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Cited by 235Endometriosis Research and TreatmentCardiovascular Disease and AdiposityInfective Endocarditis Diagnosis and Management

Endometriosis and Risk of Coronary Heart Disease

Open access
Mu, Fan, Rich-Edwards, Janet, Rimm, Eric B., Spiegelman, Donna, Missmer, Stacey A.·2016·Circulation: Cardiovascular Quality and Outcomes
DOI 10.1161/circoutcomes.115.002224PMC PMC4940126
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Abstract

Background—: Endometriosis is a prevalent gynecologic disease associated with systemic chronic inflammation, heightened oxidative stress, and atherogenic lipid profile that may increase women’s risk for coronary heart disease (CHD). Methods and Results—: We examined the prospective association between laparoscopically confirmed endometriosis and subsequent CHD among 116 430 women in the Nurses’ Health Study II (1989–2009). Participants with a history of heart disease and stroke were excluded. When compared with women without endometriosis, women with laparoscopically confirmed endometriosis had a higher risk of myocardial infarction (relative risk, 1.52; 95% confidence interval, 1.17–1.98), angiographically confirmed angina (1.91; 1.59–2.29), coronary artery bypass graft surgery/coronary angioplasty procedure/stent (1.35; 1.08–1.69), or any of these CHD end points combined (1.62; 1.39–1.89), independent of potential demographic, anthropometric, family history, reproductive, and lifestyle confounders. Relative risk for the combined CHD end point was highest among women aged ≤40 years (3.08; 2.02–4.70) and decreased as age increased (40< age ≤50 years, 1.65; 1.35–2.02; 50< age ≤55 years, 1.44; 1.07–1.94; and age >55 years, 0.98; 0.56–1.72; P value, test for heterogeneity=0.001). Having had a hysterectomy/oophorectomy was associated with higher risk of combined CHD compared with not having had a hysterectomy/oophorectomy (1.51; 1.34–1.71). A percentage of 42 of the association between endometriosis and CHD could be explained by greater frequency of hysterectomy/oophorectomy and earlier age at surgery after endometriosis diagnosis. Conclusions—: In this large, prospective cohort, laparoscopically confirmed endometriosis was associated with increased risk of CHD. The association was strongest among young women. Hysterectomy/oophorectomy was associated with higher risk of CHD and could partially explain the association between endometriosis and CHD.

Integrity signals

Registry

Crossref · 10.1161/circoutcomes.115.002224

Cites

54 of 54 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

27 of 67 cited sources checked · 10 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Chronic systemic inflammation contributes to vascular injury and progression of atheromatous plaque.

    “Chronic systemic inflammation contributes to vascular insult and atheromatous plaque progression.(16)”
    Quote in the paperSubstantial claim1 of 1 sources checked
  • Interpretationcitation

    Endometriosis and coronary heart disease may share common genetic susceptibilities.

    “Additionally, endometriosis and CHD may share common genetic susceptibilities.”
    Quote in the paperNot a substantial claim3 of 5 sources checked
    • cites [38] source
    • cites [39] source
    • cites [40] source

      The Discussion identifies genetic loci associated with coronary artery disease and raises the possibility of a shared mechanism with type 2 diabetes, not endometriosis. A search for “endometriosis” in our full-text copy found no passage addressing whether it shares genetic susceptibility with coronary heart disease; no page numbers were available. (LLM, conf=0.74)

      Experimental — accuracy not yet measured
    • cites [41] source
    • cites [42] source

      The Abstract reports a chromosome 9 allele associated with CHD risk, but it does not address endometriosis or a genetic susceptibility shared by the two conditions. A search for “endometriosis” in our copy found no passage discussing it. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
  • Premisecitation

    The CDKN2BAS1/ANRIL region on chromosome 9p21 has also been robustly associated with coronary heart disease outcomes.

    “and has also been robustly associated with CHD outcomes.(40-42)”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [40] source
    • cites [41] source
    • cites [42] source
  • Premisecitation

    Treatments for endometriosis, including hysterectomy or oophorectomy and analgesics, may increase the risk of coronary heart disease in women with endometriosis.

