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Serum IF1 concentration is independently associated to HDL levels and to coronary heart disease: the GENES study.

ABSTRACT: HDL is strongly inversely related to cardiovascular risk. Hepatic HDL uptake is controlled by ecto-F1-ATPase activity, and potentially inhibited by mitochondrial inhibitor factor 1 (IF1). We recently found that IF1 is present in serum and correlates with HDL-cholesterol (HDL-C). Here, we have evaluated the relationship between circulating IF1 and plasma lipoproteins, and we determined whether IF1 concentration is associated with the risk of coronary heart disease (CHD). Serum IF1 was measured in 648 coronary patients ages 45-74 and in 669 matched male controls, in the context of a cross-sectional study on CHD. Cardiovascular risk factors were documented for each participant, including life-style habits and biological and clinical markers. In controls, multivariate analysis demonstrated that IF1 was independently positively associated with HDL-C and apoA-I (r = 0.27 and 0.28, respectively, P < 0.001) and negatively with triglycerides (r = -0.23, P < 0.001). Mean IF1 concentration was lower in CHD patients than in controls (0.43 mg/l and 0.53 mg/l, respectively, P < 0.001). In multivariate analyses, following adjustments on cardiovascular risk factors or markers, IF1 was negatively related to CHD (P < 0.001). This relationship was maintained after adjustment for HDL-C or apoA-I. This study identifies IF1 as a new determinant of HDL-C that is inversely associated with CHD.

SUBMITTER: Genoux A

PROVIDER: S-EPMC3735951 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Serum IF1 concentration is independently associated to HDL levels and to coronary heart disease: the GENES study.

Genoux Annelise A Ruidavets Jean-Bernard JB Ferrières Jean J Combes Guillaume G Lichtenstein Laeticia L Pons Véronique V Laffargue Muriel M Taraszkiewicz Dorota D Carrié Didier D Elbaz Meyer M Perret Bertrand B Martinez Laurent O LO

Journal of lipid research 20130621 9

HDL is strongly inversely related to cardiovascular risk. Hepatic HDL uptake is controlled by ecto-F1-ATPase activity, and potentially inhibited by mitochondrial inhibitor factor 1 (IF1). We recently found that IF1 is present in serum and correlates with HDL-cholesterol (HDL-C). Here, we have evaluated the relationship between circulating IF1 and plasma lipoproteins, and we determined whether IF1 concentration is associated with the risk of coronary heart disease (CHD). Serum IF1 was measured in ...[more]

PMID: 23794714

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Project description:ImportanceLow circulating concentrations of 25-hydroxyvitamin D (25[OH]D) have been consistently associated with an increased risk of coronary heart disease (CHD) in white populations. This association has not been rigorously evaluated in other races or ethnicities, in which the distributions of 25(OH)D concentration and possibly other aspects of 25(OH)D metabolism differ.ObjectiveTo examine the association of serum 25(OH)D concentration with risk of CHD in a multiethnic population.Design, setting, and participantsWe studied 6436 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), recruited from July 2000 through September 2002, who were free of known cardiovascular disease at baseline. We measured baseline serum 25(OH)D concentrations using a mass spectrometry assay calibrated to established standards. We tested associations of 25(OH)D with adjudicated CHD events assessed through May 2012.Main outcome and measuresPrimary outcome measure was time to first adjudicated CHD event, defined as myocardial infarction, angina, cardiac arrest, or CHD death.ResultsDuring a median follow-up of 8.5 years, 361 participants had an incident CHD event (7.38 events per 1000 person-years). Associations of 25(OH)D with CHD differed by race/ethnicity (P for interaction < .05). After adjustment, lower 25(OH)D concentration was associated with a greater risk of incident CHD among participants who were white (n = 167 events; hazard ratio [HR], 1.26 [95% CI, 1.06-1.49] for each 10-ng/mL decrement in 25(OH)D) or Chinese (HR, 1.67 [95% CI, 1.07-2.61]; n = 27). In contrast, 25(OH)D was not associated with risk of CHD in participants who were black (HR, 0.93 [95% CI, 0.73-1.20]; n = 94) or Hispanic (HR, 1.01 [95% CI, 0.77-1.33]; n = 73).Conclusions and relevanceLower serum 25(OH)D concentration was associated with an increased risk of incident CHD events among participants who were white or Chinese but not black or Hispanic. Results evaluating 25(OH)D in ethnically homogeneous populations may not be broadly generalizable to other racial or ethnic groups.

Dataset Information

Serum IF1 concentration is independently associated to HDL levels and to coronary heart disease: the GENES study.

Publications

Serum IF1 concentration is independently associated to HDL levels and to coronary heart disease: the GENES study.

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