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OBJECTIVES: Healthy dietary patterns are recommended for health promotion. Metabolomics can be used to identify objective biomarkers of healthy dietary patterns, which has the potential to improve dietary assessment. We used metabolomics to identify serum metabolites associated with healthy dietary patterns and the components within these dietary patterns in middle-aged US adults. METHODS: We evaluated known metabolites associated with 4 dietary patterns [Healthy Eating Index (HEI)-2015, Alternative Healthy Eating Index (AHEI)-2010, the Dietary Approaches to Stop Hypertension (DASH) diet, Mediterranean diet (aMED)] and their components using untargeted metabolomics in two subsamples (N(1 )= 1864; N(2 )= 2091) of the Atherosclerosis Risk in Communities Study. Dietary intakes were assessed using a food frequency questionnaire. We used multivariable linear regression models to examine associations between dietary patterns and individual serum metabolites in each sample, adjusting for sociodemographic factors, health behaviors, and clinical factors. RESULTS: 21 out of 373 metabolites (HEI = 10; AHEI = 9; DASH = 15; aMED = 2) in sample 1 and 57 out of 758 metabolites (HEI = 32; AHEI = 22; DASH = 44; aMED = 22) in sample 2 were significantly associated with healthy dietary patterns after Bonferroni correction. More than half of the significant metabolites (n(1 )= 10; n(2 )= 35) were associated with more than one dietary pattern. The DASH diet had the highest number of unique metabolites (n(1 )= 7; n(2 )= 17), a majority of which were amino acids. Other diets had similar number of unique metabolites (range: 0–3), which were mostly lipids. Some of the unique metabolites were positively associated with components of every diet. For example, N-methylproline was associated with fruit and dairy intake in the DASH diet; docosahexaenoate (22:6n3) was associated with omega-3 fatty acid intake in AHEI, and 1-docosahexaenoylglycerophosphoethanolamine was associated with plant protein and saturated fat intake in HEI. CONCLUSIONS: An untargeted metabolomics approach identified many metabolites associated with healthy dietary patterns. A considerable overlap of metabolites associated with HEI, AHEI, DASH, and aMED reflects the similar food components within healthy diets. FUNDING SOURCES: NIDDK, NHLBI.

OBJECTIVES: Chronic kidney disease (CKD) is an increasing health problem in young adults and may be associated with dietary patterns. We examined the association of a plant-centered diet with incident moderate-to-very high risk CKD in young adults who were initially free of CKD. METHODS: We followed 3026 community-based participants (Black and White men and women) from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort (1985–86 to 2015–16). Diet was assessed by an interviewer-administered diet history at exam years (Y) 0, 7, and 20. Higher plant-centered diet quality was judged by higher cumulative average value of the A Priori Diet Quality Score (APDQS, range 0–132), a hypothesis-driven index based on 46 food groups. A higher APDQS is characterized by high consumption of nutritionally rich plant foods and limited meat, added sugars, and other less nutritious foods. Kidney status, assessed at 5-year intervals from Y10 to Y30, was based on estimated glomerular filtration rate (eGFR) using CKD-EPI creatinine equation and spot urine albumin-to-creatinine ratio (ACR). CKD diagnosis included new onset of micro- or macro-albuminuria (ACR ≥30 mg/g), eGFR

The authors thank Munoz-Garcia et al. for their comments.1 Our study builds on earlier work showing that improvement of the diet quality score over 20 years was associated with better performance in cognitive function tests at mean age 50 years.2 We agree that examining the influence of diet on cognitive decline during aging in this cohort will help determine whether dietary interventions modify the risk of cognitive impairment, and we plan to pursue this in future work.

Sugar-sweetened beverage (SSB) intake is associated with metabolic disorders. The reduction of SSB intake has been promoted to prevent death and disability from chronic diseases. We investigated the association between SSB intake and the risk of coronary events and death, and assessed if substitution of coffee, tea, milk, fruit juice and artificially-sweetened beverages (ASB) for SSBs was associated with a reduced risk of coronary events and death. This was a follow-up study in which data from six studies were pooled and standard observational analyses were performed. Diet intake was assessed at baseline by food-frequency questionnaires. Hazard ratios (HRs) with 95% confidence intervals for the incidence of coronary events and deaths were calculated by Cox proportional hazards regression. The effect of substituting another beverage for SSBs was calculated by taking the difference in the individual effect estimates. During the median 8.2-year follow-up, 4248 coronary events and 1630 coronary deaths were documented among 284,345 individuals. 355 ml daily increase of SSB intake was associated with an increased risk of coronary events (HR: 1.08; 95%CI: 1.02, 1.14) and possibly coronary death (HR: 1.05; 95%CI: 0.96, 1.16). Substitution analyses suggested that replacing SSBs with coffee (HR: 0.93; 95%CI: 0.87, 1.00) or ASB (HR: 0.89; 95%CI: 0.83, 0.97), might be associated with a lower risk of developing coronary events. We found that SSB intake was associated with an increased risk of coronary events and possibly coronary death. Our findings also suggest that replacing SSB's with ASBs or coffee may lower the risk of developing CHD.

OBJECTIVE: Moderate alcohol consumption has been found to be associated with lower risk of coronary heart disease and myocardial infarction, which share similar risk factors and pathophysiology with chronic kidney disease (CKD). However, there is inconsistent evidence on the association between alcohol consumption and CKD. DESIGN: Prospective cohort study. SETTING: The Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort of 4 sites in the U.S. SUBJECTS: 12,692 participants aged 45–64 years. INTERVENTION: We categorized participants into 6 alcohol consumption categories: never drinkers, former drinkers, ≤1 drink/week, 2–7 drinks/week, 8–14 drinks/week, and ≥15 drinks/week based on food frequency questionnaire responses at visit 1 (1987–1989). MAIN OUTCOME MEASURE: Incident CKD was defined as estimated glomerular filtration rate

Key Points Question What is the association between the Western dietary pattern in adults in midlife and cognitive decline in later life? Findings In this cohort study of 13 588 adults without dementia at baseline, midlife dietary pattern was not associated with cognitive decline 20 years later. Meaning The Western dietary pattern may not contribute to cognitive decline in later life., This cohort study examines the association of dietary patterns in midlife with cognitive function in later life in US adults without dementia at baseline., Importance The association of dietary patterns, or the combinations of different foods that people eat, with cognitive change and dementia is unclear. Objective To examine the association of dietary patterns in midlife with cognitive function in later life in a US population without dementia. Design, Setting, and Participants Observational cohort study with analysis of data collected from 1987 to 2017. Analysis was completed in January to February 2019. Community-dwelling black and white men and women from Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and suburban Minneapolis, Minnesota, participating in the Atherosclerosis Risk in Communities (ARIC) study were included. Exposures Two dietary pattern scores were derived from a 66-item food frequency questionnaire using principal component analysis. A Western, or unhealthy, dietary pattern was characterized by higher consumption of meats and fried foods. A so-called prudent, or healthier, dietary pattern was characterized by higher amounts of fruits and vegetables. Main Outcomes and Measures Results of 3 cognitive tests (Digit Symbol Substitution Test, Word Fluency Test, and Delayed Word Recall) performed at 3 points (1990-1992, 1996-1998, and 2011-2013) were standardized and combined to represent global cognitive function. The 20-year change in cognitive function was determined by tertile of diet pattern score using mixed-effect models. The risk of incident dementia was also determined by tertile of the diet pattern score. Results A total of 13 588 participants (7588 [55.8%] women) with a mean (SD) age of 54.6 (5.7) years at baseline were included; participants in the top third of Western and prudent diet pattern scores were considered adherent to the respective diet. Cognitive scores at baseline were lower in participants with a Western diet (z score for tertile 3 [T3], −0.17 [95% CI, −0.20 to −0.14] vs T1, 0.17 [95% CI, 0.14-0.20]) and higher in participants with a prudent diet (z score for T3, −0.09 [95% CI, −0.12 to −0.06] vs T1, −0.09 [95% −0.12 to −0.06]). Estimated 20-year change in global cognitive function did not differ by dietary pattern (difference of change in z score for Western diet, T3 vs T1: −0.01 [95% CI, −0.05 to 0.04]; and difference of change in z score for prudent diet, T3 vs T1: 0.02 [95% CI, −0.02 to 0.06]). The risk of incident dementia did not differ by dietary pattern (Western hazard ratio for T3 vs T1, 1.06 [95% CI, 0.92-1.22]; prudent hazard ratio for T3 vs T1, 0.99 [95% CI, 0.88-1.12]). Conclusions and Relevance This study found that the dietary pattern of US adults at midlife was not associated with processing speed, word fluency, memory, or incident dementia in later life.

Linoleic acid (LA) and related omega-6 fatty acids have been implicated in contributing to metabolic dysfunction. However, there is some evidence to support that certain omega-6 fatty acids, such as eicosadienoic acid (EDA), may play a beneficial role in inflammation. Although, studies have inconsistently shown EDA to be inversely associated with insulin resistance and type 2 diabetes (T2D). The present study evaluated associations of EDA with log HOMA-IR and risk of incident T2D in 5,889 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Phospholipid fatty acid profiles were determined by GC-FID. A multivariable linear regression model adjusted for age, sex, BMI, education status, smoking status, ever used alcohol, and race/ethnicity was used to determine associations between baseline EDA levels (quartiles) and log HOMA-IR; a Cox proportional hazards model estimated risk of incident T2D over a median 12 year follow-up. Individuals in the three upper quartiles of EDA had a significantly lower log HOMA-IR compared to those in the reference quartile (Q1) (coefficient, [p-value]): Q2: -0.[p We hypothesize that upregulation of EDA synthesis through preferential elongation of linoleic acid may be associated with increased insulin sensitivity leading to lowered risk for T2D. Further in vitro and in vivo studies are required to elucidate the role of EDA in mitigating insulin resistance and lowered risk of diabetes and the associated states of inflammation. Disclosure N.L. Weir: None. W. Guan: None. B. Steffen: None. L.M. Steffen: None. A.B. Karger: Research Support; Self; Siemens. M.Y. Tsai: None.