    “In addition, the treatments of endometriosis, such as hysterectomy or oophorectomy (20-24) and analgesics (25) may confer increased risk of CHD to women with endometriosis.”
    Quote in the paperSubstantial claim5 of 6 sources checked
    • cites [20] source

      The Results (Overall cardiovascular disease mortality) associate bilateral oophorectomy before age 45 with increased cardiovascular mortality, which supports the broader concern about surgical risk. But the Results (Specific cardiovascular causes of death) report no increased coronary heart disease mortality when analyzed separately; the paper does not establish this risk specifically for women with endometriosis. The analgesics portion is attached to a different citation. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [21] source
    • cites [22] source

      The Results (page not available) associate bilateral oophorectomy at hysterectomy with higher CHD mortality, and the Introduction reports an earlier finding of higher incident CHD. The paper does not establish this association specifically in women with endometriosis or for hysterectomy without oophorectomy. The sentence cites a different source for analgesics, so that part is not assessed here. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [23] source

      The Results (p. 3) associate hysterectomy and oophorectomy with increased coronary heart disease risk in women under 50, supporting the surgical-treatment portion of the claim. The paper does not establish that risk specifically in women with endometriosis, and reports a different pattern in women aged 50 or older. Analgesics are attached to a separate citation in the citing sentence. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [24] source

      The Results (page unavailable) report higher unadjusted rates of cardiovascular disease among women with a hysterectomy, with or without oophorectomy. But the study did not examine women with endometriosis as a group, and its hysterectomy associations with coronary heart disease outcomes were not statistically significant. This citation supports a possible cardiovascular association, not the specific claim of increased CHD risk in women with endometriosis; the separate analgesics citation is outside this verdict. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [25] source

      The Discussion (page unavailable) reports that NSAIDs increase the risk of non-fatal myocardial infarction, supporting a possible coronary risk from this class of analgesics. It does not establish that analgesics generally increase CHD risk in women with endometriosis. The hysterectomy and oophorectomy portion is attributed to other citations, not this paper. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Premisecitation

    Inflammatory factors such as interleukin-1, interleukin-6, and tumor necrosis factor-alpha are elevated in peritoneal fluid and peripheral blood of women with endometriosis compared with controls.

    “Various inflammatory factors, e.g. interleukin-1, interleukin-6, tumor necrosis factor-α, have been observed to be elevated both in peritoneal fluid (4-6) and the peripheral blood (4, 5, 7) of women with endometriosis compared to controls.”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [4] source
    • cites [5] source
    • cites [6] source

      The Results (page not available in our copy) report significantly higher interleukin-1β in the peritoneal fluid of women with endometriosis than controls. The paper does not establish that interleukin-6 or tumor necrosis factor-α is elevated there, or that these cytokines are elevated in peripheral blood; its peripheral-blood discussion instead concerns reduced soluble IL-1 receptor type II. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [7] source
  • May combine two claims. 27
  • Classified as probably not a substantial claim. 17

  • May combine two claims.

    Premisecitation

    Endometriosis is associated with systemic chronic inflammation, increased oxidative stress, and an atherogenic lipid profile.

    “Endometriosis has been linked to systemic chronic inflammation, heightened oxidative stress and an atherogenic lipid profile.”
    Quote in the paperSubstantial claim1 of 7 sources checked
    • cites [4] source
    • cites [5] source
    • cites [6] source

      The Discussion states that endometriosis is associated with a chronic immunoinflammatory reaction frequently observed at both local and systemic levels. The paper does not address heightened oxidative stress or an atherogenic lipid profile; searches for oxidative stress and lipid-profile terms returned no supporting passages. No page number was available in our copy. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [8] source
    • cites [9] source
    • cites [10] source
    • cites [11]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A study in 10 countries observed an average diagnostic delay of 6.7 years.

    “while a study in 10 countries observed an average delay of 6.7 years.(29)”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Chromosome 9p21 encodes the long non-coding RNA ANRIL, which regulates cell proliferation, adhesion, and apoptosis, central mechanisms of atherogenesis and endometriosis.

