Self-awareness of fast eating and its impact on diagnostic components of metabolic syndrome among middle-aged Japanese males and females.

OBJECTIVE: The aim of the present study was to examine the association between subjects with self-awareness of fast eating and diagnostic components of metabolic syndrome in Japanese middle-aged male and female. PATIENTS AND METHODS: Subjects consisted of 3208 males (average age 50.6 years) and 2055 females (average age 50.0 years). Associations between subjects with self-awareness of fast eating and multiple components of metabolic syndrome (waist circumference, body mass index [BMI], blood pressure, and related blood sample tests) were evaluated. RESULTS: Significantly more males (57.7%) acknowledged themselves as "fast eater" than females (46.5%). Self-reported fast eaters showed significantly elevated body weight, BMI, and waist circumference in both genders. However, only male self-reported fast eaters showed high levels of blood pressure, fasting blood glucose, uric acid, and low-density lipoprotein (LDL)-cholesterol. CONCLUSION: Fast eating is associated with diagnostic components of metabolic syndrome. The effect of acknowledging themselves as fast eater presents a higher impact on males than on females in the middle-aged Japanese population. The present study indicates that finding subjects with self-awareness of fast eating may lead to the prevention of developing metabolic syndrome.

Clinical significance of measuring soluble LR11, a circulating marker of atherosclerosis and HbA1c in familial hypercholesterolemia.

OBJECTIVES: The LDL receptor relative with 11 ligand-binding repeats (LR11) is closely related to atherosclerotic disease or diabetes. The aim of the study was to clarify how soluble LR11 was related to Achilles' tendon thickness (ATT) and HbA1c in familial hypercholesterolemia. DESIGN AND METHODS: The present study is a cross-sectional case-control study. We enrolled twenty-four patients with heterozygous FH (age 51.0±20.0 year; male, 50%; 20 cases with LDL receptor mutation, 1 case with proprotein convertase subtilisin/kexin type 9 (PCSK9) E32K and 3 cases without confirmed mutations). Soluble LR11 (sLR11) was measured using a sandwich enzyme-linked immunosorbent assay method. RESULTS: Univariate regression analysis showed that sLR11 had positive correlations with age and HbA1c, and inverse correlations with apoA1 in FH. There were also positive correlations of sLR11 with apoE, IDL-C and average ATT. Multivariate regression analysis showed that there were positive correlations of sLR11 to IDL-C and HbA1c independent of age and BMI. In another multivariate regression analysis on the relationships of average ATT as a dependent variable with age, BMI and sLR11 (IDL-C and HbA1c) as independent variables, sLR11 had a positive correlation with average ATT, independent of age and BMI. However, this independency did not persist after adding IDL-C and HbA1c as confounding factors. Of special note is that HbA1c showed a significant correlation with average ATT, independent of other parameters including sLR11. CONCLUSION: It is crucial to intervene in the existence of remnant lipoprotein as well as hypercholesterolemia from an early stage and conduct glycemic control to prevent the progression of atherosclerotic disease in FH.

A novel method for measuring human lipoprotein lipase and hepatic lipase activities in postheparin plasma.

The objective of this study was to establish a new lipoprotein lipase (LPL) and hepatic lipase (HL) activity assay method. Seventy normal volunteers were recruited. Lipase activities were assayed by measuring the increase in absorbance at 546 nm due to the quinoneine dye. Reaction mixture-1 (R-1) contained dioleoylglycerol solubilized with lauryldimethylaminobetaine, monoacylglycerol-specific lipase, glycerolkinase, glycerol-3-phosphate oxidase, peroxidase, ascorbic acid oxidase, and apolipoprotein C-II (apoC-II). R-2 contained Tris-HCl (pH 8.7) and 4-aminoantipyrine. Automated assay of lipase activities was performed with an automatic clinical analyzer. In the assay for HL + LPL activity, 160 microl R-1 was incubated at 37 degrees C with 2 microl of sample for 5 min, and 80 microl R-2 was added. HL activities were measured under the same conditions without apoC-II. HL and LPL activities were also measured by the conventional isotope method and for HL mass by ELISA. Lipase activity detected in a 1.6 M NaCl-eluted fraction from a heparin-Sepharose column was enhanced by adding purified apoC-II in a dose-dependent manner, whereas that eluted by 0.8 M NaCl was not. Postheparin plasma-LPL and HL activities measured in the present automated method had high correlations with those measured by conventional activity and mass methods. This automated assay method for LPL and HL activities is simple and reliable and can be applied to an automatic clinical analyzer.

