Cardiovascular disease among women with and without diabetes mellitus and bilateral oophorectomy

Appiah, Duke; Winters, Stephen J.; Allison, Matthew A.; Baumgartner, Richard N.; Groves, Frank D.; Myers, John; Hornung, Carlton A.

doi:10.1016/j.diabres.2015.02.017

Cited by 8 publications

(5 citation statements)

References 36 publications

(43 reference statements)

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“…Other studies have also identified genetic predictors of age at menopause and early menopause . In a follow‐up of the National Health and National Examination Survey, the elevated risk of CVD mortality in women with surgical menopause before age 45 years was limited to those who reported a family history of CHD, suggesting that the relation of surgical menopause and CVD may be explained by susceptibility genes that increase the risk of both outcomes . Analogously, the elevated incidence of HF among women with early menopause observed in this and other studies may reflect residual confounding of unmeasured variables.…”

Section: Discussionmentioning

confidence: 50%

Association of Age at Menopause With Incident Heart Failure: A Prospective Cohort Study and Meta‐Analysis

Appiah

Schreiner

Demerath

et al. 2016

JAHA

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Background Early age (<45 years) at menopause has been postulated to be associated with increased cardiovascular disease risk; however, evidence of its relation with heart failure ( HF ) incidence is limited. We examined whether age at menopause is associated inversely with HF incidence in the Atherosclerosis Risk In Communities ( ARIC ) study and summarized all existing data in a meta‐analysis. Methods and Results In ARIC , data were obtained from 5629 postmenopausal women (mean age 56 years, 26% with bilateral oophorectomy) without HF . During a median follow‐up of 21.4 years, 965 incident HF events occurred. In a Cox regression model adjusted for reproductive health and HF risk factors, the hazard ratios for incident HF across categories of age at menopause (<45, 45–49, 50–54, and ≥55 years) were 1.32, 1.17, 1.00 (referent), and 1.12, respectively. Compared with women with later onset of menopause (aged ≥45 years), those with early menopause had elevated HF risk (hazard ratio 1.20, 95% CI 1.01–1.43). For the meta‐analysis, we searched Medline and Embase for articles published through December 2015 that prospectively evaluated age at menopause and HF risk. Summarized estimates from the 3 included studies (3568 events) showed higher HF risk among women with early menopause compared with those with later menopause (hazard ratio 1.33, 95% CI 1.15–1.53). Conclusions These results provided evidence that early age at menopause is associated with a modestly greater risk of HF . Identification of women with early menopause offers a window of opportunity to implement interventions that will improve overall cardiovascular health during the postmenopausal years.

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Section: Discussionmentioning

confidence: 50%

Association of Age at Menopause With Incident Heart Failure: A Prospective Cohort Study and Meta‐Analysis

Appiah

Schreiner

Demerath

et al. 2016

JAHA

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“…A study of the National Health and Nutrition Examination Survey showed that the association between surgical menopause and cardiovascular disease attenuated after adjusting for family history, suggesting that susceptibility genes that increase the risk of both outcomes may explain part of this association. 27 It is also possible that disease and treatment effects may contribute to the excess risk of CAD observed in women who underwent gynecologic surgery due to malignancy. [28][29][30] Understanding the mechanistic differences across menopause groups is crucial for developing precision medicine approaches to mitigate cardiovascular risk in postmenopausal women, warranting further research into mechanisms underlying the higher rates of cardiovascular disease in women with prior surgical premature menopause.…”

Section: Discussionmentioning

confidence: 99%

Age at Menopause, Leukocyte Telomere Length, and Coronary Artery Disease in Postmenopausal Women

