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Objectives:To investigate associations of egg intake with blood pressure (BP) and the role of dietary variables and other macro- and micro-nutrients in the association.Design:We used cross-sectional data for the USA as part of the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP). INTERMAP was surveyed between 1996 and 1999, including four 24-h dietary recalls, two 24-h urine collections and eight measurements of systolic BP and diastolic BP (SBP, DBP). Average egg intake (g/d) was calculated. Multivariable linear regression models were used to estimate the association between egg intake (per each 50 g/d or per quintile) and BP. The roles of dietary variables and other macro- and micro-nutrients in this association were also investigated.Setting:In the USA.Participants:In total, 2195 US INTERMAP men and women aged 40–59 years.Results:Participants were 50 % female, 54 % non-Hispanic White and 16 % non-Hispanic Black. Mean egg intake (sd) in men and women was 30·4(29·8) and 21·6(20·5) g/d, respectively. Adjusting for demographics, socio-economics, lifestyle and urinary Na:K excretion ratios, we found non-linear associations with BP in non-obese women (P-quadratic terms: 0·004 for SBP and 0·035 for DBP).The associations remained after adjusting for dietary variables, macro/micro nutrients or minerals. Dietary cholesterol was highly correlated with egg intake and may factor in the association. No association was found in obese women and in obese or non-obese men.Conclusion:Egg intake was non-linearly associated with SBP and DBP in non-obese women, but not in obese women or men. Underlying mechanisms require additional study regarding the role of obesity and sex.

Summary Background and aims Previous studies have reported associations between higher potato intake and higher blood pressure (BP) and/or risk of hypertension and obesity. These studies rarely considered preparation methods of potatoes, overall dietary pattern or the nutrient quality of the meals. These factors may affect the association of potato intake with BP and body mass index (BMI). This study investigated potato consumption by amount, type of processing, overall dietary pattern, and nutrient quality of the meals in relation to BP and BMI. Methods Cross-sectional analyses were conducted among 2696 participants aged 40–59 y in the US and UK samples of the International Study of Macro- and Micro-Nutrients and Blood Pressure (INTERMAP). Nutrient quality of individual food items and the overall diet was assessed with the Nutrient-Rich Foods (NRF) index. Results No associations with BP or BMI were found for total potato intake nor for boiled, mashed, or baked potatoes or potato-based mixed dishes. In US women, higher intake of fried potato was associated with 2.29 mmHg (95% CI: 0.55, 3.83) higher systolic BP and with 1.14 mmHg (95% CI: 0.10, 2.17) higher diastolic BP, independent of BMI. Higher fried potato consumption was directly associated with a +0.86 kg/m2 difference in BMI (95% CI: 0.24, 1.58) in US women. These associations were not found in men. Higher intakes of fried potato meals with a lower nutritional quality (NRF index≤ 2) were positively associated with systolic (3.88 mmHg; 95% CI: 2.63, 5.53) and diastolic BP (1.62 mmHg; 95% CI: 0.48, 2.95) in US women. No associations with BP were observed for fried potato meals with a higher nutritional quality (NRF index> 2). Conclusions Fried potato was directly related to BP and BMI in women, but non-fried potato was not. Poor-nutrient quality meals were associated with intake of fried potatoes and higher BP, suggesting that accompanied dietary choices are key mediators of these associations.

Growing epidemiological evidence has shown an association of the urinary sodium (Na) to potassium (K) ratio (Na/K ratio) with blood pressure and cardiovascular diseases. However, no clear cutoff level has been defined. We investigated the cutoff level of the urinary Na/K ratio under different dietary guidelines for Japanese individuals, especially that endorsed by the 2020 revised Japanese Dietary Reference Intakes (DRIs). A population of 1145 Japanese men and women aged 40 to 59 years from the INTERMAP study was examined. Using high-quality standardized data, the averages of two 24 h urinary collections and four 24 h dietary recalls were used to calculate the 24 h urinary and dietary Na/K ratios, respectively. Associations between the urinary and dietary Na/K ratios were tested by sex- and age-adjusted partial correlation. The optimal urinary Na/K ratio cutoff level was determined by receiver operating characteristic (ROC) curves and sex-specific cross tables for recommended dietary K and salt. Overall, the average molar ratio of 24 h urinary Na/K was 4.3. We found moderate correlations (P 0.001) of the 24 h urinary Na/K ratio with 24 h urinary Na and K excretion (r = 0.52, r = -0.49, respectively) and the dietary Na/K ratio (r = 0.53). ROC curves showed that a 24 h urinary Na/K ratio of approximately 2 predicted Na and K intake that meets the dietary goals of the Japanese DRIs. The range of urinary Na/K ratios meeting the dietary goals of the Japanese DRIs for both Na and K was 1.6‒2.2 for men and 1.7‒1.9 for women. Accomplishing a urinary Na/K ratio of 2 would be desirable to achieve the DRIs dietary goals for both Na and K simultaneously in middle-aged Japanese men and women accustomed to Japanese dietary habits. This observational study is registered at www.clinicaltrials.gov as NCT00005271.

We examined associations of central family (i.e., children, parents, in-laws) social network size with healthy lifestyle factors (i.e., favorable body mass index, physical activity, diet, alcohol use, smoking). Using data on 15,511 Hispanics/Latinos 18-74 years old from the Hispanic Community Health Study/Study of Latinos, multivariable adjusted survey logistic regression was used to compute associations of social network size with healthy lifestyle factors. A one-unit higher total of central family size was associated with lower odds of healthy body mass index (OR 0.90; 95% CI 0.86-0.93) and having all five healthy lifestyle factors (OR 0.90; 95% CI 0.85-0.96). Findings suggest familial structural social support may contribute to healthy lifestyle factors and differ based on the type of relationship among Hispanics/Latinos.

Aim: The positive relationship between dietary cholesterol and serum cholesterol has been questioned by a set of recent cohort studies. This study aimed to investigate how employment status and education years relate to the association between dietary cholesterol and serum low-density lipoprotein cholesterol (LDL-C) in a Japanese population. Methods: A population-based, random sample, cross-sectional study (INTERLIPID) was performed. Among 1,145 Japanese individuals aged 40–59 years, 106 were excluded because of special diets, use of lipid-lowering drugs, hormone replacement, and missing data, leaving 1,039 individuals (533 men and 506 women). Dietary cholesterol was assessed from four 24-h dietary recalls, and LDL-C was measured enzymatically with an autoanalyzer. A standard questionnaire inquired about employment status and education years. Results: In men, a 1 standard deviation (SD) higher dietary cholesterol was associated with 3.16 mg/dL lower serum LDL-C (P = 0.009; unadjusted model). After adjustment for covariates, higher serum LDL-C was estimated per 1 SD higher intake of dietary cholesterol in nonemployed men [self-employed, homemakers, farmers, fishermen, and retired employees; β = +9.08, 95% confidence interval (CI) = +0.90–+17.27] and less educated men (β = +4.46, 95% CI = −0.97–+9.90), whereas an inverse association was observed in employed men (β = −3.02, 95% CI= −5.49–−0.54) and more educated men (β = −3.66, 95% CI = −6.25–−1.07). Conclusions: In men who were nonemployed and less educated, a higher intake of dietary cholesterol was associated with elevated concentrations of serum LDL-C, whereas an inverse association was observed in men who were employed and more educated.

A lower-than-recommended potassium intake is a well-established risk factor for increased blood pressure. Although the Japanese diet is associated with higher sodium intake and lower potassium intake, few studies have examined the source foods quantitatively. Studies on dietary patterns in association with potassium intake will be useful to provide dietary advice to increase potassium intake. Twenty-four-hour (hr) dietary recall data and 24-hr urinary potassium excretion data from Japanese participants (574 men and 571 women) in the International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) were used to calculate food sources of potassium and compare food consumption patterns among quartiles of participants categorized according to 24-hr urinary potassium excretion per unit of body weight (UK/BW). The average potassium intake was 2791 mg/day per participant, and the major sources were vegetables and fruits (1262 mg/day), fish (333 mg/day), coffee and tea (206 mg/day), and milk and dairy products (200 mg/day). Participants in the higher UK/BW quartile consumed significantly more vegetables and fruits, fish, and milk and dairy products, and ate less rice and noodles. Conclusion: Advice to increase the intake of vegetables and fruits, fish, and milk may be useful to increase potassium intake in Japan.

