Alimentary Comparison Study Research Articles

Stroke-Prone SHR as Experimental Models for Cardiovascular Disease Risk Reduction in Humans.

Since stroke-prone spontaneously hypertensive rats (SHRSP) develop hypertension and stroke without exception, the prevention or reduction of risk by various nutrients was tested on blood pressure and the mortality caused by stroke and cardiovascular diseases (CVD). In addition to sodium (Na) accelerating hypertension and stroke and potassium (K) counteracting the adverse effect of Na, taurine (Tau), rich in seafood, and magnesium (Mg) contained in soy, nuts, grains, etc., were proven to reduce stroke and CVD and improve survival. Therefore, the Cardiovascular Diseases and Alimentary Comparison Study was started in 1985 to explore the association of biomarkers of diet in 24 h urine (24U) with CVD risks, and about 100 males and 100 females aged 48-56 in each of 50 populations were studied until 1995. Linear regression analysis indicated that the 24U Tau/creatinine and Mg/creatinine ratios were inversely associated with body mass index, systolic and diastolic blood pressure, and total cholesterol. In comparison with six Euro-Western regions, 24U Tau and Mg collected from six regions, respectively, in Japan and the Mediterranean countries were significantly higher and were significantly associated with lower CVD risks. Diets rich in Tau and Mg were concluded to be contributory to the prevention of CVD in SHRSP and humans.

Grading of Japanese Diet Intakes by 24-Hour Urine Analysis of Taurine and Soy Isoflavones in Relation to Cardiovascular Risks.

To investigate the association of the Japanese diet with risks for lifestyle-related diseases, the biomarkers of seafood and soybean consumption, taurine (T) and soy isoflavones (I), and others were analyzed in 24-hour urine (24U) samples collected from participants of the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study coordinated by the World Health Organization (WHO). The data of T and I normalized for creatinine content in 24U were divided into five quintiles, T1 to T5, and I1 to I5. The total data of the collected samples were divided into 25 groups, which were obtained by 5 (T1-T5)×5 (I1-I5) according to 24U excretions of T and I corresponding to the intake of seafood and soybeans from the least to the highest, respectively. Since these two nutrients were often consumed together in the Japanese diet, this characteristic was expressed as J1 to J5 based on the amounts of 24UT and I excretions. The risks for lifestyle-related diseases, obesity (body mass index, BMI), and cholesterolemia became lower during the transition from J1 to J5, while HDL cholesterol levels became higher from J1 to J5. On the contrary, urinary salt excretion and the sodium (Na)/potassium (K) ratio became higher from J1 to J5. Systolic blood measure was significantly lower in J3 than in J5. Diastolic blood pressure was also significantly lower in J3 than in J1. In conclusion, the higher the J score, which corresponds to Japanese dietary habits, the lower the BMI and cholesterol levels, as well as mortality rate from coronary heart disease, but the higher the average life expectancy among the Japanese. However, these higher J scorings were associated with high-salt intake and high Na/K ratios; therefore, they contributed to high blood pressure and high mortality rate caused by stroke in Japan. These results indicate that low-salt intake should be recommended to the Japanese who are consuming seafood and soy regularly in order to maintain lower blood pressure and to extend healthy life expectancy with a lower risk of stroke. Moreover, high scorings of the Japanese diet correspond to the high intake of magnesium (Mg) which is rich in seafood including seaweeds and soy. Therefore, low-salt seafood and soy intake is expected to reduce the incidence of the metabolic syndrome, the risk of which is inversely related to T and Mg intake.

Cross-Sectional Inverse Association of Regular Soy Intake with Insulin Resistance in Japanese Elderly

Levels of isoflavones, biomarkers of soy intake, in 24-hour urine (24U) were inversely related to coronary heart disease (CHD) mortality in the World Health Organization’s Cardiovascular Disease and Alimentary Comparison Study. Considering 24 U isoflavone levels were highest and CHD mortality was lowest in the Japanese, who maintained the world’s longest life expectancy, the association of regular soy intake with cardiometabolic risk was investigated in Japanese adults (20–49 years old) and elderly (50–79 years old). In multivariate analysis adjusted for age, sex, and drug treatments, mean 24 U isoflavone excretion was significantly inversely associated with insulin resistance in the elderly and significantly associated with blood folate and potassium in the elderly, but also positively associated with 24 U salt in the elderly. These findings indicate that low-salt soy should be recommended to improve glucose metabolism in elderly Japanese.

