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2. Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies.

Author

Brouwer, Ingeborg, De Faire, Ulf, Eiriksdottir, Gudny, Ferrucci, Luigi, Forouhi, Nita, Geleijnse, Johanna, Hodge, Allison, Kimura, Hitomi, Laakso, Markku, Risérus, Ulf, van Westing, Anniek, Bandinelli, Stefania, Baylin, Ana, Giles, Graham, Gudnason, Vilmundur, Iso, Hiroyasu, Lemaitre, Rozenn, Ninomiya, Toshiharu, Post, Wendy, Psaty, Bruce, Salonen, Jukka, Schulze, Matthias, Tsai, Michael, Uusitupa, Matti, Wareham, Nicholas, Oh, Seung-Won, Wood, Alexis, Harris, William, Siscovick, David, Mozaffarian, Dariush, Leander, Karin, Laguzzi, Federica, Åkesson, Agneta, Marklund, Matti, Qian, Frank, Gigante, Bruna, Bartz, Traci, Bassett, Julie, Birukov, Anna, Campos, Hannia, Hirakawa, Yoichiro, Imamura, Fumiaki, Jäger, Susanne, Lankinen, Maria, Murphy, Rachel, Senn, Mackenzie, Tanaka, Toshiko, Tintle, Nathan, Virtanen, Jyrki, Yamagishi, Kazumasa, and Allison, Matthew

Subjects
biomarkers, cardiovascular diseases, family medical history, polyunsaturated fatty acids, precision medicine, Animals, Fatty Acids, Omega-3, Cardiovascular Diseases, Risk Factors, Docosahexaenoic Acids, Biomarkers
Abstract

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium. METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction. RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions. CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.

Published
2024

3. The Science of Precision Prevention: Research Opportunities and Clinical Applications to Reduce Cardiovascular Health Disparities.

Author

Pearson, Thomas, Vitalis, Debbie, Pratt, Charlotte, Campo, Rebecca, Armoundas, Antonis, Au, David, Beech, Bettina, Brazhnik, Olga, Chute, Christopher, Davidson, Karina, Diez-Roux, Ana, Fine, Lawrence, Gabriel, Davera, Groenveld, Peter, Hall, Jaclyn, Hamilton, Alison, Hu, Hui, Ji, Heng, Kind, Amy, Kraus, William, Krumholz, Harlan, Mensah, George, Merchant, Raina, Mozaffarian, Dariush, Murray, David, Neumark-Sztainer, Dianne, Goff, David, and Petersen, Maya

Subjects
data science, health equity, health promotion, implementation science, personalized medicine, precision analytics
Abstract

Precision prevention embraces personalized prevention but includes broader factors such as social determinants of health to improve cardiovascular health. The quality, quantity, precision, and diversity of data relatable to individuals and communities continue to expand. New analytical methods can be applied to these data to create tools to attribute risk, which may allow a better understanding of cardiovascular health disparities. Interventions using these analytic tools should be evaluated to establish feasibility and efficacy for addressing cardiovascular disease disparities in diverse individuals and communities. Training in these approaches is important to create the next generation of scientists and practitioners in precision prevention. This state-of-the-art review is based on a workshop convened to identify current gaps in knowledge and methods used in precision prevention intervention research, discuss opportunities to expand trials of implementation science to close the health equity gaps, and expand the education and training of a diverse precision prevention workforce.

Published
2024

4. Plasma Trimethylamine‐N ‐Oxide and Incident Ischemic Stroke: The Cardiovascular Health Study and the Multi‐Ethnic Study of Atherosclerosis

Author

Lemaitre, Rozenn N, Jensen, Paul N, Wang, Zeneng, Fretts, Amanda M, Sitlani, Colleen M, Nemet, Ina, Sotoodehnia, Nona, de Oliveira Otto, Marcia C, Zhu, Weifei, Budoff, Matt, Longstreth, WT, Psaty, Bruce M, Siscovick, David S, Hazen, Stanley L, and Mozaffarian, Dariush

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Neurosciences, Brain Disorders, Cardiovascular, Atherosclerosis, Stroke, Aging, Cerebrovascular, Women's Health, Good Health and Well Being, Aged, Female, Humans, Ischemic Stroke, Methylamines, Oxides, Prospective Studies, Risk Factors, United States, TMAO, epidemiology, risk factors, stroke, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology
Abstract

Background The association of circulating trimethylamine-N-oxide (TMAO) with stroke has received limited attention. To address this gap, we examined the associations of serial measures of plasma TMAO with incident ischemic stroke. Methods and Results We used a prospective cohort design with data pooled from 2 cohorts. The settings were the CHS (Cardiovascular Health Study), a cohort of older adults, and the MESA (Multi-Ethnic Study of Atherosclerosis), both in the United States. We measured plasma concentrations of TMAO at baseline and again during the follow-up using high-performance liquid chromatography and mass spectrometry. We assessed the association of plasma TMAO with incident ischemic stroke using proportional hazards regression adjusted for risk factors. The combined cohorts included 11 785 participants without a history of stroke, on average 73 (CHS) and 62 (MESA) years old at baseline, including 60% (CHS) and 53% (MESA) women. We identified 1031 total incident ischemic strokes during a median 15-year follow-up in the combined cohorts. In multivariable analyses, TMAO was significantly associated with incident ischemic stroke risk (hazard ratios comparing a doubling of TMAO: 1.11 [1.03-1.18], P=0.004). The association was linear over the range of TMAO concentrations and appeared restricted to those without diagnosed coronary heart disease. An association with hemorrhagic stroke was not found. Conclusions Plasma TMAO levels are associated with incident ischemic stroke in a diverse population. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005133.

