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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.

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.

Dietary assessment traditionally relies on self-reported data which are often inaccurate and may result in erroneous diet-disease risk associations. We illustrate how urinary metabolic phenotyping can be used as alternative approach for obtaining information on dietary patterns. We used two multi-pass 24-hr dietary recalls, obtained on two occasions on average three weeks apart, paired with two 24-hr urine collections from 1,848 U.S. individuals; 67 nutrients influenced the urinary metabotype measured with (1)H-NMR spectroscopy characterized by 46 structurally identified metabolites. We investigated the stability of each metabolite over time and showed that the urinary metabolic profile is more stable within individuals than reported dietary patterns. The 46 metabolites accurately predicted healthy and unhealthy dietary patterns in a free-living U.S. cohort and replicated in an independent U.K. cohort. We mapped these metabolites into a host-microbial metabolic network to identify key pathways and functions. These data can be used in future studies to evaluate how this set of diet-derived, stable, measurable bioanalytical markers are associated with disease risk. This knowledge may give new insights into biological pathways that characterize the shift from a healthy to unhealthy metabolic phenotype and hence give entry points for prevention and intervention strategies.

BackgroundPlant-based diets are associated with a lower risk of cardiovascular diseases; however, little is known how the healthiness of the diet may be associated with blood pressure (BP). We aimed to modify three plant -based diet indices: overall plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI) according to country-specific dietary guidelines to enable use across populations with diverse dietary patterns – and assessed their associations with BP.DesignWe used cross-sectional data including 4,680 men and women ages 40–59y in Japan, China, the United Kingdom, and the United States from the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP). During four visits, eight BP measurements, and four 24-h dietary recalls were collected. Multivariable regression coefficients were estimated, pooled, weighted, and adjusted extensively for lifestyle/dietary confounders.ResultsModified PDI was not associated with BP. Consumption of hPDI higher by 1SD was inversely associated with systolic (-0.82 mm Hg;95% CI:-1.32,-0.49) and diastolic BP (-0.49 mm Hg; 95% CI:-0.91, -0.28). In contrast, consumption of an uPDI was directly associated with systolic (0.77 mm Hg;95% CI:0.30,1.20). Significant associations between hPDI with BP were attenuated with separate adjustment for vegetables and whole grains; associations between uPDI and BP were attenuated after adjustment for refined grains, sugar-sweetened beverages, and meat.ConclusionAn hPDI is associated with lower BP while a uPDI is adversely related to BP. Plant-based diets rich in vegetables and whole grains and limited in refined grains, sugar-sweetened beverages, and total meat may contribute to these associations. In addition to current guidelines, the nutritional quality of consumed plant foods is as important as limiting animal-based components.Trial registration numberThe observational INTERMAP study was registered at www.clinicaltrials.gov as NCT00005271.

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 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

Motivation Large-scale population omics data can provide insight into associations between gene–environment interactions and disease. However, existing dimension reduction modelling techniques are often inefficient for extracting detailed information from these complex datasets. Results Here, we present an interactive software pipeline for exploratory analyses of population-based nuclear magnetic resonance spectral data using a COmbined Multi-block Principal components Analysis with Statistical Spectroscopy (COMPASS) within the R-library hastaLaVista framework. Principal component analysis models are generated for a sequential series of spectral regions (blocks) to provide more granular detail defining sub-populations within the dataset. Molecular identification of key differentiating signals is subsequently achieved by implementing Statistical TOtal Correlation SpectroscopY on the full spectral data to define feature patterns. Finally, the distributions of cross-correlation of the reference patterns across the spectral dataset are used to provide population statistics for identifying underlying features arising from drug intake, latent diseases and diet. The COMPASS method thus provides an efficient semi-automated approach for screening population datasets. Availability and implementation Source code is available at https://github.com/cheminfo/COMPASS. Supplementary information Supplementary data are available at Bioinformatics online.

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: 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: 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: 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.

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.

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.

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.

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.

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.

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: 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.