Genetics of Vascular Inflammation in Lower Limb Ischemia: The TNF-α Hypothesis in Peripheral Arterial Disease

Background: Vascular inflammation plays a crucial role in peripheral arterial disease (PAD), although the role of the mediators involved has not yet been properly defined. The aim of this work is to investigate gene expression and plasma biomarkers in chronic limb-threating ischemia (CLTI). Methods: Using patients from the GHAS trial, both blood and ischemic muscle samples were obtained to analyze plasma markers and mRNA expression, respectively. Statistical analy-sis was performed by using univariate (Spearman, t-Student, X2) and multivariate (multiple lo-gistic regression) tests. Results: 35 patients were available at baseline (29 for mRNA expression). Baseline characteristics (mean): Age:71.4±12.4 (79.4% male); TNF-α:10.7±4.9; hs-CRP:1.6±2.2; Neutrophil-to-lymphocyte ratio (NLR):3.5±2.8. Plasma TNF-α was found elevated (≥8.1) in 68.6% of patients, while high hs-CRP (≥0.5) in 60.5%. Diabetic patients with high level of inflammation showed significantly higher levels of NOX4 expression at baseline (p=0.0346). Plasma TNF-α had a negative correlation with eNOS expression (-0.5, p=0.015) and hs-CRP with VEGF-A (-0.63, p=0.005). The expression of NOX4 was parallel to that of plasma TNF-α (0.305, p=0.037), especial-ly in DM. Cumulative mortality at 12-month was related to NLR ≥3 (p=0.019) and TNF-α ≥8.1 (p=0.048). The best cut-off point for NLR to predict mortality was 3.4. Conclusions: NOX4 and TNF-α are crucial for the development and complications of lower limb ischemia, especially in DM. hs-CRP could have a negative influence on angiogenesis too. NLR and TNF-α represent suita-ble markers of mortality in CLTI. These results are novel because they connect muscle gene expres-sion and plasma information in patients with advanced PAD, deepening the search of new and ac-curate targets for this condition.

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Comparison of Color Doppler and computed tomography angiography (CTA) in arterial disease in patients with lower limb ischemia.

The Professional Medical Journal ◽

10.29309/tpmj/2021.28.10.6375 ◽

2021 ◽

Vol 28 (10) ◽

pp. 1381-1391

Author(s):

Muhammad Zakir ◽

Anjum Tazeen ◽

Faisal Nadeem Khan ◽

Mehreen Fatima ◽

Javed Tauqir ◽

...

Keyword(s):

Computed Tomography ◽

Peripheral Arterial Disease ◽

Computed Tomography Angiography ◽

Lower Limb ◽

Color Doppler ◽

Limb Ischemia ◽

Arterial Disease ◽

Cross Sectional ◽

Lower Limb Ischemia ◽

Peripheral Arterial

Objective: To compare the diagnostic accuracy of color Doppler ultrasound with computed tomography angiography in patients with lower limb ischemia and to assess the severity of stenosis. Study Design: Cross Sectional Analytical study. Setting: Shalamar Hospital, Lahore. Period: May 2020 to October 2020. Material & Methods: Data were collected according to the Age, Height, Weight, BMI, Duration of diabetes, Total Cholesterol, LDL, HDL, Triglyceride, Gender, Socioeconomic status, Diabetes, Hypertension, Stenosis, Collateral, calcification. Sample size of46 patients were included in this research comprising 32 males (69.6%) and 14 females (30.4%).Data entry and analysis will be done by using SPSS version-23. Results: Total numbers of 46 patients were included in this research comprising 32 males (69.6%) and 14 females (30.4%). According to the result analysis 34 patients had shown peripheral arterial disease at color Doppler and 12 patients had not shown peripheral arterial disease at color doppler. 38 patients had shown peripheral arterial disease at CTA and 8 patients had not shown peripheral arterial disease at CTA. Conclusion: This study concludes that computed tomography angiography for detection of peripheral arterial disease as the gold standard, MDCT angiography shows higher sensitivity (82.6%) than color-coded Doppler ultrasonography (73.9%) in the assessment of peripheral arterial disease.

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Does Squatting Worsen Lower Limb Ischemia in Patients with Peripheral Arterial Disease?

Indian Journal of Surgery ◽

10.1007/s12262-011-0364-9 ◽

2011 ◽

Vol 74 (4) ◽

pp. 298-300 ◽

Cited By ~ 1

Author(s):

Gargeshwari Krishnamurthy Guru Raghavendra

Keyword(s):

Peripheral Arterial Disease ◽

Lower Limb ◽

Limb Ischemia ◽

Arterial Disease ◽

Lower Limb Ischemia ◽

Peripheral Arterial

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Bridging Therapy Using B-SES for Peripheral Arterial Disease Patients with Severe Lower Limb Ischemia

Rigakuryoho Kagaku ◽

10.1589/rika.33.545 ◽

2018 ◽

Vol 33 (3) ◽

pp. 545-548

Author(s):

Kaori OCHIAI ◽

Yuuma TAMURA ◽

Kyousuke EHARA ◽

Riha SHIMIZU ◽

Yasushi MATUSHITA ◽

...

