Hideaki Nakagawa

High-Density Lipoprotein Cholesterol and Risk of Stroke in Japanese Men and Women The Oyabe Study

Background and Purpose— Evidence of an inverse relationship between serum high-density lipoprotein cholesterol (HDL-C) and the risk of stroke is sparse in Asians and in women. The purpose of this investigation was to examine the relationship in a long-term cohort study of Japanese men and women among whom stroke occurrence is higher than in Western countries. Methods— A prospective cohort study was performed involving 4989 participants (1523 men, 3466 women) 35 to 79 years of age at baseline with ≈10 years of follow-up in a rural area of Japan. End points included all stroke incidence and ischemic stroke incidence. Results— During follow-up, 132 participants developed stroke, including 81 ischemic stroke cases. Age-adjusted incidence rates per 10 000 person-years for all stroke in subjects with low HDL-C (<30 mg/dL [0.78 mmol/L]) were 103.4 in men and 49.3 in women, which were remarkably higher than in subjects with high HDL-C (≥60 mg/dL [1.56 mmol/L]) (26.4 in men and 15.5 in women). A similar relationship was observed for ischemic stroke. Multivariate-adjusted relative risks for all stroke incidence and ischemic stroke incidence were 2.89 (95% CI, 1.35 to 6.20) and 2.92 (95% CI, 1.17 to 7.32), respectively, for low versus high HDL-C participants. The relationships were independent of sex, age, body mass index, blood pressure, serum total cholesterol, alcohol consumption, and smoking. Conclusions— This 10-year follow-up study of Japanese men and women demonstrated that lower HDL-C levels were related significantly and independently to increased risk of all stroke incidence and ischemic stroke incidence.

Effects of maternal exposure to cadmium on pregnancy outcome and breast milk

Objective: The effects of cadmium (Cd) on birth weight have been discussed in the scientific literature. However, investigations on the effects of maternal body burden of Cd on the next generation during pregnancy and lactation have been limited. The relation between maternal exposure to Cd and pregnancy outcome or Cd in breast milk in Japanese mothers was investigated. Methods: Cd concentrations in urine and colostrum milk samples of 57 mothers were measured by atomic absorption spectrophotometery. The relations between maternal urinary Cd and infant growth, gestational age at birth, and Cd in breast milk were investigated. Results: The rate of perterm deliveries of mothers with higher urinary Cd (≥2 nmol/mmol creatinine (Cr)) was higher than that of mothers with lower urinary Cd (<2 nmol/mmol Cr). The gestational age was significantly correlated with urinary Cd even after adjustment for maternal age. The height and weight of newborn infants of mothers with higher urinary Cd were significantly lower than those of the newborn infants of mothers with lower urinary Cd, but these decreases were ascribed to early delivery induced by Cd. The Cd in breast milk of mothers with higher urinary Cd was significantly higher than that of mothers with lower urinary Cd. A significant positive correlation was found between maternal urinary Cd and Cd in breast milk. Conclusion: Maternal exposure to Cd seems to increase early delivery, which leads to a lower birth weight. Also, the Cd is transferred in part to the next generation through breast milk after birth.

Trends in stroke incidence and acute case fatality in a japanese rural area: The oyabe study

BACKGROUND AND PURPOSE Stroke mortality in Japan has significantly declined during recent decades. To determine the cause of this decrease, we studied the trends in stroke incidence and case fatality within 28 days after stroke in a rural area in Japan. METHODS We used a population-based registry during 1977-1991 in Oyabe, a rural area in the central part of Japan. The average population aged 25 years and older numbered 32 859 persons. Changes in age-standardized stroke incidence rate were calculated and compared between the 3 periods 1977-1981, 1982-1986, and 1987-1991. The 28-day case fatality rate was evaluated and also compared between the 3 periods by onset year. RESULTS The total number of strokes was 2068. The age-standardized incidence rate of all strokes decreased during the 15-year period, from 605 to 417 per 100 000 in men and from 476 to 329 per 100 000 in women. A marked decline was found during 1977-1986 but was not apparent during 1987-1991. Moreover, there was an increase in the group aged 75 years and older. The 28-day case fatality rates for all strokes improved from 18.0% to 14.2% in men and from 26.8% to 19.1% in women during the observation period. CONCLUSIONS These data indicate that declines in the stroke incidence and the 28- day case fatality have been associated with a marked decrease in stroke-related mortality in Japan.

Gender differences in the association between anthropometric indices of obesity and blood pressure in Japanese.

