Risk Of Critical Limb Ischemia Research Articles

A miRNA/CXCR4 signaling axis impairs monopoiesis and angiogenesis in diabetic critical limb ischemia.

Patients with peripheral artery disease (PAD) and diabetes have the highest risk of critical limb ischemia (CLI) and amputation, yet the underlying mechanisms remain incompletely understood. MicroRNA (miRNA) sequencing of plasma from diabetic patients with or without CLI was compared to diabetic mice with acute or subacute limb ischemia to identify conserved miRNAs. miRNA-KO mice on high-fat diet were generated to explore the impact on CLI. Comparison of dysregulated miRNAs from diabetic individuals with PAD and diabetic mice with limb ischemia revealed conserved miR-181 family members. High-fat-fed, diabetic Mir181a2b2-KO mice had impaired revascularization in limbs due to abrogation of circulating Ly6Chi monocytes, with reduced accumulation in ischemic skeletal muscles. M2-like KO macrophages under diabetic conditions failed to produce proangiogenic cytokines. Single-cell transcriptomics of the bone marrow niche revealed that the reduced monocytosis in diabetic KO mice was a result of impaired hematopoiesis, with increased CXCR4 signaling in bone marrow Lineage-Sca1+Kit+ (LSK) cells. Exogenous Ly6Chi monocytes from nondiabetic KO mice rescued the impaired revascularization in ischemic limbs of diabetic KO mice. Increased Cxcr4 expression was mediated by the miR-181 target, Plac8. Taken together, our results show that MiR-181a/b is a putative mediator of diabetic CLI and contributes to changes in hematopoiesis, monocytosis, and macrophage polarization.

Risk of critical limb ischemia in long-term uterine cancer survivors: A population-based study.

The risk of critical limb ischemia (CLI) which causes ischemic pain or ischemic loss in the arteries of the lower extremities in long-term uterine cancer (UC) survivors remains unclear, especially in Asian patients, who are younger at the diagnosis of UC than their Western counterparts. To conduct a nationwide population-based study to assess the risk of CLI in UC long-term survivors. UC survivors, defined as those who survived for longer than 5 years after the diagnosis, were identified and matched at a 1:4 ratio with normal controls. Stratified Cox models were used to assess the risk of CLI. From 2000 to 2005, 1889 UC survivors who received surgery alone or surgery combined with radiotherapy (RT) were classified into younger (onset age < 50 years, n = 894) and older (onset age ≥ 50 years, n = 995) groups. While compared with normal controls, the younger patients with diabetes, hypertension, and receiving hormone replacement therapy (HRT) were more likely to develop CLI. In contrast, the risk of CLI was associated with adjuvant RT, obesity, hypertension, and HRT in the older group. Among the UC survivors, those who were diagnosed at an advanced age (> 65 years, aHR = 2.48, P = 0.011), had hypertension (aHR = 2.18, P = 0.008) or received HRT (aHR = 3.52, P = 0.020) were at a higher risk of CLI. In this nationwide study, we found that the risk factors associated with CLI were similar in both cohorts except for adjuvant RT that was negligible in the younger group, but positive in the older group. Among the survivors, hypertension, advanced age, and HRT were more hazardous than RT. Secondary prevention should include CLI as a late complication in UC survivorship programs.

A Nomogram for Predicting the Risk of Critical Limb Ischemia in Adults with Hypertension: A Retrospective Study.

Peripheral arterial disease (PAD) presenting with underlying hypertension (HTN) poses a higher risk of bilateral lower limb amputation than PAD patients without HTN. While the role of HTN management of PAD patients has received limited attention. We analyzed the clinical characteristics of PAD in adults with HTN and explored risk factors for PAD to construct a nomogram for evaluating critical limb ischemia (CLI) and lesion severity. Between January 2014 and December 2019, we retrospectively evaluated 1886 patients with peripheral artery disease with coexisting HTN. Patients were randomly divided into training (n = 1320, 70%) and validation cohorts (n = 566, 30%), and according to the subjective experience of PAD [Fontaine classification (I-II vs III-IV)], patients were further classified into intermittent claudication (IC) and CLI groups. LASSO regression and multivariate Cox proportional hazard analyses were used to construct a nomogram using variables defined in the training cohort, which was validated in the validation cohort. The evaluation of the predictive discriminative, accuracy and clinical application are further analyzed. In the training cohort, optimal independent factors included age, male sex, body mass index, diabetes mellitus, heart rate, triglyceride, and uric acid (AM-BDHTU), which were included in the nomogram predicting the CLI risk (all P < 0.05). The C-index values for CLI risk in PAD with HTN patients were 0.729 (95% CI: 0.704-0.807) and 0.728 (95% CI: 0.652-0.744) in the training and validation sets, respectively. Calibration curves indicated good consistency between predicted and actual outcomes. DCA confirmed the clinical utility of the diagnostic model. The AM-BDHTU nomogram, constructed and validated using simple to obtain clinical variables, when combined with the Fontaine classification, effectively predicts the risk of CLI among PAD patients with HTN.

