Kiyomi Sakata

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.

Prospective study of screening for stomach cancer in Japan

Although screening for stomach cancer is a widespread community service in Japan, the benefits of the screening program remain unclear. Our study investigated prospectively the relation between participation in stomach‐cancer screening during the past 12 months and subsequent deaths. Data was derived from the Japan Collaborative Cohort Study, in which 480 stomach‐cancer deaths were identified during an 8‐year follow‐up period. Cox proportional hazard regression was used to estimate the relative risk of death from stomach cancer and that from other causes while adjusting for potential confounding factors. In men, screening participation was associated significantly with a reduced risk of death from stomach cancer (relative risk [RR] = 0.54; 95% confidence interval [CI] = 0.41–0.70). The extent of the risk reduction was greater than potential health selection (for deaths other than stomach, RR = 0.71). The adjustment for potential confounding variables, however, attenuated the difference in risk of death (stomach cancer, RR = 0.65; other causes, RR = 0.71). In women, the magnitude of the association between screening participation and death from stomach cancer (RR = 0.74; 95% CI = 0.52–1.07) was equal to that for deaths from non‐stomach cancers (RR = 0.74). Subgroup analysis showed that women with a parental history of stomach cancer had a reduced risk of death from stomach cancer associated with screening (RR = 0.32; 95% CI = 0.12–0.87). The present results underline the potential for selection bias in observational studies, and thus it remains an open question whether screening for stomach cancer is effective.

Absence of an association between serum uric acid and mortality from cardiovascular disease: NIPPON DATA 80, 1980–1994

Although elevated serum uric acid has been associated with an increased risk of cardiovascular disease, its importance as a risk factor is still controversial. The authors examined the relationship between serum uric acid levels and death from all causes, including cardiovascular disease and stroke. The baseline data were collected in the National Cardiovascular Survey in 1980. The survey was carried out for all household members aged 30 years or older in 300 districts, which were randomly selected throughout Japan. The number who participated in the survey was 10,897. The vital status was ascertained in 1994. Finally, 8172 subjects were available for the analyses. There were 108,284 person-years of follow-up, and 960 deaths from all causes, 249 deaths from cardiovascular disease, and 174 deaths from stroke. After adjustment for age and other cardiovascular disease risk factors, uric acid levels were not associated with mortality from all causes, cardiovascular disease, or stroke. These findings indicate that serum uric acid levels are not related to increased risk for death from all causes, including cardiovascular disease and stroke in a Japanese population.

Family history and the risk of stomach cancer death in Japan: Differences by age and gender

Familial aggregation of stomach cancer has long been observed. The effect on disease risk of family history and its magnitude according to the type of affected relatives, however, is not well known. We conducted a prospective analysis using the JACC study (Japan Collaborative Cohort Study For Evaluation of Cancer Risk, sponsored by Monbusho) data. During the follow‐up period, 662 stomach cancer deaths were documented. A positive history of stomach cancer in one or more first‐degree relatives was associated with a significantly increased risk of death from the disease in both men (RR 1.60; 95% CI 1.11–2.31) and women (RR 2.47; 95% CI 1.50–4.06). In the subanalysis stratified by age, the association between positive family history and stomach cancer was stronger in the age group from 40–59 (RR 2.62; 95% CI 1.34–5.11 for men and RR 5.88; 95% CI 2.70–12.82 for women) than in the age group from 60–79 (RR 1.31; 95% CI 0.84–2.05 for men and RR 1.44; 95% CI 0.72–2.88 for women). In the age group from 40–59, men with fathers history and women with mothers and sisters history of the disease had a significantly increased risk (RR 3.14; 95% CI 1.51–6.55, RR 10.46; 95% CI 4.54–24.12, RR 13.39; 95% CI 3.89–46.12, respectively). When 2 or more family members were affected, the increment in the risk was prominent especially in women (RR 9.45; 95% CI 4.46–20.05). These results suggest the existence of a certain subtype of stomach cancer that is inherited more often by women from one generation to the next in gender‐influenced fashion. Any preventive strategy should take into account the degree of individual susceptibility.

