plasma low-density lipoprotein cholesterol (LDL-C) progresses arteriolosclerosis (arteriosclerosis of small arteries) or not. Estimated glomerular filtration rate (e-GFR) is an indicator of the function of renal arterioles and capillaries of glomeruli. The relationship between e-GFR and plasma LDL-C was studied to estimate the effect of plasma LDL-C on the function of renal arterioles and capillaries of glomeruli to speculate the effect of plasma LDL-C on arteriolosclerosis. METHODS AND RESULTS Major coronary risk factors; blood pressure, plasma lipids, and fasting plasma glucose were compared among 4 groups of examinees of a health evaluation and promotion center separated by e-GFR, namely, Control group, Group 1, 2, 3 from highest e-GFR to lowest e-GFR. Numbers of total male and female subjects were 4602 and 2920, respectively. Plasma LDL-C levels were significantly high in Group 2 and 3 in all male subjects and high in Group 1, 2, and 3 in male subjects with age of fifties, compared with Control group. Plasma LDL-C levels were significantly high in Group 1, 2, and 3 in all female subjects and high in Group 2 and 3 in female subjects with age of fifties, compared with Control group. Plasma levels of LDL-C were not significantly different at each years of age in subjects with age of fifties in both sex. BMI and waist circumference were higher in male subjects with low e-GFR but not in female subjects. Blood pressure and fasting plasma glucose were not high in subjects in Group 1, 2, and 3, compared with Control group in all subjects and subjects with age of fifties in both sex. CONCLUSIONS We concluded that the high plasma level of LDL-C was the major risk factor among coronary risk factors to reduce GFR probably due to impairing the function of renal arterioles and capillaries of glomeruli in subjects with normal kidney function assessed by urinalysis and plasma creatinine.

A Comparison of the Abdominal Fat Distribution and Coronary Risk Markers in Body Mass Index-matched Subjects with and without Fatty Liver

Objective The close relationship between fatty liver and metabolic syndrome suggests that individuals with fatty liver may have multiple coronary risk factors. In the present study, we investigated the relationships among fatty liver, abdominal fat distribution, and coronary risk markers. Methods and Results Eighty-seven pairs of men and 42 pairs of women who were matched for age and body mass index were enrolled in the present study. The obesity-related markers, abdominal fat distribution (examined by CT), and coronary risk markers were compared in subjects with and without fatty liver. The visceral fat area was significantly larger in the men with fatty liver than in the men without fatty liver. The plasma levels of triglyceride and low-density lipoprotein cholesterol (LDL-C), as well as the homeostasis model assessment-insulin resistance level, were higher in both males and females with fatty liver than in those without fatty liver, while the plasma levels of high-density lipoprotein cholesterol (HDL-C) and adiponectin were lower in the males and females with fatty liver. The plasma levels of apolipoprotein B, remnant-like particle cholesterol (RLP-C), and oxidized LDL were higher in men with fatty liver, but not in women with fatty liver. Conclusion Both males and females with fatty liver had lower insulin sensitivity, lower plasma levels of HDL-C and adiponectin, and higher triglyceride and LDL-C levels. However, the plasma levels of apolipoprotein B, RLP-C, and oxidized LDL were only higher and closely associated with fatty liver in men. Men with fatty liver had a higher risk of coronary disease than women with fatty liver.