Background Results from observational studies regarding associations between fish (including shellfish) intake and cardiovascular disease risk factors, including blood pressure (BP) and BMI, are inconsistent. Objective To investigate associations of fish consumption and associated urinary metabolites with BP and BMI in free-living populations. Methods We used cross-sectional data from the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP), including 4680 men and women (40–59 y) from Japan, China, the United Kingdom, and United States. Dietary intakes were assessed by four 24-h dietary recalls and BP from 8 measurements. Urinary metabolites (2 timed 24-h urinary samples) associated with fish intake acquired from NMR spectroscopy were identified. Linear models were used to estimate BP and BMI differences across categories of intake and per 2 SD higher intake of fish and its biomarkers. Results No significant associations were observed between fish intake and BP. There was a direct association with fish intake and BMI in the Japanese population sample (P trend = 0.03; fully adjusted model). In Japan, trimethylamine-N-oxide (TMAO) and taurine, respectively, demonstrated area under the receiver operating characteristic curve (AUC) values of 0.81 and 0.78 in discriminating high against low fish intake, whereas homarine (a metabolite found in shellfish muscle) demonstrated an AUC of 0.80 for high/nonshellfish intake. Direct associations were observed between urinary TMAO and BMI for all regions except Japan (P

BACKGROUND: Recently, high-density lipoprotein particles (HDL-P) have been found to be more strongly inversely associated with coronary artery disease (CAD) risk than their counterpart, HDL cholesterol (HDL-C). Given that lifestyle is among the first targets in CAD prevention, we compared the associations of HDL-P and HDL-C with selected lifestyle factors. METHODS AND RESULTS: We examined 789 Japanese participants of the INTERLIPID Study: men (n=386) and women (n=403) aged 40–59 years in 1996–1998. Participants treated for dyslipidemias were excluded. Lifestyle factors included alcohol intake, smoking amount, and body mass index (BMI). Multivariable linear regression was used for cross-sectional analyses of these factors with HDL-P, HDL-C, HDL-P size subclasses (small, medium and large) and mean HDL-P size. In men, higher alcohol intake was associated with higher HDL-P and higher HDL-C. The associations of alcohol, however, were strongest with HDL-P. A higher smoking amount tended to be associated with lower HDL-P and HDL-C. In contrast, BMI was not associated with HDL-P, but was strongly inversely associated with HDL-C. While alcohol intake favored larger mean HDL-P size, smoking and BMI favored a lipid profile with smaller HDL-P subclasses and overall smaller mean HDL-P size. Similar, but generally weaker results were observed in women. CONCLUSIONS: Although both HDL-P and HDL-C are parameters of HDL, they have different associations with alcohol, smoking and BMI.

The application of metabolic phenotyping to epidemiological studies involving thousands of biofluid samples presents a challenge for the selection of analytical platforms that meet the requirements of high-throughput precision analysis and cost-effectiveness. Here direct infusion–nanoelectrospray (DI–nESI) was compared with an ultra-performance liquid chromatography (UPLC)–high-resolution mass spectrometry (HRMS) method for metabolic profiling of an exemplary set of 132 human urine samples from a large epidemiological cohort. Both methods were developed and optimized to allow the simultaneous collection of high-resolution urinary metabolic profiles and quantitative data for a selected panel of 35 metabolites. The total run time for measuring the sample set in both polarities by UPLC–HRMS was 5 days compared with 9 h by DI–nESI–HRMS. To compare the classification ability of the two MS methods, we performed exploratory analysis of the full-scan HRMS profiles to detect sex-related differences in biochemical composition. Although metabolite identification is less specific in DI–nESI–HRMS, the significant features responsible for discrimination between sexes were mostly the same in both MS-based platforms. Using the quantitative data, we showed that 10 metabolites have strong correlation (Pearson’s r > 0.9 and Passing–Bablok regression slope of 0.8–1.3) and good agreement assessed by Bland–Altman plots between UPLC–HRMS and DI–nESI–HRMS and thus can be measured using a cheaper and less sample- and time-consuming method. A further twenty metabolites showed acceptable correlation between the two methods with only five metabolites showing weak correlation (Pearson’s r < 0.4) and poor agreement due to the overestimation of the results by DI–nESI–HRMS.

Available data indicate that dietary sodium (as salt) relates directly to blood pressure (BP). Most of these findings are from studies lacking dietary data; hence, it is unclear whether this sodium–BP relationship is modulated by other dietary factors. With control for multiple nondietary factors, but not body mass index, there were direct relations to BP of 24-hour urinary sodium excretion and the urinary sodium/potassium ratio among 4680 men and women 40 to 59 years of age (17 population samples in China, Japan, United Kingdom, and United States) in the INTERMAP (International Study on Macro/Micronutrients and Blood Pressure), and among its 2195 American participants, for example, 2 SD higher 24-hour urinary sodium excretion (118.7 mmol) associated with systolic BP 3.7 mm Hg higher. These sodium–BP relations persisted with control for 13 macronutrients, 12 vitamins, 7 minerals, and 18 amino acids, for both sex, older and younger, blacks, Hispanics, whites, and socioeconomic strata. With control for body mass index, sodium–BP—but not sodium/potassium–BP—relations were attenuated. Normal weight and obese participants manifested significant positive relations to BP of urinary sodium; relations were weaker for overweight people. At lower but not higher levels of 24-hour sodium excretion, potassium intake blunted the sodium–BP relation. The adverse association of dietary sodium with BP is minimally attenuated by other dietary constituents; these findings underscore the importance of reducing salt intake for the prevention and control of prehypertension and hypertension. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00005271.

We examined associations between personality traits measured in 1958 and both all-cause and cause-specific mortality assessed 45 years later in 2003. Participants were 1,862 middle-aged men employed by the Western Electric Company. Outcomes were days to death from all causes, coronary heart disease, stroke, cancer, and causes other than circulatory diseases, cancer, accidents/homicide/suicides, or injuries (other causes). Measures in 1958 included age, education, health behaviors, biomedical risk factors, and nine content factors identified in the Minnesota Multiphasic Personality Inventory (MMPI). Four content factors-neuroticism, cynicism, extraversion, and intellectual interests-were related to the five-factor model domains of neuroticism, agreeableness, extraversion, and openness, respectively. The remaining five-psychoticism, masculinity versus femininity, religious orthodoxy, somatic complaints, and inadequacy-corresponded to the five-factor model's facets and styles (combinations of two domains) or were unrelated to the five-factor model. In age-adjusted and fully adjusted models, cynicism was associated with greater all-cause and cancer mortality. In fully adjusted models, inadequacy was associated with lower all-cause mortality and lower mortality from other causes. In age-adjusted models, religious orthodoxy was associated with lower cancer mortality. Further analyses revealed that the association between cynicism and all-cause mortality waned over time. Exploratory analyses of death from any disease of the circulatory system revealed no further associations. These findings reveal the importance of cynicism (disagreeableness) as a mortality risk factor, show that associations between cynicism and all-cause mortality are limited to certain periods of the lifespan, and highlight the need to study personality styles or types, such as inadequacy, that involve high neuroticism, low extraversion, and low conscientiousness. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

BACKGROUND: Several studies have reported that dietary salt intake may be an independent risk factor for overweight/obesity, but results from previous studies are controversial, reflecting study limitations such as use of a single spot urine or dietary recall to estimate daily salt intake rather than 24-h urine collections, and population samples from only a single country or center. OBJECTIVE: The aim of this study was to use data from the International Study of Macro-/Micro-nutrients and Blood Pressure (INTERMAP Study) to explore the relation between dietary salt intake estimated from 2 timed 24-h urine collections and body mass index (BMI; in kg/m(2)) as well as prevalence of overweight/obesity in Japan, China, the United Kingdom, and the United States. METHODS: Data were from a cross-sectional study of 4680 men and women aged 40–59 y in Japan (n = 1145), China (n = 839), the United Kingdom (n = 501), and the United States (n = 2195). General linear models were used to obtain the regression coefficients (β) of salt intake associated with BMI. Multivariable logistic regression models were used to determine the ORs and 95% CIs of overweight/obesity associated with a 1-g/d higher dietary salt intake. RESULTS: After adjustment for potential confounding factors including energy intake, salt intake 1 g/d higher was associated with BMI higher by 0.28 in Japan, 0.10 in China, 0.42 in the United Kingdom, and 0.52 in the United States, all P values

