Texture Analysis Using Preoperative Positron Emission Tomography Images May Predict the Prognosis of Patients With Resectable Oral Squamous Cell Carcinoma.

PURPOSE: Texture analysis is a computer-assisted technique used to measure intratumoral heterogeneity, which is known to have important roles in cancer research. This study aimed to assess the potential prognostic values of textural features extracted from preoperative 18F-fluorodeoxyglucose positron emission tomography images in patients with resectable oral squamous cell carcinoma. PATIENTS AND METHODS: This retrospective cohort study included patients with oral squamous cell carcinoma who underwent resection surgery. We extracted 31 textural indices from preoperative positron emission tomography images. Overall survival (OS) and disease-free survival (DFS) were chosen as the primary outcome variables, and the primary predictor variables were age, sex, primary tumor location, pathological T and N classification, histologic differentiation, resected margin, perineural and lymphovascular invasion, maximum standardized uptake value, and the 14 textural indices selected in the factor analysis. We analyzed OS and DFS using Kaplan-Meier curves, and the differences between survival curves were determined using a log-rank test. The independent prognostic factors were assessed using the Cox-proportional hazards model. RESULTS: We enrolled 81 patients (median age, 67.3 years; range, 32 to 88 years). The median follow-up duration was 50.1 months (range, 6.3 to 133.7 months). The univariable and multivariable analyses revealed that higher entropy values (≥1.91) were associated with worse OS (hazard ratio, 21.49; 95% confidence interval, 1.36 to 340.71; P = .03) and DFS (hazard ratio, 50.69; 95% confidence interval, 5.23 to 491.18; P = .001). CONCLUSIONS: This study showed that entropy is a statistically significant prognostic factor of both OS and DFS. Texture analysis using preoperative positron emission tomography images may contribute to risk stratification.

The prognostic significance of intratumoral heterogeneity of 18F-FDG uptake in patients with oral cavity squamous cell carcinoma.

PURPOSE: This study aimed to evaluate the prognostic significance of two major indices of intratumoral heterogeneity of 18F-fluorodeoxyglucose uptake by positron emission tomography (PET)/computed tomography (CT), namely heterogeneity index (HI) and heterogeneity factor (HF), in patients with oral squamous cell carcinoma. METHODS: We performed a retrospective analysis of 62 patients who underwent resective surgery. HI, HF, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained from pretreatment PET. HI was obtained by dividing SUVmax by SUVmean for the primary lesion; HF was obtained by taking the derivative (dV/dT) of the volume-threshold function from 30 to 70%. Univariate and multivariate analyses for the overall survival (OS) and disease-free survival (DFS) were performed using PET and clinicopathological parameters. RESULTS: Univariate and multivariate analyses of OS revealed that higher HI levels (threshold for the SUVmean is 30% of the SUVmax) were associated with poorer OS [hazard ratio (HR) = 11.57; 95% confidence interval (CI) = 1.45-92.28; P = 0.021]. Moreover, univariate and multivariate analyses of DFS revealed that higher TLG levels (threshold for the MTV and SUVmean is 4.0 of the SUV) were associated with poorer DFS (HR = 14.48; 95% CI = 1.27-164.78; P = 0.031). CONCLUSIONS: HI and TLG may be statistically significant prognostic factors for OS and DFS, respectively.

Effect of losartan on serum uric acid in hypertension treated with a diuretic: the COMFORT study.

It has been shown that losartan, an angiotensin II receptor blocker (ARB), reduces serum uric acid levels. However, the effects of losartan on serum uric acid levels in the patients treated with a thiazide diuretic have not been fully elucidated. We have investigated the effects of losartan compared with other ARBs on blood variables and blood pressure control in hypertensive patients treated with a thiazide diuretic using data from the COMFORT study. The present analysis included a total of 118 hypertensive subjects on combination treatment with ARBs except for losartan and a diuretic who were randomly assigned to a daily regimen of a combination pill (losartan 50 mg/hydrochlorothiazide 12.5 mg) or to continuation of two pills, an ARB except for losartan and a diuretic. Blood pressures were evaluated at 1, 3, and 6 months after randomization and changes in blood variables including serum uric acid were evaluated during 6 months treatment period. Mean follow-up blood pressure levels were not different between the combination pill (losartan treatment) group and the control (ARBs except for losartan) group. On the other hand, serum uric acid significantly decreased in the combination pill group compared with the control group (-0.44 versus + 0.10 mg/dl; p = 0.01), although hematocrit, serum creatinine, sodium and potassium were not different between the groups. These results suggest that the treatment regimen switched from a combination therapy of ARBs except for losartan and a diuretic to a combination pill (losartan/ hydrochlorothiazide) decreases serum uric acid without affecting blood pressure control.

