Food Is Medicine: A Presidential Advisory From the American Heart Association.

Unhealthy diets are a major impediment to achieving a healthier population in the United States. Although there is a relatively clear sense of what constitutes a healthy diet, most of the US population does not eat healthy food at rates consistent with the recommended clinical guidelines. An abundance of barriers, including food and nutrition insecurity, how food is marketed and advertised, access to and affordability of healthy foods, and behavioral challenges such as a focus on immediate versus delayed gratification, stand in the way of healthier dietary patterns for many Americans. Food Is Medicine may be defined as the provision of healthy food resources to prevent, manage, or treat specific clinical conditions in coordination with the health care sector. Although the field has promise, relatively few studies have been conducted with designs that provide strong evidence of associations between Food Is Medicine interventions and health outcomes or health costs. Much work needs to be done to create a stronger body of evidence that convincingly demonstrates the effectiveness and cost-effectiveness of different types of Food Is Medicine interventions. An estimated 90% of the $4.3 trillion annual cost of health care in the United States is spent on medical care for chronic disease. For many of these diseases, diet is a major risk factor, so even modest improvements in diet could have a significant impact. This presidential advisory offers an overview of the state of the field of Food Is Medicine and a road map for a new research initiative that strategically approaches the outstanding questions in the field while prioritizing a human-centered design approach to achieve high rates of patient engagement and sustained behavior change. This will ideally happen in the context of broader efforts to use a health equity-centered approach to enhance the ways in which our food system and related policies support improvements in health.

Protein Biomarkers of Ultra-Processed Food Consumption and Risk of Coronary Heart Disease, Chronic Kidney Disease, and All-Cause Mortality.

BACKGROUND: There is a need to understand the underlying biological mechanisms through which ultra-processed foods negatively affect health. Proteomics offers a valuable tool with which to examine different aspects of ultra-processed foods and their impact on health. OBJECTIVES: The aim of this study was to identify protein biomarkers of usual ultra-processed food consumption and assess their relation to the incidence of coronary heart disease (CHD), chronic kidney disease (CKD), and all-cause mortality risk. METHODS: A total of 9361 participants from the Atherosclerosis Risk in Communities visit 3 (1993-1995) were included. Dietary intake was assessed using a 66-item food-frequency questionnaire and the processing levels were categorized on the basis of the Nova classification. Plasma proteins were detected using an aptamer-based proteomic assay. We used multivariable linear regressions to examine the association between ultra-processed food and proteins, and Cox proportional hazard models to identify associations between ultra-processed food-related proteins and health outcomes. Models extensively controlled for sociodemographic characteristics, health behaviors, and clinical factors. RESULTS: Eight proteins (6 positive, 2 negative) were identified as significantly associated with ultra-processed food consumption. Over a median follow-up of 22 y, there were 1276, 3084, and 5127 cases of CHD, CKD, and death, respectively. Three, 5, and 3 ultra-processed food-related proteins were associated with each outcome, respectively. One protein (ß-glucuronidase) was significantly associated with a higher risk of all 3 outcomes, and 3 proteins (receptor-type tyrosine-protein phosphatase U, C-C motif chemokine 25, and twisted gastrulation protein homolog 1) were associated with a higher risk of 2 outcomes. CONCLUSIONS: We identified a panel of protein biomarkers that were significantly associated with ultra-processed food consumption. These proteins may be considered potential biomarkers for ultra-processed food intake and may elucidate the biological processes through which ultra-processed foods impact health outcomes.

