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
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
Cardiovascular Diabetology 2012, 11:52 doi:10.1186/1475-2840-11-52
Published: 15 May 2012Abstract
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