Background/Objectives: Coffee consumption has been found to be associated with reduced risk of chronic conditions such as liver disease. However, less is known about the association between coffee and liver-related hospitalizations and deaths. Subjects/Methods: We conducted a prospective analysis on 14,208 participants aged 45–64 years from the Atherosclerosis Risk in Communities (ARIC) study. Coffee consumption (cups/day) was assessed using food frequency questionnaires at visit 1 (1987–89) and visit 3 (1993–95). Liver-related hospitalizations were defined as a hospitalization with any International Classification of Diseases, Ninth Revision (ICD-9) code related to liver disease identified through cohort surveillance. Liver-related death was defined as any death with a liver disease ICD-9 code listed anywhere on the death certificate form. Results: There were 833 incident cases of liver-related hospitalizations over a median follow-up of 24 years and 152 liver-related deaths over a median follow-up of 25 years. Participants who were in the highest category of coffee consumption (≥3 cups/day) were more likely to be men, whites, current smokers, and current alcohol drinkers. In our fully adjusted model, consuming ≥3 cups/day of coffee was significantly associated with a reduced risk of liver-related hospitalizations compared with never drinkers (hazard ratio: 0.79, 95% CI: 0.63–0.99). There were no significant associations between coffee consumption and liver-related deaths after adjusting for covariates. Conclusions: Coffee drinkers may be at lower risk for liver-related hospitalizations. This supports current evidence that low and moderate levels of coffee may be protective to the liver.

Aim To evaluate the relationship of abdominal muscle lean tissue and adipose tissue volumes with prediabetes and diabetes. Research design and methods We measured abdominal muscle composition in 3170 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study who underwent computed tomography (CT) at Year 25 of follow-up (ages, 43-55 years). Multinomial regression analysis was used to evaluate the associations of CT-measured intermuscular adipose tissue (IMAT), lean muscle tissue (lean) and visceral adipose tissue (VAT) volumes with diabetes at any point during the CARDIA study, newly detected prediabetes, prior history of prediabetes, and normal glucose tolerance. Models were adjusted for potential confounding factors: age, sex, race, height, smoking status, hypertension, hyperlipidaemia, cardiorespiratory fitness and study centre. Results Higher IMAT, lean and VAT volumes were all separately associated with a higher prevalence of prediabetes and diabetes. Inclusion of VAT volume in models with both IMAT volume and lean volume attenuated the association of IMAT with both prediabetes and diabetes, but higher lean volume retained its association with prediabetes and diabetes. Individuals in the highest IMAT quartile, coupled with VAT in its lower three quartiles, had a higher prevalence of diabetes, but not of prediabetes, than those with both IMAT and VAT in their respective lower three quartiles. Adjusting for cardiorespiratory fitness did not substantially change the findings. Conclusion Higher IMAT volume was associated with a higher prevalence of diabetes even after adjustment for VAT volume. However, further study is warranted to understand the complicated relationship between abdominal muscle and adipose tissues.

Background: Moderate coffee consumption has been consistently associated with a lower risk of diabetes, a major precursor to chronic kidney disease (CKD). However, the association between coffee and CKD has not been fully established. Hypothesis: We hypothesized that coffee consumption was associated with a lower risk of incident CKD after adjustment for major covariates among adults in the Atherosclerosis Risk in Communities (ARIC) study. Methods: We conducted a prospective analysis of 14,209 participants aged 45-64 years from the ARIC study. Coffee consumption (cups/day) was assessed at visit 1 (1987-89) and visit 3 (1993-95) using food frequency questionnaires. Our primary outcome was incident CKD defined as eGFR 2 accompanied by ≥25% eGFR decline, CKD-related hospitalization or death, or end-stage renal disease. Results: There were 3,845 cases of incident CKD over a median of 24 years of follow-up. Men, whites, current smokers, and participants without comorbidities were more likely to consume higher amounts of coffee per day. After adjustment for demographic, clinical, and dietary factors, higher categories of coffee consumption were associated with lower risk of incident CKD ( Table ). Compared to participants who never consumed coffee, participants who consumed any amount of coffee had an 11% lower risk of CKD (HR: 0.89; 95% CI: 0.82-0.96; p for trend Conclusions: Coffee consumption was inversely associated with incident CKD after adjusting for covariates. Coffee consumption may not adversely affect kidney disease risk and may instead be protective.

Introduction: Diet beverages are calorie free beverages sweetened with non-nutritive sweeteners. People with diabetes are the highest per-capita consumers of diet beverages, tending to consume them as a replacement for dietary sources of sugar, especially in place of sugar sweetened beverages. This behavior is endorsed by dietetic and scientific organizations and diet beverages are marketed synonymously with better health, weight loss, and thus, are considered advantageous for diabetes control. The underlying public health concern is the lack of data to support or refute this concept. Hypothesis: Higher diet beverage intake is positively associated with incident Coronary Heart Disease (CHD) Methods: We pooled the data sets of the Atherosclerosis Risk in Communities (ARIC) study (1987-2014), Cardiovascular Health Study (CHS) (1989-2014), Framingham Offspring Study (FOS) (1995-2014), Jackson Heart Study (JHS) (2000-2012), and Multi-Ethnic Study of Atherosclerosis (MESA (2000-2013) to conduct a prospective examination of the association of diet beverage intake with the incidence of CHD among participants with clinically ascertained type 2 diabetes (T2D) without prevalent CHD and with valid dietary data (N=3,947). We carried out a 2-step meta-analysis using individual level, cohort-specific Cox regression analyses with identical adjustment for demographic, lifestyle, overall diet quality and clinical risk factors to generate effect estimates that were pooled together using fixed and random effects meta-analysis. Results: 1,046 participants developed adjudicated CHD during follow-up. There was a positive, graded association between diet beverage intake and risk of incident CHD (Table). Results were consistent by sex, race and age. Conclusions: Diet beverage intake is associated with increased risk of developing CHD in a population with T2D. These results suggest the need to further evaluate dietary recommendations related to diet beverages and consider their role in this high risk population.

Background: Abdominal aortic aneurysms (AAAs) develop in up to 8% of men and 6% of women over a lifetime. Although they typically remain asymptomatic, rupture of an AAA carries high mortality. Smoking and hypertension have been identified as modifiable risk factors for developing an AAA. The role of diet, however, is yet unclear. Objective: To evaluate the relationship between adherence to a DASH-style dietary pattern and the risk of incident AAA in a large, community-based cohort of middle-aged adults. Methods: Dietary intake was assessed via a 66-item FFQ at two visits in 14,322 participants enrolled in the ARIC study (Atherosclerosis Risk in Communities) without clinical AAA, incomplete dietary/covariate information or extreme energy intake at baseline. Adherence to a DASH-style dietary pattern was assessed using a previously developed dietary scoring index. Participants were followed for incident clinical AAAs using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through December 31, 2011. Cox proportional hazards models with covariate adjustment were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs). Results: During a median follow-up of 23 years, there were 539 incident AAA cases. Participants with a DASH diet score in the highest quintile had a 39% lower risk to develop AAAs than those in the lowest score quintile (HRQ5 vs. Q1: 0.61; 95% CI 0.45, 0.84; ptrend =0.004) after adjusting for sociodemographics, total caloric intake, smoking, physical activity, BMI, abdominal obesity, diabetes, hypertension, hypercholesterolemia and cardiovascular disease. Higher intake of fruits, vegetables, whole grains, low-fat dairy, and nuts and legumes was related to a decreased risk for AAA. Conclusions: Greater adherence to a DASH-style dietary pattern was found to be associated with lower incidence of AAA. Higher consumption of fruits, vegetables, whole grains, low-fat dairy as well as nuts and legumes may help to decrease the burden of AAA in U.S. adults.

Geographic differences in CVD mortality across the U.S. are well-established, but frequently overlooked. ARIC enrolled African Americans (AA) from Jackson, MS and Forsyth County, NC, areas of the Southeast with some of the highest CVD mortality rates, especially among AAs. The Minnesota Heart Survey enrolled AAs from Minnesota where CVD rates are among the lowest. However, it is not known whether AAs in Minnesota also have low rates. Using these two cohorts, we assessed whether CVD-related mortality risk among AAs differs by region. Baseline measures of CVD risk factors for MHS were taken in 1985 from a population based sample of AAs, ages 45 to 65, living in the Minneapolis-St. Paul metropolitan area. These same measures were made at ARIC visit 1 (1987-89) in AA participants of the same age residing in Jackson, MS and Forsyth County, NC. CVD and total mortality were identified using ICD codes for underlying cause of death from State and National Death Index records in both cohorts. We compared MHS and ARIC on CVD death rates using Poisson regression, prevalence of risk factors, and risk factor hazard ratios using Cox regression. After risk factor adjustment, AA men in MHS had a rate of 5.2 (95% CI: 3.2, 7.2) CVD deaths per 1000 person-years compared to 15.1 (95% CI: 13.1, 17.1) for AA men in ARIC. For AA women, MHS had 4.1 (95% CI: 2.7, 5.5) CVD deaths per 1000 person-years versus 10.2 (95% CI: 9.0, 11.4) in ARIC. CVD mortality rates were higher in Jackson than Forsyth County within ARIC. CVD death rates paralleled risk factor prevalence at baseline. Compared to MHS, ARIC had significantly higher total cholesterol (215 vs. 202 mg/dL), albeit higher HDL cholesterol (55 vs. 53 mg/dL), as well as higher anti-hypertensive medication use (41 vs. 30%), diabetes (13 vs. 11%) and BMI (30 vs. 29 kg/m 2 ), while smoking did not differ. Despite risk factor differences, hazard ratios of CVD death associated with each risk factor did not differ between studies even after inclusion of a competing risk of non-CVD death. In conclusion, the CVD death rate was lower in AAs in MHS than in AAs residing in the Southeast in ARIC largely due to lower risk factor levels, since the hazard of CVD death for each risk factor did not differ. Study differences reflect incompletely identified geographic variation that need further exploration, especially in the context of health disparities, but support maintaining low risk as a key to CVD prevention.

