Soluble TNF Receptor 2 Levels are Associated with Significant Progression of Coronary Artery Calcification
Abstract Number: 1001-P
Authors: GREGORY L. KINNEY, JANET K. SNELL-BERGEON, DAVID MAAHS, JOHN E. HOKANSON, ELAINE CORNELL, RUSSELL P. TRACY, MARIAN REWERS, Aurora, CO, Burlington, VT
Institutions: Aurora, CO; Burlington, VT
Results: Coronary artery disease (CAD) is the leading cause of death in type 1 diabetes (T1D) and has been shown to be predicted by coronary artery calcification progression (CACp). TNF-alpha (TNFa ) is a pro-inflammatory cytokine and its soluble receptor (sTNFR2) increases with activation of TNFa signaling in tissue, e.g. inflammation associated with CAD. We examined whether sTNFR2 levels predict CACp in a case-control study nested within the Coronary Artery Calcification in Type 1 diabetes (CACTI) cohort.
CAC was measured twice, 2.4 years apart by electron beam CT using 80% R-R interval and 3mm slices. sTNFR2 was measured using R&D ELISAELISA. sTNFR2 levels were log transformed for analysis; eight results were truncated due to out of range values (>6000). The cases (N=205, 138 with T1D and 67 non-DM) included all participants with significant progression of CAC, defined as an increase of >= 2.5 units of square root transformed CAC volume. Controls (N=259) were frequency matched on age, diabetes, gender and baseline CAC level, randomly selected from all participants who did not experience significant CACp.
Participants with T1D had higher sTNFR2 levels compared to non-DM (Median (range) pg/ml; 2811 (1590-6024) vs 2253 (1610-4860), p<0.0001). Using conditional logistic regression, baseline sTNFR2 levels were found to predict CAC progression: OR 4.9 [per 1 log unit] (95%CI 2.1-11.5, p=0.0002), controlling for residual effects of matching variables: diabetes, gender, baseline CAC and age. The effect of sTNFR2 on CAC progression: OR 3.2 (95%CI 1.02-10.2, p=0.047) was largely independent of follow-up time, BMI, hypertension, LDL- and HD-cholesterol, adiponectin, hsCRP and cystatin C levels. No interaction was present between the effects of T1D and sTNFR2 on CACp (p=0.29).
In conclusion increased levels of sTNFR2 were found to be a significant predictor of progression of coronary artery calcification independent of other CAD risk factors.