A Study of the Peripheral Vessels in Patients With Type 2 Diabetes Mellitus With or Without Foot Involvement.

Peripheral vascular disease (PVD) is chronic limb ischemia caused by atherosclerosis of the peripheral arteries. Diabetes mellitus (DM) is a risk factor for this disease. The probability of a diabetic foot ulcer (DFU) is higher in a patient with DM and PVD than in a patient without DM. Ankle-brachial-pressure index (ABPI) allows the measurement of blood flow towards the distal extremities, which could help timely diagnosis, initiate brief therapy, and minimize the risk of critical limb ischemia and loss. This study aims to determine the prevalence of peripheral vascular disease and assess its association with intima-media thickness (IMT) in diabetic patients with and without foot ulcers in India. In the present study, we included all type 2 DM patients. The assessment was conducted clinically by measuring Ankle Brachial Pressure Index (ABPI) radiologically by Duplex Ultrasonography (Samsung HS 70A machine), and Doppler (Linear probe- LA3 - 12A) and IMT were detected. In healthy adults, IMT ranges from 0.25 to 1.5mm, and values above 1.0mm are often considered abnormal and linked with atherosclerosis and significantly increased cardiovascular disease (CVD). In this study, 72 patients with DM were enrolled over the study period; 52 patients presented with DFU, and 20 presented without DFU. The prevalence of PVD was higher in males compared to females; 40% of the patient population in the age range of 40-49 years was with PVD, and 62.5% of patients with PVD showed an IMT value more than 1.0mm, whereas only 5% patients without PVD shows IMT value more than 1.0mm. In conclusion, among type 2 diabetic subjects, the prevalence of PVD is 72.2%, and IMT is strongly associated with PVD.

The Association of Cannabis Use Disorder with Acute Limb Ischemia and Critical Limb Ischemia.

ObjectivesHeavy cannabis use has been associated with the development of acute myocardial infarction and stroke. The objective of this study was to determine if heavy, chronic cannabis use is associated with the development of acute limb ischemia (ALI) or critical limb ischemia (CLI).MethodsWe conducted a retrospective cohort study within the National Inpatient Sample (2006–2015). Patients without cannabis use disorder (CUD) were matched to patients with CUD in a 2:1 ratio using propensity scores. Our primary outcomes were incidence of ALI and CLI. Secondary outcomes included incidence of acute mesenteric ischemia (AMI), chronic mesenteric ischemia (CMI), frequency of open or endovascular interventions, length of stay, and total costs. Sensitivity analyses were performed with alternative models, including in the entire unmatched cohort with regression models utilizing survey weights to account for sampling methodology.ResultsWe identified a cohort of 46,297 857 unmatched patients. Patients with CUD in the unmatched cohort were younger, with less cardiovascular risk factors, but higher rates of smoking and substance abuse. The matched cohort included 824,856 patients with CUD and 1,610,497 controls. Those with CUD had a higher incidence of ALI (OR 1.20 95% CI: 1.04-1.38 P=.016). Following multiple sensitivity analyses, there was no robust association between CLI and CUD. We observed no robust association of CUD with AMI, CMI, procedures performed, frequency of amputation, costs, or total length of stay.ConclusionsCannabis use disorder was associated with a significantly higher incidence of admission for acute limb ischemia. CUD was not associated with an increased risk of critical limb ischemia following sensitivity analysis. Given CUD is often seen in younger, less co-morbid patients it provides an important target for intervention in this population.