Published
2023

5. Trimethylamine N-oxide is associated with long-term mortality risk: the multi-ethnic study of atherosclerosis.

Author

Wang, Meng, Li, Xinmin, Wang, Zeneng, de Oliveira Otto, Marcia, Lemaitre, Rozenn, Fretts, Amanda, Sotoodehnia, Nona, Nemet, Ina, DiDonato, Joseph, Tang, Wai, Psaty, Bruce, Siscovick, David, Hazen, Stanley, Mozaffarian, Dariush, and Budoff, Matthew

Subjects
Cardiovascular disease, Microbiome, Mortality, Red meat, Trimethylamine N-oxide, Adult, Humans, Risk Factors, Biomarkers, Methylamines, Cardiovascular Diseases, Renal Insufficiency, Atherosclerosis, Neoplasms, Dementia
Abstract

AIMS: Little is known about associations of trimethylamine N-oxide (TMAO), a novel gut microbiota-generated metabolite of dietary phosphatidylcholine and carnitine, and its changes over time with all-cause and cause-specific mortality in the general population or in different race/ethnicity groups. The study aimed to investigate associations of serially measured plasma TMAO levels and changes in TMAO over time with all-cause and cause-specific mortality in a multi-ethnic community-based cohort. METHODS AND RESULTS: The study included 6,785 adults from the Multi-Ethnic Study of Atherosclerosis. TMAO was measured at baseline and year 5 using mass spectrometry. Primary outcomes were adjudicated all-cause mortality and cardiovascular disease (CVD) mortality. Secondary outcomes were deaths due to kidney failure, cancer, or dementia obtained from death certificates. Cox proportional hazards models with time-varying TMAO and covariates assessed the associations with adjustment for sociodemographics, lifestyles, diet, metabolic factors, and comorbidities. During a median follow-up of 16.9 years, 1704 participants died and 411 from CVD. Higher TMAO levels associated with higher risk of all-cause mortality [hazard ratio (HR): 1.12, 95% confidence interval (CI): 1.08-1.17], CVD mortality (HR: 1.09, 95% CI: 1.00-1.09), and death due to kidney failure (HR: 1.44, 95% CI: 1.25-1.66) per inter-quintile range, but not deaths due to cancer or dementia. Annualized changes in TMAO levels associated with higher risk of all-cause mortality (HR: 1.10, 95% CI: 1.05-1.14) and death due to kidney failure (HR: 1.54, 95% CI: 1.26-1.89) but not other deaths. CONCLUSION: Plasma TMAO levels were positively associated with mortality, especially deaths due to cardiovascular and renal disease, in a multi-ethnic US cohort.

Published
2023

6. The Gut Microbial Metabolite Trimethylamine N-oxide, Incident CKD, and Kidney Function Decline

Author

Wang, Meng, Tang, W.H. Wilson, Li, Xinmin S., de Oliveira Otto, Marcia C., Lee, Yujin, Lemaitre, Rozenn N., Fretts, Amanda, Nemet, Ina, Sotoodehnia, Nona, Sitlani, Colleen M., Budoff, Matthew, DiDonato, Joseph A., Wang, Zeneng, Bansal, Nisha, Shlipak, Michael G., Psaty, Bruce M., Siscovick, David S., Sarnak, Mark J., Mozaffarian, Dariush, and Hazen, Stanley L.

Published
2024
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8. Dietary Meat, Trimethylamine N-Oxide-Related Metabolites, and Incident Cardiovascular Disease Among Older Adults: The Cardiovascular Health Study.

Author

Wang, Meng, Wang, Zeneng, Lee, Yujin, Lai, Heidi, de Oliveira Otto, Marcia, Lemaitre, Rozenn, Fretts, Amanda, Sotoodehnia, Nona, DiDonato, Joseph, McKnight, Barbara, Tang, W, Psaty, Bruce, Siscovick, David, Hazen, Stanley, Mozaffarian, Dariush, and Budoff, Matthew

Subjects
cardiovascular diseases, microbiome, myocardial infarction, red meat, stroke, trimethylamine N-oxide, Animals, Atherosclerosis, Cardiovascular Diseases, Carnitine, Humans, Meat, Methylamines, Risk Factors
Abstract

BACKGROUND: Effects of animal source foods (ASF) on atherosclerotic cardiovascular disease (ASCVD) and underlying mechanisms remain controversial. We investigated prospective associations of different ASF with incident ASCVD and potential mediation by gut microbiota-generated trimethylamine N-oxide, its L-carnitine-derived intermediates γ-butyrobetaine and crotonobetaine, and traditional ASCVD risk pathways. METHODS: Among 3931 participants from a community-based US cohort aged 65+ years, ASF intakes and trimethylamine N-oxide-related metabolites were measured serially over time. Incident ASCVD (myocardial infarction, fatal coronary heart disease, stroke, other atherosclerotic death) was adjudicated over 12.5 years median follow-up. Cox proportional hazards models with time-varying exposures and covariates examined ASF-ASCVD associations; and additive hazard models, mediation proportions by different risk pathways. RESULTS: After multivariable-adjustment, higher intakes of unprocessed red meat, total meat, and total ASF associated with higher ASCVD risk, with hazard ratios (95% CI) per interquintile range of 1.15 (1.01-1.30), 1.22 (1.07-1.39), and 1.18 (1.03-1.34), respectively. Trimethylamine N-oxide-related metabolites together significantly mediated these associations, with mediation proportions (95% CI) of 10.6% (1.0-114.5), 7.8% (1.0-32.7), and 9.2% (2.2-44.5), respectively. Processed meat intake associated with a nonsignificant trend toward higher ASCVD (1.11 [0.98-1.25]); intakes of fish, poultry, and eggs were not significantly associated. Among other risk pathways, blood glucose, insulin, and C-reactive protein, but not blood pressure or blood cholesterol, each significantly mediated the total meat-ASCVD association. CONCLUSIONS: In this large, community-based cohort, higher meat intake associated with incident ASCVD, partly mediated by microbiota-derived metabolites of L-carnitine, abundant in red meat. These novel findings support biochemical links between dietary meat, gut microbiome pathways, and ASCVD.

