Serum Metabolomic Markers of Protein-Rich Foods and Incident CKD: Results From the Atherosclerosis Risk in Communities Study.

Rationale & Objective: While urine excretion of nitrogen estimates the total protein intake, biomarkers of specific dietary protein sources have been sparsely studied. Using untargeted metabolomics, this study aimed to identify serum metabolomic markers of 6 protein-rich foods and to examine whether dietary protein-related metabolites are associated with incident chronic kidney disease (CKD). Study Design: Prospective cohort study. Setting & Participants: A total of 3,726 participants from the Atherosclerosis Risk in Communities study without CKD at baseline. Exposures: Dietary intake of 6 protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, and poultry), serum metabolites. Outcomes: Incident CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2 with ≥25% estimated glomerular filtration rate decline relative to visit 1, hospitalization or death related to CKD, or end-stage kidney disease). Analytical Approach: Multivariable linear regression models estimated cross-sectional associations between protein-rich foods and serum metabolites. C statistics assessed the ability of the metabolites to improve the discrimination of highest versus lower 3 quartiles of intake of protein-rich foods beyond covariates (demographics, clinical factors, health behaviors, and the intake of nonprotein food groups). Cox regression models identified prospective associations between protein-related metabolites and incident CKD. Results: Thirty significant associations were identified between protein-rich foods and serum metabolites (fish, n = 8; nuts, n = 5; legumes, n = 0; red and processed meat, n = 5; eggs, n = 3; and poultry, n = 9). Metabolites collectively and significantly improved the discrimination of high intake of protein-rich foods compared with covariates alone (difference in C statistics = 0.033, 0.051, 0.003, 0.024, and 0.025 for fish, nuts, red and processed meat, eggs, and poultry-related metabolites, respectively; P < 1.00 × 10-16 for all). Dietary intake of fish was positively associated with 1-docosahexaenoylglycerophosphocholine (22:6n3), which was inversely associated with incident CKD (HR, 0.82; 95% CI, 0.75-0.89; P = 7.81 × 10-6). Limitations: Residual confounding and sample-storage duration. Conclusions: We identified candidate biomarkers of fish, nuts, red and processed meat, eggs, and poultry. A fish-related metabolite, 1-docosahexaenoylglycerophosphocholine (22:6n3), was associated with a lower risk of CKD.

In this study, we aimed to identify associations between protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, and poultry) and serum metabolites, which are small biological molecules involved in metabolism. Metabolites significantly associated with a protein-rich food individually and collectively improved the discrimination of the respective protein-rich food, suggesting that these metabolites should be prioritized in future diet biomarker research. We also studied associations between significant diet-related metabolites and incident kidney disease. One fish-related metabolite was associated with a lower kidney disease risk. This finding supports the recent nutritional guidelines recommending a Mediterranean diet, which includes fish as the main dietary protein source.

Diet quality is associated with adipose tissue and muscle mass: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

