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Katya Ravid, here in her lab, will lead a new center tasked with uncovering why some cancer patients are at a higher risk for developing cardiovascular issues after treatment.
Why Are Black Cancer Patients at Higher Risk for Blood Clots?
New BU center will examine link between cancer and cardiovascular diseases, with special focus on understanding and preventing health disparities
Everyone is at risk for developing a blood clot at some point in their lives—a condition that affects an estimated 900,000 people in the United States each year—but for cancer patients, the odds are higher.
Certain types of cancers drive up the risk—some blood cancers, as well as cancers of the pancreas, stomach, brain, lungs, uterus, ovaries, and kidneys—and cancer therapies can also make blood clots more likely. One out of seven cancer patients will die because of blood clotting.
And for reasons that aren’t yet clear, some Black cancer patients are at even higher risk of developing blood clots than non-Black patients.
A team at Boston University and Boston Medical Center (BMC), led by cardiovascular and disease expert Katya Ravid, has received funding from the American Heart Association (AHA) to investigate the different ways heart and blood diseases, including blood clots, emerge in cancer patients—and why the condition is more common among certain groups of patients.
“This [study] may help to better predict which cancer patients are at risk for blood clots, and to identify treatments to prevent blood clotting in some types of cancers,” says Ravid, the Barbara E. Corkey Professor of Medicine.
The research team, codirected by Vipul Chitalia, associate professor of medicine, has received more than $2.7 million from the AHA to open a new center at BU and BMC, called Cancer-Associated Thromboembolism as Affected by Health Disparities, which will closely examine the links between cancer and diseases of the heart and lungs. According to the AHA, there are more than 17 million cancer survivors in the United States as of 2020, making cardio-oncology a critical research area.
Ravid and a team of scientists are planning to use data from the Veterans Health Administration and BMC to investigate the biological mechanisms that cause blood clots, and to better understand health disparities that can increase the risk for blood clotting in people with cancer, including social factors like living conditions, diet, and race.
The risk of developing blood clots varies depending on the cancer type, something the team will dig into further during the four years of research. Combing through a huge amount of data—from 22 million veterans, 1.7 million of whom developed cancer—the researchers hope to find some answers. They will run cause-and-effect analyses using the data, Ravid says, and the team plans to use machine learning and artificial intelligence techniques to generate an accurate risk model for developing blood clots.
As a part of the award funding, BMC is partnering with Tougaloo College, a historically Black liberal arts college in Jackson, Mississippi, to develop a training program in cardio-oncology, as well as train postdoctoral fellows in this new field.
“It’s important that we pass on knowledge gained through this center, at the scientific level and professional level, to budding scientists,” Ravid says. “To me that’s part of the mission of the center.” n
Researchers Receive $20M NIH Grant to Study Protection from Alzheimer’s Disease
Malaria Vaccine—the First Ever to Immunize Against a Parasitic Infection—Gets Green Light from WHO
Why are some 100 plusyear-old men and women as cognitively alert and intact as peers 30 years younger? Why has Alzheimer’s disease (AD) not impacted them?
Thomas Perls, MD, MPH, FACP, professor of medicine, and Stacy Andersen PhD, assistant professor of medicine, and their colleagues seek to learn more about these centenarian cognitive “super-agers” thanks to a $20 million grant from the National Institute on Aging and the McKnight Foundation.
Along with George Murphy, PhD, associate professor of medicine and codirector of the Center for Regenerative Medicine, Perls and Andersen will study the resilience against AD in centenarians and their offspring.
Four and a half million people in the US currently have AD. With the baby boomer population aging, if nothing is done to significantly impact this disease, this number will increase more than threefold—to 14 million by 2040. It is the most common cause of dementia and the fifth-leading cause of death in adults older than 65. It slowly destroys memory and thinking skills and eventually, the ability to carry out the simplest tasks. The total healthcare costs for AD treatment in 2020 is estimated at $305 billion, with the cost expected to increase to more than $1 trillion as the population ages.
Centenarians delay disabilities into their mid-90s. Some remain cognitively intact despite extreme exposure to the strongest risk factor for cognitive impairment and AD—aging. “Despite the fact that aging is one of the strongest risk factors for cognitive impairment, aging in centenarians is typified by resilience and, in some cases, resistance to aging-related disability into the mid-90s,” explains Perls, who also is founder and director of the New England Centenarian Study.
By studying approximately 500 centenarian cognitive super-agers, Perls and his team hope to identify the protective factors and underlying mechanisms that offer resilience— and, in some cases, even resistance—to cognitive decline and dementia.
“We aim to discover genetic variants and biological mechanisms that protect against aging-related brain changes and AD and then translate those findings into therapeutic strategies and targets,” Perls says.
