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Background:Accurate assessment of fat intake is essential to examine relationships between diet and disease risk. However, estimating individual intakes of fat quantity by dietary assessment is difficult., Objective:We assessed the association of plasma phospholipid fatty acid levels with dietary intake of fatty acids in the INTERMAP/INTERLIPID study, conducted with a standardized protocol., Methods:The study participants were 1339 men and women ages 40-59 years from five Japanese populations one from Hawaii; four from Japan. Fatty acid intake was estimated from four standardized 24-hour dietary recalls. Plasma phospholipid fatty acid composition was analyzed by gas chromatography. We illustrated the relationship between intake and circulating fatty acid levels using Spearman's rank-correlation coefficients, mean, and median values., Results:Spearman's rank-correlation coefficients between intake (g/d) and circulating fatty acid levels (µg/ml) were -0.03 to 0.21 for saturated fatty acids and monounsaturated fatty acids and -0.04 to 0.32 for trans fatty acids. The coefficients for essential n-3 and n-6 fatty acids were moderate to high, especially for eicosapentaenoic acid (EPA), 0.60; docosahexaenoic acid (DHA), 0.41; and EPA+DHA, 0.51. The circulating levels and intake of marine-derived n-3 fatty acids showed a linear association, at least for the intake of EPA+DHA up to 2.1 g/d., Conclusion:We observed high correlation between intake and circulating levels of marine-derived n-3 fatty acids in participants from Japanese and Japanese-American populations with high and low fish intake. Plasma phospholipid marine-derived n-3 fatty acid measurements are a simple and reliable biomarker for assessing dietary intake.

To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii, in the absence of possible genetic confounders, and cross-sectionally examine the associated modifiable lifestyle factors.Overall, 1,241 (aged 40-59 years) Japanese living in Japan and Japanese-Americans in Hawaii were included. We quantified 130 serum lipid profiles (VLDL 1-5, IDL, LDL 1-6, high-density lipoprotein [HDL] 1-4, and their subfractions) using Bruker'sConcentrations of HDL4, HDL with the smallest particle size, were lower in Japanese than in Japanese-Americans of both sexes. Higher fish-derived omega-3 fatty acid intake and lower alcohol intake were associated with lower HDL4 concentrations. A 1% higher kcal intake of total omega-3 fatty acids was associated with a 9.8- mg/dL lower HDL4. Fish-derived docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid intake were inversely associated with HDL4 concentration. There was no relationship between country, sex, age, or BMI.Japanese and Japanese-Americans can be differentiated based on HDL4 concentration. High fish intake among the Japanese may contribute to their lower HDL4 concentration. Thus, HDL particle size may be an important clinical marker for coronary artery diseases or a fish consumption biomarker.

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.

Several studies have reported a J-shaped relationship between alcohol consumption and coronary heart disease (CHD) risk. However, the mechanisms of this relationship remain unclear. This study aimed to evaluate the relationships of alcohol consumption with established CHD risk factors and with macro-/micro-nutrient intake among Japanese people. Participants were 1,090 Japanese men and women aged 40-59 y enrolled in the INTERLIPID study, excluding former drinkers. Based on two 7-d alcohol records, participants were classified as non-drinkers (0 g/wk), light-drinkers (

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.

It is unclear how long-term medical utilization and costs from diverse care settings and their age-related patterns may differ by cardiovascular health (CVH) status earlier in adulthood. We followed 17,195 participants of the Chicago Heart Association Detection Project Industry (1967–1973) with linked Medicare claims (1992 to 2010). Baseline CVH is a composite measure of blood pressure, body mass index, diabetes, cholesterol, and smoking and includes four mutually exclusive strata: all factors were favorable (5.5%), one or more factors were elevated but none high (20.3%), one factor was high (40.9%), and two or more factors were high (33.2%). We assessed differences in the quantities (using negative binomial models) of and costs (using quantile regressions) for inpatient admissions, ambulatory care, home health care, and others between less favorable and all favorable CVH. All analyses adjusted for baseline age, race, sex, education, age at follow-up, year, state of residence, and death. We found that all favorable CVH in earlier adulthood was associated with lower long-term utilization and costs in all settings and the gap widened with age. Compared to all favorable CVH, the annual number of acute inpatient admissions per person was 79% greater (p-value < 0.001) for poor CVH, the median annual Medicare payment per person was $640 greater (41%, p-value < 0.001), and the mean was $4,628 greater (67%, p-value < 0.001). The cost differences were greatest for acute inpatient, followed by ambulatory, post-acute inpatient, home health, and other. Early prevention efforts may potentially result in compressed all-cause morbidity in later years of age, along with reductions in resource use and health care costs for associated conditions.

