Evidence map›Paper›PMID 30971107›Full record

SynthesisCirculation2019

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

Matti Marklund, Jason H Y Wu, Fumiaki Imamura, Liana C Del Gobbo, Amanda Fretts, Janette de Goede, Peilin Shi, Nathan Tintle, Maria Wennberg, Stella Aslibekyan and 78 more

Open access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers, 14 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
180citing papers in PubMed, 14 pooled it
22.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

180 citing papers in PubMed, 14 syntheses or guidelines pooled it, 319 citations in OpenAlex.

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  3. Dried Blood Spots to Assess Cardiovascular-Kidney-Metabolic Health.Journal of the American Heart Association · 2025
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120 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

88 authors at 3 institutions in 2 countries.

Matti MarklundDepartment of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Sweden (M.M., U.R.).
Jason H Y WuThe George Institute for Global Health and the Faculty of Medicine, University of New South Wales, Sydney, Australia (M.M., J.H.Y.W., M. Woodward).
Fumiaki ImamuraMedical Research Council Epidemiology Unit, University of Cambridge, United Kingdom (F.I., N.G.F., N.W.).
Liana C Del GobboDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (L.C.D.G.).
Amanda FrettsCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (A.F., R.N.L.).
Janette de GoedeDivision of Human Nutrition, Wageningen University, The Netherlands (J.d.G., J.M. Geleijnse).
Peilin ShiFriedman School of Nutrition Science and Policy, Tufts University, Boston, MA (P.S., N.E.-A., P.F.J., R.M., D.M.).
Nathan TintleDepartment of Mathematics and Statistics, Dordt College, Sioux Centre, IA (N.T., A.K., J. Veenstra).
Maria WennbergDepartment of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Sweden (M. Wennberg).
Stella AslibekyanDepartment of Epidemiology, University of Alabama at Birmingham (S.A.).
Tzu-An ChenUSDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX (T.-A.C., A.C.W.).
Marcia C de Oliveira OttoDivision of Epidemiology, Human Genetics and Environmental Sciences, the University of Texas Health Science Center, School of Public Health, Houston (M.C.d.O.O.).
Yoichiro HirakawaDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan (Y.H.).
Helle Højmark EriksenUnit of Epidemiology and Biostatistics, Aalborg University Hospital, Denmark (H.H.E.).
Janine KrögerDepartment of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany (J.K., M.B.S.).
Federica LaguzziUnit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (F.L., U.d.F., B.G., K.L.).
Maria LankinenInstitute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio (N. Lankinen, J. Virtanen, J.M., M.I.J.U.).
Rachel A MurphyUniversity of British Columbia, Vancouver, British Columbia, Canada (R.A.M.).
Kiesha PremSaw Swee Hock School of Public Health, National University of Singapore (K.P., W.-P.K., R.M.v.D.).
Cécilia SamieriUniv. Bordeaux, Inserm, Bordeaux Population Health Research Center, TUMR 1219, France (C.S., C.H.).
Jyrki VirtanenInstitute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio (N. Lankinen, J. Virtanen, J.M., M.I.J.U.).
Alexis C WoodUSDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX (T.-A.C., A.C.W.).
Kerry WongCentre for Epidemiology and Biostatistics, The University of Melbourne, Australia (K.W., G.G., A.H.).
Wei-Sin YangInstitute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei (W.-S.Y., K.-L.C.).
Xia ZhouDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (X.Z., L.S.).
Ana BaylinDepartments of Nutritional Sciences and Epidemiology, School of Public Health, University of Michigan, Ann Arbor (A.B.).
Jolanda M A BoerCentre for Nutrition, Prevention and Health Services, National Institute of Public Health and the Environment, Bilthoven, The Netherlands (J.M.A.B., W.M.M.V.).
Ingeborg A BrouwerHealth Sciences, Vrije Universiteit, Amsterdam, The Netherlands (I.A.B.).
Hannia CamposDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (H.C., F.B.H., E.R., Q.S., W.W.).
Paulo H M ChavesBenjamin Leon for Geriatrics Research and Education, Herbert Wertheim College of Medicine, Florida International University, Miami (P.H.M.C.).
Kuo-Liong ChienInstitute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei (W.-S.Y., K.-L.C.).
Ulf de FaireUnit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (F.L., U.d.F., B.G., K.L.).
Luc DjousséBrigham and Women's Hospital, Boston Veterans Affairs Healthcare System, MA (L.D., J.M. Gaziano).
Gudny EiriksdottirIcelandic Heart Association, Kópavogur, Iceland; and Faculty of Medicine, University of Iceland, Reykjavik (G.E., V.G., A.V.S.).
Naglaa El-AbbadiFriedman School of Nutrition Science and Policy, Tufts University, Boston, MA (P.S., N.E.-A., P.F.J., R.M., D.M.).
Nita G ForouhiMedical Research Council Epidemiology Unit, University of Cambridge, United Kingdom (F.I., N.G.F., N.W.).
J Michael GazianoBrigham and Women's Hospital, Boston Veterans Affairs Healthcare System, MA (L.D., J.M. Gaziano).
Johanna M GeleijnseDivision of Human Nutrition, Wageningen University, The Netherlands (J.d.G., J.M. Geleijnse).
Bruna GiganteUnit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (F.L., U.d.F., B.G., K.L.).
Graham GilesCentre for Epidemiology and Biostatistics, The University of Melbourne, Australia (K.W., G.G., A.H.).
