Peripheral artery disease is an obstructive, atherosclerotic disease of the lower extremities causing significant morbidity and mortality. Black Americans are disproportionately affected by this ...disease while they are also less likely to be diagnosed and promptly treated. The consequences of this disparity can be grim as Black Americans bear the burden of lower extremity amputation resulting from severe peripheral artery disease. The risk factors of peripheral artery disease and how they differentially affect certain groups are discussed in addition to a review of pharmacological and nonpharmacological treatment modalities. The purpose of this review is to highlight health care inequities and provide a review and resource of available recommendations for clinical management of all patients with peripheral artery disease.
Since 1980, the American College of Cardiology (ACC) and American Heart
Association (AHA) have translated scientific evidence into clinical practice
guidelines with recommendations to improve ...cardiovascular health. These
guidelines, based on systematic methods to evaluate and classify evidence,
provide a cornerstone of quality cardiovascular care.
In response to reports from the Institute of Medicine
1
,
2
and a mandate to evaluate new knowledge and maintain relevance at the point of
care, the ACC/AHA Task Force on Clinical Practice Guidelines (Task Force)
modified its methodology.
3
–
5
The
relationships among guidelines, data standards, appropriate use criteria, and
performance measures are addressed elsewhere.
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Peripheral arterial disease (PAD) is a global health issue that is becoming more prevalent in an aging world population. Diabetes mellitus and chronic kidney disease are also on the increase, and ...both are associated with accelerated vascular calcification and an unfavorable prognosis in PAD. These data challenge the traditional athero-centric view of PAD, instead pointing toward a disease process complicated by medial arterial calcification. Like atherosclerosis, aging is a potent risk factor for medial arterial calcification, and accelerated vascular aging may underpin the devastating manifestations of PAD, particularly in patients prone to calcification. Consequently, this review will attempt to dissect the relationship between medial arterial calcification and atherosclerosis in PAD and identify common as well as novel risk factors that may contribute to and accelerate progression of PAD. In this context, we focus on the complex interplay between oxidative stress, DNA damage, and vascular aging, as well as the unexplored role of neuropathy.
The International Working Group on the Diabetic Foot (IWGDF) has published evidence‐based guidelines on the prevention and management of diabetic foot disease since 1999. This guideline is on the ...diagnosis, prognosis, and management of peripheral artery disease (PAD) in patients with foot ulcers and diabetes and updates the previous IWGDF Guideline. Up to 50% of patients with diabetes and foot ulceration have concurrent PAD, which confers a significantly elevated risk of adverse limb events and cardiovascular disease. We know that the diagnosis, prognosis, and treatment of these patients are markedly different to patients with diabetes who do not have PAD and yet there are few good quality studies addressing this important subset of patients. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to devise clinical questions and critically important outcomes in the patient‐intervention‐comparison‐outcome (PICO) format, to conduct a systematic review of the medical‐scientific literature, and to write recommendations and their rationale. The recommendations are based on the quality of evidence found in the systematic review, expert opinion where evidence was not available, and a weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to the intervention. We here present the updated 2019 guidelines on diagnosis, prognosis, and management of PAD in patients with a foot ulcer and diabetes, and we suggest some key future topics of particular research interest.
Peripheral arterial disease (PAD) results from the systemic atherosclerotic process. In this study, we aimed to determine the relationship between plasma atherogenic index (AIP), a ratio of molar ...concentrations of triglycerides to HDL-cholesterol, and long-term outcomes after endovascular therapy (EVT) in patients with superficial femoral artery (SFA) stenosis.
We retrospectively evaluated 673 patients who underwent EVT for PAD in our tertiary center between January 2015 and December 2020. In the receiver operating characteristic (ROC) curve analysis, the AIP value with the optimum cutoff value was determined as 0.576 to detect the presence of major adverse limb events (MALEs). Patients were divided into two groups according to low AIP (<0.576 as group 1) and high AIP (>0.576 as group 2).
Among the major endpoints, long-term restenosis rates were significantly higher in patients in the high-AIP group than in the low-AIP group (
<.001). The lower extremity amputation rate was not statistically significant between the two groups. All-cause mortality rate (54 (31.6) versus 117 (68.4),
<.001) was significantly higher in patients in the high-AIP group than in the low-AIP group. In addition, the MALE rate (94 (29.2) versus 218 (62.1),
<.001) was significantly higher in patients in the high-AIP group than in those in the low-AIP group.
In conclusion, we found that AIP is a significant independent predictor of long-term MALE in patients who underwent EVT for SFA.
The effect of gender on the outcomes of revascularization procedures in young patients with premature atherosclerotic peripheral arterial disease (PAD) is not known. The objective of this study was ...to compare short-term and long-term outcomes between young males and females undergoing infra-inguinal revascularization procedures.
