We followed 828 nondemented residents of Hisayama Town, Kyushu, Japan, aged 65 years or older (88.3% of the elderly population) for 7 years starting in 1985 in order to determine the type-specific incidence of dementia and its risk factors in the general Japanese population. Only two subjects were lost to the follow-up, during which period 103 subjects developed dementia. Morphologic examination of the brains of 89 subjects (86.4%) was made by autopsy or CT. We made the initial diagnosis of dementia based on the DSM-III-R criteria, with the diagnoses of vascular dementia (VD) being based on the NINDS-AIREN criteria and Alzheimer's disease (AD) on the NINCDS-ADRDA criteria. The incidence of VD and AD increased with age for both sexes. The age-adjusted total incidence (per 1,000 person-years) of dementia was 19.3 for men and 20.9 for women. The corresponding rates for VD were 12.2 for men and 9.0 for women, and for AD, 5.1 for men and 10.9 for women. Among the VD subjects whose brain morphology we examined, the most frequent type of stroke was multiple lacunar infarcts (42%), but half these subjects lacked a stroke episode in their histories. Multivariate analysis showed that age, prior stroke episodes, systolic blood pressure, and alcohol consumption were significant independent risk factors for the occurrence of VD. In contrast, age and a low score on Hasegawa's dementia scale were significant risk factors for AD, and physical activity was a significant preventive factor for AD.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperglycemia in response to oral glucose loading rapidly suppresses endothelium-dependent vasodilation, probably through increased production of oxygen-derived free radicals. These findings strongly suggest that prolonged and repeated post-prandial hyperglycemia may play an important role in the development and progression of atherosclerosis.

There is a deficiency in endothelial NO activity in spasm arteries, which leads to the supersensitivity of the artery to the vasodilator effect of nitroglycerin and to the vasoconstrictor effect of acetylcholine in patients with CSA. This deficient endothelial NO activity plays an important role in the pathogenesis of coronary spasm.

Background-Remnant lipoproteins are atherogenic, but assays of remnants have not been available in routine clinical laboratories because of the lack of practical and validated methods. A simple and reliable method for such an assay, using an immunochemical approach, has recently been developed. This study prospectively examined whether remnant lipoprotein levels in fasting serum, measured by our method, may have prognostic value in patients with coronary artery disease (CAD). Methods and Results-Remnant lipoprotein levels in fasting serum were measured in 135 patients with CAD by an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. Patients were followed up for Յ36 months until occurrence of 1 of the following clinical coronary events: recurrent or refractory angina pectoris requiring coronary revascularization, nonfatal myocardial infarction, or cardiac death. Kaplan-Meier analysis demonstrated a significantly higher probability of developing coronary events in patients with the highest tertile of remnant levels (Ͼ5.1 mg cholesterol/dL; 75th percentile of distribution of remnant levels) than in those with the lowest tertile of remnant levels (Յ3.3 mg cholesterol/dL; 50th percentile of the distribution). Higher levels of remnants were a significant and independent predictor of developing coronary events in multivariate Cox hazard analysis including the following covariates: extent of coronary artery stenosis, age, sex, smoking, hypertension, diabetes mellitus, hypercholesterolemia, low HDL cholesterol, and hypertriglyceridemia. Conclusions-Higher levels of remnant lipoproteins in fasting serum predict future coronary events in patients with CAD independently of other risk factors. Thus, measurement of fasting remnant levels, assessed by the current immunoseparation method, may be helpful in assessment of CAD risk. (Circulation. 1999;99:2858-2860.)

Remnant lipoprotein levels were independently associated with abnormal endothelium-dependent vasomotor function in large and resistance coronary arteries in humans, indicating that remnant lipoproteins may impair endothelial vasomotor function in human coronary arteries. The decrease in coronary nitric oxide bioactivity may be responsible in part for the inhibitory effects of remnant lipoproteins.

