KLB is associated with alcohol drinking, and its gene product ß-Klotho is necessary for FGF21 regulation of alcohol preference.

Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified ß-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10-12). ß-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific ß-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.

Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.

Gain-of-function lipoprotein lipase variant rs13702 modulates lipid traits through disruption of a microRNA-410 seed site.

Genome-wide association studies (GWAS) have identified hundreds of genetic variants that are associated with lipid phenotypes. However, data supporting a functional role for these variants in the context of lipid metabolism are scarce. We investigated the association of the lipoprotein lipase (LPL) variant rs13702 with plasma lipids and explored its potential for functionality. The rs13702 minor allele had been predicted to disrupt a microRNA (miR) recognition element (MRE) seed site (MRESS) for the human microRNA-410 (miR-410). Furthermore, rs13702 is in linkage disequilibrium (LD) with several SNPs identified by GWAS. We performed a meta-analysis across ten cohorts of participants that showed a statistically significant association of rs13702 with triacylglycerols (TAG) (p = 3.18 × 10(-42)) and high-density lipoprotein cholesterol (HDL-C) (p = 1.35 × 10(-32)) with each copy of the minor allele associated with 0.060 mmol/l lower TAG and 0.041 mmol/l higher HDL-C. Our data showed that an LPL 3' UTR luciferase reporter carrying the rs13702 major T allele was reduced by 40% in response to a miR-410 mimic. We also evaluated the interaction between intake of dietary fatty acids and rs13702. Meta-analysis demonstrated a significant interaction between rs13702 and dietary polyunsaturated fatty acid (PUFA) with respect to TAG concentrations (p = 0.00153), with the magnitude of the inverse association between dietary PUFA intake and TAG concentration showing -0.007 mmol/l greater reduction. Our results suggest that rs13702 induces the allele-specific regulation of LPL by miR-410 in humans. This work provides biological and potential clinical relevance for previously reported GWAS variants associated with plasma lipid phenotypes.

Sex and race/ethnic disparities in the cross-sectional association between depressive symptoms and muscle mass: the Multi-ethnic Study of Atherosclerosis.

BACKGROUND: The cross-sectional area of total muscle mass has been reported to decrease by about 40% for those 20-60 years of age. Depressive symptoms may discourage motivation to engage in physical activity such as strength training shown to negate muscle loss. Inflammation related to depressive symptoms may also contribute to muscle atrophy. Physiological differences by sex and race/ethnicity may also modify the association between depression and muscle mass. Evidence on the relationship between depression (or depressive symptoms) and adiposity has been mounting; however, little is known about the depressive symptoms-muscle mass association. We sought to determine the association between elevated depressive symptoms (EDS) and lean muscle mass and whether this varies by sex and race/ethnicity. METHODS: Evaluating 1605 adults (45-84 years of age) from the Multi-ethnic Study of Atherosclerosis Abdominal Body Composition, Inflammation and Cardiovascular Disease Study, we examined the cross-sectional association between EDS (Center for Epidemiologic Studies for Depression Scale score≥16 and/or antidepressant use) and computed tomography-measured abdominal lean muscle mass using linear regression. Muscles were evaluated as a whole and by functionality (locomotion vs. stabilization/posture). Covariates included height, body mass index, sociodemographics, comorbidities, inflammatory markers and health behaviors (pack-years of smoking, alcohol locomotion compared to men, total intentional exercise, daily caloric intake). Sex and race/ethnicity were assessed as potential modifiers. Statistical significance was at a p<0.05 for main effects and <0.20 for interaction. RESULTS: Men with elevated depressive symptoms had 5.9 cm2 lower lean muscle mass for locomotion compared to men without EDS, fully-adjusted (CI=-10.5, -1.4, p=0.011). This was statistically significantly different from the null finding among women (interaction p=0.05). Chinese participants with EDS had 10.2 cm2 lower abdominal lean muscle mass for locomotion compared to those without EDS (fully-adjusted, CI=-18.3, -2.1, p=0.014), which was significantly different from the null relationship among White participants (interaction p=0.04). No association was observed between elevated depressive symptoms and muscle for stabilization/posture evaluating the whole population or stratified by sex or race/ethnicity. CONCLUSIONS: In the presence of elevated depressive symptoms, men and Chinese participants may have lower muscle mass, particularly for locomotion.

