Publications by authors named "Qibin Qi"

163 Publications

Comparison of Fecal Collection Methods on Variation in Gut Metagenomics and Untargeted Metabolomics.

mSphere 2021 Sep 15:e0063621. Epub 2021 Sep 15.

State Key Laboratory of Genetic Engineering School of Life Sciences, Human Phenome Institute, Fudan Universitygrid.8547.e, Shanghai, China.

Integrative analysis of high-quality metagenomics and metabolomics data from fecal samples provides novel clues for the mechanism underpinning gut microbe-human interactions. However, data regarding the influence of fecal collection methods on both metagenomics and metabolomics are sparse. Six fecal collection methods (the gold standard [GS] [i.e., immediate freezing at -80°C with no solution], 95% ethanol, RNAlater, OMNIgene Gut, fecal occult blood test [FOBT] cards, and Microlution) were used to collect 88 fecal samples from eight healthy volunteers for whole-genome shotgun sequencing (WGSS) and untargeted metabolomic profiling. Metrics assessed included the abundances of predominant phyla and α- and β-diversity at the species, gene, and pathway levels. Intraclass correlation coefficients (ICCs) were calculated for microbes and metabolites to estimate (i) stability (day 4 versus day 0 within each method), (ii) concordance (day 0 for each method versus the GS), and (iii) reliability (day 4 for each method versus the GS). For the top 4 phyla and microbial diversity metrics at the species, gene, and pathway levels, generally high stability and reliability were observed for most methods except for 95% ethanol; similar concordances were seen for different methods. For metabolomics data, 95% ethanol showed the highest stability, concordance, and reliability (median ICCs = 0.71, 0.71, and 0.65, respectively). Taken together, OMNIgene Gut, FOBT cards, RNAlater, and Microlution, but not 95% ethanol, were reliable collection methods for gut metagenomic studies. However, 95% ethanol was the best for preserving fecal metabolite profiles. We recommend using separate collecting methods for gut metagenomic sequencing and fecal metabolomic profiling in large population studies. The choice of fecal collection method is essential for studying gut microbe-human interactions in large-scale population-based research. In this study, we examined the effects of fecal collection methods and storage time at ambient temperature on variations in the gut microbiome community composition; microbial diversity metrics at the species, gene, and pathway levels; antibiotic resistance genes; and metabolome profiling. Our findings suggest using different fecal sample collection methods for different data generation purposes. OMNIgene Gut, FOBT cards, RNAlater, and Microlution, but not 95% ethanol, were reliable collection methods for gut metagenomic studies. However, 95% ethanol was the best for preserving fecal metabolite profiles.
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http://dx.doi.org/10.1128/mSphere.00636-21DOI Listing
September 2021

Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations.

Commun Biol 2021 07 28;4(1):918. Epub 2021 Jul 28.

Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.

Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much of the AI ancestry effect on LC-PUFAs, especially for low levels of n-3 LC-PUFAs. Rs174537 was also strongly associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides (TGs) and E-selectin in MESA Hispanics. Our study demonstrates that Amerind ancestry provides a useful and readily available tool to identify individuals most likely to have FADS-related n-3 LC-PUFA deficiencies and associated cardiovascular risk.
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http://dx.doi.org/10.1038/s42003-021-02431-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319323PMC
July 2021

Associations between physical activity, sedentary behaviour and left ventricular structure and function from the Echocardiographic Study of Latinos (ECHO-SOL).

Open Heart 2021 Jul;8(2)

Department of Medicine, Epidemiology & Population Health, Albert Einstein College of Medicine Department of Neurology, Bronx, New York, USA.

Objective: The cross-sectional association between accelerometer-measured physical activity (PA), sedentary behaviour (SB) and cardiac structure and function is less well described. This study's primary aim was to compare echocardiographic measures of cardiac structure and function with accelerometer measured PA and SB.

Methods: Participants included 1206 self-identified Hispanic/Latino men and women, age 45-74 years, from the Echocardiographic Study of Latinos. Standard echocardiographic measures included M-mode, two-dimensional, spectral, tissue Doppler and myocardial strain. Participants wore an Actical accelerometer at the hip for 1 week.

Results: The mean±SE age for the cohort was 56±0.4 years, 57% were women. Average moderate to vigorous PA (MVPA) was 21±1.1 min/day, light PA was 217±4.2 min/day and SB was 737±8.1 min/day. Both higher levels of light PA and MVPA (min/day) were associated with lower left ventricular (LV) mass index (LVMI)/end-diastolic volume and a lower E/e' ratio. Higher levels of MVPA (min/day) were associated with better right ventricular systolic function. Higher levels of SB were associated with increased LVMI. In a multivariable linear regression model adjusted for demographics and cardiovascular disease modifiable factors, every 10 additional min/day of light PA was associated with a 0.03 mL/m increase in left atrial volume index (LAVI) (p<0.01) and a 0.004 cm increase in tricuspid annular plane systolic excursion (p<0.01); every 10 additional min/day of MVPA was associated with a 0.18 mL/m increase in LAVI (p<0.01) and a 0.24% improvement in global circumferential strain (p<0.01).

Conclusions: Our findings highlight the potential positive association between the MVPA and light PA on cardiac structure and function.
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http://dx.doi.org/10.1136/openhrt-2021-001647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311330PMC
July 2021

Menopause is associated with immune activation in women with HIV.

J Infect Dis 2021 Jun 26. Epub 2021 Jun 26.

Division of HIV, Infectious Diseases, and Global Medicine, University of California San Francisco, San Francisco, CA, USA.

Background: Persistent immune activation due to gut barrier dysfunction is a suspected cause of morbidity in HIV, but the impact of menopause on this pathway is unknown.

