Yuichiro Goto

Regression of coronary atherosclerosis by combined LDL-apheresis and lipid-lowering drug therapy in patients with familial hypercholesterolemia: a multicenter study

The purpose of the LDL-Apheresis Regression Study (LARS) group, which included 13 institutions in Japan, was to investigate the effects on coronary atherosclerosis of LDL-apheresis combined with cholesterol-lowering drugs. Changes in coronary artery stenosis were assessed angiographically in 37 patients with familial hypercholesterolemia (7 homozygotes and 25 heterozygotes) and hypercholesterolemia which had not been defined as familial hypercholesterolemia (5 patients) by visual judgement and computer analysis. Definite regression was observed in 14 cases, including 4 homozygotes and 10 heterozygotes and others. Regression occurred as often in patients with severe coronary artery disease (2 or more vessel disease) as in those having less severe disease. Our results encourage initiation of aggressive cholesterol-lowering therapy to produce regression of coronary atherosclerosis in FH patients at high risk for cardiovascular events.

A randomized, double-blind trial comparing the efficacy and safety of pitavastatin versus pravastatin in patients with primary hypercholesterolemia

Pitavastatin (p-INN) is a novel and fully synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, with a cholesterol-lowering action stronger than that of other statins currently in use. A 12-week, multi-center, randomized, double-blind, controlled study was conducted to confirm the efficacy and safety of pitavastatin compared with pravastatin, an agent for using to reduce low density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients. Patients were recruited at 43 institutes in Japan. Following more than 4 weeks run-in period, 240 patients were randomized to receive 2 mg of pitavastatin or 10 mg of pravastatin daily. At 12 weeks post-randomization, the pitavastatin group showed significantly lower LDL-C levels by -37.6% from baseline compared with -18.4% in the pravastatin group (P<0.05). Pitavastatin also significantly lowered total cholesterol (TC) by -28.2% compared with -14.0% of pravastatin (P<0.05). The LDL-C target level of <140 mg/dl was attained in 75% of the patients treated with pitavastatin, compared with 36% of those in the pravastatin group (P<0.05). Pitavastatin also significantly reduced triglycerides (TG), apo B, C-II and C-III, compared with pravastatin, and increased HDL-C, apo A-I and A-II, to the same extent of pravastatin. Safety was assessed by monitoring adverse events and measuring clinical laboratory parameters. The adverse event profile was similar for both treatment groups and neither treatment caused clinically relevant laboratory abnormalities. These results indicated that pitavastatin was more effective than pravastatin, and both drugs were well-tolerated in the treatment of hypercholesterolemia.

Quantitation of serum apolipoprotein A-I, A-II, B, C-II, C-III and E in healthy Japanese by turbidimetric immunoassay : reference values, and age- and sex-related differences

Serum apolipoproteins (Apo) A-I, A-II, B, C-II, C-III and E were determined in healthy Japanese subjects (male 1,603, female 1,800, aged 4-95 yr) by the turbidimetric immunoassay, with six kinds of automated instruments, and the commercial reagent kits with standards. There was a high degree of interlaboratory comparability of analytical values among the 15 participating laboratories. The reference values were calculated for adult males and females (male 677, female 467, aged 21-60 yr). Apo A-I and E levels were significantly higher and Apo C-II and C-III were significantly lower in females than in males. Furthermore, serum Apo A-I and A-II tended to decrease, and Apo B to increase with age. Apo C-II, C-III and E tended to decrease after 60 yr of age.

Comparison of selectivity of LDL removal by double filtration and dextran-sulfate cellulose column plasmapheresis

The possibility of selective removal of VLDL, IDL and LDL by double filtration (DF) and dextran-sulfate cellulose (DSC) column plasmapheresis was investigated in hypercholesterolemia. Two and a half liters of plasma were treated. Sixty six percent of TC and 68% of LDL-C were removed by DF plasmapheresis. The removal rate of HDL-C was 50% which was significantly lower than that of LDL-C. The removal rate of apoprotein A-I and A-II was also significantly lower than that of apoprotein B. Sixty percent of LDL-C and 61% of apoprotein B were removed by DSC column plasmapheresis while the decrease of HDL-C, apoprotein A-I and A-II was minimal. Therefore, DSC column plasmapheresis could remove atherogenic lipoproteins more selectively than DF plasmapheresis.

The Effect of CS-514, an Inhibitor of HMG-CoA Reductase, on Serum Lipids in Healthy Volunteers

CS-514 is a competitive inhibitor of HMG-CoA reductase. The effect of this agent on serum lipids and lipoproteins was studied in 10 healthy normocholesterolemic male volunteers by giving 20 mg of CS-514 or placebo twice a day for 7 days under double-blind conditions. The mean total serum cholesterol level decreased by 18.6% in the CS-514 group, whereas it increased by 7.4% in the placebo group and the difference between the two groups was statistically significant (P less than 0.01). LDL cholesterol and LDL apo B values were reduced by 22.6% and 23.2%, respectively. Serum triglyceride level did not change significantly. No clinical or laboratory abnormalities were observed.

Comparison of selectivity of LDL removal by double filtration and dextran-sulfate cellulose column plasmapheresis, and changes of subfractionated plasma lipoproteins after plasmapheresis in heterozygous familial hypercholesterolemia

The possibility of selective removal of low density lipoprotein (LDL) by double filtration (DF) and dextran-sulfate cellulose (DSC) column plasmapheresis in hypercholesterolemia and the acute recovery process of the subfractionated plasma lipoproteins after plasmapheresis in heterozygous familial hypercholesterolemia were investigated. Sixty-six percent of the LDL cholesterol and 42% of the HDL cholesterol were removed by 2.5 L DF plasmapheresis with the second filters having average pore diameters of 30 nm and 40 nm. Fifty-nine percent of the LDL cholesterol was removed by 2.5 L DSC column plasmapheresis, while HDL cholesterol did not change. Therefore, DSC column plasmapheresis could remove LDL much more specifically than DF plasmapheresis. VLDL increased rapidly and reached the preplasmapheresis level within four days after plasmapheresis. IDL returned to the preplasmapheresis level in 2 weeks. The LDL1 level was approximately 80% of the preplasmapheresis level on the 14th day. LDL2 reached the peak at the seventh day. HDL2 and HDL3 moved in the same manner and reached the peak on the seventh day after DF plasmapheresis.