Background: Epidemiological evidence links blood pressure (BP) -lowering effects with fruit, vegetables, pulses, nuts but results are inconsistent and often rely on self-administered dietary assessment methods prone to random and systematic errors and potential under- or overestimation of relationships. Objective: To characterize urinary metabolic signatures of plant food intake (fruit, vegetables, pulses, and nuts) and subsequently to assess their associations with BP, validated across cohorts. Methods: We used untargeted metabolic profiling obtained by proton nuclear magnetic resonance spectroscopy ( 1 H NMR) of two timed repeated 24-hour urine collections derived from 2,032 free-living US participants, and replicated among 449 UK participants, all part of the cross-sectional International Study of Macro- and Micronutrients and Blood Pressure (INTERMAP) study. Associations of plant foods intakes from four 24-hour dietary recalls with 7,100 NMR features were evlauted using univariate linear regression analyses. Significant metabolites were structurally identified using analytical and statistical approaches. We compared extensively adjusted associations of plant food intake and urinary metabolites with BP in the total population (N=2,481). All analyses were extensively adjusted for potential confounders and accounted for multiple testing. Results: We found consistent, reproducible relationships of NMR signatures with plant food intake across repeated urine collections and between populations. Eleven urinary metabolites were identified and two remained unknown (1: δ 2.80 (s); 2: δ 1.16(s), 1.67 (s)). Twelve metabolites were directly correlated with plant foods ranging from 0.15 (P≤1x10 -11 ) to 0.49 (P≤5x10 -119 ), and phenylacetylglutamine was inversely associated (r=-0.18, P≤1x10 -5 ). In adjusted analyses, plant food intake was inversely associated with systolic BP (-1.29 mmHg; 95%CI: -2.38,-0.19), but not with diastolic BP. Metabolites inversely associated with systolic BP were hippurate (-2.67 mmHg;-3.71,-1.63), citrate (-2.50 mmHg; -3.55,-1.44), phenylacetylglutamine (-2.26 mmHg; -3.29,-1.23), unknown1 (-2.05 mmHg; -3.06,-1.04), 4-hydroxyhippurate (-1.45 mmHg; -2.44,-0.45), and unknown2 (-1.09 mmHg; -2.09,-0.09); with diastolic BP were phenylacetylglutamine (-1.12 mmHg; -1.84,-0.40), citrate (-1.02 mmHg; -1.76,-0.28), and unknown1 (-1.18 mmHg; -1.88,-0.47). Plant food-systolic BP associations were attenuated by further adjustment for citrate, hippurate, and unknown1, while hydroxyproline, proline and phenylacetylglutamine were potential effect modifiers. Conclusion: Urinary metabolites were consistently associated with plant food intake. Urinary metabolites that may underlie the plant food-BP association were gut-microbial co-metabolites and tricarboxylic acid cycle intermediates.

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: 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.

Correction to: Nature Food https://doi.org/10.1038/s43016-020-0093-y, published online 22 June 2020.

Background Many studies have reported the J-shaped relationship between alcohol consumption and coronary heart disease (CHD) risk; therefore, light-drinkers is generally recognized to be associated with the lower risk of CHD. However, the mechanisms of lower risk for CHD in light-drinkers are still unclear. Alcohol drinking status is likely to be associated with not only CHD risk factors but also dietary intake. Nevertheless, few studies report these relationships in detail. Purpose The purpose of this study is to evaluate the relationships of alcohol drinking status with CHD classical risk factors and the intake of macro- and micro- nutrients in Japanese. Methods Study participants were 1,090 Japanese men and women aged 40–59 years from The INTERLIPID study excepted for 55 individuals who had missing data (n=26) and were past-drinkers (n=29). Alcohol consumption was assessed with two 7-day alcohol records, and average ethanol intake (per week) was calculated. Participants were classified into following 4 groups: non-drinkers (0g/week), light-drinkers ( Results Serum HDL cholesterol levels increased and LDL cholesterol levels decreased with increasing alcohol consumption. Systolic and diastolic BP increased with increasing alcohol consumption. J-shaped relationships with alcohol consumption were observed for the proportion of current smoker, number of cigarettes, and the prevalence of hypertension; that is, light-drinkers was lowest among all groups. The prevalence of dyslipidemia was the highest in non-drinkers, and decreased with increasing alcohol consumption. In heavy-drinkers, total energy (kcal/day) was the highest, but energy intake without alcohol (kcal/day) was the lowest. For macronutrients, the intake of carbohydrate (%kcal) decreased, and the intakes of total and animal protein (%kcal) increased with increasing alcohol consumption. The intakes of total cholesterol (mg/1000kcal) and sodium (mg/1000kcal) increased, and total fiber (g/1000kcal) decreased with increasing alcohol consumption. These associations were similar in men and women. Conclusions Alcohol consumption was related with not only CHD classical risk factors but also the intake of macro- and micro-nutrients. Non-drinkers had a higher proportion of some CHD risk factors than light-drinkers. These results might influence on J-shaped relationship between alcohol consumption and CHD risk. Acknowledgement/Funding 1: Ministry of Education, Science, Sports, and Culture of Japan, 2: National Institutes of Health, Bethesda, MD, USA

