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Prospective cohort studies have found a relation between sugar-sweetened beverage consumption (SSB; sodas and fruit drinks) and dyslipidemia. There is limited evidence linking SSB consumption to emerging features of dyslipidemia, which can be characterized by variation in lipoprotein particle size, remnant-like particle (RLP), and apolipoprotein concentrations.To examine the association between SSB consumption and plasma lipoprotein cholesterol, apolipoprotein, and lipoprotein particle size concentrations among US adults.We examined participants from the Framingham Offspring Study (FOS) (1987-1995; n = 3047) and the Women's Health Study (1992; n = 26,218). Plasma LDL-C, apolipoprotein (apo) B, HDL-C, apoA1, triglyceride (TG), non-HDL-C, total: HDL-cholesterol ratio, and apoB: apoA1 concentrations were quantified in both cohorts, and apoE, apoC3, RLP-TG, and RLP-cholesterol concentrations in FOS only. Lipoprotein particle sizes were calculated from NMR signals for lipoprotein particle subclass concentrations (triglyceride-rich lipoprotein particles [TRL-P; very large, large, medium, small, and very small], LDL-particles [LDL-P; large, medium, and small], HDL-particles [HDL-P; large, medium, and small]). SSB consumption was estimated from food frequency questionnaire data. We examined the associations between SSB consumption and all lipoprotein and apoprotein measures in linear regression models, adjusting for confounding factors, such as lifestyle, diet, and traditional lipoprotein risk factors.SSB consumption was positively associated with LDL-C, apoB, TG, RLP-TG, RLP-C, non-HDL-C concentrations and total: HDL cholesterol and apoB: apoA1 ratio, and negatively associated with HDL-C and apoA1 concentrations (P-trend ranges from 0.0001 to 0.003). After adjustment for traditional lipoprotein risk factors, SSB consumers had smaller LDL-P and HDL-P sizes, lower concentrations of large LDL-P and medium HDL-P, and higher concentrations of small LDL-P, small HDL-P, and large TRL-P (P-trend ranges from 0.0001 to 0.0009).Higher SSB consumption was associated with multiple emerging features of dyslipidemia that have been linked to higher cardiometabolic risk in US adults.

This cross-sectional study examined whether the probation office setting was feasible to screen adults on probation for cardiometabolic risk factors, measure risk profiles, and estimate the prevalence of obesity, hypertension, hypercholesterolemia, and diabetes. During June and August 2019, screening included blood pressure, anthropometrics, total and high-density lipoprotein (HDL) cholesterol, and glucose. A survey included demographics, medical history, and current medication. The participation rate was 36% (

BACKGROUND: The DASH (Dietary Approaches to Stop Hypertension) diets reduced blood pressure (BP) in the DASH and DASH-Sodium trials, but the underlying mechanisms are unclear. We identified metabolites associated with systolic BP or diastolic BP (DBP) changes induced by dietary interventions (DASH versus control arms) in 2 randomized controlled feeding studies—the DASH and DASH-Sodium trials. METHODS: Metabolomic profiling was conducted in serum and urine samples collected at the end of diet interventions: DASH (n=219) and DASH-Sodium (n=395). Using multivariable linear regression models, associations were examined between metabolites and change in systolic BP and DBP. Tested for interactions between diet interventions and metabolites were the following comparisons: (1) DASH versus control diets in the DASH trial (serum), (2) DASH high-sodium versus control high-sodium diets in the DASH-Sodium trial (urine), and (3) DASH low-sodium versus control high-sodium diets in the DASH-Sodium trial (urine). RESULTS: Sixty-five significant interactions were identified (DASH trial [serum], 12; DASH high sodium [urine], 35; DASH low sodium [urine], 18) between metabolites and systolic BP or DBP. In the DASH trial, serum tryptophan betaine was associated with reductions in DBP in participants consuming the DASH diets but not control diets ( P interaction, 0.023). In the DASH-Sodium trial, urine levels of N-methylglutamate and proline derivatives (eg, stachydrine, 3-hydroxystachydrine, N-methylproline, and N-methylhydroxyproline) were associated with reductions in systolic BP or DBP in participants consuming the DASH diets but not control diets ( P interaction, CONCLUSIONS: We identified metabolites that were associated with BP lowering in response to dietary interventions. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03403166 (DASH trial). URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00000608 (DASH-Sodium trial).

Background The Dietary Approaches to Stop Hypertension (DASH) diet is recommended for cardiovascular disease prevention. We aimed to identify protein biomarkers of the DASH diet using data from 2 randomized feeding studies and validate them in an observational study, the ARIC (Atherosclerosis Risk in Communities) study. Methods and Results Large‐scale proteomic profiling was conducted in serum specimens (SomaLogic) collected at the end of 8‐week and 4‐week DASH diet interventions in multicenter, randomized controlled feeding studies of the DASH trial (N=215) and the DASH‐Sodium trial (N=396), respectively. Multivariable linear regression models were used to compare the relative abundance of 7241 proteins between the DASH and control diet interventions. Estimates from the 2 trials were meta‐analyzed using fixed‐effects models. We validated significant proteins in the ARIC study (N=10 490) using the DASH diet score. At a false discovery rate P P Conclusions We identified 19 proteins robustly associated with the DASH diet in 3 studies, which may serve as biomarkers of the DASH diet. These results suggest potential pathways that are impacted by consumption of the DASH diet. Registration URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT03403166, NCT00000608.

OBJECTIVES Studies suggest an association between elevated total serum cholesterol (TC), particularly low-density lipoprotein (LDL), and osteoarthritis (OA). We evaluated the association between total cholesterol, LDL, and high-density lipoprotein (HDL) and risk of knee OA. METHODS We studied participants from the Multicenter Osteoarthritis study (MOST) cohort at risk of developing knee OA. From baseline through 7 years, repeated knee x-rays and MRIs were obtained and knee symptoms were queried. From baseline fasting blood samples, lipids and lipoproteins were analyzed using standard assays. After excluding participants with baseline OA, we defined two sets of cases: those developing radiographic OA and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of: cartilage loss and synovitis on MRI and of knee pain using the WOMAC scale. We carried out logistic regression adjusting for age, sex, BMI, education, baseline pain, and depressive symptoms, testing total cholesterol and lipoproteins as continuous measures and did sensitivity analyses examining whether commonly used thresholds for high cholesterol, LDL or low HDL increased risk. RESULTS We studied 337 cases with incident symptomatic OA and 283 cases with incident radiographic OA. Mean age at baseline was 62 years (55% women). Neither total cholesterol, LDL nor HDL showed a significant association with radiographic or symptomatic OA. Additionally, we found no association of these lipid measures with cartilage loss, worsening synovitis or worsening knee pain. CONCLUSION Our data do not support an association between total cholesterol, LDL or HDL with OA outcomes.

Introduction: The Dietary Approaches to Stop Hypertension (DASH) diet significantly reduced blood pressure (BP) in the DASH and DASH-Sodium trials, but the underlying mechanisms are unclear. Hypothesis: We hypothesized that certain metabolites will be associated with BP reductions. Methods: Metabolomic profiling was conducted at the end of the diet interventions for participants randomly assigned to the DASH or control diet in multicenter, controlled feeding studies: DASH (N=219) and DASH-Sodium trials (N=395). Using multivariable linear regression models to examine the association between metabolites and BP change, we tested for interactions between diet and metabolites for the following comparisons: 1) DASH vs. control diets in the DASH trial, 2) DASH-high sodium vs. control-high sodium diets in the DASH-Sodium trial, and 3) DASH-low sodium vs. control-high sodium diets in the DASH-Sodium trial. Pathway overrepresentation analysis was constructed for significant metabolites. Results: Identified were 65 significant interactions [DASH=12; DASH-high sodium=35; DASH-low sodium=18]. Most amino acids (16/19), cofactors and vitamins (15/15), xenobiotics (9/13), peptides (4/5), and a nucleotide (1/1) were higher in participants consuming the DASH diets vs. the control diets. These metabolites were associated with BP reductions in participants consuming the DASH diets, but not control diets ( Figure ). Many lipid metabolites (10/12) were lower in participants consuming the DASH vs. the control diets. Lipid concentrations were associated with BP elevations in participants consuming the DASH diets and with BP reductions in participants consuming the control diets. Metabolites associated with tocopherol metabolism, ceramides, and pantothenate and CoA metabolism were overrepresented. Conclusions: Using data from randomized feeding studies, we identified metabolites that were associated with BP lowering. These metabolites highlight the pathways through which DASH diet reduced BP.