BACKGROUND: Aging is associated with changes in body composition, and preventing loss of muscle mass and accumulation of excess adipose tissue in middle-aged adults may reduce age-related conditions at older ages. Dietary intake is one lifestyle factor shown to improve or maintain body composition. However, few studies have examined the Healthy Eating Index2015 (HEI2015), a measure of diet quality, and the association with body composition in adult men and women. METHODS: Participant data (n = 3017) from the Coronary Artery Risk Development in Young Adults (CARDIA) study were used to examine the associations of the HEI2015 with body composition measures at Year 25 (Y25), including (1) 25 year-change in weight, body mass index (BMI), and waist circumference and (2) a computed tomography (CT) scan at Y25 measured muscle mass, muscle quality (better quality = less lipid within the muscle), and adipose tissue depots visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and adipose within skeletal muscle (intermuscular adipose tissue; IMAT). Dietary intake was assessed by a diet history three times over 20 years, at years 0, 7, and 20. HEI2015, averaged over three exams, was created and categorized into quintiles. Multiple regression analysis evaluated the associations of body composition stratified across quintiles of HEI2015 adjusted for demographic characteristics, energy intake, lifestyle factors, and baseline anthropometric measures as appropriate. Race-sex interaction was tested (Pinteraction  > 0.30). RESULTS: Over 25 years of follow-up, averaged HEI2015 was significantly and inversely associated with weight gain (Quintile 1 (Q1) 37.3 lb vs. 32.9 in Q5; Ptrend  = 0.01), change in BMI (Q1 5.8 kg/m2 vs. 5.0 in Q5; Ptrend  = 0.005), and change in waist circumference (Q1 17.5 cm vs. 15.2 cm in Q5; Ptrend  < 0.001). By Y25, HEI2015 was inversely associated with VAT Q1 136.8 cm3 vs. 116.6 in Q5; Ptrend  < 0.001) and IMAT volumes (Q1 9.52 vs. 8.12 cm3 in Q5; Ptrend  < 0.001). Although total muscle volume declined (Ptrend  = 0.03), lean muscle mass volume was similar across quintiles (Ptrend  = 0.55). The IMAT/total muscle mass ratio declined across HEI2015 quintiles (Ptrend  < 0.001). Finally, higher HEI2015 was associated with better muscle quality at Y25 (higher value = less lipid within the muscle; Q1 41.1 vs. 42.2 HU in Q5; Ptrend  = 0.002). HEI2015 was nonlinearly, but inversely, associated with SAT (nonlinear P = 0.011). CONCLUSIONS: Improving diet quality in young to middle-aged adults is a recommended strategy to promote better measures of body composition. Our study findings suggest that healthier food choices may influence body composition.

A Plant-Centered Diet is Inversely Associated With Radiographic Emphysema: Findings from the CARDIA Lung Study.

Background: Chronic obstructive pulmonary disease (COPD) is a significant public health concern and intercepting the development of emphysema is vital for COPD prevention. Smokers are a high-risk population for emphysema with limited prevention strategies. We aimed to determine if adherence to a nutritionally rich, plant-centered diet among young ever-smokers is associated with reduced risk of future radiographic emphysema. Methods: We studied participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Lung Prospective Cohort Study who were 18-30 years old at enrollment and followed for 30 years. We analyzed 1706 adults who reported current or former smoking by year 20. Repeated measures of diet history were used to calculate A Priori Diet Quality Scores (APDQSs), and categorized into quintiles, with higher quintiles representing higher nutritionally rich plant-centered food intake. Emphysema was assessed at year 25 (n=1351) by computed tomography (CT). Critical covariates were selected, acknowledging potential residual confounding. Results: Emphysema was observed in 13.0% of the cohort, with a mean age of 50.4 ± 3.5 years. The prevalence of emphysema was 4.5% in the highest APDQS quintile (nutritionally rich), compared with 25.4% in the lowest quintile. After adjustment for multiple covariates, including smoking, greater adherence to a plant-centered diet was inversely associated with emphysema (highest versus lowest quintile odds ratio: 0.44, 95% CI 0.19-0.99, ptrend=0.008). Conclusion: Longitudinal adherence to a nutritionally rich, plant-centered diet was associated with a decreased risk of emphysema development in middle adulthood, warranting further examination of diet as a strategy for emphysema prevention in a high-risk smoking population.

Investigating Associations of Omega-3 Fatty Acids, Lung Function Decline, and Airway Obstruction.

Rationale: Inflammation contributes to lung function decline and the development of chronic obstructive pulmonary disease. Omega-3 fatty acids have antiinflammatory properties and may benefit lung health. Objectives: To investigate associations of omega-3 fatty acids with lung function decline and incident airway obstruction in a diverse sample of adults from general-population cohorts. Methods: Complementary study designs: 1) longitudinal study of plasma phospholipid omega-3 fatty acids and repeated FEV1 and FVC measures in the NHLBI Pooled Cohorts Study and 2) two-sample Mendelian randomization (MR) study of genetically predicted omega-3 fatty acids and lung function parameters. Measurements and Main Results: The longitudinal study found that higher omega-3 fatty acid levels were associated with attenuated lung function decline in 15,063 participants, with the largest effect sizes for the most metabolically downstream omega-3 fatty acid, docosahexaenoic acid (DHA). An increase in DHA of 1% of total fatty acids was associated with attenuations of 1.4 ml/yr for FEV1 (95% confidence interval [CI], 1.1-1.8) and 2.0 ml/yr for FVC (95% CI, 1.6-2.4) and a 7% lower incidence of spirometry-defined airway obstruction (95% CI, 0.89-0.97). DHA associations persisted across sexes and smoking histories and in Black, White, and Hispanic participants, with associations of the largest magnitude in former smokers and Hispanic participants. The MR study showed similar trends toward positive associations of genetically predicted downstream omega-3 fatty acids with FEV1 and FVC. Conclusions: The longitudinal and MR studies provide evidence supporting beneficial effects of higher levels of downstream omega-3 fatty acids, especially DHA, on lung health.