Soy and fish as features of the Japanese diet and cardiovascular disease risks.

In the World Health Organization (WHO)-coordinated Cardiovascular Disease and Alimentary Comparison Study, isoflavones (I; biomarker for dietary soy) and taurine (T; biomarker for dietary fish) in 24-hour—urine (24U) were inversely related to coronary heart disease (CHD) mortality. High levels of these biomarkers are found in Japanese people, whose CHD mortality is lowest among developed countries. We analyzed the association of these biomarkers with cardiovascular disease risk in the Japanese to know their health effects within one ethnic population. First, to compare the Japanese intake of I and T with international intakes, the ratios of 24UI and 24UT to creatinine from the WHO Study were divided into quintiles for analysis. The ratio for the Japanese was the highest in the highest quintiles for both I and T, reaching 88.1%, far higher than the average ratio for the Japanese (26.3%) in the total study population. Second, 553 inhabitants of Hyogo Prefecture, Japan, aged 30 to 79 years underwent 24-U collection and blood analyses. The 24UT and 24UI were divided into tertiles and adjusted for age and sex. The highest T tertile, compared with the lowest tertile, showed significantly higher levels of high-density lipoprotein-cholesterol (HDL-C), total cholesterol, 24U sodium (Na) and potassium (K). The highest I tertile showed significantly higher folate, 24UNa and 24UK compared with the lowest tertile. The highest tertile of both T and I showed significantly higher HDL-C, folate, and 24UNa and 24UK compared with the lowest tertile. Thus, greater consumption of fish and soy were significantly associated with higher HDL-C and folate levels, possibly a contributor to Japan having the lowest CHD mortality and longest life expectancy among developed countries. As these intakes were also associated with a high intake of salt, a low-salt intake of fish and soy should be recommended for healthy life expectancy.

Taurine Intake with Magnesium Reduces Cardiometabolic Risks.

WHO-CARDIAC (Cardiovascular Diseases and Alimentary Comparison) Study revealed the quintile analyses of 24-h urinary (24 U) taurine (T) and magnesium (Mg) excretions were inversely related with cardiometabolic risks (CMR) such as obesity, hypertension and hypercholesterolemia in 50 population samples in the world. To exclude the influence of ethnicity in the study, 24 U T and Mg excretions were analyzed for the association with CMR in one ethnicity, Japanese population.24 U T/creatinine (C) ratios were divided into 5 quintiles and the ratios of Japanese to the total of each quintile were analyzed from CARDIAC Study samples. The highest 24 U T quintile consisted of 60% Japanese, indicating high seafood consumption in Japanese.Over 600 Japanese aged 30-79 were invited to a health examination for blood pressure measurement and for fasting blood and 24 U samplings. Tertile analysis of 24 U T/C ratios in relation to CMR indicated the third tertile had significantly higher HDL cholesterol, 24 U potassium (K) and 24 U salt than the first (lowest) tertile. Tertile analysis of 24 U Mg/C ratios indicated the third tertile had significantly lower body mass index and significantly higher folic acid, 24 U isoflavones, K and salt than the first tertile after age and gender adjustment. The third tertile of both T/C and Mg/C had significantly lower body mass index, LDL/HDL and Na/K ratios, and significantly higher HDL cholesterol and folic acid than the first tertile, indicating seafood eaters taking Mg rich diets had lower risks of obesity, atherosclerosis, hypertension and higher folic acid, beneficial for healthy longevity.

Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats.

