Influence of Chronic Kidney Disease on the Relationship Between Menopausal Status and Major Cardiovascular Disease in Women

Background Chronic kidney disease (CKD) is associated with early menopause, and thereby reduced endogenous estrogen exposure (EEE) and elevated risk of cardiovascular disease (CVD). Methods Included were 138 154 naturally menopausal and 63 542 nonmenopausal women from the UK Biobank. To reflect cumulative EEE, duration of EEE was estimated as the time interval between age at menarche and current age (for nonmenopausal women) or age at menopause (for menopausal women). The relationship of menopausal status with incident CVD were assessed by CKD status, further considering cumulative EEE. Results Menopausal and nonmenopausal women had a comparable risk of CVD after accounting for age. Menopausal status interacted with CKD on risk of CVD ( P for interaction=0.001). In the CKD group, menopausal women had a lower risk of CVD than nonmenopausal women (hazard ratio HR, 0.75 95% CI, 0.58–0.97), predominantly for those with EEE ≥38 years (HR, 0.64 95% CI, 0.47–0.88) but not for those with shorter EEE (HR, 1.00). In the non‐CKD group, being menopausal was not associated with risk of CVD (HR, 1.00), but was associated with a suggestively lower risk among those with longer EEE (HR, 0.90 95% CI, 0.81–1.00) and a higher risk among those with shorter EEE (HR, 1.13 [95% CI, 1.02–1.25). Conclusions The association of menopausal status with risk of CVD appears to be varied by CKD status and further influenced by cumulative exposure to endogenous estrogen. These findings may have implications for more individualized CVD risk stratification and prevention in menopausal women.