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Background: The 2018 physical activity guidelines for Americans recommend a minimum of 150 to 300 min/wk of moderate physical activity (MPA), 75 to 150 min/wk of vigorous physical activity (VPA), or an equivalent combination of both. However, it remains unclear whether higher levels of long-term VPA and MPA are, independently and jointly, associated with lower mortality. Methods: A total of 116 221 adults from 2 large prospective US cohorts (Nurses’ Health Study and Health Professionals Follow-up Study, 1988–2018) were analyzed. Detailed self-reported leisure-time physical activity was assessed with a validated questionnaire, repeated up to 15 times during the follow-up. Cox regression was used to estimate the hazard ratio and 95% CI of the association between long-term leisure-time physical activity intensity and all-cause and cause-specific mortality. Results: During 30 years of follow-up, we identified 47 596 deaths. In analyses mutually adjusted for MPA and VPA, hazard ratios comparing individuals meeting the long-term leisure-time VPA guideline (75–149 min/wk) versus no VPA were 0.81 (95% CI, 0.76–0.87) for all-cause mortality, 0.69 (95% CI, 0.60–0.78) for cardiovascular disease (CVD) mortality, and 0.85 (95% CI, 0.79–0.92) for non-CVD mortality. Meeting the long-term leisure-time MPA guideline (150–299 min/wk) was similarly associated with lower mortality: 19% to 25% lower risk of all-cause, CVD, and non-CVD mortality. Compared with those meeting the long-term leisure-time physical activity guidelines, participants who reported 2 to 4 times above the recommended minimum of long-term leisure-time VPA (150–299 min/wk) or MPA (300–599 min/wk) showed 2% to 4% and 3% to 13% lower mortality, respectively. Higher levels of either long-term leisure-time VPA (≥300 min/wk) or MPA (≥600 min/wk) did not clearly show further lower all-cause, CVD, and non-CVD mortality or harm. In joint analyses, for individuals who reported Conclusions: The nearly maximum association with lower mortality was achieved by performing ≈150 to 300 min/wk of long-term leisure-time VPA, 300 to 600 min/wk of long-term leisure-time MPA, or an equivalent combination of both.

Introduction: There is limited evidence on the association between long-term consumption of ultra-processed foods (UPF) and the risk of type 2 diabetes (T2D), among the U.S population. The overall strength of this association has also not been established. Hypothesis: Higher intake of UPF is associated with a higher risk of T2D in U.S. adults. The pooled risk estimates from published literature reinforce the positive relationship between the UPF intakes and T2D. Methods: We first assessed this relationship among 71,871 women from the Nurses’ Health Study (NHS, 1984-2016), 87,918 women from NHSII (1991-2017), and 38,847 men from the Health Professionals Follow-up Study (HPFS, 1986-2016) who were all free of T2D at baseline. Diet was assessed using food frequency questionnaires, every 2-4 years. UPF were categorized according to the Nova classification. Information on incident cases of T2D was obtained through follow-up questionnaires every 2 years. The association between UPF intake and incident T2D was examined using Cox proportional hazards models. Second, after conducting a systematic review of prospective cohort studies, risk estimates from all included cohorts were pooled in a random-effects, dose-response, meta-analysis to assess nonlinearity of the association between total UPF intake and T2D risk. Finally, the strength of the meta-evidence was assessed using NutriGrade. Results: During 5,187,678 person-years of follow-up across the three cohorts, 19,503 T2D cases were documented. The pooled multivariable-adjusted hazard ratios (HRs) for T2D between the extreme quintiles of total UPF intake (% of grams/day), was 1.36 (95% confidence interval (CI): 1.29, 1.44; P trend 2 =23.1%; P heterogeneity =0.25). Per NutriGrade, the evidence supporting the positive relationship between total UPF intake and T2D was of high quality. Conclusions: High quality evidence shows that total UPF consumption is associated with higher risk of T2D, although not all individual foods classified as ultra-processed were associated with a higher risk in these U.S. cohorts.

