PAD is not just a leg-artery disease — it is a powerful warning sign for future death, cardiovascular events, limb loss, and frailty. This review maps which signals matter most for prognosis, from MALE, polyvascular disease, diabetes and CKD to biomarkers, nutrition scores, exercise capacity, and machine-learning risk prediction.
Human-verified editorial review
Verified by World ID proof-of-human. This editorial layer was submitted from a SAIMSARA account verified as a unique human.
Abstract: The aim of this paper is to synthesize current evidence regarding the prognostic factors and clinical outcomes associated with peripheral artery disease, focusing on mortality, limb loss, and the predictive utility of emerging biomarkers and clinical scoring systems. The review utilises 373 original studies with 10030675 total participants (topic deduplicated ΣN). Across the mapped evidence, PAD emerged as a strong and consistent prognostic signal for both systemic and limb outcomes, with all-cause mortality hazard ratios ranging from 1.15 to 3.23 and a stepwise mortality gradient reaching 35–42.9% in triple-territory polyvascular disease. Major adverse limb events functioned as sentinel events, associated with markedly higher subsequent hospitalization (HR 7.21) and death (HR 3.23), while low-dose rivaroxaban plus aspirin was associated with a 43% MALE reduction in lower-extremity PAD and reduced acute limb ischemia after lower-extremity revascularization. Recurrent topic-level signals support a role for nutritional indices (GNRI, PNI), cardiac biomarkers (hs-cTnT, NT-proBNP, GDF15), inflammation-based ratios, frailty/sarcopenia, and ABI-related measures as prognostic refiners beyond traditional vascular indices, and machine-learning multi-marker panels achieved AUROC values around 0.80–0.88 for 2–3-year MALE prediction. Practically, the evidence map indicates that PAD prognosis is best approached as a multidimensional problem integrating intensified antithrombotic therapy, secondary prevention, comorbidity control (diabetes, CKD, heart failure), and structured exercise rehabilitation rather than reliance on anatomic severity alone. Heterogeneity in outcome definitions, biomarker thresholds, and the unresolved obesity paradox remain key uncertainties within the mapped literature. Future research should prioritize prospective external validation of multi-protein and machine-learning prognostic models against harmonized MALE/MACE endpoints, alongside trials testing whether biomarker- and nutrition-guided risk stratification improves long-term survival and limb preservation in PAD.
Final search date and database lock: 2026-05-04 14:26:27 CEST
Plan: Pro (expanded craft tokens; source: PubMed)
Source: PubMed
Total Abstracts/Papers: 997
Downloaded Abstracts/Papers: 997
Included original and non-original Abstracts/Papers (all): 390
Included original Abstracts/Papers (Vote counting by direction of effect): 373
Reference Index (links used in paper): 139
Total participants (topic deduplicated ΣN): 10030675
Get access to the full paper
Unlock the full evidence map
The full evidence review, including the Introduction, Methods, Results, Discussion, Conclusion, figures, and complete reference index, opens after purchase or sign-in.
The Evidence Object JSON is a separate machine-readable evidence product: a concentrated synthesis of results, topic-level evidence, and discussion across original and non-original studies. It can be directly input into your LLM, agent, or RAG workflow.
