Retinol and Retinol Binding Protein 4 Levels and Cardiometabolic Disease Risk
Journal article, 2022

Background: Despite mechanistic studies linking retinol and RBP4 (retinol binding protein 4) to the pathogenesis of cardiovascular diseases (CVD) and type 2 diabetes (T2D), epidemiological evidence is still conflicting. We investigated whether conflicting results of previous studies may be explained by differences in the association of retinol and RBP4 with cardiometabolic risk across subgroups with distinct sex, hypertension state, liver, or kidney function. Methods: We used case-cohorts nested in the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Potsdam cohort (N=27 548) comprising a random sample of participants (n=2500) and all physician-verified cases of incident CVD (n=508, median follow-up time 8.2 years) and T2D (n=820, median follow-up time 6.3 years). We estimated nonlinear and linear multivariable-adjusted associations between the biomarkers and cardiometabolic diseases by restricted cubic splines and Cox regression, respectively, testing potential interactions with hypertension, liver, and kidney function. Additionally, we performed 2-sample Mendelian Randomization analyses in publicly available data. Results: The association of retinol with cardiometabolic risk was modified by hypertension state (P interaction CVDP interaction T2D<0.001). Retinol was associated with lower cardiometabolic risk in participants with treated hypertension (hazard ratio(per SD) [95% CI]: CVD, 0.71 [0.56-0.90]; T2D, 0.81 [0.70-0.94]) but with higher cardiometabolic risk in normotensive participants (CVD, 1.32 [1.06-1.64]; T2D, 1.15 [0.98-1.36]). Our analyses also indicated a significant interaction between RBP4 and hypertension on CVD risk (P interaction=0.04). Regarding T2D risk, we observed a u-shaped association with RBP4 in women (P nonlinearity=0.01, P effect=0.02) and no statistically significant association in men. The biomarkers' interactions with liver or kidney function were not statistically significant. Hypertension state-specific associations for retinol concentrations with cardiovascular mortality risk were replicated in National Health and Nutrition Examination Survey III. Conclusions: Our findings suggest a hypertension-dependent relationship between plasma retinol and cardiometabolic risk and complex interactions of RBP4 with sex and hypertension on cardiometabolic risk.

risk

lipoprotein

hypertension

myocardial infarction

cardiovascular diseases

Author

Catarina Schiborn

Center for Diabetes Research (DZD)

German Institute of Human Nutrition Potsdam-Rehbrucke (DIfE)

Daniela Weber

German Institute of Human Nutrition Potsdam-Rehbrucke (DIfE)

Tilman Grune

German Center for Cardiovascular Research DZHK

German Institute of Human Nutrition Potsdam-Rehbrucke (DIfE)

Ronald Biemann

Leipzig University Hospital

Susanne Jager

Center for Diabetes Research (DZD)

German Institute of Human Nutrition Potsdam-Rehbrucke (DIfE)

Natascha Neu

German Institute of Human Nutrition Potsdam-Rehbrucke (DIfE)

Marie Muller von Blumencron

German Institute of Human Nutrition Potsdam-Rehbrucke (DIfE)

Andreas Fritsche

University of Tübingen

Center for Diabetes Research (DZD)

Cornelia Weikert

German Federal Institute for Risk Assessment

Matthias B. Schulze

German Institute of Human Nutrition Potsdam-Rehbrucke (DIfE)

Center for Diabetes Research (DZD)

University of Potsdam

Clemens Wittenbecher

Chalmers, Biology and Biological Engineering, Food and Nutrition Science

Circulation Research

0009-7330 (ISSN) 1524-4571 (eISSN)

Vol. 131 7 637-649

Subject Categories

General Practice

Cardiac and Cardiovascular Systems

Environmental Health and Occupational Health

DOI

10.1161/CIRCRESAHA.122.321295

PubMed

36017698

More information

Latest update

10/25/2023