Ankle-Brachial Index and Subsequent Risk of Severe Ischemic Leg Outcomes: The ARIC Study.

BackgroundAnkle‐brachial index (ABI) is used to identify lower‐extremity peripheral artery disease (PAD). However, its association with severe ischemic leg outcomes (eg, amputation) has not been investigated in the general population.Methods and ResultsAmong 13 735 ARIC (Atherosclerosis Risk in Communities) study participants without clinical manifestations of PAD (mean age, 54 [SD, 5.8] years; 44.4% men; and 73.6% White) at baseline (1987–1989), we quantified the prospective association between ABI and subsequent severe ischemic leg outcomes, critical limb ischemia (PAD with rest pain or tissue loss) and ischemic leg amputation (PAD requiring amputation) according to discharge diagnosis. Over a median follow‐up of ≈28 years, there were 221 and 129 events of critical limb ischemia and ischemic leg amputation, respectively. After adjusting for demographics, ABI ≤0.90 versus 1.11 to 1.20 had a ≈4‐fold higher risk of critical limb ischemia and ischemic leg amputation (hazard ratios, 3.85 [95% CI, 2.09–7.11] and 4.39 [95% CI, 2.08–9.27]). The magnitude of the association was modestly attenuated after multivariable adjustment (hazard ratios, 2.44 [95% CI, 1.29–4.61] and 2.72 [95% CI, 1.25–5.91], respectively). ABI 0.91 to 1.00 and 1.01 to 1.10 were also associated with these severe leg outcomes, with hazard ratios ranging from 1.7 to 2.0 after accounting for potential clinical and demographic confounders. The associations were largely consistent across various subgroups.ConclusionsIn a middle‐aged community‐based cohort, lower ABI was independently and robustly associated with increased risk of severe ischemic leg outcomes. Our results further support ABI ≤0.90 as a threshold diagnosing PAD and also suggest the importance of recognizing the prognostic value of ABI 0.91 to 1.10 for limb prognosis.

Nationwide study of six-month readmissions in critical limb ischemia: Predictors and impact of revascularization strategies.

There is a paucity of data regarding six-month readmissions in critical limb ischemia patients and the influence of management strategy during index-admission [endovascular, surgical, hybrid procedure, medical therapy, and amputation]. We aimed to investigate the incidence, predictors, and impact of management strategies on six-month readmission in patients with critical limb ischemia. A secondary analysis of the Nationwide Readmissions Database (2016-2017) was conducted. Propensity score matching was performed for subgroup analysis. We identified 50,058 patients with primary diagnosis of critical limb ischemia. Six-month all-cause and critical limb ischemia-related readmission rate was 52.36% and 10.86%, respectively. The risk of all-cause readmission was lower with amputation but was similar among other subgroups. Patients receiving surgical [HR 0.62, CI(0.48-0.79), p < 0.001] and hybrid procedure [HR 0.65 (0.46-0.93), p = 0.02] had lower risk of unplanned critical limb ischemia-related readmission compared to endovascular, though the risk of unplanned revascularization/amputation during readmission was similar between the three strategies. The risk of non-critical limb ischemia-related readmission was higher with surgical [HR 1.13, CI(1.04-1.23), p = 0.003] and hybrid procedure [HR 1.17, CI(1.08-1.28), p < 0.001], driven by increased procedure-related/wound complications. Eventhough endovascular patients were older with more severe critical limb ischemia presentation, a lower proportion received home-health or placement upon discharge from index-admission. This could account for higher readmission without higher repeat revascularization in endovascular group. The risk of critical limb ischemia and non-critical limb ischemia-related readmission differ according to the management strategy. Significant differences in discharge disposition exist depending on revascularization strategy. Study findings identify opportunities for reducing readmissions by focusing on nonprocedural aspects like wound-care, discharge planning and placement.