Methods: In 350 women with HIV from the Women's Interagency HIV Study, plasma biomarkers of gut barrier dysfunction (intestinal fatty acid binding protein; IFAB), innate immune activation (soluble CD14 and CD163; sCD14, sCD163), and systemic inflammation (interleukin-6 and tumor necrosis factor receptor 1; IL-6, TNFR1), were measured at 674 person-visits spanning ≤2 years.

Results: Menopause (post- vs. pre-menopausal status) was associated with higher plasma sCD14 and sCD163 in linear mixed-effects regression adjusting for age and other covariates (B [95% CI]=161.89ng/mL [18.37, 305.41] and 65.48 ng/mL [6.64, 124.33], respectively); but not with plasma IFAB, IL-6, or TNFR1. In piece-wise linear mixed-effects regression of biomarkers on years before/after the final menstrual period, sCD14 increased during the menopausal transition by 250.71 ng/mL per year (95% CI: 16.63, 484.79; p=0.04), but not in the pre-menopausal or post-menopausal periods.

Conclusions: In women with HIV, menopause may increase innate immune activation, but data did not support an influence on the gut barrier or inflammation. Clinical implications of immune activation during the menopausal transition warrants further investigation.
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http://dx.doi.org/10.1093/infdis/jiab341DOI Listing
June 2021

Host and gut microbial tryptophan metabolism and type 2 diabetes: an integrative analysis of host genetics, diet, gut microbiome and circulating metabolites in cohort studies.

Gut 2021 Jun 14. Epub 2021 Jun 14.

Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.

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 . We identified a novel association between a host functional variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut , a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut 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.
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http://dx.doi.org/10.1136/gutjnl-2021-324053DOI Listing
June 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Habitual use of fish oil supplements, genetic predisposition, and risk of fractures: a large population-based study.

Am J Clin Nutr 2021 09;114(3):945-954

State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China.

Background: Epidemiologic studies have suggested an inverse association between circulating concentrations of long-chain ω-3 PUFAs and fracture risk. However, whether supplementation of long-chain ω-3 PUFA (i.e. fish oil) is associated with fracture risk, and whether the association is modified by genetic predisposition to fracture risk remain unclear.

Objectives: To evaluate the associations of habitual fish oil supplement use with fracture risk, and to explore the potential effect modification by genetic predisposition.

Methods: This study included 492,713 participants from the UK Biobank who completed a questionnaire on habitual fish oil supplement use between 2006 and 2010. HRs and 95% CIs for fractures were estimated from multivariable Cox proportional hazards models. A weighted fracture-genetic risk score (GRS) was derived from 14 validated single nucleotide polymorphisms.

Results: During a median follow-up of 8.1 y, 12,070 incident fractures occurred among participants free of fracture at baseline (n = 441,756). Compared with nonuse, habitual use of fish oil supplements was associated with a lower risk of total fractures (HR = 0.93; 95% CI: 0.89, 0.97), hip fractures (HR = 0.83; 95% CI: 0.75, 0.92), and vertebrae fractures (HR = 0.85; 95% CI: 0.72, 0.99). The inverse association for total fractures was more pronounced among participants having a higher fracture-GRS than among those with a lower fracture-GRS (P-interaction <0.001). Among participants with a history of fracture at baseline (n = 50,957), fish oil use was associated with a lower risk of total recurrent fractures (HR = 0.88; 95% CI: 0.82, 0.96) and vertebrae recurrent fractures (HR = 0.64; 95% CI: 0.46, 0.88) but not with hip fracture recurrence.

Conclusions: Our findings suggest that habitual fish oil supplement use is associated with lower risks of both incident and recurrent fractures. The inverse associations of fish oil use with total fractures appeared to be more pronounced among individuals at higher genetic risk of fractures than those with lower genetic risk.
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http://dx.doi.org/10.1093/ajcn/nqab157DOI Listing
September 2021

Circulating Glycerolipids, Fatty Liver Index, and Incidence of Type 2 Diabetes: A Prospective Study Among Chinese.

J Clin Endocrinol Metab 2021 Jun;106(7):2010-2020

Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

Context: Few lipidomic studies have specifically investigated the association of circulating glycerolipids and type 2 diabetes (T2D) risk, especially among Asian populations. It remains unknown whether or to what degree fatty liver could explain the associations between glycerolipids and T2D.

Objective: We aimed to assess associations between plasma glycerolipids and incident T2D and to explore a potential role of liver fat accumulation in the associations.

Methods: This was a prospective cohort study with 6 years of follow-up. The study population included 1781 Chinese participants aged 50 to 70 years. The main outcome measure was incident T2D.

Results: At the 6-year resurvey, 463 participants had developed T2D. At the false discovery rate (FDR) of 5%, 43 of 104 glycerolipids were significantly associated with incident T2D risk after multivariate adjustment for conventional risk factors. After further controlling for glycated hemoglobin (HbA1c), 9 of the 43 glycerolipids remained significant, including 2 diacylglycerols (DAGs) (16:1/20:4, 18:2/20:5) and 7 triacylglycerols (TAGs) (46:1, 48:0, 48:1, 50:0, 50:1, 50:2, and 52:2), with relative risks (RRs) (95% CIs) ranging from 1.16 (1.05-1.27) to 1.23 (1.11-1.36) per SD increment of glycerolipids. However, additional adjustment for fatty liver index largely attenuated these findings (RR [95% CI] 0.88 [0.81 to 0.95] to 1.10 [1.01 to 1.21]). Mediation analyses suggested that the fatty liver index explained 12% to 28% of the glycerolipids-T2D associations (all P < 0.01).

Conclusion: Higher plasma levels of DAGs and TAGs were associated with increased incident T2D risk in this Chinese population, which might be partially explained by liver fat accumulation.
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http://dx.doi.org/10.1210/clinem/dgab165DOI Listing
June 2021

Dietary factors, gut microbiota, and serum trimethylamine-N-oxide associated with cardiovascular disease in the Hispanic Community Health Study/Study of Latinos.