Investigating associations of omega-3 fatty acids, lung function decline, and airway obstruction.

Rationale: Inflammation contributes to lung function decline and the development of chronic obstructive pulmonary disease. Omega-3 fatty acids have anti-inflammatory properties and may benefit lung health. Objectives: Investigate associations of omega-3 fatty acids with lung function decline and incident airway obstruction in adults of diverse races/ethnicities from general population cohorts. Methods: Complementary study designs: (1) longitudinal study of plasma phospholipid omega-3 fatty acids and repeated FEV 1 and FVC measures in the National Heart, Lung, and Blood Institute Pooled Cohorts Study, and (2) two-sample Mendelian Randomization (MR) study of genetically predicted omega-3 fatty acids and lung function parameters. Measurements and Main Results: The longitudinal study found that higher omega-3 fatty acid concentrations were associated with attenuated lung function decline in 15,063 participants, with the largest effect sizes for docosahexaenoic acid (DHA). One standard deviation higher DHA was associated with an attenuation of 1.8 mL/year for FEV 1 (95% confidence interval [CI] 1.3-2.2) and 2.4 mL/year for FVC (95% CI 1.9-3.0). One standard deviation higher DHA was also associated with a 9% lower incidence of spirometry-defined airway obstruction (95% CI 0.86-0.97). DHA associations persisted across sexes, smoking histories, and Black, white and Hispanic participants, with the largest magnitude associations in former smokers and Hispanics. The MR study showed positive associations of genetically predicted omega-3 fatty acids with FEV 1 and FVC, with statistically significant findings across multiple MR methods. Conclusions: The longitudinal and MR studies provide evidence supporting beneficial effects of higher circulating omega-3 fatty acids, especially DHA, on lung health.

Coffee Consumption May Mitigate the Risk for Acute Kidney Injury: Results From the Atherosclerosis Risk in Communities Study.

Introduction: Coffee is one of the most frequently consumed beverages worldwide and has been found to have a wide assortment of health benefits. Although habitual coffee consumption is associated with a lower incidence of chronic kidney disease, an association between coffee and acute kidney injury (AKI) has not yet been revealed. Methods: In the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort study of 14,207 adults aged 45 to 64 years, coffee consumption (cups/d) was assessed at a single visit via food frequency questionnaires and compared with incident AKI defined by hospitalization with an AKI-related International Classification of Diseases code. Results: In ARIC, there were 1694 cases of incident AKI in a median of 24 follow-up years. Higher coffee consumption was associated with lower AKI risk versus no consumption (hazard ratio [HR] <1 cup/d: 0.92 [95% CI: 0.79-1.08]; 1 cup/d: 1.08 [95% CI: 0.94-1.24]; 2 to 3 cups/d: 0.83 [95% CI: 0.72-0.95]; >3 cups/d: 0.83 [95% CI: 0.71-0.96]; reference: never, P = 0.003). Trends for AKI risk across coffee categories remained significant after multivariable adjustment for age, sex, race-center, education, total daily energy intake, physical activity, smoking, alcohol intake, diet quality (Dietary Approaches to Stop Hypertension [DASH] score), systolic blood pressure (BP), diabetes status, use of antihypertensive agents, estimated glomerular filtration rate (eGFR), and body mass index (BMI) (P = 0.02). Conclusion: Higher coffee intake was associated with a lower risk of incident AKI and could present an opportunity for cardiorenal protection through diet. Further evaluation of the physiological mechanisms underlying the cardiorenal protective effects of coffee consumption is necessary.

Blood pressure interactions with the DASH dietary pattern, sodium, and potassium: The International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP).

