Yuji Hirai

Heart rate and mortality in a Japanese general population:: An 18-year follow-up study

The predictive power of elevated heart rate for total mortality was evaluated in a Japanese general population. A total of 573 male participants, aged 40 to 64, who underwent a health examination in 1977, were followed until 1994. Heart rate (beats per minute; bpm) was measured using an electrocardiogram. During the 18 years, 82 subjects died; 18 from cerebro-cardiovascular diseases and 36 from cancer. In a multivariate proportional hazards regression model, age, elevated systolic and diastolic blood pressures, antihypertensive medication, heart rate, uric acid, vital capacity (inversely), and serum cholesterol (inversely) were significantly associated with all-cause death. Of these variables, elevated heart rate was the strongest predictor of all-cause death after adjustment for age. Resting heart rate levels were classified into five groups: < 60 (G1), 60-69 (G2), 70-79 (G3), 80-89 (G4), and > or = 90 (G5) bpm. Heart rates of 60-69 (G2) bpm showed the lowest death rate (14.3%) and heart rate > or = 90 (G5) bpm showed the highest death rate (38.2%) after adjustments for age and other confounding factors. The relative risk of G2 versus G5 was 2.68. An increased mortality risk was shown in men whose heart rate was > or = 90 bpm. Moreover, a continuous model suggested a graded increase in risk, so that risk is likely elevated even for heart rates less than 90 bpm, and lowest risk may be around 60 bpm.

Plasma Homocysteine Levels and Atherosclerosis in Japan Epidemiological Study by Use of Carotid Ultrasonography

Background and Purpose— We examined whether hyperhomocysteinemia is an independent risk factor for increased carotid artery intimal-medial wall thickness (IMT) in a large, randomly selected community in Japan where the dietary habit is different and the incidence of coronary artery disease is lower compared with those of western countries. Methods— In 1111 cases (452 men, 659 women) aged 63±10 years old (range, 40 to 94 years) recruited from a population-based survey performed in 1999, we measured fasting plasma total homocysteine levels and performed bilateral carotid B-mode ultrasound. The participants underwent measurements of other blood chemistries (total cholesterol, HDL cholesterol, glycosylated hemoglobin A1c, and creatinine). Results— For the total population, the mean total homocysteine level was 10.9 μmol/L. Total homocysteine levels were higher in men than in women and increased with aging. With multiple linear regression analysis after adjustments for age and sex, the most powerful determinant of total homocysteine levels was serum creatinine ( P <0.001). With multiple stepwise regression analysis after adjustments for age, sex, and other confounding factors, total homocysteine was significantly ( P <0.05) related to IMT. Furthermore, when mean values of IMT adjusted for age, sex, and other related factors were analyzed across total homocysteine quartiles, IMT ( P <0.05) showed a significant trend as total homocysteine level increased. Conclusions— Plasma total homocysteine levels in Japan are similar to those reported in western countries. Mild hyperhomocysteinemia is an independent risk factor for increased carotid artery wall thickness in Japan as well.

Association between alcohol intake and development of hypertension in Japanese normotensive men: 12-year follow-up study

Although it has been suggested that alcohol intake is related to hypertension, few long-term prospective studies have investigated this relationship. We therefore conducted a prospective study in male residents of a farming community in Japan to determine whether heavy drinking would predispose to the development of hypertension. A total of 325 normotensive (< 140/90 mm Hg) men were enrolled in 1977. Twelve years later, 93 (28.6%) subjects became hypertensive (defined as blood pressure > or = 140/90 mm Hg or use of antihypertensive medication). The probability of the development of hypertension in heavy drinkers predicted from a logistic regression equation was 44.6% (relative risk: 2.05 versus nondrinkers) after adjusting for age and body mass index (BMI). It was 36.2% (relative risk: 1.86 versus nondrinkers) after a further adjustment for systolic blood pressure at baseline. A high odds ratio of 2.39 for the development of hypertension with alcohol intake of < 46 g/day versus > or = 46 g/day at baseline was obtained even after adjustments for age, BMI, and confounding factors. We conclude that habitual heavy drinking of alcohol is a risk factor for the development of hypertension. This is the first report demonstrating a significant relationship between habitual alcohol intake and the development of hypertension in a long-term prospective study in Japan.