Published
2022

9. Trimethylamine N-oxide and hip fracture and bone mineral density in older adults: The cardiovascular health study.

Author

Elam, Rachel, Bůžková, Petra, Barzilay, Joshua, Wang, Zeneng, Nemet, Ina, Budoff, Matthew, Cauley, Jane, Fink, Howard, Lee, Yujin, Robbins, John, Wang, Meng, Hazen, Stanley, Mozaffarian, Dariush, and Carbone, Laura

Subjects
Animal food, Bone mineral density, Gut microbiome, Hip fracture, Osteoporosis, Trimethylamine N-oxide, Absorptiometry, Photon, Aged, Bone Density, Female, Hip Fractures, Humans, Male, Methylamines, Risk Factors
Abstract

CONTEXT: Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) may adversely affect bone by inducing oxidative stress. Whether this translates into increased fracture risk in older adults is uncertain. OBJECTIVE: Determine the associations of plasma TMAO with hip fracture and bone mineral density (BMD) in older adults. DESIGN AND SETTING: Cox hazard models and linear regression stratified by sex examined the associations of TMAO with hip fracture and BMD in the longitudinal cohort of the Cardiovascular Health Study. PARTICIPANTS: 5019 U.S. adults aged ≥65 years. EXPOSURE: Plasma TMAO. MAIN OUTCOME MEASURES: Incident hip fractures; total hip BMD dual x-ray absorptiometry in a subset (n = 1400). RESULTS: Six hundred sixty-six incident hip fractures occurred during up to 26 years of follow-up (67,574 person-years). After multivariable adjustment, TMAO was not significantly associated with hip fracture (women: hazard ratio (HR) [95% confidence interval (CI)] of 1.00[0.92,1.09] per TMAO doubling; men: 1.12[0.95,1.33]). TMAO was also not associated with total hip BMD (women: BMD difference [95% CI] of 0.42 g/cm2*100 [-0.34,1.17] per TMAO doubling; men: 0.19[-1.04,1.42]). In exploratory analyses, we found an interaction between body mass index (BMI) and the association of TMAO with hip fracture (P

Published
2022

11. Food, nutrition, and autism: from soil to fork

Author

Maitin-Shepard, Melissa, O’Tierney-Ginn, Perrie, Kraneveld, Aletta D, Lyall, Kristen, Fallin, Daniele, Arora, Manish, Fasano, Alessio, Mueller, Noel T, Wang, Xiaobin, Caulfield, Laura E, Dickerson, Aisha S, Diaz Heijtz, Rochellys, Tarui, Tomo, Blumberg, Jeffrey B, Holingue, Calliope, Schmidt, Rebecca J, Garssen, Johan, Almendinger, Katherine, Lin, Pi-I Debby, and Mozaffarian, Dariush

Published
2024
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14. Genome-wide association studies and fine-mapping identify genomic loci for n-3 and n-6 polyunsaturated fatty acids in Hispanic American and African American cohorts

Author

Yang, Chaojie, Veenstra, Jenna, Bartz, Traci M., Pahl, Matthew C., Hallmark, Brian, Chen, Yii-Der Ida, Westra, Jason, Steffen, Lyn M., Brown, Christopher D., Siscovick, David, Tsai, Michael Y., Wood, Alexis C., Rich, Stephen S., Smith, Caren E., O’Connor, Timothy D., Mozaffarian, Dariush, Grant, Struan F. A., Chilton, Floyd H., Tintle, Nathan L., Lemaitre, Rozenn N., and Manichaikul, Ani

Published
2023
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16. Trans Fatty Acid Biomarkers and Incident Type 2 Diabetes: Pooled Analysis of 12 Prospective Cohort Studies in the Fatty Acids and Outcomes Research Consortium (FORCE).

Author

Lai, Heidi TM, Imamura, Fumiaki, Korat, Andres V Ardisson, Murphy, Rachel A, Tintle, Nathan, Bassett, Julie K, Chen, Jiaying, Kröger, Janine, Chien, Kuo-Liong, Senn, Mackenzie, Wood, Alexis C, Forouhi, Nita G, Schulze, Matthias B, Harris, William S, Vasan, Ramachandran S, Hu, Frank, Giles, Graham G, Hodge, Allison, Djousse, Luc, Brouwer, Ingeborg A, Qian, Frank, Sun, Qi, Wu, Jason HY, Marklund, Matti, Lemaitre, Rozenn N, Siscovick, David S, Fretts, Amanda M, Shadyab, Aladdin H, Manson, JoAnn E, Howard, Barbara V, Robinson, Jennifer G, Wallace, Robert B, Wareham, Nick J, Chen, Yii-Der Ida, Rotter, Jerome I, Tsai, Michael Y, Micha, Renata, and Mozaffarian, Dariush