The Na/K ratio may be more strongly related to blood pressure and cardiovascular disease than sodium or potassium. The casual urine Na/K ratio can provide prompt on-site feedback, and with repeated measurements, may provide useful individual estimates of the 24-h ratio. The World Health Organization has published guidelines for sodium and potassium intake, but no generally accepted guideline prevails for the Na/K ratio. We used standardized data on 24 h and casual urinary electrolyte excretion obtained from the INTERSALT Study for 10,065 individuals aged 20–59 years from 32 countries (52 populations). Associations between the casual urinary Na/K ratio and the 24-h sodium and potassium excretion of individuals were assessed by correlation and stratification analyses. The mean 24-h sodium and potassium excretions were 156.0 mmol/24 h and 55.2 mmol/24 h, respectively; the mean 24-h urinary Na/K molar ratio was 3.24. Pearson’s correlation coefficients (r) for the casual urinary Na/K ratio with 24-h sodium and potassium excretions were 0.42 and −0.34, respectively, and these were 0.57 and −0.48 for the 24-h ratio. The urinary Na/K ratio predicted a 24-h urine Na excretion of

Background— The associations of optimal levels of all major cardiovascular disease risk factors, that is, low risk, in younger age with subsequent cardiovascular disease morbidity and mortality have been well documented. However, little is known about associations of low-risk profiles in younger age with functional disability in older age. Methods and Results— The sample included 6014 participants from the Chicago Heart Association Detection Project in Industry Study. Low-risk status, defined as untreated systolic/diastolic blood pressure ≤120/≤80 mm Hg, untreated serum total cholesterol 2 , and no diabetes mellitus, was assessed at baseline (1967 to 1973). Functional disability, categorized as (1) any disability in activities of daily living (ADLs), (2) any disability in instrumental ADLs but not in ADL, or (3) no disability, was assessed from the 2003 health survey. There were 39% women, 4% Black, with a mean age of 43 years and 6% low-risk status at baseline. After 32 years, 7% reported having limitations in performing any ADL and 11% in any instrumental ADL only. The prevalence of any ADL limitation was lowest in low-risk people and increased in a graded fashion with less-favorable risk factor groups ( P trend Conclusions— Having an optimal cardiovascular disease risk factor profile at younger age is associated with the lowest rate of functional disability in older age.

PURPOSE: It is often reported that Na intake levels are higher in Japan than in western countries. Detailed analysis of food intake and its association with Na intake are necessary for supporting further decreases in Na consumption in Japan. We investigated the association between Na and food intake by food group using data from the Japanese participants of the INTERMAP Study. METHOD: Results from the Japanese participants of the INTERMAP Study who did not use antihypertensive medication and/or consume a reduced Na diet were used (531 men and 518 women, aged 40–59 years), obtained from four 24-h dietary recalls and two 24-h urine collections from each participant. We developed a classification system with 46 food group classifications; food consumption and Na intake from these groups were compared across quartiles of participants determined by 24-h urinary Na excretion per unit of body weight (UNa/BW). RESULTS: Average daily Na intake from Japanese high-Na foods was 2552 mg/day. Participants with a higher UNa/BW consumed a significantly greater amount of high-Na Japanese foods, such as salted fish (P = 0.001) and miso soup (P < 0.001). They also had greater amount of rice (P = 0.001). Participants with lower UNa/BW consumed a significantly greater amount of western foods, such as bread (P < 0.001) and milk and dairy products (P < 0.001). CONCLUSIONS: Detailed analyses of various Japanese and western food intakes in addition to Na intake were performed. These results can be used to help draw up effective programs for the reduction in Na intake and prevention of prehypertension/hypertension in the Japanese population.

Background Data are sparse on the association of cardiovascular health ( CVH ) in younger/middle age with the incidence of dementia later in life. Methods and Results We linked the CHA (Chicago Heart Association Detection Project in Industry) study data, assessed in 1967 to 1973, with 1991 to 2010 Medicare and National Death Index data. Favorable CVH was defined as untreated systolic blood pressure/diastolic blood pressure ≤120/≤80 mm Hg, untreated serum total cholesterol 2 , and no diabetes mellitus. International Classification of Diseases, Ninth Revision (ICD‐9) codes and claims dates were used to identify the first dementia diagnosis. Cox models were used to estimate hazard ratios of incident dementia after age 65 years by baseline CVH status. Among 10 119 participants baseline aged 23 to 47 years, 32.4% were women, 9.2% were black, and 7.3% had favorable baseline CVH . The incidence rate of dementia during follow‐up after age 65 was 13.9%. After adjustment, the hazard ratio for incident dementia was lowest in those with favorable baseline CVH and increased with higher risk factor burden ( P ‐trendP ‐trend Conclusions In this large population‐based study, a favorable CVH profile at younger age is associated with a lower risk of dementia in older age.

Several studies demonstrated that visit-to-visit variability of blood pressure (BP) predicted future events of total death, stroke and cardiovascular disease. Little is known about factors associated with visit-to-visit BP variability in different countries. We recruited participants aged 40–59 years from four countries (Japan, the People’s Republic of China [PRC], the United Kingdom [UK] and the United States [US]). At each study visit, BP was measured twice by trained observers using random zero sphygmomanometers after five minutes resting. We defined visit-to-visit BP variability as variation independent of mean (VIM) by using average systolic BP of 1st and 2nd measurement across four study visits. Data on 4680 men and women were analyzed. Mean ± standard deviation of VIM values among participants in Japan, the PRC, the UK and the US were 5.44 ± 2.88, 6.85 ± 3.49, 5.65 ± 2.81 and 5.84 ± 3.01, respectively; VIM value in the PRC participants was significantly higher. Sensitivity analyses among participants without antihypertensive treatment or past history of cardiovascular disease yielded similar results. Higher VIM value was associated with older age, female gender, lower pulse rate and urinary sodium excretion and use of antihypertensive agents such as angiotensin converting enzyme inhibitors, beta blockers and calcium channel blockers. The difference of visit-to-visit BP variability between PRC and other countries remained significant after adjustment for possible confounding factors. In this large international study across four countries, visit-to-visit BP variability in the PRC was higher than in the other three countries. Reproducibility and mechanisms of these findings remain to be elucidated.

OBJECTIVE: The present study aims to compare 24-h dietary recalls with 24-h urine collections for the estimation of sodium intake at both population and individual levels in China, Japan, the United Kingdom (UK), and the United States of America (USA), using data from the International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP). METHODS: Mean differences between 24-h dietary recalls and 24-h urine collections were calculated for their agreement in estimating sodium intake at the population level; relative and absolute differences as well as misclassification of salt intake groups (salt intake

Background: Epidemiologic evidence suggests that low-fat dairy consumption may lower risk of hypertension. Dairy products may be distinctly linked to health, because of differences in nutritional composition, but little is known about specific nutrients that contribute to the dairy-blood pressure (BP) association, nor to underlying kidney function. Methods: We examined cross-sectional associations to BP of dairy product intakes, total and by type, from the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP) including 2694 participants aged 40–59 years from the UK and the USA. Eight BP, four 24-h dietary recalls and two 24-h urine samples were collected during four visits. Linear regression models adjusted for lifestyle/dietary factors to estimate BP differences per 2SD higher intakes of total-and-individual-types of dairy were calculated. Results: Multivariable linear regression coefficients were estimated and pooled. In contrast to total and whole-fat dairy, each 195 g/1000 kcal (2SD) greater low-fat dairy intake was associated with a lower SBP −2.31 mmHg and DBP −2.27 mmHg. Significant associations attenuated with adjustment for dietary phosphorus, calcium, and lactose, but strengthened with urinary calcium adjustment. Stratification by median albumin–creatinine ratio (ACR; high ACR indicates impaired kidney function) showed strong associations between low-fat dairy and BP in participants with low ACR (SBP: −3.66; DBP: −2.15 mmHg), with no association in participants with high ACR. Conclusion: Low-fat dairy consumption was associated with lower BP, especially among participants with low ACR. Dairy-rich nutrients including phosphorus and calcium may have contributed to the beneficial associations with BP.