Background: Indolepropionate (IPA), a tryptophan metabolite of human gut microbiota origin, is associated with lower risk of type 2 diabetes (T2D) in humans. The complex interplay among tryptophan intake, the gut microbiome, prebiotics, circulating IPA concentrations, and T2D risk has not been investigated. Objectives: We aimed to identify IPA-producing gut microbiota species and investigate potential diet-microbiota interaction on circulating IPA concentrations. Methods: We included 287 men from the Men’s Lifestyle Validation Study, a sub-study of the Health Professionals Follow-Up Study (HPFS), who provided up to two pairs of fecal samples and two blood samples approximately six months apart. Dietary intake was assessed using 7-day diet records. We identified microbial taxonomic features associated with plasma IPA concentrations using generalized linear regression and calculated a rank-based species score to reflect IPA-producing potential. Associations between plasma concentrations of tryptophan metabolites and T2D risk were examined in 13,032 participants from Nurses’ Health Study (NHS), NHSII, and HPFS. Results: Plasma IPA concentrations were associated with overall gut microbial profiles (permutational analysis of variance test, p=0.001). We identified 17 microbial species, such as Eubacterium eligens, Butyrivibrio crossotus , and Faecalibacterium prausnitzii , whose abundance was significantly associated with increased plasma IPA concentrations (false discovery rate < 0.05). A significant association between higher tryptophan intake and higher IPA concentrations was only observed among men who had higher fiber intake and a higher microbial species score consisting of the 17 species (p-interaction < 0.01). Similar modulation was also observed for major tryptophan food contributors including vegetables (p-interaction < 0.01), red/processed meat (p-interaction = 0.02), egg (p-interaction 0.01), dairy (p-interaction = 0.01), and whole grain (p-interaction < 0.01). Moreover, interactions persisted for all fiber subtypes (soluble/insoluble fiber and pectin). We documented 1,744 incident T2D cases during 218,603 person-years of follow-up. Plasma concentrations of tryptophan and three kynurenine-pathway metabolites (kynurenine, xanthurenate, and quinolinate) were positively associated with T2D risk while an inverse association was found for IPA. Conclusions: Specific microbial species and dietary fiber jointly modulate the associations between tryptophan intake and circulating IPA concentrations. In a subsequent analysis, IPA levels were predictive of lower T2D risk. Our findings suggest that the health effects of dietary tryptophan may depend on both gut microbiome composition and prebiotic consumption.

Introduction: The plant-based portfolio dietary pattern includes recognized cholesterol-lowering foods shown to improve several cardiovascular disease (CVD) risk factors in clinical trials. Epidemiological evidence on the association between longer-term adherence to the portfolio dietary pattern and CVD risk remains more limited. Objective: To examine whether the portfolio dietary pattern is associated with the risk of total CVD, coronary heart disease (CHD, including myocardial infarction and fatal coronary deaths), and stroke. Methods: Participants included 73,925 women in the Nurses’ Health Study (NHS) (1984-2014), 92,354 women in the NHS2 (1991-2017) and 43,970 men from the Health Professionals Follow-up Study (HPFS) (1986-2016) without CVD and cancer at baseline. Diet was assessed using validated food frequency questionnaires at baseline and every four years using a portfolio diet score (PDS) which positively ranks plant protein (soy & pulses), nuts, viscous fiber sources, phytosterols (mg/day) and plant monounsaturated fat sources, and negatively ranks foods high in saturated fat and dietary cholesterol. Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for covariates. Results: During up to 30 years of follow-up, 16,917 incident CVD cases, including 10,666 CHD cases and 6,473 stroke cases, were documented. After multivariable adjustment of lifestyle and other dietary factors, comparing the highest to the lowest quintile, participants with a higher PDS had a lower risk of total CVD (pooled HR: 0.84; 95% CI: 0.80-0.89, P trendP trendP trend=0.001). In addition, a 25-percentile higher PDS was associated with a lower risk of total CVD (pooled HR: 0.91; 95% CI: 0.88-0.93), CHD (pooled HR: 0.89; 95% CI: 0.86-0.92) and stroke (pooled HR: 0.93; 95% CI: 0.89-0.97). Results remained largely consistent across sensitivity and subgroup analyses. Conclusions: Greater adherence to the portfolio dietary pattern was consistently associated with lower risk of CVD, including CHD and stroke, in three large prospective cohorts of U.S. men and women.

Residents of Puerto Rico have repeatedly experienced adverse events over the past five years including Hurricanes Irma and Maria in 2017, earthquakes in 2019-2020, Hurricane Fiona in 2022, sociopolitical unrest, a deep economic crisis, and the COVID-19 pandemic (including strict lockdown protocols). Higher psychological resilience, or the ability to “bounce back” after adversity, has been associated with better cardiovascular health in other contexts. One potential mechanism for this relationship is that higher resilience may contribute to engaging in healthier behaviors, such as higher diet quality, more physical activity, and healthier sleep duration and quality, as well as less smoking and drinking. However, such relationships have not yet been explored in this population. We cross-sectionally surveyed 1,240 adults in Puerto Rico in 2019-2022, with recruitment both before and during the COVID-19 pandemic, as part of the Puerto Rico Observational Study of Psychosocial, Environmental, and Chronic Disease Trends (PROSPECT). Participants responded to the Brief Resilience Scale (BRS) and Brief Resilient Coping Scale (BCS). Diet was assessed with a food frequency questionnaire and diet quality was defined by the Alternate Healthy Eating Index (AHEI). Physical activity was measured via the Harvard Alumni Activity Survey. We also collected data on average hours of sleep, quality of sleep, alcohol intake, and tobacco use. Logistic regression models estimated the odds ratios (OR, 95% CI) for following each healthy behavior by established categories of resilience (high and medium vs. low), adjusted for sociodemographic factors and co-morbidities. Of the sample, 39% (452 out of 1175) and 73% (851 out of 1170) were classified with high resilience and coping using the BRS and BCS, respectively. Adults with high resilience (vs. low) on the BRS had twice the odds [OR: 2.01, 95% CI: 1.22, 3.29] of reporting healthy sleep hours (7-8 hours/night compared to either 6 or fewer/night or 9 or more/night). High resilience was also associated with higher odds of being in the upper AHEI tertile (better diet quality) [OR: 1.61 (0.97, 2.68)], and having moderate or heavy physical activity [OR: 1.54 (1.04, 2.29) compared to sedentary or light activity]. These associations persisted when further adjusting for mental health disorders, perceived stress, and social support. Moreover, the relationships were stronger among participants interviewed during the COVID-19 pandemic, suggesting that psychological resilience may be particularly relevant during an ongoing stressor. No significant associations were noted between resilience and tobacco or alcohol use. Given Puerto Rico’s susceptibility to adverse events, seeking to improve population resilience in this and similarly vulnerable populations may lead to better health over the life course.