Subjects
Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Diabetes, Clinical Research, Metabolic and endocrine, Adolescent, Adult, Biomarkers, Cohort Studies, Diabetes Mellitus, Type 2, Fatty Acids, Humans, Outcome Assessment, Health Care, Prospective Studies, Risk Factors, Trans Fatty Acids, Fatty Acids and Outcomes Research Consortium, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences, Health sciences
Abstract

ObjectiveTrans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis.Research design and methodsWe included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged ≥18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics.ResultsDuring a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94-1.25); cis/trans-18:2, 0.89 (0.73-1.07); and trans/cis-18:2, 0.87 (0.73-1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67-0.99], 0.86 [0.75-0.99], and 0.84 [0.74-0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P ≥ 0.1).ConclusionsCirculating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels.

Published
2022

17. PUFA ω-3 and ω-6 biomarkers and sleep: a pooled analysis of cohort studies on behalf of the Fatty Acids and Outcomes Research Consortium (FORCE)

Author

Murphy, Rachel A, Tintle, Nathan, Harris, William S, Darvishian, Maryam, Marklund, Matti, Virtanen, Jyrki K, Hantunen, Sari, de Mello, Vanessa D, Tuomilehto, Jaakko, Lindström, Jaana, Bolt, Matthew A, Brouwer, Ingeborg A, Wood, Alexis C, Senn, Mackenzie, Redline, Susan, Tsai, Michael Y, Gudnason, Vilmundur, Eiriksdottir, Gudny, Lindberg, Eva, Shadyab, Aladdin H, Liu, Buyun, Carnethon, Mercedes, Uusitupa, Matti, Djousse, Luc, Risérus, Ulf, Lind, Lars, van Dam, Rob M, Koh, Woon-Puay, Shi, Peilin, Siscovick, David, Lemaitre, Rozenn N, and Mozaffarian, Dariush

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Nutrition, Clinical Research, Sleep Research, Good Health and Well Being, Biomarkers, Cohort Studies, Cross-Sectional Studies, Fatty Acids, Fatty Acids, Omega-3, Humans, Outcome Assessment, Health Care, Sleep, sleep quality, omega-3, fatty acids, diet, public health, biomarkers, Engineering, Medical and Health Sciences, Nutrition & Dietetics, Clinical sciences, Nutrition and dietetics
Abstract

Backgroundn-3 and n-6 PUFAs have physiologic roles in sleep processes, but little is known regarding circulating n-3 and n-6 PUFA and sleep parameters.ObjectivesWe sought to assess associations between biomarkers of n-3 and n-6 PUFA intake with self-reported sleep duration and difficulty falling sleeping in the Fatty Acids and Outcome Research Consortium.MethodsHarmonized, de novo, individual-level analyses were performed and pooled across 12 cohorts. Participants were 35-96 y old and from 5 nations. Circulating measures included α-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA), DHA, EPA + DPA + DHA, linoleic acid, and arachidonic acid. Sleep duration (10 cohorts, n = 18,791) was categorized as short (≤6 h), 7-8 h (reference), or long (≥9 h). Difficulty falling asleep (8 cohorts, n = 12,500) was categorized as yes or no. Associations between PUFAs, sleep duration, and difficulty falling sleeping were assessed by cross-sectional multinomial logistic regression using standardized protocols and covariates. Cohort-specific multivariable-adjusted ORs per quintile of PUFAs were pooled with inverse-variance weighted meta-analysis.ResultsIn pooled analysis adjusted for sociodemographic characteristics and health status, participants with higher very long-chain n-3 PUFAs were less likely to have long sleep duration. In the top compared with the bottom quintiles, the multivariable-adjusted ORs (95% CIs) for long sleep were 0.78 (95% CI: 0.65, 0.95) for DHA and 0.76 (95% CI: 0.63, 0.93) for EPA + DPA + DHA. Significant associations for ALA and n-6 PUFA with short sleep duration or difficulty falling sleeping were not identified.ConclusionsParticipants with higher concentrations of very long-chain n-3 PUFAs were less likely to have long sleep duration. While objective biomarkers reduce recall bias and misclassification, the cross-sectional design limits assessment of the temporal nature of this relation. These novel findings across 12 cohorts highlight the need for experimental and biological assessments of very long-chain n-3 PUFAs and sleep duration.

Published
2022

18. Innovative financing for nutrition

Author

Shekar, Meera, O’Hearn, Meghan, Knudsen, Ellina, Shibuya, Kenji, Bishop, Simon, van Berchem, Hélène, Egerton-Warburton, Christopher, Shibata Okamura, Kyoko, and Mozaffarian, Dariush

Published
2023
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19. Food, nutrition, and fertility: from soil to fork

Author

Maitin-Shepard, Melissa, Werner, Erika F, Feig, Larry A, Chavarro, Jorge E, Mumford, Sunni L, Wylie, Blair, Rando, Oliver J, Gaskins, Audrey J, Sakkas, Denny, Arora, Manish, Kudesia, Rashmi, Lujan, Marla E, Braun, Joseph, and Mozaffarian, Dariush

Published
2024
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20. Longitudinal Plasma Measures of Trimethylamine N‐Oxide and Risk of Atherosclerotic Cardiovascular Disease Events in Community‐Based Older Adults

