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dc.contributor.authorWenstedt, Eliane FE
dc.contributor.authorPeters Sengers, Hessel
dc.contributor.authorBoekholdt, S Matthijs
dc.contributor.authorKhaw, Kay-Tee
dc.contributor.authorWareham, Nicholas J
dc.contributor.authorvan den Born, Bert-Jan H
dc.contributor.authorVogt, Liffert
dc.date.accessioned2022-07-01T23:30:21Z
dc.date.available2022-07-01T23:30:21Z
dc.date.issued2022-06-22
dc.identifier.issn2047-9980
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338673
dc.description.abstractBackground Experimental studies show that high-sodium intake affects the innate immune system, among others with increased circulating granulocytes. Whether this relationship exists on a population level and whether this relates to disease outcomes is unclear. We aimed to test the hypotheses that (1) sodium intake is associated with granulocytes on a population level; (2) granulocytes are associated with the presence of hypertension and both cardiovascular and renal outcomes; and (3) the relation between high-sodium intake and these outcomes is mediated by granulocytes. Methods and Results We performed an analysis in 13 804 participants from the prospective EPIC (European Prospective Investigation into Cancer)-Norfolk cohort, with a mean age of 58 years and median follow-up of 19.3 years. Analyses were carried out using calculated estimated sodium intake and sodium-to-potassium ratios from spot urines at baseline. The main outcomes were hypertension at baseline, and composite cardiovascular (mortality or cardiovascular events) and renal (mortality or renal events) outcomes during follow-up. Sodium intake and urine sodium-to-potassium ratio were positively associated with circulating granulocyte concentrations after adjustment for confounders (β=0.03; P=0.028 and β=0.06; P<0.001, respectively). Granulocytes significantly mediated the associations of, respectively, sodium intake and urine sodium-to-potassium ratio with hypertension at baseline, and cardiovascular and renal outcomes. Conclusions Sodium intake is positively associated with circulating granulocyte concentrations, and higher granulocyte concentrations associate with worse long-term cardiovascular and renal outcomes. Given the recently established immune-modulating effects of sodium and the role of immune cells in both cardiovascular and renal disease, causality for this pathway may need consideration in further studies.
dc.publisherWiley
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.subjectcardiovascular
dc.subjectgranulocytes
dc.subjecthypertension
dc.subjectrenal
dc.subjectsodium
dc.titleRelationship of Sodium Intake With Granulocytes, Renal and Cardiovascular Outcomes in the Prospective EPIC-Norfolk Cohort.
dc.typeArticle
dc.publisher.departmentoffice of The School of Clinical Medicine
dc.date.updated2022-06-24T09:42:24Z
prism.publicationDate2022
prism.publicationNameJournal of the American Heart Association
prism.startingPagee023727
dc.identifier.doi10.17863/CAM.86086
dcterms.dateAccepted2022-03-07
rioxxterms.versionofrecord10.1161/JAHA.121.023727
rioxxterms.versionVoR
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.identifier.eissn2047-9980
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (G1000143)
pubs.funder-project-idMedical Research Council (G0401527)
pubs.funder-project-idMedical Research Council (MR/N003284/1)
cam.issuedOnline2022-06-22
cam.depositDate2022-06-24
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution-NonCommercial 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial 4.0 International