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Plasma retinol-binding protein 4 (RBP4) levels and risk of coronary heart disease: a prospective analysis among women in the nurses' health study.

ABSTRACT: 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.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; Ptrend=0.003), whereas this association was 0.77 (95% confidence interval, 0.38-1.56; Ptrend=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.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.

SUBMITTER: Sun Q

PROVIDER: S-EPMC3741657 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Plasma retinol-binding protein 4 (RBP4) levels and risk of coronary heart disease: a prospective analysis among women in the nurses' health study.

Sun Qi Q Kiernan Urban A UA Shi Ling L Phillips David A DA Kahn Barbara B BB Hu Frank B FB Manson Joann E JE Albert Christine M CM Rexrode Kathryn M KM

Circulation 20130412 19

<h4>Background</h4>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.<h4>Methods and results</h4>We measured plasma levels of full-length and several C-terminally truncated subfractions ...[more]

PMID: 23584360

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Project description:BackgroundGestational diabetes mellitus (GDM) is a prevalent condition where diabetes is diagnosed during pregnancy, affecting both maternal and fetal outcomes. Retinol-binding protein 4 (RBP4) is a circulating adipokine which belongs to the lipocalin family and acts as a specific carrier protein that delivers retinol (vitamin A) from the liver to the peripheral tissues. Growing data indicate that circulating RBP4 levels may positively correlate with GDM. Thus, this systematic review and meta-analysis aimed to investigate the potential relationship between circulating RBP4 levels and GDM when measured at various stages of pregnancy.MethodsMEDLINE, CINAHL, EMCARE, EMBASE, Scopus, and Web of Science databases were searched to identify studies comparing pregnant women with and without GDM, whose circulating RBP4 levels were measured in at least one pregnancy trimester. Findings were reported using standardized mean difference (SMD) and random-effects models were used to account for variability among studies. Furthermore, the risk of bias was assessed using the RoBANS tool.ResultsOut of the 34 studies identified, 32 were included in the meta-analysis (seven with circulating RBP4 levels measured in the first trimester, 19 at 24-28 weeks, and 14 at >28 weeks of pregnancy). RBP4 levels were statistically higher in the GDM group than in controls when measured during all these pregnancy stages, with the noted RBP4 SMD being 0.322 in the first trimester (95% CI: 0.126-0.517; p < 0.001; 946 GDM cases vs. 1701 non-GDM controls); 0.628 at 24-28 weeks of gestation (95% CI: 0.290-0.966; p < 0.001; 1776 GDM cases vs. 1942 controls); and 0.875 at >28 weeks of gestation (95% CI: 0.252-1.498; p = 0.006; 870 GDM cases vs. 1942 non-GDM controls). Significant study heterogeneity was noted for all three pregnancy timepoints.ConclusionThe present findings indicate consistently higher circulating RBP4 levels in GDM cases compared to non-GDM controls, suggesting the potential relevance of RBP4 as a biomarker for GDM. However, the documented substantial study heterogeneity, alongside imprecision in effect estimates, underscores the need for further research and standardization of measurement methods to elucidate whether RBP4 can be utilized in clinical practice as a potential GDM biomarker.Systematic review registrationPROSPERO (CRD42022340097: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022340097).

Project description:BackgroundRetinol binding protein 4 (RBP4) has been proposed to play a role in the pathophysiology of coronary artery disease (CAD), but previous findings on the association of RBP4 levels with CAD are inconsistent.MethodsA meta-analysis based on observational studies was conducted to evaluate the association between circulating RBP4 levels and CAD. Databases including PubMed, Web of Science, Embase, Google Scholar and ClinicalTrials.gov database were searched for eligible studies published up to 12 July 2021. Standard mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using the inverse variance heterogeneity (IVhet) and random-effects model for data with moderate and high heterogeneity (I2 > 30%) and data with low heterogeneity were analysed using a fixed-effects model (I2 ≤ 30%). Moreover, a bias-adjusted quality-effects model was generated, and the prediction interval was also calculated under the random-effects model.ResultsTwo nested case-control studies, one cohort study and twelve case-control studies with a total of 7111 participants were included. Circulating RBP4 levels in patients with CAD were comparable to those in the controls under the IVhet model (SMD: 0.25, 95% CI: - 0.29-0.79, I2: 96.00%). The quality-effects model produced consistent results. However, the association turned to be significant under the random-effect model (SMD: 0.46, 95% CI: 0.17-0.75, I2: 96.00%), whereas the 95% predictive interval (PI) included null values (95% PI: - 0.82-1.74). Subgroup analyses illustrated a positive relationship between CAD and RBP4 levels in patients with complications (SMD: 1.34, 95% CI: 0.38-2.29, I2: 96.00%). The meta-regression analysis revealed that the mean BMI of patients (P = 0.03) and complication status (P = 0.01) influenced the variation in SMD.ConclusionsThere was low-quality evidence that patients with CAD exhibited similar circulating RBP4 levels compared with controls, and high inter-study heterogeneity was also observed. Thus, RBP4 might not be a potential risk factor for CAD. Comparisons among different subtypes of RBP4 with larger sample size are needed in the future.

Dataset Information

Plasma retinol-binding protein 4 (RBP4) levels and risk of coronary heart disease: a prospective analysis among women in the nurses' health study.

Publications

Plasma retinol-binding protein 4 (RBP4) levels and risk of coronary heart disease: a prospective analysis among women in the nurses' health study.

Similar Datasets

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