Background: Magnesium (Mg) and other mineral intakes are vital contributors to a healthy diet and appear to have a modest effect on the risk of hypertension. Studies suggest that supplemental Mg can significantly lower blood pressure (BP). Here, we investigate associations of total Mg consumption with the level of its urinary metabolomic biomarkers, and BP. Method: We used cross-sectional data from the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP) on 4269 men and women aged 40-59 years from Japan, China, United Kingdom, and United States (US). Regression coefficients with BP per 2 standard deviation (SD) higher dietary Mg from food plus supplement (obtained from 24-hr dietary recalls), urinary Mg (measured by atomic absorption flame photometry) and small molecules (analysed by direct injection mass spectrometry) were estimated using multivariable models, adjusted for age, gender, population sample, intake of total energy and other confounders (see Table). To estimate overall association, country-specific regression coefficients were pooled, weighted by inverse of their variance. Results: Average Mg intakes were 454 (SD=207) mg/day for 770 persons who reported Mg supplementation (89% from US), and 300 (SD=101) mg/day for those who did not. High correlation was found between Mg intake from food plus supplements with urinary Mg ( r =0.38, PP =6x10 -5 ). Urinary Mg excretion higher by 2.66 mmol/day was associated with a diastolic BP difference of -1.02 mm Hg (P=0.02). There was a non-significant inversed association between ascorbic acid and BP in some multivariable regression models. Conclusion: Higher intake of Mg, including supplements, was associated with lower BP levels.

Background: Evidence relating to the benefit of fish consumption on blood pressure (BP) management is inconclusive. Recent research has suggested that different patterns in fish consumption across geographic regions may modify the association between fish intake and cardiovascular outcomes. Objectives: To investigate the associations between fish intake and BP in Asian and Western population groups and to explore the associations between candidate urinary biomarkers of fish intake and BP. Methods: The International Study on Macro/Micronutrients and Blood Pressure (INTERMAP) surveyed 4680 men and women aged 40-59 years from four countries: United States of America (US), United Kingdom (UK), Peoples Republic of China (PRC) and Japan between 1996 and 1999. Standardized quality-controlled measures collected included: four 24-hour dietary recalls and two 24-hour urine collections and eight BP measurements. Proton nuclear magnetic resonance spectra of urine specimens were acquired, and partial correlation analysis adjusted for age, sex, and sample/centre were performed to identify candidate peak variables correlating to total fish and shellfish intakes. Multivariable linear regression models conducted on pooled data by geographic region (Asian: Japan and PRC; n = 1984, and Western: UK and US; n = 2696) estimated differences in BP per 2SD (33.4g/1000kcal) of total fish intake and identified urinary metabolites. Results: Japan reported the highest daily intake of fish (mean 40.3, SD 22.3 g/1000kcal) with 99% of the cohort classified as consuming fish. Mean daily fish consumption patterns were comparable between the US (9.0 SD 15.0 g/1000kcal; 53% consumers) and UK (8.5 SD, 12.4 g/1000kcal; 55% consumers). No associations were observed between total fish intake and BP in individual cohorts or by geographic region. Trimethylamine N-oxide (TMAO), taurine and homarine were identified as candidate urinary biomarkers of fish intake. Homarine showed a strong correlation with shellfish intake ( r =0.43, P β 0.32 95%CI 0.14, 0.50, P = 0.0006; fully adjusted for lifestyle and dietary intakes), this remained significant following adjustment for body mass index ( β 0.23, 95%CI 0.05, 0.41, P = 0.012). Taurine and homarine were not associated with BP. Conclusion: We observed no association between fish consumption and BP across Asian or Western populations. The differential association between urinary TMAO and DBP in Western and Asian population groups requires further investigation.

Background: Data regarding associations of egg intake, a major source of dietary cholesterol, with blood pressure (BP) are limited, especially from large, diverse population samples, and findings have been inconsistent. Methods: Associations between egg intake and BP were examined using data on 4680 men and women, aged 40-59 years, between 1996 and 1999, from the INTERMAP study that included 17 population samples in the United States (US), United Kingdom (UK), China and Japan. Data were collected from four 24-hour dietary recalls, 2 timed 24-hour urine collections and 8 BP measurements. Egg intake was calculated as amount consumed per day using the Nutrient Data Software for Research (University of Minnesota, USA). Multivariable linear regression models were used to estimate differences in BP per 2-SD of egg intake (50.71g/day). Country-specific regression coefficients were pooled, weighted by inverse of their variance to estimate overall association. Results: Of 4680 participants, 50% were women. Daily egg intake was highest among individuals from Japan (mean 37.74, SD 24.3g/day). With adjustment for age, sex, population sample, and average dietary energy intake/day, egg intake was significantly associated with SBP in both the pooled sample and the US sample. With each 2-SD higher egg intake, US mean SBP was significantly higher by 2mmHg (Model 1-Table). The associations remained significant with further adjustment for education level, family history of hypertension, smoking status, and use of dietary supplement (Model 2-Table). With further adjustment for urinary sodium and urinary potassium or BMI, the associations were no longer significant. No association was found for other countries, and for DBP. Conclusion: An adverse association between egg intake and SBP was observed in the US but not in other countries. Notably, this association was strongly attenuated by urinary sodium, urinary potassium and BMI. Further research is needed to better understand the relation of egg intake and BP.

