Peripheral Arterial Disease: Pathophysiology, Risk Factors, and Role of Antithrombotic Therapy

SummaryConflicting findings regarding the association between protein Z and atherosclerotic disease have been reported. The aim of this case-control study was to evaluate the role of protein Z in a peripheral localization of atherosclerosis. We studied protein Z levels in 120 patients (102 male, 18 female; median age: 75 years) admitted to the Unit of Vascular Surgery of the University of Florence with a clinical manifestation of peripheral arterial disease (PAD), and in 360 healthy subjects selected to be comparable to the patients group in terms of age and gender. Protein Z levels were found to be significantly (p < 0.05) lower in PAD patients [1,594 (89–3,635) ng/ml] compared to the healthy control group [1,728 (300–3,736) ng/ml].A logistic regression analysis showed, at univariate analysis, a significantly increased risk of PAD in patients with low levels of protein Z (<5th percentile of our control group: < 601 ng/ml) (OR: 5.72, 95%CI 3.07–10.66; p < 0.0001). After adjustment for age, gender and traditional cardiovascular risk factors the association was confirmed (OR: 5.83, 95%CI 2.83–12.01; p < 0.0001). Moreover, a significant association between low protein Z levels and clinical severity of the disease, evaluated through Fontaine’s stages, was reported after adjustment for age, gender, and traditional cardiovascular risk factors (general linear model, p for trend: 0.03). In conclusion, our data shows an association between low protein Z levels and the occurrence of PAD. These findings provide evidence for the role of protein Z in the pathogenesis of the atherosclerotic disease.

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Abstract #415 Peripheral Arterial Disease and Its Association with Cardiovascular Risk Factors in Type 2 Diabetes

Endocrine Practice ◽

10.1016/s1530-891x(20)47176-9 ◽

2018 ◽

Vol 24 ◽

pp. 103-104

Author(s):

Rohit Kapoor ◽

Shivam Kapoor ◽

Rishabh Kapoor

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Cardiovascular Risk ◽

Peripheral Arterial Disease ◽

Cardiovascular Risk Factors ◽

Arterial Disease ◽

Peripheral Arterial

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Faculty Opinions recommendation of Risk factors for mortality among individuals with peripheral arterial disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727847292.793537064 ◽

2017 ◽

Author(s):

Wilbert Aronow

Keyword(s):

Risk Factors ◽

Peripheral Arterial Disease ◽

Arterial Disease ◽

Peripheral Arterial

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The Role of Circulating Biomarkers in Peripheral Arterial Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22073601 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3601

Author(s):

Goren Saenz-Pipaon ◽

Esther Martinez-Aguilar ◽

Josune Orbe ◽

Arantxa González Miqueo ◽

Leopoldo Fernandez-Alonso ◽

...

Keyword(s):

Peripheral Arterial Disease ◽

Lower Limb ◽

Prediction Models ◽

Arterial Disease ◽

Cardiac Damage ◽

Thrombotic Occlusion ◽

Medical Treatments ◽

Peripheral Arterial ◽

Inflammatory Molecules

Peripheral arterial disease (PAD) of the lower extremities is a chronic illness predominantly of atherosclerotic aetiology, associated to traditional cardiovascular (CV) risk factors. It is one of the most prevalent CV conditions worldwide in subjects >65 years, estimated to increase greatly with the aging of the population, becoming a severe socioeconomic problem in the future. The narrowing and thrombotic occlusion of the lower limb arteries impairs the walking function as the disease progresses, increasing the risk of CV events (myocardial infarction and stroke), amputation and death. Despite its poor prognosis, PAD patients are scarcely identified until the disease is advanced, highlighting the need for reliable biomarkers for PAD patient stratification, that might also contribute to define more personalized medical treatments. In this review, we will discuss the usefulness of inflammatory molecules, matrix metalloproteinases (MMPs), and cardiac damage markers, as well as novel components of the liquid biopsy, extracellular vesicles (EVs), and non-coding RNAs for lower limb PAD identification, stratification, and outcome assessment. We will also explore the potential of machine learning methods to build prediction models to refine PAD assessment. In this line, the usefulness of multimarker approaches to evaluate this complex multifactorial disease will be also discussed.

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Complex antithrombotic therapy and bleeding risk in patients with peripheral arterial disease

European Heart Journal ◽

10.1093/ehjci/ehaa946.2396 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Tseng ◽

S Bhatt ◽

M Girardo ◽

D Liedl ◽

P Wennberg ◽

...

Keyword(s):

Peripheral Arterial Disease ◽

Triple Therapy ◽

Major Bleeding ◽

Antithrombotic Therapy ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Arterial Disease ◽

Risk Of Bleeding ◽

Increased Risk ◽

Peripheral Arterial

Abstract Introduction Antiplatelet therapy is the cornerstone of treatment for many atherosclerotic vascular pathologies including peripheral arterial disease (PAD). Patients with PAD often have comorbid conditions that require complex antithrombotic therapy, i.e. combined antiplatelet and anticoagulation. Methods All adult patients undergoing ankle brachial index (ABI) measurements were included in the study. ABI values between 1.00 and 1.40 were considered normal, and values below 1.00 or above 1.40 were considered PAD. Demographic, comorbidity and outcome data were obtained using diagnostic codes from the electronic health record. Three medication classes were analyzed: aspirin, non-aspirin oral antiplatelets (e.g. P2Y12 inhibitors) and oral anticoagulants (warfarin and the direct oral anticoagulants). Medication use was determined for patients who had been on a medication for at least one year. Cox proportional hazard analysis for the time to first bleeding event was analyzed. Bleeding was defined as any bleeding requiring medical evaluation (including clinically-relevant non-major bleeding and major bleeding). Results In all, 40,144 patients were included in the analysis (mean age 66±15, 43% female). Patients with PAD were more likely to be on double therapy (one antiplatelet with anticoagulation) (28% vs 19%) and triple therapy (dual antiplatelet with anticoagulation) (10% vs 4%). Unadjusted hazard ratios for bleeding risk showed increased risk of bleeding for patients with PAD (1.18, 95% confidence interval [CI]: 1.08–1.29), though the association is no longer present after adjustment for antithrombotic therapy. Adjusting for age, sex and PAD class, compared to no antithrombotic therapy, there was increased risk of bleeding for monotherapy (1.91, 95% CI: 1.61–2.26), double therapy (3.40, 95% CI: 2.89–4.00) and triple therapy (5.00, 95% CI: 4.21–5.96). Among medications, aspirin and anticoagulant use was independently associated with the greatest increase in risk of bleeding. Conclusion Patients in PAD are at increased risk of bleeding secondary to antithrombotic therapy. Complex antithrombotic therapy with double or triple therapy confer additional bleeding risk, particularly regimens containing aspirin and oral anticoagulants. Funding Acknowledgement Type of funding source: None

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