Preventive cardiology
High-Density Lipoprotein Cholesterol Efflux, Nitration of Apolipoprotein A-I, and Endothelial Function in Obese Women

https://doi.org/10.1016/j.amjcard.2011.10.008Get rights and content

Subjects at risk of atherosclerosis might have dysfunctional high-density lipoprotein (HDL) despite normal cholesterol content in the plasma. We considered whether the efflux of excess cellular cholesterol to HDL from obese subjects is associated with impaired arterial endothelial function, a biomarker of cardiovascular risk. A total of 54 overweight (body mass index [BMI] 25 to 29.9 kg/m2) or obese (BMI ≥30 kg/m2) women, aged 46 ± 11 years, were enrolled in a worksite wellness program. The HDL cholesterol averaged 57 ± 17 mg/dl and was inversely associated with the BMI (r = −0.419, p = 0.002). Endothelial function was assessed using brachial artery flow-mediated dilation. Cholesterol efflux from 3H-cholesterol–labeled baby hamster kidney cells transfected with the adenosine triphosphate-binding cassette transporter 1 showed 8.2% to 22.5% cholesterol efflux within 18 hours when incubated with 1% serum and was positively correlated with brachial artery flow-mediated dilation (p <0.05), especially in the 34 subjects with BMI ≥30 kg/m2 (r = 0.482, p = 0.004). This relation was independent of age, HDL or low-density lipoprotein cholesterol concentrations in plasma, blood pressure, or insulin resistance on stepwise multiple regression analysis (β = 0.31, R2 = 0.21, p = 0.007). Nitration of apolipoprotein A-I tyrosine residues (using sandwich enzyme-linked immunosorbent assay) was significantly greater in women with a BMI ≥30 kg/m2 and the lowest cholesterol efflux than in women with a BMI of 25 to 29.9 kg/m2 and the greatest cholesterol efflux (p = 0.01). In conclusion, we have shown that decreased cholesterol efflux by way of the adenosine triphosphate-binding cassette transporter 1 is associated with increased nitration of apolipoprotein A-I in HDL and is an independent predictor of impaired endothelial function in women with a BMI of ≥30 kg/m2. This finding suggests that the functional measures of HDL might be better markers for cardiovascular risk than the HDL cholesterol levels in this population.

Section snippets

Methods

The present study was conducted at the Clinical Center of the National Institutes of Health with employees enrolled in a worksite wellness program initiated by the National Heart, Lung, and Blood Institute. The protocol, approved by the institutional review board of the National Heart, Lung, and Blood Institute (NCT00666172), was open to women according to the body mass index (BMI; weight in kilograms divided by height in meters squared) classification of overweight (25 to 29.9 kg/m2) or obese

Results

A total of 54 consecutive women meeting the eligibility criteria (age range 26 to 66 years) were enrolled during the initial year of the protocol and were evaluated in the present study. Of the 54 women, 20 were identified as overweight (BMI 25 to 29.9 kg/m2) and 34 as obese (BMI ≥30 kg/m2; Table 1). Of the 54 women, 7 (6 with a BMI of ≥30 kg/m2 and 1 with a BMI of 25 to 29.9 kg/m2) had adult-onset diabetes. Of these 7, 6 were taking oral hypoglycemic medications and 1 required insulin. For the

Discussion

In our cohort of overweight (BMI 25 to 29.9 kg/m2) and obese (BMI ≥30 kg/m2) women, we found that HDL cholesterol levels were inversely associated with obesity, consistent with previous reports from large cohorts of men and women.13, 14, 15 The range of HDL cholesterol levels was wide, and 17 women (including 6 of 34 subjects with a BMI of ≥30 kg/m2) had values ≥60 mg/dl, well within the desirable range by current Adult Treatment Panel III guidelines.16 Using a cell-based assay to quantify the

Acknowledgments

We gratefully acknowledge the technical contributions of Maureen Sampson and John Stonik to our study.

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    This research was funded by the intramural research programs of the National Heart, Lung, and Blood Institute and the Clinical Center, National Institutes of Health, Bethesda, Maryland.

    Dr. Vazquez (Mt. Sinai School of Medicine) was a fellow in the Clinical Research Training Program, Clinical Center, National Institutes of Health, Bethesda, Maryland; his current address is New York Presbyterian Hospital, New York, New York.

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