Does a combination pill of antihypertensive drugs improve medication adherence in Japanese? A randomized controlled trial.

BACKGROUND: In order to achieve target blood pressure levels to prevent cardiovascular disease, combination therapy of antihypertensive drugs is often required, although it is thought that requiring a patient to take many different pills would reduce adherence to the medication regimen. Whether antihypertensive treatment with a single pill combining antihypertensive drugs would improve medication adherence and blood pressure control was investigated. METHODS AND RESULTS: A total of 207 hypertensive subjects were randomly assigned to a combination pill group (losartan 50mg/hydrochlorothiazide 12.5mg; n=103) or a control group (an angiotensin receptor blocker and a thiazide diuretic; n=104). Medication adherence was evaluated by pill counts at 1, 3, and 6 months after randomization. The mean adherence rates over 6 months were not different between the 2 groups: 98% in the combination pill group and 98% in the control group. Moreover, the 2 groups included similar numbers of subjects with relatively poor adherence rates (<90%) in each treatment period. The mean blood pressures over the 6-month treatment period were not different between the groups: 131/75 mmHg in the combination pill group and 130/75 mmHg in the control group (P=0.84/0.96). CONCLUSIONS: There were no appreciable effects of the combination pill of antihypertensive drugs on medication adherence or blood pressure control in Japanese patients over a 6-month period.

The influence of current and former smoking on gingival bleeding: the Hisayama study.

BACKGROUND: Previous studies have shown that smoking is a risk factor for periodontitis and that it has a suppressive effect on gingival bleeding. This study examined the relationship between smoking, including past smoking, and periodontal conditions, mainly gingival bleeding, in a community-based health investigation. METHODS: Smoking status was examined in 958 subjects, along with the quantity of tobacco currently or previously smoked (never, former light, former heavy, current light, and current heavy). We analyzed the influence of smoking on probing depth (PD), clinical attachment loss (CAL), and gingival bleeding on probing (BOP). RESULTS: In multivariate logistic regression analyses, current heavy smokers were at a significantly greater risk for having a higher proportion of teeth with PD > or =4 mm and a higher proportion of teeth with CAL > or =5 mm; however, they had a lower risk for having a high BOP than did those who had never smoked. Moreover, both former light and former heavy smokers had significantly lower risks for high BOP. When the analysis was limited to subjects with PD > or =4 mm, former heavy and current heavy smokers showed a significant suppression of high BOP compared to never smokers. CONCLUSION: This study suggests that smoking is significantly associated with PD and CAL and that current and past smoking has a suppressive effect on BOP.

Angiotensin I-converting enzyme gene polymorphism modifies the smoking-cancer association: the Hisayama Study.

We examined the long-term contribution of smoking and angiotensin I-converting enzyme (ACE) gene I/D polymorphism to total cancer deaths in a prospective study of a general Japanese population. A total of 937 subjects aged 40 years or older were selected from an original cohort of 1621 subjects and were followed up for 32 years. During the follow-up period, 176 subjects died of cancer. Cancer mortality increased significantly with increasing current smoking levels. Although no clear relationship was observed between ACE genotypes and fatal cancer, the interaction term between current smoking and ACE genotype DD was found to be significant. In stratified analysis by ACE genotype after controlling for age, sex, alcohol intake, body mass index, glucose intolerance, serum total cholesterol and systolic blood pressure, the risk of fatal cancer in currently smoking subjects with genotype DD was twofold greater than that in subjects with genotypes II and ID. Among current smokers, subjects with genotype DD also showed a significantly greater risk of death due to cancer compared with those with genotypes II and ID combined (hazard ratio 1.77; 95% confidence interval 1.04-3.00; P=0.03). In conclusion, our findings suggest that ACE genotype DD enhances the association between smoking and cancer death in the general population.