Genome-wide association study of a heart failure related metabolomic profile among African Americans in the Atherosclerosis Risk in Communities (ARIC) study.

Both the prevalence and incidence of heart failure (HF) are increasing, especially among African Americans, but no large-scale, genome-wide association study (GWAS) of HF-related metabolites has been reported. We sought to identify novel genetic variants that are associated with metabolites previously reported to relate to HF incidence. GWASs of three metabolites identified previously as risk factors for incident HF (pyroglutamine, dihydroxy docosatrienoic acid, and X-11787, being either hydroxy-leucine or hydroxy-isoleucine) were performed in 1,260 African Americans free of HF at the baseline examination of the Atherosclerosis Risk in Communities (ARIC) study. A significant association on chromosome 5q33 (rs10463316, MAF = 0.358, P-value = 1.92 × 10(-10) ) was identified for pyroglutamine. One region on chromosome 2p13 contained a nonsynonymous substitution in N-acetyltransferase 8 (NAT8) was associated with X-11787 (rs13538, MAF = 0.481, P-value = 1.71 × 10(-23) ). The smallest P-value for dihydroxy docosatrienoic acid was rs4006531 on chromosome 8q24 (MAF = 0.400, P-value = 6.98 × 10(-7) ). None of the above SNPs were individually associated with incident HF, but a genetic risk score (GRS) created by summing the most significant risk alleles from each metabolite detected 11% greater risk of HF per allele. In summary, we identified three loci associated with previously reported HF-related metabolites. Further use of metabolomics technology will facilitate replication of these findings in independent samples.

Ideal cardiovascular health is inversely associated with incident cancer: the Atherosclerosis Risk In Communities study.

BACKGROUND: The American Heart Association (AHA) has defined the concept of ideal cardiovascular health in promotion of the 2020 Strategic Impact Goals. We examined whether adherence to ideal levels of the 7 AHA cardiovascular health metrics was associated with incident cancers in the Atherosclerosis Risk In Communities (ARIC) study over 17 to 19 years of follow-up. METHODS AND RESULTS: After exclusions for missing data and prevalent cancer, 13 253 ARIC participants were included for analysis. Baseline measurements were used to classify participants according to 7 AHA cardiovascular health metrics. Combined cancer incidence (excluding nonmelanoma skin cancers) from 1987 to 2006 was captured using cancer registries and hospital surveillance; 2880 incident cancer cases occurred over follow-up. Cox regression was used to calculate hazard ratios for incident cancer. There was a significant (P trend <0.0001), graded, inverse association between the number of ideal cardiovascular health metrics at baseline and cancer incidence. Participants meeting goals for 6 to 7 ideal health metrics (2.7% of the population) had 51% lower risk of incident cancer than those meeting goals for 0 ideal health metrics. When smoking was removed from the sum of ideal health metrics, the association was attenuated with participants meeting goals for 5 to 6 health metrics having 25% lower cancer risk than those meeting goals for 0 ideal health metrics (P trend =0.03). CONCLUSIONS: Adherence to the 7 ideal health metrics defined in the AHA 2020 goals is associated with lower cancer incidence. The AHA should continue to pursue partnerships with cancer advocacy groups to achieve reductions in chronic disease prevalence.

Protein intake and lumbar bone density: the Multi-Ethnic Study of Atherosclerosis (MESA).

