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Should women with endometriosis be screened for coronary artery disease?

Published:August 26, 2016DOI:https://doi.org/10.1016/j.ejim.2016.08.021
      Recent studied have suggested that endometriosis (EM) in linked to systemic chronic inflammation, atherogenic lipid profile and oxidative stress [
      • Agic A.
      • Xu H.
      • Finas D.
      • Banz C.
      • Diedrich K.
      • Hornung D.
      Is endometriosis associated with systemic subclinical inflammation?.
      ]. As well known, all these risk factors play a key role in the pathogenesis of atherosclerotic coronary artery disease (CAD). Currently, no larger and/or randomized clinical studies have assessed the real incidence of cardiovascular (CV) events in patients with endometriosis. However, different authors have suggested that women with EM are at higher risk of CAD [
      • Mu F.
      • Rich-Edwards J.
      • Rimm E.B.
      • Spiegelman D.
      • Missmer S.A.
      Endometriosis and risk of coronary heart disease.
      ,
      • Missmer S.A.
      Commentary: Endometriosis—Epidemiologic considerations for a potentially 'high-risk' population.
      ]. Endometriosis is a chronic and estrogen-dependent gynaecological disorder defined as the presence of endometrium-like tissue thriving outside the uterus. It has been estimated that this disease affects about 10% of women in reproductive age [
      • Bulun S.E.
      Endometriosis.
      ]. EM is generally diagnosed in young women. For this reason, the elevated risk of CAD has been underestimated for long time, due to the young age of the patients. However, different authors have already demonstrated the presence of different cytokines as tumor necrosis factor alpha (TNF-α), interleukin-1 and interleukin-6 both in the peripheral blood and peritoneal fluid of woman with EM [
      • Agic A.
      • Xu H.
      • Finas D.
      • Banz C.
      • Diedrich K.
      • Hornung D.
      Is endometriosis associated with systemic subclinical inflammation?.
      ]. As previously demonstrated, chronic inflammation contributes to start and then to maintain a persistent vascular injury. Indeed, both chronic inflammation and oxidative stress are well recognized mediators in the signalling pathway that lead firstly to vascular inflammation and then to atherogenesis. Moreover, inflammation has a central role in the development and progression of atheromatous plaques [
      • Hansson G.K.
      Inflammation, atherosclerosis, and coronary artery disease.
      ]. Besides, as demonstrated by Melo et al., women with EM contemporary have a higher low density lipoprotein (LDL) and lower high density lipoprotein (HDL) levels in the peripheral blood [
      • Melo A.S.
      • Rosa-e-Silva J.C.
      • Rosa-e-Silva A.C.
      • Poli-Neto O.B.
      • Ferriani R.A.
      • Vieira C.S.
      Unfavorable lipid profile in women with endometriosis.
      ]. Although the real pathogenesis of EM has not yet completely defined, it has been demonstrated that different genetic factors are involved in the pathogenesis. Uno et al. reported a significant association between endometriosis and the CDKN2CBAS genetic variants on chromosome 9p21 [
      • Uno S.
      • Zembutsu H.
      • Hirasawa A.
      • Takahashi A.
      • Kubo M.
      • Akahane T.
      • et al.
      A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese.
      ]. Similarly, Shan et al. described that the chromosome 9p21 confers a higher risk for the development of acute myocardial infarction (AMI) [
      • Shen G.Q.
      • Rao S.
      • Martinelli N.
      • Li L.
      • Olivieri O.
      • Corrocher R.
      • et al.
      Association between four SNPs on chromosome 9p21 and myocardial infarction is replicated in an Italian population.
      ]. In their review, Santoro et al. analysed the relationship between EM and atherosclerosis. They reported that the presence of subclinical atherosclerosis in these group of women was susceptible of regression after EM surgical treatment, with a prognostic relevance for the reduction of global CV risk [
      • Santoro L.
      • D'Onofrio F.
      • Flore R.
      • Gasbarrini A.
      • Santoliquido A.
      Endometriosis and atherosclerosis: What we already know and what we have yet to discover.
      ]. The aforementioned clinical evidences clearly suggest a real higher risk of CHD in women with EM compared to standard population. Mu et al. have reported that women with laparoscopically confirmed EM had a high relative risk (RR) of AMI (RR 1.52, 95% CI 1.17–1.98), coronary artery bypass grafting (CABG) and/or percutaneous coronary intervention (PCI) (RR 1.35, 95% CI 1.08–1.69) and angiographycally confirmed angina (RR 1.91, 95% CI 1.52–.2.29), independently from anthropometrics, reproductive, lifestyle confounders and demographics parameters [
      • Mu F.
      • Rich-Edwards J.
      • Rimm E.B.
      • Spiegelman D.
      • Missmer S.A.
      Endometriosis and risk of coronary heart disease.
      ]. Another contribution in the development of CHD in women with EM is represented by the adopted therapeutic strategy. In fact, EM could be treated symptomatically with nonsteroidal anti-inflammatory drugs (NSAIDs) or surgically with hysterectomy or oophorectomy. All these treatments have been linked to a high risk of CAD in women with EM. In particular, the aim of the surgical treatment is to induce an early menopause, which indirectly increases the risk of CAD. Current guidelines on cardiovascular prevention and EM management do not take into account the relationship between EM and CAD. Why women with EM are not considered for both primary and secondary CV prevention? The reasons are different. Firstly, the lack of studies about the incidence of CV events in EM. Secondly, cardiologists are no routinely involved in the management and follow-up of EM. We believe that cardiologic evaluation should be an integral part in the management of women with EM. The aim is to assess the global CV risk both at diagnosis of EM and then during the follow-up of the disease. Moreover, promoting lifestyle changes and screening for subclinical atherosclerosis and/or unknown CHD in these woman must be considered. In the future, important improvements will arise from the use of different drugs in the treatment of EM. Indeed, in-vitro studies have suggested that statins may have a potential role in the medical management of EM, thanks to their antiproliferative, antioangiogenic, antioxidant and inflammatory properties [
      • Gibran L.
      • Maranhão R.C.
      • Abrão M.S.
      • Baracat E.C.
      • Podgaec S.
      Could statins constitute a novel treatment for endometriosis? Systematic review of the literature.
      ]. It is likely that, thanks these drugs, will be able to achieve a better control of global CV risk in women with EM. However, further studies are needed to clarify the relationship between EM and CHD ant the optimal strategy to reduce the risk of CAD.

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