Relationship between drinking and periodontitis: the Hisayama Study.

BACKGROUND: Although recent studies suggest a relationship between alcohol consumption and periodontal disease, the dose-response relationship between drinking and the severity of periodontitis is unclear. METHODS: Alcohol consumption was evaluated using the frequency of drinking and the daily alcohol intake for 961 individuals aged 40 to 79 years. Periodontal status was evaluated using probing depth (PD) and clinical attachment loss (CAL). RESULTS: Alcohol consumption was linearly associated with the extent of PD and CAL in univariate analyses (P <0.001). In multivariate logistic regression analyses, the subjects drinking 15 to 29.9 g alcohol per day (odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.1 to 6.6) or more than 30 g per day (OR = 2.5; 95% CI = 1.1 to 5.7) had a significantly higher risk of having more than 35% of their teeth with PD > or = 4 mm than non-drinkers, independent of other confounding variables. No significant relationship between drinking and CAL was observed in the multivariate analysis. CONCLUSION: These results suggest that the effect of drinking on periodontal condition is limited to subjects with deep periodontal pockets associated with more than one-third of their teeth.

Impact of fasting plasma glucose levels on gastric cancer incidence in a general Japanese population: the Hisayama study.

OBJECTIVE: Several studies have shown associations between diabetes and various types of cancer other than gastric cancer. The aim of this cohort study was to evaluate the impact of fasting plasma glucose (FPG) levels on gastric cancer occurrence. RESEARCH DESIGN AND METHODS: A total of 2,466 Japanese subjects aged > or =40 years were stratified into three groups according to FPG tertiles (<5.3 mmol/l, low FPG; 5.3-5.8 mmol/l, modest FPG; >5.8 mmol/l, high FPG) and followed up prospectively for 9 years. RESULTS: During the follow-up, 66 subjects experienced gastric cancer. In men, the age-adjusted incidences were significantly higher in the modest-FPG (7.0 per 1,000 person-years, P < 0.05) and high-FPG (7.2, P < 0.05) groups than in the low-FPG group (2.2). In women, the high-FPG group also had a significantly higher age-adjusted incidence of gastric cancer compared with the low-FPG group (2.5 vs. 0.8, P < 0.05). The multivariate analysis with Cox's proportional hazards model revealed that the risks of gastric cancer in the modest-FPG (relative risk [RR] 2.3 [95% CI 1.1-5.0]) and high-FPG (3.1 [1.5-6.4]) groups were significantly higher than that in the low-FPG group, even after adjusting for other comprehensive risk factors, including Helicobacter pylori status, smoking, and dietary factors. However, this FPG-cancer association was observed only among H. pylori-seropositive subjects. CONCLUSIONS: Our findings suggest that a modest increase in FPG is a risk factor for gastric cancer and that hyperglycemia is a possible cofactor increasing the risk posed by Helicobacter pylori infection.

Relationship between electrocardiographic abnormalities and periodontal disease: the Hisayama Study.

BACKGROUND: Recent studies have suggested a relationship between periodontitis and cardiovascular disease (CVD). This study investigated the relationship between periodontitis and electrocardiographic (ECG) abnormalities, which are known predictors of CVD. METHODS: We examined the periodontal status of 1,111 residents of Hisayama Town, Fukuoka, Japan. Nine hundred fifty-seven (957) subjects (374 males, 583 females) with > or = 10 teeth and without a medical history of CVD were included in the analysis. Probing depth (PD) and clinical attachment level (CAL) were measured on two randomly selected quadrants, one maxillary and one mandibular. A 12-lead ECG was recorded using a standard electrocardiograph. ECG abnormalities included left ventricular hypertrophy (Minnesota code 3-1) and ST depression (4-1, 2, 3). The relation of periodontal condition and ECG abnormalities was assessed with logistic regression analysis. RESULTS: Univariate analysis revealed that mean probing depth, mean attachment loss, number of teeth, and plaque index were significantly associated with ECG abnormalities, as well as with known risk factors of CVD. In multivariate analysis, the subjects with deep pockets (mean probing depth > or = 2 mm) had an increased risk for ECG abnormalities (odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.01 to 2.50) compared to the subjects with mean PD < 2 mm. Subjects with severe attachment loss (mean CAL > or = 2.5 mm) had also significant risk for ECG abnormalities (OR = 1.7; 95% CI = 1.07 to 2.67) compared to those whose mean CAL was < 2.5 mm. CONCLUSION: This study clearly shows the relationship between periodontitis and ECG abnormalities, which are important predictors of CVD.