BACKGROUND: Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet enhances potassium intake and reduces sodium intake and blood pressure (BP), but the underlying metabolic pathways are unclear. OBJECTIVES: Among free-living populations, we delineated metabolic signatures associated with the DASH diet adherence, 24-hour urinary sodium and potassium excretions, and the potential metabolic pathways involved. METHODS: We used 24-hour urinary metabolic profiling by proton nuclear magnetic resonance spectroscopy to characterize the metabolic signatures associated with the DASH dietary pattern score (DASH score) and 24-hour excretion of sodium and potassium among participants in the United States (n = 2164) and United Kingdom (n = 496) enrolled in the International Study of Macro- and Micronutrients and Blood Pressure (INTERMAP). Multiple linear regression and cross-tabulation analyses were used to investigate the DASH-BP relation and its modulation by sodium and potassium. Potential pathways associated with DASH adherence, sodium and potassium excretion, and BP were identified using mediation analyses and metabolic reaction networks. RESULTS: Adherence to the DASH diet was associated with urinary potassium excretion (correlation coefficient, r = 0.42; P < 0.0001). In multivariable regression analyses, a 5-point higher DASH score (range, 7 to 35) was associated with a lower systolic BP by 1.35 mmHg (95% CI, -1.95 to -0.80 mmHg; P = 1.2 × 10-5); control of the model for potassium but not sodium attenuated the DASH-BP relation. Two common metabolites (hippurate and citrate) mediated the potassium-BP and DASH-BP relationships, while 5 metabolites (succinate, alanine, S-methyl cysteine sulfoxide, 4-hydroxyhippurate, and phenylacetylglutamine) were found to be specific to the DASH-BP relation. CONCLUSIONS: Greater adherence to the DASH diet is associated with lower BP and higher potassium intake across levels of sodium intake. The DASH diet recommends greater intake of fruits, vegetables, and other potassium-rich foods that may replace sodium-rich processed foods and thereby influence BP through overlapping metabolic pathways. Possible DASH-specific pathways are speculated but confirmation requires further study. INTERMAP is registered as NCT00005271 at www.clinicaltrials.gov.

Egg consumption, overall diet quality, and risk of type 2 diabetes and coronary heart disease: A pooling project of US prospective cohorts.

BACKGROUND AND AIMS: Data on the relation of egg consumption with risk of type 2 diabetes (T2D) and coronary heart disease (CHD) are limited and inconsistent. Few studies have controlled for overall dietary patterns in egg-T2D or egg-CHD analyses, and it is unclear whether any observed elevated risks of T2D and CHD with frequent egg consumption is real or due to confounding by dietary habits. We tested the hypothesis that frequent egg consumption is associated with a higher risk of T2D and CHD risk after adjustment for overall dietary patterns among adults. DESIGN: We used prospective cohort design to complete time-to-event analyses. METHODS: We pooled de novo, harmonized, individual-level analyses from nine US cohorts (n = 103,811). Cox regression was used to estimate hazard ratios separately in each cohort adjusting for age, ethnicity, body mass index (BMI), exercise, smoking, alcohol intake, and dietary patterns. We pooled cohort-specific results using an inverse-variance weighted method to estimate summary relative risks. RESULTS: Median age ranged from 25 to 72 years. Median egg consumption was 1 egg per week in most of the cohorts. While egg consumption up to one per week was not associated with T2D risk, consumption of ≥2 eggs per week was associated with elevated risk [27% elevated risk of T2D comparing 7+ eggs/week with none (95% CI: 16%-37%)]. There was little evidence for heterogeneity across cohorts and we observed similar conclusions when stratified by BMI. Overall, egg consumption was not associated with the risk of CHD. However, in a sensitivity analysis, there was a 30% higher risk of CHD (95% CI: 3%-56%) restricted to older adults consuming 5-6 eggs/week. CONCLUSIONS: Our data showed an elevated risk of T2D with egg consumption of ≥2 eggs per week but not with <2 eggs/week. While there was no overall association of egg consumption with CHD risk, the elevated CHD observed with consumption of 5-6 eggs/week in older cohorts merits further investigation.

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.