We examined postoperative outcomes of male and female PAD patients under the age of 55 who underwent infra-inguinal revascularization procedures at a single tertiary institution from 2011 to 2019. Primary outcomes included 30-day morbidity, patency of the revascularization procedures, and major adverse limb events (MALE). Secondary outcomes included survival, amputation rate, reintervention rate, improvement of ankle-brachial index (ABI), and number of reinterventions.
Eighty-one infra-inguinal revascularization procedures (46 endovascular and 35 open procedures) were reviewed including 45 procedures in 37 males and 36 procedures in 31 females. Fifty-three (65.4%) of the procedures were performed in patients with chronic limb-threatening ischemia symptoms. The rest were treated for life-disabling claudication. The female patients were younger, had higher body mass index, and were more likely to have diabetes, hyperlipidemia, or chronic obstructive pulmonary disease in comparison to males. Thirty-day major adverse cardiovascular event was 0.0% and MALE was 16.0%. Mean follow-up was 806.2 days. At 1 year, primary patency was 34.4 ± 6.2%, primary assisted patency was 52.7 ± 6.5%, secondary patency was 61.8 ± 6.3%, and MALE-free rate was 47.0 ± 6.4%. For secondary outcomes at 1 year, amputation-free rate was 92.5 ± 3.2%, reintervention-free rate was 50.2 ± 6.4%, and survival was 96.2 ± 2.6%. By the end of the study, overall mortality rate was 14.8% and major amputation rate was 13.6%. No major differences were observed between males and females among these outcomes. A smaller improvement in ABI after revascularization was noted in females compared to males (female 0.2 ± 0.2 vs male 0.4 ± 0.2,
= .04). Among patients who required reintervention, females required a higher number of reinterventions than males (female 1.7 ± 2.5 vs male 0.8 ± 1.1,
= .03).
There were no significant differences in short-term and long-term outcomes between males and females under the age of 55 after infra-inguinal revascularization. Poor patency, high MALE rate, and high mid-term mortality, and amputation rates after revascularization in young PAD patients highlight the need for improved strategies to treat premature PAD.
Arterial stiffness indices predict cardiovascular outcomes in patients with coronary or kidney disease; however, there is little data on the prognostic value of arterial stiffness in patients with ...advanced peripheral arterial disease. We determined whether arterial stiffness indices predict the outcomes of major amputation or death in patients with chronic limb-threatening ischemia (CLTI).
Arterial stiffness was prospectively measured using brachial oscillometry in patients with CLTI. After measuring arterial stiffness, patients were followed in 6-month intervals for up to 3 years and evaluated for limb preservation, occurrence of major amputation, or death. Hemodynamic variables and arterial stiffness indices were used to define predictors of amputation or death.
A total of 136 patients presented with CLTI, and 134 (99%) of these patients required limb revascularization. At the end of follow-up (mean, 14 months), 24 patients (18%) were alive with a major amputation, and mortality was 7% (9 patients); 33 patients (24%) progressed to the combined outcome of major amputation or death. Patients having amputation and/or death (n = 33; 24%) initially presented with elevated pulse wave velocity (PWV) (13.41 ± 1.21 m/s vs 11.54 ± 1.65 m/s; P < .001), elevated augmentation index corrected to 75 beats per minute (40.42 ± 6.65% vs 27.12 ± 9.19%; P < .001), and high augmentation pressure (AP) (29.98 ± 4.32 mm Hg vs 13.40 ± 7.05 mm Hg; P < .001) compared with patients with preserved limbs. The initial ankle-brachial index (ABI) was lower in patients having amputation and/or death (0.43 ± 0.94 vs 0.62 ± 0.12; P < .001). Multivariable analysis identified PWV (odds ratio OR, 2.62; P = .013), AP (OR, 1.56; P < .001), and ABI (OR, 0.01; P < .001) as predictors of amputation or death. ROC analysis identified patients with PWV ≤12.7 m/s (hazard ratio, 4.71; P < .001), AP ≤22.15 mm Hg (hazard ratio, 13.03; P < .001), or ABI >0.52 with an increased rate of limb preservation.
PWV and AP, measurements of arterial stiffness, as well as the ABI, predict amputation or death in patients with CLTI.
Objective
DISRUPT PAD II was designed to evaluate the safety and performance of intravascular lithotripsy (IVL), a novel approach using pulsatile sonic pressure waves, to modify intimal and medial ...calcium in stenotic peripheral arteries.
Background
Vascular calcification restricts vessel expansion, increases the risk of vascular complications, and may impair the effect of anti‐proliferative therapy.
