Yoh Miyashita

Multicenter collaborative randomized parallel group comparative study of pitavastatin and atorvastatin in Japanese hypercholesterolemic patients Collaborative study on hypercholesterolemia drug intervention and their benefits for atherosclerosis prevention (CHIBA study)

AIMS To compare the efficacy and safety of pitavastatin and atorvastatin in Japanese patients with hypercholesterolemia. METHODS AND RESULTS Japanese patients with total cholesterol (TC) > or = 220 mg/dL were randomized to receive pitavastatin 2 mg (n=126) or atorvastatin 10 mg (n=125) for 12 weeks. The primary endpoint was percent change from baseline in non-HDL-C level after 12 weeks of treatment. Reduction of non-HDL-C by pitavastatin treatment (39.0%, P=0.456 vs. atorvastatin) was non-inferior to that by atorvastatin (40.3%). Both pitavastatin and atorvastatin also significantly reduced LDL-C by 42.6% and 44.1%, TC by 29.7% and 31.1%, and TG by 17.3% and 10.7%, respectively, at 12 weeks without intergroup differences. HDL-C showed a significant increase at 12 weeks with pitavastatin treatment (3.2%, P=0.033 vs. baseline) but not with atorvastatin treatment (1.7%, P=0.221 vs. baseline). Waist circumference, body weight and BMI were significantly correlated with percent reduction of non-HDL-C in the atorvastatin group, whereas pitavastatin showed consistent reduction of non-HDL-C regardless of the body size. In patients with metabolic syndrome, LDL-C was reduced significantly more in patients receiving pitavastatin when compared with those receiving atorvastatin. AST, ALT and gammaGTP increased significantly in patients receiving atorvastatin but not in those receiving pitavastatin. Both treatments were well tolerated. CONCLUSION Pitavastatin 2 mg and atorvastatin 10 mg are equally effective in improving the lipid profile and were well tolerated in Japanese patients with hypercholesterolemia.

Preheparin serum lipoprotein lipase mass level: the effects of age, gender, and types of hyperlipidemias

To clarify the factors regulating preheparin serum lipoprotein lipase mass (preheparin LPL mass), the correlations between preheparin LPL mass and age, gender and types of hyperlipidemias were investigated in 377 persons who underwent annual health examinations. Preheparin LPL mass level did not significantly differ in individuals from 19 to 70 years old, for both men and women. Preheparin LPL mass level correlated negatively with triglyceride (TG), positively with high density lipoprotein-cholesterol (HDL-C), and not at all with total cholesterol (TC) or low density lipoprotein-cholesterol (LDL-C). Preheparin LPL mass levels were apparently higher in women than in men, but when serum lipid levels were adjusted, preheparin LPL mass levels were identical. In type IV and IIb hyperlipidemia, preheparin LPL mass levels were lower than in type IIa patients and in normals. Remnant positive individuals had lower levels of preheparin LPL mass than the negative individuals. In conclusion, preheparin LPL mass levels were not affected by aging and gender, but were lower in the conditions in which TG catabolism was disturbed, indicating that preheparin LPL mass might reflect somewhat the amount of LPL working in the body.

The effect of insulin sensitizer, troglitazone, on lipoprotein lipase mass in preheparin serum.

Lipoprotein lipase mass exists in preheparin serum, even though the activity is scarcely found. The implication of this is unclear. We studied the effect of an insulin sensitizer, troglitazone, on this preheparin serum lipoprotein lipase mass (preheparin LPL mass) in non-insulin-dependent diabetes mellitus (NIDDM) patients as well as on serum lipid levels and low density lipoproteins (LDL) particle size. Thirty-one NIDDM patients with poor control were administered troglitazone 400 mg/day. Hemoglobin A1c had significantly decreased (13%, P < 0.001) 2 months later. Preheparin LPL mass had gradually increased and a 69% increase (P<0.01) was observed 4 months later. Triglyceride significantly decreased (23%, P < 0.01) and high density lipoprotein-cholesterol increased (10%, P < 0.01), whereas total cholesterol and LDL levels did not change 4 months later. The size of LDL increased significantly (P < 0.01). These results were consistent with the idea that preheparin LPL mass might be relating to the insulin sensitivity enhanced by troglitazone, as well as LDL particle size.