Other institutions participating in this multidisciplinary research include Albert Einstein College of Medicine, Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Columbia University, University of California Los Angeles, and the University of Utah. n
A child gets a malaria vaccination at Yala Sub-County hospital, in Yala, Kenya, on October 7, 2021.
Malaria and infectious disease expert says the vaccine could save countless children’s lives in sub-Saharan Africa—but he still has a few concerns
In a historic move, the World Health Organization (WHO) has announced their recommendation for widespread use of the first-ever malaria vaccine—green-lighting a vaccine that has the potential to prevent hundreds of millions of cases of malaria and thousands of deaths in children worldwide each year. It’s the first time a vaccine will be rolled out to combat infection caused by a parasite, rather than a virus.
Malaria is a serious mosquito-borne infection, caused by a parasite that passes through mosquito bites into humans, that is found across broad geographic regions of the world, but is most prevalent in sub-Saharan Africa. In 2019, there were 229 million cases of malaria globally and 409,000 deaths, mostly impacting children who live in the sub-Saharan African nations where rates of malaria are especially high, according to the Centers for Disease Control and Prevention.
As part of a pilot program, more than 2.3 million doses of the vaccine, developed by Glaxosmithkline and called Mosquirix, have already been administered to over 800,000 children in three countries—Kenya, Malawi, and Ghana, all of which are places where malaria is rampant. The vaccine is given in three doses to children between 5 and 17 months of age, followed by a fourth dose about 18 months later.
To find out what the Mosquirix vaccine means for global health, we reached out to BU infectious disease expert Davidson Hamer, who has treated patients with malaria and has worked to help improve tropical disease control strategies in countries around the world. He helped run the Boston University Malaria Project (ZAMBUMP) between 2001–2005, which helped strengthen surveillance programs to reduce malaria in Zambia and to establish the most effective treatment and prevention guidelines for the region’s doctors and patients. Hamer has also worked closely with the WHO to research and improve public health guidelines for other serious illnesses around the world. He is a professor of global health and medicine at BU’s School of Public Health and School of Medicine, and a faculty member at BU’s National Emerging Infectious Diseases Laboratories (NEIDL).
Q&A with Davidson Hamer
Can we put this milestone into the broader context— why is the approval of this malaria vaccine a big deal? Hamer: I’ve been watching this vaccine develop for the last 10 to 15 years and doing malaria research for about 15 years, mostly focusing on malaria control strategies in regions with high transmission. There have been other [malaria] vaccines in development—[but] this one is the one that has gone the furthest [by gaining] approval from WHO. Having a malaria vaccine is the holy grail of malaria control.
How does this vaccine work? It [builds immunity by stimulating production of antibodies against] a protein that is [given off] the parasite when it enters the bloodstream. Ideally, a vaccine would work shortly after the bite from the mosquito, to prevent parasites [from] replicating in the bloodstream…[because] we want to prevent large amounts of parasites [from being] in the bloodstream in the first place. This vaccine works later [on], after the infection is [already] in the bloodstream. The parasites [that cause malaria] have a complex life cycle and are constantly mutating … There are five major species of the [malaria-causing] parasite but Plasmodium falciparum is the major one that this vaccine targets.
Do people acquire natural immunity after they’ve had malaria? The complexity of the immune response [to malaria] is something we don’t fully yet understand. In [regions where the malaria-causing parasite is prevalent], after someone has multiple episodes of malaria early in life, they develop only partial immunity. We have seen that, if you take a sample of blood from an infected person, they may have three or four different strains [of the disease] at one time…so all of this has made developing the vaccine a challenge.
Why are children more susceptible to getting infected with malaria? Children are at high risk because they haven’t developed an immune response [to malaria] yet. It’s similar to when travelers visit places and encounter new parasites or bacteria they’ve never been exposed to before. Malaria will affect anyone of any age, if they have not been exposed to it before. An estimated 90 percent of all malaria deaths [worldwide] happen in subSaharan Africa, and [those who die] are mostly children infected from Plasmodium falciparum. You can develop partial immunity from episodes early in life…but if you have not been exposed, then the infection could lead to severe malaria, and cause anemia and other serious problems, and it kills.
How are people currently treated for malaria? The three major pillars for malaria control are bed nets treated with insecticide, insecticide on the walls of dwellings, and having access to effective treatment. The most widely used treatment is called artemisinin-based combination therapy, or ACT, which is a family of drugs developed from a Chinese herb over 1,000 years old. It is still amazingly effective on all strains of malaria, though it has shown some drug resistance in South Asia. Between 2003 and 2006, ACT became the first-line treatment for malaria in every country in Africa that has intense transmission. Can you explain how safety is determined for a vaccine like this one? The biggest way safety is determined is through controlled clinical trials. [This vaccine underwent a] phase three clinical trial between 2009 and 2011, which was a controlled trial. The [vaccine developers] then chose three countries—Kenya, Malawi, and Ghana—to test real-life effectiveness in a pilot program starting in 2018.