Associations of circulating proteins with lipoprotein profiles: proteomic analyses from the OmniHeart randomized trial and the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Within healthy dietary patterns, manipulation of the proportion of macronutrient can reduce CVD risk. However, the biological pathways underlying healthy diet-disease associations are poorly understood. Using an untargeted, large-scale proteomic profiling, we aimed to (1) identify proteins mediating the association between healthy dietary patterns varying in the proportion of macronutrient and lipoproteins, and (2) validate the associations between diet-related proteins and lipoproteins in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: In 140 adults from the OmniHeart trial, a randomized, cross-over, controlled feeding study with 3 intervention periods (carbohydrate-rich; protein-rich; unsaturated fat-rich dietary patterns), 4,958 proteins were quantified at the end of each diet intervention period using an aptamer assay (SomaLogic). We assessed differences in log2-transformed proteins in 3 between-diet comparisons using paired t-tests, examined the associations between diet-related proteins and lipoproteins using linear regression, and identified proteins mediating these associations using a causal mediation analysis. Levels of diet-related proteins and lipoprotein associations were validated in the ARIC study (n = 11,201) using multivariable linear regression models, adjusting for important confounders. RESULTS: Three between-diet comparisons identified 497 significantly different proteins (protein-rich vs. carbohydrate-rich = 18; unsaturated fat-rich vs. carbohydrate-rich = 335; protein-rich vs. unsaturated fat-rich dietary patterns = 398). Of these, 9 proteins [apolipoprotein M, afamin, collagen alpha-3(VI) chain, chitinase-3-like protein 1, inhibin beta A chain, palmitoleoyl-protein carboxylesterase NOTUM, cathelicidin antimicrobial peptide, guanylate-binding protein 2, COP9 signalosome complex subunit 7b] were positively associated with lipoproteins [high-density lipoprotein (HDL)-cholesterol (C) = 2; triglyceride = 5; non-HDL-C = 3; total cholesterol to HDL-C ratio = 1]. Another protein, sodium-coupled monocarboxylate transporter 1, was inversely associated with HDL-C and positively associated with total cholesterol to HDL-C ratio. The proportion of the association between diet and lipoproteins mediated by these 10 proteins ranged from 21 to 98%. All of the associations between diet-related proteins and lipoproteins were significant in the ARIC study, except for afamin. CONCLUSIONS: We identified proteins that mediate the association between healthy dietary patterns varying in macronutrients and lipoproteins in a randomized feeding study and an observational study. TRIAL REGISTRATION: NCT00051350 at clinicaltrials.gov.

Bitter- and Umami-Related Genes are Differentially Associated with Food Group Intakes: the Framingham Heart Study.

BACKGROUND: As suboptimal diet quality remains the leading modifiable contributor to chronic disease risk, it is important to better understand the individual-level drivers of food choices. Recently, a genetic component of food choices was proposed based on variants (SNPs) in genes related to taste perception (taste-related SNPs). OBJECTIVES: This study aimed to determine the cumulative contribution of taste-related SNPs for basic tastes (bitter, sweet, umami, salt, and sour), summarized as "polygenic taste scores," to food group intakes among adults. METHODS: Cross-sectional analyses were performed on 6230 Framingham Heart Study participants (mean age ± SD: 50 ± 14 y; 54% female). Polygenic taste scores were derived for tastes with ≥2 related SNPs identified in prior genome-wide association studies, and food group intakes (servings per week [sev/wk]) were tabulated from food frequency questionnaires. Associations were determined via linear mixed-effects models, using false discovery rates and bootstrap resampling to determine statistical significance. RESULTS: Thirty-three taste-related SNPs (9 bitter, 19 sweet, 2 umami, 2 sour, 1 salt) were identified and used to derive polygenic taste scores for bitter, sweet, umami, and sour. Per additional allele for higher bitter perception, whole grain intakes were lower by 0.17 (95% CI: -0.28, -0.06) sev/wk, and for higher umami perception, total and red/orange vegetable intakes were lower by 0.73 (95% CI: -1.12, -0.34) and 0.25 (95% CI: -0.40, -0.10) sev/wk, respectively. Subsequent analyses at the SNP level identified four novel SNP-diet associations-two bitter-related SNPs with whole grains (rs10960174 and rs6782149) and one umami-related SNP with total and red/orange vegetables (rs7691456)-which may have been driving the identified associations. CONCLUSIONS: Taste-related genes for bitter and umami were differentially associated with food choices that may impact diet quality. Hence, a benefit could be derived from leveraging knowledge of taste-related genes when developing personalized risk reduction dietary guidance.

Plasma Protein Biomarkers of Healthy Dietary Patterns: Results from the Atherosclerosis Risk in Communities Study and the Framingham Heart Study.