    “Chr9p21 encodes the long non-coding RNA(ncRNA) ANRIL, which has been demonstrated to regulate cell proliferation, adhesion and apoptosis,(43, 44) - central mechanisms of atherogenesis (13, 43) and endometriosis. (2, 3)”
    Quote in the paperSubstantial claim2 of 5 sources checked
    • cites [43] source
    • cites [44] source

      The Introduction identifies ANRIL as a non-coding RNA gene at 9p21, and the Results and Discussion link ANRIL expression to cell-cycle regulators in vascular smooth muscle cells. The paper also associates 9p21 variation with smooth muscle cell proliferation in atherosclerosis, but it does not demonstrate that ANRIL regulates adhesion or apoptosis. The citing sentence attributes its endometriosis point to other references, not this source. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [13] source
    • cites [2] source
    • cites [3] source

  • May combine two claims.

    Premisecitation

    Surgically induced menopause before natural menopause may increase coronary heart disease risk, and this elevated risk may be most evident at younger ages.

    “The surgically-induced menopause prior to a natural menopause may increase risk of CHD among women, and this elevated risk may be most evident at a younger age (i.e., before all women reach natural menopause). (20-24)”
    Quote in the paperSubstantial claim4 of 5 sources checked
    • cites [20] source

      The Results (no page supplied) associate bilateral oophorectomy before age 45 with increased cardiovascular mortality, supporting the concern about surgery before natural menopause. But the study measured deaths rather than CHD incidence, found no increase in CHD mortality considered separately, and examined mortality many years after surgery; it does not establish that the elevated risk is most evident while women are younger. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [21] source
    • cites [22] source
    • cites [23] source
    • cites [24] source

      The paper says that surgery well before natural menopause may affect cardiovascular function, and its Results report higher overall cardiovascular disease rates among women with a history of hysterectomy. It does not show that coronary heart disease risk is greatest at younger ages: the cohort was postmenopausal and aged 50–79, and the Results report no significant association for the specified coronary outcomes (MI or coronary death). Page numbers are unavailable in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Loss of ovarian function and subsequent deficiency of endogenous estrogens may be the biologic mechanism for the association between bilateral oophorectomy and cardiovascular diseases, while simple hysterectomy can interfere with ovarian blood flow and may result in premature ovarian failure.

    “Loss of ovarian function and subsequent deficiency of endogenous estrogens may be the biologic mechanism for association between bilateral oophorectomy and cardiovascular diseases, while simple hysterectomy can interfere with ovarian blood flow and may result in premature ovarian failure.(23)”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    A nationwide study from Sweden showed that hysterectomy without oophorectomy was associated with an increased risk of cardiovascular diseases in women age <50 but not in women age ≥50.

    “A nationwide study from Sweden showed that hysterectomy without oophorectomy was associated with an increased risk of cardiovascular diseases in women age<50 but not in women age ≥50.(23, 24)”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [23] source
    • cites [24] source

      The Discussion (p. 1468) reports that hysterectomy without oophorectomy was associated with higher CVD risk in unadjusted analysis, but that the association was mostly no longer significant after adjustment for risk factors. This paper analyzes a US Women's Health Initiative cohort, not a nationwide Swedish study, and it does not report the claimed difference between women under and over 50. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Bilateral oophorectomy at ages younger than 50 has been associated with increased incidence and mortality of cardiovascular diseases, although results have been inconclusive for bilateral oophorectomy at ages older than 50.

    “bilateral oophorectomy at ages younger than 50 has been associated with an increased incidence and mortality of cardiovascular diseases, although results have been inconclusive for bilateral oophorectomy at ages older than 50.(20-22)”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [20] source

      The Results report increased cardiovascular mortality after bilateral oophorectomy before age 45, particularly among women who did not continue estrogen treatment through age 45. The study measured mortality, not cardiovascular disease incidence; its significant finding is for under 45 rather than all women under 50, and the cited passages do not characterize results after age 50 as inconclusive. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [21] source
    • cites [22] source

      The Results report increased coronary heart disease mortality among women who had oophorectomy before age 50. They do not establish increased cardiovascular disease incidence, and the paper focuses on mortality after hysterectomy rather than incidence. For older women, the Results say CVD mortality estimates remained elevated at age 60 and above, although mortality outcomes did not differ statistically when stratified by age; this supports uncertainty about an age-specific effect, not a clear older-than-50 contrast. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The average diagnostic delay from symptom onset to surgical diagnosis in the Nurses' Health Study II cohort was 4 years.

