{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T13:40:10Z","timestamp":1793194810077,"version":"4.5.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"42","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["ERC-CoG-726318"],"award-info":[{"award-number":["ERC-CoG-726318"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Centre of Poland","doi-asserted-by":"crossref","award":["2997\/B\/P01\/2009\/36"],"award-info":[{"award-number":["2997\/B\/P01\/2009\/36"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RE\/13\/5\/30177"],"award-info":[{"award-number":["RE\/13\/5\/30177"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Inflammation is an important driver of hypertension. Periodontitis is a chronic inflammatory disease, which could provide a mechanism for pro-hypertensive immune activation, but evidence of a causal relationship in humans is scarce. We aimed to investigate the nature of the association between periodontitis and hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We performed a two-sample Mendelian randomization analysis in the \u223c750\u00a0000 UK-Biobank\/International Consortium of Blood Pressure-Genome-Wide Association Studies participants using single nucleotide polymorphisms (SNPs) in SIGLEC5, DEFA1A3, MTND1P5, and LOC107984137 loci GWAS-linked to periodontitis, to ascertain their effect on blood pressure (BP) estimates. This demonstrated a significant relationship between periodontitis-linked SNPs and BP phenotypes. We then performed a randomized intervention trial on the effects of treatment of periodontitis on BP. One hundred and one hypertensive patients with moderate\/severe periodontitis were randomized to intensive periodontal treatment (IPT; sub- and supragingival scaling\/chlorhexidine; n\u2009=\u200950) or control periodontal treatment (CPT; supragingival scaling; n\u2009=\u200951) with mean ambulatory 24-h (ABPM) systolic BP (SBP) as primary outcome. Intensive periodontal treatment improved periodontal status at 2\u2009months, compared to CPT. This was accompanied by a substantial reduction in mean SBP in IPT compared to the CPT (mean difference of \u221211.1\u2009mmHg; 95% CI 6.5\u201315.8; P\u2009&amp;lt;\u20090.001). Systolic BP reduction was correlated to periodontal status improvement. Diastolic BP and endothelial function (flow-mediated dilatation) were also improved by IPT. These cardiovascular changes were accompanied by reductions in circulating IFN-\u03b3 and IL-6 as well as activated (CD38+) and immunosenescent (CD57+CD28null) CD8+T cells, previously implicated in hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A causal relationship between periodontitis and BP was observed providing proof of concept for development of clinical trial in a large cohort of hypertensive patients. ClinicalTrials.gov: NCT02131922.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehz646","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T15:26:58Z","timestamp":1566401218000},"page":"3459-3470","source":"Crossref","is-referenced-by-count":312,"title":["Causal association between periodontitis and hypertension: evidence from Mendelian randomization and a randomized controlled trial of non-surgical periodontal therapy"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7444-1373","authenticated-orcid":false,"given":"Marta","family":"Czesnikiewicz-Guzik","sequence":"first","affiliation":[{"name":"Department of Periodontology and Oral Sciences Research Group, University of Glasgow Dental School , Glasgow, UK"},{"name":"Department of Dental Prophylaxis and Experimental Dentistry, Jagiellonian University Medical College , Krakow, 31-107 Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Osmenda","sequence":"additional","affiliation":[{"name":"Department of Internal and Agricultural Medicine, Jagiellonian University Medical College , 31-107, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Siedlinski","sequence":"additional","affiliation":[{"name":"Department of Internal and Agricultural Medicine, Jagiellonian University Medical College , 31-107, Krakow, Poland"},{"name":"Institute of Cardiovascular and Medical Sciences, University of Glasgow , Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Nosalski","sequence":"additional","affiliation":[{"name":"Department of Internal and Agricultural Medicine, Jagiellonian University Medical College , 31-107, Krakow, Poland"},{"name":"Institute of Cardiovascular and Medical Sciences, University of Glasgow , Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Pelka","sequence":"additional","affiliation":[{"name":"Department of Dental Prophylaxis and Experimental Dentistry, Jagiellonian University Medical College , Krakow, 31-107 Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Nowakowski","sequence":"additional","affiliation":[{"name":"Department of Dental Prophylaxis and Experimental Dentistry, Jagiellonian University Medical College , Krakow, 31-107 Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Wilk","sequence":"additional","affiliation":[{"name":"Department of Internal and Agricultural Medicine, Jagiellonian University Medical College , 31-107, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7990-2896","authenticated-orcid":false,"given":"Tomasz P","family":"Mikolajczyk","sequence":"additional","affiliation":[{"name":"Department of Internal and Agricultural Medicine, Jagiellonian University Medical College , 31-107, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6594-9386","authenticated-orcid":false,"given":"Agata","family":"Schramm-Luc","sequence":"additional","affiliation":[{"name":"Department of Internal and Agricultural Medicine, Jagiellonian University Medical College , 31-107, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Furtak","sequence":"additional","affiliation":[{"name":"Department of Dental Prophylaxis and Experimental Dentistry, Jagiellonian University Medical College , Krakow, 31-107 Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5788-575X","authenticated-orcid":false,"given":"Pawel","family":"Matusik","sequence":"additional","affiliation":[{"name":"Department of Internal and Agricultural Medicine, Jagiellonian University Medical College , 31-107, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9759-011X","authenticated-orcid":false,"given":"Joanna","family":"Koziol","sequence":"additional","affiliation":[{"name":"Department of Internal and Agricultural Medicine, Jagiellonian University Medical College , 31-107, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslaw","family":"Drozdz","sequence":"additional","affiliation":[{"name":"St. Anna\u2019s Hospital , 32-200 Miechow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Munoz-Aguilera","sequence":"additional","affiliation":[{"name":"Periodontology Unit, UCL Eastman Dental Institute , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8215-6567","authenticated-orcid":false,"given":"Maciej","family":"Tomaszewski","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester , Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Evangelou","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Caulfield","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, NIHR Biomedical Research Centre at Barts, Queen Mary University of London , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0159-4915","authenticated-orcid":false,"given":"Tomasz","family":"Grodzicki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Gerontology, Jagiellonian University Medical College , 31-107 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8654-935X","authenticated-orcid":false,"given":"Francesco","family":"D'Aiuto","sequence":"additional","affiliation":[{"name":"Periodontology Unit, UCL Eastman Dental Institute , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5039-7849","authenticated-orcid":false,"given":"Tomasz J","family":"Guzik","sequence":"additional","affiliation":[{"name":"Department of Internal and Agricultural Medicine, Jagiellonian University Medical College , 31-107, Krakow, 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