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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.

Background Significant associations between total nonesterified fatty acid (NEFA) concentrations and incident stroke have been reported in some prospective cohort studies. We evaluated the associations between incident stroke and serum concentrations of nonesterified saturated, monounsaturated, polyunsaturated, and trans fatty acids. Methods and Results CHS (Cardiovascular Health Study) participants (N=2028) who were free of stroke at baseline (1996–1997) and had an archived fasting serum sample were included in this study. A total of 35 NEFAs were quantified using gas chromatography. Cox proportional hazards regression models were used to evaluate associations of 5 subclasses (nonesterified saturated, monounsaturated, omega (n)‐6 polyunsaturated, n‐3 polyunsaturated, and trans fatty acids) of NEFAs and individual NEFAs with incident stroke. Sensitivity analysis was conducted by excluding cases with hemorrhagic stroke (n=45). A total of 338 cases of incident stroke occurred during the median 10.5‐year follow‐up period. Total n‐3 (hazard ratio [HR], 0.77 [95% CI, 0.61–0.97]) and n‐6 (HR, 1.32 [95% CI, 1.01–1.73]) subclasses of NEFA were negatively and positively associated with incident stroke, respectively. Among individual NEFAs, dihomo‐γ‐linolenic acid (20:3n‐6) was associated with higher risk (HR, 1.29 [95% CI, 1.02–1.63]), whereas cis ‐7‐hexadecenoic acid (16:1n‐9 c ) and arachidonic acid (20:4n‐6) were associated with a lower risk (HR, 0.67 [95% CI, 0.47–0.97]; HR, 0.81 [95% CI. 0.65–1.00], respectively) of incident stroke per standard deviation increment. After the exclusion of cases with hemorrhagic stroke, these associations did not remain significant. Conclusions A total of 2 NEFA subclasses and 3 individual NEFAs were associated with incident stroke. Of these, the NEFA n‐3 subclass and dihomo‐γ‐linolenic acid are diet derived and may be potential biomarkers for total stroke risk.

Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for a causal association between triglycerides (TG), TG-rich lipoproteins (TRL), and TRL remnants, and increased risk of myocardial infarction, ischaemic stroke, and aortic valve stenosis. These data also indicate that TRL and their remnants may contribute significantly to residual cardiovascular risk in patients on optimized low-density lipoprotein (LDL)-lowering therapy. This statement critically appraises current understanding of the structure, function, and metabolism of TRL, and their pathophysiological role in atherosclerotic cardiovascular disease (ASCVD). Key points are (i) a working definition of normo- and hypertriglyceridaemic states and their relation to risk of ASCVD, (ii) a conceptual framework for the generation of remnants due to dysregulation of TRL production, lipolysis, and remodelling, as well as clearance of remnant lipoproteins from the circulation, (iii) the pleiotropic proatherogenic actions of TRL and remnants at the arterial wall, (iv) challenges in defining, quantitating, and assessing the atherogenic properties of remnant particles, and (v) exploration of the relative atherogenicity of TRL and remnants compared to LDL. Assessment of these issues provides a foundation for evaluating approaches to effectively reduce levels of TRL and remnants by targeting either production, lipolysis, or hepatic clearance, or a combination of these mechanisms. This consensus statement updates current understanding in an integrated manner, thereby providing a platform for new therapeutic paradigms targeting TRL and their remnants, with the aim of reducing the risk of ASCVD., Graphical Abstract Formation of triglyceride-rich lipoprotein remnants and their role in atherogenesis. Metabolic scheme for the generation and clearance of triglyceride-rich lipoprotein remnant particles (A). In hypertriglyceridaemia, overproduction and inefficient lipolysis of both very low-density lipoprotein and chylomicrons lead to increased remnant formation. Triglyceride-rich lipoprotein remnants contribute to the initiation and progression of atherosclerotic lesions (B). Particle retention in the subendothelial space is followed by inflammation, cholesterol deposition, and macrophage foam cell formation.

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.

