Five year study of cardiovascular risk factors in Japanese people: implications concerning new onset of metabolic syndrome.

BACKGROUND: The incidence of metabolic syndrome (MetS) has not been fully studied. METHODS AND RESULTS: The data of 35,534 subjects who underwent a health examination both in 1996 and 2001 were analyzed. Since the waist circumference was not available, modified criteria of MetS was used for those with 3 or more of the following items: 1) body mass index (BMI) >or=25 kg/m(2), 2) blood pressure >or=130 mm Hg in systolic and/or >or=85 mm Hg in diastolic, 3) triglycerides >or=150 mg/dL, 4) high-density lipoprotein (HDL) cholesterol or=100 mg/dL. The subjects who underwent therapy for hypertension, diabetes mellitus, and high TG were considered to have these items. The incidence of MetS over 5 years was determined and its risks were evaluated by Cox proportional-hazards models. During the follow-up of exactly 5 years, MetS developed in 2,853 (9.32%) among 30,623 subjects who had no MetS at baseline. The subjects who developed MetS were older, and had elevated BMI, blood pressure, TG and FBG (p<0.001 for all) and lower HDL (p<0.034 for men and p<0.001 for women). Each item of MetS and their combination was associated with a higher risk to develop MetS. Obesity (BMI >or=25 kg/m(2)) alone or in combination with another item was associated with a higher risk to develop MetS suggesting it plays a key role. CONCLUSION: MetS using BMI developed in 9.32% over 5 years or 1.86%/year. Each item of MetS or their combination showed a high risk to develop MetS. Obesity was associated with a higher hazard ratio to develop MetS.

Preheparin lipoprotein lipase mass is a practical marker of insulin resistance in ambulatory type 2 diabetic patients treated with oral hypoglycemic agents.

BACKGROUND: Lipoprotein lipase (LPL) is a key enzyme in the metabolism of triglyceride (TG)-rich lipoproteins. LPL in the preheparin serum (Pr-LPL) mass reflects the insulin sensitivity of diabetic patients (DM) receiving neither insulin nor hypoglycemic agents. METHODS: To determine whether Pr-LPL mass is a marker of insulin resistance in ambulatory type 2 DM receiving oral hypoglycemic agents, we measured Pr-LPL mass using an enzyme immunoassay in 107 ambulatory DM aged 64.9+/-11.5 y. RESULTS: Pr-LPL mass was inversely correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) (-0.363, p<0.001), insulin (-0.351, p<0.001), and lnTG (-0.402, p<0.001), and was positively correlated with HDL-C (0.471, p<0.001). The correlation between Pr-LPL mass and HOMA-IR was equally strong in men and women. Despite medications, hypertension, dyslipidemia, and metabolic syndrome were associated with low Pr-LPL mass. Multiple regression analysis revealed that HOMA-IR was the strongest predictor of Pr-LPL mass. Pr-LPL mass remained constant from 07:30 to 17:30 h. CONCLUSIONS: Pr-LPL mass is a marker of insulin resistance in ambulatory type 2 DM receiving oral hypoglycemic agents, and Pr-LPL mass is stable during the daytime. Therefore, Pr-LPL mass may be more useful than HOMA-IR at diabetes clinics, especially for patients in the postprandial state.

Serum amyloid A (SAA)-induced remodeling of CSF-HDL.

Inflammation is a risk factor for Alzheimer's disease. Serum amyloid A (SAA) is an acute phase protein that dissociates apolipoprotein AI (apoAI) from plasma HDL. In cerebrospinal fluid (CSF), the SAA concentration is much higher in subjects with Alzheimer's disease than in controls. CSF-HDL is rich in apoE, which plays an important role as a ligand for lipoprotein receptors in the central nervous system (CNS). To clarify whether SAA dissociates apoE from CSF-HDL, we added recombinant SAA to CSF and determined the apoE distribution in the CSF using native two-dimensional gel electrophoresis. We found that SAA dissociated apoE from CSF-HDL in a dose-dependent manner. This effect was more evident in apoE4 carriers than in apoE3 or apoE2 carriers. After a 24-h incubation at 37 degrees C, SAA continuously dissociated apoE from CSF-HDL. Amyloid beta (Abeta) fragments (1-42) were bound to large CSF-HDL but not to apoE dissociated by SAA. In conclusion, SAA dissociates apoE from CSF-HDL. We postulate that inflammation in the CNS may impair Abeta clearance due to the loss of apoE from CSF-HDL.

Risk factors for severe coronary artery disease - a case-control study of patients who have undergone coronary artery bypass grafting.