Metabolic profiling of biological samples provides important insights into multiple physiological and pathological processes but is hindered by a lack of automated annotation and standardized methods for structure elucidation of candidate disease biomarkers. Here we describe a system for identifying molecular species derived from nuclear magnetic resonance (NMR) spectroscopy-based metabolic phenotyping studies, with detailed information on sample preparation, data acquisition and data modeling. We provide eight different modular workflows to be followed in a recommended sequential order according to their level of difficulty. This multi-platform system involves the use of statistical spectroscopic tools such as Statistical Total Correlation Spectroscopy (STOCSY), Subset Optimization by Reference Matching (STORM) and Resolution-Enhanced (RED)-STORM to identify other signals in the NMR spectra relating to the same molecule. It also uses two-dimensional NMR spectroscopic analysis, separation and pre-concentration techniques, multiple hyphenated analytical platforms and data extraction from existing databases. The complete system, using all eight workflows, would take up to a month, as it includes multi-dimensional NMR experiments that require prolonged experiment times. However, easier identification cases using fewer steps would take 2 or 3 days. This approach to biomarker discovery is efficient and cost-effective and offers increased chemical space coverage of the metabolome, resulting in faster and more accurate assignment of NMR-generated biomarkers arising from metabolic phenotyping studies. It requires a basic understanding of MATLAB to use the statistical spectroscopic tools and analytical skills to perform solid phase extraction (SPE), liquid chromatography (LC) fraction collection, LC-NMR-mass spectroscopy and one-dimensional and two-dimensional NMR experiments.

Objective: Metabolic phenotyping (metabolomics) captures systems-level information on metabolic processes by simultaneously measuring hundreds of metabolites using spectroscopic techniques. Concentrations of these metabolites are affected by genetic (host, microbiome), environmental and dietary factors and may provide insights into biochemical pathways underlying raised blood pressure (BP) in populations. Design and method: Two separate, timed 24hr urine specimens were obtained from 2,031 women and men, aged 40–59, from 8 USA population samples in the INTERMAP Study. Proton Nuclear Magnetic Resonance (1H NMR) was used to characterize a urinary metabolic signature; this was unaffected by diurnal variability and sampling time as it captures end-products of metabolism over a 24hr period. Demographic, population, medical, lifestyle and anthropometric factors were accounted for in regression models to define a urinary metabolic phenotype associated with BP. Results: 29 structurally identified urinary metabolites covaried with systolic BP (SBP), after adjustment for demographic variables, and 18 metabolites with diastolic BP (DBP), with 16 metabolites overlapping between SBP and DBP. These included metabolites related to energy metabolism, renal function, diet and gut microbiota. After adjustment for medical and lifestyle covariates, 22/14 metabolites remained associated with SBP/DBP. Joint covariate-metabolite penalized regression models identified Body Mass Index, age and family history as most important contributors, with 14 metabolites, including gut microbial co-metabolites, also included in the model. Metabolites were mapped in a symbiotic metabolic reaction network, that includes reactions mediated by 3,344 commensal gut microbial species, to highlight affected pathways (Figure). Significant single nucleotide polymorphisms (SNPs) from genome-wide association studies on cardiometabolic risk factors were mapped to genes in this network. This revealed multiple subnetworks of gene-metabolite pairs related to BP and related cardiometabolic factors and includes 54 SNPs directly related to reactions in the network. These 54 SNPs were then used as instrumental variables to test for possible causative metabolite-BP associations in an external cohort (Airwave Study).

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.

Introduction: There is limited evidence on the long-term persistence of antihypertensive therapy. Methods: We linked Medicare Part D Event data (2006 - 2012) for participants of the Chicago Heart Association Detection Project Industry Study (1967 - 1972) who were diagnosed with essential hypertension and had at least one drug (any drug) event (N = 5,578). Antihypertensive medications and therapeutic classes were identified using the Medi-Span Electronic Drug File v2. The adherence rate was defined by the proportion of days covered (PDC) in 6-month intervals from the first fill of antihypertensive medication and was calculated separately for each therapeutic class. Additionally, to identify adherence patterns as the number of medications an individual used increased, we calculated adherence rates for time intervals after each subsequent medication was filled. Fractional response generalized linear models were used to identify predictors of the adherence patterns. Results: At 6 months from the first fill, the median adherence rate was 0.72 and the mean was 0.56. Roughly 30% of the individuals in the sample did not fill any antihypertensive medication for the duration of the study. Adherence rates declined substantially over time, but the largest drop occurred within the first 12 months. Compared to individuals with a high school degree or less, individuals with more than a high school degree were on average 8.6% more adherent (p-value Conclusion: Adherence to antihypertensive therapy decreased significantly over time and with greater medication burden. Interventions are needed to improve persistence in antihypertensive therapy, particularly among those taking multiple medications.