Backgrounds and aims: Elevated common carotid artery intima-media thickness (carotid IMT) and diminished flow-mediated dilation (FMD) are early subclinical indicators of atherosclerosis. Serum total non-esterified fatty acid (NEFA) concentrations have been positively associated with subclinical atherosclerosis. The relations between individual NEFA, carotid IMT and FMD have as yet to be assessed. Methods: We investigated the associations between fasting serum individual NEFA, carotid IMT and FMD among Cardiovascular Health Study (CHS) participants with (n = 255 for carotid IMT, 301 for FMD) or without (n = 1314 for carotid IMT, 1462 for FMD) known atherosclerotic cardiovascular disease (ASCVD). Using archived samples (fasting) collected from 1996–1997 (baseline), 35 individual NEFAs were measured using gas chromatography. Carotid IMT and estimated plaque thickness (mean of maximum internal carotid IMT) were determined in 1998–1999. FMD was measured in 1997–1998. Linear regression adjusted by the Holm-Bonferroni method was used to assess relations between individual NEFA, carotid IMT and FMD. Results: In multivariable adjusted linear regression models per SD increment, the non-esterified trans fatty acid conjugated linoleic acid (trans-18:2 CLA) was positively associated with carotid IMT [β (95% CI): 44.8 (19.2, 70.4), p = 0.025] among participants with, but not without, ASCVD [2.16 (−6.74, 11.5), p = 1.000]. Non-esterified cis-palmitoleic acid (16:1n-7c) was positively associated with FMD [19.7 (8.34, 31.0), p = 0.024] among participants without, but not with ASCVD. No significant associations between NEFAs and estimated plaque thickness were observed. Conclusions: In older adults, serum non-esterified CLA and palmitoleic acid were positively associated with carotid IMT and FMD, respectively, suggesting potential modifiable biomarkers for arteriopathy.

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 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.

OBJECTIVES: To evaluate the impact of a family-based weight management intervention for children with overweight/obesity on parental nutrient biomarker concentrations and cardiometabolic risk factors (CMRF). METHODS: Secondary analysis from a randomized-controlled, parallel-arm clinical trial. Families were recruited from a largely Hispanic population and assigned to either Standard Care (SC; American Academy of Pediatrics overweight/obesity recommendations) or Standard Care + Enhanced Program (SC + EP; eight skill-building cores, subsequent monthly support sessions, targeted diet/physical activity strategies). Nutrient biomarkers (plasma carotenoids and fat soluble vitamins; red blood cell [RBC] fatty acid profiles) and CMRF (BMI, blood pressure, plasma glucose, insulin, lipid profile, inflammatory markers and adipokine concentrations) were measured in archived samples collected from the parents at baseline and at the end of the 1-year intervention. RESULTS: Parents of children in both groups (SC = 106; SC + EP = 99) had significantly lower total SFA (−3%) and trans fatty acid (−14%), and higher MUFA (2%), PUFAn-6 (2%), PUFAn-3 (7%) and beta-carotene (20%) concentrations, indicative of decreased partially-hydrogenated fat and increased vegetable oil, fish and fruit/vegetable intake, respectively. In both groups, there were significant reductions in inflammatory markers (hsCRP [−21%], TNFα [−19%] and IL-6 [−19%]), but not in BMI, blood pressure or lipid profile. Parents with children assigned to the SC + EP group had additional improvements in serum insulin (−6%) and leptin (−1.3%) concentrations. Using multiple linear regression models adjusted for sex, age, group, baseline BMI, and baseline CMRF values, improvements in circulating inflammatory and glucose metabolism markers, and adipokine concentrations were associated with higher carotenoid and PUFAn-3 (specifically 20:5n-3), and lower SFA and trans fatty acid concentrations, at the end of the 1-year intervention. CONCLUSIONS: These results suggest that a family-based childhood obesity intervention can spill over to parents, resulting in apparent healthier dietary shifts that are associated with modest improvements in some CMRF. FUNDING SOURCES: NIH, NIDDK, USDA.