[15] Editor's Choice - Revascularisation for Peripheral Artery Disease in France: Implications for the Implementation of VOYAGER-PAD. — https://doi.org/10.1016/j.ejvs.2024.01.091
[25] Development of a 3-Dimensional Prognostic Score for Patients With Symptomatic Peripheral Artery Disease: PAD Score. — https://doi.org/10.1177/0003319720920155
[31] Impact of peripheral artery disease on prognosis after percutaneous coronary intervention: Outcomes from the multicenter prospective e-ULTIMASTER registry. — https://doi.org/10.1016/j.atherosclerosis.2022.01.007
[32] Effects of cilostazol on the prognosis of lower extremity peripheral arterial disease in patients with diabetes mellitus in Korea: A nationwide population-based study. — https://doi.org/10.1016/j.atherosclerosis.2025.120634
[34] Cardiac biomarkers but not measures of vascular atherosclerosis predict mortality in patients with peripheral artery disease. — https://doi.org/10.1016/j.cca.2019.04.061
[36] Coronary Event Risk Test (CERT) as a Risk Predictor for the 10-Year Clinical Outcome of Patients with Peripheral Artery Disease. — https://doi.org/10.3390/jcm12196151
[37] Optimal cut-off value of preprocedural geriatric nutritional risk index for predicting the clinical outcomes of patients undergoing endovascular revascularization for peripheral artery disease. — https://doi.org/10.1016/j.jjcc.2020.05.015
[42] Multiple Peri-Operative Complications are Associated with Reduced Long Term Amputation Free Survival Following Revascularisation for Lower Limb Peripheral Artery Disease: A Population Based Linked Data Study. — https://doi.org/10.1016/j.ejvs.2019.11.014
[43] Recent trends in morbidity and in-hospital outcomes of in-patients with peripheral arterial disease: a nationwide population-based analysis. — https://doi.org/10.1093/eurheartj/eht288
[47] Peripheral artery disease and outcomes after myocardial infarction: an individual-patient meta-analysis of 28,771 patients in CAPRICORN, EPEHESUS, OPTIMAAL and VALIANT. — https://doi.org/10.1016/j.ijcard.2012.11.033
[49] Long-Term Prognosis of Patients With Transient Ischemic Attack or Stroke and Symptomatic Vascular Disease in Multiple Arterial Beds. — https://doi.org/10.1161/strokeaha.118.020913
[52] Prognosis of atrial fibrillation in patients with symptomatic peripheral arterial disease: data from the REduction of Atherothrombosis for Continued Health (REACH) Registry. — https://doi.org/10.1016/j.ejvs.2010.03.003
[55] Impact of geriatric nutritional risk index on prognosis in peripheral artery disease patients undergoing endovascular therapy. — https://doi.org/10.1111/jch.14659
[57] Measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data. — https://doi.org/10.1016/s2213-8587(17)30183-3
[58] Endovascular Treatment for Calcified Femoropopliteal Peripheral Artery Disease and Risk Factor Identification: Two Year Outcomes of the Evolusion Study. — https://doi.org/10.1016/j.ejvs.2025.10.002
[59] Dobutamine stress echocardiography predicts surgical outcome in patients with an aortic aneurysm and peripheral vascular disease. — https://doi.org/10.1016/0735-1097(93)90353-3
[60] Treatment with cilostazol improves clinical outcome after endovascular therapy in hemodialysis patients with peripheral artery disease. — https://doi.org/10.1016/j.jjcc.2015.05.003
[62] Walking Economy after an Arm-ergometry versus a Treadmill Supervised Exercise program in patients with Peripheral Artery Disease: Findings from the ARMEX trial. — https://doi.org/10.1016/j.heliyon.2025.e42275
[63] The Identification and Evaluation of Interleukin-7 as a Myokine Biomarker for Peripheral Artery Disease Prognosis. — https://doi.org/10.3390/jcm13123583
[64] Mono or Dual Antiplatelet Therapy for Treating Patients with Peripheral Artery Disease after Lower Extremity Revascularization: A Systematic Review and Meta-Analysis. — https://doi.org/10.3390/ph15050596
[65] Incidental renal artery stenosis is an independent predictor of mortality in patients with peripheral vascular disease. — https://doi.org/10.1681/asn.2005080827
[67] Development and evaluation of a prediction model for peripheral artery disease-related major adverse limb events using novel biomarker data. — https://doi.org/10.1016/j.jvs.2024.03.450
[70] Peripheral artery disease at the time of dialysis initiation and mortality: a prospective observational multicenter study. — https://doi.org/10.1136/bmjopen-2020-042315