Kidney Transplantation Reduces the Risk of Critical Limb Ischemia and/or Amputation Among Patients With End-stage Renal Disease on Hemodialysis

Introduction: The objective of the study was to analyze the risk of critical limb ischemia and/or amputation among patients with end-stage renal disease (ESRD) entering a hemodialysis (HD) program and to evaluate the possible protective effect associated with kidney transplantation. Methods: Retrospective cohort including all ESDR patients that started on HD program at our institution between 2000 and 2010. Collected variables included baseline characteristics (pre-entry in hemodialysis), time on HD program, kidney transplantation and the development of critical limb ischemia and/or need for minor or major amputation. Patients with previous symptomatic peripheral arterial disease or amputation were excluded. Statistics: Cox regression model adjusted for all variables related to 1) critical limb ischemia and/or minor/major amputation and 2) renal transplantation. Results: The study group included 336 patients (mean age = 63 years, 221 (66 %) male). The mean follow up was 6, 7 years, with an average time on HD of 4,2 years, and 92 patients (27,4 %) underwent transplantation. Critical limb ischemia and/or amputation free survival rates were 88,6 % and 79,6 % at 5 and 10 years, respectively. The mean follow-up was 6.5 years, and 22 revascularization procedures for critical limb ischemia, 26 minor amputations and 18 major amputations were performed. Kidney transplantation was associated with a protective effect over the development of critical limb ischemia and/or amputation (HR: 0,065; p: < 0,001), after adjustment for diabetes mellitus (HR: 7,316; p< 0,001), a total cholesterol < 125mg/ml (HR: 2,538; p=0,003), time on HD (HR: 1,000; p: 0,003) and male gender (HR: 2,109; p: 0,040). Long-term survival rates of the cohort were 56,8 % and 32,7 % at 5 and 10 years respectively, but decreased to 47 % at 1 year and 18.2 % at 5 years once critical limb ischemia and/or amputation occurred. Conclusion: Patients on HD program show a notorious risk of critical limb ischemia and/or amputation over time. Once this complication occurs patient's survival is markedly reduced. Transplantation confers an independent protective effect over the development of critical limb ischemia and/or amputation. Disclosure: Nothing to disclose

Comparative study between lymphocyte-monocyte ratio and platelet-lymphocyte ratio: novel markers for critical limb ischemia in peripheral arterial disease

Background: Peripheral arterial occlusive disease (PAOD) is frequent and often not diagnosed in time. If treatment is not initiated early, disease progression and development of Critical limb ischemia (CLI) is one possible complication. CLI is an entity with high mortality and high risk of limb amputation. As monocytes play a leading role in progression of atherosclerosis and platelets play a key role in atherosclerosis and atherothrombosis, we investigated Lymphocyte-monocyte ratio (LMR), Platelet lymphocyte ratio (PLR) and its association with CLI in peripheral arterial disease.Methods: Retrospective observational study conducted between January 2015-December 2017 including 50 patients admitted in Rajarajeswari Medical College and Hospital, Bangalore. As an optimal cut-off value, a PLR of 150 and LMR of 5 were identified. Their association with CLI noted.Results: 50 patients with critical limb ischemia, stage 3 and 4 of Fontaine classification were included in this study. 72% patients had LMR less than 5.40% patients had PLR more than 150 and 36% patients had both LMR less than 5 and PLR more than 150. 96% patients with LMR&lt;5 and 72% patients with PLR&gt;150 underwent amputation.Conclusions: An increased PLR and reduced LMR are significantly associated with patients at high risk for CLI. They are broadly available and cost effective. When done in early stage of the disease serves as a marker for CLI and aggressive treatment in such patients will reduce the risk of amputation.

Abstract P308: The Association of Height With Incident Peripheral Arterial Disease in the Atherosclerosis Risk in Communities (ARIC) Study

Background: A number of cross-sectional studies have reported shorter height as a risk factor for peripheral artery disease (PAD) defined by low ABI. People of shorter stature may have a naturally lower ABI stemming from a relatively lower ankle blood pressure, as function of the shorter distance from the heart to the distal leg arteries. If shorter height is related to PAD, height should also be associated with clinical PAD. We aimed to investigate the association of height with clinical PAD and critical limb ischemia (CLI) in a prospective cohort analysis. Methods: Using data from the ARIC Study, we investigated the association of height with development of PAD and CLI, defined based on ICD-9 codes, for the 14,668 participants at Visit 1 without prevalent PAD/CLI over a median follow-up time of 25.9 years. We modeled risk for PAD and CLI over time using Cox proportional hazards regression. Results: 6,652 (45.4%) participants were men, with a mean age of 55 (SD 6) years old, compared to 54 (SD 6) years old in women. 1,460 (22%) men and 2,321 (29%) women were African American. Men tended to be taller and have a higher weight compared to women. Within each sex, there were no significant differences by quartile of height in terms of demographic factors or clinical comorbidities. For men in height quartile 2 compared to quartile 1, there was a decreased risk of PAD in unadjusted analysis (HR=0.69; 95% CI 0.51-0.94). However, this HR was no longer significant after full adjustment (Table 1). In women, the risk of CLI was higher in the fourth quartile of height compared to quartile 1 after adjustment for demographic factors (HR=1.69; 95% CI: 1.00-2.84). However this HR also became non-significant after full adjustment. For both genders, the HR of either PAD or CLI per one SD increase in height was not significant. Conclusions: In contrast to previous cross-sectional studies which showed and association between shorter height and PAD based on ABI, our prospective study showed null associations between height and clinical PAD.