Plasma endothelin-1 level is related to renal function and smoking status but not to blood pressure: an epidemiological study.

Objective Endothelin-1 (ET-1) is a potent vasoconstrictor derived from the endothelium. Several studies with small numbers of humans have showed high plasma ET-1 levels in hypertension, but other studies have not. Furthermore, it has been shown in a small number of subjects that ET-1 is elevated in uraemic patients. However, there have been no epidemiological surveys as to whether ET-1 level is related to hypertension or end-organ damage. Methods A total of 1492 subjects received a health examination in 1999. The data for fasting ET-1 of 1450 individuals were obtained. A specific radioimmunoassay was used to measure ET-1 levels. We also measured body mass index (BMI), systolic and diastolic blood pressure (BP), haemoglobin A1c, cholesterol, blood urea nitrogen (BUN), creatinine and uric acid. We performed carotid B-mode ultrasonography and electrocardiography. Smoking habit was evaluated by questionnaire. Results Mean ET-1 was 4.93 ± 1.73 pg/ml in men and 4.84 ± 1.54 pg/ml in women. ET-1 increased with age (P < 0.001). Systolic (P < 0.001) and diastolic (P < 0.05) BP, hypertensive medication (P < 0.05), BUN (P < 0.01), creatinine (P < 0.001), uric acid (P < 0.001), intimal–medial thickness (P < 0.001), smoking (P < 0.05) and age (P < 0.001), were significantly associated with ET-1 by univariate analysis. By the use of multiple stepwise regression analysis, age (P < 0.001), creatinine (P < 0.001) and smoking (P < 0.05) remained significant. However, no relation was shown between ET-1 and BP. Conclusion Our data suggest that high ET-1 is not related to hypertension, but to subclinical renal dysfunction and smoking.

Plasma Aldosterone Levels and Development of Insulin Resistance: Prospective Study in a General Population

Aldosterone plays a role in hypertension, and hypertension is prevalent in patients with insulin resistance. Cross-sectional studies have reported that plasma aldosterone levels are higher in patients with insulin resistance. However, it is not known whether plasma aldosterone levels predict the development of insulin resistance. Subjects of the present study were 1235 local residents (490 men and 745 women) who participated in health screenings in Japan in 1999. Plasma aldosterone levels were measured by radioimmunoassay. We investigated the cross-sectional relationship between plasma aldosterone levels and insulin resistance (homeostasis model assessment index ≥1.73 according to the diagnostic criteria used in Japan) in 1088 nondiabetic participants. At the 10-year follow-up, 141 subjects had died, and 260 subjects refused re-examination. We performed a prospective analysis of 564 subjects to predict incident insulin resistance. We found a significant (P<0.001) cross-sectional relationship between plasma aldosterone and homeostasis model assessment index at baseline. In the prospective analysis, a significantly higher (P<0.05) relative risk (1.71 [95% CI: 1.03–2.84]) was observed in the highest tertile versus lowest tertile of plasma aldosterone for the development of insulin resistance, after adjustment for confounding factors. This 10-year prospective study demonstrated that plasma aldosterone levels predicted the development of insulin resistance in a general population.

LDL-C/HDL-C Ratio Predicts Carotid Intima-Media Thickness Progression Better Than HDL-C or LDL-C Alone

High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are strong predictors of atherosclerosis. Statin-induced changes in the ratio of LDL-C to HDL-C (LDL-C/HDL-C) predicted atherosclerosis progression better than LDL-C or HDL-C alone. However, the best predictor of subclinical atherosclerosis remains unknown. Our objective was to investigate this issue by measuring changes in carotid intima-media thickness (IMT). A total of 1,920 subjects received health examinations in 1999, and were followed up in 2007. Changes in IMT (follow-up IMT/baseline IMT × 100) were measured by ultrasonography. Our results showed that changes in IMT after eight years were significantly related to HDL-C (inversely, P < 0.05) and to LDL-C/HDL-C ratio (P < 0.05). When the LDL-C/HDL-C ratios were divided into quartiles, analysis of covariance showed that increases in the ratio were related to IMT progression (P < 0.05). This prospective study demonstrated the LDL-C/HDL-C ratio is a better predictor of IMT progression than HDL-C or LDL-C alone.

