Identification of type 2 diabetes loci in 433,540 East Asian individuals.

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes-NKX6-3 and ANK1-in different tissues4-6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.

Associations of Urban Blue and Green Spaces With Coronary Artery Calcification in Black Individuals and Disadvantaged Neighborhoods.

BACKGROUND: Proximity to urban blue and green spaces has been associated with improved cardiovascular health; however, few studies have examined the role of race and socioeconomic status in these associations. METHODS: Data were from the CARDIA study (Coronary Artery Risk Development in Young Adults). We included longitudinal measurements (1985-1986 to 2010-2011) of blue and green spaces, including percentage of blue space cover, distance to the nearest river, green space cover, and distance to the nearest major park. Presence of coronary artery calcification (CAC) was measured with noncontrast cardiac computed tomography in 2010 to 2011. The associations of blue and green spaces with CAC were assessed with generalized estimating equation regression with adjustment for demographics, individual and neighborhood socioeconomic status, health-related behaviors, and other health conditions. We conducted stratified analyses by race and neighborhood deprivation score to investigate whether the association varied according to social determinants of health. RESULTS: The analytic sample included 1365 Black and 1555 White participants with a mean±SD age of 50.1±3.6 years. Among Black participants, shorter distance to a river and greater green space cover were associated with lower odds of CAC (per interquartile range decrease [1.45 km] to the river: odds ratio [OR], 0.90 [95% CI, 0.84-0.96]; per 10%-point increase of green space cover: OR, 0.85 [95% CI, 0.75-0.95]). Among participants in deprived neighborhoods, greater green space cover was associated with lower odds of CAC (per a 10%-point increase: OR, 0.89 [95% CI, 0.80-0.99]), whereas shorter distance to the park was associated with higher odds of CAC (per an interquartile range decrease [5.3 km]: OR, 1.07 [95% CI, 1.00-1.15]). Black participants in deprived neighborhoods had lower odds of CAC with shorter distance to a river (per an interquartile range decrease: OR, 0.90 [95% CI, 0.82-0.98]) and greater green space cover (per a 10%-point increase: OR, 0.85 [95% CI, 0.75-0.97]). There was no statistical interaction between the blue and green spaces and race or neighborhood characteristics in association with CAC. CONCLUSIONS: Longitudinally, shorter distance to a river and greater green space cover were associated with less CAC among Black participants and those in deprived neighborhoods. Shorter distance to a park was associated with increased odds of CAC among participants in deprived neighborhoods. Black participants residing in more deprived neighborhoods showed lower odds of CAC in association with greater exposure to river and green space cover.

Association Between Mid-arm Muscle Circumference and Cognitive Function: A Longitudinal Study of Chinese Adults.

BACKGROUND: Dementia affects 55 million people worldwide and low muscle mass may be associated with cognitive decline. Mid-arm muscle circumference (MAMC) correlates with dual-energy Xray absorptiometry and bioelectrical impedance analyses, yet are not routinely available. Therefore, we examined the association between MAMC and cognitive performance in older adults. METHODS: We included community-dwelling adults ≥55 years from the China Health and Nutrition Survey. Cognitive function was estimated based on a subset of the modified Telephone Interview for Cognitive Status (0-27, low-high) during years (1991, 1993, 1997, 2000, 2004, 2006, 2009, 2011, 2015, 2018). A multivariable linear mixed-effects model was used to test whether MAMC was associated with rate of cognitive decline across age groups and cognitive function overall. RESULTS: Of 3702 adults (53% female, 63.2 ± 7.3 years), mean MAMC was 21.4 cm ± 3.0 and baseline cognitive score was 13.6 points ±6.6. We found no evidence that the age-related rate of cognitive decline differed by MAMC (P = .77). Declines between 5-year age groups ranged from -.80 [SE (standard error) .18] to -1.09 [.22] for those at a mean MAMC, as compared to -.86 [.25] to -1.24 [.31] for those at a 1 MAMC 1 standard deviation above the mean. Higher MAMC was associated with better cognitive function with .13 [.06] higher scores for each corresponding 1 standard deviation increase in MAMC across all ages. CONCLUSION: Higher MAMC at any age was associated with better cognitive performance in older adults. Understanding the relationship between muscle mass and cognition may identify at-risk subgroups needing targeted interventions to preserve cognition.

Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association.

The global obesity epidemic is well established, with increases in obesity prevalence for most countries since the 1980s. Obesity contributes directly to incident cardiovascular risk factors, including dyslipidemia, type 2 diabetes, hypertension, and sleep disorders. Obesity also leads to the development of cardiovascular disease and cardiovascular disease mortality independently of other cardiovascular risk factors. More recent data highlight abdominal obesity, as determined by waist circumference, as a cardiovascular disease risk marker that is independent of body mass index. There have also been significant advances in imaging modalities for characterizing body composition, including visceral adiposity. Studies that quantify fat depots, including ectopic fat, support excess visceral adiposity as an independent indicator of poor cardiovascular outcomes. Lifestyle modification and subsequent weight loss improve both metabolic syndrome and associated systemic inflammation and endothelial dysfunction. However, clinical trials of medical weight loss have not demonstrated a reduction in coronary artery disease rates. In contrast, prospective studies comparing patients undergoing bariatric surgery with nonsurgical patients with obesity have shown reduced coronary artery disease risk with surgery. In this statement, we summarize the impact of obesity on the diagnosis, clinical management, and outcomes of atherosclerotic cardiovascular disease, heart failure, and arrhythmias, especially sudden cardiac death and atrial fibrillation. In particular, we examine the influence of obesity on noninvasive and invasive diagnostic procedures for coronary artery disease. Moreover, we review the impact of obesity on cardiac function and outcomes related to heart failure with reduced and preserved ejection fraction. Finally, we describe the effects of lifestyle and surgical weight loss interventions on outcomes related to coronary artery disease, heart failure, and atrial fibrillation.

A doubly robust method to handle missing multilevel outcome data with application to the China Health and Nutrition Survey.

Missing data are common in longitudinal cohort studies and can lead to bias, particularly in studies with informative missingness. Many common methods for handling informatively missing data in survey samples require correctly specifying a model for missingness. Although doubly robust methods exist to provide unbiased regression coefficients in the presence of missing outcome data, these methods do not account for correlation due to clustering inherent in longitudinal or cluster-sampled studies. In this work, we developed a doubly robust method to estimate the regression of an outcome on a predictor in the presence of missing multilevel data on the outcome, which results in consistent estimation of regression coefficients assuming correct specification of either (1) the probability of missingness or (2) the outcome model. This method involves specification of separate hierarchical models for missingness and for the outcome, conditional on observed auxiliary variables and cluster-specific random effects, to account for correlation among observations. We showed this proposed estimator is doubly robust and derived its asymptotic distribution, conducted simulation studies to compare the method to an existing doubly robust method developed for independent data, and applied the method to data from the China Health and Nutrition Survey, an ongoing multilevel longitudinal cohort study.

Dynamic relationships between body fat and circulating adipokine levels from adolescence to young adulthood: The Santiago Longitudinal Study.

BACKGROUND AND AIMS: Adipose tissue secretes adipokines such as adiponectin and leptin, playing important roles in energy metabolism. The longitudinal associations between such adipokines and body fat accumulation have not been established, especially during adolescence and young adulthood and in diverse populations. The study aims to assess the longitudinal association between body fat measured with dual X-ray absorptiometry and plasma adipokines from adolescence to young adulthood. METHODS AND RESULTS: Among Hispanic/Latino participants (N = 537) aged 16.8 (SD: 0.3) years of the Santiago Longitudinal Study, we implemented structural equation modeling to estimate the sex-specific associations between adiposity (body fat percent (BF%) and proportion of trunk fat (PTF)) and adipokines (adiponectin and leptin levels) during adolescence (16 y) and these values after 6 years of follow-up (22 y). In addition, we further investigated whether the associations differed by baseline insulin resistance (IR) status. We found evidence for associations between 16 y BF% and 22 y leptin levels (ß (SE): 0.58 (0.06) for females; 0.53 (0.05) for males), between 16 y PTF and 22 y adiponectin levels (ß (SE): -0.31 (0.06) for females; -0.18 (0.06) for males) and between 16 y adiponectin levels and 22 y BF% (ß (SE): 0.12 (0.04) for both females and males). CONCLUSION: We observed dynamic relationships between adiposity and adipokines levels from late adolescence to young adulthood in a Hispanic/Latino population further demonstrating the importance of this period of the life course in the development of obesity.