A Japanese-style diet consists of meals that include grain (shushoku), fish and meat (shusai), and vegetable dishes (fukusai). Little is known about the association of such meals (designated well-balanced meals hereafter) with nutrient intake. We therefore examined the frequency of well-balanced meals required to prevent nutrient deficiency. Participants were Japanese people, ages 40 to 59 y, from Toyama, recruited for INTERMAP, in an international population-based study. Each person provided 4 in-depth 24-h dietary recalls (149 men, 150 women). The prevalence of risk ratios of not meeting the Dietary Reference Intakes for Japanese (2015) was calculated. Well-balanced diets were assessed by the Japanese Food Guide Spinning Top. We counted the frequencies of meals in which participants consumed 1.0 or more servings of all 3 dishes categories. We divided the frequency of consumption of well-balanced meals into the following 4 groups

BACKGROUND AND OBJECTIVES: Total fat intake is linked to the intake of other nutrients. Little data are available on the extent to which total fat affects diet quality in Japanese people. We investigated the relationship between total fat intake and other nutrient intake using INTERLIPID/INTERMAP data on Japanese people living in Japan. METHODS AND STUDY DESIGN: The participants included 371 men and 401 women with a healthy body mass index and between the ages of 40 and 59 from 4 population samples in Japan. Nutrient intake data were based on four in-depth 24-hour dietary recalls per person. RESULTS: Analysis of covariance adjusted for age revealed that total fat intake was positively related to intakes of calcium, thiamine, riboflavin, meat, eggs, and milks and dairy products for both sexes. Total fat intake was inversely associated with carbohydrate and cereals intake for both sexes. On average, men with total fat intake between 25.0 and 27.4% of total energy had saturated fatty acids above 7%, which is the upper limit recommended for preventing lifestyle-related diseases. Men with total fat intake less than 20% of total energy had a higher risk of not meeting the Dietary Reference Intakes for Japanese (2015) for some nutrients. CONCLUSIONS: Total fat intake was positively associated with calcium, thiamine, and riboflavin intakes and inversely associated with carbohydrate intake. Our results suggest that in 40–59-year-old men with a healthy body mass index, total fat intake between 20 and 27% of total energy may best support adequate intake of other nutrients.

Background: We examined the association of cardiovascular health at younger ages with the proportion of life lived free of morbidity, the cumulative burden of morbidity, and average healthcare costs at older ages. Methods: The CHA study (Chicago Heart Association Detection Project in Industry) is a longitudinal cohort of employed men and women 18 to 74 years of age at baseline examination in 1967 to 1973. Baseline measurements included blood pressure, cholesterol, diabetes mellitus, body mass index, and smoking. Individuals were classified into 1 of 4 strata of cardiovascular health: favorable levels of all factors, 0 factors high but ≥1 elevated risk factors, 1 high risk factor, and ≥2 high risk factors. Linked Medicare and National Death Index data from 1984 to 2010 were used to determine morbidity in older age. An individual’s all-cause morbidity score and cardiovascular morbidity score were calculated from International Classification of Disease, Ninth Revision codes for each year of follow-up. Results: We included 25 804 participants who became ≥65 years of age by 2010, representing 65% of all original CHA participants (43% female; 90% white; mean age, 44 years at baseline); 6% had favorable levels of all factors, 19% had ≥1 risk factors at elevated levels, 40% had 1 high risk factor, and 35% had ≥2 high risk factors. Favorable cardiovascular health at younger ages extended survival by almost 4 years and postponed the onset of all-cause and cardiovascular morbidity by 4.5 and 7 years, respectively, resulting in compression of morbidity in both absolute and relative terms. This translated to lower cumulative and annual healthcare costs for those in favorable cardiovascular health ( P Conclusions: Individuals in favorable cardiovascular health in early middle age live a longer, healthier life free of all types of morbidity. These findings provide strong support for prevention efforts earlier in life aimed at preserving cardiovascular health and reducing the burden of disease in older ages.

Background: Available data have indicated independent direct relations of dietary animal protein and meat to the blood pressure (BP) of individuals. Objective: In this study, we aimed to assess whether BP is associated with the intake of dietary amino acids higher relatively in animal than in vegetable protein (alanine, arginine, aspartic acid, glycine, histidine, lysine, methionine, and threonine). Design: The study was a cross-sectional epidemiologic study that involved 4680 persons aged 40–59 y from 17 random population samples in the People’s Republic of China, Japan, the United Kingdom, and the United States. BP was measured 8 times at 4 visits; dietary data (83 nutrients and 18 amino acids) were from four 24-h dietary recalls and two 24-h urine collections. Results: Dietary glycine and alanine (the percentage of total protein intake) were considered singly related directly to BP; with these 2 amino acids together in regression models (from model 1, which was controlled for age, sex, and sample, to model 5, which was controlled for 16 possible confounders), glycine, but not alanine, was significantly related to BP. Estimated average BP differences associated with a 2-SD higher glycine intake (0.71 g/24 h) were 2.0–3.0-mm Hg systolic BP (z = 2.97–4.32) stronger in Western than in East Asian participants. In Westerners, meat was the main dietary source of glycine but not in East Asians (Chinese: grains/ flour and rice/noodles; Japanese: fish/shellfish and rice/noodles). Conclusion: Dietary glycine may have an independent adverse effect on BP, which possibly contributes to direct relations of animal protein and meat to BP. Am J Clin Nutr doi: 10.3945/ajcn.112.043000.

Objective: In short-term feeding trials, replacement of other macronutrients with monounsaturated fatty acid reduces blood pressure. However, observational studies have not clearly demonstrated a relationship between monounsaturated fatty acid intake and blood pressure. We report associations of monounsaturated fatty acid intake of individuals with blood pressure in a cross-sectional study. Methods: The International Study of Macro/Micronutrients and Blood Pressure is a cross-sectional epidemiologic study of 4,680 men and women ages 40-59 from 17 population samples in China, Japan, United Kingdom, and United States. Nutrient intake data were based on four in-depth multi-pass 24-hour dietary recalls/person and two timed 24-hour urine collections/person. Blood pressure was measured eight times at four visits. Results: Mean monounsaturated fatty acid intake ranged from 8.1 %kcal (China) to 12.2%kcal (United States). With sequential models to control for possible confounders (dietary, other), linear regression analyses showed significant inverse relationship of total monounsaturated fatty acid intake with diastolic blood pressure for all participants; for 2,238 “non-intervened” individuals, the relationship was stronger. Estimated diastolic blood pressure differences with 2-SD higher monounsaturated fatty acids (5.35 %kcal) were -0.82 mm Hg (P

BACKGROUND: Accurate monitoring of changes in dietary patterns in response to food policy implementation is challenging. Metabolic profiling allows simultaneous measurement of hundreds of metabolites in urine, the concentrations of which can be affected by food intake. We hypothesised that metabolic profiles of urine samples developed under controlled feeding conditions reflect dietary intake and can be used to model and classify dietary patterns of free-living populations.METHODS: In this randomised, controlled, crossover trial, we recruited healthy volunteers (aged 21-65 years, BMI 20-35 kg/m(2)) from a database of a clinical research unit in the UK. We developed four dietary interventions with a stepwise variance in concordance with the WHO healthy eating guidelines that aim to prevent non-communicable diseases (increase fruits, vegetables, whole grains, and dietary fibre; decrease fats, sugars, and salt). Participants attended four inpatient stays (72 h each, separated by at least 5 days), during which they were given one dietary intervention. The order of diets was randomly assigned across study visits. Randomisation was done by an independent investigator, with the use of opaque, sealed, sequentially numbered envelopes that each contained one of the four dietary interventions in a random order. Participants and investigators were not masked from the dietary intervention, but investigators analysing the data were masked from the randomisation order. During each inpatient period, urine was collected daily over three timed periods: morning (0900-1300 h), afternoon (1300-1800 h), and evening and overnight (1800-0900 h); 24 h urine samples were obtained by pooling these samples. Urine samples were assessed by proton nuclear magnetic resonance ((1)H-NMR) spectroscopy, and diet-discriminatory metabolites were identified. We developed urinary metabolite models for each diet and identified the associated metabolic profiles, and then validated the models using data and samples from the INTERMAP UK cohort (n=225) and a healthy-eating Danish cohort (n=66). This study is registered with ISRCTN, number ISRCTN43087333.FINDINGS: Between Aug 13, 2013, and May 18, 2014, we contacted 300 people with a letter of invitation. 78 responded, of whom 26 were eligible and invited to attend a health screening. Of 20 eligible participants who were randomised, 19 completed all four 72 h study stays between Oct 2, 2013, and July 29, 2014, and consumed all the food provided. Analysis of (1)H-NMR spectroscopy data indicated that urinary metabolic profiles of the four diets were distinct. Significant stepwise differences in metabolite concentrations were seen between diets with the lowest and highest metabolic risks. Application of the derived metabolite models to the validation datasets confirmed the association between urinary metabolic and dietary profiles in the INTERMAP UK cohort (pINTERPRETATION: Urinary metabolite models developed in a highly controlled environment can classify groups of free-living people into consumers of diets associated with lower or higher non-communicable disease risk on the basis of multivariate metabolite patterns. This approach enables objective monitoring of dietary patterns in population settings and enhances the validity of dietary reporting.FUNDING: UK National Institute for Health Research and UK Medical Research Council.