Am J Clin Nutr 2021 06;113(6):1503-1514

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.

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.
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http://dx.doi.org/10.1093/ajcn/nqab001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168354PMC
June 2021

Large-scale association analyses identify host factors influencing human gut microbiome composition.

Nat Genet 2021 02 18;53(2):156-165. Epub 2021 Jan 18.

Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10 < P < 5 × 10) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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http://dx.doi.org/10.1038/s41588-020-00763-1DOI Listing
February 2021

Menopausal status and observed differences in the gut microbiome in women with and without HIV infection.

Menopause 2021 01 11;28(5):491-501. Epub 2021 Jan 11.

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.

Objective: Gut microbiota respond to host physiological phenomena, yet little is known regarding shifts in the gut microbiome due to menopausal hormonal and metabolic changes in women. HIV infection impacts menopause and may also cause gut dysbiosis. We therefore sought to determine the association between menopausal status and gut microbiome composition in women with and without HIV.

Methods: Gut microbiome composition was assessed in stool from 432 women (99 premenopausal HIV+, 71 premenopausal HIV-, 182 postmenopausal HIV+, 80 postmenopausal HIV-) via 16S rRNA gene sequencing. We examined cross-sectional associations of menopause with gut microbiota overall diversity and composition, and taxon and inferred metagenomic pathway abundance. Models were stratified by HIV serostatus and adjusted for age, HIV-related variables, and other potential confounders.

Results: Menopause, ie post- versus premenopausal status, was associated with overall microbial composition only in women with HIV (permutational MANOVA of Jensen Shannon Divergence: P = 0.01). In women with HIV, menopause was associated with enrichment of gram-negative order Enterobacteriales, depletion of highly abundant taxa within Prevotella copri, and alterations in other low-abundance taxa. Additionally, menopause in women with HIV was associated with enrichment of metagenomic pathways related to Enterobacteriales, including degradation of amino acids and phenolic compounds, biosynthesis of enterobactin, and energy metabolism pathways. Menopause-related differences in some low-abundance taxa were also observed in women without HIV.

Conclusions: A changing gut microbiome may be an overlooked phenomenon of reproductive aging in women with HIV. Longitudinal assessments across all reproductive stages are necessary to confirm these findings and identify health implications.
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http://dx.doi.org/10.1097/GME.0000000000001730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068580PMC
January 2021

Association of liver enzymes with incident diabetes in US Hispanic/Latino adults.

Diabet Med 2021 Aug 28;38(8):e14522. Epub 2021 Jan 28.

Albert Einstein College of Medicine, Bronx, NY, USA.

Introduction: Non-alcoholic fatty liver disease (NAFLD) has been associated with increased risk of incident diabetes. But such evidence is lacking in the Hispanic/Latino population, which has high prevalence of obesity and NAFLD.

Methods: We conducted a prospective cohort study of 6,928 adults of Hispanic/Latino background who had no diabetes, did not report excessive alcohol use, and no hepatitis B and C infection at baseline (2008-2011). We estimated risk ratios (RR) for incident diabetes, identified from visit 2 examination by glucose measurements or antidiabetic medication use, with baseline liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT)).

Results: A total of 738 adults developed diabetes during 6 years of follow-up. After adjusting for participant characteristics at baseline, versus the lowest quartile, highest quartiles of ALT and GGT were associated with risks for incident diabetes (RR for ALT: 1.51 [95% CI 1.03-2.22], p-trend = 0.006; RR for GGT: 2.39 [1.60-3.55], p-trend = 0.001). Higher GGT levels predicted increased risk of incident diabetes even among those with ALT or AST below the median levels. The associations of ALT and GGT with incident diabetes were similar among most Hispanic background but were not seen among Dominicans (p for interaction <0.05). The association of AST with incident diabetes was found only among light-to-moderate alcohol drinkers (RR = 1.50 [1.20-1.86]) but not abstainers (RR = 0.91 [0.69-1.20], p for interaction = 0.006).

Conclusion: Higher ALT and GGT levels are associated with increased risk of developing diabetes among Latinos. Liver enzyme tests might aid in diabetes prevention by identifying high-risk individuals.
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http://dx.doi.org/10.1111/dme.14522DOI Listing
August 2021

Association of Oily and Nonoily Fish Consumption and Fish Oil Supplements With Incident Type 2 Diabetes: A Large Population-Based Prospective Study.

Diabetes Care 2021 03 11;44(3):672-680. Epub 2021 Jan 11.

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY

Objective: To evaluate associations of oily and nonoily fish consumption and fish oil supplements with incident type 2 diabetes (T2D).

Research Design And Methods: We included 392,287 middle-aged and older participants (55.0% women) in the UK Biobank who were free of diabetes, major cardiovascular disease, and cancer and had information on habitual intake of major food groups and use of fish oil supplements at baseline (2006-2010). Of these, 163,706 participated in one to five rounds of 24-h dietary recalls during 2009-2012.

Results: During a median 10.1 years of follow-up, 7,262 incident cases of T2D were identified. Compared with participants who reported never consumption of oily fish, the multivariable-adjusted hazard ratios of T2D were 0.84 (95% CI 0.78-0.91), 0.78 (0.72-0.85), and 0.78 (0.71-0.86) for those who reported <1 serving/week, weekly, and ≥2 servings/week of oily fish consumption, respectively (-trend < 0.001). Consumption of nonoily fish was not associated with risk of T2D (-trend = 0.45). Participants who reported regular fish oil use at baseline had a 9% (95% CI 4-14%) lower risk of T2D compared with nonusers. Baseline regular users of fish oil who also reported fish oil use during at least one of the 24-h dietary recalls had an 18% (8-27%) lower risk of T2D compared with constant nonusers.