Methods
Disrupt PAD II was a non‐randomized, multi‐center study that enrolled 60 subjects with complex, calcified peripheral arterial stenosis at eight sites. Patients were treated with IVL and followed to 12‐months. The primary safety endpoint was major adverse events (MAE) through 30 days. The primary effectiveness endpoint was patency at 12 months as adjudicated by duplex ultrasonography (DUS). Key secondary endpoints included acute procedure success, freedom from re‐intervention, and functional outcomes.
Results
Between June 2015 and December 2015, subjects with moderate or severe calcified arterial lesions were enrolled. The final residual stenosis was 24.2%, with an average acute gain of 3.0 mm. The 30‐day MAE rate was 1.7% with one grade D dissection that resolved following stent placement. Primary patency at 12 months was 54.5%, and clinically driven TLR at 12 months was 20.7%. Optimal IVL technique defined by correct balloon sizing and avoiding therapeutic miss, improved 12‐month primary patency and TLR outcomes to 62.9% and 8.6%, respectively.
Conclusions
IVL demonstrated compelling safety with minimal vessel injury, and minimal use of adjunctive stents in a complex, difficult to treat population.
This study sought to assess the risk of target lesion revascularization (TLR) and all-cause death at 12 months and at the maximum available follow-up. Secondary objectives included the identification ...of factors which could have influenced general findings.
Recently several randomized trials comparing drug-coated balloon (DCB) with conventional plain balloon (PB) for the treatment of femoropopliteal artery disease have been reported, but no updated meta-analyses are available and questions remain surrounding the long-term antirestenotic effectiveness of the 2 therapies.
We searched main electronic databases for randomized trials comparing DCB and PB for femoropopliteal artery disease. Random effects models were used to estimate the risk of TLR and all-cause death at 12 months, whereas long-term TLR and death risk were assessed by mixed effects Poisson regression models and incident rates of each outcome per patient-year. Main analyses were supplemented by sensitivity analyses, Bayesian estimates, and trial sequential analysis.
A total of 8 eligible trials were identified. DCB was associated with a marked 12-month TLR risk reduction as compared with PB (risk ratio: 0.33; 95% confidence interval CI: 0.19 to 0.57). The risk of death was similar between groups (risk ratio: 0.96; 95% CI: 0.47 to 1.95). Long-term outcomes assessment showed a reduced incidence of TLR with DCB (0.35; 95% CI: 0.24 to 0.51) and a similar incidence of all-cause death (incidence rate ratio: 1.13; 95% CI: 0.60 to 2.15). Similar findings were observed in Bayesian analyses. Significant heterogeneity was present with evidence of differential efficacy across devices. Trial sequential analysis indicated that available evidence is sufficient to prove superior antirestenotic efficacy of DCB over PB.
DCB significantly reduces the risk of TLR as compared with PB without any effect on all-cause death. Evidence exists for differential efficacy according to the type of device used. Future trials investigating DCB angioplasty should include potentially more effective comparator therapies.
Background Peripheral arterial disease (PAD) can be diagnosed noninvasively by segmental blood pressure measurement and calculating an ankle-brachial index (ABI) or toe-brachial index (TBI). The ABI ...is known to be unreliable in patients with vascular stiffness and fails to detect the early phase of arteriosclerotic development. The toe vessels are less susceptible to vessel stiffness, which makes the TBI useful. However, the diagnostic limits used in guidelines, clinical settings, and experimental studies vary substantially. This review provides an overview of the evidence supporting the clinical use of the TBI. Methods A review of the literature identified studies reporting the use of the TBI regarding guideline recommendations, normal populations, correlations to angiographic findings, and prognostic implications. Results Eight studies conducted in a normal population were identified, of which only one study used imaging techniques to rule out arterial stenosis. A reference value of 0.71 was estimated as the lowest limit of normal based on the weighted average in studies with preheating of the limbs. A further seven studies showed correlations of the TBI with angiographic findings. The TBI had a sensitivity of 90% to 100% and a specificity of 65% to 100% for the detection of vessel stenosis. Few studies investigated the value of the TBI as a prognostic marker for cardiovascular mortality and morbidity, and no firm conclusions could be made. Studies have, however, shown correlation between the TBI and comorbidities such as kidney disease, diabetes, and microvasculature disease. Conclusions In contrast to the well-defined and evidence-based limits of the ABI, the diagnostic criteria for a pathologic TBI remain ambiguous. Although several guidelines and reviews of PAD diagnostics recommend a TBI <0.70 as cutoff, it is not strictly evidence-based. The current literature is not sufficient to conclude a specific cutoff as diagnostic for PAD. The current studies in normal populations and the correlation with angiography are sparse, and additional trials are needed to further validate the limits. Large-scale trials are needed to establish the risk of morbidity and mortality for the various diagnostic limits of the TBI.
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