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Open Access Original investigation

Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study

Gary Huang1, Dan Wang1, Unab I Khan2, Irfan Zeb3, JoAnn E Manson4, Virginia Miller5, Howard N Hodis6, Matthew J Budoff3, George R Merriam7, Mitchell S Harman8, Eliot A Brinton9, Marcelle I Cedars10, Yali Su11, Rogerio A Lobo12, Frederick Naftolin13, Nanette Santoro14, Hugh S Taylor15 and Rachel P Wildman116*

Author Affiliations

1 Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA

2 Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA

3 Division of Cardiology, Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA, USA

4 Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

5 Departments of Surgery and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA

6 Atherosclerosis Research Unit, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA

7 VA Puget Sound Health Care System and Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA

8 Kronos Longevity Research Institute, Phoenix, AZ, USA

9 Department of Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA

10 Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, CA, USA

11 SliverCreek Technologies, Gilbert, AZ, USA

12 Department of Obstetrics and Gynecology, Columbia University College of Medicine, New York, NY, USA

13 Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA

14 Department of Obstetrics and Gynecology and Women’s Health, University of Colorado-Denver School of Medicine, Aurora, CO, USA

15 Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA

16 Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Belfer Building, Room 1309, Bronx, NY 10461, USA

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Cardiovascular Diabetology 2012, 11:52  doi:10.1186/1475-2840-11-52

Published: 15 May 2012

Abstract

Background

The published literature regarding the relationships between retinol-binding protein 4 (RBP4) and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard western blot analysis of RBP4 levels.

Methods

Full-length serum RBP4 levels were measured by western blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT), and coronary artery calcification (CAC).

Results

The mean age of women was 52.9 (± 2.6) years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5) μg/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient = 0.10; P = 0.01), but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients ≤0.06, P > 0.05). Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00 [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the 2nd quartile). However, a squared RBP4 term in regression modeling was non-significant (P = 0.10).

Conclusions

In these healthy, recently postmenopausal women, higher RBP4 levels were weakly associated with elevations in triglycerides and with CAC, but not with other risk factors or CIMT. These data using the gold standard of RBP4 methodology only weakly support the possibility that perturbations in RBP4 homeostasis may be an additional risk factor for subclinical coronary atherosclerosis.

Trial registration

ClinicalTrials.gov number NCT00154180

Keywords:
Retinol-binding protein 4; Subclinical atherosclerosis; Risk factors; Women