To investigate which of four anthropometric variables of obesity has the strongest association with blood pressure (BP), and to investigate whether there are gender differences in these relationships in Asian adults, we evaluated the associations of four anthropometric variables, body mass index (BMI), waist circumference, waist-to-hip ratio and waist-to-height ratio, with BP and the prevalence of hypertension in a cross-sectional study. A total of 4,557 employees of a metal-products factory in Toyama, Japan (2,935 men and 1,622 women, aged 35 to 59 years) were included in the study. Waist circumference in men and BMI in women had the strongest associations with BP. As for the age-adjusted rate ratio (RR) of the prevalence of hypertension for one standard deviation increase in each anthropometric variable, RR was the highest for waist circumference in men (RR, 1.44; 95% confidence interval [CI], 1.31–1.58), and for BMI in women (RR, 1.61; 95% CI, 1.38–1.88). The associations of waist circumference in men and BMI in women remained significant after adjustment for each of the other variables. The associations of waist-to-height ratio with BP and the prevalence of hypertension were a little weaker than those of waist circumference for both men and women. In conclusion, among four anthropometric variables of obesity—i.e., BMI, waist circumference, waist-to-hip ratio, and waist-to-height ratio—waist circumference had the strongest association with BP and the prevalence of hypertension in men and BMI had the strongest association with BP and hypertension in women. Waist circumference in men and BMI in women should be given more importance in the screening of and guidelines on hypertension in Asians.

Causes of death and renal tubular dysfunction in residents exposed to cadmium in the environment

Objectives: To clarify the causes of death of residents with renal tubular dysfunction induced by cadmium (Cd) in the environment. Methods: A 15 year follow up study was performed with the inhabitants living in the Cd polluted Kakehashi River basin in Japan. Standardised mortality ratios (SMRs) for causes of death, classified by ICD-9, were computed using the person-years method to investigate the excess mortality of subjects with urinary β2-MG (microglobulin) ⩾1000 μg/gCr. Mortality risk analysis was performed using Cox’s proportional model to compare mortality between subjects with urinary β2-MG ⩾1000 and <1000 μg/gCr, and to investigate the relationship between the degree of urinary β2-MG and mortality. Results: Excess mortality due to heart failure and cerebral infarction in both sexes, and nephritis and nephrosis in men, was observed among subjects with urinary β2-MG ⩾1000 μg/gCr. Significant increases in mortality risk for cerebral infarction in men and for malignant neoplasms in women with urinary β2-MG ⩾1000 μg/gCr were observed during the first five year observation period. For nephritis and nephrosis, the mortality risks for men and women with urinary β2-MG ⩾1000 μg/gCr significantly increased over the 15 year observation period. The mortality risks for heart failure and cerebral infarction increased in proportion to the increased urinary β2-MG in both sexes. Increased mortality risks for nephritis and nephrosis were identified in the subjects with urinary β2-MG ⩾10000 μg/gCr in both sexes. Conclusion: Renal tubular dysfunction induced by Cd affected the causes of death, and mortality for heart failure, cerebral infarction, and nephritis and nephrosis was increased among inhabitants living in a Cd polluted area in Japan. In women, cancer mortality may have been increased while Cd pollution was ongoing.

Differences in cardiovascular disease risk factors between Japanese in Japan and Japanese-Americans in Hawaii: The INTERLIPID study

Despite increase in serum total cholesterol, high smoking rate, and frequency of adverse blood pressure levels in Japan, coronary heart disease (CHD) incidence and mortality apparently remain substantially lower at all ages in Japan than in the US and other Western societies. To better understand these differences, we compared CHD biomedical risk factors and dietary variables in Japanese living in Japan and 3rd and 4th generation Japanese emigrants living a primarily Western lifestyle in Hawaii, in an ancillary study of the INTERMAP. Men and women aged 40–59 years were examined by common standardized methods—four samples in Japan (574 men, 571 women) and a Japanese-American sample in Hawaii (136 men, 131 women). Average systolic (SBP) and diastolic (DBP) blood pressures were significantly higher in men in Japan than in Hawaii; there were no significant differences in women. The treatment rate of hypertension was much lower in Japan than Hawaii. Smoking prevalence was higher, markedly so for men, in Japan than Hawaii. Body mass index, serum total and low-density lipoprotein cholesterol, HbA1c, and fibrinogen were significantly lower in Japan than in Hawaii; high-density lipoprotein cholesterol was higher in Japan. Total fat, saturated fatty acid intake, and Keys dietary lipid score were lower in Japan than in Hawaii. Polyunsaturated/saturated fatty acid ratio and omega-3 fatty acid intake were higher in Japan than in Hawaii. In conclusion, levels of several, especially lipid, CHD risk factors were generally lower in Japanese in Japan than in Japanese in Hawaii. These differences were smaller for women than men between Japan and Hawaii. They may partly explain lower CHD incidence and mortality in Japan than Western industrialized countries.

Four Blood Pressure Indexes and the Risk of Stroke and Myocardial Infarction in Japanese Men and Women A Meta-Analysis of 16 Cohort Studies

Background— Information has been sparse on the comparison of 4 blood pressure (BP) indexes (systolic BP [SBP], diastolic BP, pulse pressure, and mean BP [MBP]) in relation to long-term incidence of stroke and myocardial infarction, particularly in middle-aged and older Asians. Methods and Results— The Japan Arteriosclerosis Longitudinal Study Group conducted a meta-analysis of 16 cohort studies in Japan. A total of 48 224 men and women 40 to 89 years of age participated at baseline, and 1231 stroke events and 220 myocardial infarction events occurred during an average 8.4-year follow-up. Multivariate-adjusted hazard ratios with a 1-SD higher value for each BP index were determined by Poisson regression. Analyses were also done in 4 age-sex groups. All 4 BP indexes were significantly related to all stroke risk. Stroke risk was most strongly related to MBP and SBP in both sexes and most weakly related to pulse pressure. Both stroke subtypes, ischemic and hemorrhagic, were most strongly related to MBP and SBP in both sexes. In addition, in men and women 70 to 89 years of age, MBP or SBP showed the strongest relation to all stroke risk. Myocardial infarction risk was most strongly related to SBP or MBP in both sexes. For any end points in any age-sex groups, pulse pressure was not the strongest predictor. Conclusions— The long-term incident risk of stroke and myocardial infarction associated with high BP in East Asian populations should be assessed mainly on the basis of SBP. MBP also may be an important predictor, but pulse pressure is a less important predictor for cardiovascular disease risk.