Contrasting Associations of Prudent and Western Dietary Patterns with Risk of Developing Venous Thromboembolism.

BACKGROUND: Published studies are inconsistent about whether differences in diet are associated with risk of venous thromboembolism. We studied the association between dietary patterns and incident venous thromboembolism in a large US cohort. METHODS: The Atherosclerosis Risk in Communities study followed 14,818 middle-aged males and females for incident venous thromboembolism over an average of 22 years between 1987 and 2015. Trained interviewers assessed dietary intake at visits 1 and 3, using a food frequency questionnaire. We derived 2 dietary pattern scores using principal component analysis and ascertained and verified hospitalized venous thromboembolism. In separate proportional hazards regression analyses, we examined associations of quintiles of the prudent and the Western dietary pattern scores with risk of developing non-cancer-related and total venous thromboembolism, adjusting for demographic characteristics, lifestyle factors, body mass index, and diabetes. RESULTS: With 860 total incident venous thromboembolism events, the hazard ratios (95% confidence intervals) of incident non-cancer-related venous thromboembolism (n = 631) across quintiles of the prudent dietary pattern score were 1 (reference), 1.04 (0.81-1.32), 0.84 (0.65-1.08), 0.70 (0.53-0.91), and 0.88 (0.67-1.15), Ptrend = .04. Across quintiles of the Western dietary pattern score, hazard ratios of non-cancer-related venous thromboembolism were 1 (reference), 1.13 (0.87-1.45), 1.20 (0.92-1.56), 1.03 (0.77-1.39), and 1.58 (1.13-2.21), Ptrend = .04. Associations were similar for total venous thromboembolism. CONCLUSIONS: In this community-based cohort, a prudent dietary pattern was associated with a lower risk of future venous thromboembolism, whereas a Western dietary pattern was associated with a higher risk.

Erratum: Qin, W., et al. Light Cigarette Smoking Increases Risk of All-Cause and Cause-Specific Mortality: Findings from the NHIS Cohort Study. Int. J. Environ Res. Public Health. 2020, 17, E5122.

The authors wish to correct the following erratum in this paper [...].

Light Cigarette Smoking Increases Risk of All-Cause and Cause-Specific Mortality: Findings from the NHIS Cohort Study.

Very few studies have examined the association between light cigarette smoking (i.e., ≤5 cigarettes per day) and mortality. The aim of this study was to examine the association of light cigarette smoking with all-cause and cause-specific mortality among adults in the United States. Data were from 13 waves of the National Health Interview Survey (1997 to 2009) that were linked to the National Death Index records through December 31, 2011. A total of 329,035 participants aged ≥18 years in the United States were included. Deaths were from all cause, cancer, cardiovascular disease (CVD) and respiratory disease and were confirmed by death certification. During a median follow-up of 8.2 years, 34,862 participants died, of which 8415 were from cancer, 9031 from CVD, and 2040 from respiratory disease. Compared with never-smokers, participants who smoked 1-2 (hazard ratios (HR) = 1.94, 95%CI = 1.73-2.16) and 3-5 cigarettes (HR = 1.99, 1.83-2.17) per day were at higher risk of all-cause mortality after adjustment for demographic variables, lifestyle factors and physician-diagnosis of chronic disease. The associations were stronger for respiratory disease-specific mortality, followed by cancer-specific mortality and CVD-specific mortality. For example, the HRs (95% CIs) of smoking 1-2 cigarettes per day were 9.75 (6.15-15.46), 2.28 (1.84-2.84) and 1.93 (1.58-2.36), respectively, for these three cause-specific mortalities. This study indicates that light cigarette smoking increases risk of all-cause and cause-specific mortality in US adults.

Association of smoking with abdominal adipose deposition and muscle composition in Coronary Artery Risk Development in Young Adults (CARDIA) participants at mid-life: A population-based cohort study.

