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Submitted on February 20, 2007
Accepted on May 9, 2007
Neuroendocrine Unit (EAL, KKM, VM, MM, EM, AK), Harris Center, Departmen of Psychiatry (DH), Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114
* To whom correspondence should be addressed. E-mail: AKlibanski{at}partners.org.
Context: Cardiovascular (CV) risk markers, including high-sensitivity C-reactive protein (hsCRP), are increasingly important in predicting cardiac events. A favorable CV risk profile might be expected in anorexia nervosa (AN) due to low body weight and dietary fat intake. However, women with AN have decreased IGF-1 levels reflecting decreased GH action, and IGF-1 deficiency is associated with elevated hsCRP. Moreover, oral estrogens, known to increase hsCRP in other populations, are commonly prescribed in AN. To date, hsCRP levels and their physiologic determinants have not been reported in women with AN.
Objective: We examined the relationship between cardiovascular risk markers, undernutrition, IGF-1 and oral estrogens, specifically hypothesizing that in the setting of undernutrition, AN would be associated with low hsCRP despite low IGF-1 levels, and that those women taking oral contraceptive pills (OCPs) would have higher hsCRP and lower IGF-1 levels.
Design: Cross-sectional.
Setting: Clinical Research Center.
Study Participants: 181 women: 140 women with AN [85 not receiving OCPs(AN-E) and 55 receiving OCPs (AN+E)] and 41 healthy controls [28 not receiving OCPs (HC-E), and 13 healthy controls receiving OCPs (HC+E)].
Main Outcome Measures: HsCRP, IL-6, IGF-1, low density lipoprotein (LDL) and high density lipoprotein (HDL).
Results: Despite low weight, more than 20% of AN+E had high-risk hsCRP levels. AN+E had higher hsCRP than AN-E. AN-E had lower mean hsCRP levels than healthy controls (HC+E and HC-E). IL-6 levels were higher in AN+E and elevated hsCRP (>3 mg/L) than in AN+E with normal hsCRP levels. IGF-1 was inversely associated with hsCRP in healthy women, suggesting a protective effect of GH on CV risk. However, this was not seen in AN. Few patients in any group had high-risk LDL or HDL levels.
Conclusions: Although hsCRP levels are lower in AN than healthy controls, OCP use puts such women at a greater than 20% chance of having hsCRP in the high cardiovascular risk (>3 mg/L) category. The elevated mean IL-6 in women with AN and high-risk hsCRP levels suggests that increased systemic inflammation may underly the hsCRP elevation in these patients. Although OCP use in AN was associated with slightly lower mean LDL and higher mean HDL, means were within the normal range and few patients in any group had high-risk LDL or HDL levels. IGF-1 levels appear to be important determinants of hsCRP in healthy young women. In contrast, IGF-1 does not appear mediate hsCRP levels in AN.
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