Serum levels of mitochondrial inhibitory factor 1 are independently associated with long-term prognosis in coronary artery disease: the GENES Study

BMC Medicine

Research Article

Michel Galinier¹  Dorota Taraszkiewicz¹  Meyer Elbaz¹  Bertrand Nassar²  Jean-Bernard Ruidavets³  Vanina Bongard³  Paul-Louis Vervueren⁴  Jean Ferrières⁴  Guillaume Combes⁵  Laurent O. Martinez⁶  Laeticia Lichtenstein⁶  Thibaut Duparc⁶  Bertrand Perret⁷  Annelise Genoux⁷ 

[1] CHU Toulouse, Toulouse University Hospital, Fédération de Cardiologie, Toulouse, France;CHU Toulouse, Toulouse University Hospital, Service de Biochimie, Pôle biologie, Hôpital de Purpan, Toulouse, France;Department of Epidemiology, Health Economics and Public Health, Inserm, Université de Toulouse, CHU Toulouse, UMR1027, Toulouse, France;Department of Epidemiology, Health Economics and Public Health, Inserm, Université de Toulouse, CHU Toulouse, UMR1027, Toulouse, France;CHU Toulouse, Toulouse University Hospital, Fédération de Cardiologie, Toulouse, France;Institute of Metabolic and Cardiovascular Diseases, I2MC, Inserm, UMR 1048, Toulouse, France;CHU Toulouse, Toulouse University Hospital, Service de Biochimie, Pôle biologie, Hôpital de Purpan, Toulouse, France;Institute of Metabolic and Cardiovascular Diseases, I2MC, Inserm, UMR 1048, Toulouse, France;Université de Toulouse, UMR1048, Toulouse, France;Institute of Metabolic and Cardiovascular Diseases, I2MC, Inserm, UMR 1048, Toulouse, France;Université de Toulouse, UMR1048, Toulouse, France;CHU Toulouse, Toulouse University Hospital, Service de Biochimie, Pôle biologie, Hôpital de Purpan, Toulouse, France;

关键词: High density lipoprotein, HDL;    Cholesterol;    ATP synthase;    F-ATPase;    Inhibitory Factor 1, IF1;    Biomarker;   

DOI  :  10.1186/s12916-016-0672-9

 received in 2016-05-03, accepted in 2016-08-10,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundEpidemiological and observational studies have established that high-density lipoprotein cholesterol (HDL-C) is an independent negative cardiovascular risk factor. However, simple measurement of HDL-C levels is no longer sufficient for cardiovascular risk assessment. Therefore, there is a critical need for novel non-invasive biomarkers that would display prognostic superiority over HDL-C. Cell surface ecto-F1-ATPase contributes to several athero-protective properties of HDL, including reverse cholesterol transport and vascular endothelial protection. Serum inhibitory factor 1 (IF1), an endogenous inhibitor of ecto-F1-ATPase, is an independent determinant of HDL-C associated with low risk of coronary artery disease (CAD). This work aimed to examine the predictive value of serum IF1 for long-term mortality in CAD patients. Its informative value was compared to that of HDL-C.MethodSerum IF1 levels were measured in 577 male participants with stable CAD (age 45–74 years) from the GENES (Genetique et ENvironnement en Europe du Sud) study. Vital status was yearly assessed, with a median follow-up of 11 years and a 29.5 % mortality rate. Cardiovascular mortality accounted for the majority (62.4 %) of deaths.ResultsIF1 levels were positively correlated with HDL-C (rs = 0.40; P < 0.001) and negatively with triglycerides (rs = −0.21, P < 0.001) and CAD severity documented by the Gensini score (rs = −0.13; P < 0.01). Total and cardiovascular mortality were lower at the highest quartiles of IF1 (HR = 0.55; 95 % CI, 0.38–0.89 and 0.50 (0.28–0.89), respectively) but not according to HDL-C. Inverse associations of IF1 with mortality remained significant, after multivariate adjustments for classical cardiovascular risk factors (age, smoking, physical activity, waist circumference, HDL-C, dyslipidemia, hypertension, and diabetes) and for powerful biological and clinical variables of prognosis, including heart rate, ankle-brachial index and biomarkers of cardiac diseases. The 10-year mortality was 28.5 % in patients with low IF1 (<0.42 mg/L) and 21.4 % in those with high IF1 (≥0.42 mg/L, P < 0.02).ConclusionsWe investigated for the first time the relation between IF1 levels and long-term prognosis in CAD patients, and found an independent negative association. IF1 measurement might be used as a novel HDL-related biomarker to better stratify risk in populations at high risk or in the setting of pharmacotherapy.

【 授权许可】

CC BY   
© The Author(s). 2016