{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T08:07:07Z","timestamp":1791619627407,"version":"4.3.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oral. Health"],"abstract":"\n Aim<\/jats:title>\n To investigate the effect of periodontal therapy on endothelial function of subjects with periodontitis in stages III or IV and established cardiovascular disease.<\/jats:p>\n <\/jats:sec>\n \n Materials and methods<\/jats:title>\n \n A triple-blinded, parallel groups, randomized clinical trial of 6 months duration, on patients with history of coronary heart disease and periodontitis in stages III or IV was performed. Intervention consisted of steps 1 (oral hygiene instructions and professional mechanical plaque removal) and 2 (subgingival instrumentation) of periodontal therapy, including an antiseptic mouth rinse for 7 days. Patients in the control group received only step 1, with the adjunctive use of a fluoride-containing mouth rinse. Endothelial function (flow-mediated dilation [FMD]) and carotid intima-media thickness (cIMT) at baseline, 3 and 6 months, and serum markers of inflammation and cell adhesion at 3 days, 10 days, 3 and 6 months after therapy, were evaluated. Demographic characteristics, cardiovascular risk factors, history of cardiovascular diseases, medication intake, lipids profile, blood pressure, and periodontal outcomes were also evaluated. Student T, Mann\u2013Whitney U, Chi-square and Fisher-exact tests were performed along with repeated measures ANOVA with\n post hoc<\/jats:italic>\n Bonferroni's corrections.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Thirty-five patients were included. In the test group, improvements in pocket depth, bleeding on probing and suppuration at 6 months were significantly better than in control patients. Reductions in mean FMD [\n test group<\/jats:italic>\n \u22123.43%; 95% confidence interval\u2014CI [\u22122.68; 9.54],\n p<\/jats:italic>\n \u2009=\u20090.487;\n control group<\/jats:italic>\n \u22126.75%; 95% CI [1.29; 12.22],\n p<\/jats:italic>\n \u2009=\u20090.012] and cIMT (\n test group<\/jats:italic>\n \u22120.05\u2005mm; 95% CI [0.01; 0.10],\n p<\/jats:italic>\n \u2009=\u20090.014;\n control group<\/jats:italic>\n \u22120.01\u2005mm; 95% CI [\u22120.03; 0.05],\n p<\/jats:italic>\n \u2009=\u20091.000) were observed in both groups from baseline to 6 months, without significant intergroup differences at any time-point. Differences between groups in serum inflammatory markers were detected at baseline and 3 days for interleukin (IL)-18, and at 10 days for IL-8.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Preliminary results from the present pilot study showed that steps 1 and 2 of periodontal treatment in subjects with periodontitis in stages III\u2013IV and established cardiovascular disease induced improvements in cIMT and periodontal outcomes, although changes in FMD were not observed.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n clinicaltrials.gov<\/jats:uri>\n , Identifier, database (NCT02716259).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/froh.2025.1488941","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T01:49:39Z","timestamp":1739152179000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Effect of periodontal therapy on endothelial function and serum biomarkers in patients with periodontitis and established cardiovascular disease: a pilot study"],"prefix":"10.3389","volume":"6","author":[{"given":"Ana","family":"Molina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagore","family":"Ambrosio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Molina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Montero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leire","family":"Virto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Herrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Figuero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariano","family":"Sanz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors, 1990\u20132019: update from the GBD 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J Am Coll Cardiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1056\/NEJM199901143400207","article-title":"Atherosclerosis\u2013an inflammatory disease","volume":"340","author":"Ross","year":"1999","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1038\/s41586-021-03392-8","article-title":"The changing landscape of atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1161\/hc0902.104353","article-title":"Inflammation and atherosclerosis","volume":"105","author":"Libby","year":"2002","journal-title":"Circulation"},{"key":"B5","doi-asserted-by":"publisher","first-page":"S162","DOI":"10.1111\/jcpe.12946","article-title":"Periodontitis: consensus report of workgroup 2 of the 2017 world workshop on the classification of periodontal and peri-implant diseases and conditions","volume":"45","author":"Papapanou","year":"2018","journal-title":"J Clin Periodontol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1111\/jcpe.12682","article-title":"Role of microbial biofilms in the maintenance of oral health and in the development of dental caries and periodontal diseases. Consensus report of group 1 of the joint EFP\/ORCA workshop on the boundaries between caries and periodontal disease","volume":"44","author":"Sanz","year":"2017","journal-title":"J Clin Periodontol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/j.1600-051X.2007.01173.x","article-title":"A systematic review and meta-analyses on C-reactive protein