Aims/hypothesis

Diabetes-related foot ulceration (DFU) is associated with increased cardiovascular risk, but the mechanisms remain unclear. Inflammation and infection are mediators of CVD, which may be important in DFU.

Methods

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−/I−), not deep but infected (D−/I+), deep with no infection (D+/I−) 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.

Results

Of 513 patients, 241 (47.0%) were in the D−/I− group, 110 (21.4%) were in the D−/I+ group, 35 (6.8%) were in the D+/I− 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 220–551) and 404 days (IQR 228–576), respectively. Infection was associated with significantly higher MACE or all-cause mortality (21.5% vs 8.7%; p<0.001) and MACE alone (13.5% vs 5.1%; p=0.003). MACE or all-cause mortality was significantly higher in the D+/I+ group (D−/I− 7.9%; D−/I+ 15.5%; D+/I− 14.3%; D+/I+ 26.8%; p<0.001), as was MACE alone (D−/I− 5.0%; D−/I+ 10.9%; D+/I− 5.7%; D+/I+ 15.7%; p=0.017). Infection and a deep ulcer were independent predictors of adverse outcomes.

Conclusions/interpretation

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.

Graphical Abstract

中文翻译：

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深部和感染性糖尿病相关足部溃疡患者发生主要不良心血管事件的风险增加

 目标/假设

糖尿病相关足溃疡 （DFU） 与心血管风险增加有关，但机制尚不清楚。炎症和感染是 CVD 的介质，这在 DFU 中可能很重要。

 方法

分析了从参加多学科 DFU 服务的患者那里前瞻性收集的数据。深部溃疡被定义为到达肌肉、肌腱或更深结构的溃疡。患者被分为四个 DFU 组：不深部且无感染 （D-/I-）、不深部但感染 （D-/I+）、深部无感染 （D+/I−） 或深部感染 （D+/I+）。事件主要不良心血管事件 （MACE） 定义为因心肌梗死、中风或短暂性脑缺血发作或心力衰竭住院。使用 logrank 检验和多变量 Cox 回归进行生存分析。

 结果

在 513 例患者中，241 例 （47.0%） 为 D-/I− 组，110 例 （21.4%） 为 D-/I+ 组，35 例 （6.8%） 为 D+/I− 组，127 例 （24.8%） 为 D+/I+ 组。中位随访 381 天 （IQR 220-551） 和 404 天 （IQR 228-576） 后，75 例患者 （14.6%） 发生 MACE 或全因死亡率，46 例患者 （9.0%） 单独发生 MACE。感染与显着较高的 MACE 或全因死亡率相关 （21.5% 对 8.7%;p<0.001）和单独的 MACE （13.5% 对 5.1%;p = 0.003）。D+/I+ 组的 MACE 或全因死亡率显著更高 （D-/I-7.9%;D−/I+ 15.5%;D+/I− 14.3%;D+/I+ 26.8%;p<0.001），单独使用 MACE 也是如此 （D-/I- 5.0%;D-/I+ 10.9%;D+/I− 5.7%;D+/I+ 15.7%;p=0.017）。感染和深部溃疡是不良结局的独立预测因子。

结论/解释

与不深或未感染的 DFU 相比，深部和/或感染的 DFU 与心血管风险增加相关。这些发现提供了一个需要研究的潜在机制解释。

 图形摘要