Low lipoprotein lipase mass in preheparin serum of type 2 diabetes mellitus patients and its recovery with insulin therapy

There exists lipoprotein lipase mass in preheparin serum, even though the activity is scarcely found. We studied the preheparin serum lipoprotein lipase mass levels (prehaparin LPL mass) in type 2 diabetes mellitus patients and the effect of insulin therapy on the levels of preheparin LPL mass. In 40 type 2 diabetes mellitus patients, preheparin LPL mass were measured by the sandwich enzyme-linked immunosorbent assay (ELISA), and were compared with those of non-diabetic healthy control. The correlation between preheparin LPL mass and Hemoglobin A(1c) (HbA(1c)), serum lipids were studied. Preheparin LPL mass were measured before and after insulin therapy. Preheparin LPL mass of type 2 diabetes mellitus patients was significantly lower than that of non-diabetic healthy control. In diabetic patients, preheparin LPL mass were negatively correlated with HbA(1c). Fifteen patients started to take insulin therapy. Preheparin LPL mass increased significantly at 4th week, when fasting blood glucose decreased. These results suggested that preheparin LPL mass was greatly regulated by insulin action.

Preheparin serum lipoprotein lipase mass is negatively related to coronary atherosclerosis

In preheparin serum, there exists lipoprotein lipase (LPL) mass with little activity. The clinical significance of this preheparin serum LPL mass (preheparin LPL mass) is unclear. We studied the levels of preheparin LPL mass in patients with coronary atherosclerosis, comparing the results with those in healthy men. We also evaluated the correlation between preheparin LPL mass and the severity of coronary atherosclerosis by comparing with other risk factors such as age, smoking, family history, hypertension, hyperuricemia, diabetes mellitus, total cholesterol, triglyceride, high density lipoprotein-cholesterol and body mass index. The subjects, 70 men presenting with symptoms of coronary artery disease, underwent coronary angiographic examination. Significant narrowness was defined as > or = 75%. Control group comprised 77 men who had annual health checks and showed no abnormal findings. Preheparin LPL mass in the stenosis group was lower than normal coronary group and also than the control group. Multivariate analysis showed that preheparin LPL mass had the highest t-value (-2.53) for the number of lesions among the risk factors listed above. These results suggest that low preheparin LPL mass may be deeply involved in the progression of coronary atherosclerosis.

Enhancement of preheparin serum lipoprotein lipase mass by bezafbirate administration

To clarify the clinical implication of preheparin serum lipoprotein lipase mass (preheparin LpL mass), we studied the relationships between preheparin LpL mass and serum lipids, including midband lipoproteins, which migrate between very low density lipoproteins and low density lipoproteins on polyacrylamide gel disc electrophoresis, in hyperlipidemias. And we also studied the changes of preheparin LpL mass in hypertriglyceridemic patients during bezafibrate administration, which is known to enhance LpL activity in postheparin plasma. Preheparin LpL mass correlated positively with high-density lipoprotein-cholesterol (HDL-C) (r=0.418, P<0.01) and negatively with triglyceride (TG) (r=-0.256, P<0.01), but did not correlate with total cholesterol (TC) in 64 hyperlipidemic (type IIa, IIb and IV) patients. The midband lipoproteins were observed in 80% of hypertriglyceridemic patients (32/40). Preheparin LpL mass in midband lipoprotein-positive subjects was lower significantly than that in midband-negative subjects. When bezafibrate (400 mg/day) was administrated to 40 hypertriglyceridemic patients for 4 months, TG level significantly decreased (-49+/-7%, P<0.01), TC levels decreased (-11+/-4%, not significant), and HDL-C levels increased (+27+/-4%, P<0.01). The midband lipoproteins disappeared in 95% of patients. Preheparin LpL mass significantly increased (+25+/-6%, P<0. 0005). In nine patients who stopped bezafibrate, TG levels significantly increased (+49+/-7%, P<0.01) and HDL-C levels decreased (-27+/-4%, P<0.01). Preheparin LPL mass significantly decreased (-25+/-6%, P<0.0005). These results suggested that bezafibrate administration enhanced preheparin LpL mass. And it might be implicated that enhanced LpL production by bezafibrate could reflect an increase of preheparin LpL mass.

Circulating angiotensin II is associated with body fat accumulation and insulin resistance in obese subjects with type 2 diabetes mellitus