OBJECTIVES: Understanding individual-level drivers of food intake is critical when personalizing dietary guidance. One likely driver is taste perception; yet, limited data relate perception of all 5 tastes (sweet, salt, sour, bitter, umami) to dietary patterns (DPs). Our aim was to determine whether a multivariable measure of taste perception, taste perception profiles, was associated with adherence to empirically derived DPs. METHODS: Participants were 367 community-dwelling adults with metabolic syndrome from PREDIMED-Plus, Valencia (55–75 years; 55% female). Six taste perception profiles were derived from 5 taste perception scores via a data-driven clustering approach: Low All (23%), High Bitter (16%), High Umami (17%), Low Bitter & Umami (20%), High All But Bitter (13%) and High All But Umami (11%). DPs were derived via principal component analysis using food groupings tabulated from food frequency questionnaires. Generalized linear models were used to examine relations between taste perception profiles and DP adherence, adjusting for confounders. RESULTS: Three DPs were identified, explaining 25% of total variance: a high fruit, vegetable and whole grain DP (Fruit/Veg), a high fat, sugar and refined grain DP (Fat/Sug) and a high alcohol, salt and processed meat DP (Alch/Salt). Adherence to the DPs differed by profile. Across all profiles, High Bitter and Low All individuals were most likely to follow the Alch/Salt DP (44% and 39% in highest tertial of adherence, respectively; P = 0.03), while those with High All But Bitter and High Umami tended to follow the Fat/Sug DP (42% and 39% in highest tertial, respectively; P = 0.08). Compared to Low All individuals, after adjusting for age, sex, physical activity, diabetes and BMI, those with Low Bitter & Umami adhered less to the Alch/Salt DP (β [95% CI] = −0.3 [−0.6, −0.03]) while those with High Umami adhered more to the Fat/Sug DP (0.4 [0.1, 0.8]). CONCLUSIONS: Among older adults with metabolic syndrome, taste perception profiles were differentially associated with adherence to empirically derived DPs, suggesting the benefit of using taste perception profiles when customizing risk reduction dietary guidance. FUNDING SOURCES: ARS/USDA, HNRCA Cassidy Student Research Award, Spanish Ministry of Health (Instituto de Salud Carlos III; SAF2016–80532-R), CIBEROBN (06/03/0035) and Generalitat Valenciana (PROMETEO 17/2017).

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

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.

Background Significant associations have been reported between serum total nonesterified fatty acid (NEFA) concentrations and coronary heart disease (CHD) mortality and incident nonfatal myocardial infarction (MI) in some prospective cohort studies. Little is known about whether individual or subclasses (saturated, polyunsaturated [n‐6 and n‐3], and trans fatty acids) of serum NEFAs relate to CHD mortality and nonfatal MI. Methods and Results CHS (Cardiovascular Health Study) participants (N=1681) who had no history of MI, angina, or revascularization or were free of MI at baseline (1996–1997) were included. NEFAs were quantified using gas chromatography. Cox regression analysis was used to evaluate associations of 5 subclasses and individual NEFAs with CHD composite (CHD mortality and nonfatal MI), CHD mortality, and incident nonfatal MI. During a median follow‐up of 11.7 years, 266 cases of CHD death and 271 cases of nonfatal MI occurred. In the fully adjusted model, no significant associations were identified between individual NEFA and CHD composite. Exploratory analyses indicated that lauric acid (12:0) was negatively associated (hazard ratio [HR], 0.76; 95% CI, 0.59–0.98; P =0.0328) and dihomo‐γ‐linolenic acid (20:3n‐6) was positively associated with CHD mortality (HR, 1.34; 95% CI, 1.02–1.76; P =0.0351). Elaidic acid (18:1n‐7 t ) was positively associated with incident nonfatal MI (HR, 1.46; 95% CI, 1.01–2.12; P =0.0445). No significant associations were observed for NEFA subclass and any outcomes. Conclusions In CHS participants, 2 NEFAs, dihomo‐γ‐linolenic and elaidic acids, were positively associated with CHD mortality and nonfatal MI, respectively, suggesting potential susceptibility biomarkers for risks of CHD mortality and nonfatal MI.

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.

Implementation of prevention policies has often been impeded or delayed due to the lack of randomized controlled trials (RCTs) with hard clinical outcomes (eg, incident disease, mortality). Despite the prominent role of RCTs in health care, it may not always be feasible to conduct RCTs of public health interventions with hard outcomes due to logistical and ethical considerations. RCTs may also lack external validity and have limited generalizability. Currently, there is insufficient guidance for policymakers charged with establishing evidence-based policy to determine whether an RCT with hard outcomes is needed before policy recommendations. In this context, the purpose of this article is to assess, in a case study, the feasibility of conducting an RCT of the oft-cited issue of sodium reduction on cardiovascular outcomes and then propose a framework for decision-making, which includes an assessment of the feasibility of conducting an RCT with hard clinical outcomes when such trials are unavailable. We designed and assessed the feasibility of potential individual- and cluster-randomized trials of sodium reduction on cardiovascular outcomes. Based on our assumptions, a trial using any of the designs considered would require tens of thousands of participants and cost hundreds of millions of dollars, which is prohibitively expensive. Our estimates may be conservative given several key challenges, such as the unknown costs of sustaining a long-term difference in sodium intake, the effect of differential cotreatment with antihypertensive medications, and long lag time to clinical outcomes. Thus, it would be extraordinarily difficult to conduct such a trial, and despite the high costs, would still be at substantial risk for a spuriously null result. A robust framework, such as the one we developed, should be used to guide policymakers when establishing evidence-based public health interventions in the absence of trials with hard clinical outcomes.

