{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T07:08:58Z","timestamp":1783926538331,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H03299"],"award-info":[{"award-number":["22H03299"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K24557"],"award-info":[{"award-number":["23K24557"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJFR205J"],"award-info":[{"award-number":["JPMJFR205J"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although positive associations between fewer remaining teeth and an increased risk of various systemic diseases have been reported, the precise dose\u2010response relationship has not been fully clarified. This study aimed to evaluate the non\u2010linearity of the dose\u2010response association between the number of lost teeth and the risk of cardiovascular diseases among middle\u2010aged adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study, with over 5 years of follow\u2010up, was based on medical claims and health check\u2010up data. Participants were adults aged 40\u201364 in Japan. The outcome was the incidence of cardiovascular diseases. Exposure variables were the number of lost teeth, which was modeled using a restricted cubic spline. A Cox proportional hazards model was fitted to estimate hazard ratios (HRs) and 95% confidence intervals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the 551,386 participants (mean age\u00a0=\u00a050.0 years [SD\u00a0=\u00a06.7], male\u00a0=\u00a052.0%), the incidence rate of cardiovascular diseases was 0.70 per 100 person\u2010years. A significant non\u2010linear dose\u2010response association was observed between the number of lost teeth and cardiovascular disease risk (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.004). Although the risk increased with greater tooth loss, the dose\u2010response curve bent at around four lost teeth, with an HR of 1.09 (1.05\u20131.14) at four teeth lost and 1.21 (1.08\u20131.37) at 27 teeth lost (reference: \u201cno tooth loss\u201d).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest no clear threshold exists in the non\u2010linear dose\u2010response association between tooth loss and cardiovascular disease risk. Comprehensive public health strategies to prevent periodontal diseases and dental caries are essential throughout life to minimize tooth loss and its systemic consequences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>This retrospective cohort study of 551,386 middle\u2010aged adults found a significant non\u2010linear dose\u2010response association between tooth loss and the risk of cardiovascular diseases. Cardiovascular disease risk increased as the number of lost teeth increased; however, the dose\u2010response curve showed an inflection at around four lost teeth, with no clear threshold observed in the association between tooth loss and cardiovascular disease risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.70167","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T06:32:38Z","timestamp":1783924358000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Non\u2010linear association between tooth loss and cardiovascular diseases among middle\u2010aged adults"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8683-4484","authenticated-orcid":false,"given":"Taro","family":"Kusama","sequence":"first","affiliation":[{"name":"Division of Statistics and Data Science Liaison Center for Innovative Dentistry Tohoku University Graduate School of Dentistry  Miyagi Japan"},{"name":"Department of International and Community Oral Health Tohoku University Graduate School of Dentistry  Miyagi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudai","family":"Tamada","sequence":"additional","affiliation":[{"name":"Department of International and Community Oral Health Tohoku University Graduate School of Dentistry  Miyagi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7195-3584","authenticated-orcid":false,"given":"Takashi","family":"Miyano","sequence":"additional","affiliation":[{"name":"Department of International and Community Oral Health Tohoku University Graduate School of Dentistry  Miyagi Japan"},{"name":"Department of Medical and Robotic Engineering Design Tokyo University of Science  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Health Care Administration and Management Kyushu University Graduate School of Medical Sciences  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Futoshi","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Health Care Administration and Management Kyushu University Graduate School of Medical Sciences  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Osaka","sequence":"additional","affiliation":[{"name":"Department of International and Community Oral Health Tohoku University Graduate School of Dentistry  Miyagi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhisa","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Health Care Administration and Management Kyushu University Graduate School of Medical Sciences  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8769-8955","authenticated-orcid":false,"given":"Kenji","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Division of Statistics and Data Science Liaison Center for Innovative Dentistry Tohoku University Graduate School of Dentistry  Miyagi Japan"},{"name":"Department of International and Community Oral Health Tohoku University Graduate School of Dentistry  Miyagi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)31146\u20108"},{"issue":"7","key":"e_1_2_10_3_1","first-page":"20s","article-title":"Global burden of severe tooth loss : a systematic review and meta\u2010analysis","volume":"93","author":"Kassebaum NJ","year":"2014","journal-title":"JDR Clin Trans 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