Peripheral Arterial Occlusive Disease Patients Research Articles

INCREASED SERUM SCLEROSTIN LEVEL IS A RISK FACTOR FOR PERIPHERAL ARTERY OCCLUSIVE DISEASE IN PATIENTS WITH HYPERTENSION

Objective: Sclerostin is associated with endothelial inflammation and vascular calcification and therefore contributes to atherosclerosis disease. Hypertension is one of risk factors of peripheral arterial occlusive disease (PAOD), is associated with increased mortality in patients with hypertension. The aim of this study was to determine the relationship between serum sclerostin level and PAOD in patients with hypertension. Design and method: Fasting blood samples and baseline characteristics were obtained from 92 hypertensive patients. ABI values were measured using an automated oscillometric device. Patients with ABIs of <0.9 were categorized into the low ABI group. The serum sclerostin and dickkopf-1 (DKK1) concentrations were determined using commercially available enzyme-linked immunosorbent assays. Results: In total, 14 patients with hypertension (15.2%) were in the low ABI group. When compared to those in the normal ABI group, the low ABI group had high rates of diabetes mellitus (P = 0.044) as well as the high serum C-reactive protein levels (P = 0.001) and sclerostin levels (P < 0.001), but the serum DKK1 level did not find this association (P = 0.639). The multivariable logistic regression analysis revealed that serum levels of sclerostin (odds ratio [OR]: 1.052, 95% confidence interval [CI]: 1.018–1.088, P = 0.002) was independently associated with PAD in patients with hypertension. Conclusions: Serum levels of sclerostin, but not DKK1, were associated with PAOD in patients with hypertension.

Antithrombotic Treatment Patterns of Patients with Symptomatic Peripheral Arterial Occlusive Disease in Germany: Evidence from Health Insurance Claims Data.

Objectives: Patients with peripheral arterial occlusive disease (PAOD) are at risk of worsening limb symptoms, major adverse cardiovascular events and exhibit an impaired life expectancy. There is a lack of evidence on the extent of pharmacological secondary prevention in PAOD patients. This study assesses treatment patterns of antithrombotic agents in symptomatic PAOD patients. Methods: This is a retrospective cohort study using data from the second largest insurance fund in Germany, BARMER. We included symptomatic PAOD patients undergoing in-hospital treatment with an index admission between 1 January 2010 and 31 December 2017. Outcomes were proportions of single antiplatelets (SAPT), dual antiplatelets (DAPT), vitamin-K antagonists (VKA), or direct oral anticoagulants (DOAC) in the 12 months prior and 6 months after the index hospitalization. Non-parametric cumulative incidence for competing risks was estimated to account for censoring and death after discharge from hospital stay. Patient flows were visualised by alluvial diagrams. All analyses were stratified by intermittent claudication (IC) and chronic limb-threatening ischaemia (CLTI). The protocol was registered to ClinicalTrials.gov (NCT03909022). Results: A total of 80,426 unique patient encounters were identified. Mean age was 72.7 (46.3% female). Amongst all patients, 25.6% were on SAPT, 4.1% on DAPT, 9.1% on VKA, 3.9% on DOAC, 3.9% on both antiplatelets and oral anticoagulation, and 53.3% without any antithrombotic therapy during the 12 months before index stay. The estimated cumulative incidence was 37.9% SAPT, 14.8% DAPT, 7.5% VKA, 4.3% DOAC, 7.4% both, and 28.1% without any antithrombotic therapy during the 6 months after index stay. The considerable increases in antiplatelet therapy were mainly driven by the group of patients without antithrombotics before index stay. As compared with IC, patients who suffered from CLTI received less often antiplatelets but more often anticoagulants both before and after index stay. Conclusions: Utilisation rates of antithrombotic therapy increased considerably after in-hospital treatment for PAOD. Yet, remarkably high rates of symptomatic patients without any blood-thinning therapy constitute a major concern with respect to adequate secondary prevention of PAOD patients.

Preoperative Factors Associated with Target Lesion Revascularization following Endovascular Therapy of the Superficial Femoral Artery.