Orbital atherectomy for calcified femoropopliteal lesions: a current review.

The orbital atherectomy system is a novel form of atherectomy that uses orbital sanding and pulsatile forces, an effective method of treatment for peripheral atherosclerotic lesions with varying levels of occlusion. Although the devices only has a general indication from the FDA to treat atherosclerotic lesions, they are effective in treating all kinds of lesions, and can therefore mitigate effects of all severities of peripheral artery disease. This approach to endovascular therapy involves the use of differential sanding to preferentially ablate fibrous, fibrofatty and calcified lesions, while deflecting healthy intima away from the crown. The eccentrically mounted crown design allows the device to employ rhythmic pulsating forces that penetrate the medial layer, and cause cracking in the lesions in order to facilitate easier balloon inflation and intravascular drug elution. The combination of vessel modification and lumen enlargement through sanding can effectively restore blood flow to the extremities, and can eliminate risk of critical limb ischemia, as well as subsequent amputation. Extensive lab testing and clinical trials have confirmed the high success rates and low major adverse events associated with this form of treatment. The device is economically viable as well, since its cost is offset by the lower frequency of adjunctive therapy sessions when compared to other devices. Considering the results outlined in this manuscript, the Diamondback 360° is an effective form of atherectomy therapy for peripheral artery disease. In-depth understanding of the operation preparation, procedure, and best imaging techniques can help to optimize outcomes.

BAD transmission and SAD distribution: a new scenario for critical limb ischemia

Most of the studies on peripheral artery disease (PAD) focused on above-the-ankle artery disease, while less is known about foot artery disease. We hypothesize a scenario were two different diseases can be present in PAD patients, big artery disease (BAD) and small artery disease (SAD), overlapping at the foot level; the aim of this study is to evaluate their prevalence and their correlation with risk factors and critical limb ischemia (CLI) in a large cohort of patients with symptomatic PAD. We retrospectively reviewed 1915 limbs of 1613 patients (502 females, mean age 72.4±10.8 years) who underwent angiography between September 2009 and November 2013. Age, sex, diabetes, smoke history, high blood pressure, dialysis and BMI were considered as risk factors. Logistic regression was performed to test the association of arterial lesions patterns and CLI, and to evaluate the association between risk factors and lesion localization. SAD was present in 414 patients (25.2%). Patients with disease of any of plantar, dorsalis pedis arteries and SAD faced higher risk of CLI (OR=13.25, 95% CI: 1.69-104.16). SAD was associated with diabetes and dialysis (both: OR=4.85; dialysis only: OR=3.60; diabetes only: OR=1.70; none: reference OR; P<0.01), weight (underweight: OR=1.10; normal: reference OR; overweight: OR=0.81; obese: OR=0.60; P=0.03), while women and tobacco smokers were less likely to have SAD (women: OR=0.68; P<0.01; tobacco use: OR=0.54; P<0.01). SAD was strongly and independently associated with CLI, diabetes and dialysis. Thus, SAD should be regarded as a leading actor in CLI.

SHORT TIME RESULT OF PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY ON ISCHEMIA DIABETIC FOOT ULCER

The frequent complication of diabetes mellitus is ischemic diabetic foot ulcers (DFUs). As compared to non-diabetic people, ischemic of foot prevalence is significantly higher in diabetic people. It is related with severe clinical manifestations and the risk of critical limb ischemia and limb loss is increasing. In this case, we performed percutaneous transluminal angioplasty (PTA) in patient with ischemic DFU. A male, 58-year old, complained severe rest pain and gangrene in the fourth toe of the left foot more than 2 months. He had a history of diabetes mellitus type 2 for 4 years ago with uncontrolled blood sugar. We perform PTA to decrease the rest pain and prevent expand of the gangrene. The result of PTA was shown instant effect to reduce rest pain, pulses are easily palpable, and there was no expansion of the gangrene.

