The first intervention phase of the Women's Health Initiative ended in 2005, but with a recent award of $32 million to the Hutchinson Center from the National Heart, Lung and Blood Institute for continued coordination of the study through early 2011, the WHI is embarking on its next phase of research.
The WHI is a major 15-year research program designed to address the most frequent causes of death, disability and poor quality of life in postmenopausal women: cardiovascular disease, cancer and osteoporosis. The Center is home to the study's coordinating hub and is the site of the Seattle clinical center.
The new phase aims to shed greater light on the health effects seen in the intervention arms of the study's first stage. The continuation also equips Center researchers and their colleagues nationwide with novel tools to search for biomarkers and genetic variations for major diseases in older women. Their findings may aid early-detection efforts for cancer and guide future research into diet, activity and chronic disease.
"The extension study will examine the long-term effects of the WHI clinical-trial treatments or interventions. Even though our participants won't be continuing intervention activities, health effects might continue for some years," said Dr. Ross Prentice, the principal investigator who leads the study with Drs. Garnet Anderson and Andrea LaCroix. He said researchers are also eager to more fully use the vast data and biological specimen resources developed during the first phase of the study.
New research contracts
The Center is also the recipient of three of 12 new WHI research contracts worth $4.6 million to investigate the impact of biological markers on common diseases affecting postmenopausal women.
The new two-year research projects apply innovative technologies to study factors affecting the major diseases in older women using blood, DNA and other biological samples and clinical data from nearly 162,000 participants in one or more of the three WHI clinical trials or the observational study. NHBLI intends to fund a second round of studies using WHI biological specimens in 2008, for a total of $35 million in funding.
There's plenty of competition among researchers for the WHI biological samples, considered one of the largest repositories of its kind in the world. "High-quality specimens from a very large group of women who have had meticulous follow-up on their health over a long period of time is an extremely valuable resource," Prentice said.
In one of the new Center projects, Dr. Chris Li, along with Drs. Sam Hanash, Martin McIntosh, Paul Lampe and Prentice, is using three different proteomics techniques to identify proteins associated with breast cancer as well as biomarkers that potentially could be used for early detection of breast cancer.
In another new project, Prentice, Hanash and McIntosh will study more than 1,000 proteins to identify proteins potentially associated with heart disease, stroke or breast cancer in the WHI observational-study participants. Much of the work will be conducted in Hanash's Public Health Sciences Division lab and in McIntosh's computational proteomics analysis lab. Together with other ongoing proteomic studies in the hormone trials, this work may lead to novel biological insights into the important effects of hormone therapy that have been observed in the WHI trials.
Prentice is also leading a genome-wide association study to examine genetic variations associated with breast-cancer risk. His work uses data from women who participated in the hormone therapy, calcium/vitamin D and low-fat diet trials, which includes blood hormone and vitamin D levels in many of the participants. Prentice and colleague Dr. Riki Peters hope to explore biologic pathways by relating treatments, blood levels and genes to breast-cancer occurrence. This study will be conducted in collaboration with Drs. Dennis Ballinger and David Cox of Perlegen Sciences Inc. in Mountain View, Calif., a subcontractor on the award.
During the past 15 years, there have been approximately 200 WHI-related ancillary studies involving researchers throughout the country. While many build directly on the central study goals, the large amount of data collected on older women opens the door to more atypical studies, too.
Anderson recently co-authored one such study on air pollution and cardiovascular risk. In one of the largest studies ever to examine the issue, the research, led by University of Washington's Dr. Joel Kaufman, suggests that air pollution may be a bigger factor in death from heart disease or stroke than previously recognized.
Using data from 66,000 WHI participants in 36 cities and after adjusting for other risk factors for heart disease and stroke, they found that living in areas with high levels of fine particulate matter was associated with heart disease and stroke risk — and had an even stronger association with death from heart disease or stroke.
The study, funded in part by the Environmental Protection Agency, was published Feb. 1 in The New England Journal of Medicine. The study substantially strengthens the evidence linking air pollution and cardiovascular disease.
Fine particulate air pollution, caused primarily by vehicle exhausts, coal-fired power plants and other industrial sources, was the sole type of air pollution associated with increased risk. The researchers found that women living in the most polluted areas of cities had the highest heart disease and stroke risk, while women living in the cleanest areas had the lowest.
Prentice said this study was a great example of the value of WHI data as a scientific resource for many kinds of studies, especially because of the diversity in the population — the participants are from various geographic areas throughout the United States and more than 17 percent are racial/ethnic minorities — and their health events have been thoroughly tracked.
More WHI data due
Researchers will continue to follow most of the WHI participants until 2010 through annual updates to their health histories. WHI scientists, including Prentice and LaCroix, recently published a new analysis of the combined data from the two hormone trials to bring the effects into sharper focus. The combined hormone-therapy arm of the trial was halted in 2002 due to safety concerns. The latest analysis suggests that risk of heart attack from hormones may not be increased in women who start the hormones less than 10 years after menopause, but there is increasing risk in women who are more distant from menopause. The study found risk of stroke from hormones does not depend on when a woman starts hormone therapy.
Prentice said there's a high level of interest in the scientific community to continue to shed greater light on women's health in the coming years through the wealth of data supplied by the study. "Even though the intervention phase of the clinical trial has ended, there's still a lot expected from the Women's Health Initiative," he said. "We hope to generate plenty of additional information that will help women make choices conducive to good health."