Obesity and obesity-related metabolic disorders, such as diabetes and chronic inflammation, have been positively associated both with postmenopausal breast cancer and with resting energy expenditure (REE). However, there is limited epidemiologic evidence on the associations between REE and risk of postmenopausal breast cancer. We used multivariable Cox proportional hazards models to examine the association between predicted REE (calculated using the Ikeda, Livingston, and Mifflin equations) and risk of postmenopausal breast cancer overall and by subtypes, and by level of body fat) among 137,283 postmenopausal women in the Women's Health Initiative (WHI). All predicted REEs were positively associated with risk of invasive breast cancer [HRq5 vs. q1 = 1.69; 95% confidence interval (CI), 1.57-1.81; HR = 1.69; 95% CI, 1.57-1.82; and HR = 1.68; 95% CI, 1.56-1.80 for Ikeda, Livingston, and Mifflin, respectively]. These positive associations were observed irrespective of the hormone receptor subtype, grade, and stage of the tumors, but were most pronounced for estrogen receptor-positive/progesterone receptor-positive tumors. After additional adjustment for body mass index (BMI), the associations were mostly attenuated and remained statistically significant for most of the outcomes. We also observed an interaction between the predicted REEs and BMI, with the associations being somewhat stronger among normal weight and overweight women than among obese women (Pinteractions < 0.05). Our findings indicate that relatively high REE is associated with increased risk of invasive breast cancer among postmenopausal women (particularly for the obesity-related tumor subtypes), irrespective of the equation used. Further studies using more objective measures of REE are, however, needed to confirm our findings.

Prevention relevance

This study showed that higher resting energy expenditure (REE) was associated with higher postmenopausal breast cancer risk. REE provides energy to support cancer-associated disorders such as obesity and inflammation. Thus, studies on its association with breast cancer can help to improve our understanding of the pathophysiology of breast cancer.

Objective

To assess the relationship between body fat distribution and incident lower-extremity arterial disease (LEAD).

Research design and methods

We included 155,925 postmenopausal women with anthropometric measures from the Women's Health Initiative who had no known LEAD at recruitment. A subset of 10,894 participants had body composition data quantified by DXA. Incident cases of symptomatic LEAD were ascertained and adjudicated through medical record review.

Results

We identified 1,152 incident cases of LEAD during a median 18.8 years follow-up. After multivariable adjustment and mutual adjustment, waist and hip circumferences were positively and inversely associated with risk of LEAD, respectively (both P-trend < 0.0001). In a subset (n = 22,561) where various cardiometabolic biomarkers were quantified, a similar positive association of waist circumference with risk of LEAD was eliminated after adjustment for diabetes and HOMA of insulin resistance (P-trend = 0.89), whereas hip circumference remained inversely associated with the risk after adjustment for major cardiometabolic traits (P-trend = 0.0031). In the DXA subset, higher trunk fat (P-trend = 0.0081) and higher leg fat (P-trend < 0.0001) were associated with higher and lower risk of LEAD, respectively. Further adjustment for diabetes, dyslipidemia, and blood pressure diminished the association for trunk fat (P-trend = 0.49), yet the inverse association for leg fat persisted (P-trend = 0.0082).

Conclusions

Among U.S. postmenopausal women, a positive association of upper-body fat with risk of LEAD appeared to be attributable to traditional risk factors, especially insulin resistance. Lower-body fat was inversely associated with risk of LEAD beyond known risk factors.