Conclusions: Our findings suggest that consumption of oily fish but not nonoily fish was associated with a lower risk of T2D. Use of fish oil supplements, especially constant use over time, was also associated with a lower risk of T2D.
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http://dx.doi.org/10.2337/dc20-2328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896269PMC
March 2021

Plasma Lipidomic Profiles and Risk of Diabetes: 2 Prospective Cohorts of HIV-Infected and HIV-Uninfected Individuals.

J Clin Endocrinol Metab 2021 03;106(4):999-1010

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.

Objectives: Antiretroviral therapy (ART) use is associated with disrupted lipid and glucose metabolism in people with HIV infection. We aimed to identify plasma lipid species associated with risk of diabetes in the context of HIV infection.

Research Design And Methods: We profiled 211 plasma lipid species in 491 HIV-infected and 203 HIV-uninfected participants aged 35 to 55 years from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Cox proportional hazards model was used to examine associations between baseline lipid species and incident diabetes (166 diabetes cases were identified during a median follow-up of 12.6 years).

Results: We identified 11 lipid species, representing independent signals for 8 lipid classes/subclasses, associated with risk of diabetes (P < 0.05 after FDR correction). After adjustment for multiple covariates, cholesteryl ester (CE) (22:4), lysophosphatidylcholine (LPC) (18:2), phosphatidylcholine (PC) (36:4), phosphatidylcholine plasmalogen (34:3), and phosphatidylethanolamine (PE) (38:2) were associated with decreased risk of diabetes (HRs = 0.70 to 0.82 per SD increment), while diacylglycerol (32:0), LPC (14:0), PC (38:3), PE (36:1), and triacylglycerol (50:1) were associated with increased risk of diabetes (HRs = 1.26 to 1.56 per SD increment). HIV serostatus did not modify any lipid-diabetes associations; however, most of these lipid species were positively associated with HIV and/or ART use, including 3 diabetes-decreased ( CE [22:4], LPC [18:2], PE [38:2]) and all 5 diabetes-increased lipid species.

Conclusions: This study identified multiple plasma lipid species associated with incident diabetes. Regardless of the directions of their associations with diabetes, most diabetes-associated lipid species were elevated in ART-treated people with HIV infection. This suggests a complex role of lipids in the link between ART and diabetes in HIV infection.
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http://dx.doi.org/10.1210/clinem/dgab011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993589PMC
March 2021

Dietary cholesterol and egg intake in relation to incident cardiovascular disease and all-cause and cause-specific mortality in postmenopausal women.

Am J Clin Nutr 2021 04;113(4):948-959

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.

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.
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http://dx.doi.org/10.1093/ajcn/nqaa353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023834PMC
April 2021

Associations among circulating sphingolipids, β-cell function, and risk of developing type 2 diabetes: A population-based cohort study in China.

PLoS Med 2020 12 9;17(12):e1003451. Epub 2020 Dec 9.

Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, China.

Background: Animal studies suggest vital roles of sphingolipids, especially ceramides, in the pathogenesis of type 2 diabetes (T2D) via pathways involved in insulin resistance, β-cell dysfunction, and inflammation, but human studies are limited. We aimed to evaluate the associations of circulating sphingolipids with incident T2D and to explore underlying mechanisms.

Methods And Findings: The current study included 826 men and 1,148 women who were aged 50-70 years, from Beijing and Shanghai, and without T2D in 2005 and who were resurveyed in 2011. Cardiometabolic traits were measured at baseline and follow-up surveys. A total of 76 sphingolipids were quantified using high-coverage targeted lipidomics. Summary data for 2-sample Mendelian randomization were obtained from genome-wide association studies of circulating sphingolipids and the China Health and Nutrition Survey (n = 5,731). During the 6-year period, 529 participants developed T2D. Eleven novel and 3 reported sphingolipids, namely ceramides (d18:1/18:1, d18:1/20:0, d18:1/20:1, d18:1/22:1), saturated sphingomyelins (C34:0, C36:0, C38:0, C40:0), unsaturated sphingomyelins (C34:1, C36:1, C42:3), hydroxyl-sphingomyelins (C34:1, C38:3), and a hexosylceramide (d18:1/20:1), were positively associated with incident T2D (relative risks [RRs]: 1.14-1.21; all P < 0.001), after multivariate adjustment including lifestyle characteristics and BMI. Network analysis further identified 5 modules, and 2 modules containing saturated sphingomyelins showed the strongest associations with increased T2D risk (RRQ4 versus Q1 = 1.59 and 1.43; both Ptrend < 0.001). Mediation analysis suggested that the detrimental associations of 13 sphingolipids with T2D were largely mediated through β-cell dysfunction, as indicated by HOMA-B (mediation proportion: 11.19%-42.42%; all P < 0.001). Moreover, Mendelian randomization evidenced a positive association between a genetically instrumented ceramide (d18:1/20:1) and T2D (odds ratio: 1.15 [95% CI 1.05-1.26]; P = 0.002). Main limitations in the current study included potential undiagnosed cases and lack of an independent population for replication.

Conclusions: In this study, we observed that a panel of novel sphingolipids with unique structures were positively associated with incident T2D, largely mediated through β-cell dysfunction, in Chinese individuals.
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http://dx.doi.org/10.1371/journal.pmed.1003451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725305PMC
December 2020

Food Insecurity and T-cell Dysregulation in Women Living With Human Immunodeficiency Virus on Antiretroviral Therapy.

Clin Infect Dis 2021 03;72(5):e112-e119

Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, San Francisco, California, USA.

Background: Food insecurity is associated with increased morbidity and mortality in people with human immunodeficiency virus (HIV) on antiretroviral therapy, but its relationship with immune dysregulation, a hallmark of HIV infection and comorbidity, is unknown.

