Elsevier

Thrombosis Research

Volume 126, Issue 6, December 2010, Pages e423-e427
Thrombosis Research

Regular Article
Osteoprotegerin is higher in peripheral arterial disease regardless of glycaemic status

https://doi.org/10.1016/j.thromres.2010.09.003Get rights and content

Abstract

Introduction

Peripheral arterial disease (PAD) and type 2 diabetes mellitus (DM) are both associated with excessive vascular calcification and elevated levels of inflammatory markers IL-6 and hsCRP. The recently identified Osteoprotegerin(OPG)/RANKL/TRAIL pathway has been implicated in vascular calcification, but data on levels in PAD and effect of co-existent DM are lacking.

Materials and Methods

4 groups of patients were recruited - 26 with PAD and DM, 35 with DM alone, 22 with PAD alone, and 21 healthy individuals. Serum OPG, RANKL, TRAIL, hsCRP and IL-6 were measured using commercial ELISA assays. Presence and severity of PAD was defined using ankle brachial index (ABI).

Results

Serum OPG (7.4 ± 0.3 vs.5.8 ± 0.2 pmol/l, p < 0.0001), TRAIL (95.5 ± 5.2 ng/ml vs. 76.2 ± 4.4 ng/ml, p = 0.006), hsCRP (2.6 ± 0.3 vs. 1.8 ± 0.3 mg/l, p = 0.048), and IL-6 (4.1 ± 0.4 vs. 2.9 ± 0.4 pg/ml, p = 0.06) were higher in patients with PAD. There was no difference in RANKL. Only OPG was significantly higher in PAD and DM (7.2 ± 0.3 pmol/l) and PAD alone (7.7 ± 0.4 pmol/l) compared to DM only (5.8 ± 0.3 pmol/l) and healthy controls (5.6 ± 0.4 pmol/l), p < 0.01, but OPG was no higher in those with DM plus PAD versus those with PAD alone (p < 0.3). Only OPG was associated with PAD severity, correlating negatively with ABI (r = -0.26, p = 0.03), independent of age, gender, glycaemic status, hsCRP and IL-6.

Conclusions

PAD is associated with higher serum OPG, regardless of the co-existence of DM. This finding, in addition to its correlation with severity of PAD, suggests that OPG may be a novel marker for the presence and severity of PAD, possibly by reflecting the degree of underlying vascular calcification.

Section snippets

Materials and Methods

Patients with documented type 2 diabetes and peripheral arterial disease were recruited from the diabetes and vascular surgery clinics in Beaumont Hospital, Dublin, Ireland. The healthy control subjects were recruited from Dublin City University, Ireland. The control group had no symptoms of intermittent claudication, normal peripheral foot pulses, no evidence of PAD on ankle brachial index (ABI) measurement, had normal glucose tolerance, as measured by a 75 gm oral glucose tolerance test

Results

There were 26 patients with PAD and DM (Group 1), 35 with DM and no PAD (Group 2), 22 with PAD and no DM (Group 3), and 21 healthy controls with neither DM nor PAD (Group 4). Demographic characteristics of the 4 groups are displayed in Table 1. All groups were matched for BMI and BMD. Healthy controls (Group 4) were younger, had lower blood pressure, lower use of statins, aspirin and medications affecting the renin-angiotensin system, lower fasting plasma glucose, higher fasting cholesterol and

Discussion

While great progress has been made in the identification of the action of the OPG/RANKL/TRAIL pathway in bone, its role in the vasculature is incompletely understood. In-vitro work suggests OPG acts as an anti-calcifying agent in vessels [5], [6] and numerous studies have consistently shown elevated levels in patients with coronary artery disease [8], [9], [10]. There has been conflicting data reported on serum OPG in individuals with PAD - a disease of marked vascular calcification.

Our finding

Conclusions

We found serum OPG, TRAIL, hsCRP and IL-6 (but not RANKL) to be significantly elevated in patients with PAD. Only OPG remained elevated in those with PAD regardless of the presence of type 2 diabetes. Additionally, only OPG correlated (negatively) with the severity of PAD as defined by ABI. These findings suggest OPG may be a more robust marker of peripheral arterial disease activity than more established biomarkers such as IL-6 and hsCRP, but further work is needed to further investigate these

Conflict of interest

There is no conflict of interest.

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    Data from this manuscript was presented at meetings in 2009 of the American Diabetes Association in New Orleans, USA and Diabetes UK in Glasgow, Scotland.

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