BACKGROUND: Dietary patterns high in healthy minimally processed plant foods play an important role in modulating the gut microbiome and promoting cardiometabolic health. Little is known on the diet-gut microbiome relationship in US Hispanics/Latinos, who have a high burden of obesity and diabetes. OBJECTIVE: In a cross-sectional analysis, we sought to examine the relationships of 3 healthy dietary patterns-the alternate Mediterranean diet (aMED), the Healthy Eating Index (HEI)-2015, and the healthful plant-based diet index (hPDI)-with the gut microbiome in US Hispanic/Latino adults, and to study the association of diet-related species with cardiometabolic traits. METHODS: The Hispanic Community Health Study/Study of Latinos is a multi-site community-based cohort. At baseline (2008-2011), diet was assessed by using 2, 24-hour recalls. Shotgun sequencing was performed on stool samples collected in 2014-17 (n = 2444). Analysis of Compositions of Microbiomes 2 (ANCOM2) was used to identify the associations of dietary pattern scores with gut microbiome species and functions, adjusting for sociodemographic, behavioral, and clinical covariates. RESULTS: Better diet quality according to multiple healthy dietary patterns was associated with a higher abundance of species from class Clostridia, including [Eubacterium] eligens, Butyrivibrio crossotus, and Lachnospiraceae bacterium TF01-11, but functions related to better diet quality differed for the dietary patterns (e.g., aMED with pyruvate:ferredoxin oxidoreductase, hPDI with L-arabinose/lactose transport). Poorer diet quality was associated with a higher abundance of Acidaminococcus intestini and with functions of manganese/iron transport, adhesin protein transport, and nitrate reduction. Some healthy diet pattern-enriched Clostridia species were related to more favorable cardiometabolic traits such as lower triglycerides and waist-to-hip ratio. CONCLUSIONS: Healthy dietary patterns in this population are associated with a higher abundance of fiber-fermenting Clostridia species in the gut microbiome, consistent with previous studies in other racial/ethnic groups. Gut microbiota may be involved in the beneficial effect of higher diet quality on cardiometabolic disease risk.

Background

The potential cardiovascular impact of dietary cholesterol intake has been actively debated for decades.

Objectives

We aimed to evaluate associations of dietary cholesterol and egg intakes with incident cardiovascular disease (CVD) and all-cause and cause-specific mortality.

Methods

We included 96,831 US postmenopausal women aged 50-79 y without known CVD or cancer during baseline enrollment (1993-1998) of the Women's Health Initiative. Dietary information was collected using a validated FFQ. Incident CVD [i.e., ischemic heart disease (IHD) and stroke] and all-cause and cause-specific mortality were ascertained and adjudicated through February 2018.

Results

A total of 9808 incident CVD cases and 19,508 all-cause deaths occurred during a median follow-up of 17.8 y and 18.9 y, respectively. After multivariable adjustment for traditional risk factors and key dietary nutrients including dietary saturated fat, there were modest associations of dietary cholesterol intake with incident CVD (HRQ5versusQ1: 1.12; 95% CI: 1.03, 1.21; P-trend < 0.001) and all-cause mortality (HRQ5versusQ1: 1.09; 95% CI: 1.02, 1.15; P-trend < 0.001). Significant positive associations were also observed between dietary cholesterol and incident IHD (P-trend = 0.007), incident ischemic stroke (P-trend = 0.002), and CVD mortality (P-trend = 0.002), whereas there was an inverse association for incident hemorrhagic stroke (P-trend = 0.037) and no association for mortality from cancer, Alzheimer disease/dementia, respiratory diseases, or other causes (P-trend > 0.05). Higher egg consumption was also associated with modestly higher risk of incident CVD (P-trend = 0.004) and all-cause mortality (P-trend < 0.001), with HRs of 1.14 (95% CI: 1.04, 1.25) and 1.14 (95% CI: 1.07, 1.22), respectively, when comparing ≥1 egg/d with <1 egg/wk.

Conclusions

Both higher dietary cholesterol intake and higher egg consumption appeared to be associated with modestly elevated risk of incident CVD and all-cause mortality in US postmenopausal women.