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.

Dietary modification has been the cornerstone of cardiovascular disease (CVD) prevention since the middle of the last century when the American Heart Association (AHA) first issued recommendations. For the vast majority of that time the focus has been on saturated fat, with or without concomitant guidance for total or unsaturated fat. Over the past few years there has been a renewed debate about the relation between dietary saturated fat and CVD risk, prompted by a series of systematic reviews that have come to what appears to be different conclusions. This triggered a robust discourse about this controversy in the media that in turn has led to confusion in the general public. The genesis of the different conclusions among the systematic reviews has been identified in several studies on the basis of isocaloric substitution analyses. When the data were analyzed on the basis of polyunsaturated fat replacing saturated fat, there was a positive relation between dietary saturated fat and CVD. When the data were analyzed on the basis of carbohydrate replacing saturated fat, there was a null relation between dietary saturated fat and CVD. When the substitution macronutrient was not taken into consideration, the differential effects of the macronutrient substitution went unrecognized and the relations judged as null. The lack of distinction among substituted macronutrients accounted for much of what appeared to be discrepancies. Dietary guidance consistent with replacing foods high in saturated fat with foods high in unsaturated fat, first recommended more than 50 y ago, remains appropriate to this day.

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.

BACKGROUND: Inverse associations have been reported between serum 25-hydroxyvitamin D [25(OH)D] and circulating cholesterol concentrations in observational studies. Postulated mechanisms include reduced bioavailability of intestinal cholesterol and alterations in endogenous cholesterol synthesis. OBJECTIVE: To explore the effect of daily supplementation with 4000 IU/d vitamin D(3) for 24 wk on surrogate biomarkers of cholesterol absorption (campesterol and β-sitosterol) and endogenous synthesis (lathosterol and desmosterol). METHODS: Ancillary study of The Vitamin D for Established Type 2 Diabetes (DDM2) trial. Patients with established type 2 diabetes (N = 127, 25–75 y, BMI 23–42 kg/m(2)) were randomly assigned to receive either 4000 IU vitamin D(3) or placebo daily for 24 wk. Of participants without changes in cholesterol-lowering medications (n = 114), plasma surrogate cholesterol absorption and endogenous synthesis biomarker concentrations were measured and merged with available measures of serum LDL cholesterol and HDL cholesterol concentrations. RESULTS: At week 24, vitamin D(3) supplementation significantly increased 25(OH)D concentrations (+21.5 ± 13.4 ng/mL) but not insulin secretion rates (primary outcome of the parent study) as reported previously. In this ancillary study there was no significant effect of vitamin D(3) supplementation on serum cholesterol profile or surrogate biomarkers of cholesterol absorption and endogenous synthesis. Compared with participants not treated with cholesterol-lowering medications, those who were treated exhibited a greater reduction in plasma campesterol concentrations in the vitamin D(3) but not placebo group (P-interaction = 0.011). Analyzing the data on the basis of cholesterol absorption status (hypo- versus hyperabsorbers) or cholesterol synthesis status (hypo- versus hypersynthesizers) did not alter these results. CONCLUSIONS: Vitamin D(3) supplementation for 24 wk had no significant effect on surrogate biomarkers of cholesterol absorption or endogenous synthesis, consistent with the lack of effect on serum cholesterol profile. Vitamin D(3) supplementation resulted in greater reduction in campesterol concentrations in participants not using compared with those using cholesterol-lowering medications. Further studies are required. This trial was registered at clinicaltrials.gov as NCT01736865.

Background: DNA methylation patterns associated with habitual diet have not been well studied. Methods: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality. Results: We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected P −3 ). Hypermethylation of cg18181703 ( SOCS3 ) was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality ( P =5.7×10 −15 ). Ten additional diet-associated CpGs were nominally associated with all-cause mortality ( P P −4 ). For example, hypermethylation of cg11250194 ( FADS2 ) was associated with lower triglyceride concentrations (MR, P =1.5×10 −14 ).and hypermethylation of cg02079413 ( SNORA54 ; NAP1L4 ) was associated with body mass index (corrected MR, P =1×10 −6 ). Conclusions: Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.