Comparison of effects of pitavastatin and atorvastatin on plasma coenzyme Q10 in heterozygous familial hypercholesterolemia: results from a crossover study.

An open, randomized, four-phased crossover study using 4 mg of pitavastatin or 20 mg of atorvastatin was performed to compare their efficacy and safety, especially regarding plasma levels of coenzyme Q10 (CoQ10) in 19 Japanese patients with heterozygous familial hypercholesterolemia. Pitavastatin and atorvastatin caused significant and almost comparable reductions in serum levels of total cholesterol (-35.4 vs. -33.8%), low-density lipoprotein cholesterol (-42.8 vs. -40.7%), and triglyceride (-26.1 vs. -29.4%), and significantly increased serum levels of high-density lipoprotein cholesterol (12.1 vs. 11.4%). Under these conditions, plasma levels of CoQ10 were reduced by atorvastatin (-26.1%, P=0.0007) but not by pitavastatin (-7.7%, P=0.39), although no adverse events or abnormalities of liver and muscle enzyme were observed after either statin treatment. It remains to be seen whether the observed changes in CoQ10 levels are related to the long-term safety of this drug.

The relationship of serum lipoprotein lipase mass with fasting serum apolipoprotein B-48 and remnant-like particle triglycerides in type 2 diabetic patients.

BACKGROUND: There have been no previous reports showing specifically the relation between lipoprotein lipase (LPL) and apolipoprotein (apo) B-48 or remnant metabolism. In this study, we have clarified the relationships of LPL mass in pre-heparin with serum apo B-48 measured by enzyme-linked immunosorbent assay, triglycerides (TG), and remnant-like particle triglycerides (RLP-TG). MATERIAL AND METHODS: Seventy-nine type 2 diabetic subjects [age, 55+/-13; body mass index (BMI), 25+/-5.0 kg/m2; fasting plasma glucose (FPG), 7.39+/-2.22 mmol/l, HbA1c, 6.5+/-1.3%, total cholesterol (TC), 5.36+/-1.09 mmol/l, TG, 2.32+/-2.53 mmol/l; HDL-C, 1.22+/-0.44 mmol/l; serum LPL mass, 45+/-22 ng/ml; apo B-48, 6.6+/-6.3 microg/ml] were recruited in this study. Fasting serum apo B-48 were measured by ELISA using anti-human apo B-48 monoclonal antibodies (MoAb) and LPL mass by ELISA using anti-bovine milk LPL MoAb. RLP-TG levels were measured using monoclonal antibodies to apo B-100 and apo A-1. RESULTS: There was no relationship of LPL mass to age, BMI, FPG, and HbA1c. Serum LPL mass was correlated inversely with TG (r=-0.529 p<0.0001) and positively with HDL-C (r=0.576, p<0.0001). Also, LPL mass showed inverse correlations with apo B-48 (r=-0.383 p<0.0001) and RLP-TG (r=-0.422 p<0.0001, n=51). Multiple regression analysis with TG, apo B-48, or RLP-TG as dependent variables, and age, gender, BMI, plasma glucose, and LPL mass as independent variables showed that LPL mass was associated independently with TG, apo B-48, or RLP-TG. CONCLUSION: The decrease in LPL protein mass could cause an increase in serum apo B-48 and RLP-TG levels, which is related to the retardation of remnant metabolism.

Course of damage to the hallux over 5 years after forefoot resection arthroplasty in rheumatoid arthritis patients.

A retrospective study of 34 feet from 20 consecutive patients with rheumatoid arthritis was performed to investigate the development of damage to the hallux over 5 years after forefoot resection arthroplasty. Radiographically we analysed changes in two valgus angles and the interphalangeal joint (IP) damage of the hallux. These parameters were measured preoperatively, 12 months postoperatively, and at the latest follow-up. Although the average HVA (between the first metatarsal and the proximal phalanx) significantly decreased from 38.7 degrees preoperatively to 8.66 degrees postoperatively, the angle increased to 23.0 degrees during the first 12 months following surgery. Further deterioration of the angle at the last follow-up was not detected (25.3 degrees ; P=0.252). The average IPV (between the proximal phalanx and the distal phalanx) angle significantly increased from 6.65 degrees preoperatively to 12.1 degrees 12 months postoperatively and thereafter slightly increased to 13.3 degrees at the latest follow-up. The average of the Sharp/van der Heijde score of the IP joint significantly increased from 5.71 preoperatively to 8.58 12 months postoperatively and thereafter slightly increased to 9.65 at the latest follow-up. The deterioration and destruction process of the hallux after resection arthroplasty occurred soon after surgery, and the progression of the deformity was temporary.