[72] Prospective multicentre study of the natural history of atherosclerotic renal artery stenosis in patients with peripheral vascular disease. — https://doi.org/10.1046/j.1365-2168.2002.02144.x
[75] Elevated C-Reactive Protein/Albumin Ratio Is Associated With Lesion Complexity, Multilevel Involvement, and Adverse Outcomes in Patients With Peripheral Artery Disease. — https://doi.org/10.1177/00033197221075853
[76] Depression and anxiety symptoms are underestimated risk factors for postoperative prognosis in patients with Type 2 diabetes and peripheral artery disease undergoing partial foot amputation: Results from a prospective cohort study. — https://doi.org/10.1016/j.jpsychores.2024.111824
[78] Predicting long-term prognosis in stable peripheral artery disease with baseline functional capacity estimated by the Duke Activity Status Index. — https://doi.org/10.1016/j.ahj.2016.10.009
[79] Association between home-based exercise using a pedometer and clinical prognosis after endovascular treatment in patients with peripheral artery disease. — https://doi.org/10.1016/j.jjcc.2022.09.005
[83] Validation and Comparison of the Prognosis Predicting Ability of Inflammation-Based Scores Following Endovascular Treatment for Peripheral Artery Disease. — https://doi.org/10.1177/00033197231161394
[84] Symptomatic Upper Extremity Peripheral Artery Disease is Associated With Poor Outcomes and a Broad Spectrum of Etiologies. — https://doi.org/10.1177/00033197231218332
[85] Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio Predict Severity and Prognosis of Lower Limb Arteriosclerosis Obliterans. — https://doi.org/10.1016/j.avsg.2019.09.005
[87] Investigating the Prognostic Potential of Plasma ST2 in Patients with Peripheral Artery Disease: Identification and Evaluation. — https://doi.org/10.3390/proteomes12030024
[92] Microbiota γ-Butyrobetaine Is Associated With Increased Risk of Major Adverse Limb Events in People With Lower Extremity Arterial Disease Undergoing Endovascular Therapy. — https://doi.org/10.1161/jaha.124.037356
[93] Bilateral low systolic toe pressure and toe-brachial index are associated with long-term mortality in patients with peripheral artery disease. — https://doi.org/10.1016/j.jvs.2019.03.073
[97] Association of the Prognosis of Ankle-brachial Index Improvement One Year Following Endovascular Therapy in Patients with Peripheral Artery Disease: Data from the I-PAD NAGANO Registry. — https://doi.org/10.2169/internalmedicine.6117-20
[98] Cardiovascular Outcome and Mortality in Patients Undergoing Endovascular Treatment for Symptomatic Peripheral Artery Disease - Short-Term Results of the Toma-Code Registry. — https://doi.org/10.1253/circj.cj-18-0105
[100] The impact of coronary artery disease and left ventricular ejection fraction on the prognosis of patients with peripheral artery disease. — https://doi.org/10.1111/imj.13600
[101] Frailty and functional outcomes after open and endovascular procedures for patients with peripheral arterial disease: A systematic review. — https://doi.org/10.1016/j.jvs.2018.12.060
[103] Low rate of revascularization procedures and poor prognosis particularly in male patients with peripheral artery disease - A propensity score matched analysis. — https://doi.org/10.1016/j.ijcard.2017.12.054
[109] Association between Body Mass Index and Clinical Outcomes of Peripheral Artery Disease after Endovascular Therapy: Data from K-VIS ELLA Registry. — https://doi.org/10.4070/kcj.2021.0040
[111] Long-term prognosis of patients with peripheral arterial disease: a comparison in patients with coronary artery disease. — https://doi.org/10.1016/j.jacc.2007.11.077
[117] Effects of lipid-lowering therapy on major adverse limb events in patients with peripheral arterial disease: A meta-analysis of randomized clinical trials. — https://doi.org/10.1177/17085381211043952
[118] Renin-Angiotensin-Aldosterone System Inhibitors, Statins, and Beta-Blockers in Diabetic Patients With Critical Limb Ischemia and Foot Lesions. — https://doi.org/10.1177/10742484221101980
[120] Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry. — https://doi.org/10.1093/eurheartj/ehu080
[122] Association of monocyte-to-high-density lipoprotein cholesterol ratio with peripheral artery disease and long-term mortality. — https://doi.org/10.1177/17085381251339242
[123] Prediction of Major Adverse Limb Events in Females with Peripheral Artery Disease using Blood-Based Biomarkers and Clinical Features. — https://doi.org/10.1007/s12265-024-10574-y