Background: Urinary sodium-to-potassium ratio may be more strongly related to blood pressure and cardiovascular disease than either urinary sodium or potassium alone. The casual urine sodium-to-potassium ratio is readily obtained, can provide prompt on-site feedback, and with repeated measurements may provide useful individual estimates of 24-hour urinary sodium-to-potassium ratio. The World Health Organization (WHO) has recently published guidelines for sodium and potassium intakes, but no generally accepted guideline prevails for favorable sodium-to-potassium ratio. Objective: Our primary aim was to compare the level of urinary Na/K ratio with the current recommended levels of Na and K intakes suggested in WHO guidelines. Methods: INTERSALT is an international study on associations of multiple urinary variables, with blood pressure (BP), based on standardized data on 24-hour and casual urinary electrolyte excretion in 10,065 individuals from 52 population samples in 32 countries. The associations between casual urinary sodium-to-potassium ratio and 24-hour urinary sodium and potassium excretion of individuals were assessed by correlation and stratification analysis. Results: Mean 24-hour sodium and potassium excretions were 156.0 mmol/24h and 55.2 mmol/24h; mean 24-hour urinary sodium-to-potassium ratio was 3.24. Pearson-r correlation coefficients of casual urinary sodium-to-potassium ratio with 24-hour sodium and potassium excretions were 0.42 and -0.34, respectively, and these were 0.57 and -0.48 for 24-hour urinary sodium-to-potassium ratio. The proportion of participants with estimated sodium chloride intake below the WHO recommended guideline of 85 mmol/day was 61.1% for those with casual urinary sodium-to-potassium ratio less than 1, and 96.3% where the 24-hour ratio was less than 1. For potassium, the proportion of people with potassium intake more than the WHO recommended guideline of 90 mmol/day was 21.3% where the casual urinary sodium-to-potassium ratio was less than 1 and 28.6% for the 24-hour urinary sodium-to-potassium ratio. Conclusions: Casual urinary sodium-to-potassium ratio less than 1 may be a useful indicator of adherence to the World Health Organization recommended levels of sodium intake, and to a lesser extent potassium intake in diverse different populations.

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

Adverse blood pressure (BP) is a major independent risk factor for epidemic cardiovascular diseases affecting almost one-quarter of the adult population worldwide. Dietary intake is a major determinant in the development and progression of high BP. Lifestyle modifications, including recommended dietary guidelines, are advocated by the American Society of Hypertension, the International Society of Hypertension, the Japanese Society of Hypertension, and many other organisations for treating all hypertensive people, prior to initiating drug therapy and as an adjunct to medication in persons already on drug therapy. Lifestyle modification can also reduce high BP and prevent development of hypertension. This review synthesizes results from the International Study of Macro/Micronutrients and Blood Pressure (INTERMAP), 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, published over the past few years on cross cultural BP differences. INTERMAP has previously reported that intakes of vegetable protein, glutamic acid, total and insoluble fibre, total polyunsaturated fatty acid and linoleic acid, total n-3 fatty acid and linolenic acid, phosphorus, calcium, magnesium, and non-heme iron were inversely related to BP. Direct associations of sugars (fructose, glucose and sucrose) and sugar-sweetened beverages, (especially combined with high sodium intake) cholesterol, glycine and alanine, and oleic acid from animal sources with BP were also reported by the INTERMAP Study.

Background Isolated systolic hypertension (ISH), defined as systolic blood pressure (SBP) ≥140 mm Hg and diastolic blood pressure (DBP) Objective The aim of this study was to assess the risk for cardiovascular disease (CVD) with ISH in younger and middle-aged adults. Methods CVD risks were explored in 15,868 men and 11,213 women 18 to 49 years of age (mean age 34 years) at baseline, 85% non-Hispanic white, free of coronary heart disease (CHD) and antihypertensive therapy, from the Chicago Heart Association Detection Project in Industry study. Participant classifications were as follows: 1) optimal-normal blood pressure (BP) (SBP Results During a 31-year average follow-up period (842,600 person-years), there were 1,728 deaths from CVD, 1,168 from CHD, and 223 from stroke. Cox proportional hazards models were adjusted for age, race, education, body mass index, current smoking, total cholesterol, and diabetes. In men, with optimal-normal BP as the reference stratum, hazard ratios for CVD and CHD mortality risk for those with ISH were 1.23 (95% confidence interval [CI]: 1.03 to 1.46) and 1.28 (95% CI: 1.04 to 1.58), respectively. ISH risks were similar to those with high-normal BP and less than those associated with isolated diastolic hypertension and systolic diastolic hypertension. In women with ISH, hazard ratios for CVD and CHD mortality risk were 1.55 (95% CI: 1.18 to 2.05) and 2.12 (95% CI: 1.49 to 3.01), respectively. ISH risks were higher than in those with high-normal BP or isolated diastolic hypertension and less than those associated with systolic diastolic hypertension. Conclusions Over long-term follow-up, younger and middle-aged adults with ISH had higher relative risk for CVD and CHD mortality than those with optimal-normal BP.