Introduction: Workplace interventions using behavioral economics approaches may provide low-cost opportunities for promoting healthy lifestyle. It is unknown if employees at higher chronic disease risk are more likely to benefit from workplace health promotion programs than employees at lower risk. This analysis assessed the differential effect of a 12-month behavioral workplace healthy eating intervention on improving dietary choices of employees’ with and without chronic disease risk. Hypothesis: We hypothesized that the intervention effect on cafeteria food purchases and diet quality would be stronger among employees with chronic disease risk compared to those without. Methods: This was a secondary data analysis of the ChooseWell 365 RCT conducted among hospital employees to test the effect of personalized feedback, peer comparisons, and financial incentives on improving cafeteria purchases, dietary intake, and weight. All hospital cafeterias used traffic-light food labeling. Published main results showed an intervention effect on cafeteria purchases but not overall diet quality or weight change. Diet quality was calculated from dietary recalls and measured via the Healthy Eating Index (HEI-2015), scored 0-100 (healthiest). Healthy purchasing scores (HPS) were calculated for each participant, weighting purchases’ color categories (red=0, yellow=0.5, green=1), scaled from 0-100 (healthiest). HEI-2015 and HPS were calculated at baseline, 6, 12, and 24 months. Participants were classified as having chronic disease risk if they self-reported hypertension, hyperlipidemia, heart disease, stroke, pre-diabetes, diabetes, cancer or another serious illness at baseline. Mixed models with random effects were used to compare dietary changes by study arm and risk categorization adjusted for body mass index, age, and race. Results: Participants (N=562) were mostly female (80.3%) and white (81.1%) with a median (p25, p75) age of 42 (33, 55) years; 38.1% reported at least one chronic disease risk condition. There was no differential intervention effect on HPS at any timepoint by chronic disease risk (all p-interaction>0.05): Among those with chronic disease risk, intervention participants increased HPS (unadjusted mean [SD]) from baseline through 24 months (68 [13] to 74 [13]) compared to control (68 [14] to 68 [16]). This was similar to the difference between intervention (67 [12] to 72 [13]) and control participants (69 [12] to 72 [12]) without risk. There was no differential intervention effect on HEI by chronic disease risk (all p-interaction>0.05). Conclusions: The ChooseWell 365 behavioral intervention improved the healthfulness of cafeteria purchases of employees with and without chronic disease risk, suggesting that workplace health promotion programs can improve lifestyle behaviors that contribute to both the prevention and treatment of chronic disease.

Introduction: Food insecurity, a condition of limited household food availability due to insufficient resources, is a critical social determinant of health. Food insecurity increases the risks for poor physical, behavioral, and mental health outcomes. Cardiovascular disease remains the leading cause of mortality in the US, and adults with food insecurity may face a high burden of cardiovascular disease risk. This study aimed to examine the associations between household food security status and ideal cardiovascular health (CVH), defined using the American Heart Association (AHA)’s new Life’s Essential 8 measure. We hypothesized that greater severity of food insecurity will be associated with lower overall cardiovascular health. Methods: Data came from 14,619 adults ≥20 years from the 2013-2018 National Health and Nutrition Examination Surveys. Food security was measured using the 18-item Household Food Security Survey Module, and categorized into households with high, marginal, low, and very low food security. Per AHA criteria, ideal CVH was calculated as scores (0-100) indicating the attainment of standards for diet, physical activity, smoking, sleep, body mass index, blood lipids, blood glucose, and blood pressure. Overall CVH was calculated as the unweighted average score across the eight metrics and overall average CVH score ≥80 was considered high CVH. We used linear and logistic regression models to examine the associations between household food security and ideal CVH outcomes, adjusting for sociodemographic characteristics. Complex survey weights were applied to all analyses. Results: In the sample, 72.7% of adults had high food security, 10.0% had marginal food security, 10.4% had low food security, and 6.8% had very low food security. The mean overall CVH score was 68.8 (SE 0.3), ranging from 70.2 (SE 0.3) for high food security to 62.7 (SE 1.8) for very low food security. After multivariate adjustment, marginal food security (β= -1.5, 95% CI -2.9, -0.1), low food security (β= -3.0, 95% CI -4.4, -1.7), and very low food security (β= -4.7, 95% CI -6.4, -3.0) were each associated with lower overall CVH scores when compared to high food security ( P-trend ). These associations were driven by lower mean scores for diet, tobacco, sleep, BMI, and blood glucose with greater severity of food insecurity ( P-trends ). Furthermore, low food security (OR 0.57, 95% CI 0.45, 0.74) and very low food security (OR 0.52, 95% CI 0.37, 0.73) were both associated with lower odds of high CVH. Results remained significant in sensitivity analyses restricting the sample to adults with family incomes ≤300% of the federal poverty level. Discussion: Household food insecurity was adversely associated with cardiovascular health metrics in a dose-response fashion. Public health interventions and policies should consider a holistic approach to health promotion among populations with food insecurity.