in relation to periodontitis","volume":"35","author":"Paraskevas","year":"2008","journal-title":"J Clin Periodontol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"706432","DOI":"10.3389\/fimmu.2021.706432","article-title":"Serum C-reactive protein and periodontitis: a systematic review and meta-analysis","volume":"12","author":"Machado","year":"2021","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1111\/prd.12302","article-title":"Periodontal diseases and association with atherosclerotic disease","volume":"83","author":"Herrera","year":"2020","journal-title":"Periodontol 2000"},{"key":"B10","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1111\/prd.12304","article-title":"Mechanisms underlying the association between periodontitis and atherosclerotic disease","volume":"83","author":"Schenkein","year":"2020","journal-title":"Periodontol 2000"},{"key":"B11","doi-asserted-by":"publisher","first-page":"S30","DOI":"10.1111\/jcpe.12079","article-title":"Periodontal bacterial invasion and infection: contribution to atherosclerotic pathology","volume":"40","author":"Reyes","year":"2013","journal-title":"J Clin Periodontol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"200110","DOI":"10.1016\/j.ijcrp.2021.200110","article-title":"The association between periodontitis and cardiovascular risks in asymptomatic healthy patients","volume":"11","author":"Donders","year":"2021","journal-title":"Int J Cardiol Cardiovasc Risk Prev"},{"key":"B13","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1111\/j.1600-051X.2008.01228.x","article-title":"Severe periodontitis in young adults is associated with sub-clinical atherosclerosis","volume":"35","author":"Cairo","year":"2008","journal-title":"J Clin Periodontol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.sdj.2016.10.004","article-title":"Is periodontitis an independent risk factor for subclinical atherosclerosis?","volume":"37","author":"Khatri","year":"2016","journal-title":"Singapore Dent J"},{"key":"B15","first-page":"125","article-title":"Periodontal variables may predict sub-clinical atherosclerosis and systemic inflammation in young adults. A cross-sectional study","volume":"2","author":"Cairo","year":"2009","journal-title":"Eur J Oral Implantol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"S70","DOI":"10.1111\/jcpe.12062","article-title":"The epidemiological evidence behind the association between periodontitis and incident atherosclerotic cardiovascular disease","volume":"40","author":"Dietrich","year":"2013","journal-title":"J Clin Periodontol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1902\/annals.1998.3.1.339","article-title":"Periodontal disease and mortality from all causes in the VA dental longitudinal study","volume":"3","author":"Garcia","year":"1998","journal-title":"Ann Periodontol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/jcpe.13290","article-title":"Treatment of stage I-III periodontitis-the EFP S3 level clinical practice guideline","volume":"47","author":"Sanz","year":"2020","journal-title":"J Clin Periodontol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1056\/NEJMoa063186","article-title":"Treatment of periodontitis and endothelial function","volume":"356","author":"Tonetti","year":"2007","journal-title":"N Engl J Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1161\/HYPERTENSIONAHA.114.03359","article-title":"Effect of periodontal therapy on arterial structure and function among aboriginal Australians: a randomized, controlled trial","volume":"64","author":"Kapellas","year":"2014","journal-title":"Hypertension"},{"key":"B21","doi-asserted-by":"publisher","first-page":"S85","DOI":"10.1111\/jcpe.12061","article-title":"Evidence that periodontal treatment improves biomarkers and CVD outcomes","volume":"40","author":"D'Aiuto","year":"2013","journal-title":"J Clin Periodontol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/jcpe.13189","article-title":"Periodontitis and cardiovascular diseases: consensus report","volume":"47","author":"Sanz","year":"2020","journal-title":"J Clin Periodontol"},{"key":"B23","volume-title":"Procedimientos en Microbiolog\u00eda Cl\u00ednica: Hemocultivo","author":"Fern\u00e1ndez E","year":"2003"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1111\/odi.12909","article-title":"Periodontal therapy and endothelial function in coronary artery disease: a randomized controlled trial","volume":"24","author":"Saffi","year":"2018","journal-title":"Oral Dis"},{"key":"B25","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1093\/eurheartj\/ehi017","article-title":"Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response","volume":"26","author":"Bots","year":"2005","journal-title":"Eur Heart J"},{"key":"B26","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.recesp.2011.09.012","article-title":"Noninvasive assessment of endothelial function in clinical practice","volume":"65","author":"Arrebola-Moreno","year":"2012","journal-title":"Rev Esp Cardiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"e013915","DOI":"10.1161\/JAHA.119.013915","article-title":"Diagnostic criteria of flow-mediated vasodilation for normal endothelial function and nitroglycerin-induced vasodilation for normal vascular smooth muscle function of the brachial artery","volume":"9","author":"Maruhashi","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"B28","doi-asserted-by":"publisher","first-page":"III33","DOI":"10.1161\/01.CIR.0000131516.65699.ba","article-title":"Measurement of arterial wall thickness as a