Dietary protein has been shown to increase urinary Ca excretion in randomised controlled trials, and diets high in protein may have detrimental effects on bone health; however, studies examining the relationship between dietary protein and bone health have conflicting results. In the present study, we examined the relationship between dietary protein (total, animal and vegetable protein) and lumbar spine trabecular volumetric bone mineral density (vBMD) among participants enrolled in the Multi-Ethnic Study of Atherosclerosis (n 1658). Protein intake was assessed using a FFQ obtained at baseline examination (2000-2). Lumbar spine vBMD was measured using quantitative computed tomography (2002-5), on average 3 years later. Multivariable linear and robust regression techniques were used to examine the associations between dietary protein and vBMD. Sex and race/ethnicity jointly modified the association of dietary protein with vBMD (P for interaction = 0·03). Among white women, higher vegetable protein intake was associated with higher vBMD (P for trend = 0·03), after adjustment for age, BMI, physical activity, alcohol consumption, current smoking, educational level, hormone therapy use, menopause and additional dietary factors. There were no consistently significant associations for total and animal protein intakes among white women or other sex and racial/ethnic groups. In conclusion, data from the present large, multi-ethnic, population-based study suggest that a higher level of protein intake, when substituted for fat, is not associated with poor bone health. Differences in the relationship between protein source and race/ethnicity of study populations may in part explain the inconsistent findings reported previously.

Physical environment may modify the association between depressive symptoms and change in waist circumference: the multi-ethnic study of atherosclerosis.

BACKGROUND: Although the bidirectional association between depressive symptoms and adiposity has been recognized, the contribution of neighborhood factors to this relationship has not been assessed. OBJECTIVE: This study evaluates whether physical and social neighborhood environments modify the bidirectional relationship between depressive symptoms and adiposity (measured by waist circumference and body mass index). METHODS: Using data on 5,122 men and women (ages 45 to 84 years) from the Multi-Ethnic Study of Atherosclerosis (MESA) we investigated whether neighborhood physical (i.e., walking environment and availability of healthy food) and social (i.e., safety, aesthetics, and social coherence) environments modified the association between the following: (1) baseline elevated depressive symptoms (Center for Epidemiologic Study Depression Scale score ≥ 16) and change in adiposity (as measured by waist circumference and body mass index) and (2) baseline overweight/obesity (waist circumference > 102 cm for men and >88 cm for women, or body mass index ≥ 25 kg/m(2)) and change in depressive symptoms using multilevel models. Neighborhood-level factors were obtained from the MESA Neighborhood Study. RESULTS: A greater increase in waist circumference in participants with vs without elevated depressive symptoms was observed in those living in poorly-rated physical environments but not in those living in better-rated environments (interaction p = 0.045). No associations were observed with body mass index. Baseline overweight/obesity was not associated with change in depressive symptoms and there was no modification by neighborhood-level factors. CONCLUSIONS: Elevated depressive symptoms were associated with greater increase in waist circumference among individuals living in poorly-rated physical environments than in those in better-rated physical environments. No association was found between overweight/obesity and change in depressive symptoms.

Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption.

We report the first genome-wide association study of habitual caffeine intake. We included 47,341 individuals of European descent based on five population-based studies within the United States. In a meta-analysis adjusted for age, sex, smoking, and eigenvectors of population variation, two loci achieved genome-wide significance: 7p21 (P = 2.4 × 10(-19)), near AHR, and 15q24 (P = 5.2 × 10(-14)), between CYP1A1 and CYP1A2. Both the AHR and CYP1A2 genes are biologically plausible candidates as CYP1A2 metabolizes caffeine and AHR regulates CYP1A2.

Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3 x 10⁻64) and lower levels of eicosapentaenoic acid (EPA, p = 5 x 10⁻58) and docosapentaenoic acid (DPA, p = 4 x 10⁻¹54). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2 x 10⁻¹²) and DPA (p = 1 x 10⁻4³) and lower docosahexaenoic acid (DHA, p = 1 x 10⁻¹5). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1 x 10⁻8). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.

Associations between metabolomic compounds and incident heart failure among African Americans: the ARIC Study.