Introduction: Despite the well-established association between diet and chronic disease risk, there is limited evidence on the association between diet change and long-term risk of diabetes in a community-based setting. Hypothesis: Decline in diet quality is associated with an increased risk for incidence of diabetes in the Atherosclerosis Risk in Communities (ARIC) Study. Methods: We included 8285 ARIC participants who had complete dietary intake assessments by food frequency questionnaire (FFQ) at both visits 1 (1987-1989) and 3 (1993-1995) and had no prevalent diabetes, cardiovascular disease, or cancer prior to visit 3. Change in diet quality was assessed using the Healthy Eating Index (HEI)-2015 and the Alternative HEI (AHEI)-2010 scores calculated at the two study visits. Change in scores was classified into five categories from moderate/large decrease to moderate/large increase. We used adjusted Cox models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between HEI-2015/AHEI-2010 score changes and incidence of diabetes, which is defined using doctor diagnosis, medication use, or elevated glucose. Results: There were 2,136 cases of incident diabetes during a median of 18.05 years of follow-up (124,639 person-years). For HEI-2015, there were no statistically significant association between dietary score change and diabetes risk, comparing the five categories of changes (adjusted HRs and 95% CIs for the five categories from decrease to increase were 1.06 [0.90-1.25],1.04 [0.90-1.21],1.00 (ref.), 0.91 [0.79-1.05], 1.04 [0.91-1.20]). Similar trends were found in AHEI-2010 scores changes, but for the moderate to large decrease group, the decrease in dietary scores was associated with a higher diabetes risk (HR 1.23, 95%CI 1.03 to 1.46), compared to the stable group. Conclusion: The results suggest that deterioration of diet quality is associated with a higher risk of diabetes.

Rationale: Dietary intake is a potential risk factor for respiratory morbidity in adult populations. Few studies capture the effect of dietary patterns, representative of the combination of nutrients consumed, on self-reported respiratory morbidity in combination with objective measures of lung function. Objectives: To evaluate patterns of dietary intake in relation to respiratory morbidity and objective measures of lung function in a U.S. population. Methods: The ARIC (Atherosclerosis Risk in Communities) study investigators enrolled 15,792 participants from four U.S. communities between 1987 and 1989 and collected data using a validated food frequency questionnaire to assess diet. Principal component analysis was applied, and patterns representative of “Western” and “Prudent” diets emerged. We investigated cross-sectional associations between dietary patterns and pulmonary assessments that included asthma and chronic obstructive pulmonary disease (COPD) diagnosis, respiratory symptoms, and lung function. Multivariable Poisson regression models included quintiles of dietary patterns and potential confounders. Interaction of dietary patterns with obesity, sex, and smoking status was assessed in relation to all outcomes. Results: Higher scores in the “Western” dietary pattern (quintile 5 vs. quintile 1) were associated with higher prevalence of COPD (prevalence ratio [PR], 1.62; 95% confidence ratio [CI], 1.33–1.97), wheeze (PR, 1.37; 95% CI, 1.11–1.69), cough (PR, 1.32; 95% CI, 1.32–1.59), and phlegm (PR, 1.27; 95% CI, 1.05–1.54) and lower percent predicted forced expiratory volume in 1 second (FEV(1)), percent predicted forced vital capacity (FVC), and FEV(1)/FVC ratio. Higher scores in the “Prudent” dietary pattern (quintile 5 vs. quintile 1) were associated with lower prevalence of COPD (PR, 0.82; 95% CI, 0.70–0.95) and cough (PR, 0.77; 95% CI, 0.67–0.89) and higher percent predicted FEV(1) and FEV(1)/FVC ratio. The prevalence of asthma was not related to dietary intake. Conclusions: A “Western” dietary pattern was associated with respiratory symptoms, lower lung function, and COPD in ARIC participants.

Background Odd-numbered chain saturated fatty acids (OCSFA) have been associated with potential health benefits. Although some OCSFA (e.g., C15:0 and C17:0) are found in meats and dairy products, sources and metabolism of C19:0 and C23:0 are relatively unknown, and the influence of non-dietary determinants, including genetic factors, on circulating levels of OCSFA is not established. Objective To elucidate the biological processes that influence circulating levels of OCSFA by investigating associations between genetic variation and OCSFA. Design We performed a meta-analysis of genome-wide association studies (GWAS) of plasma phospholipid/erythrocyte levels of C15:0, C17:0, C19:0, and C23:0 among 11,494 individuals of European descent. We also investigated relationships between specific single nucleotide polymorphisms (SNPs) in the lactase (LCT) gene, associated with adult-onset lactase intolerance, with circulating levels of dairy-derived OCSFA, and evaluated associations of candidate sphingolipid genes with C23:0 levels. Results We found no genome-wide significant evidence that common genetic variation is associated with circulating levels of C15:0 or C23:0. In two cohorts with available data, we identified one intronic SNP (rs13361131) in myosin X gene (MYO10) associated with C17:0 level (P = 1.37×10−8), and two intronic SNP (rs12874278 and rs17363566) in deleted in lymphocytic leukemia 1 (DLEU1) region associated with C19:0 level (P = 7.07×10−9). In contrast, when using a candidate-gene approach, we found evidence that three SNPs in LCT (rs11884924, rs16832067, and rs3816088) are associated with circulating C17:0 level (adjusted P = 4×10−2). In addition, nine SNPs in the ceramide synthase 4 (CERS4) region were associated with circulating C23:0 levels (adjusted P

Background Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. Objective To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. Design We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. Results Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (Freq(A) = 0.015) was associated with 0.029 servings/day (similar to 1 serving/month) lower fish consumption (P = 1.96x10(-8)). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10(-7)). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA. Conclusions These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.

Scope Tissue concentrations of omega-3 fatty acids may reduce cardiovascular disease risk, and genetic variants are associated with circulating fatty acids concentrations. Whether dietary fatty acids interact with genetic variants to modify circulating omega-3 fatty acids is unclear. We evaluated interactions between genetic variants and fatty acid intakes for circulating alpha-linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid. Methods and results We conducted meta-analyses (N = 11 668) evaluating interactions between dietary fatty acids and genetic variants (rs174538 and rs174548 in FADS1 (fatty acid desaturase 1), rs7435 in AGPAT3 (1-acyl-sn-glycerol-3-phosphate), rs4985167 in PDXDC1 (pyridoxal-dependent decarboxylase domain-containing 1), rs780094 in GCKR (glucokinase regulatory protein), and rs3734398 in ELOVL2 (fatty acid elongase 2)). Stratification by measurement compartment (plasma versus erthyrocyte) revealed compartment-specific interactions between FADS1 rs174538 and rs174548 and dietary alpha-linolenic acid and linoleic acid for docosahexaenoic acid and docosapentaenoic acid. Conclusion Our findings reinforce earlier reports that genetically based differences in circulating fatty acids may be partially due to differences in the conversion of fatty acid precursors. Further, fatty acids measurement compartment may modify gene–diet relationships, and considering compartment may improve the detection of gene–fatty acids interactions for circulating fatty acid outcomes.

Circulating trans fatty acids (TFAs), which cannot be synthesized by humans, are linked to adverse health outcomes. Although TFAs are obtained from diet, little is known about subsequent influences (e.g., relating to incorporation, metabolism, or intercompetition with other fatty acids) that could alter circulating concentrations and possibly modulate or mediate impacts on health.The objective was to elucidate novel biologic pathways that may influence circulating TFAs by evaluating associations between common genetic variation and TFA biomarkers.We performed meta-analyses using 7 cohorts of European-ancestry participants (n = 8013) having measured genome-wide variation in single-nucleotide polymorphisms (SNPs) and circulating TFA biomarkers (erythrocyte or plasma phospholipids), including trans-16:1n-7, total trans-18:1, trans/cis-18:2, cis/trans-18:2, and trans/trans-18:2. We further evaluated SNPs with genome-wide significant associations among African Americans (n = 1082), Chinese Americans (n = 669), and Hispanic Americans (n = 657) from 2 of these cohorts.Among European-ancestry participants, 31 SNPs in or near the fatty acid desaturase (FADS) 1 and 2 cluster were associated with cis/trans-18:2; a top hit was rs174548 (β = 0.0035, P = 4.90 × 10(-15)), an SNP previously associated with circulating n-3 and n-6 polyunsaturated fatty acid concentrations. No significant association was identified for other TFAs. rs174548 in FADS1/2 was also associated with cis/trans-18:2 in Hispanic Americans (β = 0.0053, P = 1.05 × 10(-6)) and Chinese Americans (β = 0.0028, P = 0.002) but not African Americans (β = 0.0009, P = 0.34); however, in African Americans, fine mapping identified a top hit in FADS2 associated with cis/trans-18:2 (rs174579: β = 0.0118, P = 4.05 × 10(-5)). The association between rs174548 and cis/trans-18:2 remained significant after further adjustment for individual circulating n-3 and n-6 fatty acids, except arachidonic acid. After adjustment for arachidonic acid concentrations, the association between rs174548 and cis/trans-18:2 was nearly eliminated in European-ancestry participants (β-coefficient reduced by 86%), with similar reductions in Hispanic Americans and Chinese Americans.Our findings provide novel evidence for genetic regulation of cis/trans-18:2 by the FADS1/2 cluster and suggest that this regulation may be influenced/mediated by concentrations of arachidonic acid, an n-6 polyunsaturated fat.

