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Sickle cell trait in African Americans is not associated with heart attack or coronary heart disease

African Americans have a disproportionately higher rate of coronary heart disease (CHD) mortality and incidence compared to their non-Hispanic white counterparts. This disparity persists even after accounting for health and lifestyle factors associated with CHD, leading Dr. Hyacinth I. Hyacinth of the University of Cincinnati College of Medicine and his team to question whether underlying genetic factors, in particular, sickle cell trait might contribute. Sickle cell trait occurs when an individual inherits one copy of a normal adult hemoglobin gene and one copy of the sickle cell variant from their parents. The prevalence of sickle cell trait in African Americans is about 8%, but 20-35% in Africans. While inheriting two sickle cell variants from each parent results in sickle cell disease, being a carrier of one copy of the variant has been generally regarded as benign. However, emerging research has suggested potential associations between sickle cell trait in African Americans and adverse clinical outcomes, such as chronic kidney disease, elevated C-reative protein levels, pulmonary embolism and even sudden death.

Given the recent associations found between between sickle cell trait and various biomarkers for cardiovascular disease, Dr. Hyacinth and his collaborators conducted an analysis to examine whether sickle cell trait was associated with a higher risk of myocardial infarction (MI) and CHD. They evaluated 23,197 African Americans from five large, population-based cohort studies, including 5,904 women from the WHI study. In their analysis, which included examining data from each study separately as well as combining the data from all five studies, they found that African American individuals with sickle cell trait did not have a higher incidence of MI or CHD and concluded these cardiovascular disorders might not be related to sickle cell trait-related sudden death.

This study was published in JAMA Network Open in January 2021.

Electra Paskett, Ph.D., WHI Principal Investigator and the Marion N. Rowley Professor of Cancer Research at The Ohio State University, had done everything right. As a three-time survivor of breast cancer, once the COVID-19 pandemic struck the United States, she knew it was particularly important to safeguard her health. Like so many of us, Dr. Paskett committed to undertaking all the recommended measures prescribed by public health experts: staying home as much as possible; employing good hygiene through routine handwashing; and, when it was necessary to leave home, donning a mask and remaining conscientious about maintaining physical distance from others.

Despite her best efforts to remain safe, Dr. Paskett came down with COVID-19 last fall, ultimately requiring a five-day hospital stay. In a guest editorial to The Cancer Letter, she movingly chronicles her experience with the virus, from onset of symptoms, to hospitalization, to discharge. She reminds us that recovery from COVID-19 is not always straightforward as, like some patients, she faced aftereffects including “brain fog” and positional orthostatic tachycardia syndrome (POTS). In presenting her experience, Dr. Paskett lists several lessons she learned along the way that may prove helpful to others confronted with a positive COVID-19 test.

A new study led by Dr. Diana Younan at the University of Southern California used data from the WHI Memory Study of Magnetic Resonance Imaging (WHIMS-MRI) to investigate whether fine particulate matter contributes to brain changes predictive of Alzheimer’s Disease. A total of 712 WHI women who had two MRI scans, one in 2005-6 and the other in 2010-11, were longitudinally analyzed. The scans were assigned a score based on patterns of grey matter atrophy that is used as an early biomarker for Alzheimer’s Disease. Air pollution was measured in the form of particulate matter (<2.5 micrometer) exposure and identified using the participant’s home addresses and spatiotemporal modeling that includes data from the US EPA Air Quality System. Dr. Younan and her team found that long term exposure to particulate matter was associated with neuroanatomical changes that increase risk for Alzheimer’s Disease by 24% over five years, even after accounting for demographic, health behaviors, and possible cerebrovascular damage. Their study provides support that particulate matter is associated with neurodegeneration.

These findings were published in the November 18th, 2020 edition of Neurology.