Characterizing the urban diet: development of an urbanized diet index.

BACKGROUND: In recent decades China has experienced rapid urbanization leading to a major nutrition transition, with increased refined carbohydrates, added sweeteners, edible oils, and animal-source foods, and reduced legumes, vegetables, and fruits. These changes have accompanied increased prevalence of cardiometabolic disease (CMD). There is no single dietary measure that summarizes the distinct food changes across regions and levels of urbanization. METHODS: Using a sample of adults (≥18 years) in the 2015 wave of the China Health and Nutrition Survey (CHNS; n = 14,024), we selected literature-based candidate dietary variables and tested their univariate associations with overall and within-region urbanization. Using iterative exclusion of select diet-related variables, we created six potential urbanized diet indices, which we examined relative to overall urbanization to select a final urbanized diet index based on a priori considerations, strength of association with urbanization, and minimal missingness. We tested stability of the final urbanized diet index across sociodemographic factors. To examine whether our new measure reflected health risk, we used mixed effects logistic regression models to examine associations between the final urbanized diet index and CMD risk factors - hypertension (HTN), overweight, and type 2 diabetes mellitus (T2DM), adjusting for sociodemographics, overall urbanization, physical activity, and including random intercepts to account for correlation at community and household level. RESULTS: We identified a final urbanized diet index that captured dietary information unique to consumption of an urbanized diet and performed well across regions. We found a positive association (R2 = 0.17, 0.01 SE) between the final urbanized diet index and overall urbanization in the fully adjusted model. The new measure was negatively associated with HTN [OR (95% CI) = 0.93 (0.88-0.99)] and positively associated with T2D [OR = 1.13; 1.05-1.21] in minimally adjusted models, but not in the fully adjusted models. CONCLUSION: We derived an urbanized diet index that captured dietary urbanization that was distinct from overall urbanization and performed well across all regions of China. This urbanized diet index provides an alternative to measures of traditional versus urbanized diet that vary across regions due to different cultural dietary traditions. In addition, the new measure is best used in combination with diet quality measures, sociodemographic, and lifestyle measures to examine distinct pathways from urbanization to health in urbanizing countries.

A method for estimating neighborhood characterization in studies of the association with availability of sit-down restaurants and supermarkets.

BACKGROUND: Although neighborhood-level access to food differs by sociodemographic factors, a majority of research on neighborhoods and food access has used a single construct of neighborhood context, such as income or race. Therefore, the many interrelated built environment and sociodemographic characteristics of neighborhoods obscure relationships between neighborhood factors and food access. METHODS: The objective of this study was to account for the many interrelated characteristics of food-related neighborhood environments and examine the association between neighborhood type and relative availability of sit-down restaurants and supermarkets. Using cluster analyses with multiple measures of neighborhood characteristics (e.g., population density, mix of land use, and sociodemographic factors) we identified six neighborhood types in 1993 in the Twin Cities Region, Minnesota. We then used mixed effects regression models to estimate differences in the relative availability of sit-down restaurants and supermarkets in 1993, 2001, and 2011 across the six neighborhood types. RESULTS: We defined six types of neighborhoods that existed in 1993, namely, urban core, inner city, urban, aging suburb, high-income suburb, and suburban edge. Between 1993 and 2011, inner city neighborhoods experienced a greater increase in the percent of sit-down restaurants compared with urban core, urban, and aging suburbs. Differences in the percent of sit-down restaurants between inner city and aging suburbs, high-income suburbs and suburban edge neighborhoods increased between 1993 and 2011. Similarly, aging suburb neighborhoods had a greater percent of supermarkets compared with urban and high-income suburb neighborhoods in 2001 and 2011, but not in 1993, suggesting a more varied distribution of food stores across neighborhoods over time. Thus, the classification of neighborhood type based on sociodemographic and built environment characteristics resulted in a complex and increasingly varied distribution of restaurants and food stores. CONCLUSIONS: The temporal increase in the relative availability of sit-down restaurants in inner cities after accounting for all restaurants might be partly related to a higher proportion of residents who eat-away-from-home, which is associated with higher calorie and fat intake.