BACKGROUND: Molecular mechanisms underlying the benefits of healthy dietary patterns are poorly understood. Identifying protein biomarkers of dietary patterns can contribute to characterizing biological pathways influenced by food intake. OBJECTIVES: This study aimed to identify protein biomarkers associated with four indexes of healthy dietary patterns: Healthy Eating Index-2015 (HEI-2015); Alternative Healthy Eating Index-2010 (AHEI-2010); DASH diet; and alternate Mediterranean Diet (aMED). METHODS: Analyses were conducted on 10,490 Black and White men and women aged 49-73 y from the ARIC study at visit 3 (1993-1995). Dietary intake data were collected using a food frequency questionnaire, and plasma proteins were quantified using an aptamer-based proteomics assay. Multivariable linear regression models were used to examine the association between 4955 proteins and dietary patterns. We performed pathway overrepresentation analysis for diet-related proteins. An independent study population from the Framingham Heart Study was used for replication analyses. RESULTS: In the multivariable-adjusted models, 282 out of 4955 proteins (5.7%) were significantly associated with at least one dietary pattern (HEI-2015: 137; AHEI-2010: 72; DASH: 254; aMED: 35; P value < 0.05/4955 = 1.01 × 10-5). There were 148 proteins that were associated with only one dietary pattern (HEI-2015: 22; AHEI-2010: 5; DASH: 121; aMED: 0), and 20 proteins were associated with all four dietary patterns. Five unique biological pathways were significantly enriched by diet-related proteins. Seven out of 20 proteins associated with all dietary patterns in the ARIC study were available for replication analyses, and 6 out of these 7 proteins were consistent in direction and significantly associated with at least 1 dietary pattern in the Framingham Heart Study (HEI-2015: 2; AHEI-2010: 4; DASH: 6; aMED: 4; P value < 0.05/7 = 7.14 × 10-3). CONCLUSIONS: A large-scale proteomic analysis identified plasma protein biomarkers that are representative of healthy dietary patterns among middle-aged and older US adult population. These protein biomarkers may be useful objective indicators of healthy dietary patterns.

Waist-to-height ratio associated cardiometabolic risk phenotype in children with overweight/obesity.

BACKGROUND: 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 quickly identify children at elevated risk for cardiometabolic disorders. The primary objective of the present study was to create sex-specific tertile cut points of WHtR and assess its association with Insulin resistance and elevated liver enzyme concentrations in children, factors using cross-sectional data from the randomized, controlled Family Weight Management Study. METHODS: Baseline data from 360 children (7-12 years, mean Body Mass Index (BMI) ≥ 85th percentile for age and sex) were used to calculate WHtR 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). Liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were categorized as normal vs. elevated (AST of < 36.0 µkat/L or ≥ 36.0 µkat/L; ALT of < 30.0 µkat/L or ≥ 30.0 µkat/L; ALT > 26 µkat/L males, > 22 µkat/L females). We examined differences in baseline cardiometabolic risk factors by WHtR tertiles and sex-specific multivariable logistic regression models to predict HOMA-IR and elevation of liver enzymes. RESULTS: Study participants had a mean WHtR of 0.59 ([SD: 0.06]). Irrespective of sex, children in WHtR T3 had higher BMIz scores, blood pressure, triglycerides, 2-h glucose, fasting 2-h insulin, and lower high-density lipoprotein cholesterol (HDL-C) concentrations than those in T2 and T1. After adjusting for covariates, the odds of elevated HOMA-IR (> 2.6) were over five-fold higher among males in T3 versus T1 [OR, 95%CI: 5.83, 2.34-14.52] and T2 [OR, 95%CI: 4.81, 1.94-11.92] and females in T3 [OR, 95%CI: 5.06, 2.10-12.20] versus T1. The odds of elevated ALT values (≥ 30) were 2.9 [95%CI: 1.01-8.41] fold higher among females in T3 compared to T1. CONCLUSION: In public health settings, WHtR may be a practical screening tool in pediatric populations to identify children at risk of metabolic syndrome.

2021 Dietary Guidance to Improve Cardiovascular Health: A Scientific Statement From the American Heart Association.

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.

Strategies for Promotion of a Healthy Lifestyle in Clinical Settings: Pillars of Ideal Cardiovascular Health: A Science Advisory From the American Heart Association.

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.

Sugar-Sweetened Beverage Consumption and Plasma Lipoprotein Cholesterol, Apolipoprotein, and Lipoprotein Particle Size Concentrations in US Adults.