Determinants of bone loss in a rural Japanese community : the Taiji Study

Abstract: The objective of this study was to assess the rate of bone loss and characterize its determinants, among the inhabitants of Taiji, a rural Japanese community. A cohort of 2261 inhabitants aged 40–79 years was established using resident registration in 1992. Fifty men and 50 women in each of four age strata between 40 and 79 years were randomly selected and completed a self-administered risk factor questionnaire. Baseline bone density of lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry in 1993. BMD was measured again on the same participants in 1996. The rates of change of lumbar spine BMD in men in their 40s, 50s, 60s and 70s were 0.20%, 0.34%, 0.43% and 0.28% respectively. Rates in women were –0.35%, –1.02%, –0.10% and –0.20% respectively. At the femoral neck, rates of change in BMD among men in their 40s, 50s, 60s and 70s were 0.09%, –0.07%, 0.34% and 0.31% respectively. Femoral neck rates of change among women were –0.55%, 0.02%, 0.49% and –0.25% respectively. The rate of change of lumbar spine BMD was –0.24% in premenopausal women with regular periods, –1.99% in premenopausal women with irregular periods and –0.33% in postmenopausal women. Anthropometric measurements at baseline were also related significantly to change in bone density. Baseline weight and height were statistically significant predictors of bone loss rate.These data provide estimates of the rate of bone loss among Japanese men and women aged 40– 79 years. They suggest that body build and menstrual function in women are important determinants of bone loss.

Biochemical Markers of Bone Turnover and Bone Loss at the Lumbar Spine and Femoral Neck: The Taiji Study

Abstract. The purpose of this study was to ascertain whether biochemical markers of bone turnover predict bone loss. The survey was carried out in Taiji, Wakayama Prefecture, Japan. From a list of inhabitants aged 40–79 years, 400 participants (50 men and 50 women in each of four age groups) were selected randomly. Bone mineral density (BMD) was measured, and blood and urine samples of all participants were examined to obtain values for eight biochemical markers: alkaline phosphatase (ALP), bone Gla protein (BGP), type I procollagen (carboxyterminal peptide of type I procollagen; PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and urinary excretion of calcium (Ca), phosphate (P), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr). Each marker was evaluated as a predictor of the rate of bone change in lumbar spine and femoral neck BMD over a 3-year period. The value of Pyr was significantly related to the change of lumbar spine BMD in men (P= 0.009), and that of BGP was found to be significant in women (P= 0.045). By contrast, none of the bone markers significantly correlated with bone loss at the femoral neck. The coefficient of determination at the lumbar spine was 5% and 7% at the femoral neck only. We conclude that biochemical markers of bone turnover cannot predict bone loss rates in middle-aged or elderly Japanese men and women over a 3-year period with sufficient accuracy for use in clinical decision making.

Bone loss at the lumbar spine and the proximal femur in a rural Japanese community, 1990-2000: the Miyama study.

Abstract: Bone mineral density (BMD) was measured over a ten year period in a cohort study in Miyama village, Wakayama Prefecture, Japan, to provide information on rate of bone loss in the mature and elderly population. Four hundred subjects were selected by sex and age decade from the full list of residents born in 1910–1949, and aged 40–79 years at the end of 1989, with 50 men and 50 women in each age decade. Baseline BMD of the lumbar spine and the proximal femur was measured using dual energy X-ray absorptiometry (DXA) in 1990 and again in 1993, 1997 and 2000. Annual rate of change in BMD (% per year) in the lumbar spine in men in their forties, fifties, sixties and seventies was 0.17, 0.55, 0.01 and −0.16, respectively, and in women, −0.87, −0.83, −0.48 and −0.48, respectively. Thus in men, BMD at the lumbar spine increased in all age strata but the oldest, when it decreased, whereas in women, it decreased in all age strata. On the other hand, BMD at the proximal femur decreased in both sexes in all age strata. Our results show that bone loss rates differ depending on the site involved, demonstrating that different strategies are needed for the prevention of bone loss in the spine and hip. Furthermore, we found evidence of differences in BMD for given age strata between birth cohorts. Data in 1990 and in 2000 showed significant improvements for men in their sixties and for women in their fifties, suggesting that future problems of osteoporosis might be less severe than has previously been predicted in Japan.

Trends in blood pressure and urinary sodium and potassium excretion in Japan : reinvestigation in the 8th year after the intersalt study

Using the identical protocol of an Intersalt Study previously conducted, we undertook a new study (Intersalt-2) 8 years later. We measured changes in various factors affecting blood pressure (BP) including urinary sodium and potassium excretion in three districts of Japan: Osaka, Tochigi, and Toyama. Also we evaluated the trends in the relationships of those factors to BP.The Intersalt Study revealed that the average sodium excretion of all three study centres was high (particularly in Toyama) while potassium excretion was relatively low. The sodium/potassium ratio was therefore relatively high. The body mass index (BMI) was favourable, but the prevalence of heavy alcohol drinkers was high.Comparing the first to the second study reveals a decrease in sodium excretion in Toyama, although that area still had the highest value of the three study centres. The average potassium excretion increased only in Osaka. Sodium/potassium ratio decreased in all centres. BMI and the prevalence of heavy drinkers among the subjects of both studies were nearly the same. The trend of the relationship of sodium to BP in Osaka changed from negative to positive. In Toyama, it changed from positive to negative. It is thought that this negative relationship might occur in conjunction with a reduction in salt consumption in a population.In conclusion this study reveals that average sodium consumption in Japan remains high while potassium consumption is still low. As a factor in the prevention of hypertension, further efforts to reduce salt consumption and increase potassium intake are still needed.