Objectives: In patients with symptomatic peripheral arterial occlusive disease (PAOD), endovascular revascularization of the superficial femoral artery (SFA) is the most frequent intervention. A major drawback of endovascular procedures is clinically driven target lesion revascularization (CD-TLR), which may cause recurrence of symptoms, re-hospitalizations, and re-interventions. Outcome studies comparing endovascular modalities are heterogeneous and focus more on intraoperative rather than preoperative aspects. Studies have not examined potential risk factors in patients’ phenotype before an intervention to prevent CD-TLR. Design: Monocentric, retrospective cohort study of 781 patients with symptomatic PAOD referred to an endovascular intervention of the SFA between 2000 and 2018. Methods: The study aim was to identify risk factors and phenotypes leading to symptomatic PAOD in patients with de novo lesions of the SFA and ≥1 CD-TLR within 12 months post-index procedure. Two groups were differentiated: patients without CD-TLR and with ≥1 CD-TLR. Patient phenotype was compared for cardiovascular (CV) risk factors, age, gender, and renal function. Results: 662 patients (84.8%) (age 73.5 ± 11.2 years; 243 women (36.7%)) with no CD-TLR were compared to 119 patients (15.2%) with ≥1 CD-TLR (age 70.9 ± 12.4 years; 55 women (46.2%)). Women, as well as subjects with dyslipidemia, had each a 1.8-time higher odds ratio of receiving multiple interventions within one year than men or subjects without dyslipidemia. Older subjects (per decade) had a lower odds ratio (0.7) for multiple interventions. Subjects with an eGFR (estimated glomerular filtration rate) <30 mL/min had 3.8 times higher and subjects with eGFR ≥30 and <60 mL/min had a 2.4 higher odds ratio of receiving multiple interventions than subjects with eGFR values ≥90 mL/min. Conclusion: Our data indicate that younger women, patients with dyslipidemia, or those with renal insufficiency are at risk for recurrent midterm CD-TLR after endovascular therapy of the SFA.

Risk of peripheral artery occlusive disease in patients with lower leg fracture who received fixation and non-fixation treatments: A population cohort study.

The risk of peripheral artery occlusive disease (PAOD) in patients with lower leg fracture who underwent fixation procedures is not yet completely understood. Therefore, the current study aimed to examine the risk of subsequent PAOD in patients with lower leg fracture who received fixation and non-fixation treatments. We included 6538 patients with lower leg fracture who received non-fixation treatment and a matched cohort comprising 26152 patients who received fixation treatment from the National Health Insurance Database. Patients were frequency matched according to age, sex, and index year. The incidence and risk of PAOD in patients with lower leg fracture who received fixation and non-fixation treatments were evaluated via the stratification of different characteristics and comorbidities. Non-fixation treatment, male sex, older age (≥ 50 years old), diabetes mellitus, and gout were associated with a significantly higher risk of lower extremity PAOD compare to each comparison group, respectively. Moreover, there was a significant correlation between fixation treatment and a lower risk of lower extremity PAOD in women (adjusted hazard ratio [aHR] = 0.58, 95% confidence interval [CI] = 0.38-0.90), women aged > 50 years (aHR = 0.61, 95% CI = 0.38-0.96), and patients with coronary artery disease (aHR = 0.43, 95% CI = (0.23-0.81). Further, patients with fixation treatment had a significantly lower risk of lower extremity PAOD within 2 years after trauma (aHR = 0.57, 95% CI = 0.34-0.97). The Kaplan-Meier analysis showed that the cumulative incidence of PAOD was significantly higher in the non-fixation treatment group than in the fixation treatment group at the end of the 10-year follow-up period (log-rank test: P = 0.022). Patients with lower leg fracture who received non-fixation treatment had a significantly higher risk of PAOD than those who received fixation treatment. Moreover, the risk of PAOD was higher in women aged > 50 years, as well as in coronary artery disease patients who received non-fixation treatment than in those who received fixation treatment. Therefore, regular assessment of vessel patency are recommended for these patients. Nevertheless, further studies must be conducted to validate the results of our study.

Association of Peripheral Arterial Occlusive Disease and Deep Venous Thrombosis with Risk of Consequent Sepsis Event: A Retrospective Population-Based Cohort Study.

Peripheral artery occlusive disease (PAOD) and deep vein thrombosis (DVT) can cause a variety of acute and chronic vascular complications and put patients at risk of subsequent sepsis. This study aimed to determine whether DVT compared with PAOD patients would increase the risk of sepsis. This study recruited 43,535 patients newly diagnosed as having PAOD and 6932 patients who were newly diagnosed as having DVT from a population of 2 million patients from the Longitudinal Health Insurance Database. Propensity score matching (PSM) between the PAOD and DVT groups was performed for age, sex, comorbidities, and prior antibiotic administration. A total of 4383 patients with PAOD and 4383 patients with DVT were analyzed for risk of sepsis. The incidence density of sepsis per 1000 person years for patients with PAOD was 25.75 (95% CI = 23.90 to 27.74) and 35.61 (95% CI = 33.29 to 38.09) for patients with DVT. After age, sex, associated comorbidities, and antibiotic administration were adjusted for, the risk of sepsis for the DVT group was 1.46-fold (95% CI = 1.32–1.62) higher than that for the PAOD group. In conclusion, patients with DVT were associated with a higher risk of subsequent sepsis than patients with PAOD. Aging was another risk factor.