    “this validation study determined that the average diagnostic delay (from symptom onset to surgical diagnosis) was 4 years in this cohort”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    31% of the association between endometriosis and coronary heart disease could be statistically accounted for by greater frequency and longer duration of postmenopausal hormone use, primarily driven by greater frequency and earlier age at hysterectomy/oophorectomy.

    “While 31% of the association could be statistically accounted for by greater frequency and longer duration of postmenopausal hormone use, this was primarily driven by greater frequency and earlier age at hysterectomy/oophorectomy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In age- and calendar-year-adjusted analyses, laparoscopically confirmed endometriosis was associated with higher risk of myocardial infarction (RR 1.63, 95% CI 1.27-2.11), angiographically confirmed angina (RR 2.07, 95% CI 1.73-2.47), coronary artery bypass graft surgery/angioplasty/stent (RR 1.49, 95% CI 1.19-1.86), and combined coronary heart disease (RR 1.73, 95% CI 1.49-2.00).

    “In age and calendar year adjusted analyses, the relative risks - comparing women with laparoscopically-confirmed endometriosis (n = 11,903 by end of follow-up) to women without - were 1.63 (95% confidence interval, 1.27 to 2.11) for myocardial infarction, 2.07 (1.73 to 2.47) for angiographically-confirmed angina, 1.49 (1.19 to 1.86) for coronary artery bypass graft surgery/angioplasty/stent and 1.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The relative risk of combined coronary heart disease associated with endometriosis was highest among women age 40 or younger (RR 3.08, 95% CI 2.02-4.70) and decreased as age increased (40<age≤50, RR 1.65, 95% CI 1.35-2.02; 50<age≤55, RR 1.44, 95% CI 1.07-1.94; age >55, RR 0.98, 95% CI 0.56-1.72; p for heterogeneity=0.001).

    “The relative risk was highest among women age≤40 (3.08, 2.02 to 4.70) and decreased as age increased (40<age ≤50, 1.65, 1.35 to 2.02; 50<age ≤55, 1.44, 1.07 to 1.94; age >55, 0.98, 0.56 to 1.72; p-value, test for heterogeneity=0.001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    After adjustment for potential confounders, laparoscopically confirmed endometriosis remained associated with higher risk of myocardial infarction (RR 1.52, 95% CI 1.17-1.98), angina (RR 1.91, 95% CI 1.59-2.29), coronary artery bypass graft surgery/angioplasty/stent (RR 1.35, 95% CI 1.08-1.69), and combined coronary heart disease (RR 1.62, 95% CI 1.39-1.89).

    “Results remained statistically significant after adjustment for potential confounders (myocardial infarction, 1.52, 1.17 to 1.98; angina, 1.91, 1.59 to 2.29; coronary artery bypass graft surgery/angioplasty/stent, 1.35, 1.08 to 1.69; combined CHD, 1.62, 1.39 to 1.89) (Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Women with endometriosis were more likely than women without endometriosis to have had a hysterectomy and/or oophorectomy and to have had these surgeries at an earlier age.

    “thus women with endometriosis are much more likely than the general population to undergo hysterectomy or oophorectomy and also receive the surgery at a much younger age.”
    • Also stated in: § Association between endometriosis and CHD · plain
      “Women with endometriosis were also much more likely to have had a hysterectomy and/or oophorectomy and to have had these at an earlier age, be surgically postmenopausal, and use postmenopausal hormones and analgesics.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Women with endometriosis had a higher absolute incidence rate of combined coronary heart disease than women without endometriosis across ages before the late 50s; the two rates crossed in the late 50s, after which the groups had similar incidence rates.