Hyperhomocysteinemia and the development of chronic kidney disease in a general population: the Hisayama study.

BACKGROUND: Hyperhomocysteinemia has been linked with various atherosclerotic diseases, but has not been evaluated sufficiently as a risk factor for the development of chronic kidney disease (CKD) in the general population. METHODS: To clarify this issue, we followed up 1,477 community-dwelling individuals without CKD, aged 40 years or older, for 5 years and examined the effects of baseline serum total homocysteine (tHcy) levels on the development of CKD. RESULTS: During follow-up, 88 subjects experienced CKD. Baseline tHcy levels were greater in men than women (1.35 versus 1.04 mg/L [10.0 versus 7.7 micromol/L]; P < 0.01). Age-adjusted 5-year incidences were 2.2% in the low tertile, 5.4% in the middle tertile, and 8.6% in the high tertile of tHcy levels for men and 3.3%, 6.0%, and 6.9% for women, respectively. The difference between the low and high tertiles was statistically significant for both sexes ( P < 0.05). In multivariate analysis, these relationships remained substantially unchanged, even after adjustment for other confounding factors, such as systolic blood pressure, antihypertensive medication, hemoglobin A 1c level, total cholesterol level, high-density lipoprotein cholesterol level, habitual smoker status, regular alcohol intake, proteinuria, and baseline kidney function (odds ratio [OR] in the high tertile of tHcy levels, 2.09; 95% confidence interval [CI], 0.66 to 6.61 for men; OR, 2.86; 95% CI, 1.10 to 7.43 for women). Furthermore, baseline tHcy level showed a significantly inverse association with rate of change in kidney function during the 5 years after being adjusted for confounding factors, including baseline kidney function. CONCLUSION: Our findings suggest that elevated serum tHcy levels are a significant risk factor for the development of CKD in the general population.

Relationship between plasma glutathione levels and cardiovascular disease in a defined population: the Hisayama study.

BACKGROUND AND PURPOSE: Glutathione (GSH) appears to have marked antioxidant activities and therefore may prevent cardiovascular disease (CVD). However, there are very few reports on this subject. In a community-based case-control study, we tested the hypothesis that low levels of plasma GSH are closely associated with CVD and its clinical types. METHODS: The association between fasting plasma total GSH (tGSH) levels and CVD were assessed using conditional logistic regression analysis among 134 CVD cases and 435 age- and sex-matched healthy control subjects. RESULTS: Mean tGSH concentrations were lower in all CVD cases than in the control subjects (3.06 versus 3.71 micromol/L; P=0.0001). Among the CVD types, both the cerebral infarction cases (2.98 versus 3.59 micromol/L; P=0.001) and cerebral hemorrhage cases (2.51 versus 3.43 micromol/L; P=0.0027) had significantly lower tGSH levels than the corresponding control groups had. The same tendency was observed for cases of subarachnoid hemorrhage (3.45 versus 3.83 micromol/L; P=0.36) and myocardial infarction (3.65 versus 3.77 micromol/L; P=0.69), but these differences were not statistically significant. After adjustment for other confounding factors, the risk of CVD was significantly lower in the third (adjusted odds ratio, 041; 95% CI, 0.21 to 0.77) and the fourth quartiles (adjusted odds ratio, 0.25; 95% CI, 0.12 to 0.51) than in the first. This association was most prominent in patients with lacunar infarction or cerebral hemorrhage. CONCLUSIONS: These findings suggest that reduced plasma tGSH levels are a risk factor for CVD, especially for cerebral small vessel disease.

Dietary factors and development of impaired glucose tolerance and diabetes in a general Japanese population: the hisayama study.