[125] Long-Term Prognostic Risk in Lower Extremity Peripheral Arterial Disease as a Function of the Number of Peripheral Arterial Lesions. — https://doi.org/10.1161/jaha.115.001823
[126] Machine Learning to Predict Long-Term Cardiac-Relative Prognosis in Patients With Extra-Cardiac Vascular Disease. — https://doi.org/10.3389/fcvm.2021.771504
[141] Prevalence and clinical impact of baseline atherosclerotic vascular disease in patients undergoing transcatheter aortic valve implantation: A meta-analysis. — https://doi.org/10.1016/j.ijcard.2025.134004
[145] Long-term prognosis of patients with peripheral arterial disease with or without polyvascular atherosclerotic disease. — https://doi.org/10.1093/eurheartj/ehp553
[149] Supervised Exercise Therapy Using Mobile Health Technology in Patients With Peripheral Arterial Disease: Pilot Randomized Controlled Trial. — https://doi.org/10.2196/24214
[157] Peripheral arterial disease: Changes in clinical outcomes and therapeutic strategies in two cohorts, from 2002 to 2008 and from 2008 to 2014. A population-based study. — https://doi.org/10.1177/2047487318770299
[160] Prognostic Value of the CHADS-VASc Score after Endovascular Therapy for Femoral Popliteal Artery Lesions. — https://doi.org/10.5551/jat.60772
[166] Mortality rates at 10 years are higher in diabetic than in non-diabetic patients with chronic lower extremity peripheral arterial disease. — https://doi.org/10.1177/1358863x16643603
[167] Effects of chronic kidney disease on clinical outcomes in patients with peripheral artery disease undergoing endovascular treatment: Analysis from the K-VIS ELLA registry. — https://doi.org/10.1016/j.ijcard.2018.03.108
[168] The prognostic value of the serum eicosapentaenoic acid to arachidonic acid ratio in relation to clinical outcomes after endovascular therapy in patients with peripheral artery disease caused by femoropopliteal artery lesions. — https://doi.org/10.1016/j.atherosclerosis.2015.02.035
[184] Evolution of Major Amputation Risk in Patients Hospitalized in France for Critical Limb Ischemia: The COPART Registry. — https://doi.org/10.1177/0003319720976823
[189] Usefulness of Lipoprotein(a) for Predicting Clinical Outcomes After Endovascular Therapy for Aortoiliac Atherosclerotic Lesions. — https://doi.org/10.1177/1526602817728068
[200] Catheter versus surgical approach for the management of concomitant aortic stenosis and coronary artery disease: An inverse probability treatment weighting analysis. — https://doi.org/10.1016/j.acvd.2022.12.004
[202] The influence of comorbidities on the prognosis after an acute heart failure decompensation and differences according to ejection fraction: Results from the EAHFE and RICA registries. — https://doi.org/10.1016/j.ejim.2023.02.026
[203] The extent of atherosclerotic lesions in crural arteries predicts survival of patients with lower limb peripheral artery disease: A new classification of crural atherosclerosis. — https://doi.org/10.1016/j.atherosclerosis.2016.04.016
[205] Lower extremity peripheral arterial disease in individuals with coronary artery disease: prognostic importance, care gaps, and impact of therapy. — https://doi.org/10.1016/j.ahj.2007.09.005
[206] Association of total white cell count with mortality and major adverse events in patients with peripheral arterial disease: a systematic review. — https://doi.org/10.1016/j.ejvs.2013.12.020
[213] Performance of prognostic markers in the prediction of wound healing or amputation among patients with foot ulcers in diabetes: a systematic review. — https://doi.org/10.1002/dmrr.2704
[216] Predictors of healing, ulcer recurrence and persistence, amputation and mortality in type 2 diabetic patients with diabetic foot: a 10-year retrospective cohort study. — https://doi.org/10.1007/s12020-020-02431-0
[226] The relationship between the Geriatric Nutritional Risk Index and all-cause mortality in patients with peripheral artery disease. — https://doi.org/10.1371/journal.pone.0325938
[231] Interpretable machine learning prediction model for major adverse cardiovascular events in patients with peripheral artery disease. — https://doi.org/10.1016/j.jvs.2025.05.022
[237] Mortality, Cardiovascular and Limb Events in Patients With Symptomatic Lower Extremity Artery Disease and Diabetes. — https://doi.org/10.1177/00033197211050144