Introduction: Recent evidence suggests that intake of ultra-processed foods (UPF) is related to unfavorable cardio-metabolic risk profiles among generally healthy populations. However, evidence on the relationship between UPF intake and cardiovascular disease (CVD) among patients with type 2 diabetes (T2D) is lacking. Hypothesis: We assessed the hypothesis that higher intake of dietary UPF is associated with higher risks of CVD among individuals with T2D. Methods: We prospectively followed 13,272 men and women participating in the Health Professionals Follow-Up Study (HPFS) and Nurses’ Health Study (NHS) with T2D at baseline and during follow-up (HPFS: 1986-2018; NHS: 1980-2014). Diet was repeatedly assessed using validated food frequency questionnaires every 2-4 years. UPF were categorized according to the Nova classification. CVD was defined as fatal and non-fatal coronary heart disease (CHD) (including nonfatal myocardial infarction, coronary artery bypass graft surgery, and coronary angioplasty and stent) and fatal and non-fatal stroke. Associations of UPF consumption with risks of CVD were assessed using Cox regression. Results: During 165,761 person-years of follow-up, 1,826 total CHD and 529 total stroke were identified and confirmed. After adjusting for demographics, lifestyle, medical history, dietary factors, and diabetes medication use, higher total intake of UPF was associated with higher risk of CHD. The multivariable-adjusted HRs (95% CIs) were 1.20 (1.02, 1.43) ( P trend = 0.03) when comparing the highest and lowest quintiles (Q5 vs. Q1) or 1.03 (1.01, 1.04) for each 1 serving/day increment of UPF. No association between UPF intake and risk of stroke was observed (Q5 vs. Q1: 0.92 (0.67, 1.24)). These results were consistent across subgroups in analyses stratified by age, sex, BMI, diet quality, physical activity, smoking, diabetes medication use, or diabetes duration. In addition, compared with participants who had a stable or decreased consumption of UPF (≤0 change in UPF) from pre- to post-diabetes diagnosis, participants who increased consumption of UPF (>0 increment of UPF intake) after diabetes diagnosis had a 15% (1%, 31%) higher risk of CHD. Conclusions: Among participants with T2D, higher dietary UPF consumption was associated with a higher risk of CHD, but not stroke. These results provide further support for the current recommendations to limit UPF consumption for the prevention of CHD among patients with diabetes.

Introduction: Ultra-processed foods (UPF) are associated with cardiovascular disease (CVD) in European populations. Evidence is limited from U.S. populations, for specific UPF subgroups, and in the diet quality context. Hypothesis: We hypothesized that U.S. women with higher UPF intake have higher CVD risk and evaluated this association by UPF subgroup and diet quality. Methods: Women from the Nurses' Health Study (NHS; n=75,639; 30-55y) and NHSII (n=90,770; 25-42y) with complete dietary intake data and without CVD/cancer at baseline were prospectively followed (1984-2014 and 1991-2015). Diet, demographics, lifestyle, and medical history were assessed every 2-4y using validated food frequency questionnaires and follow-up questionnaires. NOVA-classified UPF (% of energy) included ten subgroups: bread and cereals; sauces, spreads, and condiments; sweet snacks and desserts; savory snacks; sugar-sweetened beverages; animal-based products; ready-to-eat/heat dishes; yogurt and dairy desserts; hard liquors, and artificially sweetened beverages. The Alternative Healthy Eating Index (AHEI) measured diet quality. Primary outcomes were non-fatal myocardial infarction, fatal coronary heart disease (CHD), and non-fatal/fatal stroke. Multivariable-adjusted Cox regression estimated the associations of cumulatively-averaged UPF and subgroup intake quintiles with CVD risk. Each cohort was analyzed separately, and data were meta-analyzed (fixed effects models). Results: We identified 7,659 CVD cases (CHD=3,889; stroke=3,855) in NHS during 2,002,986 person-years of follow-up, and 1,588 CVD cases (CHD=807; stroke=786) in NHSII during 2,308,569 person-years. Pooled multivariable-adjusted hazard ratios [HRs (95%CIs)] of CVD, CHD, and stroke for the highest quintile of UPF intake ( vs. lowest) were 1.11 (1.04, 1.19; p-trend =0.002), 1.18 (1.08, 1.30; p-trend p-trend =0.37), respectively. Positive associations remained for participants with higher diet quality (AHEI above the sample median): CVD [HR=1.15 (1.05, 1.25; p-trend =0.009)] and CHD [HR=1.24 (1.09, 1.41; p-trend =0.007)]. Values of I 2 were non-significant. For UPF subgroups, intake for the highest quintile of sugar-sweetened beverages and animal-based products was significantly associated with higher risk of CVD, CHD, and stroke. Significant inverse associations were noted for bread and cereals and yogurt and dairy dessert with CVD, CHD, and stroke, for savory snacks with CHD, and for ready-to-eat/heat dishes with stroke. Conclusion: U.S. women with long-term higher total UPF intake had a higher CHD risk, even with a high-quality diet. Sugary drinks and animal-based products were predominant for CVD risk. Some UPF subgroups may contain beneficial components, warranting more nuanced food subgroup analyses. Replication is needed in racially/ethnically-diverse populations.