Demographic and sociocultural risk factors for adulthood weight gain in Hispanic/Latinos: results from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL).

BACKGROUND: United States (US) Hispanic/Latinos experience a disproportionate burden of obesity, which may in part be related to demographic or sociocultural factors, including acculturation to an US diet or inactive lifestyle. Therefore, we sought to describe the association between adulthood weight histories and demographic and sociocultural factors in a large diverse community-based cohort of US Hispanic/Latinos. METHODS: We estimated the effect of several factors on weight gain across adulthood, using multivariable linear mixed models to leverage 38,759 self-reported current body weights and weight histories recalled for 21, 45 and 65 years of age, from 15,203 adults at least 21 years of age at the baseline visit of the Hispanic Community Health Study/Study of Latinos (2008-2011). RESULTS: The average rate of weight gain was nearly 10 kg per decade in early adulthood, but slowed to < 5 kg a decade among individuals 60+ years of age. Birth cohort, gender, nativity or age at immigration, Hispanic/Latino background, and study site each significantly modified the form of the predicted adulthood weight trajectory. Among immigrants, weight gain during the 5 years post-migration was on average 0.88 kg (95% CI: 0.04, 1.72) greater than the weight gain during the 5 years prior. The rate of weight gain appeared to slow after 15 years post-migration. CONCLUSIONS: Using self-reported and weight history data in a diverse sample of US Hispanic/Latinos, we revealed that both demographic and sociocultural factors were associated with the patterning of adulthood weight gain in this sample. Given the steep rate of weight gain in this population and the fact that many Hispanic/Latinos living in the US immigrated as adults, efforts to promote weight maintenance across the life course, including after immigration, should be a top priority for promoting Hispanic/Latino health and addressing US health disparities more broadly.

Identification and functional analysis of glycemic trait loci in the China Health and Nutrition Survey.

To identify genetic contributions to type 2 diabetes (T2D) and related glycemic traits (fasting glucose, fasting insulin, and HbA1c), we conducted genome-wide association analyses (GWAS) in up to 7,178 Chinese subjects from nine provinces in the China Health and Nutrition Survey (CHNS). We examined patterns of population structure within CHNS and found that allele frequencies differed across provinces, consistent with genetic drift and population substructure. We further validated 32 previously described T2D- and glycemic trait-loci, including G6PC2 and SIX3-SIX2 associated with fasting glucose. At G6PC2, we replicated a known fasting glucose-associated variant (rs34177044) and identified a second signal (rs2232326), a low-frequency (4%), probably damaging missense variant (S324P). A variant within the lead fasting glucose-associated signal at SIX3-SIX2 co-localized with pancreatic islet expression quantitative trait loci (eQTL) for SIX3, SIX2, and three noncoding transcripts. To identify variants functionally responsible for the fasting glucose association at SIX3-SIX2, we tested five candidate variants for allelic differences in regulatory function. The rs12712928-C allele, associated with higher fasting glucose and lower transcript expression level, showed lower transcriptional activity in reporter assays and increased binding to GABP compared to the rs12712928-G, suggesting that rs12712928-C contributes to elevated fasting glucose levels by disrupting an islet enhancer, resulting in reduced gene expression. Taken together, these analyses identified multiple loci associated with glycemic traits across China, and suggest a regulatory mechanism at the SIX3-SIX2 fasting glucose GWAS locus.

Urbanization in China is associated with pronounced perturbation of plasma metabolites.

