Coronary artery disease
Diabetes Mellitus, Hypothalamic Hypoestrogenemia, and Coronary Artery Disease in Premenopausal Women (from the National Heart, Lung, and Blood Institute Sponsored WISE Study)

https://doi.org/10.1016/j.amjcard.2008.03.029Get rights and content

Diabetes mellitus (DM) portends a higher risk of coronary heart disease mortality in women compared with men. This relationship appears to be independent of traditional cardiac risk factors, and the role of reproductive hormones has been postulated. We assessed the relationship between DM, hypothalamic hypoestrogenemia (HHE), angiographic coronary artery disease (CAD), and major adverse cardiovascular events (MACE) during a median of 5.9 years in premenopausal women enrolled in the WISE Study. We evaluated 95 premenopausal women from WISE who underwent coronary angiography for suspected ischemia and were not using exogenous reproductive hormones. Results showed no difference in age between women with (n = 30) and without (n = 65) DM (43 ± 6 years). DM was associated with hypertension, HHE, angiographic CAD, and coronary artery severity score (all p <0.05). Women with DM were twice as likely to have HHE (50% vs 26%; p = 0.02) compared with women without DM. The presence of both DM and HHE was associated with increased prevalence (40% vs 12% or 13%; p = 0.006) and severity of angiographic CAD (coronary artery severity score 19.9 ± 19.2 vs 7.7 ± 4.6 or 12.3 ± 18.8; p = 0.008) compared with either HHE or DM alone, respectively. DM was moderately predictive of MACE. In conclusion, in premenopausal women undergoing coronary angiography for suspected myocardial ischemia, DM was associated with HHE. The presence of both DM and HHE predicted a greater burden of angiographic CAD. Prospective research is warranted to better understand causal relations between DM, endogenous hormones, and MACE in premenopausal women.

Section snippets

Methods

The WISE Study was a National Heart, Lung, and Blood Institute–sponsored cross-sectional, observational 4-center study that aimed to improve diagnostic testing and advance new hypotheses relative to the pathophysiologic process of ischemic heart disease in women. A total of 936 women undergoing clinically indicated coronary angiography for suspected ischemia were recruited into WISE. Our analysis was limited to 95 women of the entire cohort who were premenopausal, were not using hormone therapy

Results

Of 936 WISE study subjects, 515 were not currently using exogenous hormones, had no previous diagnosis of CAD, and had complete demographic and reproductive status data. Of these, 95 (18%) were premenopausal. Age ranged from 21 to 54 years; 23 (24%) were nonwhite, mostly African American; and mean body mass index was 31.2 ± 6.9 kg/m2, with a range of 17.7 to 52.2. Despite a high prevalence of coronary risk factors, only a minority (13%) of these premenopausal women had angiographic CAD. A total

Discussion

Our findings showed that DM was associated with HHE in premenopausal women undergoing coronary angiography for suspected myocardial ischemia. We also showed an increased prevalence and extent of angiographic coronary artery disease in women with DM and HHE compared with women without DM or with DM or HHE alone.

The exact mechanism by which DM ameliorates the female protection against coronary heart disease, especially in young premenopausal women, is not well understood. Endogenous estrogens

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    This work was supported by Contracts N01-HV-68161, N01-HV-68162, N01-HV-68163, and N01-HV-68164 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland; GCRC Grant MO1-RR00425 from the National Center for Research Resources, Bethesda, Maryland; and grants from the Gustavus and Louis Pfeiffer Research Foundation, Denville, New Jersey; The Women's Guild of Cedars-Sinai Medical Center, Los Angeles, California; and The Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, Pennsylvania.

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