Background: The potential health effects of dietary glutamine and glutamate have been studied in healthy populations, but evidence among individuals with type 2 diabetes (T2D) who have altered macronutrient metabolism and elevated cardiovascular disease (CVD) risk is limited. Objectives: We aimed to examine dietary glutamine and glutamate in relation to subsequent risk of CVD, including coronary heart disease and stroke, and all-cause and cause-specific mortality among individuals with T2D. Methods: We prospectively followed 15,040 men and women with T2D at baseline or diagnosed during follow-up (Nurses' Health Study: 1980-2014, Health Professionals Follow-Up Study: 1986-2018). Diet was repeatedly assessed using validated food frequency questionnaires every 2-4 years since baseline. Associations of energy-adjusted glutamine and glutamate intake, as well as their ratio, with CVD risk and mortality were assessed using Cox proportional hazards models with adjustments for demographics, dietary and lifestyle factors, and medical history. Results: During 196,955 and 225,371person-years of follow-up in participants with T2D, there were 2,927 incident CVD cases and 4,898 deaths, respectively. Higher intake of glutamine was associated with lower risk of incident CVD, total mortality and CVD mortality: comparing extreme quintiles, the HRs (95%CIs) were 0.88 (0.77, 0.99), 0.85 (0.77, 0.94), and 0.82 (0.69, 0.98), respectively (all P trend P trend Conclusions: In patients with T2D, dietary glutamine and glutamate demonstrated divergent associations with CVD incidence and mortality, and higher dietary glutamine-to-glutamate ratio was significantly associated with lower CVD incidence and mortality. These data suggest a potential critical role of these two amino acids in the etiology of cardiometabolic diseases and early deaths also among adults with T2D.

The association of PFASs with blood lipids, lipoproteins and apolipoproteins, and coronary heart disease (CHD) risk are inconsistent in previous studies. The aim of current study is to examine the potential association between plasma PFASs, blood lipoproteins and their subspecies defined by apolipoproteins, and whether PFASs are associated with CHD risk.A case-control study was conducted in 100 men and 102 women aged 45-70 years. We leveraged 101 participants from HPFS and NHS who were initially free of cardiovascular disease and developed a fatal or non-fatal myocardial infarction during follow-up, and randomly matched controls in a 1:1 ratio for age, smoking status, and date of blood draw. Seven plasma PFASs measurements were examined at baseline, including perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), total perfluorooctane sulfonic acid (PFOS), branched PFOS (brPFOS), linear PFOS (nPFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), with all mean CVs

Background: Evidence for the role of omega-3 fatty acids in the prevention of atrial fibrillation (AF) remain inconsistent, with some recent RCTs even suggesting possible harm. Whether long-term dietary intake of these fatty acids, as assessed using objective biomarkers, is related to AF is not known. Aims: To prospectively evaluate circulating and tissue levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and the sum of EPA and DHA (also known as the omega-3 index), with respect to incident AF. Methods: We used data from a global consortium of 13 prospective cohort studies with measurements of EPA, DPA, or DHA in adults (age≥18) identified through March 2021. Participating studies conducted de novo participant-level analyses using a prespecified analytical plan with harmonized definitions for exposures, outcomes, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. Results: Among 45,910 participants, a total of 6,229 incident cases of AF were ascertained, with median follow-up ranging from 0.9 to 29.1 years. In the multivariable analysis, per interquintile range (difference between the 90 th and 10 th percentiles for each fatty acid), DPA, DHA, and EPA+DHA ( Figure 1 ) were associated with 11%, 13%, and 9% lower incidence of AF, respectively ( P I 2 ranged from 0% for DPA to 56.7% for EPA+DHA. Associations were broadly consistent irrespective of baseline cardiovascular risk, global region, age, sex, or lipid fraction. Conclusion: Biomarkers of omega-3 fatty acids including DPA, DHA, and EPA+DHA demonstrated an inverse association with incident AF. In the absence of RCTs examining long-term dietary omega-3 intake and AF risk, our results do not suggest that higher levels of these fatty acids are associated with harm.