Schuermans,

Nakao,

Uddin

et al. 2023

Circulation Research

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Background: Premature menopause is a risk factor for accelerated cardiovascular aging, but underlying mechanisms remain incompletely understood. This study investigated the role of leukocyte telomere length (LTL), a marker of cellular aging and genomic instability, in the association of premature menopause with cardiovascular disease. Methods: Participants from the UK Biobank and Women’s Health Initiative with complete reproductive history and LTL measurements were included. Primary analyses tested the association between age at menopause and LTL using multivariable-adjusted linear regression. Secondary analyses stratified women by history of gynecologic surgery. Mendelian randomization was used to infer causal relationships between LTL and age at natural menopause. Multivariable-adjusted Cox regression and mediation analyses tested the joint associations of premature menopause and LTL with incident coronary artery disease. Results: This study included 130 254 postmenopausal women (UK Biobank: n=122 224; Women’s Health Initiative: n=8030), of whom 4809 (3.7%) had experienced menopause before age 40. Earlier menopause was associated with shorter LTL (meta-analyzed ß=−0.02 SD/5 years of earlier menopause [95% CI, −0.02 to −0.01]; P =7.2×10 -12 ). This association was stronger and significant in both cohorts for women with natural/spontaneous menopause (meta-analyzed ß=−0.04 SD/5 years of earlier menopause [95% CI, −0.04 to −0.03]; P <2.2×10 -16 ) and was independent of hormone therapy use. Mendelian randomization supported a causal association of shorter genetically predicted LTL with earlier age at natural menopause. LTL and age at menopause were independently associated with incident coronary artery disease, and mediation analyses indicated small but significant mediation effects of LTL in the association of menopausal age with coronary artery disease. Conclusions: Earlier age at menopause is associated with shorter LTL, especially among women with natural menopause. Accelerated telomere shortening may contribute to the heightened cardiovascular risk associated with premature menopause.

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“…The proportionality assumption was tested using cumulative sums of martingale residuals with a Kolmogorov-type supremum test and also by visually inspecting plots of Schoenfeld residuals versus time. Because testosterone levels decrease during the menopausal transition ( 28 ) and our previous study of women in the National Health and Nutrition Examination Survey ( 29 ) suggested that BSO before age 45 years increased the CVD risk for DM2, we examined all-cause and CVD mortality in women stratified by age at menopause (≤45 vs. >45 years), a cut point that others have also used ( 30 ). A two-tailed P value of <0.05 was considered statistically significant.…”

Section: Methodsmentioning

confidence: 99%

Androgens, Bilateral Oophorectomy, and Cardiovascular Disease Mortality in Postmenopausal Women With and Without Diabetes: The Study of Osteoporotic Fractures

et al. 2015

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OBJECTIVEDiabetes elevates cardiovascular disease (CVD) risk more markedly in women than in men. Because the high risk of CVD among women with type 2 diabetes (DM2) may be partly due to increased ovarian androgen production, we investigated whether a history of bilateral salpingo oophorectomy (BSO) is inversely associated with CVD mortality among women with DM2.RESEARCH DESIGN AND METHODSData were obtained from 7,977 women (a random subset of 564 had measurements of sex-steroid hormones) enrolled in the Study of Osteoporotic Fractures (SOF), a community-based, multicenter study that monitored women aged ≥65 years for a mean of 15.1 years. Adjusted hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards regression.RESULTSThe average age at baseline was 71.5 years, with 6.3% and 18% of participants reporting a history of diabetes or BSO, respectively. In the subset of the SOF cohort with sex-steroid hormone measurements, those with DM2 had 43.6% significantly higher levels of free testosterone that were partly explained by age and adiposity, whereas total and free testosterone levels were lower in women with BSO than in those with intact ovaries. CVD mortality was elevated in women with DM2 without BSO (HR 1.95, 95% CI 1.62–2.35) as well as in women with DM2 and BSO (HR 2.56, 95% CI 1.79–3.65; P = 0.190 for interaction). Overall, BSO was not associated with CVD mortality (HR 1.05, 95% CI 0.89–1.23).CONCLUSIONSThe association of diabetes with CVD was not reduced by BSO, suggesting that ovarian hyperandrogenemia may not be a primary mechanism to explain the high risk for CVD among women with DM2.

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Cardiovascular disease among women with and without diabetes mellitus and bilateral oophorectomy

Cited by 8 publications

References 36 publications

Association of Age at Menopause With Incident Heart Failure: A Prospective Cohort Study and Meta‐Analysis

Association of Age at Menopause With Incident Heart Failure: A Prospective Cohort Study and Meta‐Analysis

Age at Menopause, Leukocyte Telomere Length, and Coronary Artery Disease in Postmenopausal Women

Androgens, Bilateral Oophorectomy, and Cardiovascular Disease Mortality in Postmenopausal Women With and Without Diabetes: The Study of Osteoporotic Fractures

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