Heart failure is more prevalent among African Americans than in the general population. Metabolomic studies among African Americans may efficiently identify novel biomarkers of heart failure. We used untargeted methods to measure 204 stable serum metabolites and evaluated their associations with incident heart failure hospitalization (n = 276) after a median follow-up of 20 years (1987-2008) by using Cox regression in data from 1,744 African Americans aged 45-64 years without heart failure at baseline from the Jackson, Mississippi, field center of the Atherosclerosis Risk in Communities (ARIC) Study. After adjustment for established risk factors, we found that 16 metabolites (6 named with known structural identities and 10 unnamed with unknown structural identities, the latter denoted by using the format X-12345) were associated with incident heart failure (P < 0.0004 based on a modified Bonferroni procedure). Of the 6 named metabolites, 4 are involved in amino acid metabolism, 1 (prolylhydroxyproline) is a dipeptide, and 1 (erythritol) is a sugar alcohol. After additional adjustment for kidney function, 2 metabolites remained associated with incident heart failure (for metabolite X-11308, hazard ratio = 0.75, 95% confidence interval: 0.65, 0.86; for metabolite X-11787, hazard ratio = 1.23, 95% confidence interval: 1.10, 1.37). Further structural analysis revealed X-11308 to be a dihydroxy docosatrienoic acid and X-11787 to be an isoform of either hydroxyleucine or hydroxyisoleucine. Our metabolomic analysis revealed novel biomarkers associated with incident heart failure independent of traditional risk factors.

Meta-analysis investigating associations between healthy diet and fasting glucose and insulin levels and modification by loci associated with glucose homeostasis in data from 15 cohorts.

Whether loci that influence fasting glucose (FG) and fasting insulin (FI) levels, as identified by genome-wide association studies, modify associations of diet with FG or FI is unknown. We utilized data from 15 U.S. and European cohort studies comprising 51,289 persons without diabetes to test whether genotype and diet interact to influence FG or FI concentration. We constructed a diet score using study-specific quartile rankings for intakes of whole grains, fish, fruits, vegetables, and nuts/seeds (favorable) and red/processed meats, sweets, sugared beverages, and fried potatoes (unfavorable). We used linear regression within studies, followed by inverse-variance-weighted meta-analysis, to quantify 1) associations of diet score with FG and FI levels and 2) interactions of diet score with 16 FG-associated loci and 2 FI-associated loci. Diet score (per unit increase) was inversely associated with FG (ß = -0.004 mmol/L, 95% confidence interval: -0.005, -0.003) and FI (ß = -0.008 ln-pmol/L, 95% confidence interval: -0.009, -0.007) levels after adjustment for demographic factors, lifestyle, and body mass index. Genotype variation at the studied loci did not modify these associations. Healthier diets were associated with lower FG and FI concentrations regardless of genotype at previously replicated FG- and FI-associated loci. Studies focusing on genomic regions that do not yield highly statistically significant associations from main-effect genome-wide association studies may be more fruitful in identifying diet-gene interactions.

Dietary phosphorus is associated with greater left ventricular mass.

Dietary phosphorus consumption has risen steadily in the United States. Oral phosphorus loading alters key regulatory hormones and impairs vascular endothelial function, which may lead to an increase in left ventricular mass (LVM). We investigated the association of dietary phosphorus with LVM in 4494 participants from the Multi-Ethnic Study of Atherosclerosis, a community-based study of individuals who were free of known cardiovascular disease. The intake of dietary phosphorus was estimated using a 120-item food frequency questionnaire and the LVM was measured using magnetic resonance imaging. Regression models were used to determine associations of estimated dietary phosphorus with LVM and left ventricular hypertrophy (LVH). Mean estimated dietary phosphorus intake was 1167 mg/day in men and 1017 mg/day in women. After adjustment for demographics, dietary sodium, total calories, lifestyle factors, comorbidities, and established LVH risk factors, each quintile increase in the estimated dietary phosphate intake was associated with an estimated 1.1 g greater LVM. The highest gender-specific dietary phosphorus quintile was associated with an estimated 6.1 g greater LVM compared with the lowest quintile. Higher dietary phosphorus intake was associated with greater odds of LVH among women, but not men. These associations require confirmation in other studies.

Relationships of the Mediterranean dietary pattern with insulin resistance and diabetes incidence in the Multi-Ethnic Study of Atherosclerosis (MESA).