Objective: Dietary stearic acid (18:0), a major saturated fatty acid (SFA) in Western diets, does not raise plasma LDL-C concentrations relative to other shorter chain SFAs (palmitic [16:0], myristic [14:0] and lauric [12:0]), and is associated with lower CVD risk. We investigated whether the cardioprotective effects of 18:0 and its metabolic product oleic acid (18:1, a monounsaturated fatty acid) relative to 16:0 is mediated via alterations in the gut microbiome. Methods: Twenty mildly hypercholesterolemic (LDL-C>100mg/dL) post-menopausal women (50-85 years; BMI 25-35kg/m 2 ) consumed each of 3 isocaloric diets for 5 weeks according to a randomized controlled cross-over design. Diets provided 55%E carbohydrate, 15%E protein and 30%E fat with half of the fat provided by 16:0, 18:0 or 18:1, respectively. Fecal samples were collected at the end of each diet phase and shotgun metagenomic sequencing was performed. Alpha diversity (Shannon index, Simpson index and observed counts) was compared between diet groups using two-sample non-parametric tests. Beta-diversity was assessed using Bray-Curtis dissimilarity with PERMANOVA test. Differences in metagenomic features by diet group were evaluated using Partial Least Squares-Discriminant Analysis (PLS-DA) models of pairwise diet differences developed using the R package ‘mixOmics’. Results: No significant differences were observed in alpha and beta diversity between diet groups. However, the variability in microbial relative abundance was greater after participants consumed the 18:0 and 18:1 diets compared to the 16:0 diet. Specifically, mean relative abundance of Bacterioides dorei , Bacteroides vulgatus , and Ruminococcus were highest after participants consumed the 18:0 relative to the 16:0 diet and intermediate after the 18:1 diet. The relative abundance of Coprococcus , Parabacteroides distasonis , Coprobacillus and Blautia were higher after participants consumed the 18:1 relative to the 16:0 diet. These microbial species have been associated with several anti-inflammatory pathways and decreased bacterial lipopolysaccharide production. Conclusion: These data document modest but distinctive effects of dietary SFAs on gut microbiome composition and functionality, suggesting that the favorable effects of 18:0 and 18:1 relative to 16:0 on CVD risk factors could be mediated, in part, by the gut microbiome.

Background: Understanding the genetic contribution to food choices and intake is critical for the development of effective precision nutrition guidance. Recent findings by our lab suggest that genetic variants (SNPs) related to bitter and umami taste perception are differentially associated with food group intakes. The aim of this study was to examine the associations of bitter- and umami-related SNPs, combined as polygenic taste scores, with overall dietary patterns. Methods: Cross-sectional analyses were conducted in 5,817 Framingham Heart Study Offspring (1998-2001) and Third Generation (2002-05) participants (mean age ± SD: 50 ± 14 years; 54% female). Weighed polygenic taste scores were derived using SNPs identified from prior genome-wide association studies for taste perception (11 SNPs: 9 bitter and 2 umami). Higher scores indicated more alleles for higher taste perception. Empirical dietary patterns were derived using Principal Component (PC) analysis with food groups tabulated from food frequency questionnaires. Associations were assessed using linear mixed effects models with FDR adjustment. Results: Three dietary patterns were identified, explaining 32% of total variance in dietary intake: a vegetables, fruits, legumes, and fish pattern (Prudent); a refined grains, sweets, salty foods, and pizza pattern (Western); and a liquor, beer, and wine pattern (Alcohol). On average, after adjusting for age, sex, genetic PCs and energy intake, higher umami polygenic taste scores were associated with lower adherence to the Prudent dietary pattern (OR [95% CI] for upper vs. lower tertial of dietary pattern adherence scores per additional allele for higher umami perception: 0.87 [0.79, 0.97]; P = 0.01). Subsequent analysis at the SNP-level identified one umami-related SNP (rs7691456_T) independently associated with lower Prudent dietary pattern adherence ( P = 0.009), potentially driving the observed association. Both associations remained significant after additional adjustment for smoking, physical activity, and BMI. No significant associations were identified for bitter-related genes and dietary patterns. Conclusions: Among community dwelling adults, higher genetic predisposition to perceive umami was associated with lower adherence to a Prudent dietary pattern, suggesting the potential benefit of leveraging knowledge of taste-related genes in precision nutrition.

Background Greater whole grain (WG) consumption is associated with reduced risk of cardiovascular disease (CVD); however, few prospective studies have examined WG or refined grain (RG) intake and intermediate cardiometabolic risk factors. Objectives We examined the longitudinal association between WG and RG intake on changes in waist circumference (WC); fasting HDL cholesterol, triglyceride, and glucose concentrations; and blood pressure. Methods Subjects were participants in the Framingham Offspring cohort study [n = 3121; mean ± SD baseline age: 54.9 ± 0.2 y; BMI (kg/m2) 27.2 ± 0.1]. FFQ, health, and lifestyle data were collected approximately every 4 y over a median 18-y follow-up. Repeated measure mixed models were used to estimate adjusted mean changes per 4-y interval in risk factors across increasing categories of WG or RG intake. Results Greater WG intake was associated with smaller increases in WC (1.4 ± 0.2 compared with 3.0 ± 0.1 cm in the highest compared with the lowest category, respectively; P-trend

Background Higher childhood overweight/obesity has been associated with an elevated risk of insulin resistance and cardiometabolic disorders. Waist-to-height ratio (WHtR) may be a simple screening tool to identify children at risk for cardiometabolic associated obesity. This study investigated whether being in the upper tertile for WHtR predicted the odds of insulin resistance, elevated liver enzyme concentrations, and cardiometabolic risk factor measures using cross-sectional data from the Family Weight Management Study randomized controlled trial. Methods Included was baseline data (n = 360, 7–12 years, mean Body Mass Index ≥ 85th percentile for age and sex). WHtR were grouped into tertiles by sex, male: ≤0.55(T1), > 0.55-≤0.59(T2), > 0.59(T3); female: ≤0.56(T1),>0.56-≤0.6(T2), > 0.6(T3). The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was used to categorize participants as insulin-resistant (HOMA-IR ≥ 2.6) and insulin-sensitive (HOMA-IR 2.6) were over 5fold higher among children in T3 versus T1 (males) and T2 and T3 versus T1 (females). The odds of elevated ALT values (≥ 30) were 2.9 fold higher among female children in T3 compared to T1. Conclusion WHtR may be a practical screening tool in pediatric populations with overweight/obesity to identify children at risk of IR and cardiometabolically unhealthy phenotypes in public health settings.