While physical activity has been shown to decrease the risk of hypertension, the impacts of walking on hypertension risk is unclear. Furthermore, studies in older women are sparse despite high levels of hypertension and the popularity of walking as a form of exercise in this population. For his Epidemiology Master of Science thesis, Mr. Connor Miller examined whether walking volume (characterized by frequency, duration, and intensity) and speed was associated with incident hypertension among over 83,000 WHI women followed an average of 11 years. Information about walking and hypertension was collected by survey. Women were placed into 1 of 4 groups based on levels of walking volume (0, >0-3.5, 3.6-7.5, and >7.5 metabolic equivalent hours per week) and speed (<2, 2-3, 3-4, >4 miles per hour). Their analysis found that as walking volume and speed increased, the risk of hypertension decreased. Specifically, the risk of hypertension relative to non-walkers was 0.89 lower in women with the highest walking volume and 0.79 lower among the fastest walkers, even after accounting for covariates such as smoking, diet, and other chronic conditions. The authors concluded that walking should be encouraged as a hypertension prevention strategy in older women.

JoAnn E. Manson, M.D., M.P.H., Dr.P.H., Chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health at Harvard Medical School, and Professor in the Department of Epidemiology at the Harvard T.H. Chan School of Public Health, received the American Heart Association’s (AHA’s) Research Achievement Award at the AHA’s annual Scientific Sessions on November 14, 2020 for outstanding career contributions to cardiovascular research.  Described as “one of AHA’s most distinguished and historic honors”, the Research Achievement Award recognized Manson’s exceptional contributions to population science research, especially in the field of women’s cardiovascular health.

Dr. Manson is a long-term WHI principal investigator (Boston site) and a member of the WHI Steering Committee. She is also a leader or co-leader of several other research studies, including the VITamin D and OmegA-3 TriaL (VITAL); the COcoa Supplement and Multivitamin Outcomes Study (COSMOS); the cardiovascular component of the Nurses’ Health Study; and the KEEPS trial (clinical center in Boston). Her primary research interests include randomized clinical prevention trials of nutritional and lifestyle factors related to heart disease and type 2 diabetes, biomarker predictors of outcomes, and the role of endogenous and exogenous estrogens as determinants of chronic disease in women.

The faculty and staff of the Women’s Health Initiative are deeply saddened to share news of the loss of Susannah Belding, Outcomes Coordinator at the WHI Western Regional Center at Stanford University. Susannah passed away from ovarian cancer on October 16th, 2020.   She fought her disease with her usual grace and dignity up till the end.  Susannah first learned of another recurrence of her ovarian cancer, which she had dealt with in a milder form over eight years ago, on the day before her 50th birthday last July.  Within two weeks, she had learned that it had advanced to a serious life-threatening stage. 

Susannah started working on the Women’s Health Initiative in 2011. She spoke with many, many participants and their proxies from all our clinics (Stanford University, University of California – Davis, University of Nevada – Reno, University of Hawaii, University of California – Los Angeles, Torrance, University of California – Irvine, University of Arizona, and Portland) over the past nine years which she enjoyed immensely. 

Susannah was a very kind, caring person who was loved by all of us and we will all sorely miss her. This brings to focus why we do research and how valuable it is to study and learn from our participants who have challenged cancer.

The School of Public Health (SPH) recently marked its 50th year at the the University of Washington, and in celebration has named “50 Changemakers of Public Health,” a distinction bestowed upon 50 SPH alumni whose work has left an indelible mark on the field. The SPH notes that these alumni represent “leaders, trailblazers, educators, innovators, influencers, and health equity heroes that represent just a slice of the School’s community of more than 10,000 alumni worldwide who are addressing some of the most pressing population health issues of our time.”

Among the alumni named was Dr. Garnet Anderson, principal investigator of the WHI Clinical Coordinating Center and Senior Vice President and Division Director of Public Health Sciences at the Fred Hutchinson Cancer Research Center in Seattle, Washington. Dr. Anderson graduated from the SPH in 1989 with a Ph.D. in biostatistics, and has served in the leadership of the landmark WHI study since 1994. In naming Dr. Anderson, the SPH specifically cites her co-leadership of the initiative’s trial of estrogen and progestin therapy, along with the development of WHI’s vast epidemiological data resources and biorepository, which continue to aid researchers in conducting studies into chronic disease risk factors and prevention.