The relationship between endogenous estrogen, sex hormone-binding globulin, and bone loss in female residents of a rural Japanese community: the Taiji Study

Abstract. The aim of this study was to clarify the relationship between endogenous estrogen, sex hormone-binding globulin (SHBG), and bone loss in pre-, peri-, and postmenopausal female residents of Taiji, a rural Japanese community. From a list of inhabitants aged 40 to 79 years, 200 participants—50 women in each of four age decades—were randomly selected, and baseline bone mineral density (BMD) at the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry in 1993. Total estradiol (total E2) and SHBG were measured, and SHBG-unbound E2 (UBE2) was calculated using SHBG and the percent SHBG-unbound fraction ratio. BMD was measured again 3 years later, in 1996. Participants with ovariectomy or hysterectomy were excluded, and the remaining participants were categorized into four groups: premenopausal (n= 38), perimenopausal (n= 14), postmenopausal group 1 (5 years or less since menopause; n= 18), and postmenopausal group 2 (6 years or more since menopause; n= 74). The mean value of total E2 was highest in the premenopausal group (49.1 pg/ml), followed by the perimenopausal group (26.4 pg/ml), and the postmenopausal groups (0.83 pg/ml in postmenopausal group 1 and 0.96 pg/ml in postmenopausal group 2). The means for UBE2 showed the same pattern across the groups. After the multiple regression analysis of BMD at follow-up and endogenous estrogens, in premenopausal women, there were no significant associations between BMD at follow-up and serum total E2 and UBE2. In perimenopausal women, however, serum total E2 and UBE2 were significantly correlated with trochanteric BMD at follow-up (P < 0.05); and in postmenopausal group 2, they were significantly correlated with lumbar spine and Wards triangle BMD at follow-up (P < 0.001 at lumbar spine, P < 0.05 at Wards triangle). Concerning the association between BMD at follow-up and SHBG, in the premenopausal group, serum levels of SHBG were negatively correlated with BMD at the femoral neck (P < 0.05). In regard to partial regression coefficients for the change rates of BMD over 3 years and serum estrogens and SHBG concentrations, in perimenopausal women, UBE2 was correlated with the change rate of BMD at Wards triangle (P < 0.05), and in postmenopausal group 1, serum levels of SHBG were significantly negatively related to change in BMD at the trochanter (P < 0.01). No other relationships with change in BMD were observed at any sites. These findings suggest that serum E2, UBE2, and SHBG levels differentially predict BMD levels in groups of differing menstrual status. It would, however, be difficult to predict bone loss in middle-aged and elderly Japanese women over a 3-year period using these indices alone.

A cross-sectional study on association of calcium intake with blood pressure in Japanese population.

To investigate the association of calcium intake independently of other nutrients already known as predictors of hypertension, a cross-sectional study was carried out on the same population in Japan as used for the INTERSALT study. Dietary calcium intake was estimated from a 1-day 24-h recall. Sodium and potassium intakes were evaluated by 24-h urinary excretion. Data from 476 subjects aged 20–59 years, 230 men and 246 women, were analysed. The mean dietary calcium intake ranged from 557 to 608 mg/day among men, and from 528 to 639 mg/day among women. Among men, the pooled estimate of the regression coefficients of blood pressure (mm Hg) per 100 mg increase of calcium intake, adjusted for age and body mass index (BMI), were −0.42 mm Hg for systolic blood pressure (SBP) and −0.35 mm Hg for diastolic blood pressure (DBP), but there was no statistical significance. Among women, the pooled estimates of regression coefficients adjusted for age and BMI were −0.92 mm Hg for SBP and −0.83 mm Hg for DBP with statistical significance. After adjustment for age, BMI, alcohol intake and urinary excretion of sodium and potassium, the pooled estimate of calcium intake was −0.66 mm Hg for DBP with statistical significance and − 0.70 mm Hg for SBP. A significant negative association of calcium intake with blood pressure was observed among the subjects in Osaka. Our study suggests that increased calcium intake may provide a benefit of lowering blood pressure independently of other minerals such as sodium and potassium.