SS5. Soluble Inflammatory and Cellular Adhesion Molecules Predict Mortality, Cardiovascular events (MACE), and Amputation-Free Survival (AFS) in Patients Undergoing Lower Extremity Vein Bypass Surgery

Article Outline

• Objective
• Methods
• Results
• Conclusion
• Copyright

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Objective 

The long term benefits of lower extremity revascularization (LER) are limited by cardiovascular complications. This study was designed to test the hypothesis that baseline measures of systemic inflammation are predictive of postoperative outcomes following open surgical LER.

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Methods 

Prospective, three-center, cohort study of subjects (N=225) undergoing LER using autogenous vein bypass. Exclusion criteria included the presence of major infection or systemic illness. Baseline biomarkers (including high-sensitivity C-reactive protein (hsCRP), vascular cellular adhesion molecule (VCAM), and interleukin 6 (IL-6)) were obtained prior to surgery in the fasting state. The main outcomes were mortality, AFS, MACE, and graft patency. Correlation (Spearman) and Cox proportional hazard analyses were performed.

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Results 

The median follow up time was 29 ± 14.6 months. Indication for bypass was critical ischemia (CLI) in 129 cases (57%). The median hs-CRP, VCAM, and IL-6 levels for the entire cohort were 2.98 mg/l, 706.4 ng/ml, and 4.7 pg/mL; these three biomarkers were significantly correlated with each other (r values 0.39-0.66, p<0.05) and with the presence of CLI (p<0.05). All biomarkers evaluated by tertile or upper limit of reference range. After adjustment for age, diabetes, end-stage renal disease and tissue loss, all three inflammatory biomarkers were significantly associated with survival and AFS, particularly in the CLI cohort (Table). Biomarkers were also independently predictive of MACE. Baseline hsCRP had a strong univariate association with graft patency (p=.010), however this relationship was attenuated after adjustment for CLI, type of venous conduit, and outflow level.

Adjusted hazard ratios (95% CI) for study outcomes
	Overall cohort (N=225)	CLI (N=129)
Survival
Endpoints N (%)	47(21.1%)	37(28.9%)
⁎CRP (HR, CI)	2.77(1.41-5.46)	3.81(1.63-8.93)
VCAM	1.53(.95-2.47)	2.33(1.24-4.38)
IL-6	1.78 (1.11-2.85)	2.83 (1.46-5.49)
MACE
Endpoints N(%)	43 (19.3%)	31 (24.2%)
⁎CRP (HR, CI)	2.30 (1.15-4.59)	2.10 (.95-4.6)
VCAM	1.45 (.90-2.33)	1.86 (1.02-3.38)
IL6	1.28 (.81-2.01)	1.69 (.96-2.99)
AFS
Endpoints N(%)	56(21.1%)	45(35.2%)
⁎CRP (HR, CI)	2.38(1.31-4.32)	2.97(1.46-6.02)
VCAM	1.51 (.99-2.32)	2.04 (1.19-3.47)
IL6	1.76 (1.16-2.67)	1.72 (1.10-2.71)
Primary patency
Endpoints N(%)	73(32.7%)	48(37.5%)
⁎CRP (HR, CI)	1.44 (.87-2.40)	1.15 (.63-2.11)
VCAM	.90 (.65-1.24)	.85 (.57-1.25)
IL6	1.08 (.80-1.47)	1.23 (.85-1.78)

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Conclusion 

Baseline measures of systemic inflammation and cellular adhesion were independently predictive of mortality, cardiovascular events and limb-related outcomes following surgical LER. The efficacy of treatments that reduce inflammation should be explored in future investigations.