Age-related physiologic and social changes to eating has been shown to affect diet and nutrition-related diseases, but it is not known whether these changes also affect physical function. A team of WHI researchers led by Dr. Marian Neuhouser examined the relationship of eating barriers on physical function in a subset of 5,910 WHI participants. Eating barriers were both psychosocial-related (i.e., eating alone, poor eating frequency, or financial burdens to obtaining food) and physical (i.e., dentition problems or physical difficulties with cooking or shopping) and were collected by a questionnaire developed by the Nutrition and Energy Balance Scientific Interest Group. Physical function was collected during an in-person clinic visit and included grip strength and components of the Short Physical Performance Battery – a balance test, timed walking speed, and a chair stand test.

Their results showed that all the barriers to eating, with the exception of eating alone, were associated with lower physical functioning. Furthermore, as the number of eating barriers a participant had increased, her level of physical functioning decreased. Since poor physical function is highly predictive of future health events and mortality, these findings emphasize the importance of addressing health and nutrition concerns related to eating and physical functioning in older women.

These findings were published in Preventative Medicine in October 2020.

Updated WHI Investigator Datasets are now available! The data release includes Outcomes and Extension Study follow-up data through February 28, 2020, as well as updated Specimen Results datasets. Additionally, Form 159 data is now available, including a repeat of the sleep disturbance construct, new variables related to symptoms, medications for hypertension and cholesterol, current weight, and age-related macular degeneration.

Dr. Garnet Anderson, principal investigator of the WHI Clinical Coordinating Center and Senior Vice President and Division Director of Public Health Sciences at the Fred Hutchinson Cancer Research Center in Seattle, Washington, was named as a 2020 Fellow of the American Statistical Association (ASA). Fellowship with the ASA is bestowed only upon a very small percentage of the ASA membership on the basis of the candidate’s established reputation and ongoing outstanding contributions to statistical science.

A recent analysis led by Dr. Victor Eng examined nearly 90,000 WHI Observational Study participants to determine the association between smoking history and cancer screening use. Among the women in the study, 53% never smoked, 41% were former smokers, and 6% were current smokers. They discovered that over a mean 8.8 years of follow-up, active smokers were less likely to have obtained a breast, cervical, and colorectal cancer screening relative to women who never smoked. As a consequence of having lower cancer screening usage, women who were active smokers were diagnosed with a higher stages for breast and colorectal cancers. Women who were former smokers were found to have higher usage of breast and cervical cancer screening services compared to those who never smoked. The authors recommend that clinicians emphasize both the use of cancer screening services and smoking cessation for this high-risk group.

This manuscript was published in BMJ Open in August 2020.

WHI researcher, Dr. Marian Neuhouser, has been appointed to the Food and Nutrition Board. The Food and Nutrition Board was established in 1940 within the Health and Medicine Division of the National Academies of Sciences, Engineering, and Medicine. It researches issues related to the U.S. food supply, aids in the development of healthy nutrition guidelines, and evaluates the relationships between consumption, nutrition, and health maintenance and disease prevention. Dr. Neuhouser’s appointment is for a 3-year term, beginning July 1, 2020.

For women aged 65 and older, the US Preventive Services Task Force recommends a bone mineral density, or BMD, measurement to screen for osteoporosis. For younger women, a BMD measurement is recommended for those at higher risk for osteoporosis. There are however no recommendations about the frequency of BMD testing owing to lack of research.

To address this, a team of WHI investigators led by Carolyn Crandall examined the added contribution of repeating a BMD test 3-years after a baseline BMD measurement was collected. In their analysis of nearly 7,500 WHI participants, they found that a follow-up BMD measurement did not improve fracture risk discrimination beyond the baseline BMD assessment. Recognizing that BMD scans uses resources, they concluded that follow-up BMD testing should not be routinely performed in postmenopausal women.

Dr. Crandall’s manuscript was published in JAMA Internal Medicine in July 2020.