Endothelial damage is repaired by endothelial progenitor cells (EPCs), which are pivotal in preventing cardiovascular diseases and prolonging lifespan. The WHO Cardiovascular Diseases and Alimentary Comparison Study demonstrated that dietary taurine and magnesium (Mg) intake suppresses cardiovascular diseases. We herein evaluate the effects of taurine and Mg supplementation on EPC function and oxidative stress in healthy men and spontaneously hypertensive rats (SHRs). Healthy men received taurine (3 g per day) or Mg (340 mg per day) for 2 weeks. SHRs and Wistar-Kyoto (WKY) rats were housed with high-salt drinking water (1% NaCl). The SHRs received 3% taurine solution and/or a high-Mg (600 mg per 100 g) diet for 4 weeks. Their peripheral blood mononuclear cells were separated to quantify EPC colony formation. Oxidative stress markers in their peripheral blood were evaluated using a free radical analytical system and a thiobarbituric acid reactive substance (TBARS) assay. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased free radical levels and TBARS scores in healthy men. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased TBARS scores and free radical levels in SHRs. Nicotinamide adenine dinucleotide phosphate oxidase component mRNA expression was significantly higher in the renal cortex of salt-loaded SHRs than in WKY rats, in which it was suppressed by taurine and Mg supplementation. Taurine and Mg supplementation increased EPC colony formation in healthy men and improved impaired EPC function in SHRs through antioxidation, indicating that the dietary intake of taurine and Mg may prolong lifespan by preventing the progression of cardiovascular diseases.

An inverse association between magnesium in 24-h urine and cardiovascular risk factors in middle-aged subjects in 50 CARDIAC Study populations

Serum, plasma and dietary magnesium (Mg) have been reported to be inversely associated with cardiovascular disease risk factors. We examined the associations between the 24-h urinary Mg/creatinine (Cre) ratio and cardiovascular disease risk factors, such as body mass index (BMI), blood pressure (BP), serum total cholesterol (TC) and prevalence of obesity, hypertension and hypercholesterolemia. A cross-sectional analysis was conducted among 4211 participants (49.7% women) aged 48-56 years in 50 population samples from 22 countries in the World Health Organization-coordinated Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study (1985-1994). In linear regression analyses, Mg/Cre ratio was inversely associated with BMI, systolic BP (SBP), diastolic BP (DBP) and TC (P for linear trend <0.001 for each). These associations were not markedly altered by adjustment for traditional risk factors, urinary markers or cohort effects. Multivariate-adjusted mean values for the subjects in the highest Mg/Cre ratio quintile were 6.3, 3.4, 5.3 and 4.6% lower than those for the subjects in the lowest quintile for BMI, SBP, DBP and TC (P < 0.001, respectively). The prevalence of obesity, hypertension and hypercholesterolemia was 2.10 (95% confidence interval: 1.50, 2.95), 1.55 (1.25, 1.92) and 2.06 (1.63, 2.62) times higher (P < 0.001, respectively) among the subjects in the lowest Mg/Cre ratio quintile than in the subjects in the highest quintile. These associations were not appreciably altered by adjustment for potential confounding variables. In conclusion, higher 24-h urinary Mg/Cre ratio was associated with lower cardiovascular disease risk factors, including BMI, BP, TC, obesity, hypertension and hypercholesterolemia.

Resting heart rate in relation to blood pressure: Results from the World Health Organization—Cardiovascular Disease and Alimentary Comparison Study

Epidemiological studies have reported that increased heart rate (HR) is associated with cardiovascular mortality. We aimed in assessing the hypothesis that HR may influence the outcomes of cardiovascular disease via a pathway related to increases in blood pressure (BP). Data from the World Health Organization-Cardiovascular Disease and Alimentary Comparison (CARDIAC) Study were analyzed to examine the association between resting HR and BP in a sample of 8541 adults aged 48-56 participating in the CARDIAC baseline surveys. Increased heart rates were significantly correlated with both systolic and diastolic BP (SBP and DBP) in men and women. The overall results (e.g. the pooled regression coefficients) suggest that an increase in each unit of heart rate (beat per minute) was associated with 0.27 mmHg increase in SBP, and 0.09 mmHg in DBP in the total study population sample, and 0.203 mmHg increase in SBP, and 0.252 mmHg increase in DBP in the sub-sample in which subjects with anti-hypertensive medication use were excluded in the analysis. The study, by using a large population-based sample, indicates that increased resting heart rates are associated with increased blood pressure. The result supports the hypothesis that the influence of heart rates on cardiovascular mortality may be mediated by elevated blood pressure.

