P-336 Presence of stage III/IV endometriosis associated with systemic inflammation poses as individual risk factor for coronary heart disease in Indian women: Inklings for the search
Authors: Chakraborty P , Sharma S , Kalapahar S , Mitra I , Ghosh S , Chattopadhyay R , Chaudhury K 
Published: June 2023

Abstract

Study question
Can investigating endometriosis—cardiovascular interaction identify women with stage III/IV endometriosis and elucidate pathophysiology of the female heart at a broader level?

Summary answer
Endothelial dysfunction can occur in absence of structural atherosclerotic changes in young Indian women with endometriosis urging lifelong multidisciplinary care to manage long-term health impact.

What is known already
Chronic inflammation, enhanced oxidative stress, endothelial dysfunction, and cellular proliferation are hallmarks of both atherosclerosis and endometriosis with unveiled cellular and molecular overlaps between the duos. Further, treatment/s of endometriosis, like, hysterectomy or oophorectomy and/or analgesics confer increased risk of coronary heart disease (CHD) to women with endometriosis. However, CHD in women with endometriosis remains understudied, under-recognized, and underdiagnosed. Incidentally, early atherosclerosis cannot be explained exclusively by traditional cardiovascular risk factors. Aim of the present study was to correlate subclinical atherosclerosis with metabolic parameters and markers of endothelial inflammation in Indian women with stage III/IV endometriosis.

Study design, size, duration
This observational prospective cohort study constituted 1407 consented women diagnosed with laparoscopically confirmed endometriosis (Group A; n = 718) with age matched control (Group B; n = 689) (counterpart/s of male infertility) from October 2021 to September 2022. Sub-clinical atherosclerosis was investigated before laparoscopy by ultrasound evaluation of carotid intima-media thickness (cIMT) and flow-mediated dilation (FMD). Serum samples were stored at -80 °C for evaluation of biochemical and inflammatory parameters. European Society of Cardiology guidelines were followed for standard definition/s.

Participants/materials, setting, methods
Traditional (obesity, hypertension) and metabolic (dyslipidaemia, diabetes, hyperhomocysteinemia) cardiovascular risk factor/s were assessed during evaluation and chemiluminescence respectively. Serum levels of interleukin (IL)-6, IL-8, IL-10, TNF-a, VEGF, and VCAM-1 were determined by enzyme-linked-immunosorbent assay/s. Univariate comparisons and bivariate correlations were conducted by Student’s t-test, and Spearman correlation respectively. Adjusted relative risks (aRR) with 95% confidence intervals (CI) were calculated by Cox-proportional hazard/s model among Group A vs Group B. Statistical significance was set at p &lt; 0.05.

Main results and the role of chance
62.95% and 37.04% women had stage III and stage IV endometriosis respectively as defined according to European Society for Human Reproduction and Embryology 2014 guideline. aRR (adjusted for demographic, obesity, diabetes mellitus, reproductive history, and migraine), documented a higher risk of hypertension (aRR 1.43; 95%CI 1.33–1.54) in women with endometriosis. On stratification of group A in less than and more than 40 years, laboratory parameters were similar except for significantly higher (p &lt; 0.01) serum values of homocysteine, low density lipoprotein and cholesterol, in both age range of group A. FMD, indirect marker of endothelial dysfunction, was found to be lower in group A compared to controls (mean difference: −7.54, 95% CI: -10.32− -4.73; p&lt; 0.001, however, cIMT was similar between both cohort/s. aRR of endometriosis in relation with hypercholesterolemia (1.07; 95%CI 1.01–1.25; p &lt; 0.001), hypertension (1.22; 95%CI 1.14–1.30; p &lt; 0.001), and hyperhomocysteinemia (1.04; 95%CI 0.96–1.12; p &lt; 0.08) decreased with increasing age (&gt;40 years). Systemic inflammation markers, showed an inverse relationship (p &lt; 0.001) between values of FMD and serum levels of IL-6 (r = –0.34), TNF-a (r = –0.85), and VCAM-1 (r = –0.28) in group A. Other correlations were not statistically significant.

Limitations, reasons for caution
This observational study is not supported by patients with typical cardiovascular risk factors and hence limits generalizability of evidence to other ethnicities. Further, no information on hormonal treatments, such as dianogest (a synthetic progesterone) and/or leuprolide (gonadotropin-releasing hormone analog) are available to assess extent of association between endometriosis and CHD.

Wider implications of the findings
Higher propensity of subclinical atherosclerosis in younger women with laparoscopically-confirmed endometriosis represent higher systemic inflammation cueing to increased risk for CHD. This suggests the need for risk awareness and subsequent screening for CHD and healthy lifestyle promotion among gynaecologist/s and public health specialists.

Trial registration number
Not applicable