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Inflammation and infection are mediators of CVD, which may be important in DFU.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Prospectively collected data from patients attending a multidisciplinary DFU service were analysed. A deep ulcer was defined as one that reached muscle, tendon or deeper structures. Patients were categorised into four DFU groups: not deep and no infection (D\u2212\/I\u2212), not deep but infected (D\u2212\/I+), deep with no infection (D+\/I\u2212) or deep with infection (D+\/I+). Incident major adverse cardiovascular events (MACE) were defined as hospitalisation for myocardial infarction, stroke or transient ischaemic attack, or heart failure. Survival analyses were performed using the logrank test and multivariate Cox regression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Of 513 patients, 241 (47.0%) were in the D\u2212\/I\u2212 group, 110 (21.4%) were in the D\u2212\/I+ group, 35 (6.8%) were in the D+\/I\u2212 group and 127 (24.8%) were in the D+\/I+ group. MACE or all-cause mortality occurred in 75 patients (14.6%), and MACE alone occurred in 46 patients (9.0%) after median follow-up of 381 days (IQR 220\u2013551) and 404 days (IQR 228\u2013576), respectively. Infection was associated with significantly higher MACE or all-cause mortality (21.5% vs 8.7%; <jats:italic>p<\/jats:italic>&lt;0.001) and MACE alone (13.5% vs 5.1%; <jats:italic>p<\/jats:italic>=0.003). MACE or all-cause mortality was significantly higher in the D+\/I+ group (D\u2212\/I\u2212 7.9%; D\u2212\/I+ 15.5%; D+\/I\u2212 14.3%; D+\/I+ 26.8%; <jats:italic>p<\/jats:italic>&lt;0.001), as was MACE alone (D\u2212\/I\u2212 5.0%; D\u2212\/I+ 10.9%; D+\/I\u2212 5.7%; D+\/I+ 15.7%; <jats:italic>p<\/jats:italic>=0.017). Infection and a deep ulcer were independent predictors of adverse outcomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\/interpretation<\/jats:title>\n            <jats:p>Deep and\/or infected DFUs are associated with increased cardiovascular risk compared with DFUs that are not deep or infected. These findings provide a potential mechanistic explanation that requires investigation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical Abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1007\/s00125-024-06316-z","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T15:01:49Z","timestamp":1730991709000},"page":"460-470","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Increased risk of major adverse cardiovascular events in patients with deep and infected diabetes-related foot ulcers"],"prefix":"10.1007","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7222-7314","authenticated-orcid":false,"given":"Nick S. 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This activity has been supported by the Western Australian Future Health Research and Innovation Fund (WA Near Miss Awards Emerging Leaders 2022, to EJH).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"NSRL has received research funding from Sanofi as part of a Clinical Fellowship in Endocrinology and Diabetes, education support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, CSL Seqirus, Eli Lilly, Novartis and Pfizer, and speaker honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Menarini, Novartis and Sanofi, and has participated in advisory boards for Eli Lilly. GD has delivered paid lectures for AstraZeneca, Pfizer and Amgen, and provides consultancy services for and has equity interest in Artrya Ltd.\u00a0The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"All authors were involved in the conception, design and conduct of the study and interpretation of the results. NSRL was involved in the statistical analysis and wrote the first draft of the manuscript. All authors edited, reviewed and approved the final version of the manuscript. NSRL is the guarantor of this work, and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}