BACKGROUND: Smokers have lower risk of obesity, which some consider a "beneficial" side effect of smoking. However, some studies suggest that smoking is simultaneously associated with higher central adiposity and, more specifically, ectopic adipose deposition. Little is known about the association of smoking with intermuscular adipose tissue (IMAT), an ectopic adipose depot associated with cardiovascular disease (CVD) risk and a key determinant of muscle quality and function. We tested the hypothesis that smokers have higher abdominal IMAT and lower lean muscle quality than never smokers. METHODS AND FINDINGS: We measured abdominal muscle total, lean, and adipose volumes (in cubic centimeters) and attenuation (in Hounsfield units [HU]) along with subcutaneous (SAT) and visceral adipose tissue (VAT) volumes using computed tomography (CT) in 3,020 middle-aged Coronary Artery Risk Development in Young Adults (CARDIA) participants (age 42-58, 56.3% women, 52.6% white race) at the year 25 (Y25) visit. The longitudinal CARDIA study was initiated in 1985 with the recruitment of young adult participants (aged 18-30 years) equally balanced by female and male sex and black and white race at 4 field centers located in Birmingham, AL, Chicago, IL, Minneapolis, MN, and Oakland, CA. Multivariable linear models included potential confounders such as physical activity and dietary habits along with traditional CVD risk factors. Current smokers had lower BMI than never smokers. Nevertheless, in the fully adjusted multivariable model with potential confounders, including BMI and CVD risk factors, adjusted mean (95% CI) IMAT volume was 2.66 (2.55-2.76) cm3 in current smokers (n = 524), 2.36 (2.29-2.43) cm3 in former smokers (n = 944), and 2.23 (2.18-2.29) cm3 in never smokers (n = 1,552) (p = 0.007 for comparison of former versus never smoker, and p < 0.001 for comparison of current smoker versus never and former smoker). Moreover, compared to participants who never smoked throughout life (41.6 [41.3-41.9] HU), current smokers (40.4 [39.9-40.9] HU) and former smokers (40.8 [40.5-41.2] HU) had lower lean muscle attenuation suggesting lower muscle quality in the fully adjusted model (p < 0.001 for comparison of never smokers with either of the other two strata). Among participants who had ever smoked, pack-years of smoking exposure were directly associated with IMAT volume (ß [95% CI]: 0.017 [0.010-0.025]) (p < 0.001). Despite having less SAT, current smokers also had higher VAT/SAT ratio than never smokers. These findings must be viewed with caution as residual confounding and/or reverse causation may contribute to these associations. CONCLUSIONS: We found that, compared to those who never smoked, current and former smokers had abdominal muscle composition that was higher in adipose tissue volume, a finding consistent with higher CVD risk and age-related physical deconditioning. These findings challenge the belief that smoking-associated weight loss or maintenance confers a health benefit.

Adherence to a Mediterranean-style eating pattern and risk of diabetes in a U.S. prospective cohort study.

BACKGROUND: A Mediterranean-style eating pattern is consistently associated with a decreased diabetes risk in Mediterranean and European populations. However, results in U.S. populations are inconsistent. The objective of this study was to assess whether a Mediterranean-style eating pattern would be associated with diabetes risk in a large, nationally representative U.S. cohort of black and white men and women. METHODS: Participants from the Atherosclerosis Risk in Communities study prospective cohort without diabetes, cardiovascular disease, or cancer at baseline (visit 1, 1987-1989; n = 11,991) were included (mean age 54 years, 56% female, 75% white). Alternate Mediterranean Diet scores (aMed) were calculated using the mean dietary intake self-reported at visit 1 and visit 3 (1993-1995) or visit 1 only for participants censored before visit 3. Participants were followed from visit 1 through 31 December 2016 for incident diabetes. We used Cox regression models to characterize associations of aMed (quintiles as well as per 1-point higher) with incident diabetes adjusted for energy intake, age, sex, race and study center, and education (Model 1) for all participants then stratified by race and body mass index (BMI). Model 2 included potential mediating behavioral and clinical measures associated with diabetes. Results are presented as hazard ratios and 95% confidence intervals. RESULTS: Over a median follow-up of 22 years, there were 4024 incident cases of diabetes. Higher aMed scores were associated with lower diabetes risk [Model 1: 0.83 (0.73-0.94) for Q5 vs Q1 (p-trend < 0.001) and 0.96 (0.95-0.98) for 1-point higher]. Associations were stronger for black vs white participants (interaction p < 0.001) and weaker for obese vs normal BMI (interaction p < 0.01). Associations were attenuated but statistically significant in Model 2. CONCLUSIONS: An eating pattern high in fruits, vegetables, whole grains, legumes, nuts, and fish, and moderate in alcohol was associated with a lower risk of diabetes in a community-based U.S.

