What is the clinical evidence from this study?

Study design: Observational. Population: Peripheral arterial disease (n=69). Intervention: Critical limb ischemia vs. Intermittent claudication and healthy controls. Primary outcome: Plasma levels of VEGF and sTie2 (p=<0.001).

What question did this study set out to answer?

Determine whether circulating regulators of angiogenesis are altered in peripheral arterial disease and correlate with clinical disease severity.

April 20, 2026Journal of the American College of CardiologyOpen Access

Plasma Levels of Soluble Tie2 and Vascular Endothelial Growth Factor Distinguish Critical Limb Ischemia From Intermittent Claudication in Patients With Peripheral Arterial Disease

Q: What are the key findings of this study?

Critical limb ischemia was associated with significantly increased plasma levels of VEGF and sTie2 compared to intermittent claudication or healthy controls (P<0.001).

Q: What question did this study set out to answer?

Determine whether circulating regulators of angiogenesis are altered in peripheral arterial disease and correlate with clinical disease severity.

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Key result

Critical limb ischemia is linked to significantly higher plasma VEGF and sTie2 levels.

P<0.001
n=69

Why the study?

Alterations in angiogenic growth factors occur in cardiovascular disease, but whether these factors are altered in PAD or correlate with disease severity is unknown.

Are plasma levels of angiogenic growth factors altered in patients with peripheral arterial disease and do they correlate with disease severity?

Key Points

Determine whether circulating regulators of angiogenesis are altered in peripheral arterial disease and correlate with clinical disease severity.
Measured plasma Ang2, sTie2, VEGF, sVEGFR-1, and PlGF by ELISA in patients with peripheral arterial disease (n=46; 23 with intermittent claudication and 23 with critical limb ischemia) and healthy controls (n=23).
Cultured endothelial cells with recombinant VEGF in vitro to evaluate its direct effect on sTie2 shedding.
Plasma sTie2 (p < 0.01), Ang2 (p < 0.001), and VEGF (p < 0.01) were significantly higher in peripheral arterial disease patients than healthy controls, whereas PlGF and sVEGFR-1 showed no differences.
Plasma VEGF and sTie2 were comparable between controls and intermittent claudication, but were significantly elevated in critical limb ischemia (p < 0.001 vs. control or claudication), independent of cardiovascular risk factors or ankle-brachial index.
Plasma Ang2 was significantly higher in both claudication and critical limb ischemia than controls (p < 0.0001), and in vitro VEGF exposure significantly stimulated endothelial sTie2 shedding.

Study Design

Type

Observational (n=69)

Structured PICO

Are plasma levels of angiogenic growth factors altered in patients with peripheral arterial disease and do they correlate with disease severity?

Population

69 participants, comprising 46 patients with peripheral arterial disease (23 with intermittent claudication, 23 with critical limb ischemia) and 23 healthy control subjects.

Comparator

Healthy control subjects (n=23) and comparison between PAD severity groups (IC vs CLI)

Outcome

Plasma concentrations of angiopoietin-2 (Ang2), soluble Tie2 (sTie2), vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGFR-1), and placenta growth factor (PlGF)surrogate

Main Result

p-value: p=<0.001

Plasma levels of VEGF and sTie2 are significantly elevated in critical limb ischemia compared to intermittent claudication, suggesting their potential utility as biomarkers for severe peripheral arterial disease.

Discussion

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Implication

May aid PAD severity stratification in clinic; leaves open biomarker utility pending prospective validation.

Cite This Study

Findley et al. (2008) conducted an observational in Peripheral arterial disease (n=69). Critical limb ischemia vs. Intermittent claudication and healthy controls was evaluated on Plasma levels of VEGF and sTie2 (p=<0.001). Critical limb ischemia was associated with significantly increased plasma levels of VEGF and sTie2 compared to intermittent claudication or healthy controls (P<0.001).

synapsesocial.com/papers/69e598db85ab6d890cfade44 https://doi.org/10.1016/j.jacc.2008.02.045

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Plasma Levels of Soluble Tie2 and Vascular Endothelial Growth Factor Distinguish Critical Limb Ischemia From Intermittent Claudication in Patients With Peripheral Arterial Disease

Key Points

Study Design

Structured PICO

Main Result

Discussion

Implication

Cite This Study

Plasma Levels of Soluble Tie2 and Vascular Endothelial Growth Factor Distinguish Critical Limb Ischemia From Intermittent Claudication in Patients With Peripheral Arterial Disease

Key Points

Study Design

Structured PICO

Main Result

Discussion

Implication

Cite This Study

Also Consider

Also Consider