Abstract 3649: Menstrual Cycling and Mechanisms of Cardiovascular Disease Events in Post-Menopausal Women: Results from the NIH-NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE)
Background: Menstrual cycling irregularity is being associated with greater frequency of diabetes and adverse cardiovascular (CV) events, suggesting a mechanistic link between ovarian dysfunction, CAD risk factors, and CAD. Confirmation of this link and potential explanatory mechanism(s) have not been established.
Methods: We compared 686 postmenopausal women with and without a history of irregular cycles who were undergoing coronary angiography for suspected ischemia and enrolled in the WISE study. Coronary angiography was assessed by a core laboratory, and the women were prospectively followed for a median of 5.9 years. Chi square and rank sums analyses were used to compare the women on the presence and severity of CAD, CAD risk factors, and CV events. Multivariate Cox regression, adjusting for angiographic CAD and CAD risk factors was used to define time to death, MI, stroke, and angina hospitalization.
Results: Overall mean age was 62, 18% were non-white, 130 (19%) reported a history of irregular cycles, and 42% had CAD (≥ 50% stenosis). Women with irregular cycles were younger (p=0.01) but did not exhibit more diabetes, obesity, or metabolic syndrome than those with regular cycles. They became menopausal at a younger age (42 ±10 vs 46 ±8, p=0.001) and had more frequent hysterectomy or oophorectomy (both p<0.01). Women with irregular cycles had a similar adjusted prevalence and severity of angiographic CAD compared to those without irregular cycles, yet had a doubled risk for MI (6% vs. 3%, p=0.02) and higher angina hospitalization rate (34% vs. 28%, p=0.01). No differences were found for the incidence of stroke or death. The relationship was maintained in risk-adjusted models controlling for metabolic syndrome, ethnicity and angiographic CAD severity (p=0.01 for MI and p=0.01 for angina hospitalization).
Conclusion: Although less commonly applied, a history of menstrual cycling irregularity may be an important clinical marker of downstream risk, which is not immediately explained by the presence or severity of CAD risk factors or angiographic CAD. Additional, non-CAD risk factors, such as hormonal, inflammatory and thrombotic variables, may play a role mechanistically in the link between menstrual irregularity and adverse events.