Adipocytes express all components of the renin-angiotensin system, and the renin-angiotensin system is involved in obesity and insulin resistance. Circulating angiotensin II (Ang II) is detectable in blood, but its significance in human obesity remains unknown. The aim of this study was to investigate plasma Ang II in obese patients with type 2 diabetes mellitus (T2D) and the change during weight loss. Fifty Japanese obese subjects with T2D (body weight, 75.0 +/- 14.1 kg; body mass index, 29.1 +/- 3.7 kg/m(2); visceral fat area [VFA], 169.3 +/- 54.3 cm(2); hemoglobin A(1c), 7.6% +/- 1.5%) were enrolled. The subjects were prescribed a diet of daily caloric intake of 20 kcal/kg for 24 weeks. Plasma Ang II was measured by radioimmunoassay. Leptin, adiponectin, and lipoprotein lipase mass in preheparin serum were also measured as adipocyte-derived factors. After 24 weeks of weight reduction diet, the mean body weight, VFA, and hemoglobin A(1c) decreased significantly by 2.3%, 7.0%, and 8.3%, respectively. The mean plasma Ang II decreased by 24% (P < .0001) and correlated with body weight both at baseline (r = 0.425, P = .0018) and at 24 weeks (r = 0.332, P = .0181). The change in Ang II correlated with changes in body weight (r = 0.335, P = .0167) and VFA (r = 0.329, P = .0191). The change in Ang II also correlated positively with change in leptin (r = 0.348, P = .0127) and tended to correlate negatively with change in lipoprotein lipase mass in preheparin serum (r = -0.260, P = .0683), which is a marker of insulin sensitivity. Plasma Ang II is associated with body weight, decreases during weight loss, and is associated with markers of insulin resistance in obese subjects with T2D.

Improvement of cardio‐ankle vascular index by glimepiride in type 2 diabetic patients

Aims:  Glimepiride, a third generation sulfonylurea (SU), is known to have extrapancreatic effects, but its vascular effect is unclear. We investigated the efficacy of glimepiride in improving arterial stiffness assessed by cardio‐ankle vascular index (CAVI) in type 2 diabetic patients, compared with glibenclamide, a conventional SU.

Clinical efficacy of the direct assay method using polymers for serum high density lipoprotein cholesterol.

The clinical efficacy and accuracy of the homogeneous assay method for the serum high density lipoprotein (HDL)‐cholesterol determination were evaluated. The principle is as follows: low density lipoproteins (LDL) and very low density lipoproteins (VLDL) were coated by polymers and polyanion to be blocked from cholesterol esterase and cholesterol oxidase. The reaction of these enzymes for HDL cholesterol was enhanced with a detergent, and HDL cholesterol was selectively measured. Both within‐run (n = 3, 20 times) and between‐run (n =3, 7 days) CVs were < 2%. The repeated freezing and thawing (4 times) of three distinct sera resulted in no changes of HDL cholesterol values. Additions of lipid emulsion (Triglyceride = 100 mg/dl) and free bilirubin (20 mg/dl) gave no effect. Linearity was found up to 300 mg/dl. Increases in HDL cholesterol values by the addition of VLDL (total cholesterol (TD) = 300 mg/dl) or LDL (TC = 300 mg/dl) to the tested sera were < 0.5%. The correlation coefficient of the new method with a precipitation method was 0.995 (n = 64). HDL‐C values for patients with hyperlipidemia (Type IIa, IIb, or III, IV, and V) by this method were comparable with those obtained by the precipitation method. From these results, we concluded that the new method meets the requirements for accuracy, precision, ease of handling massive samples, and was clinically useful. J. Clin. Lab. Anal. 11:82–86.

Effects of body weight reduction on cardio-ankle vascular index (CAVI)

OBJECTIVE Obesity is associated with type 2 diabetes, dyslipidemia and hypertension, contributing to atherogenesis. Weight reduction is the fundamental therapy for obesity. Recently, a novel arterial stiffness parameter called cardio-ankle vascular index (CAVI) has been developed. We hypothesized that CAVI may be a candidate marker of increased vascular stiffness in obese patients. The aim of this study is to investigate the effect of weight reduction on CAVI. SUBJECTS AND METHODS Using CAVI as an indicator, we assessed the changes in arterial stiffness in 47 obese Japanese subjects (aged 46 ± 13 years) who underwent a 12-week weight reduction program consisting of a calorie restriction diet (20-25 kcal/day) and exercise therapy. Visceral fat area (VFA) was evaluated by CT. RESULTS At baseline, CAVI correlated positively with age (r = 0.70), blood pressure (r = 0.23), VFA (r = 0.26) and HbA1c (r = 0.39). After 12 weeks of weight reduction, mean BMI decreased from 33.3 ± 7.5 to 30.7 ± 6.4 kg/m(2) (p < 0.0001), and mean CAVI decreased from 8.3 to 7.9 (p < 0.01). The change in VFA correlated positively with change in CAVI in subjects with decrease in CAVI (r = 0.47). Furthermore, change in VFA was a significant independent predictor for change in CAVI. No significant correlation was observed between change in CAVI and clinical variables such as BMI, HbA1c and lipids. CONCLUSION This study demonstrated that CAVI decreased after weight reduction, and was associated with a decrease in VFA. CAVI reduction maybe a marker of improved vascular stiffness after weight reduction in subjects with visceral adiposity.