Factors associated with serum high mobility group box 1 (HMGB1) levels in a general population

High mobility group box 1 (HMGB1), a nonhistone chromatin-associated protein, is implicated as a mediator of both infectious and non-infectious inflammatory conditions. Clinical research on this protein in humans just has begun; serum HMGB1 was reported to be elevated in a small number of critically ill patients suffering from sepsis. However, the kinetics, distribution and factors associated with circulating HMGB1 are unknown in a general population. In this study, we examined these issues in a large population of healthy subjects. Fasting blood samples were obtained from 626 subjects (237 males and 389 females). HMGB1 levels showed a skewed distribution with a mean of 1.65 +/- 0.04 ng/ml. Multiple stepwise regression analyses found that white blood cell (WBC) counts (P = .016) and the soluble form of receptor for advanced glycation end products (sRAGE; P < .001, inversely), which is also known to be a receptor for HMGB1, were independently associated with HMGB1 levels. We demonstrated for the first time that circulating HMGB1 levels were inversely associated with sRAGE levels in a general population. Because RAGE is involved in HMGB1 signaling, our present study suggests that sRAGE may capture and eliminate circulating HMGB1 in humans.

Is insulin resistance or diabetes mellitus associated with stroke?: An 18-year follow-up study

Insulin resistance and/or diabetes are risk factors for coronary artery disease. However, it is still controversial whether they are associated with the development of stroke. A total of 304 Japanese men and women, aged 20-69 years, were selected on the basis of casual high blood glucose concentrations from 2732 participants of a population-based health examination in 1980. They all underwent a 50 g oral glucose tolerance test in 1981. Homa IR (index of insulin resistance) and Homa beta-cells (index of beta-cell function) were calculated from their fasting insulin and glucose using the formulas for the homeostasis model. They were followed-up for 18 years. Incidence of stroke was investigated by computed tomography. During 18 years, 28 subjects had a stroke; 21 had ischemic and nine had hemorrhagic strokes (two had both). Baseline variables, which showed an independent association with the incidence of stroke in the Cox proportional hazard model, were blood pressure, use of anti-hypertensive medications, and Homa beta-cell index (inversely) after adjustments for age and sex. After further adjustment for blood pressure using a step-forward method, Homa beta-cell was significantly related to the incidence of stroke (Hazard ratio: 0.65, 95% confidence interval: 0.44-0.95). In addition to hypertension, diabetes but not insulin resistance, is a risk factor for stroke.

High-sensitive troponin T is associated with atrial fibrillation in a general population

by the working status and the presence of CVD will be shown against the control group. The severity of CVD was not considered in their analysis, and expenditure for CVD medication was not considered while evaluating the association between CVD and income poverty. I would like to recommend further analysis with separation of their global definition of CVD into each disease component and also by considering the comorbidity of CVD with other diseases, which would yield precise information on the association between income poverty and chronic health conditions. I wish to express my appreciation to the members of Hygiene and Public Health, Nippon Medical School, for the preparation of this study. The author of this manuscript has certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (2010;144:1–2.).

Factors associated with plasma ghrelin level in Japanese general population

Objective  Ghrelin is a novel gastric peptide identified in 1999 as a ‘hunger hormone’. Plasma ghrelin level is decreased in human obesity. Factors associated with ghrelin have been mainly investigated in western countries where the prevalence of obesity is high. The aim of this study is to examine factors associated with plasma ghrelin in a Japanese general population where obesity is not so common.