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: HCHS/SOL showed that a sizeable proportion of Hispanics/Latinos (80% of men, 71% of women) had at least 1 major CVD risk factor (RF), with marked variations by ethnic background. Little is known about changes in CVD RF profiles over time in this population. Objective: To describe ~6-year changes in CVD RF profiles and examine associations with demographic and socioeconomic/ sociocultural factors. Methods: HCHS/SOL is a multi-center prospective community-based study of 16,415 Hispanic/Latino adults of Cuban, Dominican, Mexican, Puerto Rican, Central American, and South American backgrounds, aged 18-74 at Visit 1 (2008-11). Visit 2 (2014-17) is ongoing and 8,413 persons (~60% of the cohort to be studied) attended as of Sept. 2016. Analyses included 7,789 men and women with complete data. CVD RF profiles were defined as having 0 (0RF) or any 1 or more (1+RF) of the following: hypercholesterolemia, hypertension, obesity, diabetes, and smoking (see definitions in Table). Adjusted percent increases in number of RFs were computed. Multinomial logistic regression was used to examine associations of Visit 1 characteristics with change in RFs, adjusted for sociodemographic, sociocultural, and lifestyle factors. Results: After 5.8 years, 29% of men and 27% of women had increases in number of RFs; changes occurred more frequently in persons with 1+ RF at Visit 1 than in those with 0RF and varied by background ( Table ). Significantly higher odds of increase in number of RFs (vs. 0RF at both visits) were seen with older age (OR=1.07, 95% CI=1.06-1.08 per 1 yr) and male sex (1.74, 1.37-2.21); lower odds with higher education (0.60; 0.44-0.83 for > vs. < high school) and income (0.56, 0.38-0.81 for >$50,000 vs. Conclusions: In just a few years, a large percent of US Hispanic/Latino adults had an increase in number of adverse RFs, which varied by background; age, sex, education, and income were associated with RF increases. Greater efforts are needed to prevent CVD RFs in this population.

Introduction: We investigate the association between cardiovascular health at young and middle age and medical care costs and utilization in old age. Methods: We linked Chicago Heart Association (CHA) study participants’ baseline cardiovascular health (CVH) (18-59 yrs) to their Medicare claims (1991-2010) for all Part A and Part B services, including inpatient and skilled nursing facility, outpatient, home health, durable medical equipment, and hospice care. Baseline CVH is a composite measure of BP, cholesterol, diabetes, BMI, and smoking and is divided into four strata representing increasing burden. Medical care utilization (e.g., admissions and visits) and costs (in 2010 dollars) were calculated from the claims. We analyzed both the overall costs and the composition of costs among various medical care services and by CVD (non-CVD) morbidity and sex. Conditional quantile regressions were used to estimate the association between increased CVH and costs and negative binomial regressions were used for the number of inpatient admissions and outpatient visits, and the length of inpatient or hospice stay. Results: Among the 22,236 participants (222,816 person-years) 41.7% are female, 5.7% had favorable levels of all factors, 19.6% had 1+ risk factors at elevated levels, 40.9% had 1 high risk factor, and 33.7% had 2+ high risk factors. The median (mean) health care costs over the sample is $12,477 ($189,598) per person year in 2010 dollars, poorer CVH was associated with higher total medical care costs and a greater proportion of spending on home health visits (Figure). A greater CVH burden was associated with greater utilization and length of stay. Individuals with 2+ high risk factors on average have 0.22 more inpatient admissions per year and their inpatient stay is almost 2.91 days longer per year than individuals with favorable CVH. Conclusion: Unfavorable CVH early in life is associated with higher medical care cost burden in old age. Future interventions to improve CVH may result in reduced healthcare costs and utilization.

Background: Social ties within social networks have been shown to influence healthy lifestyles. However, little is known about the association among size of familial social networks, social network dynamics (such as frequency of contact and perceived connectedness), and healthy lifestyle factors in Hispanic/Latino adults. We examined cross-sectional associations of central family social network size, as well as frequency of contact with central family members (children, parents, in-laws) and perceived connectedness to extended family members (uncles, aunts, and other relatives), with individual healthy lifestyle factors. Methods: Data were analyzed from 15,511 self-identified Hispanic/Latino adults ages 18-74 years from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Size of central family, frequency of contact with central family members in past 2 weeks, and perceived connectedness to extended family, were categorized into approximate tertiles based on the distribution of the data. Healthy lifestyle factors included alcohol use (men 2 , physical activity in the highest sex-specific 40%, and healthy diet in the highest sex-specific 40%. Survey logistic regression was used to compute odds ratios [OR] and 95% confidence intervals [CI], with models adjusted for age, sex, education, income, Hispanic/Latino background, employment status, religion, church attendance, marital status, acculturation, and language preference. Results: Compared to participants with a central family social network of 0-3 individuals, those with a family social network of 4-5 members were significantly less likely to have a healthy diet (OR: 0.86; 95% CI: 0.74, 0.99) or a healthy BMI (OR: 0.74; 95% CI: 0.65, 0.85). Also, those with 6-11 members were also significantly less likely to have a healthy BMI (OR: 0.58; 95% CI: 0.49, 0.69). Individuals reporting frequent contact with 3-4 and 5-11 family members were less likely to have a healthy BMI (OR: 0.76; 95% CI: 0.66, 0.87; OR: 0.60; 95% CI: 0.51, 0.72; respectively) versus those reporting frequent contact with only 0-2 family members. However, individuals who reported feeling connected to 3-5 extended family members were more likely to have a healthy diet (OR: 1.16; 95% CI: 1.00, 1.36) and healthy BMI (OR: 1.15; 95% CI: 1.00, 1.33), and those who felt connected to 6-7 extended family members were more likely to be non-smokers and to have a healthy BMI (OR: 1.16; 95% CI: 1.00, 1.34; OR: 1.20, 95% CI: 1.20; 95% CI: 1.04, 1.38; respectively) versus those who reported feeling connected to 0-2 extended family members. Conclusions: These findings suggest that social network size and dynamics may play an important role in influencing healthy lifestyle factors among Hispanic/Latino adults. Further, specific influences may differ based on the type of relationship.