OBJECTIVE Chronically high nonesterified fatty acids (NEFAs) are a marker of metabolic dysfunction and likely increase risk of type 2 diabetes. By comparison, n-3 fatty acids (FAs) have been shown to have various health benefits and may protect against disease development. In 5,697 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we examined whether serum levels of NEFAs relate to risk of incident type 2 diabetes and further tested whether plasma n-3 FA levels may interact with this relation. RESEARCH DESIGN AND METHODS NEFAs were measured in fasting serum using an enzymatic colorimetric assay and phospholipid n-3 FAs eicosapentaenoic and docosahexaenoic acids were determined in plasma through gas chromatography-flame ionization detection in 5,697 MESA participants. Cox proportional hazards regression evaluated the association between NEFA levels and incident type 2 diabetes and whether plasma n-3 FAs modified this association adjusting for age, sex, race, education, field center, smoking, and alcohol use. RESULTS Over a mean 11.4 years of the study period, higher diabetes incidence was found across successive NEFA quartiles (Q) (hazard ratio [95% CI]): Q1, 1.0; Q2, 1.35 (1.07, 1.71); Q3, 1.58 (1.24, 2.00); and Q4, 1.86 (1.45, 2.38) (Ptrend < 0.001). A significant interaction of n-3 FAs on the relation between NEFAs and type 2 diabetes was also observed (Pinteraction = 0.03). For individuals with lower n-3 levels ( CONCLUSIONS NEFAs are a marker of type 2 diabetes and may have clinical utility for detecting risk of its development. The modifying influence of n-3 FAs suggests a protective effect against disease and/or metabolic dysfunction related to NEFAs and requires further study.

Background: Higher dietary acid load can result in metabolic acidosis and is associated with faster kidney disease progression in patients with chronic kidney disease (CKD). However, the relationship between dietary acid load and incident CKD has not been evaluated. Methods: We conducted prospective analyses of the Atherosclerosis Risk in Communities study participants without CKD at baseline (1987-1989, n = 15,055). Dietary acid load was estimated using the equation for potential renal acid load by Remer and Manz, incorporating dietary intake data from a food frequency questionnaire. Incident CKD was assessed from baseline through 2010 and defined as estimated glomerular filtration rate (eGFR) 2 accompanied by 25% eGFR decline, CKD-related hospitalization or death or end-stage renal disease identified by linkage to the US Renal Data System registry. Results: In the overall study population, 55% were female, 26% were African-American and mean age at baseline was 54 years. During a median follow-up of 21 years, there were 2,351 (15.6%) incident CKD cases. After adjusting for demographics (age, sex, race-center), established risk factors (diabetes status, hypertension status, overweight/obese status, smoking status, education level, physical activity), caloric intake and baseline eGFR, higher dietary acid load were associated with higher risk of incident CKD (hazard ratio [HR] for quartile 4 vs. 1: 1.13, 95% CI 1.01-1.28, p for trend = 0.02; HR per interquartile range increase: 1.06, 95% CI 1.00-1.11, p = 0.04). Conclusion: Dietary acid load is associated with incident CKD in a population-based sample. These data suggest a potential avenue for CKD risk reduction through diet.

Very long-chain saturated fatty acids (VLSFAs) are saturated fatty acids with 20 or more carbons. In contrast to the more abundant saturated fatty acids, such as palmitic acid, there is growing evidence that circulating VLSFAs may have beneficial biological properties. Whether genetic factors influence circulating levels of VLSFAs is not known. We investigated the association of common genetic variation with plasma phospholipid/erythrocyte levels of three VLSFAs by performing genome-wide association studies in seven population-based cohorts comprising 10,129 subjects of European ancestry. We observed associations of circulating VLSFA concentrations with common variants in two genes, serine palmitoyl-transferase long-chain base subunit 3 (SPTLC3), a gene involved in the rate-limiting step of de novo sphingolipid synthesis, and ceramide synthase 4 (CERS4). The SPTLC3 variant at rs680379 was associated with higher arachidic acid (20:0 , P = 5.81 × 10(-13)). The CERS4 variant at rs2100944 was associated with higher levels of 20:0 (P = 2.65 × 10(-40)) and in analyses that adjusted for 20:0, with lower levels of behenic acid (P = 4.22 × 10(-26)) and lignoceric acid (P = 3.20 × 10(-21)). These novel associations suggest an inter-relationship of circulating VLSFAs and sphingolipid synthesis.

Background: Epidemiologic evidence regarding niacin, folate, vitamin B-6, and vitamin B-12 intake in relation to cognitive function is limited, especially in midlife.Objective: We hypothesize that higher intake of these B vitamins in young adulthood is associated with better cognition later in life.Design: This study comprised a community-based multicenter cohort of black and white men and women aged 18-30 y in 1985-1986 (year 0, i.e., baseline) from the Coronary Artery Risk Development in Young Adults (CARDIA) study (n = 3136). We examined participants' CARDIA diet history at years 0, 7, and 20 to assess nutrient intake, including dietary and supplemental B vitamins. We measured cognitive function at year 25 (mean ± SD age: 50 ± 4 y) through the use of the Rey Auditory Verbal Learning Test (RAVLT) for verbal memory, the Digit Symbol Substitution Test (DSST) for psychomotor speed, and a modified Stroop interference test for executive function. Higher RAVLT and DSST scores and a lower Stroop score indicated better cognitive function. We used multivariable-adjusted linear regressions to estimate mean differences in cognitive scores and 95% CIs.Results: Comparing the highest quintile with the lowest (quintile 5 compared with quintile 1), cumulative total intake of niacin was significantly associated with 3.92 more digits on the DSST (95% CI: 2.28, 5.55; P-trend < 0.01) and 1.89 points lower interference score on the Stroop test (95% CI: -3.10, -0.68; P-trend = 0.05). Total folate was associated with 2.56 more digits on the DSST (95% CI: 0.82, 4.31; P-trend = 0.01). We also found that higher intakes of vitamin B-6 (quartile 5 compared with quartile 1: 2.62; 95% CI: 0.97, 4.28; P-trend = 0.02) and vitamin B-12 (quartile 5 compared with quartile 1: 2.08; 95% CI: 0.52, 3.65; P-trend = 0.02) resulted in better psychomotor speed measured by DSST scores.Conclusion: Higher intake of B vitamins throughout young adulthood was associated with better cognitive function in midlife.