Background: Preclinical studies suggested that high intakes of sulfur amino acids (SAA), including methionine and cysteine, may increase risk of age-related chronic diseases. Until now, no epidemiologic studies have investigated habitual dietary intake of SAA in relation to risk of cardiovascular disease (CVD) and mortality. Methods: We prospectively followed 120,699 participants in the Nurses’ Health Study (1984-2016) and Health Professionals Follow-up Study (1986-2016) cohorts who had no known history of cancer, CVD, or diabetes at baseline. Diet was assessed using a validated food frequency questionnaire that was updated every 2-4 years. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD and all-cause and CVD mortality across quintiles of energy adjusted SAA intake. Results: During up to 32 years of follow up, we documented 13,547 incident CVD events and 33,958 deaths, of which 7637 were due to CVD. Participants on average consumed more than 2-fold the recommended daily allowance of SAA (19 mg/kg/day), and the main food sources included beef, chicken, and milk. After adjustment for non-dietary and dietary risk factors including total energy intake, higher SAA intake was significantly associated with higher risks of CVD, CVD mortality, and all-cause mortality in men and women. In the meta-analysis combining both cohorts, comparing participants in the highest quintile with those in the lowest quintile of SAA intake, HRs (95% CI) were 1.12 (1.05, 1.20) for CVD, 1.28 (1.11, 1.47) for CVD mortality, and 1.15 (1.11, 1.19) for all-cause mortality. These associations were similar across strata of age, body mass index, physical activity, ratio of animal to plant protein, smoking, and alcohol consumption (p interaction > 0.05 for all), and they remained significant after further adjustment for total protein intake. Conclusions: Our data suggest that high SAA intake is associated with greater risks of CVD and mortality in men and women.

Background: The relationship between sodium intake and cardiovascular disease (CVD) remains controversial, in part, due to inaccurate assessment of sodium intake. 24-hour urinary excretion over multiple days is considered the optimal method. Methods: We included individual participant data from 6 prospective cohorts among generally healthy adults with sodium and potassium excretion assessed by at least two 24-hour urine collections. Out of 10,709 participants (54% women; mean [SD] age, 51.5 [12.6] years), 571 incident CVD events (including myocardial infarction, coronary revascularization, and stroke) were ascertained during a median follow-up of 8.8 years. We analyzed each cohort using consistent methods and combined the results using random-effects meta-analysis. Results: Median 24-hour urinary sodium excretion (10 th -90 th percentile) was 3,270 (2,099-4,899) mg. Higher sodium excretion, lower potassium excretion and higher sodium-to-potassium ratio were all associated with higher risk of CVD events after controlling for confounding factors (all P values for trend≤0.02); there was no evidence of nonlinearity. The hazard ratio [HR] comparing top with bottom quartiles was 1.67 [95% confidence interval [CI]: 1.21-2.30] for sodium, 0.77 [0.57-1.02] for potassium and 1.72 [1.27-2.32] for sodium-to-potassium ratio. Each 1,000 mg/d increment in sodium excretion was associated with an 18% increase in CVD risk (95%CI: 5%-32%) and each 1,000 mg/d increment in potassium excretion was associated with 18% lower risk (95%CI: 6%-28%). Conclusions: Higher sodium and lower potassium intakes, measured in multiple 24-hour urine samples, were associated with higher risk of CVD in a dose-response manner. These findings support current recommendations to reduce sodium and increase potassium intakes.

