Diabetic foot ulcer is associated with cardiovascular-related mortality and morbidity – a systematic review and meta-analysis of 8062 patients

Chin, Brian Zhaojie; Lee, Peng; Sia, Ching-Hui; Hong, Choon Chiet

doi:10.1007/s12020-024-03696-5

Cited by 3 publications

(1 citation statement)

References 37 publications

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“…Although relevant micro- and macrovascular complication rates have declined substantially in high-income countries over the past 30 years ( 11 , 12 ), it is not known whether this is also the case for DFU. Cardiovascular risk reduction is a major part of diabetes care, and it is likely that peripheral arterial disease and microvascular sclerosis associated with DFU reflects established arterial disease elsewhere in the body ( 13 ). A possible decrease in CVD risk factors could impact DFU prevalence.…”

Section: Introductionmentioning

confidence: 99%

Decreasing lifetime prevalence of diabetes-related foot ulcers in Norway: repeated cross-sectional population-based surveys from the HUNT study (1995-2019)

Riise,

Igland,

Graue

et al. 2024

Front. Endocrinol.

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Background and aimsDiabetes-related foot ulcers (DFU) are a persistent healthcare challenge, impacting both patients and healthcare systems, with adverse effects on quality of life and productivity. Our primary aim was to examine the trends in lifetime prevalence of DFU, as well as other micro- and macrovascular complications in the Trøndelag Health Study (HUNT) in Norway.MethodsThis study consists of individuals ≥20 years with diabetes participating in the population-based cross-sectional HUNT surveys (1995-2019). Prevalence ratios, comparing the lifetime prevalence of DFU and other relevant micro- and macrovascular complications between the HUNT surveys, were calculated using Poisson regression.ResultsThe lifetime prevalence (95% confidence interval (CI)) of a DFU requiring three or more weeks to heal was 11.0% (9.5-12.7) in HUNT2, 7.5% (6.3-8.8) in HUNT3 and 5.3% (4.4-6.3) in HUNT4. The decrease in DFU prevalence from 1995 to 2019 was observed in both men and women, for all age groups, and for both type 1 and type 2 diabetes. The highest lifetime prevalence of DFU was found among those with type 1 diabetes. The decrease in HbA1c from HUNT2 to HUNT4 did not differ between those with and without a DFU. The prevalence of chronic kidney disease (eGFR <60 mL/min/1.73 m2 (eGFR categories G3-G5)) increased in both individuals with and without a DFU.ConclusionResults from the HUNT surveys show a substantial decline in the lifetime prevalence of DFU from 1995 to 2019.

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Section: Introductionmentioning

confidence: 99%

Decreasing lifetime prevalence of diabetes-related foot ulcers in Norway: repeated cross-sectional population-based surveys from the HUNT study (1995-2019)

Riise,

Igland,

Graue

et al. 2024

Front. Endocrinol.

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Increased risk of major adverse cardiovascular events in patients with deep and infected diabetes-related foot ulcers

Lan,

Hiew,

Ferreira

et al. 2024

Diabetologia

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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

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Unravelling the cardio-renal-metabolic-foot connection in people with diabetes-related foot ulceration: a narrative review

Lan,

Dwivedi,

Fegan

et al. 2024

Cardiovasc Diabetol

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Diabetes-related foot ulceration (DFU), a serious but preventable complication of diabetes, is a leading cause of hospitalisation, lower extremity amputation and disability worldwide. People with DFU have a greater burden of cardiovascular risk factors, heart failure and chronic kidney disease, resulting in over two-fold higher risk of cardiovascular death compared with people with diabetes without DFU. Here, we propose a “cardio-renal-metabolic-foot” connection in people with diabetes based on shared pathophysiological mechanisms linking DFU with cardiovascular and renal disease. Whilst these mechanistic links remain to be fully elucidated, systemic inflammation and infection in the context of DFU are postulated as key mediators in the development, and progression of, cardiovascular and renal disease. However, cardiovascular and renal disease are also implicated in the pathogenesis of DFU, highlighting the multi-directional interplay between conditions. The impact of screening, prevention, and early management of cardiovascular complications associated with DFU requires further research. Multi-modality cardiac imaging could play a role in unravelling disease mechanisms leading to novel therapeutic strategies, as well as facilitating personalised risk assessment and management. Recent clinical trials have transformed the therapeutic landscape for people with type 2 diabetes, by demonstrating that sodium glucose co-transporter 2 inhibitors, glucagon-like peptide-1 agonists and non-steroidal mineralocorticoid receptor antagonists improve cardiovascular and renal outcomes. Although dedicated research in people with DFU is warranted, these therapies could target multiple facets of the “cardio-renal-metabolic-foot” connection. The holistic, person-centred approach to managing DFU should incorporate new multidisciplinary models of care focusing on the prevention and management of cardiovascular and kidney disease. Graphical abstract The cardio-renal-metabolic-foot connection in people with diabetes. There is a critical need for (1) a better understanding of mechanisms connecting DFU with cardiovascular and kidney disease, perhaps guided by cardiac imaging, novel biomarkers, multi-omics and artificial intelligence to facilitate current treatments and the development of novel therapeutic strategies, (2) more data from clinical trials, registries and biobanks to inform clinical guidelines and evidence-based medicine, and (3) health system-wide integration of structured models of care with a contemporary emphasis on cardio-renal-metabolic-foot health to improve patient outcomes. DFU diabetes-related foot ulceration. Created with BioRender.com

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Diabetic foot ulcer is associated with cardiovascular-related mortality and morbidity – a systematic review and meta-analysis of 8062 patients

Cited by 3 publications

References 37 publications

Decreasing lifetime prevalence of diabetes-related foot ulcers in Norway: repeated cross-sectional population-based surveys from the HUNT study (1995-2019)

Decreasing lifetime prevalence of diabetes-related foot ulcers in Norway: repeated cross-sectional population-based surveys from the HUNT study (1995-2019)

Increased risk of major adverse cardiovascular events in patients with deep and infected diabetes-related foot ulcers

Unravelling the cardio-renal-metabolic-foot connection in people with diabetes-related foot ulceration: a narrative review

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