The relationship between cardiometabolic abnormalities and mortality in the Women's Health Initiative: A comparison of associations among women with cancer to women without cancer

Cancer. 2025 Mar 15;131(6):e35804. doi: 10.1002/cncr.35804.

Abstract

Background: Prior studies of participants with breast and other obesity-associated cancers in the Women's Health Initiative (WHI) showed worse mortality and cardiovascular disease (CVD) outcomes for individuals with a higher number of cardiometabolic risk factors at study entry. The purpose of this analysis is to compare the relationship between cardiometabolic abnormalities and mortality among women with and without cancer in the WHI.

Methods: Women with one of five early-stage obesity-associated cancers (breast, colorectal, endometrial, ovarian, and non-Hodgkin lymphoma) and controls without any new or prior history of cancer were selected from the WHI-Life and Longevity after Cancer ancillary study. Cardiometabolic abnormalities included high waist circumference (≥88 cm), hypertension (>130/85 mm Hg), and self-reported history of diabetes and/or elevated cholesterol. Multivariable Cox proportional hazards models (all-cause mortality) and Fine-Gray models (CVD and non-CVD mortality) were used to evaluate the association between cardiometabolic risk factors and survival outcomes for the cancer and noncancer cohorts.

Results: A total of 7491 and 35,508 women were studied in the cancer and noncancer cohorts, respectively. Adjusted analyses showed that increased number of cardiometabolic abnormalities was associated with increased short-term risk of all-cause mortality, with the association being stronger among the noncancer "controls" compared to the cancer cohort (interaction p value = .02). Associations were similar between cancer cases and controls in competing risk models for CVD and non-CVD mortality.

Conclusion: Preexisting cardiovascular abnormalities are an important predictor of adverse health outcomes among women with and without cancer in the WHI.

Keywords: all‐cause mortality; cardiometabolic abnormalities; cardiovascular outcomes; metabolic syndrome; obesity‐associated cancer.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Breast Neoplasms* / complications
  • Breast Neoplasms* / epidemiology
  • Breast Neoplasms* / mortality
  • Cardiometabolic Risk Factors
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / etiology
  • Cardiovascular Diseases* / mortality
  • Case-Control Studies
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / mortality
  • Endometrial Neoplasms / complications
  • Endometrial Neoplasms / epidemiology
  • Endometrial Neoplasms / mortality
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / epidemiology
  • Lymphoma, Non-Hodgkin / complications
  • Lymphoma, Non-Hodgkin / epidemiology
  • Lymphoma, Non-Hodgkin / mortality
  • Middle Aged
  • Neoplasms* / complications
  • Neoplasms* / epidemiology
  • Neoplasms* / mortality
  • Obesity / complications
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / mortality
  • Proportional Hazards Models
  • Risk Factors
  • Waist Circumference
  • Women's Health*