The aetiopathogenesis of cardiovascular diseases (CVD) is multifactorial. Adverse blood pressure (BP) is a major independent risk factor for epidemic CVD affecting about 40% of the adult population worldwide and resulting in significant morbidity and mortality. Metabolic phenotyping of biological fluids has proven its application in characterisin g low molecule weight metabolites providing novel insights into gene -environmental -gut microbiome interaction in relations to a disease state. In this review, we synthesi s e key results from the International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) Study, a cross - sectional epidemiological study of 4,680 men and women aged 40 -59 years from Japan, the People’s Republic of China, the United Kingdom, and the United States. We describe the advancements we have made on: 1) analytical techniques for high throughput metabolic phenotyping; 2) statistical analyses for biomarker identification; 3) discovery of unique food - specific biomarkers; and 4) application of metabolome -wide association (MWA) studies to gain a better understanding into the molecular mechanisms of cross cultural and regional BP differences.

Background Association between casual and 24-h urinary sodium-to-potassium (Na/K) ratio is well recognized, although it has not been validated in diverse demographic groups. Our aim was to assess utility across and within populations of casual urine to estimate 24-h urinary Na/K ratio using data from the INTERSALT Study. Methods The INTERSALT Study collected cross-sectional standardized data on casual urinary sodium and potassium and also on timed 24-h urinary sodium and potassium for 10 065 individuals from 52 population samples in 32 countries (1985–87). Pearson correlation coefficients and agreement were computed for Na/K ratio of casual urine against 24-h urinary Na/K ratio both at population and individual levels. Results Pearson correlation coefficients relating means of 24-h urine and casual urine Na/K ratio were r = 0.96 and r = 0.69 in analyses across populations and individuals, respectively. Correlations of casual urine Na/creatinine and K/creatinine ratios with 24-h urinary Na and K excretion, respectively, were lower than correlation of casual and 24-h urinary Na/K ratio in analyses across populations and individuals. The bias estimate with the Bland–Altman method, defined as the difference between Na/K ratio of 24-h urine and casual urine, was approximately 0.4 across both populations and individuals. Spread around, the mean bias was higher for individuals than populations. Conclusion With appropriate bias correction, casual urine Na/K ratio may be a useful, low-burden alternative method to 24-h urine for estimation of population urinary Na/K ratio. It may also be applicable for assessment of the urinary Na/K ratio of individuals, with use of repeated measurements to reduce measurement error and increase precision.

Background Favorable levels of all readily measurable major cardiovascular disease risk factors (ie, low risk [ LR ]) are associated with lower risks of cardiovascular disease morbidity and mortality. Data are not available on LR prevalence among Hispanic/Latino adults of diverse ethnic backgrounds. This study aimed to describe the prevalence of a low cardiovascular disease risk profile among Hispanic/Latino adults in the United States and to examine cross‐sectional associations of LR with measures of acculturation. Methods and Results The multicenter, prospective, population‐based Hispanic Community Health Study/Study of Latinos examined 16 415 men and women aged 18 to 74 years at baseline (2008–2011) with diverse Hispanic/Latino backgrounds. Analyses involved 14 757 adults (mean age 41.3 years; 60.6% women). LR was defined using national guidelines for favorable levels of serum cholesterol, blood pressure, and body mass index and by not having diabetes mellitus and not currently smoking. Age‐adjusted LR prevalence was low (8.4% overall; 5.1% for men, 11.2% for women) and varied by background (4.2% in men of Mexican heritage versus 15.0% in women of Cuban heritage). Lower acculturation (assessed using proxy measures) was significantly associated with higher odds of a LR profile among women only: Age‐adjusted odds ratios of having LR were 1.64 (95% CI 1.24–2.17) for foreign‐born versus US ‐born women and 1.96 (95% CI 1.49–2.58) for women residing in the United States Conclusions Among diverse US Hispanic/Latino adults, the prevalence of a LR profile is low. Lower acculturation is associated with higher odds of a LR profile among women but not men. Comprehensive public health strategies are needed to improve the cardiovascular health of US Hispanic/Latino adults.

ObjectiveMeasurement error in self-reported total sugars intake may obscure associations between sugars consumption and health outcomes, and the sum of 24 h urinary sucrose and fructose may serve as a predictive biomarker of total sugars intake.DesignThe Study of Latinos: Nutrition & Physical Activity Assessment Study (SOLNAS) was an ancillary study to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) cohort. Doubly labelled water and 24 h urinary sucrose and fructose were used as biomarkers of energy and sugars intake, respectively. Participants’ diets were assessed by up to three 24 h recalls (88 % had two or more recalls). Procedures were repeated approximately 6 months after the initial visit among a subset of ninety-six participants.SettingFour centres (Bronx, NY; Chicago, IL; Miami, FL; San Diego, CA) across the USA.SubjectsMen and women (n 477) aged 18–74 years.ResultsThe geometric mean of total sugars was 167·5 (95 % CI 154·4, 181·7) g/d for the biomarker-predicted and 90·6 (95 % CI 87·6, 93·6) g/d for the self-reported total sugars intake. Self-reported total sugars intake was not correlated with biomarker-predicted sugars intake (r=−0·06, P=0·20, n 450). Among the reliability sample (n 90), the reproducibility coefficient was 0·59 for biomarker-predicted and 0·20 for self-reported total sugars intake.ConclusionsPossible explanations for the lack of association between biomarker-predicted and self-reported sugars intake include measurement error in self-reported diet, high intra-individual variability in sugars intake, and/or urinary sucrose and fructose may not be a suitable proxy for total sugars intake in this study population.

PURPOSE: It has been hypothesized that leptin-induced appetite suppression is impaired in obese individuals, but little human evidence is available documenting this. We investigated relations between serum leptin and total energy intake using INTERLIPID/INTERMAP data on Japanese-Americans in Hawaii and Japanese in Japan. METHODS: Serum leptin and nutrient intakes were examined by standardized methods in men and women aged 40–59 years from two population samples, one Japanese-American in Hawaii (88 men, 94 women), the other Japanese in central Japan (123 men, 111 women). Multiple linear regression analyses stratified by BMI category (

Recent guidelines highlight the importance of improving cardiovascular health in the general population in addition to disease prevention among high risk individuals. We investigated factors associated with ethnic and nativity-related differences in the prevalence of low cardiovascular risk (optimal levels of all major cardiovascular risk factors).We used logistic regression to estimate differences in likelihood of being low risk (not currently smoking; no diabetes; untreated total cholesterol200mg/dL; untreated blood pressure120/80; and body mass index25 kg/m(2)) among 8693 foreign- and U.S.-born Mexican-American and non-Hispanic White 2003-2008 U.S. National Health and Nutrition Examination Survey participants before and after adjustment for socioeconomic, lifestyle, and acculturation-related factors.Foreign-born Mexican-Americans were more likely to be low risk than non-Hispanic Whites after adjustment for all covariates (Odds Ratio [OR]: 1.53; 95% Confidence Interval [CI]: 1.00, 2.34). In contrast, U.S.-born Mexican-Americans were less likely to be low risk compared to Whites (OR: 0.60; 95% CI: 0.43, 0.84). Differences between foreign-born and U.S.-born Mexican-Americans were largely attenuated after adjustment for acculturation indicators.Our findings support the healthy migrant hypothesis and suggest that acculturation-related factors may be important drivers of ethnic and nativity-related differences in low cardiovascular risk.

Background— A nutrient-wide approach may be useful to comprehensively test and validate associations between nutrients (derived from foods and supplements) and blood pressure (BP) in an unbiased manner. Methods and Results— Data from 4680 participants aged 40 to 59 years in the cross-sectional International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) were stratified randomly into training and testing sets. US National Health and Nutrition Examination Survey (NHANES) four cross-sectional cohorts (1999–2000, 2001–2002, 2003–2004, 2005–2006) were used for external validation. We performed multiple linear regression analyses associating each of 82 nutrients and 3 urine electrolytes with systolic and diastolic BP in the INTERMAP training set. Significant findings were validated in the INTERMAP testing set and further in the NHANES cohorts (false discovery rate P Conclusions— We identified significant inverse associations between B vitamins and BP, relationships hitherto poorly investigated. Our analyses represent a systematic unbiased approach to the evaluation and validation of nutrient-BP associations.