Methods: In 241 women participating in the Women's Interagency HIV Study, peripheral blood mononuclear cells were characterized by flow cytometry to identify cell subsets, comprising surface markers of activation (%CD38+HLADR+), senescence (%CD57+CD28-), exhaustion (%PD-1+), and co-stimulation (%CD57- CD28+) on CD4+ and CD8+ T cells. Mixed-effects linear regression models were used to assess the relationships of food insecurity with immune outcomes, accounting for repeated measures at ≤3 study visits and adjusting for sociodemographic and clinical factors.

Results: At the baseline study visit, 71% of participants identified as non-Hispanic Black, 75% were virally suppressed, and 43% experienced food insecurity. Food insecurity was associated with increased activation of CD4+ and CD8+ T cells, increased senescence of CD8+ T cells, and decreased co-stimulation of CD4+ and CD8+ T cells (all P < .05), adjusting for age, race/ethnicity, income, education, substance use, smoking, HIV viral load, and CD4 count. In stratified analyses, the association of food insecurity with CD4+ T-cell activation was more pronounced in women with uncontrolled HIV (viral load >40 copies/mL and CD4 <500 cells/mm3) but remained statistically significant in those with controlled HIV.

Conclusions: Food insecurity may contribute to the persistent immune activation and senescence in women with HIV on antiretroviral therapy, independently of HIV control. Reducing food insecurity may be important for decreasing non-AIDS-related disease risk in this population.
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http://dx.doi.org/10.1093/cid/ciaa1771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935377PMC
March 2021

The Assessment of Different Diets and Mortality Fails to Address Unmeasured Confounding-Reply.

JAMA Intern Med 2021 Jan;181(1):138-139

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamainternmed.2020.1388DOI Listing
January 2021

A Genome-wide Association Study Discovers 46 Loci of the Human Metabolome in the Hispanic Community Health Study/Study of Latinos.

Am J Hum Genet 2020 11 7;107(5):849-863. Epub 2020 Oct 7.

Human Genetics Center, University of Texas Health Science Center, Houston, TX 77030, USA. Electronic address:

Variation in levels of the human metabolome reflect changes in homeostasis, providing a window into health and disease. The genetic impact on circulating metabolites in Hispanics, a population with high cardiometabolic disease burden, is largely unknown. We conducted genome-wide association analyses on 640 circulating metabolites in 3,926 Hispanic Community Health Study/Study of Latinos participants. The estimated heritability for 640 metabolites ranged between 0%-54% with a median at 2.5%. We discovered 46 variant-metabolite pairs (p value < 1.2 × 10, minor allele frequency ≥ 1%, proportion of variance explained [PEV] mean = 3.4%, PEV = 1%-22%) with generalized effects in two population-based studies and confirmed 301 known locus-metabolite associations. Half of the identified variants with generalized effect were located in genes, including five nonsynonymous variants. We identified co-localization with the expression quantitative trait loci at 105 discovered and 151 known loci-metabolites sets. rs5855544, upstream of SLC51A, was associated with higher levels of three steroid sulfates and co-localized with expression levels of SLC51A in several tissues. Mendelian randomization (MR) analysis identified several metabolites associated with coronary heart disease (CHD) and type 2 diabetes. For example, two variants located in or near CYP4F2 (rs2108622 and rs79400241, respectively), involved in vitamin E metabolism, were associated with the levels of octadecanedioate and vitamin E metabolites (gamma-CEHC and gamma-CEHC glucuronide); MR analysis showed that genetically high levels of these metabolites were associated with lower odds of CHD. Our findings document the genetic architecture of circulating metabolites in an underrepresented Hispanic/Latino community, shedding light on disease etiology.
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http://dx.doi.org/10.1016/j.ajhg.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675000PMC
November 2020

Modeling daily and weekly moderate and vigorous physical activity using zero-inflated mixture Poisson distribution.

Stat Med 2020 12 18;39(30):4687-4703. Epub 2020 Sep 18.

Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.

Recently developed accelerometer devices have been used in large epidemiological studies for continuous and objective monitoring of physical activities. Typically, physical movements are summarized as minutes in light, moderate, and vigorous physical activities in each wearing day. Because of preponderance of zeros, zero-inflated distributions have been used for modeling the daily moderate or higher levels of physical activity. Yet, these models do not fully account for variations in daily physical activity and cannot be extended to model weekly physical activity explicitly, while the weekly physical activity is considered as an indicator for a subject's average level of physical activity. To overcome these limitations, we propose to use a zero-inflated Poisson mixture distribution that can model daily and weekly physical activity in same family of mixture distributions. Under this method, the likelihood of an inactive day and the amount of exercise in an active day are simultaneously modeled by a joint random effects model to incorporate heterogeneity across participants. If needed, the method has the flexibility to include an additional random effect to address extra variations in daily physical activity. Maximum likelihood estimation can be obtained through Gaussian quadrature technique, which is implemented conveniently in an R package GLMMadaptive. Method performances are examined using simulation studies. The method is applied to data from the Hispanic Community Health Study/Study of Latinos to examine the relationship between physical activity and BMI groups and within a participant the difference in physical activity between weekends and weekdays.
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http://dx.doi.org/10.1002/sim.8748DOI Listing
December 2020

Are sedentary behavior and physical activity independently associated with cardiometabolic benefits? The Hispanic Community Health Study/Study of Latinos.

BMC Public Health 2020 Sep 14;20(1):1400. Epub 2020 Sep 14.

Department of Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Belfer Bldg, 1312C, Bronx, New York, 10461, USA.

Background: Whether physical activity can reduce cardiometabolic risk particularly in understudied populations such as US Hispanics/Latinos is of public health interest. We prospectively examined the association of physical activity and cardiometabolic biomarkers in n = 8049 participants of the Hispanic Community Health Study/Study of Latinos, a community-based cohort study of 16,415 adults aged 18-74 yr who self-identified as Hispanic/Latino from four US urban centers.