Background We sought to determine the associations between individual nonesterified fatty acids (NEFAs) and disability and mobility limitation. Methods We studied 1 734 participants in the Cardiovascular Health Study (CHS), an ongoing population-based cohort study of community-living older American adults. We measured 35 individual NEFA species in fasting serum samples obtained at the 1996–1997 clinic visit. Using yearly assessments of activities of daily living and self-reported mobility, we identified participants with incident disability or mobility limitation during 15 years of follow-up. Cox proportional hazards regression models were used to determine the associations between per SD increment in the individual NEFAs and incident disability and mobility limitations with adjustment for potential confounding factors. Results Higher concentrations of total and a broad range of individual NEFA species were associated with risk of disability and mobility limitation (disability: HR per SD of total NEFA [SD = 174.70] = 1.11, 95% CI = 1.04–1.18, p = .001; mobility limitation: HR per SD of total NEFA = 1.09, 95% CI = 1.02–1.16, p = .01). Among individual saturated NEFAs (SFAs), myristic (14:0) and palmitic (16:0) acids were significantly associated with higher risk of both disability and mobility limitations, but longer-chain FAs were not. Most individual monounsaturated (MUFA), n-6 polyunsaturated fatty acids (PUFAs), and trans FAs were positively significantly associated with higher risks of both disability and mobility limitation. In contrast, most n-3 PUFA species were not associated with disability or mobility limitation. Conclusions Higher risks of disability and mobility limitation were observed for proinflammatory intermediate-chain SFAs, MUFAs, n-6 PUFAs, and trans FAs. Our findings indicated no significant association for anti-inflammatory n-3 PUFAs.

Summary Objective Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Saturated and n-6 fatty acids (FAs) increase, whereas n-3 FAs reduce inflammation. We examined whether FA levels affected the development of OA. Design We studied participants from the Multicenter Osteoarthritis study (MOST) at risk of developing knee OA. After baseline, repeated knee x-rays and MRIs were obtained and knee symptoms queried through 60 month follow-up. Using baseline fasting samples, serum FAs were analyzed with standard assays. After excluding participants with baseline OA, we defined two sets of cases: those developing radiographic OA and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage loss and synovitis and of knee pain using WOMAC and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of saturated, n-3 and n-6 FAs adjusting for age, sex, BMI, education, race, baseline pain and depressive symptoms. Results We studied 260 cases with incident symptomatic and 259 with incident radiographic OA. Mean age was 61 years (61% women). We found no signficant nor suggestive associations of FA levels with incident OA (e.g., for incident symptomatic OA, OR per s.d. increase in n-3 FA 1.00 (0.85, 1.18) nor with any OA outcome in knee or hand. Conclusion Despite previously described effects on systemic inflammation, blood levels of FAs were not associated with risk of later knee OA or other OA outcomes.

Background Excess visceral adiposity is associated with increased risk of cardiometabolic disorders. Short‐term well‐controlled clinical trials suggest that regular avocado consumption favorably affects body weight, visceral adiposity, and satiety. Methods and Results The HAT Trial (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled parallel‐arm trial designed to test whether consuming 1 large avocado per day for 6 months in a diverse group of free‐living individuals (N=1008) with an elevated waist circumference compared with a habitual diet would decrease visceral adiposity as measured by magnetic resonance imaging. Secondary and additional end points related to risk factors associated with cardiometabolic disorders were assessed. The primary outcome, change in visceral adipose tissue volume during the intervention period, was not significantly different between the Avocado Supplemented and Habitual Diet Groups (estimated mean difference (0.017 L [−0.024 L, 0.058 L], P =0.405). No significant group differences were observed for the secondary outcomes of hepatic fat fraction, hsCRP (high‐sensitivity C‐reactive protein), and components of the metabolic syndrome. Of the additional outcome measures, modest but nominally significant reductions in total and low‐density lipoprotein cholesterol were observed in the Avocado Supplemented compared with the Habitual Diet Group. Changes in the other additional and post hoc measures (body weight, body mass index, insulin, very low‐density lipoprotein concentrations, and total cholesterol:high‐density lipoprotein cholesterol ratio) were similar between the 2 groups. Conclusions Addition of 1 avocado per day to the habitual diet for 6 months in free‐living individuals with elevated waist circumference did not reduce visceral adipose tissue volume and had minimal effect on risk factors associated with cardiometabolic disorders. Registration URL: https://clinicaltrials.gov ; Unique identifier: NCT03528031.

Background: Heart failure (HF) is highly prevalent among older adults and is associated with high costs. Although serum total nonesterified fatty acids (NEFAs) have been positively associated with HF risk, the contribution of each individual NEFA to HF risk has not been examined. Objective: The aim of this study was to examine the association of individual fasting NEFAs with HF risk in older adults. Methods: In this prospective cohort study of older adults, we measured 35 individual NEFAs in 2,140 participants of the Cardiovascular Health Study using gas chromatography. HF was ascertained using review of medical records by an endpoint committee. Results: The mean age was 77.7 ± 4.4 years, and 38.8% were male. During a median follow-up of 9.7 (maximum 19.0) years, 655 new cases of HF occurred. In a multivariable Cox regression model controlling for demographic and anthropometric variables, field center, education, serum albumin, glomerular filtration rate, physical activity, alcohol consumption, smoking, hormone replacement therapy, unintentional weight loss, and all other measured NEFAs, we observed inverse associations (HR [95% CI] per standard deviation) of nonesterified pentadecanoic (15:0) (0.73 [0.57–0.94]), γ-linolenic acid (GLA) (0.87 [0.75–1.00]), and docosahexaenoic acid (DHA) (0.73 [0.61–0.88]) acids with HF, and positive associations of nonesterified stearic (18:0) (1.30 [1.04–1.63]) and nervonic (24:1n-9) (1.17 [1.06–1.29]) acids with HF. Conclusion: Our data are consistent with a higher risk of HF with nonesterified stearic and nervonic acids and a lower risk with nonesterified 15:0, GLA, and DHA in older adults. If confirmed in other studies, specific NEFAs may provide new targets for HF prevention.

Background In animal models cis-palmitoleic acid (9-hexadecenoic acid; 16:1n-7c), a lipokine, improves insulin sensitivity, inflammation, and lipoprotein profiles; in humans trans-palmitoleic acid (16:1n-7t) has been associated with lower incidence of type 2 diabetes. The response to dose-escalation of supplements containing cis- and trans-palmitoleic acid has not been evaluated. Objectives We examined dose-escalation effects of oral supplementation with seabuckthorn oil and seabuckthorn oil augmented in 16:1n-7t on serum phospholipid fatty acids (PLFAs). Methods Thirteen participants (7 women and 6 men; age 48 ± 16 y, BMI 30.4 ± 3.7 kg/m2) participated in a randomized, double-blind, crossover, dose-escalation trial of unmodified seabuckthorn oils relatively high in 16:1n-7c (380, 760, and 1520 mg 16:1n-7c/d) and seabuckthorn oils augmented in 16:1n-7t (120, 240, and 480 mg 16:1n-7t/d). Each of the 3 escalation doses was provided for 3 wk, with a 4-wk washout period between the 2 supplements. At the end of each dose period, fasting blood samples were used to determine the primary outcomes (serum concentrations of the PLFAs 16:1n-7t and 16:1n-7c) and the secondary outcomes (glucose homeostasis, serum lipids, and clinical measures). Trends across doses were evaluated using linear regression. Results Compared with baseline, supplementation with seabuckthorn oil augmented in 16:1n-7t increased phospholipid 16:1n-7t by 26.6% at the highest dose (P = 0.0343). Supplementation with unmodified seabuckthorn oil resulted in a positive trend across the dose-escalations (P-trend = 0.0199). No significant effects of either supplement were identified on blood glucose, insulin, lipids, or other clinical measures, although this dosing study was not powered to detect such effects. No carryover or adverse effects were observed. Conclusions Supplementation with seabuckthorn oil augmented in 16:1n-7t and unmodified seabuckthorn oil moderately increased concentrations of their corresponding PLFAs in metabolically healthy adults, supporting the use of supplementation with these fatty acids to test potential clinical effects in humans.This trial was registered at clinicaltrials.gov as NCT02311790.