Low mean platelet volume is associated with critical limb ischemia in peripheral arterial occlusive disease

Mean platelet volume (MPV) was recently published as a possible marker of coronary artery disease in patients at high risk for major adverse cardiac events. Because platelets play an important role in atherosclerosis, we examined the relationship between critical limb ischemia (CLI) and MPV in patients with peripheral arterial occlusive disease (PAOD). Our study comprised 2124 PAOD patients. Univariate logistic regression was performed to analyze potential predictors for CLI. Nagelkerke’s R² is reported. Cross validation was performed using the leave-one-out principle. ROC analyses were performed to identify the best cut off value for MPV predicting CLI; to this end, Youden’s index was calculated. For CLI diabetes (p < 0.001, OR 2.44, 95% CI 1.97–3.02), hsCRP (p < 0.001, OR 1.01, 95% CI 1.01–1.01), age (p < 0.001, OR 1.05, 95% CI 1.04–1.06), thrombocytosis (p = 0.025, OR 1.84, 95%CI 1.08–3.14), and MPV (p = 0.003, OR 0.84, 95% CI 0.75–0.94) were significant independent predictors for CLI. ROC analysis (AUC: 0.55, 95% CI 0.52–0.58, p < 0.001) showed ≤10.2 as the best cut off value for MPV to predict CLI. As there is a significant relationship between low MPV and a high risk for CLI in PAOD patients, MPV can be used to identify patients who are likely to develop CLI.

Low molecular weight fucoidan ameliorates hindlimb ischemic injury in type 2 diabetic rats

Ethnopharmacological relevanceLow molecular weight fucoidan (LMWF), extracted from Laminaria japonica Areschoug, is a traditional Chinese medicine, commonly used to alleviate edema, particularly for feet with numbness and pain. Aim of the studyDiabetic mellitus (DM) patients are at high risk of developing peripheral arterial disease (PAD). Individuals with DM and PAD co-morbidity have a much higher risk of critical limb ischemia. LMWF showed several beneficial effects, such as anti-inflammation, anti-thrombosis, and enhancing revascularization. Therefore, we hypothesized that LMWF might be beneficial to diabetes-induced PAD, and investigated the therapeutic potential of LMWF on diabetic PAD rats. Materials and methodsType 2 diabetic Goto-Kakizaki (GK) rats were made PAD by injection of sodium laurate into femoral artery. LMWF (20, 40 or 80mg/kg/day) or cilostazol (100mg/kg/day) were given to diabetic PAD rats for 4 weeks, respectively. The effects of LMWF on foot ulceration and claudication, plantar blood flow, collateral vessel formation, endothelium morphology, gastrocnemius injury, platelet aggregation, vessel vasodilation, and the expressions of inflammation factors, VEGF, eNOS, and nitric oxide were measured. ResultsWe found that LMWF markedly ameliorated foot ulceration and claudication, and improved the plantar perfusion by reversing hyperreactive platelet aggregation, ameliorating endothelium-dependent vasodilation and revascularization on diabetic PAD rats. In addition, upregulation of several inflammatory factors, such as ICAM-1 and IL-1β in the gastrocnemius muscles of ischemic hindlimb were suppressed by LMWF administration. And eNOS phosphorylation at Ser1177 and NO production were significantly enhanced in LMWF-treated diabetic PAD rats. ConclusionsTaken together, our findings demonstrated that LMWF exhibits therapeutic effect on hindlimb ischemia in type 2 diabetic rats likely through ameliorating endothelium eNOS dysfunction and enhancing revascularization, thus, providing a potential supplementary non-invasive treatment for diabetes-induced PAD.

Results of peripheral bypass surgery in patients with critical limb ischemia (CRITISCH registry).