Effect of Angioplasty on Sarcopenia in Peripheral Arterial Occlusive Disease Patients

For many reasons, patients with peripheral arterial occlusive disease (PAOD) are unable to walk well. Among them, sarcopenia may be one factor. The relationship between PAOD and sarcopenia is not well known. We conducted this study to determine whether sarcopenia improved after treatment in patients with PAOD.

A Reperfusion BOLD-MRI Tissue Perfusion Protocol Reliably Differentiate Patients with Peripheral Arterial Occlusive Disease from Healthy Controls.

There is no established technique that directly quantifies lower limb tissue perfusion. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) is an MRI technique that can determine skeletal muscle perfusion. BOLD-MRI relies on magnetic differences of oxygenated and deoxygenated hemoglobin, and regional changes in oxy/deoxyhemoglobin ratio can be recorded by T2* weighted MRI sequences. We aimed to test whether BOLD-MRI can differentiate lower limb tissue perfusion in peripheral arterial occlusive disease (PAOD) patients and healthy controls. Twenty-two PAOD patients and ten healthy elderly volunteers underwent lower limb BOLD-MRI. Reactive hyperemia was provoked by transient cuff compression and images of the gastrocnemius and soleus muscles were continuously acquired at rest, during ischemia and reperfusion. Key BOLD parameters were baseline T2* absolute value and time to T2* peak value after cuff deflation (TTP). Correlations between imaging parameters and ankle-brachial index (ABI) was investigated. The mean TTP was considerably prolonged in PAOD patients compared to healthy controls (m. gastrocnemius: 111 ± 46 versus 48 ± 22 s, p = 0.000253; m. soleus: 100 ± 42 versus 41 ± 30 s, p = 0.000216). Both gastrocnemius and soleus TTP values correlated strongly with ABI (−0.82 and −0.78, p < 0.01). BOLD-MRI during reactive hyperemia differentiated most PAOD patients from healthy controls. TTP was the most decisive parameter and strongly correlated with the ABI.

Obesity-Related Indices Are Associated with Peripheral Artery Occlusive Disease in Patients with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (DM) is an increasing global health issue. Peripheral artery occlusive disease (PAOD) is a common complication of diabetes, and it is a complex and costly disease. The association between type 2 DM and obesity is well known, however, the relationship between obesity and PAOD in patients with type 2 DM has yet to be elucidated. Therefore, the aim of this study was to examine associations between obesity-related indices and PAOD in patients with type 2 DM. A total of 1872 outpatients with type 2 DM were recruited from two hospitals in southern Taiwan. An ankle–brachial index (ABI) < 0.9 in either leg was considered to indicate the presence of PAOD. The following obesity-related indices were investigated: conicity index (CI), waist–hip ratio (WHR), body roundness index (BRI), waist-to-height ratio (WHtR), abdominal volume index, a body shape index (ABSI), visceral adiposity index (VAI), lipid accumulation product (LAP), body adiposity index, body mass index and triglyceride–glucose index. Overall, 4.1% of the enrolled patients had an ABI < 0.9. High values of the following obesity-related indices were significantly associated with a low ABI: WHtR (p = 0.045), VAI (p = 0.003), CI (p = 0.042), BRI (p = 0.021) and ABSI (p = 0.043). Furthermore, WHR (area under the curve (AUC) = 0.661), CI (AUC = 0.660) and LAP (AUC = 0.642) had the best performance (all p < 0.001) to predict PAOD. In conclusion, high WHtR, BRI, CI, VAI and BAI values were associated with a low ABI in the enrolled patients, and WHR, CI and LAP were the most powerful predictors of PAOD.

Clinical Impact of Stent Graft Thrombosis in Femoropopliteal Arterial Lesions.