Lack of biomarkers is a challenge for the accurate assessment of protein intake and interpretation of observational study data. The study aims to identify biomarkers of a protein-rich dietary pattern.The Optimal Macronutrient Intake Trial to Prevent Heart Disease (OmniHeart) trial is a randomized cross-over feeding study which tested three dietary patterns with varied macronutrient content (carbohydrate-rich; protein-rich with about half from plant sources; and unsaturated fat-rich). In 156 adults, differences in log-transformed plasma metabolite levels at the end of the protein- and carbohydrate-rich diet periods using paired t-tests is examined. Partial least-squares discriminant analysis is used to identify a set of metabolites which are influential in discriminating between the protein-rich versus carbohydrate-rich dietary patterns. Of 839 known metabolites, 102 metabolites differ significantly between the protein-rich and the carbohydrate-rich dietary patterns after Bonferroni correction, the majority of which are lipids (n = 35), amino acids (n = 27), and xenobiotics (n = 24). Metabolites which are the most influential in discriminating between the protein-rich and the carbohydrate-rich dietary patterns represent plant protein intake, food or beverage intake, and preparation methods.The study identifies many plasma metabolites associated with the protein-rich dietary pattern. If replicated, these metabolites may be used to assess level of adherence to a similar dietary pattern.

Engagement in healthy lifestyle behaviors is suboptimal. The vast majority of the US population does not meet current recommendations. A healthy lifestyle is defined by consuming a healthy dietary pattern, engaging in regular physical activity, avoiding exposure to tobacco products, habitually attaining adequate amounts of sleep, and managing stress levels. For all these health behaviors there are well-established guidelines; however, promotion in clinical settings can be challenging. It is critical to overcome these challenges because greater promotion of heathy lifestyle practices in clinical settings effectively motivates and initiates patient behavior change. The 5A Model (assess, advise, agree, assist, and arrange) was developed to provide a framework for clinical counseling with requisite attention to the demands of clinical settings. In this science advisory, we present strategies, based on the 5A Model, that clinicians and other health care professionals can use for efficient lifestyle-related behavior change counseling in patients at all levels of cardiovascular disease risk at every visit. In addition, we discuss the underlying role of psychological health and well-being in lifestyle-related behavior change counseling, and how clinicians can leverage health technologies when providing brief patient-centered counseling. Greater attention to healthy lifestyle behaviors during routine clinician visits will contribute to promoting cardiovascular health.

Poor diet quality is strongly associated with elevated risk of cardiovascular disease morbidity and mortality. This scientific statement emphasizes the importance of dietary patterns beyond individual foods or nutrients, underscores the critical role of nutrition early in life, presents elements of heart-healthy dietary patterns, and highlights structural challenges that impede adherence to heart-healthy dietary patterns. Evidence-based dietary pattern guidance to promote cardiometabolic health includes the following: (1) adjust energy intake and expenditure to achieve and maintain a healthy body weight; (2) eat plenty and a variety of fruits and vegetables; (3) choose whole grain foods and products; (4) choose healthy sources of protein (mostly plants; regular intake of fish and seafood; low-fat or fat-free dairy products; and if meat or poultry is desired, choose lean cuts and unprocessed forms); (5) use liquid plant oils rather than tropical oils and partially hydrogenated fats; (6) choose minimally processed foods instead of ultra-processed foods; (7) minimize the intake of beverages and foods with added sugars; (8) choose and prepare foods with little or no salt; (9) if you do not drink alcohol, do not start; if you choose to drink alcohol, limit intake; and (10) adhere to this guidance regardless of where food is prepared or consumed. Challenges that impede adherence to heart-healthy dietary patterns include targeted marketing of unhealthy foods, neighborhood segregation, food and nutrition insecurity, and structural racism. Creating an environment that facilitates, rather than impedes, adherence to heart-healthy dietary patterns among all individuals is a public health imperative.

Guidelines for designing, conducting, documenting, and reporting human nutrition randomized controlled trials (RCTs) have as yet to be developed and disseminated as reference for investigators, funders, regulators, institutions, assessors, trainees, and others involved in human nutrition research. Diet-related interventions can include diet and/or behavioral manipulation, provision of foods or entire meals, or delivery of dietary components in individual food items or supplements. This Perspective introduces a series of papers that outline core principles for the design and conduct of human nutrition RCTs, documentation and reporting of all aspects of clinical trial management, and data analysis and reporting of results. Human nutrition RCTs have unique considerations delineated in these papers. Conducting them with the highest scientific rigor is essential to the development of evidence-based dietary guidance for promoting optimal health and advancing health care.

Parental involvement has been shown to favorably affect childhood weight-management interventions, but whether these interventions influence parental diet and cardiometabolic health outcomes is unclear.The aim was to evaluate whether a 1-y family-based childhood weight-management intervention altered parental nutrient biomarker concentrations and cardiometabolic risk factors (CMRFs).Secondary analysis from a randomized-controlled, parallel-arm clinical trial (NCT00851201). Families were recruited from a largely Hispanic population and assigned to either standard care (SC; American Academy of Pediatrics overweight/obesity recommendations) or SC + enhanced program (SC+EP; targeted diet/physical activity strategies, skill building, and monthly support sessions). Nutrient biomarkers (plasma carotenoids and fat-soluble vitamins, RBC fatty acid profiles) and CMRFs (BMI, blood pressure, glucose, insulin, lipid profile, inflammatory and endothelial dysfunction markers, adipokines) were measured in archived samples collected from parents of participating children at baseline and end of the 1-y intervention.Parents in both groups (SC = 106 and SC+EP = 99) had significant reductions inThe benefits of a family-based childhood weight-management intervention can spill over to parents, resulting in apparent healthier dietary shifts that are associated with modest improvements in some CMRFs.

Supplemental Digital Content is available in the text., Background: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia. Methods: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake. Results: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16–3.07] mg/dL per allele; P

Background: Healthy dietary patterns are related to better cognitive health in aging populations. While levels of individual nutrients in neural tissues are individually associated with cognitive function, the investigation of nutrient patterns in human brain tissue has not been conducted.Methods: Brain tissues were acquired from frontal and temporal cortices of 47 centenarians from the Georgia Centenarian Study. Fat-soluble nutrients (carotenoids, vitamins A, E, K, and fatty acids [FA]) were measured and averaged from the two brain regions. Nutrient patterns were constructed using principal component analysis. Cognitive composite scores were constructed from cognitive assessment from the time point closest to death. Dementia status was rated by Global Deterioration Scale (GDS). Pearson's correlation coefficients between NP scores and cognitive composite scores were calculated controlling for sex, education, hypertension, diabetes, and APOE ε4 allele.Result: Among non-demented subjects (GDS = 1–3, n = 23), a nutrient pattern higher in carotenoids was consistently associated with better performance on global cognition (r = 0.38, p = 0.070), memory (r = 0.38, p = 0.073), language (r = 0.42, p = 0.046), and lower depression (r = −0.40, p = 0.090). The findings were confirmed with univariate analysis.Conclusion: Both multivariate and univariate analyses demonstrate that brain nutrient pattern explained mainly by carotenoid concentrations is correlated with cognitive function among subjects who had no dementia. Investigation of their synergistic roles on the prevention of age-related cognitive impairment remains to be performed.