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for the association of serum 25-hydroxyvitamin D [25(OH)D] and pulmonary function. We conducted the largest cross-sectional meta-analysis of the 25(OH)D– pulmonary function association to date, based on nine European ancestry (EA) cohorts (n=22,838) and five African ancestry (AA) cohorts (n=4,290) in the CHARGE Consortium. Data were analyzed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean (SD) serum 25(OH)D was 68 (29) nmol/L for EAs and 49 (21) nmol/L for AAs. For each 1 nmol/L higher 25(OH)D, forced expiratory volume in the first second (FEV1) was higher by 1.1 mL in EAs (95% CI: 0.9,1.3; P=2.5×10-21) and 1.8 mL (95% CI: 1.1,2.5; P=1.6×10-7) in Aas (Prace difference=0.06), and forced vital capacity (FVC) was higher by 1.3 mL in EAs (95% CI: 1.0,1.6; P=1.1×10-20) and 1.5 mL (95% CI: 0.8,2.3; P=1.2×10-4) in AAs (Prace difference=0.56). Among EAs, the 25(OH)D–FVC association was stronger in smokers: per 1nmol/L higher 25(OH)D, FVC was higher by 1.7 mL (95% CI: 1.1,2.3) for current smokers and 1.7 mL (95% CI: 1.2,2.1) for former smokers, compared to 0.8 mL (95% CI: 0.4,1.2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EAs, a stronger association was observed for smokers compared to never smokers, which supports the importance of vitamin D in vulnerable populations.Cohort FundingThis work was supported by National Institutes of Health (NIH) grant number R21 HL125574 funded by the National Heart, Lung, and Blood Institute (NHLBI) and the NIH Office of Dietary Supplements (ODS) (co-Principal Investigators [co-PIs]: DBH and PAC). The corresponding author (PAC) had full access to the data for the meta-analysis, and had final responsibility for the decision to submit for publication. No funding source had any role in the analysis of the data, the writing of the manuscript, or the decision to submit it. This work was also supported in part by R01HL077612 (PI: RGB) and by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (ZO1 ES043012, PI: SJL). SJL is supported by the Intramural Research Program of NIH, National Institute of Environmental Health Sciences. Infrastructure for the CHARGE Consortium is supported in part by the NHLBI grant R01HL105756.The Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study has been funded by NIH contracts N01-AG-1-2100 and 271201200022C, the National Institute on Aging (NIA) Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063. The researchers are indebted to the participants for their willingness to participate in the study.The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by NHLBI contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C. 25(OH)D measurements were conducted with the support of R01 HL103706 from the NHLBI and R01 HL103706-S1 from the NIH ODS. The authors thank the staff and participants of the ARIC study for their important contributions.This Cardiovascular Health Study (CHS) research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants U01HL080295, R01HL085251, R01HL087652, R01HL105756, R01HL103612, R01HL120393, and R01HL130114 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from NIA. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Vitamin D measurements were made possible by NHLBI (R01HL084443-01A2).This work in Framingham Heart Study was supported by NHLBI’s Framingham Heart Study contract (N01-HC-25195 and HHSN268201500001I). Vitamin D measurements in the Framingham study were made possible by NIA (R01 AG14759 to SLB.).The Health Aging and Body Composition cohort study was supported by NIA contracts N01AG62101, N01AG2103, and N01AG62106, NIA grant R01-AG028050, NINR grant R01-NR012459, and in part by the Intramural Research Program of the NIA, NIH. This research was further supported by RC1AG035835, and the serum vitamin D assays were supported by R01AG029364.The Multi-Ethnic Study of Atherosclerosis (MESA) study is conducted and supported by NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from NHLBI, UL1-TR-000040, UL1-TR-001079, and UL1-TR-001881 from NCRR, and DK063491 from the NIDDK. The MESA Lung study was supported by grants R01 HL077612, RC1 HL100543 and R01 HL093081 from NHLBI. Support for the Mineral Metabolite dataset was provided by grant HL096875.The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, the Netherlands; the Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Dutch Ministry of Education, Culture, and Science; the Dutch Ministry for Health, Welfare, and Sports; the European Commission (DG XII), and the Municipality of Rotterdam. LL was a postdoctoral fellow of the Research Foundation—Flanders (FWO) in Brussels, Belgium. Part of this work was supported by a FWO-grant G035014N. DSM Nutritional Products AG, Kaiseraugst, Switzerland, sponsored the Vitamin D serum analyses. The authors are grateful to the study participants, the staff from the Rotterdam Study, and the participating general practitioners and pharmacists.The Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, and HHSN268200900041C from the National Heart, Lung, and Blood Institute (NHLBI), the Intramural Research Program of the National Institute on Aging (NIA), and an intra-agency agreement between NIA and NHLBI (AG0005).Author DisclosureDr. Psaty serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson.All other authors have no conflicts of interest. There is no commercial support or financial interest from the tobacco industry for the research presented.The study sponsors were not involved in study design, data collection, data analysis, data interpretation, report writing, or decisions to submit the paper for publication. PAC and DBH had final responsibility for the decision to submit for publication.Online Supporting MaterialSupplemental table, figures, and methods are available.Abbreviation Footnote25(OH)D25-Hydroxyvitamin DAAAfrican AncestryAGESAge, Gene, Environment, Susceptibility Study—Reykjavik, IcelandARICAtherosclerosis Risk in Communities StudyCARDIACoronary Artery Risk Development in Young Adults StudyCHARGECohorts for Heart and Aging Research in Genomic Epidemiology ConsortiumCHSCardiovascular Health StudyCLIAChemiluminescence ImmunoassayCOPDChronic Obstructive Pulmonary DiseaseEAEuropean AncestryFEV1Forced Expiratory Volume in the First SecondFHS (Offspring)Framingham Heart Study—Offspring CohortFHS (Gen3)Framingham Heart Study—Generation 3 CohortFVCForced Vital CapacityHABCHealth, Aging, and Body Composition StudyLC-MS/MSLiquid Chromatography in Tandem with Mass SpectrometryMESAMulti-Ethnic Study of AtherosclerosisNHANESNational Health and Nutrition Examination SurveyPFTPulmonary Function TestRIARadioimmunoassayRSRotterdam (Netherlands) Study

Background: Peripheral arterial disease (PAD) is a costly source of morbidity and mortality among older persons in the United States. Dietary intake plays a role in the development of atherosclerotic cardiovascular disease; however, few studies have examined the relation of food intake or diet patterns with PAD. Objectives: We examined the relationship between habitual dietary intake at midlife and incident PAD over approximately 20 years of follow-up. Methods: Among 14,082 participants enrolled in the Atherosclerosis Risk in Communities (ARIC) study initially free of PAD, dietary intake was assessed at baseline in 1987-1989 using a Harvard food frequency questionnaire. Food groups were created and principal components analysis was used to develop “healthy” and “Western” dietary patterns; both were categorized into quintiles or quartiles. Incident PAD was defined by an ankle-brachial index (ABI) measure of < 0.90 at either of two subsequent exams (1993-1995, 1996-1998), or a hospital discharge diagnosis of PAD, leg amputation, or leg revascularization procedures through 2012. Cox proportional hazards models adjusted for relevant confounders assessed the relations of each food group or diet pattern with incident PAD. Results: During a mean follow up of 19.9 years, 1569 participants developed incident PAD. A total of 64.7% of cases had their incident event defined via ICD-9 codes, while 35.3% had incident PAD defined by ABI. In models adjusted for demographics, behaviors, and food groups, the hazard ratios for incident PAD increased across quintiles of meat consumption (Q2 vs. Q1 1.38 [95% CI 1.16, 1.64], Q3 vs. Q1 1.40 [1.18, 1.67], Q4 vs. Q1 1.47 [1.23, 1.77], Q5 vs. Q1 1.66 [1.36, 2.03], p for trend Conclusions: In this prospective population-based cohort study, greater meat consumption was associated with higher risk of incident PAD, while both moderate alcohol consumption and coffee consumption were associated with lower risk of incident PAD. Whether these associations are causal remains to be seen.

Introduction: Endothelial NO synthase ( eNOS ) gene polymorphism at position 894 (G>T, Glu298Asp ) resulting in a T allele is related to higher blood pressure (BP) levels, but the association of Glu298Asp and temporal increase in BP in adulthood has not been studied, nor is it known whether the association between Glu298Asp and BP is modified by habitual intake of fruits and vegetables, an abundant source of nitrate for conversion to NO. Hypothesis: We hypothesized that homozygous (TT) or heterozygous genotype (GT) status of Glu298Asp is associated with BP increase over a course of 9 years among black and white adults, compared to normal genotype (GG). Further, the association is amplified by higher habitual intake of fruits and vegetables. Methods: Among 9488 white (mean age: 54.3 years, 47.0% men) and 2861 black members of the ARIC cohort (mean age: 53.4 years, 37.2% men) at baseline (1987-1989), genotyping of the NOS3 Glu298Asp polymorphism (rs1799983) was conducted using the TaqMan assay (Applied Biosystems, Foster City, CA, USA). The rs1799983 levels 1.5-2, 0.5-1.49, NOS3 G894T (TT or GT vs. GG) with level and change of SBP and DBP, adjusting for age, sex, genotypes, BMI, smoking status, diabetes, and physical activity. The analysis was also conducted within each quartile of vegetables and fruit intake, with further adjustment for the diet score without fruit and vegetables intake. Results: The genotypes of TT, GT and GG of Glu298Asp were present in 800 (8.4%), 4057 (42.8%), 4631 (48.8%) white participants, and 26 (0.9%), 510 (17.8%), 2335 (81.3%) black participants. Among whites with the genotype GT/TT, DBP increased 2.46 mmHg (95% CI: 0.02, 4.90) over 9 years compared to GG participants. The interaction between Glu298Asp and intake of fruit and vegetables was not statistically significant. There was no statistically significant association between GT/TT and SBP, nor with 9-year change of SBP or DBP among black participants. Conclusion: Carrier status of the GT/TT genotypes of Glu298Asp is associated with higher level of DBP among white adults, but not with SBP over a course of 9 years compared to the GG genotype of Glu298Asp . There is no interaction found between Glu298Asp and intake of fruit and vegetables in association with SBP or DBP.

Objectives To examine the association between midlife cardiovascular health and physical performance 25 years later. Design Cohort study (Atherosclerosis Risk in Communities Study); multinomial logistic and logistic regression adjusted for demographic characteristics and clinical measures. Setting Four U.S. communities: Forsyth County, North Carolina; Washington County, Maryland; Minneapolis, Minnesota; and Jackson, Mississippi. Participants: Individuals aged 54.2 ± 5.8 at baseline (N = 15,744; 55% female, 27% black). Measurements Cardiovascular health was measured at baseline using the American Heart Association's Life's Simple 7 (LS7) score (0–14) and LS7 component categories (poor, intermediate, ideal) for each risk factor. The Short Physical Performance Battery (SPPB) was used to quantify physical function as ordinal (0–12) and categorical (low (0–6), fair (7–9), good (10–12) outcomes. Results Mean baseline LS7 score was 7.9 ± 2.4; 6,144 (39%) individuals returned 25 years later for the fifth ARIC examination, at which point the SPPB was administered. Of 5,916 individuals who completed the SPPB, 3,288 (50%) had good physical performance. Each 1-unit increase in LS7 score was associated with a 17% higher SPPB score (rate ratio (RR) = 1.17, 95% confidence interval (CI) = 1.15–1.19) and a 29% greater chance of having a late-life SPPB score of 10 or greater compared to SPPB score of less than 10 (RR = 1.29, 95% CI = 1.25–1.34). Ideal baseline glucose (RR = 2.53, 95% CI = 2.24–2.87), smoking (RR = 1.97, 95% CI = 1.81–2.15), blood pressure (RR = 1.70, 95% CI = 1.54–1.88), body mass index (RR = 1.51, 95% CI = 1.37–1.66), and physical activity (RR = 1.31, 95% CI = 1.20–1.43) had the strongest associations with late-life SPPB score, adjusting for other LS7 components. Conclusion Better cardiovascular health during midlife may lead better physical functioning in older age.

