0470 : Serum IF1 concentration as a predictor of mortality in coronary heart disease patients

Aim The ecto-F1-ATPase/P2Y13 pathway plays a key role in reverse cholesterol transport. Exogenous IF1, known as the natural mitochondrial specific inhibitor of F1-ATPase activity, inhibits ecto-F1-ATPase activity and decreases HDL-C uptake by hepatocytes. We previously found that IF1 is present in human serum and is negatively associated with coronary heart disease (CHD). Here, we investigated the relationship between serum IF1 concentration and mortality in CHD patients. Methods Serum IF1 was measured in 624 CHD patients aged 45-74 from the GENES (Genetique et ENvironement en Europe du Sud) study. After 9.1 years follow up, mortality rate was 24.5%. Results Patients who had died were older at inclusion, were more often treated for dyslipidemia or diabetes mellitus, had higher tobacco consumption, CRP level but lower physical activity. Resting heart rate and the Gensini score of CHD severity were higher while LVEF (Left Ventricular Ejection Fraction) was decreased. They also had lower serum IF1 concentration (0.41 vs 0,44μg/ml, p=0.03). In CHD patients, IF1 concentration was negatively associated with triglycerides, Gensini score and resting heart rate and positively with physical activity, HDL-C and LVEF. HDL-C was correlated with the Gensini score but not with resting heart rate and LVEF. Serum IF1 in the two highest quartiles (≥0,42μg/ml) was associated with significantly reduced mortality risk, even after multivariate adjustments for classical cardiovascular risk factors and Gensini score (HR=0.55, p=0.026 for the highest quartile). Significance was lost after adjustment for LVEF (HR=0.72, p=0.23). Conclusion High serum IF1 is predictor of reduced mortality in CHD patients. This prognostic value remains significant whatever the value of HDL-C and Gensini score, a marker of atheroma diffusion, but was lost after adjustment for LVEF. Correlation between serum IF1 concentration and LVEF might underlie the relationship between IF1 level and mortality.