Background The risk of stroke in individuals with very low low-density lipoprotein cholesterol (LDL-C) concentrations remains high. We sought to prioritize predictive risk factors for stroke in Chinese participants with LDL-C concentrations Methods The training dataset included 9327 individuals with LDL-C concentrations Results During a mean 8.5–9.0-year follow-up period, we identified 388 ischemic stroke cases and 145 hemorrhagic stroke cases in the training dataset and 20 ischemic stroke cases and 8 hemorrhagic stroke cases in the validation dataset. Of 15 examined predictors, poorly controlled blood pressure and very low LDL-C concentrations (≤ 40 mg/dL) were the top hierarchical predictors of both ischemic stroke risk and hemorrhagic stroke risk. The groups, characterized by the presence of 2–3 of aforementioned risk factors, were associated with a higher risk of ischemic stroke (hazard ratio (HR) 7.03; 95% confidence interval (CI) 5.01–9.85 in the training dataset; HR 4.68, 95%CI 1.58–13.9 in the validation dataset) and hemorrhagic stroke (HR 3.94, 95%CI 2.54–6.11 in the training dataset; HR 4.73, 95%CI 0.81–27.6 in the validation dataset), relative to the lowest risk groups (presence of 0–1 of these factors). There was a linear association between cumulative average LDL-C concentrations and stroke risk. LDL-C concentrations ≤ 40 mg/dL was significantly associated with increased risk of ischemic stroke (HR 2.07, 95%CI 1.53, 2.80) and hemorrhagic stroke (HR 2.70, 95%CI 1.70, 4.30) compared to LDL-C concentrations of 55–70 mg/dL, after adjustment for age, hypertension status, and other covariates. Conclusion Individuals with extremely low LDL-C concentrations without previous lipid-modifying treatment could still be at high stroke risk. Trial registration Chinese Clinical Trial Register, ChiCTR-TNRC-11001489. Registered on 24-08-2011.

To formulate precision nutrition prescriptions, it is essential to understand the relationship between dietary assessment, ethnicity and cardiometabolic disease. Erythrocyte (RBC) fatty acid (FA) profiles reflect long-term dietary fat intake but have not been rigorously compared with short-term FA intake in women of African ancestry who have paradoxically low triglycerides with high fat intake. We compared the type of dietary fat consumed (proportion of total fat) using food records with fasting RBC FA (mol%) determined by gas chromatography in 130 female, healthy, federal employees without diabetes (12% African Immigrants (AI), 47% African Americans (AA), 41% White Americans (WA)); mean age 43+10 y and BMI 30 + 6 kg/m2). Diet quality and home prepared meals were similar across ethnicities. AI reported the lowest energy intake. Regardless of absolute energy intake, macronutrient distributions were similar. Fat intake differed by ethnicity; WA had the highest saturated FA (SFA) and lowest eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and omega-3 index (EPA + DHA), while AI and AA had similar SFA, EPA and DHA intake. AI women had the highest RBC DHA and omega-3 index. Associations between FA intake and RBC profiles were significant for DHA (r=0.3, p Disclosure A. B. Courville: None. S. T. Chung: None. S. Yang: None. L. Mabundo: None. C. K. Cravalho: None. S. Matta: None. A. Villalobos-perez: None. J. M. Dawson: None. A. H. Lichtenstein: None. A. E. Sumner: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases

ObjectiveTo prospectively examine the association between low-density lipoprotein (LDL) cholesterol (LDL-C) concentrations and intracerebral hemorrhage (ICH) risk.MethodsThe current cohort study included 96,043 participants (mean age 51.3 years) who were free of stroke, myocardial infarction, and cancer at baseline (2006). Serum LDL-C concentrations were assessed in 2006, 2008, 2010, and 2012. Cumulative average LDL-C concentrations were calculated from all available LDL-C data during that period. Incident ICH was confirmed by review of medical records.ResultsWe identified 753 incident ICH cases during 9 years of follow-up. The ICH risk was similar among participants with LDL concentrations of 70 to 99 mg/dL and those with LDL-C concentrations ≥100 mg/dL. In contrast, participants with LDL-C concentrations ConclusionsWe observed a significant association between lower LDL-C and higher risk of ICH when LDL-C was

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D). We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based cohort studies. Hepatic fat was measured using computed tomography or ultrasound imaging and DNA methylation was assessed at >400,000 cytosine-guanine dinucleotides (CpGs) in whole blood or CD14+ monocytes using a commercial array. We identified 22 CpGs associated with hepatic fat in EA participants at a false discovery rate

Food intake data collected using subjective tools are prone to inaccuracies and biases. An objective assessment of food intake, such as metabolomic profiling, may offer a more accurate method if unique metabolites can be identified. To explore this option, we used samples generated from a randomized and controlled cross-over trial during which participants (N = 10; 65 ± 8 year, BMI, 29.8 ± 3.2 kg/m2) consumed each of the three diets enriched in different types of carbohydrate. Plasma metabolite concentrations were measured at the end of each diet phase using gas chromatography/time-of-flight mass spectrometry and ultra-high pressure liquid chromatography/quadrupole time-of-flight tandem mass spectrometry. Participants were provided, in random order, with diets enriched in three carbohydrate types (simple carbohydrate (SC), refined carbohydrate (RC) and unrefined carbohydrate (URC)) for 4.5 weeks per phase and separated by two-week washout periods. Data were analyzed using partial least square-discrimination analysis, receiver operating characteristics (ROC curve) and hierarchical analysis. Among the known metabolites, 3-methylhistidine, phenylethylamine, cysteine, betaine and pipecolic acid were identified as biomarkers in the URC diet compared to the RC diet, and the later three metabolites were differentiated and compared to SC diet. Hierarchical analysis indicated that the plasma metabolites at the end of each diet phase were more strongly clustered by the participant than the carbohydrate type. Hence, although differences in plasma metabolite concentrations were observed after participants consumed diets differing in carbohydrate type, individual variation was a stronger predictor of plasma metabolite concentrations than dietary carbohydrate type. These findings limited the potential of metabolic profiling to address this variable.

Objective: Evidence suggests perception of sweet, salt, sour, bitter, and umami tastes may be independently related to food preferences and intake. Our objective was to determine whether a collective measure of taste perception for all 5 tastes—“taste perception profiles”—was related to adherence to a Mediterranean diet (MedD). Methods: Participants were 367 older adults (55-75 years; 55% female) with metabolic syndrome from PREDIMED-Plus, Valencia. A data-driven clustering approach identified six taste perception profiles from baseline taste perception scores: Low All ( n = 85), High Bitter ( n = 41), High Umami ( n = 61), Low Bitter & Umami ( n = 59), High All But Bitter ( n = 72) and High All But Umami ( n = 49). A MedD adherence score was tabulated from a questionnaire which captured adherence to 17 pre-determined MedD criteria (range = 0-17; 1 point per criteria met). Generalized linear models were used to determine the relations between taste perception profiles and MedD adherence scores, with confounder adjustment. Results: Across profiles, there were no significant differences in MedD adherence scores (unadjusted mean range = 8.1-8.6; ANOVA, p = 0.97); however, there were significant differences in the criteria met by each profile. For High All But Bitter and Low All profiles, 71% vs. 42% of individuals, respectively, met criteria for adequate vegetable intake (chi square = 12.8, p = 0.03); and for High All But Umami and High All But Bitter profiles, 95% vs. 65% of individuals, respectively, reported preferring lean over red meat (chi square = 12.5, p = 0.03). After adjusting for age, sex, physical activity, smoking status, diabetes, medication use and energy intake, compared to individuals with Low All (reference), those with High All But Bitter were more likely to meet criteria for adequate vegetable (OR [95% CI] = 2.9 [1.3, 6.6]), adequate sofrito (2.4 [1.1, 5.4]) and moderate wine (4.1 [1.5, 11.3]) intakes, and less likely to meet criteria for low non-whole grain pasta/rice (0.3 [0.1, 0.8]), white bread (0.3 [0.1, 0.6]) and red/processed meat (0.3 [0.2, 0.7]) intakes, and to report preferring lean over red meat (0.3 [0.1, 0.8]) and using extra virgin olive oil as a main cooking fat (0.4 [0.2, 0.95]); individuals with High Bitter were more likely to meet criteria for adequate fruit (2.7 [1.3, 5.5]) and less likely to meet criteria for low sugar-sweetened beverage (0.4 [0.2, 0.8]) intakes, while those with High Umami were more likely to meet criterion for adequate vegetable intake (2.2 [1.1, 4.5]). Neither Low Bitter & Umami nor High All But Umami were significantly associated with MedD adherence. Conclusions: Among older adults with metabolic syndrome, taste perception profiles were associated with differential patterns of adherence to a MedD, supporting the use of taste perception profiles when developing individualized dietary modification strategies to improve cardiometabolic risk factors.