Type 2 diabetes (T2D) is a highly prevalent but preventable disorder. We assessed the association between an a priori Mediterranean diet (MeDiet) score and fasting glucose and insulin at baseline and incident T2D after a 6-year follow-up in the Multi-Ethnic Study of Atherosclerosis. Dietary intake was measured at baseline using a 127-item FFQ in 5390 men and women aged 45-84 years free of prevalent diabetes and clinical CVD. A MeDiet score was created based on the intake of ten food components: vegetables; whole grains; nuts; legumes; fruits; ratio of monounsaturated:saturated fat; red and processed meat; dairy products; fish; alcohol. Multivariable linear and proportional hazards models were used to estimate the association of the MeDiet, categorised in quintiles, with baseline insulin and glucose, and incident diabetes, respectively. The models were adjusted for demographic, physiological and behavioural characteristics. After multivariable adjustment, individuals with a higher MeDiet score had lower baseline mean insulin levels (Q1: 5·8 (95% CI 5·6, 6·0) µmol/l; Q5: 4·8 (95% CI 4·6, 5·0) µmol/l; P for trend < 0·0001). A higher MeDiet score was also associated with significantly lower glucose levels after basic adjustment, but was attenuated after adjustment for waist circumference. During the follow-up, 412 incident diabetes events accrued. The MeDiet was not significantly related to the risk of incident diabetes (P for trend = 0·64). In summary, greater consistency with a Mediterranean-style diet, reflected by a higher a priori MeDiet score, was cross-sectionally associated with lower insulin levels among non-diabetics, and with lower blood glucose before adjustment for obesity, but not with a lower incidence of diabetes.

Circulating phylloquinone concentrations of adults in the United States differ according to race and ethnicity.

Differences in micronutrient status are reported to contribute to racial and ethnic differences in chronic diseases. Diseases related to vitamin K are reported to differ by race and ethnicity, but it is unclear if circulating vitamin K concentrations similarly differ. We examined racial and ethnic differences in serum phylloquionone (K1) in the Multiethnic Study of Atherosclerosis (MESA) (mean ± SD age = 62 ± 10 y; 52% female; 262 white, 180 African American, 169 Hispanic, 93 Chinese American). Overall, 25% had serum K1 <0.1 nmol/L (the lower limit of detection). The prevalence of low serum K1 was 4% in Chinese Americans compared with 24% of whites, 29% of African Americans, and 33% of Hispanics. Compared with whites, Chinese Americans were significantly less likely to have serum K1 <0.1 nmol/L [OR (95% CI): 0.23 (0.09-0.23), adjusted for serum TG, K1 intake, age, sex, BMI, smoking, total cholesterol, site, season, and lipid-lowering medication use]. African Americans and Hispanics had similar odds to whites for having serum K1 <0.1 nmol/L [OR(95% CI): 1.30 (0.79-2.15) and 1.19 (0.66-2.15), respectively; fully adjusted]. In participants with detectable concentrations (n = 523), (natural log) serum K1 was higher in the Chinese Americans compared with whites, African Americans, and Hispanics (geometric mean ± SEM = 2.2 ± 0.1 nmol/L vs. 1.2 ± 0.1 nmol/L, 1.5 ± 0.1 nmol/L, and 1.1 ± 0.1 nmol/L, respectively, adjusted for serum TG, K1 intake, and additional covariates; all P < 0.001). These findings suggest circulating K1 differs by race and ethnicity in U.S. adults, especially among those of Chinese American descent, which merits consideration in the design and interpretation of future population-based and clinical studies of vitamin K and related diseases.

Dietary intakes of zinc and heme iron from red meat, but not from other sources, are associated with greater risk of metabolic syndrome and cardiovascular disease.