surrogate marker for atherosclerosis","volume":"109","author":"de Groot","year":"2004","journal-title":"Circulation"},{"key":"B29","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1093\/oxfordjournals.aje.a009302","article-title":"Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) study, 1987\u20131993","volume":"146","author":"Chambless","year":"1997","journal-title":"Am J Epidemiol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1161\/CIRCULATIONAHA.120.046361","article-title":"Carotid intima-media thickness progression as surrogate marker for cardiovascular risk: meta-analysis of 119 clinical trials involving 100 667 patients","volume":"142","author":"Willeit","year":"2020","journal-title":"Circulation"},{"key":"B31","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1056\/NEJM199901073400103","article-title":"Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular health study collaborative research group","volume":"340","author":"O'Leary","year":"1999","journal-title":"N Engl J Med"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1096\/fj.08-119578","article-title":"Treatment of periodontal disease results in improvements in endothelial dysfunction and reduction of the carotid intima-media thickness","volume":"23","author":"Piconi","year":"2009","journal-title":"FASEB J"},{"key":"B33","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/jcpe.12076","article-title":"Non-surgical periodontal therapy decreases serum elastase levels in aggressive but not in chronic periodontitis","volume":"40","author":"Eickholz","year":"2013","journal-title":"J Clin Periodontol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1111\/jre.12543","article-title":"Increased systemic levels of inflammatory mediators following one-stage full-mouth scaling and root planing","volume":"53","author":"Morozumi","year":"2018","journal-title":"J Periodontal Res"},{"key":"B35","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1111\/jcpe.12451","article-title":"Acute-phase response following full-mouth versus quadrant non-surgical periodontal treatment: a randomized clinical trial","volume":"42","author":"Graziani","year":"2015","journal-title":"J Clin Periodontol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1111\/j.1600-051X.2012.01942.x","article-title":"Non-surgical periodontal therapy reduces coronary heart disease risk markers: a randomized controlled trial","volume":"39","author":"Bokhari","year":"2012","journal-title":"J Clin Periodontol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1111\/prd.12299","article-title":"Periodontal therapy and cardiovascular risk","volume":"83","author":"Orlandi","year":"2020","journal-title":"Periodontol 2000"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3227","DOI":"10.1093\/eurheartj\/ehab484","article-title":"2021 ESC guidelines on cardiovascular disease prevention in clinical practice","volume":"42","author":"Visseren","year":"2021","journal-title":"Eur Heart J"},{"key":"B39","doi-asserted-by":"publisher","first-page":"2949","DOI":"10.1093\/eurheartj\/eht296","article-title":"2013 ESC guidelines on the management of stable coronary artery disease: the task force on the management of stable coronary artery disease of the European Society of Cardiology","volume":"34","author":"Montalescot","year":"2013","journal-title":"Eur Heart J"},{"key":"B40","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1177\/0022034521995157","article-title":"Host modulation and treatment of periodontal disease","volume":"100","author":"Balta","year":"2021","journal-title":"J Dent Res"},{"key":"B41","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/S0140-6736(00)04053-8","article-title":"Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial","volume":"357","author":"Smilde","year":"2001","journal-title":"Lancet"},{"key":"B42","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1161\/01.CIR.88.1.20","article-title":"Beneficial effects of colestipol-niacin therapy on the common carotid artery. Two- and four-year reduction of intima-media thickness measured by ultrasound","volume":"88","author":"Blankenhorn","year":"1993","journal-title":"Circulation"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1016\/S0735-1097(98)00170-3","article-title":"B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the regression growth evaluation statin study (REGRESS)","volume":"31","author":"de Groot","year":"1998","journal-title":"J Am Coll Cardiol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/jcpe.13639","article-title":"Treatment of stage IV periodontitis: the EFP S3 level clinical practice guideline","volume":"49","author":"Herrera","year":"2022","journal-title":"J Clin Periodontol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5334\/gh.400","article-title":"Periodontitis and cardiovascular diseases. Consensus report","volume":"15","author":"Sanz","year":"2020","journal-title":"Glob Heart"}],"container-title":["Frontiers in Oral Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/froh.2025.1488941\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T01:49:42Z","timestamp":1739152182000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/froh.2025.1488941\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,10]]},"references-count":45,"alternative-id":["10.3389\/froh.2025.1488941"],"URL":"https:\/\/doi.org\/10.3389\/froh.2025.1488941","relation":{},"ISSN":["2673-4842"],"issn-type":[{"value":"2673-4842","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,10]]},"article-number":"1488941"}}