    “Figure 1 demonstrates that women with endometriosis had a higher absolute incidence rate of combined CHD compared to women without endometriosis across ages before late the 50s; the two absolute incidence rates crossed at ages in the late 50s - after which the two groups had similar incidence rates (Figure 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Women with endometriosis were much more likely to have had a hysterectomy and/or oophorectomy, to have had these at an earlier age, to be surgically postmenopausal, and to use postmenopausal hormones and analgesics.

    “Women with endometriosis were also much more likely to have had a hysterectomy and/or oophorectomy and to have had these at an earlier age, be surgically postmenopausal, and use postmenopausal hormones and analgesics.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The increased risk of coronary heart disease in women with endometriosis was greatest among younger women, and there was no increased risk from endometriosis after women reached the late 50s.

    “We observed that the increased risk of CHD in women with endometriosis was greatest among younger women, and there was no increased risk from endometriosis after women reached the late 50s.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Elevated low-density lipoprotein concentration enhances its retention under the arterial wall, and retention and oxidation of low-density lipoprotein are fundamental events in atherogenesis.

    “Elevated concentration of low-density lipoprotein enhances its retention under the arterial wall(17); retention and oxidation of low-density lipoprotein are fundamental events in atherogenesis.(18)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [17] source
    • cites [18] source

  • May combine two claims.

    Premisecitation

    Women with endometriosis have higher serum low-density lipoprotein and lower high-density lipoprotein levels.

    “Moreover, women with endometriosis have been suggested to have higher serum levels of low-density lipoprotien (10-12) but lower high-density lipoprotein. (10, 11)”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [10] source
    • cites [11]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [12] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Reactive oxygen species contribute to atherogenesis as mediators of signaling pathways that lead to vascular inflammation.

    “Increasing evidence supports that reactive oxygen species contributes to the process of atherogenesis, as important mediators of signaling pathways that lead to vascular inflammation.(15)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The response rate across the 20 years since enrollment was consistently over 90% for each questionnaire cycle and did not vary by endometriosis status.

    “The response rate across the 20 years since enrollment has been consistently over 90% for each questionnaire cycle and did not vary by endometriosis status.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Non-fatal myocardial infarctions were classified as confirmed if they met World Health Organization criteria: symptoms and either diagnostic electrocardiographic changes or raised cardiac enzymes.

    “Non-fatal myocardial infarctions were classed as “confirmed” if they met the criteria of the World Health Organization: symptoms and either diagnostic electrocardiographic changes or raised cardiac enzymes,(30)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Results were unchanged when multiple imputation was applied instead of the missing indicator method to address missing data in any covariate.

    “Results were also unchanged when multiple imputation was applied instead of the missing indicator method to address missing data in any covariate.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Fatal myocardial infarction was confirmed by hospital records, the National Death Index, or autopsy.

    “Fatal myocardial infarction was confirmed by hospital records, the National Death Index, or autopsy.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Clinicians blinded to questionnaire information reviewed medical records for self-reported non-fatal myocardial infarction events.

    “Clinicians blinded to the questionnaire information reviewed medical records from self-reported non-fatal myocardial infarction events.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Marginal structural models with inverse probability weighting were applied to adjust for potential time-dependent confounding.

    “Therefore, we also applied marginal structural models with inverse probability weighting to adjust for potential time-dependent confounding.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    Missing covariate values were handled by the missing indicator method, and multiple imputation was performed as a sensitivity analysis.

    “Missing covariate values were handled by the missing indicator method.(31) Multiple imputation to handle the missing data also was performed as a sensitivity analysis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductcitation

    The association between endometriosis and combined coronary heart disease was stratified by age groups, and the interaction between age and endometriosis was tested with likelihood ratio tests.

    “we stratified the association between endometriosis and combined CHD by age groups (<40, 40-50, 50-55, ≥55), and tested the statistical significance of the interaction between age and endometriosis with likelihood ratio tests.(33)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] source

  • May combine two claims.