Yukio Yamori: scientist and master in food culture of longevity

World Health Organization (WHO) data clearly demonstrate that Japanese are enjoying the longest life-span, women living average 86 years, and men 79 years. Impressively, more than 28 395 centenarians are at present living in Japan, whereas their number was approximately 200 in 1963. The applicability of dietary control of hypertension and stroke to humans has been supported by epidemiological studies in Japan as well as by the WHO cardiovascular diseases and alimentary comparison (CARDIAC) study. Biomedical Reviews 2008; 19: v-vi.

WORLDWIDE EPIDEMIC OF OBESITY: HOPE FOR JAPANESE DIETS

1. WHO-coordinated Cardiovascular Diseases and Alimentary Comparison Study (CARDIAC) and its follow-up, MONALISA Study covering 60 populations in 25 countries indicated an increasing prevalence of obesity, even in developing countries. 2. The index of obesity, BMI was confirmed to be related positively with both systolic and diastolic blood pressure (BP) in 60 CARDIAC populations and with the age-adjusted mortality rates of coronary heart diseases (CHD) in 25 populations where reliable demographic data were available. 3. CHD mortality rates were inversely related with biomarkers for soy bean and fish intakes, isoflavones and taurine in 24-h urine samples in 25 CARDIAC study populations. 4. Population samples were divided into two groups: soy eaters and non-eaters as well as fish eaters and non-eaters, respectively, based on WHO-CARDIAC study data. Soy eaters as well as fish eaters had significantly lower BMI, BP and serum cholesterol levels, which are three major CHD risk factors. 5. BMI was inversely related with 24-h urinary isoflavones excretion, the biomarker of soy intake and also with 24-h urinary excretion of histidine, relatively rich in fish. 6. Since both nutrients, isoflavones as phytoestrogen and histidine as the precursor of histamine may affect central appetite mechanisms, soy and fish intake may be recommended to control obesity, the major common risk of lifestyle-related diseases.

FISH and LIFESTYLE‐RELATED DISEASE PREVENTION: EXPERIMENTAL AND EPIDEMIOLOGICAL EVIDENCE FOR ANTI‐ATHEROGENIC POTENTIAL OF TAURINE

1. Taurine supplementation attenuated the development of hypertension and stroke in stroke-prone spontaneously hypertensive rats (SHRSP). 2. WHO-CARDIAC (Cardiovascular Diseases Alimentary Comparison) study revealed wide differences in 24-h urinary taurine excretion, which were inversely associated with age-adjusted mortality rates of coronary heart diseases (CHD). 3. Hypercholesterolemia as well as arterial fat deposition related to the cause of CHD was attenuated by dietary taurine supplementation in SHRSP on high-fat cholesterol diet. 4. Taurine affected the gene expression of 7alpha-hydroxylase and thus regulated serum cholesterol level through the control of the rate limiting step of cholesterol excretion into bile acids. 5. Taurine attenuated atherogenesis due to the control of oxidative stress through the inhibition of the production of oxidative LDL and to its scavenger effect on hypochlorous acid (HOCl) from leucocytes and macrophages. 6. Taurine may act as an immunomodulator of cytokine production, which is involved in atherogenesis.

1FS02-2 Geoethnic-sensitive and cross-culture differences of dietary patterns and blood pressure in Chinese: Findings from the WHO cardiovascular diseases and alimentary comparison study

1FS02-2 Geoethnic-sensitive and cross-culture differences of dietary patterns and blood pressure in Chinese: Findings from the WHO cardiovascular diseases and alimentary comparison study

Inverse relationship between urinary markers of animal protein intake and blood pressure in Chinese: results from the WHO Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study.

