Abstract 10590: Serum Inhibitory Factor 1 Concentration Positively Correlates with HDL-Cholesterol Level and is a New Independent Determinant of Cardiovascular Heart Disease Risk
Background: A high level of HDL-cholesterol (HDL-C) is the only one established negative risk factor for coronary artery disease (CAD). The HDL protective effect is mainly attributed to their major role in reverse cholesterol transport. In this process, the HDL uptake by the liver involves a newly identified F1-ATPase/P2Y13 pathway, which may be inhibited by mitochondrial inhibitor factor 1 (IF1). We recently identified IF1 in human serum and the aim of this study was to evaluate serum IF1 as a new determinant of HDL-C and to determine whether IF1 level predicts risk of CAD.
Methods: Serum IF1 level was measured, by a competitive ELISA immunoassay developed in our laboratory, in the GENES Study, a cross-sectional case-control study which include 800 male cases and 800 age-paired controls, aged 45-75. Cases were patients admitted for a first coronary event, either unstable angina pectoris or definite myocardial infarction. Controls were randomly selected from the general population, using electoral rolls. A complete investigation of cardiovascular risk was collected for each patient, including evaluation of habits, biological and clinical markers.
Results: In the general population, serum IF1 level was strongly correlated with the lipoprotein profile, positively with HDL markers (HDL-C, apo A-I and lipoparticle AI levels), and negatively with triglyceride-rich lipoproteins markers. A multivariate analysis identified serum IF1 as a new independent determinant of HDL level. Average IF1 concentration was 20 % lower in cases (0.43 ± 0.13 µg/ml) in comparison with controls (0.53 ± 0.15 µg/ml) (p<0.001). In a multivariate model including classical risk factors, physical activity, smoking and alcohol habits, CRP and lipoprotein levels, IF1 levels were negatively related with the CAD risk.
Conclusions: IF1 appears as a new independent determinant of apo A-I and HDL-C levels and is negatively associated with cardiovascular risk. Assessing plasma IF1 might help to document the cardiovascular risk profile, particularly in patients with low levels of apo A-I and/or HDL-C.
- © 2011 by American Heart Association, Inc.