BACKGROUND: There have been few prospective studies on diet and glucose abnormalities as determined by oral glucose tolerance test. METHODS: To investigate the impact of dietary factors on the development of glucose intolerance including diabetes and impaired glucose tolerance, we performed a follow-up survey of 1,075 subjects aged 40-74 years of normal glucose tolerance from 1988 through 1993/1994 by repeated 75 g oral glucose tolerance test and dietary survey. Information on habitual food consumption was obtained using a semiquantitative food frequency method. RESULTS: Of the total subjects studied, 119 (11.1%) developed impaired glucose tolerance and 24 (2.2%) developed diabetes during the follow-up. At baseline, the age-adjusted amount of alcohol intake was significantly higher in males who developed glucose intolerance than in those who did not (26.7 g vs. 15.7 g, p < 0.05), while the polyunsaturated/saturated fatty acids (P/S) ratio was significantly higher in females with future glucose intolerance (1.42 vs. 1.31, p < 0.05). Among the female subjects who developed glucose intolerance, the intake of animal fat less decreased during the follow-up period compared with normal subjects, resulting in a significant decrease in the P/S ratio (-0.09 vs. 0.05, p < 0.05). In a multiple logistic regression analysis, alcohol intake at baseline for males and decreased P/S ratio during the follow-up for females remained a significant risk factor for glucose intolerance independent of other dietary and non-dietary factors as well. CONCLUSIONS: These results suggest that a high intake of alcohol and a decreased P/S ratio contribute to the risk of glucose intolerance in contemporary Japanese.

Formal synthesis of squalamine from desmosterol.

The key intermediate to squalamine, (5alpha,7alpha,24R)-7,24-dihydroxy-cholestan-3-one, was synthesized from the 3-O-acetyl-24R,25-dihydroxy derivative of desmosterol via 10 steps in 16% overall yield and squalamine was also prepared via two further steps in 7.4% total yield from the desmosterol derivative.

Trends in the incidence, mortality, and survival rate of cardiovascular disease in a Japanese community: the Hisayama study.

BACKGROUND AND PURPOSE: The slowdown of a steeply declining trend in cardiovascular mortality has been reported in Japan, but precise reasons for this trend are uncertain. METHODS: We established 3 study cohorts of Hisayama residents aged > or =40 years without a history of stroke or myocardial infarction in 1961 (1618 subjects, first cohort), 1974 (2038 subjects, second cohort), and 1988 (2637 subjects, third cohort). We followed up with each cohort for 12 years, comparing the incidence, mortality, and survival rate of cardiovascular disease. RESULTS: The age-adjusted incidence of cerebral infarction significantly declined by 37% for men and by 32% for women from the first to the second cohort. It continued to decline by 29% for men, but the decline decelerated for women in the third cohort. The incidence of cerebral hemorrhage steeply declined by 61% from the first to the second cohort in men only, while it was sustained for both sexes in the third cohort. Stroke mortality continuously declined as a result of these incidence changes and significant improvement of survival. In contrast, the incidence and mortality rate of coronary heart disease were unchanged except for the increasing incidence in the elderly. The prevalence of severe hypertension and current smoking significantly decreased, while that of glucose intolerance, hypercholesterolemia, and obesity greatly increased among the cohorts. CONCLUSIONS: Our data suggest that the decline in stroke incidence is slowing down and that the incidence of coronary heart disease has been increasing in the elderly in recent years. Insufficient control of hypertension and the increase in metabolic disorders may contribute to these trends.

Ten-year prognosis of stroke and risk factors for death in a Japanese community: the Hisayama study.