[242] Toe pressure should be part of a vascular surgeon's first-line investigation in the assessment of lower extremity artery disease and cardiovascular risk of a patient. — https://doi.org/10.1016/j.jvs.2020.06.104
[243] High leg salvage rate after infrainguinal bypass surgery for ischemic tissue loss (Fontaine IV) is compromised by the short life expectancy. — https://doi.org/10.1177/145749691009900410
[248] Differences in major limb outcomes by indication for lower extremity endovascular revascularization in patients receiving hemodialysis. — https://doi.org/10.1007/s00380-022-02195-9
[249] Risk stratification and mortality prediction in octo- and nonagenarians with peripheral artery disease: a retrospective analysis. — https://doi.org/10.1186/s12872-021-02177-1
[252] The relationship between sarcopenia and one-year mortality in patients with critical limb ischemia undergoing endovascular therapy below the knee. — https://doi.org/10.1177/17085381221124702
[258] Obesity Paradox in Peripheral Arterial Disease: Results of a Propensity Match Analysis from the National Inpatient Sample. — https://doi.org/10.7759/cureus.4704
[262] Prolonged vs Short Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With or Without Peripheral Arterial Disease: A Subgroup Analysis of the PRODIGY Randomized Clinical Trial. — https://doi.org/10.1001/jamacardio.2016.2811
[270] Investigation of Growth Differentiation Factor 15 as a Prognostic Biomarker for Major Adverse Limb Events in Peripheral Artery Disease. — https://doi.org/10.3390/jcm14155239
[281] Reduction in Acute Limb Ischemia With Rivaroxaban Versus Placebo in Peripheral Artery Disease After Lower Extremity Revascularization: Insights From VOYAGER PAD. — https://doi.org/10.1161/circulationaha.121.055146
[286] The association of comorbid depression with mortality and amputation risk in patients with chronic limb-threatening ischemia. — https://doi.org/10.1016/j.jvs.2023.09.001
[288] Referral from vascular surgery to cardiovascular rehabilitation and related outcomes in patients with peripheral arterial disease: the THINKPAD-RELOADED survey. — https://doi.org/10.4081/monaldi.2019.1101
[295] Predictors for the Development of Major Adverse Limb Events after Percutaneous Revascularization-Gender-Related Characteristics. — https://doi.org/10.3390/medicina59030480
[305] Long-term prognosis of diabetic patients with critical limb ischemia: a population-based cohort study. — https://doi.org/10.2337/dc08-1223
[311] High-Sensitivity Cardiac Troponin Predicts Major Cardiovascular Events in Diabetic Patients With Critical Limb Ischemia and Foot Lesions. — https://doi.org/10.3389/fcvm.2021.595701
[312] Cryptogenic mechanism in ischaemic stroke patients is a predictor of 5-year survival: A population-based study. — https://doi.org/10.1177/2396987316669216
[325] Interferon Gamma and Tumor Necrosis Factor Alpha Are Inflammatory Biomarkers for Major Adverse Cardiovascular Events in Patients with Peripheral Artery Disease. — https://doi.org/10.3390/biomedicines13071586
[333] Decreased ankle/brachial indices in relation to morbidity and mortality in patients with peripheral arterial disease. — https://doi.org/10.1177/1358863x9700200302
[348] Prediction of 2-Year Major Adverse Limb Event-Free Survival After Percutaneous Transluminal Angioplasty and Stenting for Lower Limb Atherosclerosis Obliterans: A Machine Learning-Based Study. — https://doi.org/10.3389/fcvm.2022.783336
[360] Patients carrying CYP2C19 loss of function alleles have a reduced response to clopidogrel therapy and a greater risk of in-stent restenosis after endovascular treatment of lower extremity peripheral arterial disease. — https://doi.org/10.1016/j.jvs.2014.03.293
[361] Prevalence and prognostic impact of non-cardiac co-morbidities in heart failure outpatients with preserved and reduced ejection fraction: a community-based study. — https://doi.org/10.1002/ejhf.1202
[368] Long-term survival in elderly patients hospitalized for heart failure: 14-year follow-up from a prospective randomized trial. — https://doi.org/10.1001/archinte.166.17.1892
[382] Predictors of All-Cause Mortality After Successful Transcatheter Aortic Valve Implantation in Patients With Atrial Fibrillation. — https://doi.org/10.1016/j.amjcard.2023.08.067
[384] Short and long-term clinical impact of transcatheter aortic valve implantation in Portugal according to different access routes: Data from the Portuguese National Registry of TAVI. — https://doi.org/10.1016/j.repc.2020.02.014