INTRODUCTION: Urbanization is associated with major changes in environmental and lifestyle exposures that may influence metabolic signatures. OBJECTIVES: We investigated cross-sectional urban and rural differences in plasma metabolome analyzed by liquid chromatography/mass spectrometry platform in 500 Chinese adults aged 25-68 years from two neighboring southern Chinese provinces. METHODS: We first examined the overall metabolome differences by urban and rural residential location, using Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) and random forest classification. We then tested the association between urbanization status and individual metabolites using a linear regression adjusting for age, sex, and province and conducted pathway analysis (Fisher's exact test) to identify metabolic pathways differed by urbanization status. RESULTS: We observed distinct overall metabolome by urbanization status in OPLS-DA and random forest classification. Using linear regression, out of a total of 1108 unique metabolite features identified in this sample, we found that 266 metabolites were differed by urbanization status (positive false discovery rate-adjusted p-value, q-value < 0.05). For example, the following metabolites were positively associated with urbanization status: caffeine metabolites from xanthine metabolism, hazardous pollutants like 4-hydroxychlorothalonil and perfluorooctanesulfonate, and metabolites implicated in cardiometabolic diseases, such as branched-chain amino acids. In pathway analysis, we found that xanthine metabolism pathways differed by urbanization status (q-value = 1.64E-04). CONCLUSION: We detected profound differences in host metabolites by urbanization status. Urban residents were characterized by metabolites signaling caffeine metabolism and toxic pollutants and metabolites on known pathways to cardiometabolic disease risks, compared to their rural counterparts. Our findings highlight the importance of considering urbanization in metabolomics analysis.

Education, Race/Ethnicity, and Causes of Premature Mortality Among Middle-Aged Adults in 4 US Urban Communities: Results From CARDIA, 1985-2017.

Objectives. To assess causes of premature death and whether race/ethnicity or education is more strongly and independently associated with premature mortality in a diverse sample of middle-aged adults in the United States.Methods. The Coronary Artery Risk Development in Young Adults study (CARDIA) is a longitudinal cohort study of 5114 participants recruited in 1985 to 1986 and followed for up to 29 years, with rigorous ascertainment of all deaths; recruitment was balanced regarding sex, Black and White race/ethnicity, education level (high school or less vs. greater than high school), and age group (18-24 and 25-30 years). This analysis included all 349 deaths that had been fully reviewed through month 348. Our primary outcome was years of potential life lost (YPLL).Results. The age-adjusted mortality rate per 1000 persons was 45.17 among Black men, 25.20 among White men, 17.63 among Black women, and 10.10 among White women. Homicide and AIDS were associated with the most YPLL, but cancer and cardiovascular disease were the most common causes of death. In multivariable models, each level of education achieved was associated with 1.37 fewer YPLL (P = .007); race/ethnicity was not independently associated with YPLL.Conclusions. Lower education level was an independent predictor of greater YPLL.

GIS-Based Home Neighborhood Food Outlet Counts, Street Connectivity, and Frequency of Use of Neighborhood Restaurants and Food Stores.