Background: A healthy diet may be protective against cognitive decline by mechanisms that involve improved vascular risk factors such as hypertension and dysglycemia, and reduced systemic inflammation. In this population-based study, we hypothesized that midlife diet pattern would be associated with cognitive decline over 21-years. Methods: This study included 13,603 participants in the ARIC population-based cohort recruited from four U.S. sites who were aged 45 to 64 at baseline (1987-89) when diet was measured. Participants recorded diet using a 66-item food frequency questionnaire. Two dietary patterns, called “Meat and Fried” and the “Balanced Diet”, were named after the most representative foods that emerged from constructs derived from a principal component analysis of 30 food groups. A higher diet pattern score represented greater adherence. Cognitive testing, including the digit symbol substitution, the word fluency and delayed word recall tests, were combined to a z-score at each visit (visits 2, 1990-92; 4, 1996-98 and 5, 2011-2013). Test scores for participants not attending subsequent visits were imputed using Multiple Imputation by Chained Equations to account for cohort attrition. Cognitive performance at visit 2 was compared by tertile (T) of each diet pattern. Using mixed effects models with a random slope and intercept , we determined the 21-year change in cognitive function by diet pattern tertile, adjusting for demographics and medical history. Results: At visit 2, adherence to the Meat and Fried pattern was associated with lower cognitive test scores (z-score T3: -0.172, SD 0.985; T1: 0.149, SD 0.981, p-trend Conclusion: Although participants with a diet pattern high in meat and fried foods had lower cognition at time of first assessment, diet patterns at midlife did not carry independent associations with cognitive decline.

ObjectiveDietary fatty acid composition likely affects prediabetic conditions such as isolated impaired fasting glucose (IFG) or impaired glucose tolerance (IGT); however, this risk has not been evaluated in a large population nor has it been followed prospectively.DesignDiet, physical activity, anthropometric, socio-economic and blood glucose data from the Atherosclerosis Risk in Communities (ARIC) study were obtained from BioLINCC. Cox proportional hazards regression models were used to evaluate associations of dietary SFA, MUFA, PUFA,n-3 fatty acid (FA) andn-6 FA intakes with incidence of one (isolated IFG) or two (IFG with IGT) prediabetic conditions at the end of 12-year follow-up.SettingStudy volunteers were from counties in North Carolina, Mississippi, Minnesota and Maryland, USA.SubjectsData from 5288 volunteers who participated in the ARIC study were used for all analyses reported herein.ResultsThe study population was 62% male and 84 % white, mean age 53·5 (sd5·7) years and mean BMI 26·2 (sd4·6) kg/m2. A moderately high intake of dietary MUFA (10–15 % of total daily energy) was associated with a 10 % reduced risk of isolated IFG incidence, while a high intake ofn-3 FA (>0·15 % of total daily energy) was associated with a 10 % increase in risk. Curiously, moderately high intake ofn-6 PUFA (4–5 % of total daily energy) was associated with a 12 % reduction in IFG and IGT incidence.ConclusionsMUFA,n-3 andn-6 FA contribute differently to the development of isolated IFGv. IFG with IGT; and their mechanism may be more complex than originally proposed.

MUFAs are unsaturated FAs with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels are associated with cardiometabolic disorders, including CVD, T2D, and metabolic syndrome (MS). Previous genome-wide association studies (GWASs) have identified seven loci for plasma and erythrocyte palmitoleic and oleic acid levels in populations of European origin. To identify additional MUFA-associated loci and the potential functional variant at each locus, we performed ethnic-specific GWAS meta-analyses and trans-ethnic meta-analyses in more than 15,000 participants of Chinese and European ancestry. We identified novel genome-wide significant associations for vaccenic acid at FADS1/2 and PKD2L1 [log(10)(Bayes factor). >= 8.07] and for gondoic acid at FADS1/2 and GCKR [log(10)(Bayes factor) >= 6.22], and also observed improved fine-mapping resolutions at FADS1/2 and GCKR loci. The greatest improvement was observed at GCKR, where the number of variants in the 99\% credible set was reduced from 16 (covering 94.8 kb) to 5 (covering 19.6 kb, including a missense variant rs1260326) after trans-ethnic meta-analysis. We also confirmed the previously reported associations of PKD2L1, FADS1/2, GCKR, and HIF1AN with palmitoleic acid and of FADS1/2 and LPCAT3 with oleic acid in the Chinese-specific GWAS and the trans-ethnic meta-analyses. Pathway-based analyses suggested that the identified loci were in unsaturated FA metabolism and signaling pathways.(jl) Our findings provide novel insight into the genetic basis relevant to MUFA metabolism and biology. Infrastructure for the CHARGE Consortium was supported in part by the National Heart, Lung, and Blood Institute grant HL105756. The NHAPC study was supported by the major project of the Ministry of Science and Technology of China (2016YFC1304903) and the National Natural Science Foundation of China (81471013, 30930081, 81170734, and 81321062). The ARIC Study was carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C and grants R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by grant UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The CARDIA study was conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham (HHSN268201300025C and HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging. Genotyping of the CARDIA participants was supported by National Human Genome Research Institute grants U01-HG-004729, U01-HG-004446, and U01-HG-004424. Statistical analyses and FA measures were funded by National Heart, Lung, and Blood Institute grant R01-HL-084099 (M.F.). The CHS was supported by National Heart, Lung, and Blood Institute contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086; and National Heart, Lung, and Blood Institute grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, and R01HL085710, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through National Institute on Aging grant R01AG023629. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences CTSI grant UL1TR000124 and the National Institute of Diabetes and Digestive and Kidney Diseases Diabetes Research Center grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The HPFS and NHS were supported by National Institutes of Health research grants UM1 CA186107, R01 HL034594, UM1 CA167552, R01 HL35464, HL60712, and CA055075; National Heart, Lung, and Blood Institute career development award R00HL098459; American Diabetes Association research grant 1-12-JF-13; and American Heart Association grant 11SDG7380016. The MESA study and MESA SHARe were supported by National Heart, Lung, and Blood Institute contracts N01-HC-95159 through N01-HC-95169 and RR-024156. Funding for MESA SHARe genotyping was provided by National Heart, Lung, and Blood Institute contract N02HL64278. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences CTSI grant UL1TR000124 and the National Institute of Diabetes and Digestive and Kidney Diseases Diabetes Research Center grant DK063491 (Southern California Diabetes Endocrinology Research Center).; The GOLDN study was funded by National Heart, Lung, and Blood Institute grants U01HL072524 and HL54776. The InCHIANTI baseline (1998-2000) was supported as a ``targeted project (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by National Institute on Aging contracts 263 MD 9164 and 263 MD 821336. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Sí

Background— Previous studies on intake of linoleic acid (LA), the predominant n-6 fatty acid, and coronary heart disease (CHD) risk have generated inconsistent results. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the relation of dietary LA intake and CHD risk. Methods and Results— We searched MEDLINE and EMBASE databases through June 2013 for prospective cohort studies that reported the association between dietary LA and CHD events. In addition, we used unpublished data from cohort studies in a previous pooling project. We pooled the multivariate-adjusted relative risk (RR) to compare the highest with the lowest categories of LA intake using fixed-effect meta-analysis. We identified 13 published and unpublished cohort studies with a total of 310 602 individuals and 12 479 total CHD events, including 5882 CHD deaths. When the highest category was compared with the lowest category, dietary LA was associated with a 15% lower risk of CHD events (pooled RR, 0.85; 95% confidence intervals, 0.78–0.92; I 2 =35.5%) and a 21% lower risk of CHD deaths (pooled RR, 0.79; 95% confidence intervals, 0.71–0.89; I 2 =0.0%). A 5% of energy increment in LA intake replacing energy from saturated fat intake was associated with a 9% lower risk of CHD events (RR, 0.91; 95% confidence intervals, 0.87–0.96) and a 13% lower risk of CHD deaths (RR, 0.87; 95% confidence intervals, 0.82–0.94). Conclusions— In prospective observational studies, dietary LA intake is inversely associated with CHD risk in a dose–response manner. These data provide support for current recommendations to replace saturated fat with polyunsaturated fat for primary prevention of CHD.

Dietary protein has been shown to increase urinary Ca excretion in randomised controlled trials, and diets high in protein may have detrimental effects on bone health; however, studies examining the relationship between dietary protein and bone health have conflicting results. In the present study, we examined the relationship between dietary protein (total, animal and vegetable protein) and lumbar spine trabecular volumetric bone mineral density (vBMD) among participants enrolled in the Multi-Ethnic Study of Atherosclerosis (n 1658). Protein intake was assessed using a FFQ obtained at baseline examination (2000–2). Lumbar spine vBMD was measured using quantitative computed tomography (2002–5), on average 3 years later. Multivariable linear and robust regression techniques were used to examine the associations between dietary protein and vBMD. Sex and race/ethnicity jointly modified the association of dietary protein with vBMD (P for interaction = 0·03). Among white women, higher vegetable protein intake was associated with higher vBMD (P for trend = 0·03), after adjustment for age, BMI, physical activity, alcohol consumption, current smoking, educational level, hormone therapy use, menopause and additional dietary factors. There were no consistently significant associations for total and animal protein intakes among white women or other sex and racial/ethnic groups. In conclusion, data from the present large, multi-ethnic, population-based study suggest that a higher level of protein intake, when substituted for fat, is not associated with poor bone health. Differences in the relationship between protein source and race/ethnicity of study populations may in part explain the inconsistent findings reported previously.