Author

Lee, Yujin, Nemet, Ina, Wang, Zeneng, Lai, Heidi TM, de Oliveira Otto, Marcia C, Lemaitre, Rozenn N, Fretts, Amanda M, Sotoodehnia, Nona, Budoff, Matthew, DiDonato, Joseph A, McKnight, Barbara, Tang, WH Wilson, Psaty, Bruce M, Siscovick, David S, Hazen, Stanley L, and Mozaffarian, Dariush

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Aging, Nutrition, Cardiovascular, Clinical Research, Heart Disease - Coronary Heart Disease, Prevention, Kidney Disease, Heart Disease, Atherosclerosis, Good Health and Well Being, Aged, Biomarkers, Cardiovascular Diseases, Humans, Methylamines, Middle Aged, Prospective Studies, Risk Factors, animal food, atherosclerotic cardiovascular disease, renal function, trimethylamine N-oxide, trimethylamine N‐oxide, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology
Abstract

Background Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite of dietary choline, L-carnitine, and phosphatidylcholine-rich foods. On the basis of experimental studies and patients with prevalent disease, elevated plasma TMAO may increase risk of atherosclerotic cardiovascular disease (ASCVD). TMAO is also renally cleared and may interact with and causally contribute to renal dysfunction. Yet, how serial TMAO levels relate to incident and recurrent ASCVD in community-based populations and the potential mediating or modifying role of renal function are not established. Methods and Results We investigated associations of serial measures of plasma TMAO, assessed at baseline and 7 years, with incident and recurrent ASCVD in a community-based cohort of 4131 (incident) and 1449 (recurrent) older US adults. TMAO was measured using stable isotope dilution liquid chromatography-tandem mass spectrometry (laboratory coefficient of variation,

Published
2021

21. Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants in the CHREBP (Carbohydrate Responsive Element Binding Protein) Locus and HDL-C (High-Density Lipoprotein Cholesterol) and Triglyceride Concentrations.

Author

Haslam, Danielle E, Peloso, Gina M, Guirette, Melanie, Imamura, Fumiaki, Bartz, Traci M, Pitsillides, Achilleas N, Wang, Carol A, Li-Gao, Ruifang, Westra, Jason M, Pitkänen, Niina, Young, Kristin L, Graff, Mariaelisa, Wood, Alexis C, Braun, Kim VE, Luan, Jian'an, Kähönen, Mika, Kiefte-de Jong, Jessica C, Ghanbari, Mohsen, Tintle, Nathan, Lemaitre, Rozenn N, Mook-Kanamori, Dennis O, North, Kari, Helminen, Mika, Mossavar-Rahmani, Yasmin, Snetselaar, Linda, Martin, Lisa W, Viikari, Jorma S, Oddy, Wendy H, Pennell, Craig E, Rosendall, Frits R, Ikram, M Arfan, Uitterlinden, Andre G, Psaty, Bruce M, Mozaffarian, Dariush, Rotter, Jerome I, Taylor, Kent D, Lehtimäki, Terho, Raitakari, Olli T, Livingston, Kara A, Voortman, Trudy, Forouhi, Nita G, Wareham, Nick J, de Mutsert, Renée, Rich, Steven S, Manson, JoAnn E, Mora, Samia, Ridker, Paul M, Merino, Jordi, Meigs, James B, Dashti, Hassan S, Chasman, Daniel I, Lichtenstein, Alice H, Smith, Caren E, Dupuis, Josée, Herman, Mark A, and McKeown, Nicola M

Subjects
Humans, Triglycerides, Polymorphism, Single Nucleotide, Adult, Middle Aged, Female, Male, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Cholesterol, HDL, Meta-Analysis as Topic, Sugar-Sweetened Beverages, carbohydrates, dyslipidemia, epidemiology, genetics, nutrition, sugars, triglyceride, Cardiovascular, Genetics, Human Genome
Abstract

BackgroundChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia.MethodsData from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake.ResultsIn a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16-3.07] mg/dL per allele; P

Published
2021

25. n–6 fatty acid biomarkers and incident atrial fibrillation: an individual participant-level pooled analysis of 11 international prospective studies

Author

Garg, Parveen K., Guan, Weihua, Nomura, Sarah, Weir, Natalie L., Tintle, Nathan, Virtanen, Jyrki K., Hirakawa, Yoichiro, Qian, Frank, Sun, Qi, Rimm, Eric, Lemaitre, Rozenn N., Jensen, Paul N., Heckbert, Susan R., Imamura, Fumiaki, Steur, Marinka, Leander, Karin, Laguzzi, Federica, Voortman, Trudy, Ninomiya, Toshiharu, Mozaffarian, Dariush, Harris, William S., Siscovick, David S., and Tsai, Michael Y.

Published
2023
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26. Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies

Author

Laguzzi, Federica, Åkesson, Agneta, Marklund, Matti, Qian, Frank, Gigante, Bruna, Bartz, Traci M., Bassett, Julie K., Birukov, Anna, Campos, Hannia, Hirakawa, Yoichiro, Imamura, Fumiaki, Jäger, Susanne, Lankinen, Maria, Murphy, Rachel A., Senn, Mackenzie, Tanaka, Toshiko, Tintle, Nathan, Virtanen, Jyrki K., Yamagishi, Kazumasa, Allison, Matthew, Brouwer, Ingeborg A., De Faire, Ulf, Eiriksdottir, Gudny., Ferrucci, Luigi, Forouhi, Nita G., Geleijnse, Johanna M., Hodge, Allison M, Kimura, Hitomi, Laakso, Markku, Risérus, Ulf, van Westing, Anniek C., Bandinelli, Stefania, Baylin, Ana, Giles, Graham G., Gudnason, Vilmundur, Iso, Hiroyasu, Lemaitre, Rozenn N., Ninomiya, Toshiharu, Post, Wendy S., Psaty, Bruce M., Salonen, Jukka T., Schulze, Matthias B., Tsai, Michael Y., Uusitupa, Matti, Wareham, Nicholas J., Oh, Seung-Won, Wood, Alexis C., Harris, William S., Siscovick, David, Mozaffarian, Dariush, and Leander, Karin