Eliseo GuallarDivision of Environmental Epidemiology, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (E.G.).
Vilmundur GudnasonIcelandic Heart Association, Kópavogur, Iceland; and Faculty of Medicine, University of Iceland, Reykjavik (G.E., V.G., A.V.S.).
Tamara HarrisNational Institute on Aging, Bethesda, MD (T.H.).
William S HarrisDepartment of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls (W.S.H.).
Catherine HelmerUniv. Bordeaux, Inserm, Bordeaux Population Health Research Center, TUMR 1219, France (C.S., C.H.).
Mai-Lis HelleniusDepartment of Medicine, Cardiology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (M.-L.H.).
Allison HodgeCentre for Epidemiology and Biostatistics, The University of Melbourne, Australia (K.W., G.G., A.H.).
Frank B HuDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (H.C., F.B.H., E.R., Q.S., W.W.).
Paul F JacquesFriedman School of Nutrition Science and Policy, Tufts University, Boston, MA (P.S., N.E.-A., P.F.J., R.M., D.M.).
Jan-Håkan JanssonDepartment of Public Health and Clinical Medicine, Research Unit Skellefteå, Umeå University, Umeå, Sweden (J.-H.J.).
Anya KalsbeekDepartment of Mathematics and Statistics, Dordt College, Sioux Centre, IA (N.T., A.K., J. Veenstra).
Kay-Tee KhawDepartment of Public Health and Primary Care, University of Cambridge School of Clinical Medicine, United Kingdom (K.-T.K., R.L.).
Woon-Puay KohSaw Swee Hock School of Public Health, National University of Singapore (K.P., W.-P.K., R.M.v.D.).
Markku LaaksoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland (M. Laakso).
Karin LeanderUnit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (F.L., U.d.F., B.G., K.L.).
Hung-Ju LinDepartment of Internal Medicine, National Taiwan University Hospital, Taipei (K.-L.C., H.-J.L.).
Lars LindDepartment of Medical Sciences, Uppsala University, Sweden (L.L., J.S.).
Robert LubenDepartment of Public Health and Primary Care, University of Cambridge School of Clinical Medicine, United Kingdom (K.-T.K., R.L.).
Juhua LuoDepartment of Epidemiology and Biostatistics, Indiana University, Bloomington (J.L.).
Barbara McKnightDepartment of Biostatistics, School of Public Health, University of Washington, Seattle (B.M.).
Jaakko MursuInstitute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio (N. Lankinen, J. Virtanen, J.M., M.I.J.U.).
Toshiharu NinomiyaDepartment of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan (T.N.).
Kim OvervadDepartment of Public Health, Section for Epidemiology, Aarhus University, Denmark (K.O.).
Bruce M PsatyCardiovascular Health Study, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle (B.M.P.).
Eric RimmDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (H.C., F.B.H., E.R., Q.S., W.W.).
Matthias B SchulzeDepartment of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany (J.K., M.B.S.).
David SiscovickThe New York Academy of Medicine (D.S.).
Michael Skjelbo NielsenDepartment of Cardiology, Aalborg University Hospital, Denmark (K.O., M.S.N.).
Albert V SmithIcelandic Heart Association, Kópavogur, Iceland; and Faculty of Medicine, University of Iceland, Reykjavik (G.E., V.G., A.V.S.).
Brian T SteffenDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (B.T.S., M.Y.T.).
Lyn SteffenDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (X.Z., L.S.).
Qi SunDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (H.C., F.B.H., E.R., Q.S., W.W.).
Johan SundströmDepartment of Medical Sciences, Uppsala University, Sweden (L.L., J.S.).
Michael Y TsaiDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (B.T.S., M.Y.T.).
Hugh Tunstall-PedoeCardiovascular Epidemiology Unit, Institute of Cardiovascular Research, University of Dundee, United Kingdom (H.T.-P., M. Woodward).
Matti I J UusitupaInstitute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio (N. Lankinen, J. Virtanen, J.M., M.I.J.U.).
Rob M van DamSaw Swee Hock School of Public Health, National University of Singapore (K.P., W.-P.K., R.M.v.D.).
Jenna VeenstraDepartment of Mathematics and Statistics, Dordt College, Sioux Centre, IA (N.T., A.K., J. Veenstra).
W M Monique VerschurenCentre for Nutrition, Prevention and Health Services, National Institute of Public Health and the Environment, Bilthoven, The Netherlands (J.M.A.B., W.M.M.V.).
Nick WarehamMedical Research Council Epidemiology Unit, University of Cambridge, United Kingdom (F.I., N.G.F., N.W.).
Walter WillettDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (H.C., F.B.H., E.R., Q.S., W.W.).
Mark WoodwardThe George Institute for Global Health and the Faculty of Medicine, University of New South Wales, Sydney, Australia (M.M., J.H.Y.W., M. Woodward).
Jian-Min YuanDivision of Cancer Control and Population Sciences, UPMC Hillman Cancer, and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA (J.-M.Y.).
Renata MichaFriedman School of Nutrition Science and Policy, Tufts University, Boston, MA (P.S., N.E.-A., P.F.J., R.M., D.M.).
Rozenn N LemaitreCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (A.F., R.N.L.).
Dariush MozaffarianFriedman School of Nutrition Science and Policy, Tufts University, Boston, MA (P.S., N.E.-A., P.F.J., R.M., D.M.).
Ulf RisérusDepartment of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Sweden (M.M., U.R.).
Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE)
University of Minnesota · USAarhus University · DKNew York Academy of Medicine · US