Researchers have linked neighborhood food availability to the overall frequency of using food outlets without noting if those outlets were within or outside of participants' neighborhoods. We aimed to examine the association of neighborhood restaurant and food store availability with frequency of use of neighborhood food outlets, and whether such an association was modified by neighborhood street connectivity using a large and diverse population-based cohort of middle-aged U.S. adults. We used self-reported frequency of use of fast food restaurants, sit-down restaurants, and grocery stores in respondents' home neighborhoods using data from the Coronary Artery Risk Development in Young Adults study Year 20 exam in 2005-2006 (n = 2860; Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA) and geographically matched GIS-measured neighborhood-level food resource, street, and U.S. Census data. We used mixed-effects logistic regression to examine the associations of the GIS-measured count of neighborhood fast food restaurants, sit-down restaurants, and grocery stores with self-reported frequency of using neighborhood restaurants and food stores and whether such associations differed by GIS-measured neighborhood street connectivity among those who perceived at least one such food outlet. In multivariate analyses, we observed a positive association between the GIS-measured count of neighborhood sit-down restaurants (OR = 1.02, 95% CI 1.00-1.04) and the self-reported frequency of using neighborhood sit-down restaurants. We observed no statistically significant association between GIS-measured count of neighborhood fast food restaurants and self-reported frequency of using neighborhood fast food restaurants, nor did we observe a statistically significant association between GIS-measured count of neighborhood grocery stores and self-reported frequency of using neighborhood grocery stores. We observed inverse associations between GIS-measured neighborhood street connectivity and the self-reported frequencies of using neighborhood fast food restaurants (OR = 0.42, 95% CI 0.26-0.68) and grocery stores (OR = - 2.26, 95% CI - 4.52 to - 0.01). Neighborhood street connectivity did not modify the association between GIS-measured neighborhood restaurant and food store count and the self-reported frequency of using neighborhood restaurants and food stores. Our findings suggest that, for those who perceived at least one sit-down restaurant in their neighborhood, individuals who have more GIS-measured sit-down restaurants in their neighborhoods reported more frequent use of sit-down restaurants than those whose neighborhoods contain fewer such restaurants. Our results also suggest that, for those who perceived at least one fast food restaurant in their neighborhood, individuals who live in neighborhoods with greater GIS-measured street connectivity reported less use of neighborhood fast food restaurants than those who live in neighborhoods with less street connectivity. The count of neighborhood sit-down restaurants and the connectivity of neighborhood street networks appear important in understanding the use of neighborhood food resources.

Cross-sectional association between diet quality and cardiometabolic risk by education level in Mexican adults.

OBJECTIVE: Understanding the association between diet quality and cardiometabolic risk by education level is important for preventing increased cardiometabolic risk in the Mexican population, especially considering pre-existing disparities in diet quality. The present study examined the cross-sectional association of overall diet quality with cardiometabolic risk, overall and by education level, among Mexican men and women. DESIGN: Cardiometabolic risk was defined by using biomarkers and diet quality by the Mexican Diet Quality Index. We computed sex-specific multivariable logistic regression models. SETTING: Mexico. PARTICIPANTS: Mexican men (n 634) and women (n 875) participating in the Mexican National Health and Nutrition Survey 2012. RESULTS: We did not find associations of diet quality with cardiometabolic risk factors in the total sample or in men by education level. However, we observed that for each 10-unit increase in the dietary quality score, the odds of diabetes risk in women with no reading/writing skills was 0·47 (95 % CI 0·26, 0·85) relative to the odds in women with ≥10 years of school (referent). Similarly, for each 10-unit increase of the dietary quality score, the odds of having three v. no lipid biomarker level beyond the risk threshold in lower-educated women was 0·27 (95 % CI 0·12, 0·63) relative to the odds in higher-educated women. CONCLUSIONS: Diet quality has a stronger protective association with some cardiometabolic disease risk factors for lower- than higher-educated Mexican women, but no association with cardiometabolic disease risk factors among men. Future research will be needed to understand what diet factors could be influencing the cardiometabolic disease risk disparities in this population.

Racial Differences in the Associations Between Food Insecurity and Fibroblast Growth Factor 23 in the Coronary Artery Risk Development in Young Adults Study.

OBJECTIVE: Food insecurity is associated with consumption of phosphate additive-laden processed food and beverage products, which could result in higher levels of fibroblast growth factor 23 (FGF23) to compensate for the increased dietary phosphate load. We sought to determine whether food insecurity is associated with higher levels of FGF23. We stratified analyses by race since differences may occur between food insecurity and diet quality across races. DESIGN AND METHODS: The longitudinal community-based Coronary Artery Risk Development in Young Adults Study recruited from 4 US centers: Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA, during the cohort inception in 1985/1986. This analysis included 3,421 black and white participants from Coronary Artery Risk Development in Young Adults follow-up years 20, 25, and 30 who were enrolled in the study between the ages of 18 and 30 years. Econometric fixed effects models stratified by race that adjust by design for all time-invariant covariates were used to model the longitudinal association of food insecurity, defined as the self-reported ability to afford desired quantity and quality of food. The main outcome of interest was changing to the highest quartile of plasma FGF-23 concentrations. RESULTS: During follow-up, 29% of blacks and 14% of whites experienced change in food security. Developing food insecurity was associated with a 1.48 greater odds of increasing to the highest quartile of FGF23 (95% confidence interval 1.02-2.15) among blacks; however, there was no significant longitudinal association among whites (odds ratio = 1.14, 95% confidence interval 0.67-1.95). CONCLUSIONS: Among blacks, food insecurity was associated with an increase in levels of FGF23. Although phosphate consumption was presumed to mediate the association between food insecurity and FGF23 levels, we were unable to directly test this pathway.