Cadmium exposure and trace elements in human breast milk.

The interrelations of the seven elements, calcium (Ca), magnesium (Mg), sodium (Na), potassium (K), phosphorus (P), copper (Cu), zinc (Zn), and cadmium (Cd) in human breast milk were examined in Japanese mothers to clarify the effects of Cd exposure on these important elements for infant growth. Breast milk and urine samples were obtained from 68 mothers, aged 19-38 years, at 5-8 days postpartum. The concentrations were determined by inductively-coupled plasma atomic emission spectrometry for Ca, Mg, Na, K, P, by flame atomic absorption spectrophotometry for Cu and Zn, and by flameless atomic absorption spectrophotometry for Cd. Geometrical mean Cd concentrations were 0.28 (geometrical standard deviation=1.82) microg/l in breast milk and 1.00 (1.93) microg/g creatinine in urine. Among the above elements only Cd concentration in breast milk was significantly correlated with urinary Cd concentration (r=0.451, P<0.001). Significant positive correlations were found between Cu and Ca (r=0.500, P<0.001), Cu and Mg (r=0.378, P<0.01), and Zn and Mg (r=0.355, P<0.01) in breast milk. Cd concentration in breast milk showed an inverse relationship with Ca concentration in breast milk (r=-0.248, P<0.05). These results indicate that the Cd concentration in breast milk closely reflects Cd body burden, with increased Cd in breast milk possibly affecting Ca secretion in breast milk.

Cadmium induced renal dysfunction among residents of rice farming area downstream from a zinc-mineralized belt in Thailand

High levels of cadmium (Cd) in paddy soil and rice, and a concurrent increase in urinary Cd of inhabitants in the Mae Sot District, Tak Province, Thailand first emerged in 2003. Risk factors such as occupation, sources of staple food and drinking water as well as biomarkers of adverse renal effects of the increased body burden of Cd were investigated in 795 residents, 30 years or older, whose urinary Cd levels were between 0.02 and 106mug/g creatinine. Farmers who consumed their own rice and residents who sourced drinking water from wells and/or the river demonstrated increased urinary Cd. Age-adjusted mean urinary cadmium for male and female subjects who consumed well water was 5.7mug/g vs. 6.1mug/g creatinine while the corresponding value for male and female subjects who did not consume well water was 3.7mug/g vs. 4.8mug/g creatinine, respectively. Increased urinary levels of beta(2)-microglobulin and N-acetyl-beta-d-glucosaminidase were observed with the increase in urinary Cd, indicating tubular dysfunction and renal damage associated with increase in Cd body burden. Consumption of well water and rice grown in the contaminated area increase the body burden of Cd. Cessation of exposure is essential to prevent and possibly recover from Cd toxicity, especially among the residents whose kidney damage and malfunction may be reversible.

Epidemiology of idiopathic cardiomyopathy in Japan: results from a nationwide survey

Objective: To estimate the total number of patients with idiopathic cardiomyopathy in Japan and the prevalence of the disorder. Design: A nationwide epidemiological survey. Setting: Hospitals selected randomly from among all hospitals in Japan. Patients: Patients presenting with any of the three types of idiopathic cardiomyopathy: dilated cardiomyopathy, hypertrophic cardiomyopathy, and restrictive cardiomyopathy. Main outcome measures: The total number of patients in Japan was estimated using the sampling and response rates in each stratum with respect to hospital size. The second survey was conducted for patients reported in the first survey in order to obtain detailed information, including age, sex, and specific clinical data. Results: Estimated patient totals and 95% confidence intervals (CI) were 17 700 (95% CI 16 500 to 18 800) for dilated cardiomyopathy, 21 900 (95% CI 20 600 to 23 200) for hypertrophic cardiomyopathy, and 300 (95% CI 250 to 350) for restrictive cardiomyopathy. Crude prevalence per 100 000 population was estimated as 14.0 for dilated cardiomyopathy, 17.3 for hypertrophic cardiomyopathy, and 0.2 for restrictive cardiomyopathy; crude incidence per 100 000 person-years was estimated as 3.58, 4.14, and 0.06, respectively. Conclusions: The total number and prevalence of patients with idiopathic cardiomyopathy in Japan are estimated for the first time in a nationwide survey. The prevalence of dilated cardiomyopathy in Japan appears to be about half that of Western populations, while that of hypertrophic cardiomyopathy is about the same.