    Premisecitation

    Women with endometriosis have increased oxidative stress markers and decreased antioxidants in peritoneal fluid and peripheral blood.

    “Studies also have suggested an increase of markers of oxidative stress but a decrease of antioxidants in the peritoneal fluid (8, 9) and peripheral blood (10, 11) among women with endometriosis.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [8] source
    • cites [9] source
    • cites [10] source
    • cites [11]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    Endometriosis may promote coronary artery atherosclerosis formation and progression, thereby increasing the risk of coronary heart disease.

    “Therefore, the presence of endometriosis may promote coronary artery atherosclerosis formation and progression, increasing the risk of CHD.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    High-density lipoprotein is antiatherogenic and removes cholesterol from cells in the arterial intima.

    “In contrast, high-density lipoprotein is antiatherogenic, removing cholesterol from cells in the arterial intima.(19)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    In the hysterectomy/oophorectomy analysis, adjustment included household income, husband's education, geographic region, infertility history, and analgesics use.

    “to further account for risk factors of hysterectomy, we added adjustment for household income, husband's education and geographic region of residence. We also further adjusted for potential indication for hysterectomy including infertility history and analgesics use (in addition to oral contraceptive) as indicators of endometriosis clinical severity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The longitudinal study design, large sample size, and 20 years of follow-up allowed the study to document the prospective association between surgically diagnosed endometriosis and subsequent risk of coronary heart disease.

    “The longitudinal study design, large sample size and 20 years of follow-up allowed us to document the prospective association between surgically diagnosed endometriosis and subsequent risk of CHD.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The mediation proportion estimated from this model can be interpreted as the mediation proportion to be observed in this study population or any other study population with a similar proportion of treatment and a similar age distribution.

    “The mediation proportion estimated from this model can be interpreted as the mediation proportion to be observed in this study population or any other study population with a similar proportion of treatment and a similar age distribution.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The likely prevalence of undiagnosed endometriosis should not exceed 2% of the unexposed population and is therefore too low to impact the results.

    “as Zondervan (51) et al. quantified, the likely prevalence of undiagnosed endometriosis should not exceed 2% of the unexposed population, and therefore too low to impact on the results, particularly in our large study population among whom undiagnosed endometriosis become diluted among tens of thousands of those with no endometriosis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [51] source

  • May combine two claims.

    Study design and conductreasoning

    The unexposed group may include asymptomatic endometriosis or symptomatic endometriosis without confirmatory diagnosis; if so, the results would be biased toward the null.

    “our unexposed group (i.e. never clinically or surgically diagnosed with endometriosis) may include asymptomatic endometriosis or symptomatic without confirmatory diagnosis. If so, our results would be biased toward the null.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Because results of multivariable Cox models and marginal structural models were almost identical, potential bias from time-varying confounding in multivariable Cox models was negligible.

    “Moreover, because the results of multivariable Cox models and marginal structural models were almost identical, the potential bias that may remain within multivariable Cox models for adjustment of time-varying confounding (32) was negligible.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The observed increased risk associated with surgical menopause from hysterectomy/oophorectomy among women with endometriosis may have started to diminish with age partially because nearly every woman had reached menopause by age 55.

    “It is possible that the observed increased risk associated with surgical menopause from hysterectomy/oophorectomy among women with endometriosis started to diminish with age partially because nearly every woman had reached menopause by age 55.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The timing of exposure was defined by time of surgical diagnosis, not disease onset.

    “Finally, the timing of exposure was defined by time of surgical diagnosis, not disease onset.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Hysterectomy/oophorectomy was associated with higher risk of coronary heart disease and could explain a portion of the association between endometriosis and coronary heart disease.

    “Hysterectomy/oophorectomy was associated with higher risk of CHD and could explain a portion of the association between endometriosis and CHD.”
    Quote in the paperSubstantial claim
39 of 39

  • The paper relies on this without support.

    This is the first prospective cohort study investigating the association between endometriosis and coronary heart disease.

    “To our knowledge, this is the first prospective cohort study investigating the association between endometriosis and CHD.”

  • The paper relies on this without support.