Reference intervals for serum apolipoproteins A-I, A-II, B, C-II, C-III, and E in healthy Japanese determined with a commercial immunoturbidimetric assay and effects of sex, age, smoking, drinking, and Lp(a) level

BACKGROUND Apolipoproteins, which are contained in lipoprotein particles, play important roles in the transport of lipids. METHODS Serum levels of apolipoproteins (apo) A-I, A-II, B, C-II, C-III, and E were determined by immunoturbidimetry in a healthy Japanese study population (1018 men and 1167 women, age 20-69 years) to establish reference intervals. RESULTS Among the 2185 subjects examined, the mean serum value for apoA-I was 1.42 +/- 0.20 g/l, for apoA-II was 0.30 +/- 0.05 g/l, for apoB was 0.87 +/- 0.18 g/l, for apoC-II was 29 +/- 13 mg/l, for apoC-III was 75 +/- 20 mg/l, and for apoE was 36 +/- 9 mg/l. A sex difference was detected in the mean serum concentrations of all six apolipoproteins. Alcohol consumption and cigarette use had a slight effect on serum apolipoprotein concentrations. Age effects were observed among women in apoB, apoC-II, and apoC-III concentrations. Moreover, individuals with elevated serum lipoprotein (a) [Lp(a), >300 mg/l] also displayed increased serum apoB and apoC-II levels and an increased apoB/apoA-I ratio. CONCLUSION The reference intervals for apolipoproteins in Japanese adults that we established, using commercially available reagents for automated analyzers, will be helpful for assessing risk of coronary heart disease and pathological conditions of patients with hyperlipidemia. We recommend use of these reference intervals for the clinical interpretation of serum apolipoprotein concentrations.

Effects of eicosapentaenoic acid on plasma lipoprotein subfractions and activities of lecithin: cholesterol acyltransferase and lipid transfer protein

The effects of 12 weeks eicosapentaenoic acid (EPA) administration (2.7 g/day) on plasma lipoprotein subfraction levels and on activities of lecithin: cholesterol acyltransferase (LCAT) and lipid transfer protein (LTP) were investigated. Plasma VLDL-C, VLDL-TG, VLDL-PL, VLDL-apo B, VLDL-apo C-II and VLDL-apo C-III levels were decreased by 32.8% (P less than 0.05), 31.2% (P less than 0.01), 31.5% (P less than 0.05), 32.5% (P less than 0.05), 34.7% (P less than 0.05) and 34.1% (P less than 0.05), respectively. EPA did not change plasma IDL-TC, IDL-TG, IDL-PL and IDL-apo B levels. Plasma large, light LDL (LDL1)-TC, LDL1-PL and LDL1-apo B levels were decreased by EPA by 18.7% (P less than 0.02), 19.1% (P less than 0.01) and 23.3% (P less than 0.01) while LDL1-TG level was not changed. Plasma small, heavy LDL (LDL2)-TC level was increased by 25.7% (P less than 0.02) while LDL2-TG, LDL2-PL and LDL2-apo B levels were not altered. Plasma HDL2-TC, HDL2-TG, HDL2-PL and HDL2-apo A-I levels stayed unchanged by EPA treatment. EPA did not affect plasma HDL3-TC, HDL3-PL and HDL3-apo A-I levels but decreased HDL3-TG level significantly (P less than 0.02). LCAT activity was not altered by EPA. LTP activity was increased by 24.8% at 4 weeks (P less than 0.02) and by 32.1% (P less than 0.001) at 12 weeks EPA treatment. We conclude that EPA reduces plasma large, light LDL levels as well as plasma VLDL amounts and stimulates LTP activities.

Dose-dependent hypolipidemic effect of an inhibitor of HMG-CoA reductase, pravastatin (CS-514)) in hypercholesterolemic subjects A double blind test

The hypolipidemic effect of a new HMG-CoA reductase inhibitor, pravastatin, was examined. The reductions of serum cholesterol and LDL-cholesterol were dose-dependent and significant differences were observed between placebo and 10 or 20 mg groups (P less than 0.01), and 10 and 20 mg (P less than 0.05) groups. The reduction rate of cholesterol after 8 weeks during medication was 16.1% in the 10 mg group, 20.5% in the 20 mg group compared to baseline serum cholesterol levels. LDL-cholesterol decreased by 23.9% in the 10 mg group, and 29.8% compared to baseline LDL-cholesterol in the 20 mg group. The lowering of total cholesterol was entirely attributed to a reduction in LDL-cholesterol.

Disappearing False Aneurysm of the Ventricular Septum Without Rupture: A Complication of Acute Inferior Myocardial Infarction—A Case Report

An interseptal false aneurysm of the left ventricle due to the dissection of the septum in a patient with acute inferior myocardial infarction is described. The aneurysm was demonstrated as a cystic bulge of the left ventricular cavity into the inferoposterior interventricular septum with a small orifice from the left ventricle without any protrusion or rupture into the right ventricular cavity. Two-dimensional echocardiography, magnetic resonance imaging, and dy namic computed tomography were the most useful and reliable noninvasive di agnostic modalities. Repeated examinations demonstrated a significant reduction of the aneu rysm in six months.