Sexual dimorphism in the immune system is evidenced by a higher prevalence of autoimmune diseases in women and higher susceptibility to infectious diseases in men. However, the molecular basis of these sex-based differences is not fully understood. We have characterized the transcriptome profiles of peripheral blood monocytes from males and postmenopausal females with chronic low-grade inflammation. We identified 41 sexually differentially expressed genes [adjustedpvalue (FDR) CEACAM1,FCGR2B, andSLAMF7) and antigen presentation (e.g.,AIM2,CD1E, andUBA1) with a higher expression in females than males. Moreover, signaling pathways of immune or inflammatory responses, including interferon (IFN) signaling [z-score = 2.45, -log(p) = 3.88], were found to be more upregulated in female versus male monocytes, based on a set of genes exhibiting sex-biased expression (p< 0.03). The contribution of IFN signaling to the sexual transcriptional differences was further confirmed by direct comparisons of the monocyte sex-biased genes with IFN signature genes (ISGs) that were previously curated in mouse macrophages. ISGs showed a greater overlap with female-biased genes than male-biased genes and a higher overall expression in female than male monocytes, particularly for the genes of antiviral and inflammatory responses to IFN. Given the role of IFN in immune defense and autoimmunity, our results suggest that sexual dimorphism in immune functions may be associated with more priming of innate immune pathways in female than male monocytes. These findings highlight the role of sex on the human immune transcriptome.

Background Studies regarding whether light to moderate alcohol consumption is associated with a lower risk of cardiovascular diseases (CVD) have generated mixed results. Further, few studies have examined the potential impact of alcohol consumption on diverse disease outcomes simultaneously. We aimed to prospectively study the dose-response association between alcohol consumption and risk of CVD, cancer, and mortality. Methods This study included 83,732 adult Chinese participants, free of CVD and cancer at baseline. Participants were categorized into 6 groups based on self-report alcohol consumption: 0, 1–25, 26–150, 151–350, 351–750, and > 750 g alcohol/wk. Incident cases of CVD, cancers, and mortality were confirmed by medical records. Hazard ratios (HRs) for the composite risk of these three outcomes, and each individual outcome, were calculated using Cox proportional hazard model. Results During a median follow-up of 10.0 years, there were 6411 incident cases of CVD, 2947 cancers and 6646 deaths. We observed a J-shaped relation between alcohol intake and risk of CVD, cancer, and mortality, with the lowest risk at 25 g/wk., which is equivalent to ~ 2 servings/wk. Compared to consuming 1–25 g/wk., the adjusted HR for composite outcomes was 1.38 (95% confidence interval (CI):1.29–1.49) for non-drinker, 1.15 (95% CI: 1.04–1.27) for 26–150 g/wk., 1.22 (95% CI: 1.10–1.34) for 151–350 g/wk., 1.33 (95% CI: 1.21–1.46) for 351–750 g/wk., and 1.57 (95% CI: 1.30–1.90) for > 750 g/wk., after adjusting for age, sex, lifestyle, social economic status, and medication use. Conclusions Light alcohol consumption at ~ 25 g/wk was associated with lower risk of CVD, cancer, and mortality than none or higher consumption in Chinese adults.

BACKGROUND Lifestyle interventions are the first-line treatment for obesity, but participant weight loss is typically low. OBJECTIVES We evaluated the efficacy of an alternative lifestyle intervention [Healthy Weight for Living (HWL)] compared with a modified Diabetes Prevention Program (m-DPP). HWL was based on a revised health behavior change model emphasizing hunger management and the development of healthy food preferences. m-DPP was a standard Diabetes Prevention Program implemented with counselor time matched to HWL. Participants were adult dependents of military personnel and had overweight or obesity. METHODS Participants were randomly assigned to HWL (n = 121) or m-DPP (n = 117), delivered primarily by group videoconference with additional midweek emails. The primary outcome was 12-mo weight change. Secondary outcomes included 6-mo changes in cardiometabolic risk factors and diet. Intention-to-treat (ITT) and complete case (CC) analyses were performed using linear mixed models. RESULTS Retention did not differ between groups (72% and 66% for HWL and m-DPP at 12 mo, respectively; P = 0.30). Mean ± SE adjusted 12-mo weight loss in the ITT cohort was 7.46 ± 0.85 kg for HWL and 7.32 ± 0.87 kg for m-DPP (P = 0.91); in the CC cohort, it was 7.83 ± 0.82 kg for HWL and 6.86 ± 0.88 kg for m-DPP (P = 0.43). Thirty-eight percent of HWL and 30% of m-DPP completers achieved ≥10% weight loss (P = 0.32). Improvements in systolic blood pressure, LDL cholesterol, triglycerides, fasting glucose, general health, sleep, and mood were similar across groups; improvements in diastolic blood pressure were greater in m-DPP. Adjusted group mean reductions in energy intake were not significantly different between groups, but HWL participants were more adherent to their dietary prescription for lower glycemic index and high fiber and protein (P = 0.05 to

Taste perception is a primary driver of food choices; however, little is known about how perception of all five tastes (sweet, salt, sour, bitter, umami) collectively inform dietary patterns. Our aim was to examine the associations between a multivariable measure of taste perception—taste perception profiles—and empirically derived dietary patterns. The cohort included 367 community-dwelling adults (55–75 years; 55% female; BMI = 32.2 ± 3.6 kg/m2) with metabolic syndrome from PREDIMED-Plus, Valencia. Six taste perception profiles were previously derived via data-driven clustering (Low All, High Bitter, High Umami, Low Bitter and Umami, High All But Bitter, High All But Umami); three dietary patterns were derived via principal component analysis (% variance explained = 20.2). Cross-sectional associations between profiles and tertials of dietary pattern adherence were examined by multinomial logistic regression. Overall, there were several significant differences in dietary pattern adherence between profiles: the vegetables, fruits, and whole grains pattern was significantly more common for the High All But Umami profile (OR range for high vs. low adherence relative to other profiles (1.45–1.99; 95% CI minimum lower, maximum upper bounds: 1.05, 2.74), the non-extra virgin olive oils, sweets, and refined grains pattern tended to be less common for Low All or High Bitter profiles (OR range: 0.54–0.82), while the alcohol, salty foods, and animal fats pattern tended to be less common for Low Bitter and Umami and more common for High All But Bitter profiles (OR range: 0.55–0.75 and 1.11–1.81, respectively). In conclusion, among older adults with metabolic syndrome, taste perception profiles were differentially associated with dietary patterns, suggesting the benefit of integrating taste perception into personalized nutrition guidance.

Compare the postprandial fatty acid metabolism of isotopically labeled stearate (U-The neutrality of 18:0 on plasma LDL-cholesterol concentrations is not attributable to a single factor. Compared with 18:1, 18:0 had higher plasma area under the curve because of lower clearance and oxidation rates, underwent both a direct and a multistage conversion to 18:1, and was preferentially incorporated into cholesteryl esters and triglycerides.