The potential role of nutritional factors in the development of peripheral arterial disease (PAD) remains poorly understood. We evaluated multiple recommended eating patterns as reflected by predefined diet quality indices in relation to long-term risk of PAD. We included 138 506 US postmenopausal women in the Women’s Health Initiative who had no known PAD at baseline (1993–1998). Four diet quality indices, including alternate Mediterranean diet index, alternate Healthy Eating Index-2010, Dietary Approaches to Stop Hypertension diet index, and Healthy Eating Index-2015, were derived using dietary information collected by a validated food frequency questionnaire at baseline. Incident cases of symptomatic PAD in the lower extremities were ascertained and adjudicated through March 2019 via medical record review. During a median 18.6 years of follow-up, 1036 incident PAD cases were identified. After multivariable adjustment, all diet quality scores were significantly and inversely associated with 21% (for alternate Healthy Eating Index 2010) to 34% (for Dietary Approaches to Stop Hypertension index) lower risk of PAD when comparing the highest with the lowest quartiles (all P-fortrend values ≤0.010). Among contributing food groups and nutrients, intakes of legumes, dietary fiber, and vegetable protein were associated lower risk of PAD, while intakes of unprocessed red meat, processed meat, and regular soft drinks were associated with higher risk. In a broad sample of US postmenopausal women, adhering to different recommended eating patterns is associated with lower risk of PAD. Our findings suggest that current clinical and public health strategies that recommend healthful eating patterns may also be applicable to PAD prevention. (

Background

Obesity and related comorbidities are major health concerns among many US immigrant populations. Emerging evidence suggests a potential involvement of the gut microbiome. Here, we evaluated gut microbiome features and their associations with immigration, dietary intake, and obesity in 2640 individuals from a population-based study of US Hispanics/Latinos.

Results

The fecal shotgun metagenomics data indicate that greater US exposure is associated with reduced ɑ-diversity, reduced functions of fiber degradation, and alterations in individual taxa, potentially related to a westernized diet. However, a majority of gut bacterial genera show paradoxical associations, being reduced with US exposure and increased with fiber intake, but increased with obesity. The observed paradoxical associations are not explained by host characteristics or variation in bacterial species but might be related to potential microbial co-occurrence, as seen by positive correlations among Roseburia, Prevotella, Dorea, and Coprococcus. In the conditional analysis with mutual adjustment, including all genera associated with both obesity and US exposure in the same model, the positive associations of Roseburia and Prevotella with obesity did not persist, suggesting that their positive associations with obesity might be due to their co-occurrence and correlations with obesity-related taxa, such as Dorea and Coprococcus.

Conclusions

Among US Hispanics/Latinos, US exposure is associated with unfavorable gut microbiome profiles for obesity risk, potentially related to westernized diet during acculturation. Microbial co-occurrence could be an important factor to consider in future studies relating individual gut microbiome taxa to environmental factors and host health and disease.

Background

Trimethylamine-N-oxide (TMAO), a diet-derived and gut microbiota-related metabolite, is associated with cardiovascular disease (CVD). However, major dietary determinants and specific gut bacterial taxa related to TMAO remain to be identified in humans.

Objectives

We aimed to identify dietary and gut microbial factors associated with circulating TMAO.

Methods

This cross-sectional study included 3972 participants (57.3% women) aged 18-74 y from the Hispanic Community Health Study/Study of Latinos in the United States. Dietary information was collected by 24-h dietary recalls at baseline interview (2008-2011), and baseline serum TMAO and its precursors were measured by an untargeted approach. Gut microbiome was profiled by shotgun metagenomic sequencing in a subset of participants (n = 626) during a follow-up visit (2016-2018). Logistic and linear regression were used to examine associations of inverse-normalized metabolites with prevalent CVD, dietary intake, and bacterial species, respectively, after adjustment for sociodemographic, behavioral, and clinical factors.

Results

TMAO was positively associated with prevalent CVD (case number = 279; OR = 1.34; 95% CI: 1.17, 1.54, per 1-SD). Fish (P = 1.26 × 10-17), red meat (P = 3.33 × 10-16), and egg (P = 3.89 × 10-5) intakes were top dietary factors positively associated with TMAO. We identified 9 gut bacterial species significantly associated with TMAO (false discovery rate <0.05). All 4 species positively associated with TMAO belong to the order Clostridiales, of which 3 might have homologous genes encoding carnitine monooxygenase, an enzyme converting carnitine to trimethylamine (TMA). The red meat-TMAO association was more pronounced in participants with higher abundances of these 4 species compared with those with lower abundance (Pinteraction = 0.013), but such microbial modification was not observed for fish-TMAO or egg-TMAO associations.