This study sought to elucidate the clinical impact and prognosis of stent graft (SG) thrombosis. The VIABAHN SG offers a favorable outcome in long peripheral artery occlusive disease (PAOD) lesions in the femoropopliteal artery. One concern after SG deployment is the incidence of stent thrombosis and consequent acute limb ischemia (ALI). In this retrospective multicenter study, we collected the clinical data of PAOD patients treated with VIABAHN SG who subsequently experienced SG thrombosis. The clinical symptoms of SG thrombosis, patency after reintervention, and predictors of loss of patency after reintervention were examined. VIABAHN SGs were used for 1,215 patients; SG thrombosis occurred in 159 (13%) patients at a median of 6.4 months (interquartile range: 2.8 to 13.5 months) after SG implantation; 21 (13%) patients presented with ALI. A total of 131 (82%) patients underwent reintervention for SG thrombosis, whereas 2 (1%) underwent primary major amputation and the remaining 26 (16%) were treated conservatively. The patency rate 1 year after reintervention, freedom from major adverse limb events, and limb salvage after reintervention were 54.9%, 73.6%, and 92.5%, respectively. Critical limb-threatening ischemia at SG implantation and ALI presentation at SG thrombosis were positively associated with an increased risk of rethrombosis, whereas distal stent diameter was negatively associated with the risk of rethrombosis. SG thrombosis is associated with a considerable risk of ALI, but the risk of primary major amputation was not high. Clinical outcomes after reinterventions for thrombosed SGs were suboptimal.

Post-exercise pulsatility index indicates treatment effects in peripheral arterial occlusive disease (PAOD).

BackgroundHypothesis: Post-exercise measurements better discriminate PAOD-patients from healthy persons and they more sensitively detect hemodynamic improvements after treatment procedures than resting measurements.MethodsA total of 19 healthy volunteers and 23 consecutive PAOD-patients underwent measurements of peak systolic velocity (PSV), end-diastolic velocity (EDV), minimal diastolic velocity (MDV), time-averaged maximum velocities (TAMAX), resistance index (RI) and pulsatility index (PI) before and after a standard exercise test (at 1, 2, 3, 4 and 5 min) before and after treatment (incl. epidemiological data, PAOD risk factors and comorbidities).ResultsIn resting values, healthy persons and PAOD-patients did not differ significantly in any of the hemodynamic parameters. PSV increased after treatment in PAOD-patients by 5 cm/s (paired t‑test, p: 0.025); however, when the amplitude of autoregulatory changes related to the resting values were calculated, PAOD-patients showed clearly less hemodynamic changes after exercise than healthy persons (p: 0.04; 0.002; <0.001 for PSV, TAMAX and PI, resp.). The time course after exercise was compared by repeated measures of ANOVA. Healthy persons differed significantly in PI, RI and PSV from PAOD patients before and after treatment (p<0.001 each). The PAOD-patients revealed a significantly improved PI after treatment (p: 0.042). The only factor contributing significantly to PI independently from grouping was direct arterial vascularization as compared to discontinuous effects by an obstructed arterial tree.ConclusionHealthy persons cannot be well differentiated from PAOD-patients solely by hemodynamics at rest but by characteristic changes after standard exercise. Treatment effects are reflected by higher PI-values after exercise.

Intensive Rehabilitation Program in Arterial Occlusive Disease Patients

Peripheral arterial occlusive disease (PAOD) limits walking efficiency and distance. The main disabling symptom is vasculopathy that leads to claudicatio intermittens and limits walking efficiency. Stretching techniques are effective in treatments for retractions and are used to improve flexibility of triceps surae and range of motion of the ankle. The aim of this study is to evaluate the effects of a combined walking and stretching program on walking efficiency in elderly PAOD patients. Seventy patients with PAOD stage II of the Leriche–Fontaine classification were randomly assigned into a stretching group (SG) or conditioning group (CG). Both groups participated in an eleven-day intensive rehabilitation program based on walking and strength training, while the SG performed five extra sessions of stretching. Walking autonomy was assessed through treadmill and overground tests with the recording of initial and absolute pain. A univariate ANOVA analysis was applied for the differences between the initial and final outcomes. Walking autonomy improved in both groups (p &lt; 0.01), while only the SG improved flexibility (from −14.0 ± 8.1 to −10.3 ± 8.3 cm; p &lt; 0.01). An intensive eleven-day rehabilitation program based on walking, strength, and stretching exercises is effective to improve the onset and the delay of pain during walking in patients with PAOD.