Experimental studies have found that the functionality of HDL cholesterol may be lost in the presence of diabetes mellitus (DM).We aimed to elucidate whether DM modified the association between HDL-cholesterol concentrations and cardiovascular disease (CVD) outcomes.Included were 91,354 Chinese adults (8244 participants with DM and 83,110 participants without DM) free of CVD or cancer at baseline (2006) and without use of lipid-lowering drugs at baseline and during follow-up. The primary endpoint of interest was a composite of CVDs (myocardial infarction, ischemic stroke, and hemorrhagic stroke). Cumulative average HDL-cholesterol concentrations were calculated from all available HDL-cholesterol measures at baseline (2006) and during the follow-up period (2008, 2010, 2012, and 2014).During a mean of 10.4 y of follow-up, there were 5076 CVD events identified. There was a significant interaction between DM and HDL-cholesterol concentrations on CVD risk (Pinteraction = 0.003). The association between HDL-cholesterol concentrations and CVD followed a U-shaped curve in individuals without DM (Pnonlinearity 0.001). The adjusted HR of CVD was 1.26 (95% CI: 1.07, 1.48) for HDL-cholesterol concentrations 1.04 mmol/L and 1.76 (95% CI: 1.53, 2.03) for HDL-cholesterol concentrations 2.07 mmol/L, relative to the lowest-risk group (HDL-cholesterol concentrations of 1.30-1.42 mmol/L). In participants with DM, higher HDL-cholesterol concentrations were associated with a higher risk of CVD, in a dose-response manner (Pnonlinearity = 0.44; Ptrend 0.001). The adjusted HR of CVD was 1.62 (95% CI: 1.19, 2.20) for HDL-cholesterol concentrations 2.07 mmol/L, relative to HDL-cholesterol concentrations of 1.30-1.42 mmol/L.High HDL-cholesterol concentrations were paradoxically associated with high risk of composite CVD outcomes in individuals with or without DM. However, low HDL-cholesterol concentrations failed to predict future CVD risk in individuals with DM.

It is critical that diet quality be assessed and discussed at the point of care with clinicians and other members of the healthcare team to reduce the incidence and improve the management of diet-related chronic disease, especially cardiovascular disease. Dietary screening or counseling is not usually a component of routine medical visits. Moreover, numerous barriers exist to the implementation of screening and counseling, including lack of training and knowledge, lack of time, sense of futility, lack of reimbursement, competing demands during the visit, and absence of validated rapid diet screener tools with coupled clinical decision support to identify actionable modifications for improvement. With more widespread use of electronic health records, there is an enormous unmet opportunity to provide evidence-based clinician-delivered dietary guidance using rapid diet screener tools that must be addressed. In this scientific statement from the American Heart Association, we provide rationale for the widespread adoption of rapid diet screener tools in primary care and relevant specialty care prevention settings, discuss the theory- and practice-based criteria of a rapid diet screener tool that supports valid and feasible diet assessment and counseling in clinical settings, review existing tools, and discuss opportunities and challenges for integrating a rapid diet screener tool into clinician workflows through the electronic health record.

ObjectiveObesity and dysmetabolism are major risk factors for atrial fibrillation (AF). Expansion of fat depots is associated with increased circulating total non-esterified fatty acids (NEFAs), elevated levels of which are associated with incident AF. We undertook comprehensive serum measurement of individual NEFA to identify specific associations with new-onset AF late in life.MethodsThe present study focused on participants with available serum and free of AF selected from the Cardiovascular Health Study, a community-based longitudinal investigation of older US adults. Thirty-five individual NEFAs were measured by gas chromatography. Cox regression was used to evaluate the association of individual NEFAs with incident AF.ResultsThe study sample included 1872 participants (age 77.7±4.4). During median follow-up of 11.3 years, 715 cases of incident AF occurred. After concurrent adjustment of all NEFAs and full adjustment for potential confounders, higher serum concentration of nervonic acid (24:1 n-9), a long-chain monounsaturated fatty acid, was associated with higher risk of AF (HR per SD: 1.18, 95% CI 1.08 to 1.29; pConclusionsAmong older adults, serum levels of non-esterified nervonic acid were positively associated, while serum levels of non-esterified GLA were inversely associated, with incident AF. If confirmed, these results could offer new strategies for AF prevention and early intervention in this segment of the population at highest risk.

Optimizing diet quality in conjunction with statin therapy is currently the most common approach for coronary artery disease (CAD) risk management. Although effects on the cardiovascular system have been extensively investigated, little is known about the effect of these interventions in the colon and subsequent associations with CAD progression. To address this gap, Ossabaw pigs were randomly allocated to receive, for a six-month period, isocaloric amounts of either a heart healthy-type diet (HHD; high in unrefined carbohydrate, unsaturated fat, fiber, supplemented with fish oil, and low in cholesterol) or a Western-type diet (WD; high in refined carbohydrate, saturated fat and cholesterol, and low in fiber), without or with atorvastatin therapy. At the end of the intervention period, colon samples were harvested, mucosa fraction isolated, and RNA sequenced. Gene differential expression and enrichment analyses indicated that dietary patterns and atorvastatin therapy differentially altered gene expression, with diet-statin interactions. Atorvastatin had a more profound effect on differential gene expression than diet. In pigs not receiving atorvastatin, the WD upregulated "LXR/RXR Activation" pathway compared to pigs fed the HHD. Enrichment analysis indicated that atorvastatin therapy lowered inflammatory status in the HHD-fed pigs, whereas it induced a colitis-like gene expression phenotype in the WD-fed pigs. No significant association was identified between gene expression phenotypes and severity of atherosclerotic lesions in the left anterior descending-left circumflex bifurcation artery. These data suggested diet quality modulated the response to atorvastatin therapy in colonic mucosa, and these effects were unrelated to atherosclerotic lesion development.

Background: Experimental studies found that the functionality of high density lipoprotein cholesterol (HDL-C) may be lost in the presence of diabetes mellitus (DM). We prospectively tested whether DM modified the association between HDL-C concentrations and cardiovascular disease (CVD).Methods: Included were 91,354 Chinese adults (8,244 participants with DM and 83,110 participants without DM) without use of lipid-lowering drugs and free of CVD or cancer at baseline (2006). The primary endpoint of interest was a composite of CVD (myocardial infarction, ischemic stroke and hemorrhagic stroke). Cumulative average HDL-C concentrations were calculated from all available HDL-C measures at baseline (2006) and during the follow-up period (2008, 2010, 2012 and 2014).Results: During a mean of 10.4 year of follow-up, there were 5,076 CVD events identified. Presence of DM significantly modified the association between HDL-C concentrations and CVD risk (Pinteraction =0.003). The association between HDL-C concentrations and CVD followed a U-shaped curve in individuals without DM (Pnonlinearity 2.07 mmol/L, relative to the lowest risk group (HDL-C concentrations of 1.30-1.42mmol/L). In participants with DM, higher HDL-C concentrations were associated with a higher risk of CVD, in a dose-response manner (Pnonlinearity =0.44; Ptrend 2.07 mmol/L, relative to HDL-C concentrations of 1.30-1.42mmol/L. Conclusion: High HDL-C concentrations were paradoxically associated with increased risk of composite CVD outcomes in individuals with or without DM. However, low HDL-C concentrations failed to predict future CVD risk in individuals with DM.

The independent effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on chronic inflammation through their downstream lipid mediators, including the specialized pro-resolving lipid mediators (SPM), remain unstudied. Therefore, we compared the effects of EPA and DHA supplementation on monocyte inflammatory response and plasma polyunsaturated fatty acids (PUFA) SPM lipidome.After a 4-week lead-in phase (baseline), 9 men and 12 postmenopausal women (50-75 years) with chronic inflammation received two phases of 10-week supplementation with 3 g/day EPA and DHA in a random order, separated by a 10-week washout.Compared with baseline, EPA and DHA supplementation differently modulated LPS-stimulated monocyte cytokine expression. EPA lowered TNFA (p 0.001) whereas DHA reduced TNFA (p 0.001), IL6 (p 0.02), MCP1 (p 0.03), and IL10 (p 0.01). DHA lowered IL10 expression relative to EPA (p = 0.03). Relative to baseline, EPA, but not DHA, decreased the ratios of TNFA/IL10 and MCP1/IL10 (both p 0.01). EPA and DHA also significantly changed plasma PUFA SPM lipidome by replacing n-6 AA derivatives with their respective derivatives including 18-hydroxy-EPA (+5 fold by EPA) and 17- and 14-hydroxy-DHA (+3 folds by DHA). However, DHA showed a wider effect than EPA by also significantly increasing EPA derivatives and DPA-derived SPM at a greater expense of AA derivatives. Different groups of PUFA derivatives mediated the differential effects of EPA and DHA on monocyte cytokine expression.EPA and DHA had distinct effects on monocyte inflammatory response with a broader effect of DHA in attenuating pro-inflammatory cytokines. These differential effects were potentially mediated by different groups of PUFA derivatives, suggesting immunomodulatory activities of SPM and their intermediates.