A novel method for measuring human hepatic lipase activity in postheparin plasma.

The objective of this study was to establish a hepatic lipase (HL) assay method that can be applied to automatic clinical analyzers. Seventy-four hyperlipidemic subjects (men/women 45/29) were recruited. Lipase activity was assayed measuring the increase in absorbance at 546 nm due to quinonediimine dye production. Reaction mixture R-1 contained 50 mM Tris-HCl (pH 9.5), 0.5 mM glycerol-1,2-dioleate, 0.4% (unless otherwise noted) polyoxyethylene-nonylphenylether, 3 mM ATP, 3 mM MgCl(2), 1.5 mM CaCl(2), monoacylglycerol-specific lipase, glycerol kinase, glycerol-3-phosphate oxidase, 0.075% N,N-bis-(4-sulfobutyl)-3-methylaniline-2 Na, peroxidase, ascorbic acid oxidase. Reaction mixture R-2 contained 50 mM Tris-HCl (pH9.5), 0.15% 4-aminoantypirine. Automated assay for activity was performed with a Model 7080 Hitachi analyzer. In the lipase assay, 160 microl of R-1 was incubated at 37 degrees C with 3 microl of samples for 5 min, and 80 microl of R-2 was added. Within-run coefficient of variations was 0.9-1.0%. Calibration curve of lipase activity was linear (r = 0.999) between 0 and 320 U/l. Analytical recoveries of purified HL added to plasma were 96.6-99.8%. HL activity in postheparin plasma measured in this method had a closer correlation with HL mass by a sandwich ELISA (r = 0.888, P < 0.0001) than those in the conventional method using [(14)C-]triolein (r = 0.730, P < 0.0001). This assay method for HL activity can be applied to an automatic clinical analyzer.

Relationship of lipoprotein lipase and hepatic triacylglycerol lipase activity to serum adiponectin levels in Japanese hyperlipidemic men.

OBJECTIVE: The aim of this study was to determine how lipoprotein lipase (LPL) and hepatic triacylglycerol lipase (HTGL) activity relate to serum adiponectin levels. RESEARCH DESIGN AND METHODS: Fifty-five hyperlipidemic Japanese men were recruited for this study. LPL and HTGL activity in post-heparin plasma (PHP) was measured using Triton X-100 emulsified-[14C] triolein. The remaining activity in the presence of 1M NaCl was defined as HTGL activity. Serum adiponectin levels were determined by an enzyme-linked immunosorbent assay system. RESULT: LPL activity had a positive relationship with HDL2, but had no relation with HDL3, while HTGL had positive relationship with HDL3, but had no relationship with HDL2. LPL activity showed a positive relationship [r = 0.345, p = 0.010] to serum adiponectin levels, while and HTGL activity showed an inverse relationship [r = - 0.365 p = 0.006]. Multiple regression analysis with LPL and HTGL as dependent variables and age, BMI, serum adiponectin and the homeostasis model assessment of insulin resistance (HOMA-IR) as independent variables showed LPL and HTGL's association to adiponectin did not persist after adjustments for these covariants. However, the association of LPL activity to HOMA-IR was found to persist after adjustments of age, BMI, and serum adiponectin. CONCLUSIONS: There was a co-linearity between insulin sensitivity and adiponectin as well as insulin sensitivity and LPL/HTGL activity.

Circulating matrix metalloproteinases and their inhibitors in premature coronary atherosclerosis.