AimOn the basis of the CRITISCH registry outcomes in patients with critical limb ischemia (CLI) undergoing lower extremity bypass surgery were analyzed according to the site of distal anastomosis and type of bypass material.Patients and methodsA total of 284 patients with lower extremity bypasses consisting of 75 patients with bypasses above the knee (group 1), 80 with bypasses below the knee (group 2) and 129 crural or pedal bypasses (group 3) were included in the study. Altogether, 159 autologous saphenous vein grafts and 125 synthetic grafts were used.ResultsThere were no perioperative complications in 191 out of the 284 patients (67.3 %) and 236 of the 284 patients (83.1 %) had open bypasses at hospital discharge. An uneventful postoperative course was observed in 76 % of the patients in group 1, 62.5 % in group 2 and 65.1 % in group 3. Amputation-free survival was 86 % at 1 year in group 1, 65 % in group 2 and 69 % in group 3. For bypasses above the knee synthetic grafts were at least not inferior to vein grafts (amputation-free survival at 1 year: prosthetic bypasses 92 % and saphenous vein grafts 71 %, p = 0.147), whereas in the crural/pedal bypass group vein grafts showed better amputation-free survival at 1 year (76 %) compared with synthetic bypasses (56 %, p = 0.105). Patients with a PREVENT III (PIII) CLI risk score ≤3 exhibited better amputation-free survival at 1 year (78 %) compared to patients with a PIII CLI risk score of 4–7 (69 %, p = 0.053). The same applied to patients with Rutherford class 4 vs. Rutherford class 6 CLI.ConclusionIn patients with CLI and above-knee bypasses, vein grafts confer no benefits compared with synthetic grafts for at least 1 year follow-up; however, in the case of more distal anastomoses vein grafts should be preferred.

The AST/ALT (De-Ritis) ratio: A novel marker for critical limb ischemia in peripheral arterial occlusive disease patients.

The aspartat aminotransferase (AST)/alanin aminotransferase (ALT) (De-Ritis) ratio (AAR) is an easily applicable blood test. An elevated AAR on the one hand has been associated with an increase in nonalcoholic fatty liver disease (NAFLD). NAFLD on the other hand is associated with an increase in cardiovascular disease, all-cause mortality, and diabetes. As the AAR is also elevated in case of muscular damage, we investigated AAR and its association with critical limb ischemia (CLI) in peripheral arterial occlusive disease (PAOD) patients.In our cross-sectional study, we included 1782 PAOD patients treated at our institution from 2005 to 2010. Patients with chronic alcohol consumption (>20 g/day) were excluded. AAR was calculated and the cohort was categorized into tertiles according to the AAR. An optimal cut-off value for the continuous AAR was calculated by applying a receiver operating curve analysis to discriminate between CLI and non-CLI.In our cohort, occurrence of CLI significantly increased with an elevation in AAR. As an optimal cut-off value, an AAR of 1.67 (sensitivity 34.1%, specificity 81.0%) was identified. Two groups were categorized, 1st group containing 1385 patients (AAR < 1.67) and a 2nd group with 397 patients (AAR > 1.67). CLI was more frequent in AAR > 1.67 patients (166 [41.9%]) compared to AAR < 1.67 patients (329 [23.8%]) (P < 0.001), as was prior myocardial infarction (28 [7.1%] vs 54 [3.9%], P = 0.01). Regarding inflammatory parameters, C-reactive protein (median 8.1 mg/L [2.9–28.23] vs median 4.3 mg/L [2.0–11.5]) and fibrinogen (median 427.5 mg/dL [344.25–530.0] vs 388.0 mg/dL [327.0–493.0]) also significantly differed in the 2 patient groups (both P < 0.001). Finally, an AAR > 1.67 was associated with an odds ratio (OR) of 2.0 (95% confidence interval [CI] 1.7–2.3) for CLI even after adjustment for other well-established vascular risk factors.An increased AAR is significantly associated with patients at high risk for CLI and other cardiovascular endpoints. The AAR is a broadly available and cheap marker, which might be useful to highlight patients at high risk for vascular endpoints.

Graz Critical Limb Ischemia Score: A Risk Score for Critical Limb Ischemia in Peripheral Arterial Occlusive Disease.

