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Circulating Estradiol Is an Independent Predictor of Progression of Carotid Artery Intima-Media Thickness in Middle-Aged Men

Institute of Internal Medicine (Å.T., K.W., C.O., B.F.), The Wallenberg Laboratory for Cardiovascular Research (Å.T., J.H., K.W., J.W., B.F.), and Department of Clinical Pharmacology (C.O.), Sahlgrenska University Hospital, Göteborg University, S-413 45 Göteborg, Sweden; and Medical Advisors at AstraZeneca (J.H., J.W.), S-431 83 Mölndal, Sweden

Address all correspondence and requests for reprints to: Åsa Tivesten, Wallenberg Laboratory for Cardiovascular Research, Bruna Stråket 16, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. E-mail: asa.tivesten{at}medic.gu.se.

Context: Estrogen treatment of men with prostate cancer is associated with increased cardiovascular morbidity and mortality; however, the role of endogenous estrogen levels for atherosclerotic disease in men is unknown.

Objective: The objective of the study was to determine whether endogenous serum estradiol (E₂) levels predict the progression of carotid artery intima-media thickness in men.

Design, Setting and Participants: This was a population-based, prospective cohort study (the Atherosclerosis and Insulin Resistance study) conducted in Göteborg, Sweden, among 313 Caucasian men without cardiovascular or other clinically overt diseases. Carotid artery intima-media thickness, an index of preclinical atherosclerosis, was measured by ultrasound at baseline (58 yr of age) and after 3 yr of follow-up. Serum sex hormone levels and cardiovascular risk factors (body mass index, waist to hip ratio, systolic blood pressure, serum triglycerides, plasma c-peptide, and smoking status) were assessed at study entry.

Intervention: There was no intervention.

Main Outcome Measures: Association between baseline total and free E₂ levels and progression of carotid intima-media thickness over 3 yr with adjustments for cardiovascular risk factors was measured.

Results: In univariate analyses, both total and free E₂ levels at baseline were positively associated with the annual change in intima-media thickness. In linear regression models including E₂ and cardiovascular risk factors, low-density lipoprotein and high-density lipoprotein cholesterol and E₂ were identified as independent predictors of progression of carotid artery intima-media thickness (total E₂ beta = 0.187, P = 0.001; and free E₂ beta = 0.183, P = 0.003).

Conclusions: Circulating E₂ is a predictor of progression of carotid artery intima-media thickness in middle-aged men. Further studies are needed to investigate the role of endogenous E₂ for incident cardiovascular disease events.

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