Funding

Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Validity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI GIOVANNUCCI, EDWARD · 1991 to 2009
$41.8M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Transgenic CoreP30DK046200 · NIDDK · TUFTS MEDICAL CENTER · PI HU, FRANK B · 1992 to 2021
$25.0M
Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3M
Genome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2M
University of Alabama at Birmingham's Diabetes Research CenterP30DK079626 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BARBARA A GOWER · 2013 to 2026
$19.5M
Physicians' Health Study II: Prevention Trial of VitaminsR01CA097193 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI GAZIANO, J. MICHAEL · 2002 to 2011
$15.7M
RISK FACTORS FOR CVD IN WOMENR01HL034594 · NHLBI · TULANE UNIVERSITY OF LOUISIANA · PI JoAnn Elisabeth Manson, Lu Qi · 1985 to 2026
$13.8M
Epidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8M
Cancer Epidemiology Cohort in Male Health ProfessionalsUM1CA167552 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI WILLETT, WALTER C. · 2012 to 2016
$11.5M
British Heart FoundationCancer Research UK 14136Chief Scientist OfficeIntramural NIH HHS ZIA AG007380Medical Research Council G0401527Medical Research Council G1000143Medical Research Council MC_UU_12015/1Medical Research Council MC_UU_12015/5Medical Research Council MR/N003284/1NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCI NIH HHS P01 CA055075NCI NIH HHS R01 CA034944NCI NIH HHS R01 CA040360NCI NIH HHS R01 CA049449NCI NIH HHS R01 CA097193NCI NIH HHS R01 CA144034NCI NIH HHS U01 CA182876NCI NIH HHS UM1 CA167552NCI NIH HHS UM1 CA182876NCI NIH HHS UM1 CA186107NCRR NIH HHS UL1 RR025005NHGRI NIH HHS U01 HG004402NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201600001CNHLBI NIH HHS HHSN268201600002CNHLBI NIH HHS HHSN268201600003CNHLBI NIH HHS HHSN268201600004CNHLBI NIH HHS HHSN268201600018CNHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS R01 HL026490NHLBI NIH HHS R01 HL034594NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL081549NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01 HL088521NHLBI NIH HHS R21 HL088081NHLBI NIH HHS U01 HL080295NIAAA NIH HHS R01 AA011181NIA NIH HHS N01 AG012100NIA NIH HHS R01 AG023629NIDDK NIH HHS P30 DK046200NIDDK NIH HHS P30 DK079626
6 · The paper itself

Abstract

backgroundGlobal dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

methodsWe performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).

resultsIn 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.

conclusionsIn pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

Indexed as

Arachidonic AcidCardiovascular DiseasesDietary FatsDiet, HealthyLinoleic AcidPrimary PreventionRisk Reduction BehaviorAgedBiomarkersFemaleHumansMaleMiddle AgedNutritive ValueObservational Studies as TopicProtective FactorsArachidonic AcidBiomarkersDietary FatsLinoleic Acidarachidonic acidbiomarkerscardiovascular diseasesdietepidemiologylinoleic acidprimary prevention

Identifiers

PMID30971107
PMCPMC6582360
OpenAlexW2929715122

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.