This issue of the relationship between animal protein intake and blood pressure (BP) is unsolved. We examined the associations between urinary 3-methylhistidine (3MH) excretion (a biological marker of animal protein intake) and BP in 11 Chinese population samples (Urumqi, Altai, Lhasa, Tulufan, Hetian, Guiyang, Guangzhou, Shanghai, Beijing, Shijiazhuang and Taipei). This was a multi-centre cross-sectional study. In each centre, 100 men and 100 women aged 48-56 years were selected randomly from the general population. 3-methylhistidine in 24-hour (24-h) urine collections was measured by an Amino Acid Analyzer (Hitachi 835, Ibaragi, Japan). The total study sample included 966 men and 1025 women. Subjects who failed to collect complete 24-h urine samples were excluded in data analyses regarding associations between 3MH and BP. The results showed that: (1) for within-centre analyses of individuals, the 3MH and 3MH to creatinine ratios (3MH:cre) were significantly and negatively associated with BP and hypertension. These associations remained significant after adjustment for age, sex, sodium to potassium ratio, body mass index, calcium and magnesium. The pooled regression coefficients (SE) of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on 3MH were -0.020 (0.01) and -0.018 (0.01), and of SBP and DBP on 3MH:cre were -0.022 (0.01) and -0.016 (0.01), respectively. Subjects with lower 3MH excretion had higher relative risks of hypertension than those who had higher 3MH excretion. (2) In cross-centre analyses, mean SBP and DBP were significantly and negatively associated with the mean 3MH:cre across the 11 population samples (R(2) = 0.56, P < 0.01). The results provide strong evidence that animal protein intake is associated inversely with BP in Chinese populations.

Diet-related factors, educational levels and blood pressure in a Chinese population sample: findings from the Japan-China Cooperative Research Project.

As part of the Japan-China Cooperative Research Project of the WHO-Cardiovascular Disease and Alimentary Comparison Study, a cross-sectional study was carried out to investigate risk factors for high blood pressure (BP) in male adults in Chongqing, China. Subjects with hypertension (HT) were defined as those if they had systolic BP (SBP) > or = 140 mmHg or diastolic BP (DBP) > or = 90 mmHg or if they were receiving anti-hypertensive drug therapy. Subjects were also categorized into three groups according to their level of education, i.e., low- (< or = 6 years), intermediate- (7-9 years), or high- (> or = 10 years) level education. The results were as follows. (a) 20.3% of subjects had HT, 16.7% had hypercholesterolemia (serum total cholesterol > or = 220 mg/dl), and 23.4% were overweight (body mass index > or = 25 kg/m2). (b) After adjustment for age, SBP and DBP showed a significant positive association with body mass index, urinary sodium (Na) excretion, and total cholesterol (TC) to high-density lipoprotein (HDL) cholesterol ratio (TC/HDL). SBP and DBP tended to be negatively associated with 24 h urinary potassium (K) and magnesium (Mg) excretion. (c) Subjects with the highest educational level had the lowest prevalence of HT (11.6%), followed by those with the low (22.6%) and the intermediate (25.0%) educational levels (p<0.05). (d) Logistic regression analysis indicated that the relative risks (95%CI) of being overweight, high TC/HDL ratio, high Na excretion and lower educational level (<10 years) for risk of HT were 5.39 (2.42-11.98), 1.73 (1.13-2.63), 1.30 (1.06-1.58), and 2.56 (1.41-6.71) respectively. (e) Subjects with the highest educational level had significantly lower Na, significantly lower Na/K ratio excretion, and significantly higher K and Mg excretion values than those with intermediate or low educational levels. In conclusion, BP was strongly associated with BMI, salt intake and other diet-related factors in the study sample. The results emphasize that education plays an important role in public health for the control of high BP in the Chinese population.

Different associations of blood pressure with 24-hour urinary sodium excretion among pre- and post-menopausal women. WHO Cardiovascular Diseases and Alimentary Comparison (WHO-CARDIAC) Study.

Having found no definite relationship between blood pressure (BP) and 24h sodium excretion in women aged 48-56 years (in contrast to the results in men of the same age) in the WHO Cardiovascular Diseases and Alimentary Comparison (WHO-CARDIAC) Study, we analyzed the data to investigate whether the sodium-BP association differed between pre- and post-menopausal women. The WHO-CARDIAC is a multicenter cross-sectional study, involving, as of July 2000, 60 collaborating centers in 25 countries. In each center, 100 men and 100 women aged 48-56 years were selected randomly from the general population of the area. In this report, 2,212 women in 21 centers located in 17 countries worldwide, who had data on menopausal status, were studied. After adjustment for age, body mass index (BMI) and 24h urinary potassium excretion, 24h sodium excretion was positively and significantly associated with systolic blood pressure (SBP) [pooled regression coefficient: 0.037 (SE 0.01), P < 0.01] and with diastolic blood pressure (DBP) [0.023 (0.006), P< 0.01] in post-menopausal women. Pooled regression coefficients of sodium-BP association were not significant in pre-menopausal women (P< 0.05). Cross-center correlation analyses of the 21 centers showed that 24h sodium excretion was positively associated with SBP and DBP in both pre- and post-menopausal women, and this positive association between sodium excretion and SBP was significant in post-menopausal women (R2 = 0.23, P = 0.029). Different associations between sodium and BP were observed in women with pre- and post-menopausal status. There may be a tendency for salt sensitivity to increase at the menopause.

