Highlights
- •Iron balance may influence women's older age at first atherosclerotic event vs. men.
- •A magnetic resonance arterial wall biomarker sensitive to endogenous iron was used.
- •Arterial wall MRI-T2* parallelled hsCRP in early but not later menopause nor in men.
- •Ferritin's link to MRI-T2* in women was lost after 2 years and was absent in men.
- •Targeting iron homeostasis to lower incident atherosclerosis warrants further study.
Abstract
Objective
Age at first atherosclerotic event is typically older for women vs. men; monthly iron
loss has been postulated to contribute to this advantage. We investigated the relationship
between an MRI-based arterial wall biomarker and the serum inflammatory biomarker
high-sensitivity C-reactive protein (hsCRP) in perimenopausal women vs. men.
Methods and Results
Women without evident atherosclerotic disease were prospectively enrolled and observed
over 24 months of menopause transition, indicated by hormone levels and reduction
in median number of menstrual cycles from 4 [3–6] per year to 0 [0–1] per year (P < 0.01). Higher hsCRP predicted shorter carotid artery wall T2* in women entering
the menopause transition (r = −0.3139, P = 0.0014); this relationship weakened after 24 months of perimenopause in women (r = −0.1718,
P = 0.0859) and was not significant in a cohort of men matched for age and cardiovascular
risk category (r = −0.0310, P = 0.8362). Serum ferritin increased from baseline to 24-month follow-up during women's
menopause transition (37 [20–79] to 67 [36–97] ng/mL, P < 0.01), but still remained lower compared to men (111 [45–220] ng/mL, P < 0.01). Circulating ferritin levels correlated with arterial wall T2* values in
women at baseline (r = −0.3163, P = 0.0013) but not in women after 24 months (r = −0.0730, P = 0.4684) of menopause transition nor in men (r = 0.0862, P = 0.5644).
Conclusions
An arterial wall iron-based imaging biomarker reflects degree of systemic inflammation
in younger women, whereas this relationship is lost as women transition through menopause
to become more similar to men. Iron homeostasis and inflammation in the arterial wall
microenvironment warrants further investigation as a potential early target for interventions
that mitigate atherosclerosis risk.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: March 22, 2015
Accepted:
March 16,
2015
Received in revised form:
February 15,
2015
Received:
January 21,
2015
Identification
Copyright
© 2015 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
ScienceDirect
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