Background: Clinical trial data show that reduction in total energy intake enhances weight loss regardless of the macronutrient composition of the diet. Few studies have documented dietary patterns or nutrient intakes that favor leanness [BMI (in kg/m2) ≤25] in free-living populations. Objective: This investigation examined associations of usual energy, food, and nutrient intakes with BMI among US participants of the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP). Design: The INTERMAP is an international cross-sectional study of dietary factors and blood pressure in men and women (ages 40–59 y) that includes 8 US population samples. The present study included data from 1794 Americans who were not consuming a special diet and who provided four 24-h dietary recalls and 2 timed 24-h urine collections. Multivariable linear regression with the residual method was used to adjust for energy intake; sex-specific associations were assessed for dietary intakes and urinary excretions with BMI adjusted for potential confounders including physical activity. Results: Lower energy intake was associated with lower BMI in both sexes. Univariately, higher intakes of fresh fruit, pasta, and rice and lower intakes of meat were associated with lower BMI; these associations were attenuated in multivariable analyses. Lower urinary sodium and intakes of total and animal protein, dietary cholesterol, saturated fats, and heme iron and higher urinary potassium and intakes of carbohydrates, dietary fiber, and magnesium were associated with lower BMI in both sexes. Conclusion: The consumption of foods higher in nutrient-dense carbohydrate and lower in animal protein and saturated fat is associated with lower total energy intakes, more favorable micronutrient intakes, and lower BMI.

Information on dietary supplements, medications, and other xenobiotics in epidemiologic surveys is usually obtained from questionnaires and is subject to recall and reporting biases. The authors used metabolite data obtained from hydrogen-1 (or proton) nuclear magnetic resonance ( 1H NMR) analysis of human urine specimens from the International Study of Macro-/Micro-Nutrients and Blood Pressure (INTERMAP Study) to validate self-reported analgesic use. Metabolic profiling of two 24-hour urine specimens per individual was carried out for 4,630 participants aged 40-59 years from 17 population samples in Japan, China, the United Kingdom, and the United States (data collection, 1996-1999). 1H NMR-detected acetaminophen and ibuprofen use was low (�4%) among East Asian population samples and higher (>16%) in Western population samples. In a comparison of self-reported acetaminophen and ibuprofen use with 1H NMR-detected acetaminophen and ibuprofen metabolites among 496 participants from Chicago, Illinois, and Belfast, Northern Ireland, the overall rate of concordance was 81%-84%; the rate of underreporting was 15%-17%; and the rate of underdetection was approximately 1%. Comparison of self-reported unspecified analgesic use with 1H NMR-detected acetaminophen and ibuprofen metabolites among 2,660 Western INTERMAP participants revealed similar levels of concordance and underreporting. Screening for urinary metabolites of acetaminophen and ibuprofen improved the accuracy of exposure information. This approach has the potential to reduce recall bias and other biases in epidemiologic studies for a range of substances, including pharmaceuticals, dietary supplements, and foods. © 2012 The Author.

Previously, we found significantly higher serum leptin in Japanese-Americans in Hawaii than Japanese in Japan. We investigated whether differences in dietary and other lifestyle factors explain higher serum leptin concentrations in Japanese living a Western lifestyle in Hawaii compared with Japanese in Japan.Serum leptin and nutrient intakes were examined by standardized methods in men and women ages 40-59 years from two population samples, one Japanese-American in Hawaii (88 men, 94 women), the other Japanese in central Japan (123 men, 111 women). Multiple linear regression models were used to assess role of dietary and other lifestyle traits in accounting for serum leptin difference between Hawaii and Japan. Mean leptin was significantly higher in Hawaii than Japan (7.2 ± 6.8 vs 3.7 ± 2.3 ng/ml in men, P0.0001; 12.8 ± 6.6 vs 8.5 ± 5.0 in women0.0001). In men, higher BMI in Hawaii explained over 90% of the difference in serum leptin; in women, only 47%. In multiple linear regression analyses in women, further adjustment for physical activity and dietary factors--alcohol, dietary fiber, iron--produced a further reduction in the coefficient for the difference, total reduction 70.7%; P-value for the Hawaii-Japan difference became 0.126.The significantly higher mean leptin concentration in Hawaii than Japan may be attributable largely to differences in BMI. Differences in nutrient intake in the two samples were associated with only modest relationship to the leptin difference.

Individuals with favorable levels of readily measured cardiovascular disease (CVD) risk factors (low risk, LR) experience low long-term rates of CVD mortality and greater longevity. The purpose of the current study was to compare nutrient/food intakes of LR participants with participants not LR in the INTERMAP study.Men and women (40-59 years) from 17 population samples in four countries (China, Japan, UK, US) provided four 24-h dietary recalls and two timed 24-h urine collections. LR was defined as meeting all of the following CVD risk criteria: systolic/diastolic blood pressure (BP) ≤ 120/ ≤ 80 mmHg; no drug treatment for high BP, hyperlipidemia, or CVD; non-smoking; BMI25.0 kg/m(2) (US, UK) or23.0 kg/m(2) (China, Japan); alcohol consumption26.0 g/day (men)/13.0 g/day (women); and no history of diabetes or CVD. Multivariate logistic regression was used to examine associations of nutrient/food intakes with LR.LR individuals reported higher intake of vegetable protein, fiber, magnesium, non-heme iron, potassium; lower energy intake; lower intake of cholesterol, saturated fatty acids, animal protein; and lower 24-h urinary sodium compared with individuals not LR. With regard to foods, LR individuals reported higher intake of fruits, vegetables, grains, pasta/rice, fish; lower intakes of meats, processed meats, high-fat dairy, and sugar-sweetened beverages than individuals not LR.Lower energy intake and differential intake of multiple specific nutrients and foods are characteristic of individuals at low risk for developing CVD. Identification of dietary habits associated with LR is important for further development of public health efforts aimed at reduction/prevention of CVD.

OBJECTIVE: A direct relationship of dietary cholesterol to blood pressure of men has been reported in a few observational studies from the USA. It is not clear whether this association prevails consistently, for example, in populations with varied dietary habits, across ethnic groups, and sexes. Cross-sectional data from the International Study of Macro/Micro-nutrients and Blood Pressure (INTERMAP) were used to assess relations of dietary cholesterol intake to blood pressure in men and women from four countries. METHODS: Data include 83 nutrients from four multipass 24-h dietary recalls and two-timed 24-h urine collections; eight blood pressure readings, and questionnaire data, for 4680 participants ages 40-59 years from 17 population samples in Japan, People's Republic of China, UK, and USA. RESULTS: With sequential models to control for multiple possible confounders (dietary, other), linear regression analyses showed that dietary cholesterol was directly related to SBP for all participants and for nonhypertensive individuals, but not to DBP. With adjustment for 12 variables, estimated SBP differences with 2SD for higher cholesterol intake (131.0 mg/1000 kcal) were 0.9 mmHg (P < 0.05) for all participants and 1.1 mmHg (P < 0.01) for nonhypertensive individuals, findings attenuated with addition of height and weight to the model. CONCLUSION: INTERMAP found a low-order, positive relationship of dietary cholesterol intake to SBP with control for multiple possible confounders. Reduction of dietary cholesterol intake may contribute to prevention and control of adverse blood pressure levels in general populations. J Hypertens

Rates of heart disease and stroke vary markedly between north and south China. A 1H NMR spectroscopy-based metabolome-wide association approach was used to identify urinary metabolites that discriminate between southern and northern Chinese population samples, to investigate population biomarkers that might relate to the difference in cardiovascular disease risk. NMR spectra were acquired from two 24-h urine specimens per person for 523 northern and 244 southern Chinese participants in the INTERMAP Study of macro/micronutrients and blood pressure. Discriminating metabolites were identified using orthogonal partial least squares discriminant analysis and assessed for statistical significance with conservative family wise error rate < 0.01 to minimize false positive findings. Urinary metabolites significantly ((P < 1.2 × 10-16 to 2.9 × 10-69) higher in northern than southern Chinese populations included dimethylglycine, alanine, lactate, branched-chain amino acids (isoleucine, leucine, valine), N-acetyls of glycoprotein fragments (including uromodulin), N-acetyl neuraminic acid, pentanoic/heptanoic acid, and methylguanidine; metabolites significantly (P < 1.1 × 10-12 to 2 × 10-127) higher in the south were gut microbial cometabolites (hippurate, 4-cresyl sulfate, phenylacetylglutamine, 2-hydroxyisobutyrate), succinate, creatine, scyllo-inositol, prolinebetaine, and trans-aconitate. These findings indicate the importance of environmental influences (e.g., diet), endogenous metabolism, and mammalian-gut microbial cometabolism, which may help explain north-south China differences in cardiovascular disease risk. © 2010 American Chemical Society.