Background: Immigration studies reported that dyslipidemia is more prevalent in people living in a western lifestyle. However, it is not clear what kind of lifestyle and dietary factors contribute to this difference. Aim: To investigate whether lifestyle including dietary factors could explain the difference in serum lipids between Japanese in Japan and Japanese-Americans in Hawaii living a western lifestyle. Methods: Analyses were conducted in the INTERLIPID study, where four standardized in-depth 24-h dietary recalls were performed. Non-fasting blood was drawn from the participants who included 1,087 Japanese and 176 Japanese-American. Participants’ characteristics were described as means and SD , t test was used for the comparison of means between Hawaii and Japan. Multiple linear regression models were used to examine relationships between dietary and lifestyle factors and the difference in serum lipids levels (low-density lipoprotein cholesterol [LDL-C] and log transformed triglycerides [log-TG]) between Hawaii and Japan, adjusting for age, sex and site as the basic model. Other confounders were then added separately to the basic model. Percentage reduction of regression coefficient for the difference between Hawaii and Japan was calculated. Results: In men, LDL-C levels were significantly higher in Japanese-Americans (138.3 mg/dl) compared to Japanese in Japan (120.3mg/dl, P Conclusion: BMI explained about half of the higher LDL-C and TG levels in Japanese-Americans in Hawaii compared to Japanese in Japan. BMI together with other macro-nutrients contributed to about 70% of the difference. Further investigation is required to explore the remaining difference.

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

High intakes of dietary sodium are associated with elevated blood pressure levels and an increased risk of cardiovascular disease. National and international guidelines recommend reduced sodium intake in the general population, which necessitates population-wide surveillance. We assessed the utility of casual (spot) urine specimens in estimating 24-hour urinary sodium excretion as a marker of sodium intake in the International Cooperative Study on Salt, Other Factors, and Blood Pressure. There were 5,693 participants recruited in 1984–1987 at the ages of 20–59 years from 29 North American and European samples. Participants were randomly assigned to test or validation data sets. Equations derived from casual urinary sodium concentration and other variables in the test data were applied to the validation data set. Correlations between observed and estimated 24-hour sodium excretion were 0.50 for individual men and 0.51 for individual women; the values were 0.79 and 0.71, respectively, for population samples. Bias in mean values (observed minus estimated) was small; for men and women, the values were −1.6 mmol per 24 hours and 2.3 mmol per 24 hours, respectively, at the individual level and −1.8 mmol per 24 hours and 2.2 mmol per 24 hours, respectively, at the population level. Proportions of individuals with urinary 24-hour sodium excretion above the recommended levels were slightly overestimated by the models. Casual urine specimens may be a useful, low-burden, low-cost alternative to 24-hour urine collections for estimation of population sodium intakes; ongoing calibration with study-specific 24-hour urinary collections is recommended to increase validity.

Investigators in the Chicago Healthy Aging Study (CHAS) reexamined 1,395 surviving participants aged 65–84 years (28% women) from the Chicago Heart Association Detection Project in Industry (CHA) 1967–1973 cohort whose cardiovascular disease (CVD) risk profiles were originally ascertained at ages 25–44 years. CHAS investigators reexamined 421 participants who were low-risk (LR) at baseline and 974 participants who were non-LR at baseline. LR was defined as having favorable levels of 4 major CVD risk factors: serum total cholesterol level

Background: Epidemiologic evidence suggests that fruit consumption may lower the risk of cardiovascular diseases through blood pressure (BP)–lowering effects; little is known on the independent effect of raw fruit and fruit juice on BP. Objective: The objective was to quantify associations of raw fruit and fruit juice consumption with BP by using cross-sectional data from the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP) of 4680 men and women aged 40–59 y from Japan, China, the United Kingdom, and the United States. Design: During 4 visits, 8 BP, four 24-h dietary recalls, and two 24-h urine samples were collected. Country-specific multivariate-controlled linear regression coefficients, including adjustment for urinary sodium excretion, were estimated and pooled weighted by inverse of their variance. Results: The average total raw fruit consumption varied from a mean 6 SD 52 6 65 g/1000 kcal in the United States to 68 6 70 g/1000 kcal in China. Individual raw fruit intake was not associated with BP in pooled analyses for all countries or in participants from Western countries, although a positive association with diastolic BP was observed in East Asian participants (per 50 g/1000 kcal; 0.37 mm Hg; 95% CI: 0.02, 0.71). Positive relationships with diastolic BP were found for citrus fruit intake in Western consumers (per 25 g/1000 kcal; 0.47 mm Hg; 95% CI: 0.12, 0.81) and for apple intake in East Asian consumers (0.40 mm Hg; 95% CI: 0.03, 0.78). Among East Asian banana consumers, banana intake was inversely associated with diastolic BP (21.01 mm Hg; 95% CI: 21.88, 20.02). Fruit juice intake, which was negligible in Asia, was not related to BP in Western countries. Conclusion: Consistent associations were not found between raw fruit and fruit juice consumption of individuals and BP. This observational study was registered at www.clinicaltrials.gov as NCT00005271. Am J Clin Nutr doi: 10.3945/ajcn.112.046300.

