Abstract 18865: Novel Cardiovascular Risk Factor Prediction of Cardiovascular Events in the (Type 2 Diabetes) FIELD Study and Effects of Fenofibrate
Background: Inflammation and oxidative stress are implicated in the pathogenesis of cardiovascular disease (CVD). In the Fenofibrate and Event Lowering in Diabetes (FIELD) study, comicronized fenofibrate, 200 mg daily for 5 years, reduced secondary CVD endpoints and prespecified microvascular disease in type 2 diabetes.
Aims: Predictive power for CVD of baseline measures of oxidative stress and inflammation and effects of 16 weeks fenofibrate treatment were evaluated in the FIELD cohort.
Methods: In (n=9760) male and female type 2 diabetes patients ELISAs and fluorescence spectroscopy were used to quantify risk markers in sera at baseline (before) and after 6 weeks of fenofibrate. Risk markers related to oxidative stress: Oxidized LDL (OxLDL), myeloperoxidase (MPO)), low molecular weight-fluorophores (LWM-F); inflammation: cell adhesion molecules sVCAM, sICAM, sE-Selectin, interleukin-6 (IL-6) and (anti-inflammatory) interleukin-10 (IL-10) and the pro-inflammatory pro-oxidant adipokine leptin. Correlations between baseline biomarker and HbA1c levels were calculated. Changes in biomarkers due to fenofibrate were analyzed on the log scale, and back-transformed to be presented as relative changes.
Results: Statistically significant predictors of CVD in the combined fenofibrate and placebo groups were baseline Ox-LDL, LMW-F, IL-6, sICAM, sVCAM, sE-Selectin, which were positively related to CVD risk, and leptin which was negatively related to CVD risk; all P<0.05. Results were statistically significant in both fenofibrate and placebo groups except for Ox-LDL, sE-Selectin (both groups), and LMW-F (placebo). Baseline marker tertiles were related to future CVD events and variation in their levels was only weakly related <7% to concurrent HbA1c levels. Relative to baseline fenofibrate changed (geometric mean, 95% CI) biomarker levels: Ox-LDL -17%, MPO -6%; LMW-F +21%, IL-6 -4%; sICAM +4%, sVCAM +4%, sE-Selectin -6%, leptin +5%; all p<0.001.
Conclusions: In type 2 diabetes CVD events over 5 years were predicted by baseline levels of oxidative stress and inflammation, which were not strongly related to glycemia. Fenofibrate has favorable effects on some, but not all measures of oxidative stress and inflammation.
- © 2010 by American Heart Association, Inc.