Background: Plant-based diets have been associated with lower risk of type 2 diabetes mellitus and cardiovascular disease (CVD) and are recommended for both health and environmental benefits. However, the association between changes in plant-based diet quality and mortality remains unclear. Methods: We investigated the associations between 12-year changes (from 1986 to 1998) in plant-based diet quality assessed by 3 plant-based diet indices (score range, 18–90)—an overall plant-based diet index (PDI), a healthful PDI, and an unhealthful PDI—and subsequent total and cause-specific mortality (1998–2014). Participants were 49 407 women in the Nurses’ Health Study (NHS) and 25 907 men in the Health Professionals Follow-Up Study (HPFS) who were free from CVD and cancer in 1998. Multivariable-adjusted Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% CIs. Results: We documented 10 686 deaths including 2046 CVD deaths and 3091 cancer deaths in the NHS over 725 316 person-years of follow-up and 6490 deaths including 1872 CVD deaths and 1772 cancer deaths in the HPFS over 371 322 person-years of follow-up. Compared with participants whose indices remained stable, among those with the greatest increases in diet scores (highest quintile), the pooled multivariable-adjusted HRs for total mortality were 0.95 (95% CI, 0.90–1.00) for PDI, 0.90 (95% CI, 0.85–0.95) for healthful PDI, and 1.12 (95% CI, 1.07–1.18) for unhealthful PDI. Among participants with the greatest decrease (lowest quintile), the multivariable-adjusted HRs were 1.09 (95% CI, 1.04–1.15) for PDI, 1.10 (95% CI, 1.05–1.15) for healthful PDI, and 0.93 (95% CI, 0.88–0.98) for unhealthful PDI. For CVD mortality, the risk associated with a 10-point increase in each PDI was 7% lower (95% CI, 1–12%) for PDI, 9% lower (95% CI, 4–14%) for healthful PDI, and 8% higher (95% CI, 2–14%) for unhealthful PDI. There were no consistent associations between changes in plant-based diet indices and cancer mortality. Conclusions: Improving plant-based diet quality over a 12-year period was associated with a lower risk of total and CVD mortality, whereas increased consumption of an unhealthful plant-based diet was associated with a higher risk of total and CVD mortality.

Background: Plant-based diets have been associated with a lower risk of type 2 diabetes. However, the underlying mechanisms are not completely understood, and the evidence using objective approaches to assess the adherence of plant-based diets is limited. Methods: In the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study, we characterized the plasma metabolome related to plant-based diets and examined its association with the incidence of type 2 diabetes among 10 699 participants. Plasma metabolomic profiling was conducted by liquid chromatography-tandem mass spectrometry. Adherence to plant-based diets was assessed by three plant-based diet indices derived from the food frequency questionnaire: an overall plant-based diet index (PDI), a healthful PDI (hPDI), and an unhealthful PDI (uPDI). Metabolomic signatures reflecting the adherence to plant-based diets were created using elastic net regression, and their associations with risk of type 2 diabetes were subsequently evaluated using multivariable Cox proportional hazards regression. Results: Among 263 metabolites measured, nearly half were significantly associated with PDI (41.4%, 109 of 263), hPDI (51.7%, 136 of 263), and uPDI (40.3%, 106 of 263) after Bonferroni correction. We developed a metabolomic signature comprising 53 metabolites for PDI, 76 metabolites for hPDI, and 88 metabolites for uPDI, each robustly correlated with the corresponding diet index (r=0.34-0.36 for PDI, 0.43-0.44 for hPDI, and 0.36-0.37 for uPDI). We observed an inverse association of PDI metabolomic signature (HR 0.86, 95% CI 0.79-0.93 per one standard deviation) and hPDI metabolomic signature (0.79, 0.72-0.86) with type 2 diabetes risk after adjustment for body mass index and other potential confounders. These two inverse associations remained significant even further adjusting for the corresponding diet index PDI and hPDI. The metabolomic signature for uPDI was not associated with type 2 diabetes risk (1.00, 0.93-1.09). Conclusion: Plasma metabolome can robustly reflect adherence and metabolic response to plant-based diets. Metabolomic signatures reflecting greater adherence to an overall plant-based diet, especially a healthful plant-based diet, were associated with a lower risk of type 2 diabetes. These findings support and provide mechanistic insights on the important role of healthful plant-based diets in diabetes prevention.

Introduction: Cardiovascular disease (CVD) primordial prevention tools applicable to diverse populations are scarce. Hypothesis: We assessed the hypothesis that the Healthy Heart Score, a lifestyle-based tool to estimate CVD risk, will perform well in estimating CVD risk in an African American population. Methods: The Jackson Heart Study (JHS) is a prospective cohort, community-based study in Jackson, Mississippi that recruited participants between September 2000 and March 2004 (baseline), with a mean follow up of 12 years. A total of 5306 African American were recruited, 3041 individuals free of CVD at baseline were included for the current analysis. CVD incidence was defined as the first occurrence of fatal/non-fatal myocardial infarction (MI), stroke or fatal coronary heart disease (CHD). The Healthy Heart Score is a lifestyle-based CVD risk prediction model based on 9 components: body mass index (BMI), physical activity, cereal fiber, fruit and vegetables, red and processed meat, nuts, sugar and sweetened beverages and alcohol intake. Gender-specific beta coefficients from its derivation cohorts were used to assess the performance of the Healthy Heart Score. Model discrimination was assessed using Harrell′s C-Index for survival data and time dependent Area Under the Curve (AUC). Model calibration was evaluated through calibration plots. Results: A total of 189 CVD events occurred (111 in women and 78 in men, average age at baseline 53.1 (12.7) years). The Healthy Heart Score showed high-moderate discrimination for CVD events (C-statistic 0.75 (95% CI, 0.71-0.78)) but with little improvement over the age-only model. The time dependent AUC analysis showed similar results for CVD events and improved performance in the first year with the complete model (age only: AUC 0.76 (95% CI, 0.65-0.88) vs. Healthy Heart Score 0.78 (95% CI 0.68-0.89)). Both the age-only and Healthy Heart Score models had better performance in participants without diabetes at baseline. The Healthy Heart Score model showed good calibration. Conclusions and Relevance . In African Americans with a high prevalence of clinical CVD risk factors, the Hearty Heart Score does not improve prediction of mid-life CVD events beyond what is obtained by age alone.