Background: New food biomarkers are needed to objectively evaluate the effect of diet on health and to check adherence to dietary recommendations and healthy eating patterns. Objective: We developed a strategy for food biomarker discovery, which combined nutritional intervention with metabolic phenotyping and biomarker validation in a large-scale epidemiologic study. Design: We administered a standardized diet to 8 individuals and established a putative urinary biomarker of fruit consumption by using 1 H nuclear magnetic resonance (NMR) spectroscopic profiling. The origin of the biomarker was confirmed by using targeted NMR spectroscopy of various fruit. Excretion kinetics of the biomarker were measured. The biomarker was validated by using urinary NMR spectra from UK participants of the INTERMAP (International Collaborative Study of Macronutrients, Micronutrients, and Blood Pressure) (n = 499) in which citrus consumption was ascertained from four 24-h dietary recalls per person. Finally, dietary patterns of citrus consumers (n = 787) and nonconsumers (n = 1211) were compared. Results: We identified proline betaine as a putative biomarker of citrus consumption. High concentrations were observed only in citrus fruit. Most proline betaine was excreted � 14 h after a firstorder excretion profile. Biomarker validation in the epidemiologic data showed a sensitivity of 86.3% for elevated proline betaine excretion in participants who reported citrus consumption and a specificity of 90.6% (P , 0.0001). In comparison with noncitrus consumers, citrus consumers had lower intakes of fats, lower urinary sodium-potassium ratios, and higher intakes of vegetable protein, fiber, and most micronutrients. Conclusion: The biomarker identification and validation strategy has the potential to identify biomarkers for healthier eating patterns associated with a reduced risk of major chronic diseases. The trials were registered at clinicaltrials.gov as NCT01102049 and NCT01102062. Am J Clin Nutr 2010;92:436‐43.

The application of a (1)H nuclear magnetic resonance (NMR) spectroscopy-based screening method for determining the use of two widely available analgesics (acetaminophen and ibuprofen) in epidemiologic studies has been investigated. We used samples and data from the cross-sectional INTERMAP Study involving participants from Japan (n = 1145), China (n = 839), U.K. (n = 501), and the U.S. (n = 2195). An orthogonal projection to latent structures discriminant analysis (OPLS-DA) algorithm with an incorporated Monte Carlo resampling function was applied to the NMR data set to determine which spectra contained analgesic metabolites. OPLS-DA preprocessing parameters (normalization, bin width, scaling, and input parameters) were assessed systematically to identify an optimal acetaminophen prediction model. Subsets of INTERMAP spectra were examined to verify and validate the presence/absence of acetaminophen/ibuprofen based on known chemical shift and coupling patterns. The optimized and validated acetaminophen model correctly predicted 98.2%, and the ibuprofen model correctly predicted 99.0% of the urine specimens containing these drug metabolites. The acetaminophen and ibuprofen models were subsequently used to predict the presence/absence of these drug metabolites for the remaining INTERMAP specimens. The acetaminophen model identified 415 out of 8436 spectra as containing acetaminophen metabolite signals while the ibuprofen model identified 245 out of 8604 spectra as containing ibuprofen metabolite signals from the global data set after excluding samples used to construct the prediction models. The NMR-based metabolic screening strategy provides a new objective approach for evaluation of self-reported medication data and is extendable to other aspects of population xenometabolome profiling.

Raised blood pressure is a leading cause of morbidity and mortality worldwide; improved nutritional approaches to population-wide prevention are required. Few data are available on dietary phosphorus and blood pressure and none are available on possible combined effects of phosphorus, magnesium, and calcium on blood pressure. The International Study of Macro- and Micro-Nutrients and Blood Pressure is a cross-sectional epidemiologic study of 4680 men and women ages 40 to 59 from 17 population samples in Japan, China, United Kingdom, and United States. Blood pressure was measured 8 times at 4 visits. Dietary intakes were obtained from four 24-hour recalls plus data on supplement use. Dietary phosphorus was inversely associated with blood pressure in a series of predefined multiple regression models, with the successive addition of potential confounders, both nondietary and dietary. Estimated blood pressure differences per 232 mg/1000 kcal (2 SD) of higher dietary phosphorus were −1.1 to −2.3 mm Hg systolic/−0.6 to −1.5 mm Hg diastolic (n=4680) and −1.6 to −3.5 mm Hg systolic/−0.8 to −1.8 mm Hg diastolic for 2238 “nonintervened” individuals, ie, those without special diet/nutritional supplements or diagnosis/treatment for cardiovascular disease or diabetes. Dietary calcium and magnesium, correlated with phosphorus (partial r =0.71 and r =0.68), were inversely associated with blood pressure. Blood pressures were lower by 1.9 to 4.2 mm Hg systolic/1.2 to 2.4 mm Hg diastolic for people with intakes above versus below country-specific medians for all 3 of the minerals. These results indicate the potential for increased phosphorus/mineral intake to lower blood pressure as part of the recommendations for healthier eating patterns for the prevention and control of prehypertension and hypertension.

Findings from short-term randomized trials indicate that dietary supplements of omega-3 polyunsaturated fatty acids (PFA) lower blood pressure of hypertensive persons, but effect size in nonhypertensive individuals is small and nonsignificant. Data are lacking on food omega-3 PFA and blood pressure in general populations. The International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP) is an international cross-sectional epidemio- logic study of 4680 men and women ages 40 to 59 from 17 population-based samples in China, Japan, United Kingdom, and United States. We report associations of food omega-3 PFA intake (total, linolenic acid, long-chain) of individuals with blood pressure. Systolic and diastolic blood pressure were measured 8 times at 4 visits. With several models to control for possible confounders (dietary, other), linear regression analyses showed inverse relationship of total omega-3 PFA from food (percent kilocalories, from four 24-hour dietary recalls) to systolic and diastolic blood pressures. With adjustment for 17 variables, estimated systolic blood pressure/diastolic blood pressure differences with 2 standard deviation higher (0.67% kcal) omega-3 PFA were 0.55/0.57 mm Hg (Z-score 1.33, 2.00); for 2238 persons without medical or dietary intervention, 1.01/0.98 mm Hg (Z 1.63, 2.25); for 2038 nonhypertensive persons from this sub-cohort, 0.91/0.92 mm Hg (Z 1.80, 2.38). For linolenic acid (largely from vegetable foods), blood pressure differences were similar, eg, for the 2238 "nonintervened" individuals, 0.97/0.87 mm Hg (Z 1.52, 1.95); blood pressure differences were 0.32/0.45 mm Hg for long-chain omega-3 PFA (largely from fish). In summary, food omega-3 PFA intake related inversely to blood pressure, including in nonhypertensive persons, with small estimated effect size. Food omega-3 PFA may contribute to prevention and control of adverse blood pressure levels. (Hypertension. 2007;50:313-319.)

OBJECTIVE: This study is to examine the relationship between dietary selenium intake and 24-h urinary selenium excretion in Japanese population samples participating in the INTERMAP Study. METHODS: Using highly standardized methods, we assessed individual dietary selenium intake from four 24-h dietary recalls and measured urinary selenium excretion in two timed 24-h urine collections in 1145 Japanese participants (574 men and 571 women) ages 40–59 years in four areas of Japan. RESULTS: The medians of dietary selenium intake were 177.5 μg/day in men and 139.8 μg/day in women; the medians of 24-h urinary selenium excretion were 127.9 μg/day in men and 109.4 μg/day in women, that is, urinary excretion was estimated to be 73% of dietary intake in men and 77% in women. Dietary selenium intake was significantly correlated with 24-h urinary selenium excretion (r = 0.24 in men, r = 0.18 in women; P

Prospective cohort studies have shown inverse associations between fibre intake and CVD, possibly mediated by blood pressure (BP). However, little is known about the impact of types of fibre on BP. We examined cross-sectional associations with BP of total, insoluble and soluble fibre intakes. Data were used from the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP) study, including 2195 men and women aged between 40 and 59 years from the USA. During four visits, eight BP, four 24 h dietary recalls and two 24 h urine samples were collected. Linear regression models adjusted for lifestyle and dietary confounders to estimate BP differences per 2 sd higher intakes of total and individual types of fibre were calculated. After multivariable adjustment, total fibre intake higher by 6·8 g/4184 kJ (6·8 g/1000 kcal) was associated with a 1·69 mmHg lower systolic blood pressure (SBP; 95% CI -2·97, -0·41) and attenuated to -1·01 mmHg (95% CI -2·35, 0·34) after adjustment for urinary K. Insoluble fibre intake higher by 4·6 g/4184 kJ (4·6 g/1000 kcal) was associated with a 1·81 mmHg lower SBP (95% CI -3·65, 0·04), additionally adjusted for soluble fibre and urinary K excretion, whereas soluble fibre was not associated with BP. Raw fruit was the main source of total and insoluble fibre, followed by whole grains and vegetables. In conclusion, higher intakes of fibre, especially insoluble, may contribute to lower BP, independent of nutrients associated with higher intakes of fibre-rich foods.

