Cross-sectional and longitudinal associations of Iron biomarkers and cardiovascular risk factors in pre- and postmenopausal women: leveraging repeated measurements to address natural variability

Abstract Background The association between iron biomarkers and cardiovascular disease risk factors (CVD-RFs) remains unclear. We aimed to 1) evaluate the cross-sectional and longitudinal associations between iron biomarkers (serum ferritin, transferrin saturation (TSAT), transferrin) and CVD-RFs among women, and 2) explore if these associations were modified by menopausal status. Method Cross-sectional and longitudinal analyses including 2542 and 1482 women from CoLaus cohort, respectively. Multiple linear regression and multilevel mixed models were used to analyse the associations between Iron biomarkers and CVD-RFs. Variability of outcomes and iron markers between surveys was accessed using intraclass correlation (ICC). Results In the cross-sectional analysis, after multivariable adjustment, high ferritin levels were associated with higher insulin and transferrin levels were associated with higher levels of glucose, insulin, total and HDL-cholesterol, and systolic and diastolic blood pressure. No association between CVD-RFs and TSAT was found. All iron biomarkers indicated low reliability across reproductive stages but were stronger in the perimenopausal group. In the longitudinal analysis, we found significant association only between transferrin and lower levels of glucose and diastolic blood pressure. The associations between iron biomarkers and CVD-RFs did not change according to menopausal status. Conclusion In cross-sectional analysis, transferrin was associated with several CVD-RFs, and the associations did not change according to menopausal status. Conversely, in the longitudinal analyses, changes in transferrin were associated only with lower glucose and diastolic blood pressure levels. These differences might stem from the substantial longitudinal variation of iron biomarkers, underscoring the need for multiple iron measurements in longitudinal analyses.