Earlier findings published by WHI investigators identified an increased risk of developing breast cancer among clinical trial participants without prior hysterectomy who had received treatment with combination estrogen-plus-progestin hormone replacement therapy over a median of 5.6 years. Conversely, trial participants with prior hysterectomy who underwent estrogen-only therapy for a median of 7.2 years experienced a reduced risk for developing breast cancer. Prior analyses, conducted in 2013 and 2015, noted that these effects endured over a median cumulative follow-up period of 13 years for both therapies.

A recent follow-up analysis, led by WHI investigator Rowan Chlebowski, found that after more than 20 years of median follow-up, the protective effects of estrogen-alone therapy continued to endure, as did the increased risks for developing breast cancer attributed to estrogen-plus-progestin therapy. Despite many years having passed since withdrawal of hormone treatment, the investigators attributed the lasting impacts of each therapy to altered cellular processes in breast tissue affecting cell death (apoptosis). While estrogen-alone therapy is presently not indicated as a prophylaxis for breast cancer due to prior findings suggesting increased risk of stroke and potential influences on hormone-targeted drugs, the authors indicate that other factors may be involved and recommend further work in this arena.

Decisions pertaining to the use and selection of hormone-replacement therapy should be undertaken in partnership with a qualified medical professional and should take into account the numerous personal and health history factors that may influence the benefit/risk calculation of utilizing a particular treatment course.

These findings were published in JAMA in July 2020.

In early July 2020, the National Institute on Aging announced findings linking vision impairment to enhanced risk of developing dementia or mild cognitive impairment (MCI). The study enlisted the participation and study data from 1,061 participants enrolled in the WHI Sight Examination and WHI Memory Study cohorts, and was conducted over the course of the past 20 years.

The study found that risk of cognitive impairment could be correlated with worsening of visual impairment, with the highest risk found among women whose (n = 183) objectively measured vision acuity threshold was 20/100 or worse, followed by 20/80 or worse, then 20/40 or worse. The study also included 206 women who self-reported visual impairment, but it was found that self-reported impairment was not associated with an increased risk for dementia. The investigators note that further research is necessary to identify how specific ophthalmic interventions may influence risk for developing dementia or MCI.

These findings were published in JAMA Ophthalmology in April 2020.

COVID-19 presents an evolving world-wide health and economic crisis.  Many WHI participants are in a high-risk group for experiencing the serious health consequences of this novel coronavirus pandemic if infected. In keeping with the WHI mission to address the major health concerns of older women, the WHI Steering Committee determined that it is critical to assess the impact of this pandemic in the WHI population.  Information from these well-characterized older women could significantly add to the science broadly on the epidemiology of the SARS-CoV-2 infection and adverse outcomes, knowledge and practice of preventive measures, and the impact of social distancing on quality of life. Recognizing that this is a fast moving and complex situation, the WHI Steering Committee approved the development and implementation of a survey instrument to be administered online for WHI participants with email access, and mailed surveys otherwise, augmented with telephone-based interviews for a selected subset of participants, in the June-August 2020.  The survey is meant to stimulate rapid reports on the impact of SARS-CoV-2 and support new ancillary studies within our cohort of women currently 70 years and older.  The RFPs for manuscript proposals or ancillary studies for COVID-19 related research provide additional details. Investigators with interest in these data who missed the June 24 deadline for manuscript proposals may consider applying for access through the usual P&P approval process.  Finally, the WHI will be sponsoring a Scientific Interest Group (SIG), open to all interested researchers, that will seek to catalyze discussion and formation of new study and paper proposals around COVID-19-related research topics.

Dr. Wactawski-Wende is the PI of one of the original 16 vangard WHI clinics since 1993.

“Dr. Wactawski-Wende has made seminal contributions that have significantly impacted health care practice and disease prevention for women in the U.S. and around the world,”
University of Buffalo President Satish K. Tripathi 

Read more…

An article summarizing this recently published paper by Kerryn W. Reding PhD, MPH, RN et al. appeared in OncologyNurseAdvisor.com

The Steering Committee has decided to postpone the May 6-7 meeting because of uncertainties regarding the COVID-19 outbreak. In lieu of an in-person meeting, there will be a series of webinars offered, which will include updates on some of the major WHI-affiliated studies. This series begins Monday, April 27th.  Please see below for a complete schedule of presentations and speakers.  If you have questions, please contact Ellen Kim at the Clinical Coordinating Center.