Keyword(s):

Peripheral Arterial Disease ◽

Lower Limb ◽

Limb Ischemia ◽

Arterial Disease ◽

Bridging Therapy ◽

Lower Limb Ischemia ◽

Peripheral Arterial

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VS19P PATTERN OF PERIPHERAL ARTERIAL DISEASE IN CRITICAL LOWER LIMB ISCHEMIA

ANZ Journal of Surgery ◽

10.1111/j.1445-2197.2007.04134_19.x ◽

2007 ◽

Vol 77 (s1) ◽

pp. A101-A101

Author(s):

C. Han ◽

M. Westcott ◽

W. Morrison

Keyword(s):

Peripheral Arterial Disease ◽

Lower Limb ◽

Limb Ischemia ◽

Arterial Disease ◽

Lower Limb Ischemia ◽

Peripheral Arterial

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Hyperfibrinogenemia in Peripheral Arterial Disease: Coexistent and Independent Risk Factor (A Report of Two Cases and Review of Literature)

PRILOZI ◽

10.2478/prilozi-2018-0046 ◽

2018 ◽

Vol 39 (2-3) ◽

pp. 93-96

Author(s):

Marijan Bosevski ◽

Gorjan Krstevski ◽

Irena Mitevska ◽

Emilija Antova ◽

Golubinka Bosevska

Keyword(s):

Diabetes Mellitus ◽

Risk Factor ◽

Lower Limb ◽

Case Reports ◽

Limb Ischemia ◽

Arterial Disease ◽

Lower Limb Ischemia ◽

Left Limb ◽

Peripheral Arterial

Abstract These case reports aim to show that hyperfibrinogenemia is a risk factor for the progression and prognosis of peripheral arterial disease (PAD), in patients with and without diabetes mellitus type 2. We present a patient with PAD who has type 2 diabetes mellitus, who has previously been repeatedly treated for lower limb ischemia with multiple vascular surgeries performed. A few weeks before admission the patient developed critical lower limb ischemia, which was treated with an iliaco-popliteal and femorofemoral bypass. The patient had elevated serum fibrinogen values. In the current admission, renewed left limb ischemia was diagnosed, and surgically evaluated with a recommendation for amputation of the left limb as a surgical recommendation. Our second patient had a stable intermittent claudication, dyslipidemia and hyperfibrinogenemia. He was successfully treated for those risk factors. Regular monitoring of the patient showed improved claudication distance and quality of life Our case reports, supported by a literature review, demonstrate that hyperfibrinogenemia is a possible risk factor for progression and the prognosis of PAD.

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Patient Perception of Lower Limb Non-Contrast Magnetic Resonance Angiography and Digital Subtraction Angiography in Diabetic Patients with Peripheral Arterial Disease

Cardiovascular Imaging Asia ◽

10.22468/cvia.2017.00087 ◽

2017 ◽

Vol 1 (4) ◽

pp. 240 ◽

Cited By ~ 1

Author(s):

Matthew W. Lukies ◽

Danielle Richmond ◽

Emma K. Hornsey ◽

Gemma Paterson ◽

Pei Heng Ko ◽

...

Keyword(s):

Magnetic Resonance ◽

Magnetic Resonance Angiography ◽

Peripheral Arterial Disease ◽

Digital Subtraction Angiography ◽

Lower Limb ◽

Arterial Disease ◽

Diabetic Patients ◽

Digital Subtraction ◽

Contrast Magnetic Resonance ◽

Peripheral Arterial

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Is There a Risk Factor More Responsible for Disaster?

Acta Medica Marisiensis ◽

10.1515/amma-2015-0054 ◽

2015 ◽

Vol 61 (3) ◽

pp. 245-247

Author(s):

Carasca Cosmin ◽

Muresan Vasile Adrian ◽

Tilea Ioan ◽

Magdas Annamaria ◽

Carasca Emilian ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Peripheral Arterial Disease ◽

Lower Limb ◽

Limb Ischemia ◽

Arterial Disease ◽

Risk Level ◽

Critical Ischemia ◽

Medium Risk ◽

Peripheral Arterial

Abstract Background: Risk factors for peripheral arterial disease are generally the same as those responsible for the ischemic heart disease and in both cases are overlapping risk factors involved in the etiology of atherosclerosis, such as smoking, dyslipidemia, diabetes and hypertension. Case report: We present a case of a 61 years old male, whose ischemic peripheral symptoms began in 2003, at the age of 49, presenting as a Leriche syndrome. The patient was subjected to first revascularization procedure consisting in aortic-bifemoral grafting in the same year. General examination revealed no risk factors except smoking. Only a year after, he returns with critical right lower limb ischemia due to bypass thrombosis, therefore two thrombectomies were performed followed by a right side femoro-popliteal bypassing with Dacron prosthesis. The patient’s condition was good until 2008 when a femoro-popliteal bypass using inverted autologus saphenous vein was imposed due to occlusion of the previous graft. In 2013 the patient was readmitted to hospital with left lower limb critical ischemia. A femoro-popliteal bypass was performed, followed by two thrombectomies and the amputation of the left thigh. Up to this date, the patient kept smoking. Discussions: Although our patient has a low/medium risk level of atherosclerosis by Framingham score and a minimum Prevent III score, all the surgical revascularization procedures were not able to avoid the amputation. Conclusions: There are enough reasons to believe that smoking as a single risk factor can strongly influence the unfavorable progression to amputation in patients with peripheral arterial disease.

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