Longitudinal Associations of Smoke-Free Policies and Incident Cardiovascular Disease: CARDIA Study.

BACKGROUND: Smoke-free legislation has been associated with lower rates of cardiovascular disease hospital admissions in ecological studies. However, prior studies lacked detailed information on individual-level factors (eg, sociodemographic and clinical characteristics) that could potentially confound associations. Our objective was to estimate associations of smoke-free policies with incident cardiovascular disease in a longitudinal cohort after controlling for sociodemographics, cardiovascular disease risk factors, and policy covariates. METHODS: Longitudinal data from 3783 black and white adults in the CARDIA study (Coronary Artery Risk Development in Young Adults; 1995-2015) were linked to state, county, and local 100% smoke-free policies in bars, restaurants, and nonhospitality workplaces by Census tract. Extended Cox regression estimated hazard ratios (HRs) of incident cardiovascular disease associated with time-dependent smoke-free policy exposures. Models were adjusted for sociodemographic characteristics, cardiovascular disease risk factors, state cigarette tax, participant-reported presence of a smoking ban at their workplace, field center, and metropolitan statistical area poverty. RESULTS: During a median follow-up of 20 years (68 332 total person-years), 172 participants had an incident cardiovascular disease event (2.5 per 1000 person-years). Over the follow-up period, 80% of participants lived in areas with smoke-free policies in restaurants, 67% in bars, and 65% in nonhospitality workplaces. In fully adjusted models, participants living in an area with a restaurant, bar, or workplace smoke-free policy had a lower risk of incident cardiovascular disease compared with those in areas without smoke-free policies (HR, 0.75, 95% confidence interval, 0.49-1.15; HR, 0.76, 95% confidence interval, 0.47-1.24; HR, 0.54, 95% confidence interval, 0.34-0.86, respectively; HR, 0.58, 95% confidence interval, 0.33-1.00 for living in an area with all 3 types of policies compared with none). The estimated preventive fraction was 25% for restaurant policies, 24% for bar policies, and 46% for workplace policies. CONCLUSIONS: Consistent with prior ecological studies, these individual-based data add to the evidence that 100% smoke-free policies are associated with lower risk of cardiovascular disease among middle-aged adults.

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets.

Perceived and objective characteristics of the neighborhood environment are associated with accelerometer-measured sedentary time and physical activity, the CARDIA Study.

We investigated cross-sectional and longitudinal associations of neighborhood environment characteristics with accelerometer-measured sedentary time (SED), light-intensity physical activity (LPA), and moderate-to-vigorous intensity physical activity (MVPA). Participants were 2120 men and women in the year 20 (2005-2006) and year 30 CARDIA exams (2015-2016). Year 20 neighborhood characteristics included neighborhood cohesion, resources for physical activity, poverty, and racial residential segregation. Physical activity was measured by accelerometer at years 20 and 30. Multivariable linear regression models examined associations of standardized neighborhood measures at year 20 with SED, LPA, and MVPA assessed that year, and with 10-year changes in SED, LPA, and MVPA. Cross-sectionally, a one standard deviation (SD) increase in cohesion was associated with 4.06 less SED min/day (95% CI: -7.98, -0.15), and 4.46 more LPA min/day (95% CI: 0.88, 8.03). Each one SD increase in resources was associated with 1.19 more MVPA min/day (95% CI: 0.06, 2.31). A one SD increase in poverty was associated with 11.18 less SED min/day (95% CI: -21.16, -1.18) and 10.60 more LPA min/day (95% CI: 1.79, 19.41) among black men. No neighborhood characteristic was associated with 10-year changes in physical activity in the full sample; however, a one SD increase in cohesion was associated with a 10-year decrease of 25.44 SED min/day (95% CI: -46.73, -4.14) and an increase of 19.0 LPA min/day (95% CI, 1.89, 36.10) in black men. Characteristics of the neighborhood environment are associated with accelerometer-measured physical activity. Differences were observed by race and sex, with more robust findings observed in black men.