OBJECTIVES: In humans, perception for each taste (sweet, salt, sour, bitter and umami) has been independently related to food preferences and intake. Yet, the collective influence of perception of all 5 tastes on diet and cardiometabolic health remains unexplored. Therefore, our objective was to investigate the relations between a collective measure of taste perception – “taste perception profiles” – and adiposity. METHODS: We analyzed baseline data of 367 older adults (55–75 years; 55% female) with metabolic syndrome (MetS) participating in the PREDIMED-Plus Valencia trial. Taste perception was assessed for sweet, salt, sour, bitter and umami using sucrose, NaCl, citric acid, phenylthiocarbamide and monopotassium L-glutamate, respectively, and evaluated on a 0–5 scale. Taste perception profiles were derived from perception scores using predictive modeling and k-means clustering (KCA). Multivariable linear regression was used to evaluate the relations between taste perception profiles and BMI, body weight (BW) and waist circumference (WC), after adjustment for confounders. RESULTS: KCA identified 7 taste perception profiles: Low All (n = 79), High Umami (n = 61), High Bitter (n = 49), High Bitter & Umami (n = 44), High Sweet, Salt & Sour (n = 51), High All But Bitter (n = 49) and High All But Umami (n = 34). After adjusting for age, sex, physical activity, smoking, diabetes, medication use and energy intake, BMI, BW and WC were highest for the Low All profile (adjusted means: 33.4 kg/m(2), 87.5 kg and 108.4 cm; reference). Comparatively, mean BMI and BW were lower for High Bitter (–1.9 kg/m(2); –5.4 kg), High Bitter & Umami (–1.7; –4.7), High Sweet, Salt & Sour (–1.3; –4.6) and High All But Bitter (–1.7; –5.0) profiles; and WC was lower for High Bitter & Umami (–3.4 cm) and High All But Bitter (–4.9) profiles (all P

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.

Background Limited data are available on the prospective relationship between beverage consumption and plasma lipid and lipoprotein concentrations. Two major sources of sugar in the US diet are sugar‐sweetened beverages ( SSBs ) and 100% fruit juices. Low‐calorie sweetened beverages are common replacements. Methods and Results Fasting plasma lipoprotein concentrations were measured in the FOS (Framingham Offspring Study) (1991–2014; N=3146) and Generation Three (2002–2001; N=3584) cohorts. Beverage intakes were estimated from food frequency questionnaires and grouped into 5 intake categories. Mixed‐effect linear regression models were used to examine 4‐year changes in lipoprotein measures, and Cox proportional hazard models were used to estimate hazard ratios for incident dyslipidemia, adjusting for potential confounding factors. We found that regular (>1 serving per day) versus low (SSB consumption was associated with a greater mean decrease in high‐density lipoprotein cholesterol (β±standard error −1.6±0.4 mg/dL; P trend P trend =0.003) concentrations. Long‐term regular SSB consumers also had a higher incidence of high triglyceride (hazard ratio, 1.52; 95% CI, 1.03–2.25) compared with low consumers. Although recent regular low‐calorie sweetened beverage consumers had a higher incidence of high non–high‐density lipoprotein cholesterol (hazard ratio, 1.40; 95% CI , 1.17–1.69) and low‐density lipoprotein cholesterol (hazard ratio, 1.27; 95% CI, 1.05–1.53) concentrations compared with low consumers, cumulative average intakes of low‐calorie sweetened beverages were not associated with changes in non–high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol concentrations, or incident dyslipidemias. Conclusions SSB intake was associated with adverse changes in high‐density lipoprotein cholesterol and triglyceride concentrations, along with a higher risk of incident dyslipidemia, suggesting that increased SSB consumption may contribute to the development of dyslipidemia.

BACKGROUND: Dietary carbohydrate type may influence cardiometabolic risk through alterations in the gut microbiome and microbial-derived metabolites, but evidence is limited. OBJECTIVES: We explored the relative effects of an isocaloric exchange of dietary simple, refined, and unrefined carbohydrate on gut microbiota composition/function, and selected microbial metabolite concentrations. METHODS: Participants [n = 11; age: 65 ± 8 y; BMI (in kg/m(2)): 29.8 ± 3.2] were provided with each of 3 diets for 4.5 wk with 2-wk washout, according to a randomized, crossover design. Diets [60% of energy (%E) carbohydrate, 15%E protein, and 25%E fat] differed in type of carbohydrate. Fecal microbial composition, metatranscriptomics, and microbial-derived SCFA and secondary bile acid (SBA) concentrations were assessed at the end of each phase and associated with cardiometabolic risk factors (CMRFs). RESULTS: Roseburia abundance was higher (11% compared with 5%) and fecal SBA concentrations were lower (lithocolic acid –50% and deoxycholic acid –64%) after consumption of the unrefined carbohydrate diet relative to the simple carbohydrate diet [false discovery rate (FDR): all P