To investigate the clinical significance of circulating matrix metalloproteinases (MMPs) and their tissue inhibitos (TIMPs) in patients with premature coronary atheroscrelosis, we studied 53 consecutive male patients with angiographically defined premature (<65 years) and stable coronary artery disease. Plasma levels of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 were determined in peripheral blood by a sandwich enzyme immunoassay, and the results were compared with those from 133 age-matched control males. There were significant differences in all the MMPs and TIMPs (p<0.001) between patients and controls. In the patient group, the levels of MMP-9 (mean +/- SD (ng/ml) 27.2 +/- 15.2/21.8 +/- 15.2) and TIMP-1 (130.4 +/- 55.7/94.5 +/- 26.3) were significantly higher, and the levels of MMP-2 (632.5 +/- 191.6/727.6 +/- 171.4), MMP-3 (53.1 +/- 31.2/79.6 +/- 29.9), and TIMP-2 (24.7 +/- 15.2/35.4 +/- 16.4) were significantly lower than those of controls. We found significant positive correlation between plasma MMP-9 levels and low-density lipoprotein (LDL)-cholesterol levels (Rs = 0.168, p = 0.022), and significant negative correlation between plasma MMP-9 levels and high-density lipoprotein (HDL)-cholesterol levels (Rs = -0.164, p = 0.026) by Spearman rank correlation test. In contrast, plasma MMP-2 (Rs = 0.181, p = 0.014) and MMP-3 (Rs = 0.260, p = 0.0004) levels were positively correlated with HDL-cholesterol levels. TIMP-2 levels were negatively correlated with total cholesterol (Rs = -0.197, p = 0.007) and LDL-cholesterol (Rs = -0.168, p=0.022) levels. These results suggest that the circulating levels of MMPs and TIMPs are altered in patients with premature coronary atherosclerosis and that plasma lipoprotein cholesterol levels correlate with these, possibly as a result of the lipoprotein-vessel wall interactions.

Effect of common methylenetetrahydrofolate reductase gene mutation on coronary artery disease in familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by primary hypercholesterolemia and premature coronary artery disease (CAD). However, the development of CAD in FH shows considerable interindividual variations. Elevated levels of plasma homocysteine have been recognized as independent risk factors for CAD. A 5,10-methylenetetrahydrofolate reductase (MTHFR) gene mutation (valine [V] was substituted for alanine [A]) has been reported to be associated with elevated levels of plasma homocysteine in mutant homozygotes (i.e., VV). We studied 199 consecutive male heterozygous FH patients, 99 with and 100 without CAD. In the CAD group, genotype VV and V alleles were significantly more frequent than in the non-CAD group (15% vs 7% in genotypes [p = 0.035] and 0.41 vs 0.30 in alleles [p = 0.017]). The mean ages at onset in the CAD group were 50, 51, and 43 years for genotypes AA, AV, and VV, respectively (p <0.05); the age of onset of CAD in genotype VV was significantly lower than in the other 2 genotypes. Kaplan-Meier survivor curves indicated that the development of CAD was significantly accelerated by MTHFR mutation, probably in a gene dose-dependent manner. Furthermore, only MTHFR genotype VV was shown to be an independent predictor of the early onset of CAD in a stepwise multiple regression analysis. The mean plasma homocysteine levels of genotype VV were significantly higher than those of the other 2 genotypes. Thus, the MTHFR mutation appears to accelerate the onset of CAD through elevation of plasma homocysteine levels in male heterozygous patients with FH.

Plasma homocysteine level and development of coronary artery disease.

BACKGROUND: The plasma level of homocysteine is an independent risk factor for atherosclerotic vascular disease. The relationship between plasma homocysteine level and the onset of coronary artery disease (CAD) has not been established. OBJECTIVE: To investigate the relationship between plasma homocysteine level and the age at which CAD was diagnosed. METHODS: Fifty-seven male patients aged < or = 65 years (mean age 53 years) with angiographically proven symptomatic CAD seen consecutively and 138 age-matched male control subjects (mean age 52 years) free from atherosclerotic vascular disease were studied. They were divided into two subgroups, a group of younger subjects (aged < or = 55 years) and a group of older subjects (aged 56-65 years). RESULTS: Plasma homocysteine levels in CAD patients significantly exceeded those of control subjects (means 13.4 versus 10.6 nmol/ml, P = 0.0002). Plasma homocysteine level of subjects in younger CAD group was significantly higher than that of subjects in older CAD group (15.0 versus 11.3 nmol/ml, P = 0.03), and age and logarithmically transformed plasma homocysteine level exhibited a significant negative correlation (r = -0.28, P = 0.03) for subjects in CAD group. Among control subjects, members of our two age subgroups had similar plasma homocysteine levels. Younger CAD patients had significantly higher plasma homocysteine levels than did younger controls (15.0 versus 10.4 nmol/ml, P < 0.0001). However, for older groups there was no significant difference between plasma homocysteine levels in CAD patients and controls (11.3 versus 10.9 nmol/ml). Multiple regression analysis showed that only logarithmically transformed plasma homocysteine level was a significant predictor for age of onset of CAD. CONCLUSION: An elevated level of plasma homocysteine is more important in the development of premature CAD than it is in that of late-onset CAD among men.