Editor's Choice – The GermanVasc Score: A Pragmatic Risk Score Predicts Five Year Amputation Free Survival in Patients with Peripheral Arterial Occlusive Disease

ObjectivePatients with peripheral arterial occlusive disease (PAOD) face an increased risk of both lower limb amputation and death. To date, it has been challenging to predict the long term outcomes for PAOD. The aim was to develop a risk score to predict worse five year amputation free survival (AFS).MethodsIn this retrospective analysis of claims data, symptomatic PAOD patients were split into training and validation sets. Variables in the model were patient age and sex, Elixhauser comorbidities, and the 190 most common secondary diagnoses. Penalised Cox regression (least absolute shrinkage and selection operator [LASSO]) with tenfold cross validation for variable selection was performed and patients were categorised into five risk groups using the ten most important variables. All analyses were stratified by intermittent claudication (IC) and chronic limb threatening ischaemia (CLTI).ResultsIn total, 87 293 patients with PAOD (female 45.3%, mean age 71.4 ± 11.1 years) were included in the analysis. The most important variable predicting worse five year AFS was patient age >80 years. The GermanVasc score exhibited good predictive accuracy both for IC (c statistic = 0.70, 95% confidence interval [CI] 0.69–0.71) and CLTI (c statistic = 0.69, 95% CI 0.68–0.70) with adequate calibration due largely to alignment of observed and expected risk. Depending on the cumulative point score, the five year risk of amputation or death ranged from 9% (low risk) to 48% (high risk) for IC, and from 25% to 88% for CLTI.ConclusionThe GermanVasc score predicts worse five year AFS stratified for inpatients suffering from IC and CLTI, with good predictive accuracy. By separating low from high risk patients, the GermanVasc score may support patient centred consent. Patients with peripheral arterial occlusive disease (PAOD) face an increased risk of both lower limb amputation and death. To date, it has been challenging to predict the long term outcomes for PAOD. The aim was to develop a risk score to predict worse five year amputation free survival (AFS). In this retrospective analysis of claims data, symptomatic PAOD patients were split into training and validation sets. Variables in the model were patient age and sex, Elixhauser comorbidities, and the 190 most common secondary diagnoses. Penalised Cox regression (least absolute shrinkage and selection operator [LASSO]) with tenfold cross validation for variable selection was performed and patients were categorised into five risk groups using the ten most important variables. All analyses were stratified by intermittent claudication (IC) and chronic limb threatening ischaemia (CLTI). In total, 87 293 patients with PAOD (female 45.3%, mean age 71.4 ± 11.1 years) were included in the analysis. The most important variable predicting worse five year AFS was patient age >80 years. The GermanVasc score exhibited good predictive accuracy both for IC (c statistic = 0.70, 95% confidence interval [CI] 0.69–0.71) and CLTI (c statistic = 0.69, 95% CI 0.68–0.70) with adequate calibration due largely to alignment of observed and expected risk. Depending on the cumulative point score, the five year risk of amputation or death ranged from 9% (low risk) to 48% (high risk) for IC, and from 25% to 88% for CLTI. The GermanVasc score predicts worse five year AFS stratified for inpatients suffering from IC and CLTI, with good predictive accuracy. By separating low from high risk patients, the GermanVasc score may support patient centred consent.

Cutaneous microcirculation in patients with peripheral arterial occlusive disease: Comparison of capillary blood circulation in the nail fold of finger and toe.

In patients with peripheral arterial occlusive disease (PAOD) a restricted circulation in cutaneous microvessels has been reported. In this study the velocity of erythrocytes (very) in finger nailfold capillaries - a vascular area without upstream macroangiopathy - and also in toe nailfold capillaries - a post-stenotic area -was investigated using capillary microscopy in apparently healthy subjects and patients with PAOD. Already in finger nailfold capillaries very of patients with PAOD under resting conditions was significantly lower than in capillaries of healthy subjects. This was also true for the circulation in toe capillaries. In addition, the erythrocyte velocities under resting conditions in the toe capillaries were significantly lower than in the finger capillaries. Similar results were found for the duration and the maximum velocity of postocclusive hyperemia. It is concluded that the resting blood flow in the skin microcirculation is impaired in PAOD patients, both under resting conditions and during postocclusive hyperemia in finger as well in toe nailfold capillaries.

Circulatory Rejuvenated EPCs Derived from PAOD Patients Treated by CD34+ Cells and Hyperbaric Oxygen Therapy Salvaged the Nude Mouse Limb against Critical Ischemia.

This study tested whether circulatory endothelial progenitor cells (EPCs) derived from peripheral arterial occlusive disease (PAOD) patients after receiving combined autologous CD34+ cell and hyperbaric oxygen (HBO) therapy (defined as rejuvenated EPCs) would salvage nude mouse limbs against critical limb ischemia (CLI). Adult-male nude mice (n = 40) were equally categorized into group 1 (sham-operated control), group 2 (CLI), group 3 (CLI-EPCs (6 × 105) derived from PAOD patient’s circulatory blood prior to CD34+ cell and HBO treatment (EPCPr-T) by intramuscular injection at 3 h after CLI induction) and group 4 (CLI-EPCs (6 × 105) derived from PAOD patient’s circulatory blood after CD34+ cell and HBO treatment (EPCAf-T) by the identical injection method). By 2, 7 and 14 days after the CLI procedure, the ischemic to normal blood flow (INBF) ratio was highest in group 1, lowest in group 2 and significantly lower in group 4 than in group 3 (p < 0.0001). The protein levels of endothelial functional integrity (CD31/von Willebrand factor (vWF)/endothelial nitric-oxide synthase (eNOS)) expressed a similar pattern to that of INBF. In contrast, apoptotic/mitochondrial-damaged (mitochondrial-Bax/caspase-3/PARP/cytosolic-cytochrome-C) biomarkers and fibrosis (Smad3/TGF-ß) exhibited an opposite pattern, whereas the protein expressions of anti-fibrosis (Smad1/5 and BMP-2) and mitochondrial integrity (mitochondrial-cytochrome-C) showed an identical pattern of INBF (all p < 0.0001). The protein expressions of angiogenesis biomarkers (VEGF/SDF-1α/HIF-1α) were progressively increased from groups 1 to 3 (all p < 0.0010). The number of small vessels and endothelial cell surface markers (CD31+/vWF+) in the CLI area displayed an identical pattern of INBF (all p < 0.0001). CLI automatic amputation was higher in group 2 than in other groups (all p < 0.001). In conclusion, EPCs from HBO-C34+ cell therapy significantly restored the blood flow and salvaged the CLI in nude mice.

A Near Infrared Spectroscopy System for Assessing Rehabilitation on Peripheral Arterial Occlusion Patients

PurposeA near-infrared spectroscopy system was developed to evaluate peripheral arterial occlusive disease (PAOD). The wireless device can take measurements when patients are doing rehabilitation exercise.MethodsTwo LED modules with wavelengths of 740 nm, 808 nm and 850 nm were placed over 32 mm away from the photodiode to detect the deep backscattering from muscle tissue. The absorbance difference from the extent of tissue oxygenation was extracted using a modified Beer’s law. Measurements taken on different muscle groups were applied to determine which branch of artery is occluded.ResultsThe changes in oxygenation of gastrocnemius and tibialis anterior muscle were recorded when PAOD patients were riding a stationary bicycle. The drop in oxygenation with exercise generally should recover within 15 min of continuing exercise. Otherwise, the artery is not capable to provide enough blood supply to the exercising muscles. Since gastrocnemius is the primary muscle used in biking exercise, the compensatory vasodilation in gastrocnemius leads to hypoperfusion in tibialis anterior muscle.ConclusionThis NIRS system is helpful for detecting the changes in tissue oxygenation during exercise. Muscle hypoxia was more obvious during exercise when the artery had some degree of occlusion.

Comorbidity Patterns Among Patients with Peripheral Arterial Occlusive Disease in Germany: A Trend Analysis of Health Insurance Claims Data

Patients suffering from peripheral arterial occlusive disease (PAOD) are a central target population for multidisciplinary vascular medicine. This study aimed to highlight trends in treatment patterns and comorbidities using up to date longitudinal patient related data from Germany. This study is a retrospective health insurance claims data analysis of patients insured by the second largest health insurance provider in Germany, BARMER. All PAOD patient hospitalisations between 2008 and 2016 were included. The comorbidities were categorised with Elixhauser groups using WHO ICD-10 codes and summarised as the linear van Walraven score (vWS). A trend analysis of the comorbidities was performed after standardisation by age and sex. A total of 156 217 patients underwent 202 961 hospitalisations (49.4% for chronic limb threatening ischaemia in 2016) with PAOD during the study period. Although the estimated annual incidence of PAOD among the BARMER cohort decreased slightly (− 4.4%), an increase was observed in the prevalence of PAOD (+ 23.1%), number of hospitalisations (+ 25.1%), peripheral vascular interventions (PVI, + 61.1%), and disease related reimbursement costs (+ 31%) from 2008 to 2016. Meanwhile, the number of major amputations decreased (− 15.1%). The proportion of patients aged 71–80 years increased about +10% among PAOD patients and the mean vWS also increased by two points during the study period. Considerable increases were found in the rates of hypertension, renal failure, and hypothyroidism, whereas the rates of diabetes and congestive heart failure decreased over time. Increasing numbers of PVI performed on these ageing and sicker patients lead to rising costs but correlate with decreasing major amputation rates.

K-134, a phosphodiesterase 3 inhibitor, reduces vascular inflammation and hypoxia, and prevents rupture of experimental abdominal aortic aneurysms

ObjectiveAbdominal aortic aneurysm (AAA) is a chronic inflammatory disease, which frequently results in fatal rupture; however, no pharmacologic treatment exists to inhibit AAA growth and prevent rupture. In this study, we investigated whether K-134, a novel phosphodiesterase 3 inhibitor, could limit the progression and rupture of AAA using multiple experimental models. MethodsA hypoperfusion-induced AAA rat model was developed by inserting of a small catheter and via tight ligation of the infrarenal aorta. Rats were fed with a 0.15% K-134-containing diet (K-134(+) group) or a normal diet (K-134(-) group) from 7 days before the experiment to 28 days after model creation (pretreatment protocol). After the administration period, elastin fragmentation, macrophage infiltration, reactive oxygen species expression, matrix metalloproteinase levels, aneurysmal tissue hypoxia, and adventitial vasa vasorum (VV) stenosis were assessed. In the delayed treatment protocol, rats with AAA >3 mm were randomly divided to K-134(+) or K-134(-) group 7 days after model creation, and the effect of K-134 on suppressing preexisting AAA was examined. Further, elastase-induced rat model and angiotensin II-infused ApoE-/- mouse model were also used to examine the ability of K-134 to prevent rupture. ResultsK-134 prevented AAA rupture and significantly improved survival in the pretreatment protocol (P < .01). In the K-134(+) group, elastin degeneration was prevented; macrophage infiltration and reactive oxygen species production were significantly decreased. At 14 days, the enzymatic activity of matrix metalloproteinase-9 was significantly decreased. Further, K-134 inhibited intimal hyperplasia and VV stenosis. Expressions of hypoxic markers, hypoxia-inducible factor-1α, and pimonidazole, in the aneurysmal wall were also attenuated. In the delayed treatment protocol, K-134 also improved survival of rats with preexisting AAA. Similarly, in the elastase-induced rat model and angiotensin II-infused ApoE-/- mouse model, K-134 inhibited rupture and significantly improved survival (P < .01). ConclusionsK-134 prevented the rupture of AAA and improved survival through suppressing inflammatory reaction. The inhibition of intimal hyperplasia in the adventitial VV may be associated with reduced hypoxia in the aneurysmal tissue. (JVS–Vascular Science 2020;1:219-32.) Clinical RelevanceThis study shows that K-134, a novel phosphodiesterase 3 inhibitor, suppressed abdominal aortic aneurysm (AAA) rupture. Considering that K-134 had already undergone a phase Ⅱ study in the United States for claudication in peripheral artery occlusive disease patients with good tolerance, K-134 may become a promising new therapeutic option for AAAs and could undergo clinical trials for patients with small AAA.

Editor's Choice - Comorbidity Patterns Among Patients with Peripheral Arterial Occlusive Disease in Germany: A Trend Analysis of Health Insurance Claims Data.

Patients suffering from peripheral arterial occlusive disease (PAOD) are a central target population for multidisciplinary vascular medicine. This study aimed to highlight trends in treatment patterns and comorbidities using up to date longitudinal patient related data from Germany. This study is a retrospective health insurance claims data analysis of patients insured by the second largest health insurance provider in Germany, BARMER. All PAOD patient hospitalisations between 2008 and 2016 were included. The comorbidities were categorised with Elixhauser groups using WHO ICD-10 codes and summarised as the linear van Walraven score (vWS). A trend analysis of the comorbidities was performed after standardisation by age and sex. A total of 156217 patients underwent 202961 hospitalisations (49.4% for chronic limb threatening ischaemia in 2016) with PAOD during the study period. Although the estimated annual incidence of PAOD among the BARMER cohort decreased slightly (- 4.4%), an increase was observed in the prevalence of PAOD (+ 23.1%), number of hospitalisations (+ 25.1%), peripheral vascular interventions (PVI,+ 61.1%), and disease related reimbursement costs (+ 31%) from 2008 to 2016. Meanwhile, the number of major amputations decreased (- 15.1%). The proportion of patients aged 71-80 years increased about+10% among PAOD patients and the mean vWS also increased by two points during the study period. Considerable increases were found in the rates of hypertension, renal failure, and hypothyroidism, whereas the rates of diabetes and congestive heart failure decreased over time. Increasing numbers of PVI performed on these ageing and sicker patients lead to rising costs but correlate with decreasing major amputation rates.

Quantification of muscle mass in the legs of patients with peripheral arterial occlusive disease: associations between volumetric and cross-sectional single-slice measurements for identification of atrophy and focal sarcopenia.

Sarcopenia, commonly determined by measuring skeletal muscle mass index (SMI) at the third lumbar level, has been identified as a predictor of clinical outcome in a variety of diseases. For patients with peripheral arterial occlusive disease (PAOD), we hypothesized that lower extremity SMI (LESMI) might be a more precise predictor of outcome and the extent of chronic ischemia than the systemic muscle mass at the L3 level. We investigated the association between complete muscle volume and muscle area derived with single-slice 2-dimensional measurements in the legs to identify at which level cross-sectional single-slice measurements are most representative of the muscle volume and investigated whether LESMI is associated with systemic sarcopenia and PAOD severity. Muscle volumes and areas were semiautomatically segmented from computed tomography (CT) scans of the affected and contralateral legs of 50 PAOD patients with Fontaine stage IIb and 50 PAOD patients with Fontaine stage IV. The muscle mass was determined for the complete volumes of the upper and lower legs and for cross-sectional slices at 40%, 50%, and 60% of the length of the femur and tibia. Patients were determined as sarcopenic based on sex-specific cut-off values at the L3 spinal segment. Two observers segmented 20 randomly selected patients to determine the interobserver reliability with the intraclass correlation coefficient. The correlation between the LESMI of the complete muscle volume and the three cross-sectional slices in all 200 upper and 200 lower legs was moderately strong to strong. Interobserver reliability of cross-sectional slice segmentation was excellent. The LESMI, both measured volumetrically and cross-sectionally, were significantly lower in patients with sarcopenia compared to patients without sarcopenia. The LESMI was lower in patients with Fontaine stage IV compared to patients with Fontaine stage IIb for both volumetric and cross-sectional measurements. Segmentation of skeletal muscle mass from cross-sectional single-slice CT in the upper and lower leg can accurately and precisely substitute complete volume segmentations. These findings warrant the use of measurements based on cross-sectional single-slice CT for assessing the LESMI. Patients with systemic sarcopenia are also at increased risk for muscle mass loss in the lower extremities. In the current study, LESMI was lower in patients with Fontaine class IV PAOD compared to patients with Fontaine class IIb PAOD. Future studies should assess the predictive value of the LESMI on clinical outcomes in PAOD patients.

Red Blood Cell Distribution Width Predicts 1-month Complications after Percutaneous Transluminal Angioplasty.

SummaryBackgroundThe identification of patients at higher risk of developing percutaneous transluminal angioplasty (PTA)-related complications is pivotal for achieving better clinical outcomes. We carried out a single-center, observational, retrospective study to explore whether in-hospital changes of red blood cell distribution width (RDW) may help predicting early development of PTA-related complications.MethodsThe study population consisted of all consecutive patients who underwent PTA for severe peripheral artery occlusive disease (PAOD) during a 2-year period. RDW was measured at hospital admission and discharge, and the delta was calculated. Patient follow-up was routinely performed 1-month after hospital discharge, and was based on thoughtful medical assessment and arterial ultrasonography. The control population consisted of 352 ostensibly healthy subjects.ResultsThe final PTA group consisted of 224 patients. Hemoglobin was lower, whilst mean corpuscular volume (MCV) and RDW were higher in PAOD cases than in controls. Overall, 11 PAOD patients (4.9%) developed clinically significant PTA-related complications 1-month after hospital discharge. Patients who developed 1-month PTA-related complications had lower hemoglobin concentration, but higher RDW and delta RDW than those who did not. Patients with delta RDW >1 had 60% higher risk of developing 1-month PTA-related complications and 88% higher risk of developing early reocclusion. Overall, RDW exhibited an area under the curve (AUC) of 0.68 and 0.74 for predicting 1-month PTA-related complications and early reocclusion, respectively.ConclusionsThe results of this study suggest that RDW may play a role for guiding the clinical decision making of PTA patients immediately after hospital discharge.