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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.

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.

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.

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.

An eyeglass cleaning cloth with the WHI 2020 Meeting logo was included in the meeting announcement mailed to all participants. These were mailed between February and March. If you have not received this gift, please contact us by e-mail.

Due to public health concerns, the 2020 WHI Annual Meeting has been cancelled. We hope to hold the event next year and will let you know when plans for a future meeting are made.