Conclusion

In US Hispanics/Latinos, fish, red meat, and egg intakes are major dietary factors associated with serum TMAO. The identified potential TMA-producing gut microbiota and microbial modification on the red meat-TMAO association support microbial TMA production from dietary carnitine, whereas the fish-TMAO association is independent of gut microbiota.

Introduction

We studied the replication and generalization of previously identified metabolites potentially associated with global cognitive function in multiple race/ethnicities and assessed the contribution of diet to these associations.

Methods

We tested metabolite-cognitive function associations in U.S.A. Hispanic/Latino adults (n = 2222) from the Community Health Study/ Study of Latinos (HCHS/SOL) and in European (n = 1365) and African (n = 478) Americans from the Atherosclerosis Risk In Communities (ARIC) Study. We applied Mendelian Randomization (MR) analyses to assess causal associations between the metabolites and cognitive function and between Mediterranean diet and cognitive function.

Results

Six metabolites were consistently associated with lower global cognitive function across all studies. Of these, four were sugar-related (e.g., ribitol). MR analyses provided weak evidence for a potential causal effect of ribitol on cognitive function and bi-directional effects of cognitive performance on diet.

Discussion

Several diet-related metabolites were associated with global cognitive function across studies with different race/ethnicities.

Highlights

Metabolites associated with cognitive function in Puerto Rican adults were recently identified. We demonstrate the generalizability of these associations across diverse race/ethnicities. Most identified metabolites are related to sugars. Mendelian Randomization (MR) provides weak evidence for a causal effect of ribitol on cognitive function. Beta-cryptoxanthin and other metabolites highlight the importance of a healthy diet.

AIMS:Central adiposity is associated with increased cardiovascular disease (CVD) risk, even among people with normal body mass index (BMI). We tested the hypothesis that regional body fat deposits (trunk or leg fat) are associated with altered risk of CVD among postmenopausal women with normal BMI. METHODS AND RESULTS:We included 2683 postmenopausal women with normal BMI (18.5 to <25 kg/m2) who participated in the Women's Health Initiative and had no known CVD at baseline. Body composition was determined by dual energy X-ray absorptiometry. Incident CVD events including coronary heart disease and stroke were ascertained through February 2017. During a median 17.9 years of follow-up, 291 incident CVD cases occurred. After adjustment for demographic, lifestyle, and clinical risk factors, neither whole-body fat mass nor fat percentage was associated with CVD risk. Higher percent trunk fat was associated with increased risk of CVD [highest vs. lowest quartile hazard ratio (HR) = 1.91, 95% confidence interval (CI) 1.33-2.74; P-trend <0.001], whereas higher percent leg fat was associated with decreased risk of CVD (highest vs. lowest quartile HR = 0.62, 95% CI 0.43-0.89; P-trend = 0.008). The association for trunk fat was attenuated yet remained significant after further adjustment for waist circumference or waist-to-hip ratio. Higher percent trunk fat combined with lower percent leg fat was associated with particularly high risk of CVD (HR comparing extreme groups = 3.33, 95% CI 1.46-7.62). CONCLUSION:Among postmenopausal women with normal BMI, both elevated trunk fat and reduced leg fat are associated with increased risk of CVD.

Objective

Tryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota.

Method

We analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites.

Results

Tryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with T2D risk. We identified multiple host genetic variants, dietary factors, gut bacteria and their potential interplay associated with these T2D-relaetd metabolites. Intakes of fibre-rich foods, but not protein/tryptophan-rich foods, were the dietary factors most strongly associated with tryptophan metabolites. The fibre-indolepropionate association was partially explained by indolepropionate-associated gut bacteria, mostly fibre-using Firmicutes. We identified a novel association between a host functional LCT variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut Bifidobacterium, a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut Bifidobacterium and serum indolepropionate only among genetically lactase non-persistent individuals.

Conclusion

Higher milk intake among lactase non-persistent individuals, and higher fibre intake were associated with a favourable profile of circulating tryptophan metabolites for T2D, potentially through the host-microbial cross-talk shifting tryptophan metabolism toward gut microbial indolepropionate production.