BACKGROUND AND PURPOSE: There have been very few population-based cohort studies of long-term prognosis and risk factors for death after stroke. We examined the 10-year prognosis, causes, and risk factors of death after stroke in a Japanese cohort. METHODS: During a 26-year follow-up of a cohort of 1621 subjects > or =40 years of age, 333 subjects developed first-ever stroke and were prospectively followed up for 10 years after onset. During these 10-year follow-up periods, 268 of the 333 stroke patients died. Of those, 239 (89.2%) underwent autopsy. RESULTS: The risk of death was greatest in the first year after first-stroke onset in both sexes (men, 40.3%; women, 43.7%). Thereafter, the survival curves decreased gradually, and risk of death reached 80.7% for men and 80.2% for women by the end of the 10-year follow-up. The 30-day case fatality rate was substantially greater in patients with cerebral hemorrhage (63.3%) or subarachnoid hemorrhage (58.6%) than in patients with cerebral infarction (9.0%). The risk of dying after the first stroke was twice the risk for stroke-free subjects. The most common cause of death was the index stroke in the first year. Thereafter, the impact of the first stroke gradually decreased, while that of recurrent stroke increased. Multivariate analysis revealed that age, lower body mass index, and hemorrhagic stroke were significant risk factors for death after stroke. CONCLUSIONS: Our findings suggest that the risk of death after first-ever stroke is high, in part because of the larger proportion of hemorrhagic stroke in Japanese relative to stroke victims in Western countries.

Aerobic denitrifying bacteria that produce low levels of nitrous oxide.

Most denitrifiers produce nitrous oxide (N(2)O) instead of dinitrogen (N(2)) under aerobic conditions. We isolated and characterized novel aerobic denitrifiers that produce low levels of N(2)O under aerobic conditions. We monitored the denitrification activities of two of the isolates, strains TR2 and K50, in batch and continuous cultures. Both strains reduced nitrate (NO(3)(-)) to N(2) at rates of 0.9 and 0.03 micro mol min(-1) unit of optical density at 540 nm(-1) at dissolved oxygen (O(2)) (DO) concentrations of 39 and 38 micro mol liter(-1), respectively. At the same DO level, the typical denitrifier Pseudomonas stutzeri and the previously described aerobic denitrifier Paracoccus denitrificans did not produce N(2) but evolved more than 10-fold more N(2)O than strains TR2 and K50 evolved. The isolates denitrified NO(3)(-) with concomitant consumption of O(2). These results indicated that strains TR2 and K50 are aerobic denitrifiers. These two isolates were taxonomically placed in the beta subclass of the class Proteobacteria and were identified as P. stutzeri TR2 and Pseudomonas sp. strain K50. These strains should be useful for future investigations of the mechanisms of denitrifying bacteria that regulate N(2)O emission, the single-stage process for nitrogen removal, and microbial N(2)O emission into the ecosystem.

Age- and sex-specific prevalence of diabetes and impaired glucose regulation in 11 Asian cohorts.

OBJECTIVE: To report the age- and sex-specific prevalence of diabetes and impaired glucose regulation (IGR) according to revised World Health Organization criteria for diabetes in Asian populations. RESEARCH DESIGN AND METHODS: We performed 11 studies of 4 countries, comprising 24,335 subjects (10,851 men and 13,484 women) aged 30-89 years who attended the 2-h oral glucose tolerance test and met the inclusion criteria for data analysis. RESULTS: The prevalence of diabetes increased with age and reached the peak at 70-89 years of age in Chinese and Japanese subjects but peaked at 60-69 years of age followed by a decline at the 70 years of age in Indian subjects. At 30-79 years of age, the 10-year age-specific prevalence of diabetes was higher in Indian than in Chinese and Japanese subjects. Indian subjects also had a higher prevalence of IGR in the younger age-groups (30-49 years) compared with that for Chinese and Japanese subjects. Impaired glucose tolerance was more prevalent than impaired fasting glycemia in all Asian populations studied for all age-groups. CONCLUSIONS: Indians had the highest prevalence of diabetes among Asian countries. The age at which the peak prevalence of diabetes was reached was approximately 10 years younger in Indian compared with Chinese and Japanese subjects. Diabetes and IGR will be underestimated in Asians based on the fasting glucose testing alone.

Insulin-mediated effects of alcohol intake on serum lipid levels in a general population: the Hisayama Study.