In the field of human nutrition, randomized controlled trials (RCTs) are considered the gold standard for establishing causal relations between exposure to nutrients, foods, or dietary patterns and prespecified outcome measures, such as body composition, biomarkers, or event rates. Evidence-based dietary guidance is frequently derived from systematic reviews and meta-analyses of these RCTs. Each decision made during the design and conduct of human nutrition RCTs will affect the utility and generalizability of the study results. Within the context of limited resources, the goal is to maximize the generalizability of the findings while producing the highest quality data and maintaining the highest levels of ethics and scientific integrity. The aim of this document is to discuss critical aspects of conducting human nutrition RCTs, including considerations for study design (parallel, crossover, factorial, cluster), institutional ethics approval (institutional review boards), recruitment and screening, intervention implementation, adherence and retention assessment, and statistical analyses considerations. Additional topics include distinguishing between efficacy and effectiveness, defining the research question(s), monitoring biomarker and outcome measures, and collecting and archiving data. Addressed are specific aspects of planning and conducting human nutrition RCTs, including types of interventions, inclusion/exclusion criteria, participant burden, randomization and blinding, trial initiation and monitoring, and the analysis plan.

Diet quality and statin therapy are established modulators of coronary artery disease (CAD) progression, but their effect on the gastrointestinal tract and subsequent sequelae that could affect CAD progression are relatively unexplored. To address this gap, Ossabaw pigs (N = 32) were randomly assigned to receive isocaloric amounts of a Western-type diet (WD; high in saturated fat, refined carbohydrate, and cholesterol, and low in fiber) or a heart healthy-type diet (HHD; high in unsaturated fat, whole grains, fruits and vegetables, supplemented with fish oil, and low in cholesterol), with or without atorvastatin, for 6 months. At the end of the study, RNA sequencing with 100 base pair single end reads on NextSeq 500 platform was conducted in isolated pig jejunal mucosa. A two-factor edgeR analysis revealed that the dietary patterns resulted in three differentially expressed genes related to lipid metabolism (SCD, FADS1, and SQLE). The expression of these genes was associated with cardiometabolic risk factors and atherosclerotic lesion severity. Subsequent gene enrichment analysis indicated the WD, compared to the HHD, resulted in higher interferon signaling and inflammation, with some of these genes being significantly associated with serum TNF-α and/or hsCRP concentrations, but not atherosclerotic lesion severity. No significant effect of atorvastatin therapy on gene expression, nor its interaction with dietary patterns, was identified. In conclusion, Western and heart healthy-type dietary patterns differentially affect the expression of genes associated with lipid metabolism, interferon signaling, and inflammation in the jejunum of Ossabaw pigs.

Introduction: Serum non-esterified fatty acids (NEFAs) have been linked to both local and systemic inflammation and are higher in individuals with obesity, diabetes, cardiovascular disease, and ischemic stroke risk. Significant associations between total plasma NEFA concentrations and incident ischemic stroke have been reported in some but not all prospective studies. Given the functional and structural diversity among circulating NEFA, the associations of individual or clusters of circulating NEFAs may provide additional insight into their relationship with incident stroke. Hypothesis: Fasting serum n-3 NEFAs are inversely associated, and saturated and trans NEFAs are positively associated with incident stroke. Methods: We analyzed the incidence of stroke among Cardiovascular Health Study (CHS) participants who were free of stroke in 1996-1997 and underwent fasting NEFA profile measurement. At baseline, mean age was 77.8±4.5, body mass index was 26.7±4.4 and 61% were female. A total of 38 individual NEFAs in 5 classes (saturated, monounsaturated, polyunsaturated n-6, polyunsaturated n-3 and trans NEFAs) were measured using gas chromatography. Cox regression was used to evaluate the association of individual NEFA species with incident stroke, adjusting for: age, sex, race, and field center (model 1); model 1 covariates plus smoking, education, physical activity, alcohol consumption, eGFR, BMI, aspirin use, waist circumference, hypertension, prevalent diabetes, and cholesterol (model 2). Results: A total of 338 cases of incident stroke occurred during median follow-up of 10.5 years. In the fully adjusted model, trans -palmitoleic acid was inversely associated with incident stroke (HR per 1 mol% of NEFA composition: 0.03 [95% CI: 0.00 to 0.77], P P Conclusion: Among fasting serum NEFA, docosahexaenoic acid and trans -palmitoleic acid were inversely associated with incident stroke, suggesting that these fatty acids may protect older adults from stroke.

Introduction: Puerto Rican adults living on the US mainland tend to have poor quality diets and adverse cardiometabolic risk. Plasma metabolomic signatures reflect dietary intakes and variability in metabolic response to diet. Hypothesis: A plasma metabolomic signature reflecting adherence to the American Heart Association (AHA) dietary guidelines will be associated with cardiometabolic risk. Methods: We used LC/MS to measure plasma metabolites (>700) among Boston Puerto Rican Health Study participants, aged 45-75 years, without (n=252) and with (n=254) type 2 diabetes (T2D). We calculated a modified version of a previously validated AHA diet score (AHA-DS), which included variety and amounts of fruits/vegetables, whole grains, fish, saturated fat, trans fat, sodium, and added sugars. We used elastic net regression to identify a metabolomic signature that associated with higher adherence to the AHA-DS among those without T2D (training set) and replicated the associations among those with T2D (testing set). A metabolomic score was calculated as the weighted sum of the diet associated metabolites. We used general linear models to determine the cross-sectional associations between the AHA-DS, metabolomic score, and cardiometabolic risk factors. Results: A diet-associated metabolomic signature with 58 metabolites, primarily lipids and amino acids, was identified. This metabolomic score correlated moderately with the AHA-DS among those with and without T2D (r=0.42-0.46, P -12 ). In all participants (n=506), the metabolomic score, but not the AHA-DS, was significantly associated with higher HDL-C and LDL-C concentrations, and lower waist circumference ( P Conclusions: In individuals of Puerto Rican descent, we identified a metabolomic signature that reflected adherence and metabolic response to the AHA dietary guidelines and that associated with cardiometabolic risk factors.

Background: Beyond taste perception, taste receptors in the mouth and gastrointestinal tract have been linked to the regulation of energy balance, endocrine function and glucose homeostasis. Despite this, little is known about the relationship between perception for the 5 tastes (sweet, salt, sour, bitter and umami) and diet-related chronic disease risk. Objective: To investigate the association between perception for the 5 tastes and diabetes status. Methods: A cross-sectional baseline analysis was performed on older (55-75 years), overweight (BMI, ≥27- Results: The prevalence of diabetes in this cohort was 38%. Compared to individuals without diabetes, individuals with diabetes had significantly lower bitter taste perception (unadjusted means: 1.6 versus 1.1 units, respectively) (t-test p Conclusions: Among older adults with metabolic syndrome, higher bitter taste perception was associated with lower odds of being diagnosed with diabetes. Further investigations are warranted to confirm these observations and to determine whether bitter taste receptors may provide a possible therapeutic target for diabetes prevention and treatment.