Abstract 16512: Amputation in Patients With Pad With and Without Diabetes: Insights From the EUCLID Trial

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nicholas Govsyeyev ◽  
Mark R Nehler ◽  
Cecilia C Low Wang ◽  
Sarah Kavanagh ◽  
William R Hiatt ◽  
...  

Background/Introduction: Amputation is a major morbidity of peripheral artery disease (PAD). Although traditionally attributed to ischemia, the multifactorial nature is increasingly recognized, particularly in those with concomitant diabetes mellitus (DM). Elucidating the drivers of amputation in PAD with and without DM may be important in developing strategies for prevention. Purpose: To elucidate the primary drivers of amputations in patients with PAD with and without DM. Methods: EUCLID randomized 13,885 patients with PAD. Investigators prospectively reported all amputations. In this post-hoc analysis, amputations (major – ankle and above, minor – distal to ankle) were retrospectively adjudicated using safety data when available to characterize the drivers including infection, ischemia, or multifactorial. Etiologies were evaluated by DM status at baseline. Results: A total of 415 patients (3% of total) underwent 533 (260 major and 263 minor) amputations over a median of 30 months. Of these, 360 (68%) occurred in the 5,345 patients with DM (n/N of 6.7%) and 173 (32%) occurred in the 8,450 patients without DM (n/N of 2.0%). There were 172 non-traumatic amputations with sufficient documentation to determine drivers. Ischemia was the primary driver overall (51%) followed by infection (27%) and multifactorial (22%). The primary driver, however, varied by DM status with the dominant driver in those with DM being infection (59%) and in those without DM, ischemia (82%) ( Fig. 1 ). The etiology varied for major and minor with the former driven by ischemia (65%) and the latter driven by infection (59%). Conclusions: Amputations in PAD appear to have different primary drivers depending on concomitant DM. Infection may have a larger role in those with DM and ischemia in those without DM. Further research to elucidate the pathobiology and predictors of these outcomes may help in the development of strategies for prevention.

2018 ◽  
Vol 15 (6) ◽  
pp. 504-510 ◽  
Author(s):  
Lars Richter ◽  
Eva Freisinger ◽  
Florian Lüders ◽  
Katrin Gebauer ◽  
Matthias Meyborg ◽  
...  

Background: The prevalence of diabetes mellitus and its associated complications such as peripheral artery disease is increasing worldwide. We aimed to explore the distinct impact of type 1 diabetes mellitus and type 2 diabetes mellitus on treatment and on short- and long-term outcome in patients with peripheral artery disease. Methods: Retrospective analysis of anonymized data of hospitalized patients covered by a large German health insurance. Assessment of patient’s characteristics (comorbidities, complications, etc.) and outcome using multivariable Cox regression and Kaplan–Meier curves. Results: Among 41,702 patients with peripheral artery disease, 339 (0.8%) had type 1 diabetes mellitus and 13,151 (31.5%) had type 2 diabetes mellitus. Patients with diabetes mellitus had more comorbidities and complications than patients without diabetes mellitus ( p < 0.001). Type 1 diabetes mellitus patients exhibited the highest risk for limb amputation at 4-year follow-up (44.6% vs 35.1%, p < 0.001), while type 2 diabetes mellitus patients had higher mortality than type 1 diabetes mellitus (43.6% vs 31.0%, p < 0.001). Conclusion: Although the fraction of type 1 diabetes mellitus among patients with peripheral artery disease and diabetes mellitus is low, it represents a subset of patients being at particular high risk for limb amputation. Research focused on elaborating the determinants of limb amputation and mortality in peripheral artery disease patients with diabetes mellitus is warranted to improve the poor prognosis of these patients.


Open Heart ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. e000955 ◽  
Author(s):  
Cian P McCarthy ◽  
Shreya Shrestha ◽  
Nasrien Ibrahim ◽  
Roland R J van Kimmenade ◽  
Hanna K Gaggin ◽  
...  

BackgroundPatients with diabetes mellitus (DM) are at substantial risk of developing peripheral artery disease (PAD). We recently developed a clinical/proteomic panel to predict obstructive PAD. In this study, we compare the accuracy of this panel for the diagnosis of PAD in patients with and without DM.Methods and resultsThe HART PAD panel consists of one clinical variable (history of hypertension) and concentrations of six biomarkers (midkine, kidney injury molecule-1, interleukin-23, follicle-stimulating hormone, angiopoietin-1 and eotaxin-1). In a prospective cohort of 354 patients undergoing peripheral and/or coronary angiography, performance of this diagnostic panel to detect ≥50% stenosis in at least one peripheral vessel was assessed in patients with (n=94) and without DM (n=260). The model had an area under the receiver operating characteristic curve (AUC) of 0.85 for obstructive PAD. At optimal cut-off, the model had 84% sensitivity, 75% specificity, positive predictive value (PPV) of 84% and negative predictive value (NPV) of 75% for detection of PAD among patients with DM, similar as in those without DM. In those with DM, partitioning the model into five levels resulted in a PPV of 95% and NPV of 100% in the highest and lowest levels, respectively. Abnormal scores were associated with a shorter time to revascularisation during 4.3 years of follow-up.ConclusionA clinical/biomarker model can predict with high accuracy the presence of PAD among patients with DM.Trial registration numberNCT00842868.


2019 ◽  
Vol 24 (5) ◽  
pp. 383-394 ◽  
Author(s):  
Prakash Krishnan ◽  
Pedro R Moreno ◽  
Irene C Turnbull ◽  
Meerarani Purushothaman ◽  
Urooj Zafar ◽  
...  

Diabetes mellitus (DM) and chronic kidney disease (CKD) separately are known to facilitate the progression of medial arterial calcification (MAC) in patients with symptomatic peripheral artery disease (PAD), but their combined effect on MAC and associated mediators of calcification is not well studied. The association of MAC and calcification inducer bone morphogenetic protein (BMP-2) and inhibitor fetuin-A, with PAD, is well known. Our aim was to investigate the association of MAC with alterations in BMP-2 and fetuin-A protein expression in patients with PAD with DM and/or CKD. Peripheral artery plaques (50) collected during directional atherectomy from symptomatic patients with PAD were evaluated, grouped into no-DM/no-CKD ( n = 14), DM alone ( n = 10), CKD alone ( n = 12), and DM+CKD ( n = 14). MAC density was evaluated using hematoxylin and eosin, and alizarin red stain. Analysis of inflammation, neovascularization, BMP-2 and fetuin-A protein density was performed by immunohistochemistry. MAC density, inflammation grade and neovessel content were significantly higher in DM+CKD versus no-DM/no-CKD and CKD ( p < 0.01). BMP-2 protein density was significantly higher in DM+CKD versus all other groups ( p < 0.01), whereas fetuin-A protein density was significantly lower in DM+CKD versus all other groups ( p < 0.001). The combined presence of DM+CKD may be associated with MAC severity in PAD plaques more so than DM or CKD alone, as illustrated in this study, where levels of calcification mediators BMP-2 and fetuin-A protein were related most robustly to DM+CKD. Further understanding of mechanisms involved in mediating calcification and their association with DM and CKD may be useful in improving management and developing therapeutic interventions.


2009 ◽  
Vol 6 (2) ◽  
pp. 80-86 ◽  
Author(s):  
S. Tavintharan ◽  
Ning Cheung ◽  
Su Chi Lim ◽  
Wanting Tay ◽  
Anoop Shankar ◽  
...  

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