Published
2024
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27. Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies

Author

O’Keefe, James H., Tintle, Nathan L., Harris, William S., O’Keefe, Evan L., Sala-Vila, Aleix, Attia, John, Garg, G. Manohar, Hure, Alexis, Bork, Christian Sørensen, Schmidt, Erik Berg, Venø, Stine Krogh, Chien, Kuo-Liong, Chen, Yun-Yu (Amelia), Egert, Sarah, Feldreich, Tobias Rudholm, Ärnlöv, Johan, Lind, Lars, Forouhi, Nita G., Geleijnse, Johanna M., Pertiwi, Kamalita, Imamura, Fumiaki, de Mello Laaksonen, Vanessa, Uusitupa, W. Matti, Tuomilehto, Jaakko, Laakso, Markku, Lankinen, Maria Anneli, Laurin, Danielle, Carmichael, Pierre-Hugues, Lindsay, Joan, Leander, Karin, Laguzzi, Federica, Swenson, Brenton R., Longstreth, William T., Manson, JoAnn E., Mora, Samia, Cook, Nancy R., Marklund, Matti, Melo van Lent, Debora, Murphy, Rachel, Gudnason, Vilmundur, Ninomiya, Toshihara, Hirakawa, Yoichiro, Qian, Frank, Sun, Qi, Hu, Frank, Ardisson Korat, Andres V., Risérus, Ulf, Lázaro, Iolanda, Samieri, Cecilia, Le Goff, Mélanie, Helmer, Catherine, Steur, Marinka, Voortman, Trudy, Ikram, M. Kamran, Tanaka, Toshiko, Das, Jayanta K., Ferrucci, Luigi, Bandinelli, Stefania, Tsai, Michael, Guan, Weihua, Garg, Parveen, Verschuren, W.M. Monique, Boer, Jolanda M.A., Biokstra, Anneke, Virtanen, Jyrki, Wagner, Michael, Westra, Jason, Albuisson, Luc, Yamagishi, Kazumasa, Siscovick, David S., Lemaitre, Rozenn N., and Mozaffarian, Dariush

Published
2024
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30. Protocol for a randomized controlled trial of medically tailored meals compared to usual care among individuals with type 2 diabetes in Australia

Author

Law, Kristy K., Coyle, Daisy H., Neal, Bruce, Huang, Liping, Barrett, Eden M., Arnott, Clare, Chow, Clara K., Di Tanna, Gian Luca, Lung, Thomas, Mozaffarian, Dariush, Berkowitz, Seth A., Wong, Jencia, Wu, Ted, Twigg, Stephen, Gauld, Amanda, Simmons, David, Piya, Milan K., MacMillan, Freya, Khoo, Chee L., Tian, Maoyi, Trieu, Kathy, and Wu, Jason H.Y.

Published
2023
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32. Omega-3 Fatty Acid Biomarkers and Incident Atrial Fibrillation

Author

Qian, Frank, Tintle, Nathan, Jensen, Paul N., Lemaitre, Rozenn N., Imamura, Fumiaki, Feldreich, Tobias Rudholm, Nomura, Sarah Oppeneer, Guan, Weihua, Laguzzi, Federica, Kim, Eunjung, Virtanen, Jyrki K., Steur, Marinka, Bork, Christian S., Hirakawa, Yoichiro, O'Donoghue, Michelle L., Sala-Vila, Aleix, Ardisson Korat, Andres V., Sun, Qi, Rimm, Eric B., Psaty, Bruce M., Heckbert, Susan R., Forouhi, Nita G., Wareham, Nicholas J., Marklund, Matti, Risérus, Ulf, Lind, Lars, Ärnlöv, Johan, Garg, Parveen, Tsai, Michael Y., Pankow, James, Misialek, Jeffrey R., Gigante, Bruna, Leander, Karin, Pester, Julie A., Albert, Christine M., Kavousi, Maryam, Ikram, Arfan, Voortman, Trudy, Schmidt, Erik B., Ninomiya, Toshiharu, Morrow, David A., Bayés-Genís, Antoni, O’Keefe, James H., Ong, Kwok Leung, Wu, Jason H.Y., Mozaffarian, Dariush, Harris, William S., and Siscovick, David S.

Published
2023
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47. Global, regional, and national consumption of animal-source foods between 1990 and 2018: findings from the Global Dietary Database