BACKGROUND: Prospective cohort studies have found a relation between sugar-sweetened beverage (SSB) consumption (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. OBJECTIVES: To examine the association between SSB consumption and plasma lipoprotein cholesterol, apolipoprotein, and lipoprotein particle size concentrations among US adults. METHODS: We examined participants from the Framingham Offspring Study (FOS; 1987-1995, n = 3047) and the Women's Health Study (1992, n = 26,218). Concentrations of plasma LDL cholesterol, apolipoprotein B (apoB), HDL cholesterol, apolipoprotein A1 (apoA1), triglyceride (TG), and non-HDL cholesterol, as well as total cholesterol:HDL cholesterol ratio and apoB:apoA1 ratio, were quantified in both cohorts; concentrations of apolipoprotein E, apolipoprotein C3, RLP-TG, and RLP cholesterol (RLP-C) were measured in the FOS only. Lipoprotein particle sizes were calculated from nuclear magnetic resonance signals for lipoprotein particle subclass concentrations (TG-rich lipoprotein particles [TRL-Ps]: very large, large, medium, small, and very small; LDL particles [LDL-Ps]: large, medium, and small; HDL particles [HDL-Ps]: 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. RESULTS: SSB consumption was positively associated with LDL cholesterol, apoB, TG, RLP-TG, RLP-C, and non-HDL cholesterol concentrations and total cholesterol:HDL cholesterol and apoB:apoA1 ratios; and negatively associated with HDL cholesterol and apoA1 concentrations (P-trend range: <0.0001 to 0.008). After adjustment for traditional lipoprotein risk factors, SSB consumers had smaller LDL-P and HDL-P sizes; lower concentrations of large LDL-Ps and medium HDL-Ps; and higher concentrations of small LDL-Ps, small HDL-Ps, and large TRL-Ps (P-trend range: <0.0001 to 0.001). CONCLUSIONS: Higher SSB consumption was associated with multiple emerging features of dyslipidemia that have been linked to higher cardiometabolic risk in US adults.

Triglyceride Paradox Is Related to Lipoprotein Size, Visceral Adiposity and Stearoyl-CoA Desaturase Activity in Black Versus White Women.

RATIONALE: In black women, triglycerides are paradoxically normal in the presence of insulin resistance. This relationship may be explained by race-related differences in central adiposity and SCD (stearoyl-CoA desaturase)-1 enzyme activity index. OBJECTIVE: In a cross-sectional study, to compare fasting and postprandial triglyceride-rich lipoprotein particle (TRLP) concentrations and size in black compared with white pre- and postmenopausal women and determine the relationship between TRLP subfractions and whole-body insulin sensitivity, hepatic and visceral fat, and SCD-1 levels. METHODS AND RESULTS: In 122 federally employed women without diabetes mellitus, 73 black (58 African American and 15 African immigrant) and 49 white; age, 44±10 (mean±SD) years; body mass index, 30.0±5.6 kg/m2, we measured lipoprotein subfractions using nuclear magnetic resonance. Hepatic fat was measured by proton magnetic resonance spectroscopy, insulin sensitivity index calculated by minimal modeling from a frequently sampled intravenous glucose test, and red blood cell fatty acid profiles were measured by gas chromatography and were used to estimate SCD-1 indices. Hepatic fat, insulin sensitivity index, and SCD-1 were similar in black women and lower than in whites, regardless of menopausal status. Fasting and postprandial large, medium, and small TRLPs, but not very small TRLPs, were lower in black women. Fasting large, medium, and very small TRLPs negatively correlated with insulin sensitivity index and positively correlated with visceral and hepatic fat and SCD-1 activity in both groups. In multivariate models, visceral fat and SCD-1 were associated with total fasting TRLP concentrations (adjR2, 0.39; P=0.001). Black women had smaller postprandial changes in large (P=0.005) and medium TRLPs (P=0.007). CONCLUSIONS: Lower visceral fat and SCD-1 activity may contribute to the paradoxical association of lower fasting and postprandial TRLP subfractions despite insulin resistance in black compared with white pre- and postmenopausal women. Similar concentrations of very small TRLPs are related to insulin resistance and could be important mediators of cardiometabolic disease risk in women. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01809288.

Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society.

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.

Dietary Cholesterol and Cardiovascular Risk: A Science Advisory From the American Heart Association.

