Study Provides Overview of Female Reproductive Factors and Heart Failure Risk

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Leveraging data from the UK Biobank study, a new study offers insight into the risk of new-onset heart failure based on female reproductive risk factors among a cohort more than 220,000 women.

An analysis of data from more than 220,000 women is providing an overview of associations between female reproductive factors and risk of new-onset heart failure.

Results of the analysis, which leveraged data from the UK Biobank Study, indicate younger maternal age at first live birth and last live birth, having 3 or more children, and history of stillbirth were all associated with increased risk of new-onset heart failure later in life.1

“Our findings carry the promise for a better understanding of the [heart failure] pathogenesis in women and emphasize the importance of female reproductive history in [heart failure] risk assessment,” investigators wrote.1

Led by Maryam Kavousi, MD, PhD, of the Department of Epidemiology at the University Medical Center Rotterdam, the current study was launched with the intent of conducting a comprehensive evaluation of associations of multiple female reproductive factors with risk of new-onset heart failure. With this in mind, investigators designed their study as an analysis of data from within the UK Biobank cohort.1

A large-scale, long-term biobank study launched in 2006, the UK Biobank contains data related to 500,000 individuals aged 40-69 years of age in the UK.2 Limiting their study to those enrolled between 2007-2010 without a history of prevalent heart failure, investigators identified 229,026 women for inclusion in the current study.1

This cohort had a mean age of 56.5 (SD, 8.1) years, 90.6% were White, the mean BMI was 27.0 (SD, 5.1) kg/m2, and 3.4% (n=7831) had a history of diabetes. Investigators pointed out 73.6% of women were postmenopausal at baseline, 13.7% had a hysterectomy and/or oophorectomy, and 85.0% had ever been pregnant.1

The primary outcome of interest in the study was new-onset heart failure, which was defined using ICD-10 with code I50. Associations between reproductive factors and heart failure was assessed using Cox proportional hazards models with adjustment for potential confounding.1

During a median follow-up of 11.8 (IQR, 11.1-12.6) years, heart failure occurred among 4202 participants, which correlates to an incidence rate of 1.58 per 1000 person-years. In fully adjusted models, multiple reproductive factors were associated with an apparent increase in risk for new-onset heart failure.1

Reproductive Risk Factors Associated with New-Onset Heart Failure1:

  • Menarche before 12 years of age (vs 12-13 years): HR, 1.09 [95% CI, 1.01-1.18]
  • Menopause before 45 years of age (vs 50-51 years): HR, 1.15 [95% CI, 1.03-1.28]
  • Menopause at 45-49 years (vs 50-51 years): HR, 1.11 [95% CI, 1.01-1.23]
  • Maternal age at first live birth before 21 years (vs 24-26 years): HR, 1.42 [95% CI, 1.28-1.59]
  • Maternal age at first live birth at 21-23 years (vs 24-26 years): HR, 1.14 [95% CI, 1.03-1.26]
  • Maternal age at last live birth before 26 years (vs 20-31 years) HR, 1.19 [95% CI, 1.07-1.33]
  • Having 3 or 4 children (vs having 1 or 2 children): HR, 1.09 [95% CI, 1.02-1.17]
  • Having more than 4 children (vs having 1 or 2 children): HR, 1.25 [95% CI, 1.05-1.47]

“Our findings emphasize that age at menarche, maternal age, number of pregnancies, pregnancy loss, and timing of menopause are markers of [heart failure] risk. These woman-specific risk factors contribute to sex differences in [heart failure] pathogenesis and disease burden,” investigators added.1 “More-over, risk assessment should be regarded as an iterative process as new information on female reproductive health becomes available. This longitudinal knowledge can facilitate optimization of cardiovascular health for women throughout their life course.”


  1. Zhu F, Qi H, Bos M, Boersma E, Kavousi M. Female Reproductive Factors and Risk of New-Onset Heart Failure: Findings From UK Biobank [published online ahead of print, 2023 Apr 17]. JACC Heart Fail. 2023;S2213-1779(23)00136-1. doi:10.1016/j.jchf.2023.02.019
  2. Sudlow C, al JAet, al TLet. UK Biobank Background. About Us. Accessed April 28, 2023.