Estimation of Cardiovascular Risk from Self-Reported Knowledge of Risk Factors: Insights from the Minnesota Heart Survey.

BACKGROUND: Cost-effective primary prevention of cardiovascular disease (CVD) relies on accuracy of risk assessment. Current risk scores require clinical and laboratory measures, are expensive and are often difficult to apply in the population setting. OBJECTIVE: This study sought to estimate CVD risk from individuals' knowledge of their own CVD risk factors and compare it to the risk calculated from measured risk factors. METHODS: Using the ACC/AHA Pooled Cohort Risk Equations (PCE), we calculated 10-year CVD risk for 9856 primary prevention individuals aged 40-79 in the Minnesota Heart Survey (MHS). Using log-linear regression models, we estimated PCE risk from the individual's self-reported knowledge of four dichotomous risk factors: hypertension, hypercholesterolemia, diabetes, and smoking. Age was included in all models, and models were developed separately in women and men. Model performance was assessed internally using leave-one-out cross-validation. RESULTS: The median measured PCE CVD risk in women was 2.1% (IQR: 0.8-5.6%), and in men was 6.3% (3.1-13.0%). Using the newly developed equations, the median estimated risk was 2.2% (0.9-5.8%) in women, and 6.9% (3.2-13.1%) in men. Using a threshold of 7.5% to categorize low and high risk, the novel risk calculation gave an accuracy of 95% for women and 87% for men compared to the measured PCE risk. The negative predictive value was 97% for women and 91% in men. CONCLUSION: Self-reported knowledge of risk may be useful in the identification of individuals at low risk for CV events, however, should always be followed up with measurement of risk factors if symptoms or history suggest CVD.

Diet quality, change in diet quality and risk of incident CVD and diabetes.

OBJECTIVE: The objective of this study was to assess the prospective association between diet quality, as well as a 6-year change in diet quality, and risk of incident CVD and diabetes in a community-based population. DESIGN: We used Cox regression models to estimate the prospective association between diet quality, assessed using the Healthy Eating Index (HEI)-2015 and the Alternative HEI (AHEI)-2010 scores, as well as change in diet quality, and incident CVD and diabetes. SETTING: The ARIC Study recruited 15 792 black and white men and women (45-64 years) from four US communities. PARTICIPANTS: We included 10 808 study participants who reported usual dietary intake via FFQ at visit 1 (1987-1989) and who had not developed CVD, diabetes, or cancer at baseline. RESULTS: Overall, 3070 participants developed CVD (median follow-up of 26 years) and 3452 developed diabetes (median follow-up of 22 years) after visit 1. Higher diet score at the initial visit was associated with a significantly lower risk of CVD (HR per 10 % higher HEI-2015 diet quality score: 0·90 (95 % CI: 0·86, 0·95) and HR per 10 % higher AHEI-2010 diet quality score: 0·96 (95 % CI: 0·93, 0·99)). We did not observe a significant association between initial diet score and incident diabetes. There were no significant associations between change in diet score and CVD or diabetes risk in the overall study population. CONCLUSIONS: Higher diet quality assessed using HEI-2015 and AHEI-2010 was strongly associated with lower CVD risk but not diabetes risk within a middle-aged, community-based US population.

Alcohol Consumption and Incident Kidney Disease: Results From the Atherosclerosis Risk in Communities Study.