Ethnic and environmental differences in various markers of dietary intake and blood pressure among Chinese Han and three other minority peoples of China: results from the WHO Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study.

Our aim was to examine differences in dietary intake and blood pressure (BP) and their associations in four different ethnic Chinese populations, the Han, the Uygur, the Kazak and Tibetan subjects. This study used a sub-database of the Chinese sample of the WHO-Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. The WHO-CARDIAC Study was a multicenter cross-sectional study. In each center, 100 men and 100 women aged 48-56 years were selected at random from the local population. Various markers of dietary intake and their relation with BP were studied. The results of the present study indicated the following. 1) There were significant differences in mean BP and prevalence rates of hypertension, with both being higher in the Kazak and Tibetan subjects than in Han and Uygur subjects. 2) The highest mean body mass index (BMI) was observed in the Kazak subjects, while the highest 24-h urinary sodium (Na) and sodium to potassium (Na/K) ratio excretion were observed in the Tibetan subjects. There were also significant differences in other factors, such as magnesium, 3-methylhistidine (3MH) (a biological marker of animal protein intake) and taurine (a biological marker of seafood intake) excretion levels among the four ethnic peoples. 3) In general, BMI, Na and/or Na/K ratios were positively, and 3MH/creatinine and taurine/creatinine ratios were negatively associated with BP. 4) After adjustment for age, sex and potassium, subjects with obesity (BMI > or =26 kg/m2) had significantly higher relative risk of being hypertensive (HT) than those with BMI<26 kg/m2 in the Han, Uygur and Kazak populations; and subjects with elevated sodium excretion (Na > or =244 mmol/day) had significantly higher relative risk of being HT than those with Na<244 mmol/day in the Han, Uygur and Tibetan populations. In conclusion, mean BP and prevalence rates of hypertension were significantly different among the four ethnic groups. These differences are likely to be due, at least in part, to the differences in several diet-related factors, which in turn are associated with culture and environmental differences. Different health promotion strategies might thus be emphasized in different populations.

Twenty-four hour urinary sodium and 3-methylhistidine excretion in relation to blood pressure in Chinese: results from the China-Japan cooperative research for the WHO-CARDIAC Study.

We examined the associations between sodium and blood pressure (BP), and between 3-methylhistidine (3MH) (a marker of animal protein intake) and BP in four Chinese population samples (Guiyang, Guangzhou, Shanghai and Shijiazhuang). This work was a constituent part of the World Health Organization (WHO) Cardiovascular Disease and Alimentary Comparison (CARDIAC) Study. Each population sample consisted of 100 men and 100 women aged 48-56 yr and randomly selected using a cross-sectional study design. Twenty-four hour urine samples were collected. Urinary sodium and potassium excretion levels were measured by the flame photometry method, and 3MH was measured using a Hitachi Amino Acid Analyzer 835 (Hitachi, Ibaraki, Japan). After excluding subjects who did not complete the 24-h urine collection (as assessed by urinary creatinine excretion in relation to weight), the total study group included 314 men and 355 women. The results showed that (1) Sodium was positively, and 3MH negatively associated with systolic and diastolic BP (SBP, DBP) in both the total sample and in those who were not administered anti-hypertensive drugs; these associations were all significant (p< 0.05), and remained so after adjustment for age, sex, body mass index [BMI, weight (kg)/height (m2)], alcohol intake and potassium excretion. Sodium and 3MH were also observed to exert a combined effect on BPs. In general, subjects who had higher sodium and lower 3MH levels had higher mean SBP and DBP. This combined effect was particularly clear on SBP. (3) A positive association between sodium and BP, and a negative association between 3MH and BP were also shown in subjects who had BMI less than 26 kg/m2. In conclusion, the study confirmed and further extended previous observations on the study of salt and animal protein intake in relation to BP in middle-aged Chinese. The results support recommendations for a reduction in high salt intake for the control of high BP in the general population and in those with lower BMI. The results also provide important evidence that adequate animal protein intake may have a favorable effect on BP.