Objectives: The aim of this study was to evaluate the relationship between a lifestyle score including sleep duration and CVD risk, and to estimate whether adding sleep duration into a traditional lifestyle score improved CVD risk prediction. Methods: A prospective analysis was conducted among 67250 women in the Nurses’ Health Study and 29279 men in the Health Professionals Follow-up Study who were followed from 1986 to 2016. The traditional lifestyle score was defined as not smoking, normal BMI(18.5-24.9 kg/m 2 ), ≥30 min/d of moderate physical activity, higher diet quality (top 40% of AHEI), moderate alcohol intake (women:5-15g/day; men:5-30g/day). Low-risk sleep duration, defined as sleeping ≥6 to Results: A total of 11826 incident CVD cases were documented. In multivariable-adjusted models, each low-risk factor was independently and significantly associated with lower risk of CVD, CHD, and stroke. The multivariable-adjusted HRs (95% CIs) comparing six with zero low-risk factors in the healthy lifestyle score were 0.17(0.12, 0.23) for CVD, 0.15(0.10, 0.22) for CHD, and 0.19(0.12, 0.33) for stroke. Approximately 67% of CVD and CHD cases, and 62% stroke cases were attributable to poor adherence to a healthy lifestyle. P- value for likelihood ratio test comparing nested models including the traditional lifestyle score vs traditional lifestyle score plus sleep duration was P Conclusions: Incorporating sleep duration into traditional lifestyle scores improves prediction of CVD risk and warrants consideration for inclusion in lifestyle recommendations.

Introduction: Although non-appetitive eating phenotypes are associated with body mass index, the extent to which they are associated with hypertension is unknown. Hypothesis: We hypothesize that non-appetitive eating phenotypes are associated with hypertension. Methods: We examined participants in a substudy on disordered eating conducted in 2013-2015, nested within the prospective cohort, Nurses’ Health Study 2. Non-appetitive eating was defined by: 1) binge eating with loss of control; 2) disinhibited eating; 3) coping-motivated eating; and 4) food addiction. Prevalent hypertension was defined by self-reported clinician diagnosis. Odds ratios and 95% confidence intervals (OR, 95% CI) were used to estimate the association of non-appetitive eating with prevalent hypertension, adjusted for age and race. The difference method was used to estimate the proportion of the associations mediated by body mass index. Results: After excluding missing exposure (n=421), the analytic sample included n=4,687 women (of n=5,108 women). Average age was 60 years (range: 49 to 68); 18% (n=824) reported binge eating with loss of control; average disinhibited eating score was 3 (range: 0 to 7); average coping-motivated eating score was 2 (range: 1 to 5); and 7% (n=349) reported food addiction. Non-appetitive eating was associated with higher odds of hypertension. Binge eating with loss of control was associated with 60% higher odds (95% CI: 1.37, 1.87) of hypertension. Per unit, disinhibited eating was associated with 18% (95% CI: 1.14, 1.21) and coping-motivated eating was associated with 38% (95% CI: 1.29, 1.47) higher odds of hypertension. Food addiction (yes versus no) was associated with a 108% higher odds (95% CI: 1.67, 2.60) of hypertension. Body mass index mediated more than 85% of the associations of each non-appetitive eating phenotype with hypertension. Conclusions: Non-appetitive eating is associated with hypertension. Body mass index explained almost all of the associations between non-appetitive eating and hypertension. Prospective studies are needed to confirm the direction of the associations.

Background: The optimal intake levels of fruit and vegetables for maintaining long-term health are uncertain. Methods: We followed 66 719 women from the Nurses’ Health Study (1984–2014) and 42 016 men from the Health Professionals Follow-up Study (1986–2014) who were free from cardiovascular disease (CVD), cancer, and diabetes at baseline. Diet was assessed using a validated semiquantitative food frequency questionnaire at baseline and updated every 2 to 4 years. We also conducted a dose-response meta-analysis, including results from our 2 cohorts and 24 other prospective cohort studies. Results: We documented 33 898 deaths during the follow-up. After adjustment for known and suspected confounding variables and risk factors, we observed nonlinear inverse associations of fruit and vegetable intake with total mortality and cause-specific mortality attributable to cancer, CVD, and respiratory disease (all P nonlinear P nonlinear Conclusions: Higher intakes of fruit and vegetables were associated with lower mortality; the risk reduction plateaued at ≈5 servings of fruit and vegetables per day. These findings support current dietary recommendations to increase intake of fruits and vegetables, but not fruit juices and potatoes.