Background-The circulating levels of secretory nonpancreatic type II phospholipase A 2 (sPLA 2 ) are increased in various chronic inflammatory diseases and the increase in the levels correlates with the disease severity. sPLA 2 may possibly play a role in atherogenesis and is highly expressed in atherosclerotic arterial walls that are known to have inflammatory features. Thus, this study prospectively examined whether circulating levels of sPLA 2 may have a significant risk and prognostic values in patients with coronary artery disease (CAD). Methods and Results-Plasma levels of sPLA 2 were measured in 142 patients with CAD and in 93 control subjects by a radioimmunoassay. The sPLA 2 levels had a significant and positive relations with serum levels of C-reactive protein, a marker of systemic inflammation, and with the number of the traditional coronary risk factors associated with individuals. Multivariate logistic regression analysis showed that higher levels of sPLA 2 (Ͼ246 ng/dL; 75th percentile of sPLA 2 distribution in controls) were a significant and independent risk factor for the presence of CAD. In multivariate Cox hazard analysis, the higher levels of sPLA 2 were a significant predictor of developing coronary events (ie, coronary revascularization, myocardial infarction, coronary death) during a 2-year follow-up period in patients with CAD independent of other risk factors, including CRP levels, an established inflammatory predictor. Conclusions-The increase in circulating levels of sPLA 2 is a significant risk factor for the presence of CAD and predicts clinical coronary events independent of other risk factors in patients with CAD; these results may reflect possible relation of sPLA 2 levels with inflammatory activity in atherosclerotic arteries. (Circulation. 1999;100:1280-1284.)

4H-SiC(0001), (000 " 1 1), and (11 " 2 20) have been directly oxidized by N 2 O at 1300 C, and metal-oxide-semiconductor (MOS) interfaces have been characterized. The interface state density has been significantly reduced by N 2 O oxidation on any face, compared to conventional wet O 2 oxidation at 1150 C. Planar n-channel metal-oxide-semiconductor field-effect transistors (MOSFETs) fabricated on 4H-SiC(0001), (000 " 1 1) and (11 " 2 20) faces have shown effective channel mobilities of 26, 43, and 78 cm 2 /Vs, respectively. Secondary ion mass spectrometry analyses have revealed a clear pileup of nitrogen atoms near the MOS interface. The thickness of the interfacial transition layer can be decreased by N 2 O oxidation. The crystal face dependence of the interface structure is discussed. A simple consideration of chemistry indicates that NO, generated from the decomposition of N 2 O, may be a more efficient oxidant of carbon than O 2 .

The dehydroepiandrosterone (DHEA) concentration decreases with age. There is evidence that DHEA has a protective effect against age-related disorders, including cardiovascular disease. Accordingly, we examined the effect of DHEA supplementation (25 mg/d) on endothelial function, insulin sensitivity, and fibrinolytic activity in 24 men with hypercholesterolemia (mean age, 54 +/- 1 yr). All subjects were enrolled in a randomized, double-blind study. Flow-mediated dilation of brachial artery after transient occlusion, which was expressed as the percent change from the baseline value of the diameter, increased significantly with DHEA supplementation [DHEA: baseline, 3.9 +/- 0.5%; 4 wk, 6.9 +/- 0.7%; 8 wk, 7.9 +/- 0.6%; 12 wk, 8.4 +/- 0.7% (P < 0.01 vs. baseline for all, by ANOVA); placebo: 4.1 +/- 0.6%, 4.5 +/- 0.5%, 3.9 +/- 0.5%, and 4.4 +/- 0.6% (P < 0.01 for all, by ANOVA)]. There was a significant concurrent reduction in the plasma levels of plasminogen activator inhibitor type 1 during DHEA supplementation [DHEA: 9.1 +/- 2.2, 6.4 +/- 2.3, 5.5 +/- 2.8, and 5.1 +/- 2.0 IU/ml (P < 0.01 vs. baseline, by ANOVA); placebo: 9.0 +/- 2.1, 10.4 +/- 2.2, 9.5 +/- 2.2, and 9.6 +/- 2.1 IU/ml (P < 0.01, by ANOVA)]. DHEA supplementation also decreased steady state plasma glucose [DHEA: baseline, 178.9 +/- 12.2; 12 wk, 132.0 +/- 12.8 mg/dl (P < 0.01, by ANOVA); placebo: 181.0 +/- 13.8 and 179.6 +/- 12.4 mg/dl (P < 0.01, by ANOVA)]. In contrast, steady state plasma insulin did not change during the study in either group. The low dose DHEA supplementation improves vascular endothelial function and insulin sensitivity and decreases the plasminogen activator inhibitor type 1 concentration. These beneficial changes have the potential to attenuate the development of age-related disorders such as cardiovascular disease.