Preventive nutritional factors in epidemiology: interaction between sodium and calcium.

1. It is generally believed, though difficult to prove, that diet plays a role in the risk of various diseases. Components of difficulties include several issues such as dietary assessment method, regression dilution bias, multicolinearity and interaction among nutrients. 2. The present study focuses on colinearity and interaction between sodium and calcium, which should be cautiously examined in nutritional epidemiological studies in relation to blood pressure and bone mineral density. 3. The World Health Organization's International Cooperative Cardiovascular Diseases and Alimentary Comparison study showed significant multicolinearity among urinary sodium, calcium and urea nitrogen as well as urinary calcium and magnesium. Urinary sodium and calcium had significant correlation (r = 0.438, P < 0.05, n = 48) by cross-centre analysis. 4. Interaction between sodium and calcium on bone mineral density is studied using the data set from bone mineral density screening for 1658 females, aged 20-40 years, in Yokohama, Japan. Among those who have lower calcium intake (< 600 mg/day), higher calcium intake (%) from small fish, which is likely to be associated with a high salt diet, related to significantly lower mineral bone density. 5. Interaction between sodium and calcium on bone mineral density among young Japanese females is suggested. Moderate sodium restriction is needed for prevention of not only cardiovascular diseases but also osteoporosis.

International cooperative study on the relationship between dietary factors and blood pressure: a preliminary report from the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. The CARDIAC Cooperative Study Research Group.

1. To investigate the epidemiological relationship of dietary factors to blood pressure (BP) and major cardiovascular diseases, we carried out the international cooperative Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study, which so far involves 48 centers in 20 countries as of August 1991. From each population, 100 men and 100 women aged 50-54 years were randomly selected for BP measurement, 24-h urine collection, blood tests, and medical interview. Various biological markers of diets from urine and blood were analyzed centrally in the Izumo CARDIAC center. 2. Cross center analysis using simple linear regression revealed strong significant correlations of body mass index (BMI) to systolic BP (SBP; p < 0.01) and diastolic BP (DBP; p < 0.001) in men. 24-h urinary sodium (Na) excretion in men also showed significant correlations with SBP (p < 0.05) and DBP p < 0.05) even after controlling for the effect of BMI (SBP; p < 0.05, DBP; p < 0.05). 3. Within center analysis using multiple linear regression implied that BMI and Na strongly adversely affect BP, whereas magnesium may have beneficial influence on BP. 4. Multicolinearities among 24h urinary sodium, calcium, and urea nitrogen were noted in men.

Cardiovascular Diseases and Alimentary Comparison Study

Data from 49 men and 48 women included in the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study in Perth, Western Australia, were analyzed. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were positively correlated (p less than 0.01) with urine sodium, creatine, taurine, histidine, and 3-methyl histidine but not with calcium, magnesium, or potassium. SBP was related (p less than 0.01) with body mass index (BMI). Urine nitrogen, creatinine, and amino acids correlated (p less than 0.001) with each other and with urine sodium, potassium, calcium, and magnesium. Urine magnesium correlated (p less than 0.001) with urine calcium and potassium; urine calcium was not related significantly to urine sodium or potassium. In backwards multiple regression with data from urine collections, SBP was significantly related only to urine sodium (11.9% of variance explained). If alcohol was included as an independent variable, reducing the number of valid cases because of missing values, both alcohol and urine sodium were significant in regression (19.9% of variance explained). In men, DBP was significantly related to BMI and the ratio of 3-methylhistidine to creatine (23.7% of variance explained). For DBP in women, urine sodium was the only variable needed in regression (58.4% of variance explained). Interpretation must be cautious, because these analyses are based on relatively few cases and on single 24-h urine samples. The data are in keeping with suggestions that obesity, alcohol consumption, a meat diet, and sodium intake are important factors predisposing to elevation of blood pressure.