Abstract
Introduction: The impact of gender on the development of cardiovascular disease has long been recognized. The potential effect of sex-specific cardiovascular risk factors on molecular mediators of oxidative stress has received limited attention and the results remain conflicting.
Hypothesis: To assess the link between retinol binding protein 4 (RBP4) and menopause-specific cardiovascular risk factors, on indices of early subclinical atherosclerosis, in a sample of apparently healthy young, postmenopausal women.
Methods: This cross-sectional study included a total of 123 healthy postmenopausal women, recruited from a University Menopause Clinic. Participating women were, not on hormone therapy, antihypertensive or hypolipidemic treatment and had a menopausal age of up to 10 years. Fasting venous blood samples were obtained for hormonal and biochemical assessment, including levels of RBP4. Sonographical studies were performed on the same day and included carotid-femoral pulse wave velocity (PWV) and calculation of the carotid artery stiffness index (SI).
Major results: Univariate analysis showed that RBP4 values correlated positively with age, total cholesterol, triglycerides, LDL-cholesterol, testosterone-to-estrogen ratio; negatively with circulating estrogen and almost significantly with homocysteine levels. Levels of homocysteine were inversely associated with RBP4 (homocysteine: RBP4 <10.5ng/ml vs ≥10.5ng/ml: 11.2±2.81μmol/L vs 12.52±3.44μmol/L, p-value=0.049 ANCOVA, adjusted for age, BMI, HOMA-IR). Multivariate analysis showed that PWV values were predicted by RBP4 (b-coefficient=0.435, p-value=0.006), age, pulse pressure, homocysteine. S.I. beta was predicted independently by RBP4 levels (b-coefficient=0.324, p-value=0.039). Both models were adjusted for menopausal age, LDL-cholesterol, FEI, smoking, HOMA-IR.
Conclusion: RBP4 levels are linked with measures of local carotid and aortic arterial stiffness, in this sample of healthy postmenopausal women. This association seems to be mediated by higher levels of homocysteine, which may interfere with retinoic acid synthesis. Larger studies are required to further elucidate the significance of our findings.
References
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Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study