Objective: Obesity often clusters with other major cardiovascular disease risk factors, yet a subset of the obese appears to be protected from these risks. Two obesity phenotypes are described, (i) “metabolically healthy” obese, broadly defined as body mass index (BMI) ≥ 30 kg/m2 and favorable levels of blood pressure, lipids, and glucose; and (ii) “at risk” obese, BMI ≥ 30 with unfavorable levels of these risk factors. More than 30% of obese American adults are metabolically healthy. Diet and activity determinants of obesity phenotypes are unclear. We hypothesized that metabolically healthy obese have more favorable behavioral factors, including less adverse diet composition and higher activity levels than at risk obese in the multi-ethnic group of 775 obese American adults ages 40-59 years from the International Population Study on Macro/Micronutrients and Blood Pressure (INTERMAP) cohort. Design and Methods: In gender-stratified analyses, mean values for diet composition and activity behavior variables, adjusted for age, race, and education, were compared between metabolically healthy and at risk obese. Results: Nearly one in five (149/775 or 19%) of obese American INTERMAP participants were classified as metabolically healthy obese. Diet composition and most activity behaviors were similar between obesity phenotypes, although metabolically healthy obese women reported higher sleep duration than at risk obese women. Conclusions: These results do not support hypotheses that diet composition and/or physical activity account for the absence of cardiometabolic abnormalities in metabolically healthy obese.

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.

Objectives: Little is known about the relationship of acculturation and favorable cardiovascular (CV) health (i.e., low CV risk) in the Hispanic/Latino population. Methods: Age-adjusted prevalences (weighted for sampling probability and non-response) are reported. Logistic regression was used to examine associations of acculturation (measured using nativity and length of residence: 2 ; and no major ECG abnormalities) in 15,047 HCHS/SOL participants (52.4% women) of Central American, South American, Cuban, Dominican, Mexican, Puerto Rican background, and Hispanic/Latino men and women identifying as other or >1 background group. We also tested whether these associations varied by Hispanic/Latino background. Results: Among women, age-adjusted low CV risk prevalence was highest for those living in the US < 10 years (15.4%) and similar for those living in the US ≥ 10 years (9.4%) and born in the US (9.2%). Low CV risk prevalence in was lower in men, but patterns were similar by acculturation ( Conclusions: These findings highlight the role that acculturation plays in shaping cardiovascular health in Hispanics/Latinos.

Background: High dietary sodium (Na), low dietary potassium (K) and high dietary sodium/potassium (Na/K) ratio are associated with adverse blood pressure levels and excess risks of cardiovascular diseases. 24-h urine collection is the gold standard for measuring dietary Na, K and Na/K ratio. Recommended levels of Na and K intakes are suggested in WHO guidelines; less than 85 mmol/day for Na; at least 90 mmol/day for K; there is no definitive guideline for Na/K ratio. Objective: Our primary aim was to compare the level of urinary Na/K ratio with the current recommended levels of Na and K intakes suggested in WHO guidelines. Methods: INTERMAP is an international study on associations of multiple dietary variables with blood pressure (BP), based on two timed 24-hr urine collections and dietary data from 4 in-depth 24-h dietary recalls in 4,680 men and women ages 40-59 years in China, Japan, United Kingdom and United States (US). Na/K ratio of 24-hr urine stratified in 1 unit intervals was compared with the current recommended levels of Na and K intakes suggested in WHO guidelines. Na intake was evaluated by urinary Na excretion; K intake by dietary K intake. Results: Thirty-one of the 4,680 INTERMAP participants (0.7%) had urinary Na/K ratio less than 1. The proportions of participants with Na excretion less than 2 g/day (85 mmol/day) among all 4,680 individuals were 77% (n=24), 19% (n=117), and 0.2% (n=11) in those with urinary Na/K ratio less than 1, 1 to 2, and more than 4, respectively. In US samples (n=2,195) the proportions were 88% (n=15), 19% (n=70), and 0.3% (n=6), respectively. The proportions of participants with dietary K intake more than 3.51 g/day (90 mmol/day) among all 4,680 individuals were 71% (n=22), 38% (n=233), and 2.4% (n=111) in those with urinary Na/K ratio less than 1, 1 to 2, and more than 4, respectively. In US samples the proportions were 59% (n=10), 38% (n=138), and 2.1% (n=47), respectively. Conclusions: WHO recommends Na intake less than 85 mmol/day, and K intake more than 90 mmol/day. Urinary Na/K ratio less than 1 is needed to ensure reasonable compliance with these recommendations. Currently, very few people satisfy urinary Na/K ratio less than 1, so population-wide efforts are needed to reduce salt (sodium chloride) and increase K intake.