For those unable to attend, it is expected that videos of the presentations will be posted to the website.

Webinar Schedule 

All times Pacific Daylight Time

​Date and Time ​Presentations and Speakers
(slide decks posted, if available)
Videos and Chat Transcripts
​Monday, April 27th
11:00am-12:00 noon
​LILAC (Garnet Anderson, Bette Caan, and Electra Paskett)
Video (1:18:37)
Chat Transcript (PDF)
​Wednesday, May 6th
10:00am-11:30am
​WHIMS (Steve Rapp) and WHISPER (Laura Baker)*
Video (1:23:00)
Chat Transcript (PDF)
​Thursday, May 7th
10:00am-11:30am
​WHISH (Marcia Stefanick) and OPACH (Andrea LaCroix)*

Video (1:31:56)
Chat Transcript (PDF)
​Thursday, June 11th
10:00am-11:00am
​COSMOS (JoAnn Manson and Howie Sesso) and
WHI COVID-19 Study Update
(Garnet Anderson and Sally Shumaker)

Video (0:46:42)
Chat Transcript (PDF)

*These webinars will also incorporate poster presentations from abstracts originally submitted for the 2020 meeting.

Poster Abstracts Selected for Webinar Presentation

Please click here to read the selected poster abstracts.

Date of PresentationPresenterInstitutionTitle
April 27Tracy E. CraneUniversity of ArizonaDietary Patterns and Fatigue after a Cancer Diagnosis: Results for Women’s Health Initiative
April 27Mandana Kamgar, MD, MPHDepartment of Medicine, Division of Oncology, Medical College of WisconsinPeripheral Neuropathy after Breast Cancer: an Analysis of Data from the Women’s Health Initiative Life and Longevity After Cancer Cohort.
May 6Emily Gower and Jonathan FixUNCRisk Factors for Missed Influenza and Pneumococcal Vaccination amongst Participants in the Women’s Health Initiative
May 6Kathleen HaydenWake HealthClonal Hematopoiesis of Indeterminate Potential and the Risk of Mild Cognitive Impairment or Probable Dementia in the Women’s Health Initiative Memory Study
May 6Iris Leng, MD, PhDWake ForestIs there an association between baseline macro nutrients intake and changes in cognition? Results from the Women’s Health Initiative Memory Study (WHIMS)
May 6Margaret L. ScalesWake ForestWomen’s Health Initiative Sleep HyPoxia Effects on Resilience (WHISPER): Consent and Sleep Assessment Enrollment and Retention Success.
May 6Chrisandra Shufelt, MD, MS, FACP, NCMP Bilateral Oophorectomy vs Ovarian Conservation at the Time of Hysterectomy and All-cause Mortality: Women’s Health Initiative Observational Study (WHI-OS)
May 7Anna Batorsky / Nora FranceschiniNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium; TOPMed MESA Multi-Omics Working GroupDifferential DNA Methylation associated with kidney function across three ethnic groups.
May 7Bernhard HaringUniversity of Wurzburg, GermanyBlood Pressure Variability and Risk of Heart Failure in Postmenopausal Women. Results from the Women’s Health Initiative
May 7Purva JainUCSDStanding time with and without ambulation and mortality over 6 years of follow-up: the WHI OPACH Study
May 7Marian Neuhouser / Lesley TinkerFHCRCUnderstanding the role of nutrition in health promotion and disease prevention in the Women’s Health Initiative (WHI) using biomarkers
May 7Benjamin T. Schumacher, MPH Accelerometer-Measured Daily Steps and Incident Fall Risk in Older Women: The OPACH Study
May 7Sylvia SmollerEinsteinDiastolic Blood Pressure Levels And Mortality Among Older Women: Results From The Women’s Health Initiative Long Life Study