To investigate risk factors for coronary artery disease (CAD), we analyzed the clinical parameters of patients with a coronary artery bypass graft (CABG) in a case-control study. Eighty-eight patients (75 males and 13 females) who underwent CABG surgery between 2001 and 2002 were compared with age- and sex-matched healthy controls randomly chosen from the registry of Kobari Health Care Center. Wilcoxon's signed rank test and McNemar's test were used for pairwise comparisons. Multivariate logistic regression analysis was used to identify significant risk factors for CABG. Significant differences between the patients and controls were observed in HDL-C (p < 0.001), HbA(1c) (p < 0.001), Brinkman Index (BI; p < 0.001), body mass index (BMI; p = 0.002), and systolic blood pressure (SBP; p = 0.013). Subjects with an abnormal BMI, HbA(1c), or HDL-C or high BI value made up a significantly higher proportion of the patients who underwent CABG, compared to their age- and sex-matched controls. Multivariate logistic regression analysis identified high levels of HbA(1c), low levels of HDL-C, and high scores on the BI as significant risk factors for needing a CABG. These results demonstrate that, despite the modification of laboratory determinations by antecedent treatment, HDL-C, HbA(1c), BI, BMI, and SBP are significant indicators of risk for CAD.

Estimating the fasting triglyceride concentration from the postprandial HDL-cholesterol and apolipoprotein CIII concentrations.

Hypertriglyceridemia is an important risk factor for atherosclerosis. In the fasting state, the triglyceride (TG) concentration is correlated significantly with the high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein CIII (apoCIII) concentrations. A postprandial change is evident in TG, but negligible in HDL-C and apoCIII. We investigated whether the fasting TG concentration could be estimated from the postprandial HDL-C and apoCIII concentrations. We measured the TG, HDL-C, and apoCIII concentrations at seven points a day in 58 inpatients. Multiple regression analysis showed that the actual fasting TG concentration was strongly correlated with the TG concentration estimated from the fasting HDL-C and apoCIII concentrations (ln[TG](fasting)=0.0140[apoCIII](fasting)-0.724[HDL-C](fasting)-0.142, r=0.852, p<0.001). This equation was also fit to the fasting data from 163 outpatients (r=0.883, p<0.001). Although the TG concentration increased by up to 28.2%, the HDL-C and apoCIII concentrations changed little during the day. When we substituted the postprandial HDL-C and apoCIII concentrations for the respective fasting values in this equation, there were still strong positive correlations (r=0.794-0.840) between the actual and estimated fasting TG concentrations throughout the day. In conclusion, the fasting TG concentration can be estimated from the postprandial HDL-C and apoCIII concentrations.

Severe starvation hypoglycemia and congestive heart failure induced by thyroid crisis, with accidentally induced severe liver dysfunction and disseminated intravascular coagulation.

A 69-year-old woman caught a cold resulting in nausea, vomiting, diarrhea and severe anorexia. Then she suffered progressively from dyspnea and leg edema, and finally became delirious. On admission severe hypoglycemia, hypothermia, marked tachycardia, generalized edema, mild jaundice and cachexy were noted. EKG showed atrial fibrillation. A chest X-ray, chest CT and echocardiography showed congestive heart failure. Therapeutic use of diuretics induced shock leading to serious liver dysfunction and disseminated intravascular coagulation. However, combined therapy by intravenous glucose, digitalis, diuretics, anti-fibrinolytic drug and hydrocortisone were effective. Addition of antithyroid therapy brought a further favorable outcome.

LCAT-dependent conversion rate is a determinant of plasma prebeta1-HDL concentration in healthy Japanese.

BACKGROUND: Prebeta1-HDL acts as a primary acceptor of cellular cholesterol. Prebeta1-HDL is converted into alpha-migrating high-density lipoprotein (HDL) by lecithin/cholesterol acyltransferase (LCAT). We examined whether the LCAT-dependent conversion rate of prebeta1-HDL is a determinant of the plasma prebeta1-HDL concentration in healthy Japanese. METHODS: We measured the conversion half time (CHT(prebeta1)), the time required for 50% of baseline prebeta1-HDL to be changed into alpha-migrating HDL by LCAT, in 100 healthy Japanese (47 men, 53 women, 22-88 years). RESULTS: Prebeta1-HDL concentration, as determined by immunoassay, was significantly lower in younger women (<50 years, n=24) than in older women (>or=50 years, n=29) (16.8+/-3.3 vs. 21.7+/-8.0 mg/l apolipoprotein AI (apoAI), p<0.01). There was no significant difference in prebeta1-HDL concentration between younger (n=24) and older (n=23) men (21.2+/-6.8 vs. 22.5+/-6.6 mg/l apoAI). The mean CHT(prebeta1) for all subjects was 47.4+/-13.0 min, and was not influenced by gender or age. Prebeta1-HDL concentration was positively correlated with CHT(prebeta1) in both men and women, suggesting that high prebeta1-HDL levels may reflect delayed conversion of prebeta1-HDL. CONCLUSION: LCAT-dependent conversion rate is a determinant of plasma prebeta1-HDL concentration in healthy Japanese. We speculate that prebeta1-HDL concentration may be used as a metabolic marker for HDL maturation.