Background and Purpose— We report on trends in poststroke survival, both in the early period after stroke and over the long term. We examine these trends by stroke subtype. Methods— The Minnesota Stroke Survey is a study of all hospitalized patients with acute stroke aged 30 to 74 years in the Minneapolis–St Paul metropolis. Validated stroke events were sampled for survey years 1980, 1985, 1990, 1995, and 2000 and subtyped as ischemic or hemorrhagic by neuroimaging for survey years 1990, 1995, and 2000. Survival was obtained by linkage to vital statistics data through the year 2010. Results— There were 3773 acute stroke events. Age-adjusted 10-year survival improved from 1980 to 2000 (men 29.5% and 46.5%; P P P =0.0001; women 38% and 55.3%; P P =0.06; women 39.2% and 49.6%; P =0.2). Markers of stroke severity including unconsciousness or major neurological deficits at admission declined from 1980 to 2000 while neuroimaging use increased. Conclusions— These poststroke survival trends are likely because of multiple factors, including more sensitive case ascertainment shifting the case mix toward less severe strokes, improved stroke care and risk factor management, and overall improvements in population health and longevity.

Association between fruit intake and risk of type 2 diabetes is inconsistent. In this study, we performed a meta-analysis of all prospective cohort studies to clarify the association between fruit intake and risk of type 2 diabetes. Relevant studies were identified by searches of the PubMed and Embase databases up to November 2013. The summary relative risks of association were obtained using a fixed- or random-effects model. A total of nine prospective studies (403,259 participants, including 27,940 with incident type 2 diabetes) from seven publications were included in the meta-analysis of fruit intake and risk of type 2 diabetes. We found that individuals in the highest category of fruit intake had a reduced risk of type 2 dia- betes (relative risk 0.92, 95 % confidence interval 0.86-0.97, p = 0.003) compared to those in the lowest category, with moderate evidence of between-study heter- ogeneity (I 2 = 37.6 %, p = 0.12). There was an evident non-linear association of fruit intake with type 2 diabetes (P for nonlinearity \0.001). A non-linear threshold of 200 g/day of fruit intake was identified and the risk of type 2 diabetes reduced by about 13 % at this cut-off. Our findings are consistent with diet recommendations to con- sume about 200 g/day of fruits to prevent type 2 diabetes.

Background and aim: Dietary patterns are associated cross-sectionally with cellular adhesion molecules (CAMs). We studied prospective associations of three dietary patterns with CAMs. Methods and results: In the Coronary Artery Risk Development in Young Adults (CARDIA) study, diet was assessed at years 0 (1985-86) and 7 (1992-93) examinations. Four circulating CAMs (E-selectin, P-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), and vascular cellular adhesion molecule (VCAM)) were assayed at years 7 and 15 (2000-01). We created one index score "A Priori Diet Quality Score" and derived dietary patterns using principal components analysis (PCA). Multivariable linear regression models predicted year 15 CAMs from averaged (year 0/7) dietary patterns. The A Priori Diet Quality Score rated 46 food groups beneficial, neutral or adverse based on hypothesized health effects. We derived two PCA dietary patterns: "fruit and vegetables (FV)" (high intakes of fruit, vegetables, and whole grains) and "meat" (high intakes of red meat, refined grain, and butter). All dietary patterns were related to E-selectin and sICAM-1. P-selectin was not related to the FV dietary pattern. VCAM was only related to the A Priori Diet Quality Score. Strongest associations were for the meat dietary pattern with E-selectin (effect size 28% of an SD (+3.9/13.7 ng/mL)) and P-selectin (effect size 37% of an SD (+4.1/11.2 ng/mL)) and the A Priori Diet Quality Score with sICAM-1 (effect size 34% of an SD (-15.1/44.7 ng/mL)) and VCAM (effect size of 26% of an SD (-45.1/170.3 ng/mL)). Conclusion: This prospective analysis suggests that dietary patterns are associated with CAMs. (C) 2014 Elsevier B. V. All rights reserved.

Background— Omega6 (n6) polyunsaturated fatty acids (PUFAs) and their metabolites are involved in cell signaling, inflammation, clot formation, and other crucial biological processes. Genetic components, such as variants of fatty acid desaturase ( FADS ) genes, determine the composition of n6 PUFAs. Methods and Results— To elucidate undiscovered biological pathways that may influence n6 PUFA composition, we conducted genome-wide association studies and meta-analyses of associations of common genetic variants with 6 plasma n6 PUFAs in 8631 white adults (55% women) across 5 prospective studies. Plasma phospholipid or total plasma fatty acids were analyzed by similar gas chromatography techniques. The n6 fatty acids linoleic acid (LA), γ-linolenic acid (GLA), dihomo-GLA, arachidonic acid, and adrenic acid were expressed as percentage of total fatty acids. We performed linear regression with robust SEs to test for single-nucleotide polymorphism–fatty acid associations, with pooling using inverse-variance–weighted meta-analysis. Novel regions were identified on chromosome 10 associated with LA (rs10740118; P =8.1×10 −9 ; near NRBF2 ), on chromosome 16 with LA, GLA, dihomo-GLA, and arachidonic acid (rs16966952; P =1.2×10 −15 , 5.0×10 −11 , 7.6×10 −65 , and 2.4×10 −10 , respectively; NTAN1 ), and on chromosome 6 with adrenic acid after adjustment for arachidonic acid (rs3134950; P =2.1×10 −10 ; AGPAT1 ). We confirmed previous findings of the FADS cluster on chromosome 11 with LA and arachidonic acid, and further observed novel genome-wide significant association of this cluster with GLA, dihomo-GLA, and adrenic acid ( P =2.3×10 −72 , 2.6×10 −151 , and 6.3×10 −140 , respectively). Conclusions— Our findings suggest that along with the FADS gene cluster, additional genes may influence n6 PUFA composition.

Background: Effects of alcohol consumption on health and disease are complex and involve a number of cellular and metabolic processes. Objective: We examined the association between alcohol consumption habits and metabolomic profiles. Design: We conducted a cross-sectional study to explore the association of alcohol consumption habits measured by using a questionnaire with serum metabolites measured by using untargeted mass spectrometry in 1977 African Americans from the Jackson field center in the Atherosclerosis Risk in Communities Study. The whole sample was split into a discovery set (n = 1500) and a replication set (n = 477). Alcohol consumption habits were treated as an ordinal variable, with nondrinkers as the reference group and quartiles of current drinkers as ordinal groups with higher values. For each metabolite, a linear regression was conducted to estimate its relation with alcohol consumption habits separately in both sets. A modified Bonferroni procedure was used in the discovery set to adjust the significance threshold (P < 1.9 × 10−4). Results: In 356 named metabolites, 39 metabolites were significantly associated with alcohol consumption habits in both discovery and replication sets. In general, alcohol consumption was associated with higher levels of most metabolites such as those in amino acid and lipid pathways and with lower levels of γ-glutamyl dipeptides. Three pathways, 2-hydroxybutyrate-related metabolites, γ-glutamyl dipeptides, and lysophosphatidylcholines, which are considered to be involved in inflammation and oxidation, were associated with incident cardiovascular diseases. Conclusions: To our knowledge, this is the largest metabolomic study thus far conducted in nonwhites. Metabolomic biomarkers of alcohol consumption were identified and replicated. The results lend new insight into potential mediating effects between alcohol consumption and future health and disease.

The human metabolome is a measurable outcome of interactions among an individual's inherited genome, microbiome, and dietary intake. We explored the relationship between dietary intake and serum untargeted metabolomic profiles in a subsample of 1,977 African Americans from the Atherosclerosis Risk in Communities (ARIC) Study in 1987-1989. For each metabolite, we conducted linear regression to estimate its relationships with each food group and food category. Potential confounding factors included age, sex, body mass index (weight (kg)/height (m)(2)), energy intake, kidney function, and food groups. We used a modified Bonferroni correction to determine statistical significance. In total, 48 pairs of diet-metabolite associations were identified, including multiple novel associations. The food group "sugar-rich foods and beverages" was inversely associated with 5 metabolites in the 2-hydroxybutyrate-related subpathway and positively associated with 5 γ-glutamyl dipeptides. The hypothesized mechanism of these associations may be through oxidative stress. "Sugar-rich foods and beverages" were also inversely associated with 7 unsaturated long-chain fatty acids. These findings suggest that the contribution of a sugar-rich dietary pattern to increased cardiovascular disease risk may be partially attributed to oxidative stress and disordered lipid profiles. Metabolomics may reveal novel metabolic biomarkers of dietary intake and provide insight into biochemical pathways underlying nutritional effects on disease development.