Author

Abbott, Pamela, Abdollahi, Morteza, Abedi, Parvin, Abumweis, Suhad, Adair, Linda, Al Nsour, Mohannad, Al-Daghri, Nasser, Al-Hamad, Nawal, Al-Hooti, Suad, Al-Zenki, Sameer, Alam, Iftikhar, Ali, Jemal H, Alissa, Eman, Anderson, Simon, Anzid, Karim, Arambepola, Carukshi, Arici, Mustafa, Arsenault, Joanne, Asciak, Renzo, Barbieri, Helene E, Barengo, Noël, Barquera, Simon, Bas, Murat, Becker, Wulf, Beer-Borst, Sigrid, Bergman, Per, Biró, Lajos, Boindala, Sesikeran, Bovet, Pascal, Bradshaw, Debbie, Bukhary, Noriklil BI, Bundhamcharoen, Kanitta, Caballero, Mauricio, Calleja, Neville, Cao, Xia, Capanzana, Mario, Carmikle, Jan, Castetbon, Katia, Castro, Michelle, Cerdena, Corazon, Chang, Hsing-Yi, Charlton, Karen, Chen, Yu, Chen, Mei F, Chiplonkar, Shashi, Cho, Yoonsu, Chuah, Khun-Aik, Costanzo, Simona, Cowan, Melanie, Damasceno, Albertino, Dastgiri, Saeed, De Henauw, Stefaan, DeRidder, Karin, Ding, Eric, Dommarco, Rivera, Don, Rokiah, Duante, Charmaine, Duleva, Vesselka, Duran Aguero, Samuel, Ekbote, Veena, El Ati, Jalila, El Hamdouchi, Asmaa, El-kour, Tatyana, Eldridge, Alison, Elmadfa, Ibrahim, Esteghamati, Alireza, Etemad, Zohreh, Fadzil, Fariza, Farzadfar, Farshad, Fernandez, Anne, Fernando, Dulitha, Fisberg, Regina, Forsyth, Simon, Gamboa-Delgado, Edna, Garriguet, Didier, Gaspoz, Jean-Michel, Gauci, Dorothy, Geleijnse, Marianne, Ginnela, Brahmam, Grosso, Giuseppe, Guessous, Idris, Gulliford, Martin, Gunnarsdottir, Ingibjorg, Hadden, Wilbur, Hadziomeragic, Aida, Haerpfer, Christian, Hakeem, Rubina, Haque, Aminul, Hashemian, Maryam, Hemalatha, Rajkumar, Henjum, Sigrun, Hinkov, Hristo, Hjdaud, Zaiton, Hoffman, Daniel, Hopping, Beth, Houshiar-rad, Anahita, Hsieh, Yao-Te, Hung, Shu-Yi, Huybrechts, Inge, Hwalla, Nahla C, Ibrahim, Hajah M, Ikeda, Nayu, Illescas-Zarate, Daniel, Inoue, Manami, Janakiram, Chandrashekar, Jayawardena, Ranil, Jeewon, Rajesh, Jitnarin, Nattinee, Johansson, Lars, Jonsdottir, Olof, Jundishapur, Ahvaz, Kally, Ola, Kandiah, Mirnalini, Karupaiah, Tilakavati, Keinan-Boker, Lital, Kelishadi, Roya, Khadilkar, Anuradha, Kim, Cho-il, Koksal, Eda, Konig, Jurgen, Korkalo, Liisa, Koster, Jeremy, Kovalskys, Irina, Krishnan, Anand, Kruger, Herculina, Kuriyan-Raj, Rebecca, Kweon, Sanghui, Lachat, Carl, Lai, Yuen, Lanerolle, Pulani, Laxmaiah, Avula, Leclercq, Catherine, Lee, Meei-Shyuan, Lee, Hae-Jeung, Lemming, Eva W, Li, Yanping, Lindström, Jaana, Ling, Annie, Liputo, Nur IL, Lopez-Jaramillo, Patricio, Luke, Amy, Lukito, Widjaja, Lupotto, Elisabette, Ma, Yi, Mahdy, Zaleha A, Malekzadeh, Reza, Manan, Wan, Marchioni, Dirce, Marques, Lydia L, Marques-Vidal, Pedro, Martin-Prevel, Yves, Mathee, Angie, Matsumura, Yasuhiro, Mazumdar, Paramita, Memon, Anjum, Mensink, Gert, Meyer, Alexa, Mirmiran, Parvin, Mirzaei, Masoud, Misra, Puneet, Misra, Anoop, Mitchell, Claudette, Mohamed, Hamid JBJ, Mohammadi-Nasrabadi, Fatemeh, Mohammadifard, Noushin, Moy, Foong M, Musaiger, Abdulrahman, Mwaniki, Elizabeth, Myhre, Jannicke, Nagalla, Balakrishna, Naska, Androniki, Ng, Swee A, Ng, Shu W, Ngoan, Le TN, Noshad, Sina, Ochoa, Angelica, Ocke, Marga, Odenkirk, Jillian, Oh, Kyungwon, Oleas, Mariana, Olivares, Sonia, Orfanos, Philippos, Ortiz-Ulloa, Johana, Otero, Johanna, Ovaskainen, Marja-Leena, Pakseresht, Mohammadreza, Palacios, Cristina, Palmer, Pam, Pan, Wen-Harn, Panagiotakos, Demosthenes, Parajuli, Rajendra, Park, Myungsook, Pekcan, Gulden, Petrova, Stefka, Piaseu, Noppawan, Pitsavos, Christos, Polasa, Kalpagam, Posada, Luz, Pourfarzi, Farhad, Preston, Alan M, Rached, Ingrid, Rahbar, Ali R, Rehm, Colin, Richter, Almut, Riley, Leanne, Salanave, Benoit, Sánchez-Romero, Luz M, Sarrafzadegan, Nizal, Sawada, Norie, Sekiyama, Makiko, Selamat, Rusidah, Shamsuddin, Khadijah, Shariff, Zalilah M, Sharma, Sangita, Sibai, Abla M, Sinkko, Harri, Sioen, Isabelle, Sisa, Ivan, Skeaff, Sheila, Steingrimsdottir, Laufey, Strand, Tor, Suarez-Ortegon, Milton F, Swaminathan, Sumathi, Swan, Gillian, Sygnowska, Elzbieta, Szabo, Maria, Szponar, Lucjan, Tan-Khouw, Ilse, Tapanainen, Heli, Tayyem, Reema, Tedla, Bemnet, Tedstone, Alison, Templeton, Robert, Termote, Celine, Thanopoulou, Anastasia, Thorgeirsdottir, Holmfridur, Thorsdottir, Inga, Trichopoulos, Dimitrios, Trichopoulou, Antonia, Tsugane, Shoichiro, Turrini, Aida, van Oosterhout, Coline, Vartiainen, Erkki, Veerman, J Lennert, Virtanen, Suvi, Vollenweider, Peter, Vossenaar, Marieke, Waidyatilaka, Indu, Waskiewicz, Anna, Waterham, Eveline, Wieler, Lothar, Wondwossen, Tizita, Wu, Suh, Yaakub, Roseyati, Yap, Mabel, Yusof, Safiah, Zaghloul, Sahar, Zajkás, Gábor, Zapata, Maria, Zarina, Khairul, Zohoori, Fatemeh V, Miller, Victoria, Reedy, Julia, Cudhea, Frederick, Zhang, Jianyi, Shi, Peilin, Erndt-Marino, Josh, Coates, Jennifer, Micha, Renata, Webb, Patrick, and Mozaffarian, Dariush