Critical limb ischemia (CLI), a frequently encountered disorder, is associated with a high rate of limb amputation and mortality. To identify patients at high risk for CLI, we developed a simple risk score for peripheral arterial occlusive disease (PAOD).In our cross-sectional study, we first evaluated 1000 consecutive PAOD patients treated at our institution from 2005 to 2007, documenting clinical symptoms, comorbidities, and concomitant medication. We calculated odds ratios (OR) in a binary logistic regression model to find possible risk factors for CLI. We then verified the score in a second step that included the 1124 PAOD patients we treated between 2007 and 2011.In the first patient group, the greatest risk factors for CLI were age ≥75 years (OR 2.0), type 2 diabetes (OR 3.1), prior myocardial infarction (OR 2.5), and therapy with low molecular weight heparins (2.8). We scored 1 point for each of those conditions. One point was given for age between 65 and 75 years (OR 1.6) as well as for therapy with cardiac glycosides (OR 1.9) or loop diuretic therapy (OR 1.5). As statin therapy was protective for CLI with an OR of 0.5, we subtracted 1 point for those patients.In the second group, we could prove that frequency of CLI was significantly higher in patients with a high CLI score. The score correlated well with inflammatory parameters (c-reactive protein and fibrinogen). We were also able to define 3 different risk groups for low (score −1 to 1), intermediate (score 2–4), and high CLI risk (score >4).We developed a simple risk stratification scheme that is based on conditions that can be easily assessed from the medical history, without any laboratory parameters. This score should help to identify PAOD patients at high risk for CLI.

Association of the Derived Neutrophil-Lymphocyte Ratio With Critical Limb Ischemia.

Neutrophil and leukocyte counts are laboratory parameters that reflect the systemic inflammatory response in patients with atherosclerotic diseases. Based on the means of these parameters, the derived neutrophil-lymphocyte ratio (dNLR) can be calculated. We investigated a possible association of critical limb ischemia (CLI) and the dNLR in patients with peripheral arterial disease (PAD). We performed a retrospective data analysis including 1995 patients with PAD treated at our department in the years 2005 to 2010. The cohort was divided into tertiles according to dNLR. Higher dNLR values were associated with an increased CLI rate. In the tertile with lowest dNLR, the CLI rate was 20.4%, in the second tertile the CLI rate was 26.1%, and in the third tertile the CLI rate was 36.1%. Statistical significance was shown using a Jonckheere-Terpstra test (P < .001). A high dNLR is associated with an increased rate of CLI in patients with PAD. This might be a useful parameter to highlight patients at increased risk of CLI.

Elevated Blood Urea Nitrogen is Associated With Critical Limb Ischemia in Peripheral Arterial Disease Patients.

As renal function is often impaired in atherosclerosis patients, accelerating atherosclerosis per se and creating a vicious cycle, we investigated the association of blood urea nitrogen (BUN) and critical limb ischemia (CLI) in peripheral arterial occlusive disease (PAOD) patients.Our cross-sectional study included 1521 PAOD patients, with normal and impaired renal function treated at our institution from 2005 to 2010. Patients on renal replacement therapy were excluded. The cohort was divided into tertiles according to the serum BUN levels. An optimal cutoff value for the continuous BUN was calculated by applying a receiver-operating curve analysis to discriminate between CLI and non-CLI.In our cohort, CLI increased significantly with an increase in BUN (13.1% in the first tertile, 18.7% in the second tertile, 29.0% in the third tertile, P for trend <0.001). A BUN of 17.7 mg/dL was identified as an optimal cutoff. Accordingly, there were 2 groups of patients: 636 patients with BUN ≤ 17.7 and 885 patients with BUN > 17.7. CLI was more frequent in BUN > 17.7 patients (342 [38.6%]) than in BUN ≤ 17.7 patients (134 [21.1%]) (P < 0.001); the same applied to prior myocardial infarction (45 [5.1%] vs 15 [2.4%], P = 0.007) and congestive heart failure (86 [9.7%] vs 31 [4.9%], P < 0.001). A BUN > 17.7 was associated with an odds ratio of 1.6 (95% confidence interval: 1.3–1.9, P < 0.001) for CLI even after the adjustment for other established vascular risk factors such as age ≥75 and type 2 diabetes.An increased BUN is significantly associated with a high risk for CLI and other vascular endpoints. The BUN is an easily determinable, broadly available, and inexpensive marker that could be used to identify patients at high risk for vascular endpoints.