Methods: We assessed physical activity using accelerometry in 2008-2011 at visit 1. We assessed cardiometabolic biomarkers twice: once at visit 1 and collected a second measure in 2014-2017 at visit 2. We used survey linear regression models with changes in cardiometabolic markers as the dependent variables and quartiles of sedentary behavior or whether adults met guidelines for moderate-to-vigorous physical activity as the independent variables.

Results: In normoglycemic adults without cardiovascular disease, but not in adults with evidence of cardiometabolic disease, those who were in the lowest quartile for sedentary behavior (< 10.08 h/day) had a significant decline in mean LDL-cholesterol of - 3.94 mg/dL (95% CI: - 6.37, - 1.52) compared to adults in the highest quartile (≥13.0 h/day) who exhibited a significant increase in LDL-cholesterol of 0.14 mg/dL (95% CI, - 2.15,2.42) over the six year period (P < 0.02 in fully adjusted models.) There was also a trend toward lower mean increase in HbA1c comparing the lowest with the highest quartile of sedentary behavior. Overall regardless of glycemic level or evidence of cardiometabolic disease, adults who met guidelines for moderate-to-vigorous physical activity at visit 1, had significantly lower mean increases in level of fasting glucose compared to adults not meeting guidelines in fully adjusted models.

Conclusions: In this cohort of Hispanics/Latinos, being free of cardiometabolic disease and having low levels of sedentary behavior were associated with health benefits. Among all adults regardless of cardiometabolic disease, meeting guidelines for moderate-to-vigorous physical activity was associated with health benefits. Overall these data suggest that an active lifestyle may blunt the association of advancing age with worsening cardiometabolic risk factors.
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http://dx.doi.org/10.1186/s12889-020-09497-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490882PMC
September 2020

Accelerometer-assessed physical activity and incident diabetes in a population covering the adult life span: the Hispanic Community Health Study/Study of Latinos.

Am J Clin Nutr 2020 11;112(5):1318-1327

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.

Background: The association between accelerometer-assessed physical activity and risk of diabetes remains unclear, especially among US Hispanic/Latino adults who have lower levels of physical activity and a higher diabetes burden compared with other racial/ethnical populations in the country.

Objectives: To examine the association between accelerometer-assessed physical activity and incident diabetes in a US Hispanic/Latino population.

Methods: We included 7280 participants of the Hispanic Community Health Study/Study of Latinos who aged 18-74 y and free of diabetes at baseline. Data on moderate-to-vigorous physical activity (MVPA) were collected using a 7-d accelerometer measurement. Incident diabetes was assessed after a mean ± SD of 6.0 ± 0.8 y using standard procedures including blood tests. RRs and 95% CIs of diabetes associated with MVPA were estimated using survey Poisson regressions. The associations of MVPA with 6-y changes in adiposity measures were also examined.

Results: A total of 871 incident cases of diabetes were identified. MVPA was inversely and nonlinearly associated with risk of diabetes (P-nonlinearity = 0.006), with benefits accruing rapidly at the lower end of MVPA range (<30 min/d) and leveling off thereafter. The association differed by population age (P-interaction = 0.006). Higher MVPA was associated with lower risk of diabetes among individuals older than 50 y (RRQ4 versus Q1 = 0.50; 95% CI: 0.35, 0.73; P-trend < 0.001) but not among younger individuals (RRQ4 versus Q1 = 0.98; 95% CI: 0.66, 1.47; P-trend = 0.92). An inverse association between MVPA and 6-y gain in waist circumference was also limited to the older group (P-interaction with age < 0.001).

Conclusions: Among US Hispanic/Latino adults, baseline accelerometer-derived MVPA was inversely associated with incident diabetes only among individuals aged 50 y and older. Further studies are needed to confirm our findings and to clarify potential mechanisms underlying the possible age differences in the MVPA-diabetes association. This study was registered at clinicaltrials.gov as NCT02060344.
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http://dx.doi.org/10.1093/ajcn/nqaa232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657343PMC
November 2020

Underuse of Cardiovascular Medications in Individuals With Known Lower Extremity Peripheral Artery Disease: HCHS/SOL.

J Am Heart Assoc 2020 08 5;9(16):e015451. Epub 2020 Aug 5.

Department of Epidemiology and Population Health Albert Einstein College of Medicine Bronx NY.

Background Underuse of cardiovascular medications for secondary prevention among individuals with peripheral artery disease (PAD) has been reported. Little is known about PAD treatment status in the Hispanic/Latino population in the United States, who may have limited access to health care and who have worse clinical outcomes than non-Hispanic individuals. Methods and Results We studied the use of cardiovascular therapies in 1244 Hispanic/Latino individuals recruited from 4 sites in the United States, including 826 individuals who reported diagnosis of PAD by physician and 418 individuals with coronary artery disease alone, in the Hispanic Community Health Study/Study of Latinos. We compared the prevalence of using antiplatelet therapy, lipid-lowering therapy and antihypertensive therapy by PAD and coronary artery disease status. Among those with PAD, we studied factors associated with taking cardiovascular medications, including demographic and socioeconomic factors, acculturation, access to health care and comorbidities, using multivariable regression models. The overall prevalence for individuals with PAD taking antiplatelet therapy, lipid-lowering therapy and, among hypertensive individuals, antihypertensive therapy was 31%, 26% and 57%, respectively. Individuals of Mexican background had the lowest use for all classes of cardiovascular medications. Older age, number of doctor visits and existing hypertension and diabetes mellitus were significantly associated with taking cardiovascular therapies in adjusted models. Compared with those with PAD alone, individuals with PAD and concurrent coronary artery disease were 1.52 (95% CI, 1.20-1.93) and 1.74 (1.30-2.32) times more likely to use antiplatelet agents and statins according to multivariable analysis. No significant difference of antihypertensive medication use was found among PAD patients with or without coronary artery disease. Conclusions Hispanic/Latino individuals with known PAD underuse cardiovascular medications recommended in clinical guidelines. More efforts should be directed to improve treatment in this important group.
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http://dx.doi.org/10.1161/JAHA.119.015451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660818PMC
August 2020

Classical monocyte transcriptomes reveal significant anti-inflammatory statin effect in women with chronic HIV.