Metabolic syndrome (MetS), Type 2 diabetes (T2D), and cardiovascular disease (CVD) share an inflammatory etiology and are known to be influenced by diet. We investigated associations of hypothesized prooxidative (Fe) and antioxidative (Zn, Mg, ß-carotene, vitamin C, vitamin E) micronutrients with incident MetS, T2D, and CVD in the Multi-Ethnic Study of Atherosclerosis. Participants, 45-84 y at baseline (2000-2002), were followed through 2010. Diet was assessed by FFQ. After adjusting for demographics and behavioral confounders, including BMI, dietary vitamin E intake was inversely associated with incident MetS and CVD [HR for extreme quintiles: MetS = 0.78 (95% CI = 0.62, 0.97), P-trend = 0.01; CVD: HR = 0.69 (95% CI = 0.46, 1.03), P-trend = 0.04]. Intakes of heme iron and Zn from red meat, but not from other sources, were positively associated with risk of MetS [heme iron from red meat: HR = 1.25 (95% CI = 0.99,1.56), P-trend = 0.03; Zn from red meat: HR = 1.29 (95% CI = 1.03,1.61), P-trend = 0.04] and CVD [heme iron from red meat: HR = 1.65 (95% CI = 1.10,2.47), P-trend = 0.01; Zn from red meat: HR = 1.51 (95% CI = 1.02, 2.24), P-trend = 0.01]. Dietary intakes of nonheme iron, Mg, vitamin C, and ß-carotene were not associated with risk of MetS, T2D, or CVD. Data provided little support for the associations between specific micronutrients and MetS, T2D, or CVD. However, nutrients consumed in red meat, or red meat as a whole, may increase risk of MetS and CVD.

DASH eating pattern is associated with favorable left ventricular function in the multi-ethnic study of atherosclerosis.

OBJECTIVE: Potential associations between consistency with the Dietary Approaches to Stop Hypertension (DASH) diet and preclinical stages of heart failure (HF) in a large multiethnic cohort have not been evaluated. This study sought to determine the cross-sectional relationship between the DASH eating pattern and left ventricular (LV) function in the Multi-Ethnic Study of Atherosclerosis (MESA). DESIGN: A total of 4506 men and women from four ethnic groups (40% white, 24% African American, 22% Hispanic American, and 14% Chinese American) aged 45-84 years and free of clinical cardiovascular disease (CVD) were studied. Diet was assessed using a validated food-frequency questionnaire. LV functional parameters including end-diastolic volume, stroke volume, and LV ejection fraction were measured by magnetic resonance imaging. Multivariate analyses were conducted to examine the association between LV function and DASH eating pattern (including high consumption of fruits, vegetables, whole grains, poultry, fish, nuts, and low-fat dairy products and low consumption of red meat, sweets, and sugar-sweetened beverages). RESULTS: A 1-unit increase in DASH eating pattern score was associated with a 0.26 ml increase in end-diastolic volume and increases of 0.10 ml/m(2) in stroke volume, adjusted for key confounders. A 1-unit increase in DASH eating pattern score was also associated with a 0.04% increase in ejection fraction, but the relationship was marginally significant (p = 0.08). CONCLUSIONS: In this population, greater DASH diet consistency is associated with favorable LV function. DASH dietary patterns could be protective against HF.

Associations of socioeconomic status and processed food intake with serum phosphorus concentration in community-living adults: the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVE: Higher serum phosphorus concentrations are associated with cardiovascular disease events and mortality. Low socioeconomic status is linked with higher serum phosphorus concentration, but the reasons are unclear. Poor individuals disproportionately consume inexpensive processed foods commonly enriched with phosphorus-based food preservatives. Accordingly, we hypothesized that excess intake of these foods accounts for a relationship between lower socioeconomic status and higher serum phosphorus concentration. DESIGN: Cross-sectional analysis. SETTING AND PARTICIPANTS: We examined a random cohort of 2,664 participants with available phosphorus measurements in the Multi-Ethnic Study of Atherosclerosis, a community-based sample of individuals free of clinically apparent cardiovascular disease from across the United States. PREDICTOR VARIABLES: Socioeconomic status, the intake of foods commonly enriched with phosphorus-based food additives (processed meats, sodas), and frequency of fast-food consumption. OUTCOMES: Fasting morning serum phosphorus concentrations. RESULTS: In unadjusted analyses, lower income and lower educational achievement categories were associated with modestly higher serum phosphorus concentration (by 0.02 to 0.10 mg/dL, P < .05 for all). These associations were attenuated in models adjusted for demographic and clinical factors, almost entirely due to adjustment for female gender. In multivariable-adjusted analyses, there were no statistically significant associations of processed meat intake or frequency of fast-food consumption with serum phosphorus. In contrast, each serving per day higher soda intake was associated with 0.02 mg/dL lower serum phosphorus concentration (95% confidence interval, -0.04, -0.01). CONCLUSIONS: Greater intake of foods commonly enriched with phosphorus additives was not associated with higher serum phosphorus concentration in a community-living sample with largely preserved kidney function. These results suggest that excess intake of processed and fast foods may not impact fasting serum phosphorus concentrations among individuals without kidney disease.