To determine whether the beneficial effects of alcohol on lipid concentrations are mediated by insulin levels, we performed a cross-sectional analysis in 2103 nondiabetic men and women aged 40 to 79 years from a general Japanese population in Hisayama. The multivariate-adjusted sum of fasting and 2-hour postloading insulin levels and the insulin resistance index significantly decreased with elevating alcohol intake levels in men (P < 0.01 for the trend) but not in women. No dose-response relations between alcohol intake and glucose levels were observed. In both sexes, high-density lipoprotein cholesterol (HDLC) significantly increased with elevated alcohol intake (P < 0.01), whereas total cholesterol and low-density lipoprotein cholesterol (LDLC) were inversely correlated with alcohol intake (P < 0.01). In contrast, triglycerides (TGs) levels in men showed a J-shaped relation to alcohol dose, with moderate drinkers (10-29 g/d) having the lowest levels. Estimates using regression models indicated that for men, 10% of the alcohol-induced increase in HDLC and 2% of the alcohol-induced decrease in LDLC were insulin mediated. It was also estimated for male subjects that 36% of the reduction in TGs due to low to moderate alcohol intake was mediated by low levels of insulin and that this insulin-mediated pathway reduced the positive alcohol-TG relation by 13% in cases of moderate to heavy drinking. Our data suggest that regular alcohol consumption dose-dependently increased insulin sensitivity among male nondiabetics, but the insulin-mediated beneficial effects of alcohol on lipid concentrations were relatively small.

Risk factors for renal glomerular and vascular changes in an autopsy-based population survey: the Hisayama study.

BACKGROUND: Information of the effect of cardiovascular risk factors on renal glomerular and vascular changes is scarce in the general population. METHOD: Between 1962 and 1994, 1394 autopsies were performed in Hisayama, for a total autopsy rate of 80%. Of these, 839 individuals who preserved adequate renal tissues and had recent health examinations data before death were eligible for the present study. We examined the degree of glomerular sclerosis, renal arteriolar hyalinosis, and arteriosclerosis, and evaluated their risk factors by means of a logistic regression model. RESULTS: The development of glomerular sclerosis, arteriolar hyalinosis, and arteriosclerosis were 16%, 16%, and 18% in men, respectively, and 27%, 15%, and 24% in women, respectively. All these frequencies increased linearly with advancing age. In the multivariate analysis, both age and systolic blood pressure were significant independent risk factors for almost all these glomerular and vascular changes. In addition, glucose intolerance and proteinuria for men were found to be significant risk factors for glomerular sclerosis. Elevated total cholesterol levels significantly increased the risk of arteriolar hyalinosis in men. Electrocardiogram (ECG) abnormalities were an independent risk factor for arteriosclerosis in both men and women, and proteinuria was an additional risk factor in women. Alcohol intake tended to have a protective effect on glomerular sclerosis and arteriosclerosis in women. CONCLUSION: Our data confirmed that age and systolic blood pressure are common risk factors for all glomerular and renal vascular changes in the general population. In addition, glucose intolerance, total cholesterol, ECG abnormalities, and proteinuria affect either glomerular or vascular changes.

Validity of the JNC VI recommendations for the management of hypertension in a general population of Japanese elderly: the Hisayama study.

BACKGROUND: It is not known whether the treatment recommendations presented in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure are applicable to the Japanese elderly population. METHODS: We followed up 588 cardiovascular disease-free residents of a Japanese community who were 60 years or older from November 1, 1961, through October 31, 1993. Treated hypertensive patients were excluded from the analysis. During this period, CVD occurred in 179 subjects. The incidences were estimated by the pooling of repeated observations method. RESULTS: The age- and sex-adjusted incidences of cardiovascular disease significantly increased with elevated blood pressure levels. The hazard ratio for stage 3 hypertension was 5.34 (95% confidence interval, 2.66-10.71; P<.001) compared with optimal blood pressure after adjustment for other covariates. Among subjects aged 60 to 79 years, the incidences for stages 1 through 3 hypertension were significantly higher than for those with optimal and normal blood pressure. In comparison, among those 80 years or older, the incidence was significantly higher only in patients with stage 3 hypertension. We further estimated the incidences according to the risk stratification system. In the younger elderly subjects, the incidences increased with rising blood pressure levels in each risk stratum. Similar relationships were not observed among the older elderly subjects. CONCLUSIONS: Our findings demonstrate that the recommendations of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure were potentially applicable to the Japanese elderly subjects 79 years or younger. Based on our findings, however, hypertension might not be a risk factor for cardiovascular disease among very old hypertensive patients with advanced atherosclerosis.