Plasma Retinol-Binding Protein 4 (RBP4) Levels and Risk of Coronary Heart Disease

Background— Retinol-binding protein 4 (RBP4) may play an important role in the origin of insulin resistance and metabolic syndrome. Few prospective data are available on the relationship between RBP4 and coronary heart disease (CHD). Furthermore, previous studies did not distinguish among full-length and truncated forms of RBP4 that might have various biological activities. Methods and Results— We measured plasma levels of full-length and several C-terminally truncated subfractions of RBP4 among 468 women who developed CHD and 472 matched controls in the Nurses’ Health Study cohort during 16 years of follow-up (1990–2006). We observed a temporal variation in the association of full-length RBP4 levels with CHD risk ( P =0.04 for testing proportional hazard assumption). In the first 8 years of follow-up, after multivariate adjustment for covariates, the odds ratio of CHD risk comparing extreme quartiles of full-length RBP4 levels was 3.56 (95% confidence interval, 1.21–10.51; P trend =0.003), whereas this association was 0.77 (95% confidence interval, 0.38–1.56; P trend =0.44) in the follow-up period of 9 to 16 years. Results were similar for total RBP4 levels (summed levels of all RBP4 isoforms). Levels of the primary truncated isoform, RBP4-L, were not associated with CHD risk in any follow-up period; the odds ratios for extreme quartiles were 1.29 (95% confidence interval, 0.50–3.32) and 1.20 (95% confidence interval, 0.64–2.26) in the first and second 8 years of follow-up, respectively. Conclusions— In this cohort of women, higher circulating full-length and total RBP4 levels were associated with increased risk of CHD in a time-dependent fashion. Additional data are warranted to confirm the present findings.