The elimination of specific dietary cholesterol target recommendations in recent guidelines has raised questions about its role with respect to cardiovascular disease. This advisory was developed after a review of human studies on the relationship of dietary cholesterol with blood lipids, lipoproteins, and cardiovascular disease risk to address questions about the relevance of dietary cholesterol guidance for heart health. Evidence from observational studies conducted in several countries generally does not indicate a significant association with cardiovascular disease risk. Although meta-analyses of intervention studies differ in their findings, most associate intakes of cholesterol that exceed current average levels with elevated total or low-density lipoprotein cholesterol concentrations. Dietary guidance should focus on healthy dietary patterns (eg, Mediterranean-style and DASH [Dietary Approaches to Stop Hypertension]-style diets) that are inherently relatively low in cholesterol with typical levels similar to the current US intake. These patterns emphasize fruits, vegetables, whole grains, low-fat or fat-free dairy products, lean protein sources, nuts, seeds, and liquid vegetable oils. A recommendation that gives a specific dietary cholesterol target within the context of food-based advice is challenging for clinicians and consumers to implement; hence, guidance focused on dietary patterns is more likely to improve diet quality and to promote cardiovascular health.

The risk of ischemic stroke and hemorrhagic stroke in Chinese adults with low-density lipoprotein cholesterol concentrations < 70 mg/dL.

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 < 70 mg/dL using a survival conditional inference tree, a machine learning method. METHODS: The training dataset included 9327 individuals with LDL-C concentrations < 70 mg/dL who were free of cardiovascular diseases and did not use lipid-modifying drugs from the Kailuan I study (N = 101,510). We examined the validity of this algorithm in a second Chinese cohort of 1753 participants with LDL-C concentrations < 70 mg/dL from the Kailuan II study (N = 35,856). 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.

Whole- and Refined-Grain Consumption and Longitudinal Changes in Cardiometabolic Risk Factors in the Framingham Offspring Cohort.

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 < 0.001), fasting glucose concentration (0.7 ± 0.4 compared with 2.6 ± 0.2 mg/dL; P-trend < 0.001), and systolic blood pressure (SBP; 0.2 ± 0.5 compared with 1.4 ± 0.3 mm Hg; P-trend < 0.001) per 4-y interval. When stratified by sex, a stronger association with WC was observed among females than males. Higher intake of WG was associated with greater increases in HDL cholesterol and declines in triglyceride concentrations; however, these differences did not remain significant after adjustment for change in WC. Conversely, greater RG intake was associated with greater increases in WC (2.7 ± 0.2 compared with 1.8 ± 0.1 cm, P-trend < 0.001) and less decline in triglyceride concentration (-0.3 ± 1.3 compared with -7.0 ± 0.7 mg/dL, P-trend < 0.001). CONCLUSIONS: Among middle- to older-age adults, replacing RG with WG may be an effective dietary modification to attenuate abdominal adiposity, dyslipidemia, and hyperglycemia over time, thereby reducing the risk of cardiometabolic diseases.

Data-Driven Clustering Approach to Derive Taste Perception Profiles from Sweet, Salt, Sour, Bitter, and Umami Perception Scores: An Illustration among Older Adults with Metabolic Syndrome.

BACKGROUND: Current approaches to studying relations between taste perception and diet quality typically consider each taste-sweet, salt, sour, bitter, umami-separately or aggregately, as total taste scores. Consistent with studying dietary patterns rather than single foods or total energy, an additional approach may be to study all 5 tastes collectively as "taste perception profiles." OBJECTIVE: We developed a data-driven clustering approach to derive taste perception profiles from taste perception scores and examined whether profiles outperformed total taste scores for capturing individual variability in taste perception. METHODS: The cohort included 367 community-dwelling adults [55-75 y; 55% female; BMI (kg/m2): 32.2 ± 3.6] with metabolic syndrome from PREDIMED-Plus, Valencia. Cluster analysis identified subgroups of individuals with similar patterns in taste perception (taste perception profiles); quantitative criteria were used to select the cluster algorithm, determine the optimal number of clusters, and assess the profiles' validity and stability. Goodness-of-fit parameters from adjusted linear regression evaluated the individual variability captured by each approach. RESULTS: A k-means algorithm with 6 clusters best fit the data and identified the following taste perception profiles: Low All, High Bitter, High Umami, Low Bitter & Umami, High All But Bitter and High All But Umami. All profiles were valid and stable. Compared with total taste scores, taste perception profiles explained more variability in bitter and umami perception (adjusted R2: 0.19 vs. 0.63, respectively; 0.40 vs. 0.65, respectively) and were comparable for sweet, salt, and sour. In addition, taste perception profiles captured differential perceptions of each taste within individuals, whereas these patterns were lost with total taste scores. CONCLUSIONS: Among older adults with metabolic syndrome, taste perception profiles derived via data-driven clustering may provide a valuable approach to capture individual variability in perception of all 5 tastes and their collective influence on diet quality. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870.