Cardiovasc Res 2021 03;117(4):1166-1177

Laboratory of Inflammation Biology, La Jolla Institute for Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.

Aims: During virally suppressed chronic HIV infection, persistent inflammation contributes to the development of cardiovascular disease (CVD), a major comorbidity in people living with HIV (LWH). Classical blood monocytes (CMs) remain activated during antiretroviral therapy and are a major source of pro-inflammatory and pro-thrombotic factors that contribute to atherosclerotic plaque development and instability.

Methods And Results: Here, we identify transcriptomic changes in circulating CMs in peripheral blood mononuclear cell samples from participants of the Women's Interagency HIV Study, selected by HIV and subclinical CVD (sCVD) status. We flow-sorted CM from participants of the Women's Interagency HIV Study and deep-sequenced their mRNA (n = 92). CMs of HIV+ participants showed elevated interleukin (IL)-6, IL-1β, and IL-12β, overlapping with many transcripts identified in sCVD+ participants. In sCVD+ participants LWH, those reporting statin use showed reduced pro-inflammatory gene expression to a level comparable with healthy (HIV-sCVD-) participants. Statin non-users maintained an elevated inflammatory profile and increased cytokine production.

Conclusion: Statin therapy has been associated with a lower risk of cardiac events, such as myocardial infarction in the general population, but not in those LWH. Our data suggest that women LWH may benefit from statin therapy even in the absence of overt CVD.
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http://dx.doi.org/10.1093/cvr/cvaa188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983000PMC
March 2021

Association Between Healthy Eating Patterns and Risk of Cardiovascular Disease.

JAMA Intern Med 2020 08;180(8):1090-1100

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Importance: The 2015-2020 Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with long-term risk of cardiovascular disease (CVD).

Objective: To examine the associations of dietary scores for 4 healthy eating patterns with risk of incident CVD.

Design, Setting, And Participants: Prospective cohort study of initially healthy women from the Nurses' Health Study (NHS) (1984-2016) and the NHS II (1991-2017) and men from the Health Professionals Follow-up Study (HPFS) (1986-2012). The dates of analysis were July 25 to December 4, 2019.

Exposures: Healthy Eating Index-2015 (HEI-2015), Alternate Mediterranean Diet Score (AMED), Healthful Plant-Based Diet Index (HPDI), and Alternate Healthy Eating Index (AHEI).

Main Outcomes And Measures: Cardiovascular disease events, including fatal and nonfatal coronary heart disease (CHD) and stroke.

Results: The final study sample included 74 930 women in the NHS (mean [SD] baseline age, 50.2 [7.2] years), 90 864 women in the NHS II (mean [SD] baseline age, 36.1 [4.7] years), and 43 339 men in the HPFS (mean [SD] baseline age, 53.2 [9.6] years). During a total of 5 257 190 person-years of follow-up, 23 366 incident CVD cases were documented (18 092 CHD and 5687 stroke) (some individuals were diagnosed as having both CHD and stroke). Comparing the highest with the lowest quintiles, the pooled multivariable-adjusted hazard ratios (HRs) of CVD were 0.83 (95% CI, 0.79-0.86) for the HEI-2015, 0.83 (95% CI, 0.79-0.86) for the AMED, 0.86 (95% CI, 0.82-0.89) for the HPDI, and 0.79 (95% CI, 0.75-0.82) for the AHEI (P for trend <.001 for all). In addition, a 25-percentile higher dietary score was associated with 10% to 20% lower risk of CVD (pooled HR, 0.80 [95% CI, 0.77-0.83] for the HEI-2015; 0.90 [95% CI, 0.87-0.92] for the AMED; 0.86 [95% CI, 0.82-0.89] for the HPDI; and 0.81 [95% CI, 0.78-0.84] for the AHEI). These dietary scores were statistically significantly associated with lower risk of both CHD and stroke. In analyses stratified by race/ethnicity and other potential risk factors for CVD, the inverse associations between these scores and risk of CVD were consistent in most subgroups.

Conclusions And Relevance: In 3 large prospective cohorts with up to 32 years of follow-up, greater adherence to various healthy eating patterns was consistently associated with lower risk of CVD. These findings support the recommendations of the 2015-2020 Dietary Guidelines for Americans that multiple healthy eating patterns can be adapted to individual food traditions and preferences.
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http://dx.doi.org/10.1001/jamainternmed.2020.2176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296454PMC
August 2020

Serum sphingolipids and incident diabetes in a US population with high diabetes burden: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Am J Clin Nutr 2020 07;112(1):57-65

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.

Background: Genetic or pharmacological inhibition of de novo sphingolipid synthases prevented diabetes in animal studies.

Objectives: We sought to evaluate prospective associations of serum sphingolipids with incident diabetes in a population-based cohort.

Methods: We included 2010 participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18-74 y who were free of diabetes and other major chronic diseases at baseline (2008-2011). Metabolomic profiling of fasting serum was performed using a global, untargeted approach. A total of 43 sphingolipids were quantified and, considering subclasses and chemical structures of individual species, 6 sphingolipid scores were constructed. Diabetes status was assessed using standard procedures including blood tests. Multivariable survey Poisson regressions were applied to estimate RR and 95% CI of incident diabetes associated with individual sphingolipids or sphingolipid scores.