Published
2022
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48. Regulation of Added Substances in the Food Supply by the Food and Drug Administration Human Foods Program.

Author

Pomeranz, Jennifer L., Broad Leib, Emily M., and Mozaffarian, Dariush

Subjects
FOOD supply laws, LEGAL procedure, FOOD additives, FOOD safety, LEGISLATION, HEALTH policy, DECISION making, FOOD industry, POTASSIUM compounds, COURTS, FOOD supply, PUBLIC health, SPICES, GOVERNMENT regulation, SELF-perception, RULES, SALT
Abstract

The US food supply is increasingly associated with diet-related diseases, toxicity, cancer, and other health harms. These public health concerns are partly attributable to a loophole in federal law. The Food and Drug Administration (FDA) evaluates the premarket safety of ingredients regulated as food additives but allows the food industry to self-regulate and determine which substances to classify as generally recognized as safe (GRAS) based on undisclosed data and conclusions that the FDA never sees. Furthermore, the FDA lacks a formal approach for reviewing food additives and GRAS substances already found in the food supply. Substances in the food supply thus include innocuous ingredients (e.g., black pepper), those that are harmful at high levels (e.g., salt), those that are of questionable safety (e.g., potassium bromate), and those that are unknown to the FDA and the public. A recent court decision codified these gaps in the FDA's current approach, leaving states to try to fill the regulatory void. The FDA and Congress should consider several policy options to ensure that the FDA is meeting its mission to ensure a safe food supply. (Am J Public Health. 2024;114(10):1061–1070. https://doi.org/10.2105/AJPH.2024.307755) [ABSTRACT FROM AUTHOR]

Published
2024
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49. Trimethylamine N-Oxide and Related Gut Microbe-Derived Metabolites and Incident Heart Failure Development in Community-Based Populations.

Author

Tang, W. H. Wilson, Lemaitre, Rozenn N., Jensen, Paul N., Meng Wang, Zeneng Wang, Li, Xinmin S., Nemet, Ina, Yujin Lee, Lai, Heidi T. M., de Oliveira Otto, Marcia C., Fretts, Amanda M., Sotoodehnia, Nona, DiDonato, Joseph A., Bäckhed, Fredrik, Psaty, Bruce M., Siscovick, David S., Budoff, Matthew J., Mozaffarian, Dariush, and Hazen, Stanley L.

Abstract

BACKGROUND: Growing evidence indicates that trimethylamine N-oxide, a gut microbial metabolite of dietary choline and carnitine, promotes both cardiovascular disease and chronic kidney disease risk. It remains unclear how circulating concentrations of trimethylamine N-oxide and its related dietary and gut microbe-derived metabolites (choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine) affect incident heart failure (HF). METHODS: We evaluated 11 768 participants from the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis with serial measures of metabolites. Cox proportional hazard models were used to examine the associations between metabolites and incident HF, adjusted for cardiovascular disease risk factors. RESULTS: In all, 2102 cases of HF occurred over a median follow-up of 15.9 years. After adjusting for traditional risk factors, higher concentrations of trimethylamine N-oxide (hazard ratio, 1.15 [95% CI, 1.09-1.20]; P<0.001), choline (hazard ratio, 1.44 [95% CI, 1.26-1.64]; P<0.001), and crotonobetaine (hazard ratio, 1.24 [95% CI, 1.16-1.32]; P<0.001) were associated with increased risk for incident HF. After further adjustment for renal function (potential confounder or mediator), these associations did not reach Bonferroni-corrected statistical significance (P=0.01, 0.049, and 0.006, respectively). Betaine and carnitine were nominally associated with a higher incidence of HF (P<0.05). In exploratory analyses, results were similar for subtypes of HF based on left ventricular ejection fraction, and associations appeared generally stronger among Black and Hispanic/Latino versus White adults, although there were no interactions for any metabolites with race. CONCLUSIONS: In this pooled analysis of 2 well-phenotyped, diverse, community-based cohorts, circulating concentrations of gut microbe-derived metabolites such as trimethylamine N-oxide, choline, and crotonobetaine were independently associated with a higher risk of developing HF. [ABSTRACT FROM AUTHOR]

Published
2024
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