Sex differences in subclinical atherosclerosis by race/ethnicity in the multi-ethnic study of atherosclerosis.

Sex differences in cardiovascular disease mortality are more pronounced among non-Hispanic whites than other racial/ethnic groups, but it is unknown whether this variation is present in the earlier subclinical stages of disease. The authors examined racial/ethnic variation in sex differences in coronary artery calcification (CAC) and carotid intimal media thickness at baseline in 2000-2002 among participants (n = 6,726) in the Multi-Ethnic Study of Atherosclerosis using binomial and linear regression. Models adjusted for risk factors in several stages: age, traditional cardiovascular disease risk factors, behavioral risk factors, psychosocial factors, and adult socioeconomic position. Women had a lower prevalence of any CAC and smaller amounts of CAC when present than men in all racial/ethnic groups. Sex differences in the prevalence of CAC were more pronounced in non-Hispanic whites than in African Americans and Chinese Americans after adjustment for traditional cardiovascular disease risk factors, and further adjustment for behavioral factors, psychosocial factors, and socioeconomic position did not modify these results (for race/sex, P(interaction) = 0.047). Similar patterns were observed for amount of CAC among adults with CAC. Racial/ethnic variation in sex differences for carotid intimal media thickness was less pronounced. In conclusion, coronary artery calcification is differentially patterned by sex across racial/ethnic groups.

Dietary micronutrient intakes are associated with markers of inflammation but not with markers of subclinical atherosclerosis.

Few studies have examined associations of dietary micronutrients with markers of inflammation and subclinical atherosclerosis. The present study investigated associations of heme iron, nonheme iron, zinc (Zn), magnesium (Mg), ß-carotene, vitamin C, and vitamin E with C-reactive protein (CRP), IL-6, total homocysteine (tHcy), fibrinogen, coronary artery calcium, and common and internal carotid artery intima media thickness. Micronutrient intakes and markers of inflammation and subclinical atherosclerosis were studied in 5,181 participants from the Multi-Ethnic Study of Atherosclerosis who were aged 45-84 y and free of diabetes and cardiovascular disease. Models were adjusted for energy intake, demographics, lifestyle characteristics, and BMI. Dietary nonheme iron and Mg intakes were inversely associated with tHcy concentrations (mean tHcy: 9.11, 8.86, 8.74, 8.71, and 8.50 µmol/L, and 9.20, 9.00, 8.65, 8.76, and 8.33 µmol/L across increasing quintiles of nonheme iron and Mg, respectively; P-trend < 0.001 for both). However, dietary Zn and heme iron were positively associated with CRP [mean: 1.73, 1.75, 1.78, 1.88, and 1.96 mg/L across increasing quintiles of Zn and 1.72, 1.76, 1.83, 1.86, and 1.94 mg/L across increasing quintiles of heme iron (P-trend = 0.002 and 0.01, respectively). Other tested micronutrient-marker associations were not significant. In conclusion, of the 49 tested associations, only 7 were significant. Although this study does not provide strong support for associations between the micronutrients and markers of inflammation and subclinical atherosclerosis, the results are consistent with dietary guidelines that advocate for a balanced diet that includes a variety of plant foods containing Mg, Zn, and nonheme iron.