Michael Sobel1, Mayumi Yagi2, Katherine Moreno2, Ted R Kohler3, Gale L Tang3, Errol S Wijelath3, Julieann Marshall4, Richard D Kenagy4. 1. Division of Vascular Surgery, VA Puget Sound Health Care System, Seattle, WA, USA; University of Washington, Seattle, WA, USA. Electronic address: sobelm@uw.edu. 2. Division of Vascular Surgery, VA Puget Sound Health Care System, Seattle, WA, USA. 3. Division of Vascular Surgery, VA Puget Sound Health Care System, Seattle, WA, USA; University of Washington, Seattle, WA, USA. 4. University of Washington, Seattle, WA, USA.
Abstract
OBJECTIVES: One third of infrainguinal vein bypasses may fail within the first 1.5 years. Pro- and anti-inflammatory mechanisms are thought to be involved in these graft stenoses and occlusions. In previous studies, low levels of anti-phosphorylcholine IgM (anti-PC IgM, an innate anti-inflammatory IgM) have been associated with increased cardiovascular events. In this study, the peri-operative dynamics of anti-PC IgM levels were established during leg bypass surgery, and associations assessed between anti-PC IgM levels and primary graft patency. DESIGN AND METHODS: This was a prospective, observational cohort study of infrainguinal autogenous vein bypass for peripheral arterial occlusive disease involving four university affiliated hospitals. Plasma cytokine and anti-PC IgM levels were measured pre- and post-operatively. The outcome of interest was loss of primary graft patency because of occlusion or intervention for graft stenosis. RESULTS: One hundred and forty-two consecutive patients were enrolled: mean age 66 (46-91); 91% white race and male; 72.5% critical limb ischaemia (Fontaine III or IV). Median pre-operative anti-PC IgM levels were 49 units/mL (IQR 32.3-107.7, mean 89.8 + 101 sd). During follow up of an average of 1.8 years (1 month-7.4 years), 50 (35.2%) grafts lost primary patency. Pre-operative levels of interleukin 6 or C-reactive protein did not predict graft failure. Patients with pre-operative anti-PC IgM values in the lowest quartile had a twofold increased risk of graft failure (multivariable Cox proportional hazard, p = .03, HR 2.11, 95% CI 1.09-4.07), even after accounting for the other significant factors of conduit diameter, distal anastomosis, smoking, and the severity of leg ischaemia. CONCLUSIONS: Low levels of anti-PC IgM are associated with vein bypass graft failure. This biological mediator may be a useful marker to identify patients at higher risk, and offers the potential for novel, directed therapies for vascular inflammation and its consequences.
OBJECTIVES: One third of infrainguinal vein bypasses may fail within the first 1.5 years. Pro- and anti-inflammatory mechanisms are thought to be involved in these graft stenoses and occlusions. In previous studies, low levels of anti-phosphorylcholineIgM (anti-PCIgM, an innate anti-inflammatory IgM) have been associated with increased cardiovascular events. In this study, the peri-operative dynamics of anti-PCIgM levels were established during leg bypass surgery, and associations assessed between anti-PCIgM levels and primary graft patency. DESIGN AND METHODS: This was a prospective, observational cohort study of infrainguinal autogenous vein bypass for peripheral arterial occlusive disease involving four university affiliated hospitals. Plasma cytokine and anti-PCIgM levels were measured pre- and post-operatively. The outcome of interest was loss of primary graft patency because of occlusion or intervention for graft stenosis. RESULTS: One hundred and forty-two consecutive patients were enrolled: mean age 66 (46-91); 91% white race and male; 72.5% critical limb ischaemia (Fontaine III or IV). Median pre-operative anti-PCIgM levels were 49 units/mL (IQR 32.3-107.7, mean 89.8 + 101 sd). During follow up of an average of 1.8 years (1 month-7.4 years), 50 (35.2%) grafts lost primary patency. Pre-operative levels of interleukin 6 or C-reactive protein did not predict graft failure. Patients with pre-operative anti-PCIgM values in the lowest quartile had a twofold increased risk of graft failure (multivariable Cox proportional hazard, p = .03, HR 2.11, 95% CI 1.09-4.07), even after accounting for the other significant factors of conduit diameter, distal anastomosis, smoking, and the severity of leg ischaemia. CONCLUSIONS: Low levels of anti-PCIgM are associated with vein bypass graft failure. This biological mediator may be a useful marker to identify patients at higher risk, and offers the potential for novel, directed therapies for vascular inflammation and its consequences.
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