Results: There were 224 incident cases of diabetes identified during, on average, 6 y of follow-up. After adjustment for socioeconomic and lifestyle factors, a ceramide score (RR Q4 versus Q1 = 2.40; 95% CI: 1.24, 4.65; P-trend = 0.003) and a score of sphingomyelins with fully saturated sphingoid-fatty acid pairs (RR Q4 versus Q1 = 3.15; 95% CI: 1.75, 5.67; P-trend <0.001) both were positively associated with risk of diabetes, whereas scores of glycosylceramides, lactosylceramides, or other unsaturated sphingomyelins (even if having an SFA base) were not associated with risk of diabetes. After additional adjustment for numerous traditional risk factors (especially triglycerides), both associations were attenuated and only the saturated-sphingomyelin score remained associated with risk of diabetes (RR Q4 versus Q1 = 1.98; 95% CI: 1.09, 3.59; P-trend = 0.031).

Conclusions: Our findings suggest that a cluster of saturated sphingomyelins may be associated with elevated risk of diabetes beyond traditional risk factors, which needs to be verified in other population studies. This study was registered at clinicaltrials.gov as NCT02060344.
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http://dx.doi.org/10.1093/ajcn/nqaa114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326587PMC
July 2020

Objectively measured sedentary time, physical activity and liver enzyme elevations in US Hispanics/Latinos.

Liver Int 2020 08 25;40(8):1883-1894. Epub 2020 May 25.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background & Aims: Sedentariness and physical inactiveness are associated with deleterious health outcomes, but their associations with liver enzyme elevations remain uncertain.

Methods: In 10 385 US Hispanics/Latinos from the Hispanic Community Health Study/Study of Latinos, we examined associations of sedentary time and moderate-to-vigorous physical activity (MVPA) measured by accelerometers with liver enzyme elevations. Elevated alanine aminotransferase (ALT), aspartate aminotransferase and γ-glutamyltransferase (GGT) were defined as the highest gender-specific deciles. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated using weighted Poisson regressions.

Results: After adjusting for demographical/socioeconomic factors and MVPA, increasing quartiles of sedentary time were associated with a higher prevalence of elevated ALT (PRs [95% CI] = 1.0, 1.17 [0.92-1.47], 1.21 [0.96, 1.53] and 1.51 [1.13-2.02]; P-trend = .007) and elevated GGT (PRs [95% CI] = 1.0, 1.06 [0.82-1.36], 1.35 [1.06-1.73] and 1.66 [1.27-2.16]; P-trend = .0001). These associations were attenuated but remained significant after further adjustment for cardiometabolic traits including body-mass index, waist-hip-ratio, lipids and homeostatic model assessment of insulin resistance. In contrast, increasing quartiles of MVPA were associated with a lower prevalence of elevated ALT (PRs [95% CI] =1.0, 0.97 [0.77-1.23], 0.84 [0.66-1.06] and 0.72 [0.54-0.96]; P-trend = .01) after adjusting for demographical/socioeconomic factors and sedentary time, but this association became non-significant after further adjustment for cardiometabolic traits. Notably, the association of sedentary time with GGT elevation was significant both in individuals meeting the US Physical Activity Guidelines for Americans (MVPA ≥150 minutes/week) and in those who did not (both P-trend ≤ .003).

Conclusions: Our findings suggest that objectively measured sedentary time is independently associated with elevated ALT and GGT in US Hispanics/Latinos.
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http://dx.doi.org/10.1111/liv.14514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609452PMC
August 2020

Sedentary time and peripheral artery disease: The Hispanic Community Health Study/Study of Latinos.

Am Heart J 2020 04 8;222:208-219. Epub 2020 Feb 8.

University of California San Diego, La Jolla, CA, USA.

Background: Experimental evidence suggests that sedentary time (ST) may contribute to cardiovascular disease by eliciting detrimental hemodynamic changes in the lower limbs. However, little is known about objectively measured ST and lower extremity peripheral artery disease (PAD).

Methods: We included 7,609 Hispanic/Latinos (ages 45-74) from the Hispanic Community Health Study/Study of Latinos. PAD was measured using the ankle brachial index (≤0.9). ST was measured using accelerometry. We used multivariable logistic regression to assess associations of quartiles of ST and PAD, and then used the same logistic models with restricted cubic splines to investigate continuous nonlinear associations of ST and PAD. Models were sequentially adjusted for traditional PAD risk factors, leg pain, and moderate- to vigorous-intensity physical activity (MVPA).

Results: Median ST was 12.2 h/d, and 5.4% of individuals had PAD. In fully adjusted restricted cubic splines models accounting for traditional PAD risk factors, leg pain, and MVPA, ST had a significant overall (P = .048) and nonlinear (P = .024) association with PAD. A threshold effect was seen such that time spent above median ST was associated with higher odds of PAD. That is, compared to median ST, 1, 2, and 3 hours above median ST were associated with a PAD odds ratio of 1.16 (95% CI = 1.02-1.31), 1.44 (1.06-1.94), and 1.80 (1.11-2.90), respectively.

Conclusions: Among Hispanic/Latino adults, ST was associated with higher odds of PAD, independent of leg pain, MVPA, and traditional PAD risk factors. Notably, we observed a threshold effect such that these associations were only observed at the highest levels of ST.
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http://dx.doi.org/10.1016/j.ahj.2020.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085461PMC
April 2020

Author Correction: Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity.

Genome Biol 2020 Feb 25;21(1):50. Epub 2020 Feb 25.

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.

Following publication of the original paper [1], an error was reported in the third paragraph in the section "Analysis of GMB composition and its correlates" (page 3 of the PDF). The first sentence of the text should refer to Table 2, but mistakenly refers to Table 1.
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http://dx.doi.org/10.1186/s13059-020-01970-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043042PMC
February 2020
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