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 Huang, Dan Wang, Unab I Khan, Irfan Zeb, JoAnn E Manson, Virginia Miller, Howard N Hodis, Matthew J Budoff, George R Merriam, Mitchell S Harman, Eliot A Brinton, Marcelle I Cedars, Yali Su, Rogerio A Lobo, Frederick Naftolin, Nanette Santoro, Hugh S Taylor, Rachel P Wildman, Gary Huang, Dan Wang, Unab I Khan, Irfan Zeb, JoAnn E Manson, Virginia Miller, Howard N Hodis, Matthew J Budoff, George R Merriam, Mitchell S Harman, Eliot A Brinton, Marcelle I Cedars, Yali Su, Rogerio A Lobo, Frederick Naftolin, Nanette Santoro, Hugh S Taylor, Rachel P Wildman

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.

Figures

Figure 1
Figure 1
Prevalence (%) of CAC score > 0 by RBP4 Quartiles.

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