The relationship between cardiovascular disease (CVD) risk factors and dietary intake is unknown among individuals with spinal cord injury (SCI).To investigate the relationship between consumption of selected food groups (dairy, whole grains, fruits, vegetables, and meat) and CVD risk factors in individuals with chronic SCI.A cross-sectional substudy of individuals with SCI to assess CVD risk factors and dietary intake in comparison with age-, gender-, and race-matched able-bodied individuals enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary history, blood pressure, waist circumference (WC), fasting blood glucose, high-sensitivity C-reactive protein (hs-CRP), lipids, glucose, and insulin data were collected from 100 SCI participants who were 38 to 55 years old with SCI1 year and compared to 100 matched control participants from the CARDIA study.Statistically significant differences between SCI and CARDIA participants were identified in WC (39.2 vs 36.2 in.; P.001) and high-density lipoprotein cholesterol (HDL-C; 39.2 vs 47.5 mg/dL; P.001). Blood pressure, total cholesterol, triglycerides, glucose, insulin, and hs-CRP were similar between SCI and CARDIA participants. No significant relation between CVD risk factors and selected food groups was seen in the SCI participants.SCI participants had adverse WC and HDL-C compared to controls. This study did not identify a relationship between consumption of selected food groups and CVD risk factors.

Objective To assess the awareness and implementation of lipid guidelines among primary pediatric providers. Study design An online survey was administered to primary pediatric providers (n = 1488): pediatricians, family medicine/general practitioners, and advanced practitioners (nurse practitioners/physician assistants) in Minnesota. The survey was conducted over 12 weeks in 2012-2013. A multiple-choice questionnaire was used to evaluate the participants' knowledge, screening, and management attitudes regarding pediatric lipid guidelines. Results The overall response rate was 39% (n = 548 of 1402 successful e-mails). Respondents were primarily pediatricians and family medicine practitioners (37% each), followed by general practitioners (11%) and advanced practitioners (nurse practitioners, 5.5%; physician assistants, 1.6%). Although 74% of providers reportedly believed that lipid screening and treatment would reduce future cardiovascular risk, 34% performed no screening, 50% screened selectively, and only 16% performed universal screening. Pediatricians were more likely to screen, with 30% performing universal screening and 41% performing selective screening. Among perceived barriers to screening, providers reported uneasiness addressing lipid disorders (43%), and unfamiliarity with screening guidelines (31%). The majority (83%) were uncomfortable managing lipid disorders, and 57% were opposed to the use of lipid-lowering medications in children. Conclusion These findings underscore the need to further educate providers and supply easily accessible information on the screening and treatment of childhood lipid disorders.

The composition of dietary intake plays an important role in metabolism, maintaining health and preventing chronic disease. Because we eat many foods every day and not just one nutrient or food, nutrition researchers began studying the whole diet by characterizing usual dietary intake as ‘diet patterns’, ‘diet quality’, diet scores, or diet indexes. Because self-report dietary intake is typically misreported, employing metabolomic biomarkers or a panel of biomarkers may better classify usual dietary intake or diet pattern than the use of self-reported dietary intake alone. We reviewed the current metabolomic literature with the aim of identifying relevant compounds among dietary pattern studies that may be useful in future dietary-metabolomic research. The most common diet patterns were the Western pattern (or high meat intake) and the plant-based pattern (or high in fruit and vegetables, and low in meat). Similar findings of greater carnitine and TMAO concentrations were demonstrated for the diet patterns high in meat. The plant-based diet patterns had higher glycerophosphatidylcholines and sphingolipids, but lower TMAO concentrations. However, the metabolomic pattern varied regardless of the common intake of high or low meat pattern. This may be partly explained by several methodologic differences in study design, which make comparison of the study findings difficult.

A prediction model was developed in the Framingham Heart Study (FHS) to evaluate the short-term risk of hypertension. Our goal was to determine the predictive ability of the FHS hypertension model in a cohort of young adults advancing into middle age and compare it with the predictive ability of prehypertension and individual components of the FHS model. We studied 4388 participants, aged 18 to 30 years without hypertension at baseline, enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, who participated in 2 consecutive examinations occurring 5 years apart between the baseline (1985–1986) and year 25 examination (2010–2011). Weibull regression was used to assess the association of the FHS model overall, individual components of the FHS model, and prehypertension with incident hypertension. During the 25-year follow-up period, 1179 participants developed incident hypertension. The FHS hypertension model (c-index=0.84; 95% confidence interval, 0.83–0.85) performed well in discriminating those who did and did not develop hypertension and was better than prehypertension alone (c-index=0.71; 95% confidence interval, 0.70–0.73). The predicted risk from the FHS hypertension model was systematically lower than the observed hypertension incidence initially (χ 2 =249.4; P 2 =14.6; P =0.067). In summary, the FHS model performed better than prehypertension and may be a useful tool for identifying young adults with a high risk for developing hypertension.

The objective of this study was to describe longitudinal relations of serum total free fatty acids (FFAs) to insulin resistance (IR) and cardiovascular (CV) risk factors from adolescence into adulthood. The cohort included participants in a longitudinal study of obesity and IR with complete data, including anthropometric measures, FFAs, IR measured by euglycemic clamp, blood pressure, fasting serum lipids, and insulin at mean 15 and 22 years of age (n = 207) and their parents (n = 272). FFAs and IR were not significantly related at mean 15 years of age but were significantly related at mean age 22 years. FFA did not relate to BMI at either age. FFA at 15 years of age estimated IR at 22 years of age. In parents (mean age 51 years), FFA was significantly correlated with BMI, percent body fat, systolic blood pressure, LDL, and IR. Associations with all risk factors except IR in parents were attenuated by adjustment for BMI. Most 22 years of age correlations with parents were higher than corresponding 15 years of age correlations. This study finds that FFA is associated with IR starting in young adulthood. The relation between FFA and CV risk factors does not become significant until later adulthood. The results support a significant impact of early metabolic dysfunction on later CV risk.

The benefits of fish oil fatty acids eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) on plasma lipid profiles have been inconsistent but may partially depend on individual Apolipoprotein E (APOE) genotypes. We aimed to determine whether APOE genotype modifies the association of lipid profile characteristics with plasma EPA and DHA levels.APOE genotype was determined in this cross-sectional analysis of 2340 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Relative plasma phospholipid EPA and DHA levels, plasma lipids, and lipoprotein subclass particle sizes and concentrations were measured.Significant gene-EPA interactions were found with HDL-C, and particle concentrations of large and total HDL (p(interaction) = 0.0002, 0.006, and 0.007, respectively). The above lipid targets were positively associated with EPA in the E2 groups, whereas negative trends were observed among the E4 participants. Gene-DHA interactions were noted for small LDL particle concentrations alone (p(interaction) = 0.01), where a positive trend was found among E4 but not E2 or E3 participants.These results indicate a significant contribution of the APOE genotype to the EPA-lipid profile relationship; however, the results do not explain the differences in previous findings regarding LDL-C, triglycerides or total cholesterol. Future investigators examining the effects of EPA on HDL-C or lipoprotein characteristics may consider including APOE genotype in their analyses.

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.

Background— Decades-old animal experiments suggested that dietary long-chain monounsaturated fatty acids (LCMUFAs) caused cardiotoxicity, leading, for example, development of Canola oil (Canadian oil low in erucic acid) from rapeseed. However, potential cardiotoxicity in humans and contemporary dietary sources of LCMUFAs are unknown. Methods and Results— We prospectively investigated the associations of plasma phospholipid LCMUFAs (20:1, 22:1, and 24:1), assessed as objective biomarkers of exposure, with incidence congestive heart failure in 2 independent cohorts: 3694 older adults (mean age, 75.2±5.2 years) in the Cardiovascular Health Study (CHS; 1992–2006) and 3577 middle-aged adults (mean age, 54.1±5.8 years) in the Atherosclerosis Risk in Communities Study, Minnesota subcohort (ARIC; 1987–2008). We further examined dietary correlates of circulating LCMUFAs in CHS and ARIC and US dietary sources of LCMUFAs in the 2003–2010 National Health and Nutrition Examination Survey (NHANES). In CHS, 997 congestive heart failure events occurred during 39 238 person-years; in ARIC, 330 events congestive heart failure events occurred during 64 438 person-years. After multivariable adjustment, higher levels of 22:1 and 24:1 were positively associated with greater incident congestive heart failure in both CHS and ARIC; hazard ratios were 1.34 (95% confidence interval, 1.02–1.76) and 1.57 (95% confidence interval, 1.11–2.23) for highest versus lowest quintiles of 22:1, respectively, and 1.75 (95% confidence interval, 1.23–2.50) and 1.92 (95% confidence interval, 1.22–3.03) for 24:1, respectively ( P for trend ≤0.03 each). A variety of foods were related to circulating LCMUFAs in CHS and ARIC, consistent with food sources of LCMUFAs in NHANES, including fish, poultry, meats, whole grains, and mustard. Conclusions— Higher circulating levels of 22:1 and 24:1, with apparently diverse dietary sources, were associated with incident congestive heart failure in 2 independent cohorts, suggesting possible cardiotoxicity of LCMUFAs in humans.

Objectives. We described 27-year secular trends in added-sugar intake and body mass index (BMI) among Americans aged 25 to 74 years. Methods. The Minnesota Heart Survey (1980–1982 to 2007–2009) is a surveillance study of cardiovascular risk factors among residents of the Minneapolis–St Paul area. We used generalized linear mixed regressions to describe trends in added-sugar intake and BMI by gender and age groups and intake trends by weight status. Results. BMI increased concurrently with added-sugar intake in both genders and all age and weight groups. Percentage of energy intake from added sugar increased by 54% in women between 1980 to 1982 and 2000 to 2002, but declined somewhat in 2007 to 2009; men followed the same pattern (all P Conclusions. Limiting added-sugar intake should be part of energy balance strategies in response to the obesity epidemic.