    Self-reported physician-diagnosed angina confirmed by angiography, coronary artery bypass graft surgery/angioplasty/stent, and time of diagnosis are accurate enough for the study's coronary heart disease outcome classification.

    “Physician-diagnosed angina confirmed by angiography, coronary artery bypass graft surgery/angioplasty/stent and time of diagnosis were self-reported.”

  • The paper relies on this without support.

    The missing data mechanism is such that the missing indicator method and multiple imputation yield valid estimates.

    “Missing covariate values were handled by the missing indicator method.(31) Multiple imputation to handle the missing data also was performed as a sensitivity analysis.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The NHS II studies were limited to investigating the association between endometriosis, IHD risk and hypertension risk.

    “The NHS II studies were limited to investigating the association between endometriosis, IHD risk and hypertension risk. 30,31”

    From Risk of cardiovascular outcomes among women with endometriosis in the United Kingdom: a retrospective matched cohort study (2021) · cites this paper as [30]

    The Abstract’s Methods and Results and the Methods’ Assessment of CHD show that this NHS II study investigated endometriosis and coronary heart disease risk, including myocardial infarction and angina. The paper does not investigate hypertension risk as an outcome, so it supports only the IHD portion of the sentence. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Certain reproductive factors, including endometriosis, pelvic inflammatory disease, first trimester bleeding without miscarriage, and anaemia in pregnancy, have been linked to an increased risk of future cardiovascular disease events.

    “Certain reproductive factors, including endometriosis, pelvic inflammatory disease, first trimester bleeding without miscarriage, and anaemia in pregnancy, have been linked to an increased risk of future cardiovascular disease events”

    From Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review (2020) · cites this paper as [19]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Reported age bands differ from the planned bands at their boundaries

    Minor

    The methods place age 40 in the 40-50 group and age 55 in the ≥55 group. The reported results instead place age 40 in the youngest group and age 55 in the 50-55 group.

1 of 1

Cites

Flagged first, then by citations

2 of the 56 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Miettinen OS. Theoretical Epidemiology: Principles of Occurrence Research. New York, NY: John Wiley & Sons; 1985.

Cited by

Sorted by citations

Related

Authors
Mu, F., Rich-Edwards, J., Rimm, E. B., Spiegelman, D., & Missmer, S. A.
Affiliations
Brigham and Women's Hospital (US)
ORCID
Venue
Circulation: Cardiovascular Quality and Outcomes
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2016-05
Volume
9
Issue
3
Pages
257-264
ISSN
  • 1941-7705 (ISSN-L)
  • 1941-7713
DOI
10.1161/circoutcomes.115.002224
PMC
PMC4940126
OpenAlex
W2326334786
Cited by
235
References
56
Citations by year
2026: 31 · 2025: 31 · 2024: 29 · 2023: 22 · 2022: 29 · 2021: 27 · 2020: 19 · 2019: 16 · 2018: 12 · 2017: 11 · 2016: 6
FWCI
19.95
Type
journal article
Language
en
Open access
Locations
  • Circulation Cardiovascular Quality and Outcomes (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
  • National Cancer Institute (R01CA050385)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD057210, R01HD052473)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
  • Health Sciences › Medicine › Epidemiology › Infective Endocarditis Diagnosis and Management
Keywords
endometriosis, coronary artery disease, myocardial infarction, angina pectoris, coronary artery bypass grafting, coronary angioplasty, hysterectomy, oophorectomy, young women, chronic inflammation, oxidative stress, atherogenic lipid profile, Nurses' Health Study II, age at surgery, cardiovascular risk in women
MeSH terms
Adult, Age Factors, Angina Pectoris, Coronary Artery Bypass, Coronary Artery Disease, Coronary Disease, Endometriosis, Female, Humans, Hysterectomy, Longitudinal Studies, Middle Aged, Myocardial Infarction, Nurses, Ovariectomy, Laparoscopy, Prospective Studies, Risk Factors, Time Factors, United States, Stents, Treatment Outcome, Risk Assessment, Percutaneous Coronary Intervention

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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