The relationship between cardiometabolic abnormalities and mortality among women with and without cancer in the Women’s Health Initiative (WHI).
Authors: Raychaudhuri Sreejata , Stefanick Marcia L. , Reding Kerryn , Vasbinder Alexi , Cheng Richard , Barac Ana , McLaughlin Eric , Pennell Michael , Simon Michael S. 
Published: June 2024

e24007 Background: Prior studies of women with obesity-associated cancers in the Women’s Health Initiative (WHI) showed higher overall and mortality due to cardiovascular disease (CVD) for women with a higher number of cardiometabolic risk factors at baseline. It is unclear if this risk differs from women without cancer. In order to determine if this relationship differs among both groups, we compared the association between cardiometabolic risk factors and mortality among women in the WHI with and without cancer. Methods: Women with one of five early-stage obesity-associated cancers (breast, colorectal, endometrial, ovarian, non-Hodgkin lymphoma), and matched controls without history of cancer, were selected from the WHI-Life and Longevity After Cancer (LILAC) study. Cardiometabolic risk factors included high waist circumference (WC) (≥88 cm), systemic hypertension ( > 130/85 mm Hg) measured at study visits, and self-reported history of diabetes and elevated cholesterol. Multivariable Cox proportional hazards models (all-cause mortality) and Fine-Gray models (CVD and non-CVD mortality) were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) to evaluate the association between baseline cardiometabolic risk factors and survival outcomes for the cancer and non-cancer cohorts in separate models. Sensitivity analyses included women in the cancer-cohort who received cardiotoxic chemotherapy. Results: A total of 7,491 and 35,508 women were analyzed in the cancer and non-cancer cohorts respectively. CVD was the most common cause of death (excluding cancer) in both non-cancer (41.4%) and cancer (41.5%) cohorts. Adjusted Cox models showed that the proportion of deaths due to any cause, by number of cardiometabolic risk factors, was significantly higher in the non-cancer compared to the cancer cohort (p-value = 0.02), with the HR values being higher for those with 3-4 risk factors compared to 1-2. Similar results were seen for each individual risk factor except for WC. Regarding CVD and non-CVD mortality, in competing risks models, there were no significant differences in the risk of death by number of risk factors, between the cancer and non-cancer cohorts (p = 0.21 and 0.22) respectively. Sensitivity analyses for women who received a cardiotoxic regimen, (81.5% anthracyclines alone, 13.4% anti-HER2 alone, and 5.1% both) showed no differences in the results for all-cause mortality, and CVD mortality. However, for non-CVD mortality, the proportion of deaths was significantly higher for women in the non-cancer cohort (p = 0.03). Conclusions: Cardiometabolic risk factors had a greater impact on mortality among women without cancer compared to those with cancer, except for death due to CVD which was similar between groups, suggesting that CVD risk reducing interventions are of equal importance for women with and without cancer.