OBJECTIVE(S): Moderate alcohol consumption has been found to be associated with lower risk of coronary heart disease and myocardial infarction, which share similar risk factors and pathophysiology with chronic kidney disease (CKD). However, there is inconsistent evidence on the association between alcohol consumption and CKD. DESIGN AND METHODS: We conducted a prospective analysis of 12,692 participants aged 45-64 years from the Atherosclerosis Risk in Communities (ARIC) study. We categorized participants into 6 alcohol consumption categories: never drinkers, former drinkers, ≤1 drink per week, 2 to 7 drinks per week, 8 to 14 drinks per week, and ≥15 drinks per week based on food frequency questionnaire responses at visit 1 (1987-1989). Incident CKD was defined as estimated glomerular filtration rate <60 mL/minute/1.73 m2 accompanied by ≥25% estimated glomerular filtration rate decline, a kidney disease-related hospitalization or death or end-stage renal disease. RESULTS: During a median follow-up of 24 years, there were 3,664 cases of incident CKD. Current drinkers were more likely to be men, whites, and to have a higher income level and education level. After adjusting for total energy intake, age, sex, race-center, income, education level, health insurance, smoking, and physical activity, there was no significant association between being a former drinker and risk of incident CKD. Participants who drank ≤1 drink per week, 2 to 7 drinks per week, 8 to 14 drinks per week, and ≥15 drinks per week had, respectively, a 12% (hazard ratio [HR]: 0.88, 95% confidence interval [CI]: 0.79-0.97), 20% (HR: 0.80, 95% CI: 0.72-0.89), 29% (HR: 0.71, 95% CI: 0.62-0.83), and 23% (HR: 0.77, 95% CI: 0.65-0.91) lower risk of CKD compared with never drinkers. CONCLUSION(S): Consuming a low or moderate amount of alcohol may lower the risk of developing CKD. Therefore, moderate consumption of alcohol may not likely be harmful to the kidneys.

Beneficial associations of low and large doses of leisure time physical activity with all-cause, cardiovascular disease and cancer mortality: a national cohort study of 88,140 US adults.

BACKGROUND: Evidence on the role of very low or very high volumes of leisure time physical activity (PA) on the risk of all-cause and cause-specific mortality is limited. We aimed to examine the associations of different levels of leisure time PA with the risk of all-cause, cardiovascular disease (CVD) and cancer-specific mortality. METHODS: Data were from 12 waves of the National Health Interview Surveys (1997-2008) linked to the National Death Index records through 31 December 2011. A total of 88 140 eligible participants aged 40-85 years were included. RESULTS: Compared with inactive individuals, those performing 10-59 min/week of PA had 18% lower risk of all-cause mortality (hazard ratio (HR): 0.82, 95% confidence interval (CI): 0.72-0.95). Those who reported 1-2 times (150-299 min/week) the recommended level of leisure time PA had 31% (HR: 0.69, 95%CI: 0.63-0.75) reduced risk of all-cause mortality. Importantly, the continued benefits were observed among those performing leisure time PA 10 or more times (≥1500 min/week) the recommended minimum level (HR: 0.54, 95% CI: 0.45-0.64). For 10-59, 150-299 and ≥1500 min/week of PA, the corresponding HRs (95% CIs) for CVD-specific mortality were 0.88 (0.67-1.17), 0.63 (0.52-0.78) and 0.67 (0.45-0.99), respectively: for cancer-specific mortality were 0.86 (0.66-1.11), 0.76 (0.64-0.89) and 0.53 (0.39-0.73), respectively. In addition, there was a larger reduction in all-cause and cause-specific mortality for vigorous vs. moderate intensity PA. CONCLUSIONS: We found that beneficial association between leisure time PA and mortality starts from a low dose. Doing more vigorous exercise could lead to additional health benefits.

Association of abdominal muscle composition with prediabetes and diabetes: The CARDIA study.

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

Omega-3 Fatty Acids and Genome-Wide Interaction Analyses Reveal DPP10-Pulmonary Function Association.

RATIONALE: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health. OBJECTIVE: To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility. METHODS: Associations of n-3 PUFA biomarkers (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV1, FVC, and FEV1/FVC) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N = 16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N = 11,962) and replicated in one cohort (N = 1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of SNP associations and their interactions with n-3 PUFAs. RESULTS: DPA and DHA were positively associated with FEV1 and FVC (P < 0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P2df = 9.4 × 10-9 across discovery and replication cohorts). The rs11693320-A allele (frequency, ∼80%) was associated with lower FVC (PSNP = 2.1 × 10-9; ßSNP = -161.0 ml), and the association was attenuated by higher DHA levels (PSNP×DHA interaction = 2.1 × 10-7; ßSNP×DHA interaction = 36.2 ml). CONCLUSIONS: We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction.