Anemia and Outcome in Outpatients With Peripheral Artery Disease

Angiology ◽  
2015 ◽  
Vol 67 (5) ◽  
pp. 484-489 ◽  
Author(s):  
Paulina Perez ◽  
Carlos Esteban ◽  
Pedro Enrique Jiménez Caballero ◽  
Juan Francisco Sánchez Muñoz-Torrero ◽  
María Teresa Pascual Soria ◽  
...  

The influence of anemia on outcome in stable outpatients with peripheral artery disease (PAD) has not been consistently investigated. We used data from the Factores de Riesgo y ENfermedad Arterial (FRENA) Registry to compare ischemic events and mortality rates in stable outpatients with symptomatic PAD and anemia. Of 1663 patients with PAD, 208 (12.5%) had anemia. Over 18 months, patients with anemia had a higher rate of myocardial infarction (MI; rate ratio [RR]: 2.10; 95% confidence interval [CI]: 1.04-3.99), limb amputation (RR: 2.98; 95%CI: 1.70-5.05), and higher mortality (RR: 3.58; 95%CI: 2.39-5.28) than those without anemia. The rates of ischemic stroke (RR: 0.75; 95%CI: 0.23-1.93) and major bleeding (RR: 0.93; 95%CI: 0.15-3.51) were similar. On multivariable analysis, anemia was associated with an increased risk to die (hazard ratio [HR]: 2.32; 95%CI: 1.53-3.50) but not to develop MI (HR: 1.49; 95%CI: 0.73-3.05) or to have limb amputation (HR: 1.49; 95%CI: 0.86-2.59). In stable outpatients with PAD, anemia was associated with increased mortality but not with an increased rate of subsequent ischemic events or major bleeding.

Angiology ◽  
2017 ◽  
Vol 69 (6) ◽  
pp. 507-512 ◽  
Author(s):  
Pere Altes ◽  
Paulina Perez ◽  
Carlos Esteban ◽  
Juan Francisco Sánchez Muñoz-Torrero ◽  
Eduardo Aguilar ◽  
...  

The influence of raised fibrinogen levels on outcome in stable outpatients with peripheral arterial disease (PAD) has not been consistently investigated. We used data from the Factores de Riesgo y ENfermedad Arterial (FRENA) registry to compare ischemic events, major bleeding, and mortality in stable outpatients with PAD, according to their baseline plasma fibrinogen levels. Of 1363 outpatients with PAD recruited in FRENA, 558 (41%) had fibrinogen levels >450 mg/100 mL. Over 18 months, 43 patients presented with acute myocardial infarction, 37 had an ischemic stroke, 51 underwent limb amputation, 19 had major bleeding, and 90 died. Compared to patients with normal levels, those with raised fibrinogen levels had an over 2-fold higher rate of ischemic stroke (rate ratio [RR]: 2.30; 95% confidence interval [CI]: 1.19-4.59), limb amputation (RR: 2.58; 95% CI: 1.46-4.67), or death (RR: 2.27; 95% CI: 1.49-3.51) and an over 3-fold higher rate of major bleeding (RR: 3.90; 95% CI: 1.45-12.1). On multivariate analysis, patients with raised fibrinogen levels had an increased risk of developing subsequent ischemic events (hazard ratio [HR]: 1.61; 95% CI: 1.11-2.32) and major bleeding (HR: 3.42; 95% CI: 1.22-9.61). Stable outpatients with PAD and raised plasma fibrinogen levels had increased rates of subsequent ischemic events and major bleeding.


Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Jung-Im Shin ◽  
Morgan Grams ◽  
Josef Coresh ◽  
Alex Chang ◽  
Kunihiro Matsushita

Introduction: Proteinuria is shown to be associated with increased risk of peripheral artery disease (PAD). However, its association with the risk of lower limb amputation in patients with PAD is unknown. Hypothesis: We hypothesized that proteinuria is associated with the risk of amputation in patients with PAD in a graded fashion. Methods: We identified 3,388 PAD patients with data on urine dipstick proteinuria within two years prior to PAD diagnosis between 1997 and 2017 in the Geisinger Health System (mean age 69.7 years, 44.8% female, 97.4% non-Hispanic White, 57.8% diabetic). We quantified the association of proteinuria with the risk of amputation using Cox proportional hazards models, adjusting for demographics, calendar year, estimated glomerular filtration rate, HbA1c, comorbidities including diabetic retinopathy/neuropathy, and medication use (antiplatelet drug, statin, and renin-angiotensin system inhibitor). Results: There were 55.2% with negative dipstick proteinuria, 11.1% trace, 14.1% with 1+, and 19.5% with ≥2+. A total of 245 patients underwent amputations over a median follow-up of 3.4 years. Incidence rate of amputation was 1.15 per 100 person-years for dipstick negative, 1.47 for trace, 2.11 for 1+, and 3.78 for ≥2+. This dose-response relationship remained similar even after accounting for potential confounders (p-trend=0.015), with particularly evident association for ≥2+ of dipstick (an adjusted hazard ratio of 1.52 [95% confidence interval: 1.08-2.17, p=0.017) (Figure). When we added proteinuria to other covariates, the risk discrimination slightly improved (Δc-statistic 0.007 [0.001-0.014]). Conclusions: Higher proteinuria was associated with a greater risk of lower limb amputation among patients with newly diagnosed PAD. Our results suggest the importance of considering proteinuria in risk assessment of limb loss in PAD patients.


2019 ◽  
Vol 24 (5) ◽  
pp. 422-430 ◽  
Author(s):  
Charles W Hopley ◽  
Sarah Kavanagh ◽  
Manesh R Patel ◽  
Cara Ostrom ◽  
Iris Baumgartner ◽  
...  

In patients with symptomatic peripheral artery disease (PAD), the impact of chronic kidney disease (CKD) on major adverse cardiovascular events has not been fully evaluated. The Examining Use of Ticagrelor In PAD (EUCLID) trial randomized 13,885 patients with PAD to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. This post hoc analysis compared the incidence of the primary composite endpoint (cardiovascular death, myocardial infarction (MI), or ischemic stroke) in patients with CKD (eGFR < 60 mL/min/1.73 m2) with those without CKD (eGFR ⩾ 60 mL/min/1.73 m2). The primary safety endpoint was thrombolysis in MI (TIMI) major bleeding. A total of 13,483 patients were included; 3332 (25%) had CKD, of whom 237 had stage 4/5 disease. Median follow-up was approximately 30 months. After statistical adjustment, patients with CKD had a higher rate of the primary endpoint compared with those without CKD (6.75 vs 3.72 events/100 patient-years; adjusted hazard ratio (HR) 1.45, 95% CI 1.30–1.63). CKD was not associated with increased risk of hospitalization for acute limb ischemia (ALI) (adjusted HR 0.96, 95% CI 0.69–1.34) or major amputation (adjusted HR 0.92, 95% CI 0.66–1.28). CKD was not associated with a significantly increased risk of major bleeding (adjusted HR 1.21, 95% CI 0.89–1.64), but minor bleeding was significantly increased (adjusted HR 1.51, 95% CI 1.07–2.15). In conclusion, patients with PAD and CKD had higher rates of cardiovascular death, MI, and ischemic stroke, but similar rates of ALI, major amputation, and TIMI major bleeding when compared with patients without CKD. ClinicalTrials.gov Identifier: NCT01732822


Author(s):  
Ian C. Gilchrist ◽  
David A. Morrow ◽  
Mark A. Creager ◽  
Jeffrey W. Olin ◽  
Benjamin M. Scirica ◽  
...  

Background Patients with peripheral artery disease are at increased risk of both major adverse cardiovascular events (MACEs) and limb events. The pathobiology of limb events is likely multifactorial. Observational studies suggest a benefit of statin therapy for reducing the risk of limb ischemic events while randomized trials demonstrate a benefit with more potent antithrombotic therapies, particularly those targeting thrombin. Whether the effects of these therapeutic pathways are independent and complementary is not known. Methods and Results The TRA 2°P‐TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events–Thrombolysis in Myocardial Infarction 50) trial demonstrated that vorapaxar significantly reduced MACEs and limb events. The purpose of the current analysis was to evaluate the association of statin use and intensity and the occurrence of MACEs and limb events in 5845 patients with symptomatic peripheral artery disease randomized in TRA 2°P‐TIMI 50 and then to understand whether statin use modified the benefits of vorapaxar for MACEs or limb ischemic events. We found that statin therapy was associated with significantly lower risk of MACEs (hazard ratio [HR], 0.77; 95% CI, 0.66–0.89; P <0.001) and limb ischemic events (HR, 0.73; 95% CI, 0.60–0.89; P =0.002). The benefit of vorapaxar for reducing MACEs and limb events was consistent regardless of background statin ( P ‐interaction=0.715 and 0.073, respectively). Event rates were lowest in patients receiving the combination of statin therapy and vorapaxar. Conclusions In conclusion, statin use and intensity is associated with significantly lower rates of MACEs and limb ischemic events. Thrombin inhibition with vorapaxar is effective regardless of background statin therapy. These results suggest that targeting both lipid and thrombotic risk in peripheral artery disease is necessary in order to optimize outcomes.


2021 ◽  
pp. 1358863X2199286
Author(s):  
Keiichi Hishikari ◽  
Hiroyuki Hikita ◽  
Fumichika Abe ◽  
Naruhiko Ito ◽  
Yoshinori Kanno ◽  
...  

This study evaluated the incidence, predictors, and impact of bleeding requiring hospitalization following successful endovascular therapy (EVT) for peripheral artery disease. Platelet inhibition after EVT reduces the risk of major adverse limb events but increases the risk of bleeding. The incidence of post-discharge bleeding after EVT, its independent predictors, and its prognostic importance in clinical practice have not been fully addressed. We evaluated 779 consecutive patients who underwent EVT. We found that 77 patients (9.9%) were hospitalized for major bleeding during follow-up after EVT (median 39 months, range 22–66 months), with almost half (48.1%) of the bleeding categorized as gastrointestinal bleeding. Significant predictors of post-discharge bleeding were hemodialysis (hazard ratio (HR), 3.12; 95% CI: 1.93 to 5.05; p < 0.001) and dual antiplatelet therapy (DAPT) use (HR, 1.87; 95% CI: 1.03 to 3.41; p = 0.041). During follow-up, the all-cause mortality-free survival rate was significantly worse in patients who had experienced major bleeding than in those who had not (log-rank test χ2 = 54.6; p < 0.001). Cox proportional hazards analysis showed that major bleeding (HR, 2.78; 95% CI: 1.90 to 4.06; p < 0.001) was an independent predictor of all-cause death after EVT. Hospitalization for post-discharge bleeding after EVT is associated with a substantially increased risk of death, even after successful EVT. We concluded that patients’ predicted bleeding risk should be considered when selecting patients likely to benefit from EVT, and that the risk should be considered especially thoroughly in hemodialysis patients.


2019 ◽  
Vol 24 (38) ◽  
pp. 4511-4515 ◽  
Author(s):  
A. Koutsoumpelis ◽  
C. Argyriou ◽  
K.M. Tasopoulou ◽  
E.I. Georgakarakos ◽  
G.S. Georgiadis

Background: Peripheral artery disease is a common manifestation of systemic atherosclerosis which strongly correlates to cardiovascular morbidity and mortality. In addition, the progression of peripheral artery disease leads to an increased risk of limb loss. In order to reduce these events, the benchmark of treatment and research over the last years has been the antiplatelet therapy which aims at inhibition of platelet aggregation. Over the last years, new studies combining antiplatelet agents in different therapeutic schemes have been proven efficacious. Unfortunately, patients remain still at high risk of CV events. Novel Oral Anticoagulants have been introduced as alternatives to warfarin, in the prevention and treatment of venous thromboembolism. The rationale of using medication which acts on platelet activation and the coagulation pathway of thrombosis has led investigators to examine the role of Noac's in preventing CV events in patients with peripheral artery disease, stable or unstable. Methods: The aim of this study is to review the current evidence with respect to recently published studies concerning the use of Novel anticoagulants in peripheral artery disease. Results: The Compass trial has shown that a combination of rivaroxaban with traditional therapy may produce promising results in reducing amputation rates, stroke, cardiac events, and mortality, however, there are still safety issues with bleeding requiring acute care. The ePAD study has provided us with insight concerning safety and efficacy after peripheral angioplasty or stenting and actually the need for further research. The Voyager Pad study, following the steps of Compass, is studying the effect and safety of the addition of rivaroxaban to traditional therapy in the highest risk population aka patients undergoing peripheral revascularization. The evidence concerning patients with concomitant atrial fibrillation appears to be insufficient, however, recent guidelines propose the use of novel oral anticoagulants. Conclusion: For the time being, novel oral anticoagulants in combination with aspirin may provide an alternative treatment in PAD, however, it is deemed necessary to identify patient subgroups who will benefit the most.


Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1407
Author(s):  
Robert K. Clemens ◽  
Monika Hunjadi ◽  
Andreas Ritsch ◽  
Lucia Rohrer ◽  
Thomas O. Meier ◽  
...  

Background: Cholesterol efflux is an important mechanism by which high-density lipoproteins (HDLs) protect against cardiovascular disease. As peripheral artery disease (PAD) is associated with high mortality rates, mainly due to cardiovascular causes, we investigated whether cholesterol efflux capacity (CEC) of apolipoprotein B (apoB)-depleted plasma, a widely used surrogate of HDL function, may serve as a predictive marker for mortality in this patient population. Methods: In this prospective single-center study (median follow-up time: 9.3 years), apoB-containing lipoproteins were precipitated from plasma of 95 patients with PAD and incubated with J744-macrophages, which were loaded with radiolabeled cholesterol. CEC was defined as the fractional radiolabel released during 4 h of incubation. Results: Baseline CEC was lower in PAD patients that currently smoked (p = 0.015) and had a history of myocardial infarction (p = 0.011). Moreover, CEC showed a significant correlation with HDL-cholesterol (p = 0.003) and apolipoprotein A-I levels (p = 0.001) as well as the ankle-brachial index (ABI, p = 0.018). However, CEC did not differ between survivors and non-survivors. Neither revealed Kaplan–Meier and Cox regression analyses any significant association of CEC with all-cause mortality rates. Conclusion: Taken together, CEC is associated with ABI but does not predict all-cause mortality in patients with PAD.


Angiology ◽  
2019 ◽  
Vol 71 (4) ◽  
pp. 303-314
Author(s):  
Rupert Bauersachs ◽  
Sebastian Debus ◽  
Mark Nehler ◽  
Maria Huelsebeck ◽  
Janita Balradj ◽  
...  

Patients with peripheral artery disease (PAD) have an increased risk of cardiovascular (CV) and limb events, but the disease is frequently underdiagnosed and treatment options are limited. This review examines the disease burden of symptomatic PAD as well as key guideline recommendations. Publications were identified using the ProQuest portal to access the Medline, Medline In-Process, and Embase databases. Search terms for symptomatic PAD were combined with terms relevant to epidemiology, burden, treatment practice, and physiopathology. Articles in English published between January 2001 and September 2016 were screened according to the population, interventions, comparator, outcomes, and study design criteria. Relevant publications (n = 200) were identified. The reported incidence and prevalence of PAD varied depending on the definitions used and the study populations. Patients generally had a poor prognosis, with an increased risk of mortality, CV, and limb events and decreased quality of life. Guideline recommendations included ankle–brachial index measurements, exercise testing, and angiography for diagnosis and risk factor modification, antiplatelets, cilostazol, exercise therapy, or surgical interventions for treatment, depending on the patient profile. The clinical, humanistic, and economic burden of disease in patients with symptomatic PAD is substantial and needs to be reduced through improved PAD management.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Elena M. Yubero-Serrano ◽  
Juan F. Alcalá-Diaz ◽  
Francisco M. Gutierrez-Mariscal ◽  
Antonio P. Arenas-de Larriva ◽  
Patricia J. Peña-Orihuela ◽  
...  

Abstract Background Peripheral artery disease (PAD) is recognized as a significant predictor of mortality and adverse cardiovascular outcomes in patients with coronary heart disease (CHD). In fact, coexisting PAD and CHD is strongly associated with a greater coronary event recurrence compared with either one of them alone. High-density lipoprotein (HDL)-mediated cholesterol efflux capacity (CEC) is found to be inversely associated with an increased risk of incident CHD. However, this association is not established in patients with PAD in the context of secondary prevention. In this sense, our main aim was to evaluate the association between CEC and PAD in patients with CHD and whether the concurrent presence of PAD and T2DM influences this association. Methods CHD patients (n = 1002) from the CORDIOPREV study were classified according to the presence or absence of PAD (ankle-brachial index, ABI ≤ 0.9 and ABI > 0.9 and < 1.4, respectively) and T2DM status. CEC was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma was performed. Results The presence of PAD determined low CEC in non-T2DM and newly-diagnosed T2DM patients. Coexisting PAD and newly-diagnosed T2DM provided and additive effect providing an impaired CEC compared to non-T2DM patients with PAD. In established T2DM patients, the presence of PAD did not determine differences in CEC, compared to those without PAD, which may be restored by glucose-lowering treatment. Conclusions Our findings suggest an inverse relationship between CEC and PAD in CHD patients. These results support the importance of identifying underlying mechanisms of PAD, in the context of secondary prevention, that provide potential therapeutic targets, that is the case of CEC, and establishing strategies to prevent or reduce the high risk of cardiovascular events of these patients. Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT00924937. Unique Identifier: NCT00924937


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