PURPOSE: Low-carbohydrate diets (LCD) are a popular dietary strategy for weight reduction. The effects of LCD on long-term outcome vary depending on type of LCD, possibly due to the fact that effects on cardiometabolic risk factors may vary with different types of LCD. Accordingly, we studied these relations. METHODS: We assessed serum concentrations of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), high-sensitivity C-reactive protein (CRP), total cholesterol, glycated hemoglobin, and uric acid, and nutrient intakes by standardized methods in men and women ages 40–59 years from four population samples of Japanese in Japan (553 men and 544 women, combined). For people consuming usual, animal-based, and plant-based LCDs, we calculated LCD scores, based on relative level of fat, protein, and carbohydrate, by modifying the methods of Halton et al. Instead of calculating scores based on animal or vegetable fat, we used saturated fatty acids (SFA) or monounsaturated fatty acids (MUFA) + polyunsaturated fatty acids (PUFA). RESULTS: In multivariate regression analyses with adjustment for site, age, sex, BMI, smoking, alcohol intake, physical activity, and years of education, all three LCD scores were significantly positively related to HDLc (all P < 0.001), but not to LDLc. The plant-based LCD score was significantly inversely related to log CRP (coefficient = −0.010, P = 0.018). CONCLUSIONS: All three LCD scores were significantly positively related to HDLc. The plant-based LCD score was significantly inversely related to CRP. Carbohydrate intake below 50 % of total energy with higher intakes of vegetable protein and MUFA + PUFA, and lower intakes of SFA may be favorable for reducing cardiometabolic risk factors.

BACKGROUND: Cardiovascular risk factor research has recently broadened its focus based on new data indicating the benefits of low risk, i.e. favorable levels of all major risk factors. The aims of this study were to assess further the relation of low risk to coronary heart disease risk, and implications for prevention. DESIGN: We conducted a prospective population-based Italian study, of 7438 men and 13 009 women aged 35-69 years, with a mean follow-up of 10.4 years and validated first coronary events. METHODS: Baseline coronary heart disease risk was classified into three categories: low risk; unfavorable but not high risk; and high risk. To analyze the relation of these risk profiles to coronary heart disease incidence, age-adjusted, sex-averaged coronary heart disease incidence was calculated for persons free of coronary heart disease and stroke, stratified as baseline low risk, unfavorable but not high risk or high risk. To assess the independent relationship of individual risk factors to coronary heart disease incidence, multivariate proportional hazards models were computed for combinations of risk factors. RESULTS: Only 2.7% of participants met low risk criteria; 81.4% were high risk. Age-adjusted coronary heart disease incidence for the whole cohort was 37.1 out of 10000 person-years (men 59.0; women 15.3). No coronary heart disease events occurred in low-risk men, only two in low-risk women. For women and men who were not high risk, the age-sex standardized coronary heart disease rate was 62% lower than for high-risk participants. Blood pressure, need for antihypertensive medication, smoking, hyperglycemia, diabetes, total and high-density lipoprotein cholesterol were independently related to coronary heart disease risk. CONCLUSIONS: Favorable levels of all modifiable readily measured risk factors - rare among Italian adults - assure minimal coronary heart disease risk. Population-wide prevention is needed, especially improved lifestyles, to increase the proportion of the population at low risk. © 2006 The European Society of Cardiology.

Objective— We investigated whether dietary factors explain higher plasma fibrinogen levels in Japanese emigrants living a Western lifestyle in Hawaii compared with Japanese in Japan. Methods and Results— Plasma fibrinogen and nutrient intakes were examined by standardized methods in men and women 40 to 59 years of age from a Japanese-American sample in Hawaii (100 men and 106 women) and 4 population samples in Japan (569 men and 567 women). Multiple linear regression models were used to examine the relationship between dietary factors and the plasma fibrinogen difference between Hawaii and Japan. Average plasma fibrinogen was significantly higher in Hawaii compared with Japan ( P Conclusions— Higher intake of iron, sugar, and caffeine, in addition to obesity, account largely for higher fibrinogen levels with Westernized lifestyle.

Objectives. We explored differences between Black and White men for cardiovascular disease (CVD) mortality across major risk factor levels. Methods. Major CVD risk factors were measured among 300 647 White and 20 223 Black men aged 35 to 57 years who were screened for the Multiple Risk Factor Intervention Trial (MRFIT). Hazard ratios for CVD deaths for Black and White men over 25 years of follow-up were calculated for subgroups stratified according to risk factor levels. Results. CVD was responsible for 2518 deaths among Black men and 30772 deaths among White men. The age-adjusted Black-to-White CVD hazard ratio was 1.35 (95% confidence interval [CI]=1.29, 1.40); the risk- and income-adjusted ratio was 1.05 (95% CI=1.01, 1.10). CVD mortality rates were dramatically lower in cases of favorable risk profiles. However, fully adjusted Black-to-White CVD hazard ratios within groups at low, intermediate, high, and very high levels of overall risk were 1.76, 1.20, 1.10, and 0.94, respectively. Similar gradients were evident for individual risk factors. Conclusions. Higher CVD mortality rates among Black men were largely mediated by risk factors and income. These data underscore the need for sustained primordial risk factor prevention among Black men.

Objective To assess dietary supplement use and its association with micronutrient intakes and adequacy among 2,195 US men and women aged 40 to 59 years from eight diverse population samples surveyed by the International Population Study on Macronutrients and Blood Pressure. Design Four 24-hour dietary recalls were collected, including information on dietary supplements. The Nutrition Data System (NDS) was used for nutrient analyses. Supplements not in NDS were classified separately (non-NDS). Intake of non-NDS supplements was documented. Participants were classified as not supplement users and supplement users, subclassified—due to concerns about nutritional value—as users of NDS supplements only (mostly vitamins and minerals) and users of non-NDS supplements (eg, botanicals, animal products, and enzymes). To assess effects of supplement use on micronutrient intake and adequacy, mean intakes from supplements, foods, and foods plus supplements were compared with Dietary Reference Intakes. Participants Two thousand one hundred ninety-five US participants; 1,136 used supplements. Statistical Analyses χ 2 tests, multivariate logistic regression, and means were used to assess differences in and factors related to supplement use and to determine dietary adequacy. Results Supplement use was more common among women, older participants, more educated participants, and Asian Americans. Body mass index and current cigarette smoking were significantly and inversely associated with supplement use; past smoking and education were significantly and positively associated with supplement use. Intake from foods plus supplements was considerably higher than from foods alone for vitamins A, C, and E; niacin; folate; and iron. Conclusions Supplement use is common among middle-aged Americans and sizably increases daily intakes of several micronutrients. These data underscore the importance of dietary supplement assessment.

Twenty-four-hour urinary albumin excretion (UAE) is considered the gold standard for determining albumin level in epidemiologic studies, but this measure is inconvenient and often unavailable. Simpler alternatives include the albumin:creatinine ratio (ACR) and urinary albumin concentration (UAC) obtained from a single sample. The authors assessed the strengths and weaknesses of ACR and UAC as alternatives to UAE using albumin measurements from two 24-hour urine samples collected in 1996–1999 from 4,678 participants aged 40–59 years in the International Study of Macronutrients and Blood Pressure (17 population samples from four countries). The authors compared ACR and UAC with regard to correlations with UAE, daily within-person variability, and associations with known predictors of UAE. Rank-order correlations of ACR with UAE were 0.949 and 0.942 for men and women, respectively, versus 0.881 and 0.816 for UAC. Mean within-person coefficients of variation were 34.0–40.0% for the three measures, with the smallest values being observed for UAC. Average correlations with blood pressure were similar for UAE, ACR, and UAC, but the correlation with body mass index was lower for ACR (0.118 for ACR and 0.188 for UAC vs. 0.211 for UAE) because of high correlation between body mass index and creatinine level. Thus, UAC and ACR are acceptable alternatives to the more complex UAE, and the simpler UAC may be preferable to ACR in some respects.