Understanding cardiovascular risks in endometriosis patients

A recent study reveals that women with endometriosis have a higher risk of cardiovascular disease due to increased arterial stiffness, endothelial dysfunction, and accumulation of advanced glycation end-products, highlighting the need for early detection and comprehensive treatment approaches.

A recent study published in Scientific Reports reports that endometriosis increases the risk of cardiovascular events.

What is endometriosis?

Endometriosis is a chronic gynecological disease that occurs when endometrial-like tissue grows outside of the uterine cavity, including the pelvic peritoneum, rectovaginal septum, ovaries, bladder, and intestines. Approximately 10% of reproductive-age women develop endometriosis.

Although the exact pathogenesis of endometriosis is not clear, several mechanisms have been proposed. For example, endometriosis may occur due to coelomic metaplasia, immune system dysfunction, and retrograde menstruation.

Previous studies have reported elevated levels of inflammatory cytokines, particularly interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and IL-6 in the serum and peritoneal fluid of endometriosis patients. Elevated cytokine levels induce chronic inflammatory processes, which ultimately damages the vascular endothelium and atherosclerosis.

Endothelial dysfunction and cardiovascular risk

The endothelium is a single layer of cells lining the lumen of vessels that regulates vascular homeostasis by modifying vascular tone and controlling immune cell migration and hemostasis processes. Endothelial dysfunction can arise due to the reduced production or availability of nitric oxide (NO_x), as well as an imbalance between endothelium-derived relaxing and contracting factors.

Atherosclerosis can be diagnosed by the presence of reactive hyperemia, which is measured by changes in the peripheral arterial tone. In addition to endothelial dysfunction, skin accumulation of advanced glycation end-products (AGEs) is also associated with an increased risk of cardiac events.

AGEs are bioactive compounds that are generated during nonenzymatic reactions between amino acids in proteins/macromolecules and reducing sugars. The accumulation of AGEs can lead to arterial stiffness by cross-linking collagen within the arterial wall, oxidative stress, atherosclerosis, and inflammation, all of which can lead to cardiovascular disease.

About the study

The current study hypothesized that, as compared to the healthy controls, women with endometriosis exhibit endothelial dysfunction, higher AGE skin accumulation, and increased arterial stiffness.

A total of 45 women, including 21 endometriosis patients and 24 healthy controls, between 20 and 40 years of age were included in the current study. Study participants were recruited from the Department of Obstetrics and Gynecology of the Medical University of Warsaw between December 2021 and April 2022.

Endometriosis patients were diagnosed with either ovarian endometriomas or deep infiltrating endometriosis (DIE) through transvaginal ultrasound (TVUS), magnetic resonance imaging (MRI), or surgery. Women without any abnormalities in ultrasound imaging were considered healthy controls and were matched with endometriosis patients by age and body mass index (BMI).

The EndoPAT 2000, a non-invasive diagnostic device, was used to detect endothelial function and arterial stiffness by estimating the Augmentation Index (AI), Reactive Hyperemia Index (RHI), and Augmentation Index at 75 beats/min (AI@75). RHI values less than 1.67 reflected endothelial dysfunction. AGE Reader device was used to measure skin AGE level accumulation.

Study findings

No differences in age, BMI, or average blood pressure levels were observed between endometriosis patients and healthy study participants. As compared to healthy controls, the mean RHI was lower in endometriosis patients. Furthermore, based on AGE Reader measurements, the mean skin autofluorescence was significantly higher in endometriosis patients, thus indicating that these patients are at an increased risk of cardiovascular disease.

Consistent with current study findings, one previous study also indicated that women with endometriosis are more susceptible to developing hypercholesterolemia and hypertension, both of which are risk factors for atherosclerotic cardiovascular disease. Multiple studies have indicated that chronic inflammation in endometriosis increases the risk of allergic disorders, autoimmune diseases, and certain cancers.

Conclusions

A higher AGE skin accumulation and greater prevalence of endothelial dysfunction was observed in patients with endometriosis as compared to healthy controls, which suggests a higher cardiovascular risk in this population. These findings indicate that early endometriosis diagnosis may aid in the early detection and treatment of atherosclerosis.

Both local and systemic aspects of endometriosis must be considered while designing therapies to treat this disease. Thus, future studies are needed to explore the systemic effects of this disease to support the development of comprehensive interventions that address the overall endometriosis-related health risks.

Journal reference:

• Smyk, J. M., Danielecka, Z., Kotowska, M., et al. (2024) Cardiovascular risks and endothelial dysfunction in reproductive-age women with endometriosis. Scientific Reports. 14(1), pp.1-8. doi:10.1038/s41598-024-73841-7