Comparison of the Postprandial Metabolic Fate of U-13C Stearic Acid and U-13C Oleic Acid in Postmenopausal Women.

OBJECTIVE: Compare the postprandial fatty acid metabolism of isotopically labeled stearate (U-13C18:0) and oleate (U-13C18:1). Approach and Results: In conjunction with a randomized-controlled crossover trial, 6 hypercholesterolemic postmenopausal women (≥50 years; body mass index: 25.6±3.0 kg/m2; LDL [low-density lipoprotein]-cholesterol ≥110 mg/dL) consumed isocaloric diets enriched in 18:0 or 18:1 (10%-15% E) for 5 weeks each. On day 1 of week 5, following a 12-hour fast, participants receive their experimental diet divided into 13 hourly meals beginning at 8 am. U-13C18:0 or U-13C18:1 was incorporated into the 1:00 pm meal (1.0 mg/kg body weight). Serial blood and breath samples were collected over 12 hours and fasting samples at 24 and 48 hours. Plasma and lipid subfraction fatty acid profiles were assessed by gas chromatography-flame ionization detector, isotope-enrichment by liquid chromatography time-of-flight mass spectrometry, and fatty acid oxidation rate (expired 13CO2) by isotope ratio mass spectrometry. Both diets resulted in similar plasma LDL-cholesterol concentrations. Kinetic curves showed that U-13C18:0 had a higher plasma area under the curve (66%), lower plasma clearance rate (-46%), and a lower cumulative oxidation rate (-34%) than U-13C18:1. Three labeled plasma metabolites of U-13C18:0 were detected: 13C16:0, 13C16:1, and 13C18:1. No plasma metabolites of U-13C18:1 were detected within the study time-frame. Higher incorporation of 18:0 in cholesteryl ester and triglyceride fractions was observed on the 18:0 compared with the 18:1 diet. CONCLUSIONS: 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.

Serum Individual Nonesterified Fatty Acids and Risk of Heart Failure in Older Adults.

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.

Alcohol consumption and risk of cardiovascular disease, cancer and mortality: a prospective cohort study.

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.

Innovation to Create a Healthy and Sustainable Food System: A Science Advisory From the American Heart Association.

Current dietary intakes of North Americans are inconsistent with the Dietary Guidelines for Americans. This occurs in the context of a food system that precludes healthy foods as the default choices. To develop a food system that is both healthy and sustainable requires innovation. This science advisory from the American Heart Association describes both innovative approaches to developing a healthy and sustainable food system and the current evidence base for the associations between these approaches and positive changes in dietary behaviors, dietary intakes, and when available, health outcomes. Innovation can occur through policy, private sector, public health, medical, community, or individual-level approaches and could ignite and further public-private partnerships. New product innovations, reformulations, taxes, incentives, product placement/choice architecture, innovative marketing practices, menu and product labeling, worksite wellness initiatives, community campaigns, nutrition prescriptions, mobile health technologies, and gaming offer potential benefits. Some innovations have been observed to increase the purchasing of healthy foods or have increased diversity in food choices, but there remains limited evidence linking these innovations with health outcomes. The demonstration of evidence-based improvements in health outcomes is challenging for any preventive interventions, especially those related to diet, because of competing lifestyle and environmental risk factors that are difficult to quantify. A key next step in creating a healthier and more sustainable food system is to build innovative system-level approaches that improve individual behaviors, strengthen industry and community efforts, and align policies with evidence-based recommendations. To enable healthier food choices and favorably impact cardiovascular health, immediate action is needed to promote favorable innovation at all levels of the food system.

Supplementation with Seabuckthorn Oil Augmented in 16:1n-7t Increases Serum Trans-Palmitoleic Acid in Metabolically Healthy Adults: A Randomized Crossover Dose-Escalation Study.

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.