A study for the ages, Women’s Health Initiative makes lasting contributions to cardiology

BUFFALO, N.Y. — For nearly 30 years, the Women’s Health Initiative has yielded important findings that continue to shed light on factors affecting disease and risk of death in postmenopausal women. WHI’s contributions to cardiology are especially impressive, right up there with other well-known studies such as Framingham, and the Atherosclerosis Risk in Communities (ARIC).

The broad scope of WHI’s impact on cardiovascular health has been detailed in a recent paper in the Journal of the American College of Cardiology, which invited the major epidemiology studies on cardiovascular disease to submit legacy papers.

“WHI is the largest investigation of women’s health, including cardiovascular health, ever conducted in a national cohort of older postmenopausal women recruited from the community setting,” said Michael J. LaMonte, PhD, research professor of epidemiology and environmental health in the University at Buffalo’s School of Public Health and Health Professions, and the lead author on the paper, which included contributions from 20 WHI investigators.

The Women’s Health Initiative enrolled more than 161,000 women aged 50-79 at study entry in the 1990s. That, LaMonte says, provided the unprecedented opportunity to study the development of cardiovascular disease, as well as several other major conditions that contribute to the burden of aging-related diseases among women later in life, such as breast cancer, osteoporosis and cognitive functioning.

“WHI is a really unique population-based investigation,” LaMonte said, adding that it continues to make important contributions through a number of follow-up studies that have allowed researchers to study women over age 80.

“Because women of this age are the most rapidly increasing group of adults in terms of population aging, the understanding that WHI can uniquely provide on how to maximize quality life years in this age group is paramount to public health in the coming decades,” LaMonte said.

In addition, because of its sheer size, WHI was able to publish data on major cardiovascular outcomes — such as first heart attack and stroke — early in the study’s progression. It’s also one of the largest and most diverse cohorts of U.S. women ever studied.

Through the WHI, researchers learned that cardiovascular diseases were the most common causes of death among the postmenopausal women enrolled in the study, accounting for nearly 31% of deaths reported through March 2021.

Other notable contributions to cardiovascular research include:

• Reproductive factors such as pregnancy losses, stillbirths and absence of breast feeding have been evaluated as predictors of coronary heart disease among WHI participants.
  
• The finding that cardiovascular disease was the leading cause of death, over 10 years of follow-up post diagnosis, for women with localized breast cancer diagnosed at age 70 or older.
  
• The surprising observation that lean body mass was more strongly related to developing atrial fibrillation than fat mass, and the risk of atrial fibrillation associated with body mass index (BMI) was largely attributable to its association with lower lean mass.
  
• Using accelerometers worn at the hip for seven consecutive days in 6,489 women aged 63-99, WHI showed that physical activity intensity thresholds commonly used in younger adults resulted in substantial underestimation for older women of time spent doing moderate to vigorous physical activity, and that lighter intensity activities (less than guideline recommended) were associated with lower rates of cardiovascular disease events and mortality.
  
• The finding that only 27% of WHI women reported sleeping 8 hours or more per night. WHI participants with insomnia had a 38% higher risk for coronary heart disease. The WHI Memory Study found that women who slept 6 or fewer or 8 or more hours per night had a 35% higher risk of cognitive decline, regardless of cardiovascular disease status.
  

And there’s plenty more to come. LaMonte and colleagues are currently conducting the WHI Strong and Healthy (WHISH) trial, the first-ever randomized controlled trial on physical activity to prevent primary, or first, heart attacks and strokes.

“The WHISH trial is poised to provide a definitive test of the hypothesis that increasing physical activity in later life reduces the risk of having a heart attack or stroke,” LaMonte said, adding that the results could have a major impact on existing clinical guidelines and public health recommendations.

Future ancillary studies also will focus on vascular brain health, blood pressure, and heart failure, as well as the physical and mental health impacts the COVID-19 pandemic has had on aging women.

All the while, senior WHI scientists continue to train the next generation of investigators, ensuring that there is ample brain power and energy to keep the Women’s Health Initiative science moving well into the future, LaMonte said.

“I had the opportunity to join WHI at UB, and it is a privilege to now foster growth of new investigators in Buffalo and elsewhere,” he added.

“There are so many opportunities to leverage the existing WHI data resource to continue to add new information so that we can learn even more about prevention of cardiovascular disease and other conditions in aging women,” he added.