Longitudinal Associations of Cigarette Prices With Smoking Cessation: The Coronary Artery Risk Development in Young Adults Study.

INTRODUCTION: Few studies have used longitudinal cohort data to examine associations of cigarette prices with smoking cessation or whether price sensitivity varies by income or education. This study examines these associations in a multicenter US cohort and explores whether associations vary by education and income. METHODS: Longitudinal data from baseline daily cigarette smokers aged 18-30 years in the Coronary Artery Risk Development in Young Adults study were linked to inflation-adjusted cigarette carton prices from the Council for Community and Economic Research Cost of Living Index based on residential address at baseline and in years 7, 10, and 15 (1985-2001). Multivariable Cox models estimated hazard ratios (HRs) of first (any) smoking cessation and sustained smoking cessation (no relapse) associated with each $1 increase in time-dependent cigarette price over 15 years of follow-up. Models were adjusted for sociodemographic, health-related, and policy covariates. We assessed effect modification by education and household income. RESULTS: Among 1489 participants, a $1.00 higher cigarette carton price was associated with a 16% higher likelihood of first smoking cessation (HR = 1.16, 95% CI = 1.11 to 1.21) and an 8% higher likelihood of sustained smoking cessation (HR = 1.08, 95% CI = 1.02 to 1.14). Associations were strongest among participants with lower income for first cessation, and among those with higher income for sustained cessation. Associations were strongest for participants with less than a high school degree for both outcomes. CONCLUSIONS: Results suggest higher cigarette prices promote smoking cessation among young to middle-aged adults, and that price sensitivity may differ by socioeconomic status. IMPLICATIONS: Few studies have examined longitudinal associations of cigarette prices with smoking cessation, and findings are mixed on whether price sensitivity varies by education or income. In a cohort of US adult daily smokers, cigarette prices were associated with greater likelihood of both a first cessation and sustained cessation. Price associations with first cessation were stronger among low-income smokers, but associations with sustained cessation were stronger among high-income smokers. Results suggest that although higher cigarette prices may promote short-term smoking cessation among smokers at all income levels, additional supports may be needed to facilitate sustained smoking cessation among low-income smokers.

Associations of Bar and Restaurant Smoking Bans With Smoking Behavior in the CARDIA Study: A 25-Year Study.

Indoor smoking bans have often been associated with reductions in smoking prevalence. However, few studies have evaluated their association with within-person changes in smoking behaviors. We linked longitudinal data from 5,105 adults aged 18-30 years at baseline from the Coronary Artery Risk Development in Young Adults (CARDIA) Study (1985-2011) to state, county, and local policies mandating 100% smoke-free bars and restaurants by census tract. We used fixed-effects models to examine the association of smoking bans with within-person change in current smoking risk, smoking intensity (smoking ≥10 cigarettes/day on average vs. <10 cigarettes/day), and quitting attempts, using both linear and nonlinear adjustment for secular trends. In models assuming a linear secular trend, smoking bans were associated with a decline in current smoking risk and smoking intensity and an increased likelihood of a quitting attempt. The association with current smoking was greatest among participants with a bachelor's degree or higher. In models with a nonlinear secular trend, pooled results were attenuated (confidence intervals included the null), but effect modification results were largely unchanged. Findings suggest that smoking ban associations may be difficult to disentangle from other tobacco control interventions and emphasize the importance of evaluating equity throughout policy implementation.