What is the potential impact of this malaria vaccine being widely available to communities that need it? I think this is going to be an additional tool that is going to help us reduce deaths and illness. It’s not the solution to fully eliminating malaria, but it’s a big step forward. I have a couple of concerns, and I think we need to look at using this in conjunction with other innovative approaches that researchers have been studying. I want to see more of their results from the pilot study to learn more about the safety profile. Even if the effectiveness isn’t amazing, anything over a 30 percent reduction in deaths and severe illness is going to have a big impact.
What are your concerns? This is a vaccine that uses an adjuvant— which is a substance that strengthens the quality and intensity of the immune response. This adjuvant is extracted from a certain type of tree only found in Chile. Since extracting it from these trees is the only source, it raises the question, are they going to be able to produce the amount of doses needed if countries accept this into their regular vaccine program?
Now that the WHO has recommended its use, what has to happen next for the vaccine to become more widely available? Countries are going to need to decide if the effectiveness is worth the added benefit. I think a lot of countries that have very intense transmission rates will probably seriously consider it. That requires funding in countries that are considering adding it to their national vaccination programs for it to become widely available. The work for other malaria vaccines will continue, and it [will be] exciting to see which countries will take this up in their national vaccination programs. n
Walking Is Good, but Moderate to Vigorous Exercise Boosts Fitness Three Times More
With help from 2,000 Framingham Heart Study participants, BU researchers explored how much being sedentary, walking, and routine exercise impacts fitness
Exercise is healthy. That is common knowledge. But just how rigorous should that exercise be in order to really impact a person’s fitness level? And, if you sit all day at a desk, but still manage to get out and exercise, does that negate your six, seven, or eight hours of sedentary behavior?
These were the sort of questions Matthew Nayor, MD, MPH, assistant professor of medicine, and his team set out to answer in the largest study to date aimed at understanding the relationship between regular physical activity and a person’s physical fitness.
Their findings, which appear in the European Heart Journal, came from a study of approximately 2,000 participants from the Framingham Heart Study. They found that bouts of moderate to vigorous exercise—working out with more intensity than, say, walking 10,000 steps over the course of a day—drastically improved a person’s fitness, compared to milder forms of exercise.
“By establishing the relationship between different forms of habitual physical activity and detailed fitness measures,” Nayor says, “we hope that our study will provide important information that can ultimately be used to improve physical fitness and overall health across the life course.”
Nayor is also a cardiologist specializing in heart failure at Boston Medical Center. We caught up with Nayor to explain the results of the study and what people should know about exercise in relation to fitness.
Q&A with Matthew Nayor
People might see a study that finds that moderate to vigorous activity is the best way to improve fitness, and think, isn’t that obvious? But your research is more specific than that, so can you tell us what was surprising or perhaps revealing about your work? Matthew Nayor: While there is a wealth of evidence supporting the health benefits of both physical activity and higher levels of fitness, the actual links between the two are less well understood, especially in the general population (as opposed to athletes or individuals with specific medical problems). Our study was designed to address this gap, but we were also interested in answering several specific questions.
First, we wondered how different intensities of physical activity might lead to improvements in the body’s responses during the beginning, middle, and peak of exercise. We expected to find that higher amounts of moderate-vigorous physical activity, like exercise, would lead to better peak exercise performance, but we were surprised to see that higher intensity
activity was also more efficient than walking in improving the body’s ability to start and sustain lower levels of exertion.
We were also uncertain whether the number of steps per day or less time spent sedentary would truly impact peak fitness levels. We found that they were associated with higher fitness levels in our study group. These findings were consistent across categories of age, sex, and health status, confirming the relevance of maintaining physical activity [throughout the day] for everyone.
Second, we asked, how do different combinations of the three activity measures contribute to peak fitness? Intriguingly, we observed that individuals with higher-than-average steps per day, or moderate-vigorous physical activity, had higher-than-average fitness levels, regardless of how much time they spent sedentary. So, it seems that much of the negative effect that being sedentary has on fitness may be offset by also having higher levels of activity and exercise.
Our third question was, are more recent physical activity habits more important than previous exercise habits in determining current levels of fitness? Interestingly, we found that participants with high activity values at one assessment and low values at another assessment, performed eight years apart, had equivalent levels of fitness, whether or not the high value coincided with the fitness testing. This suggests that there may be a “memory effect” of previous physical activity on current levels of fitness.
A lot of people wear Fitbits or their Apple Watch to track their daily step counts these days, and they might think, hey, I did 10,000 steps today! But it sounds like your research suggests that while walking is valuable, it’s not the same as exercise? Well, I think we need to be a little careful with this interpretation. It is important to note that higher steps were associated with higher fitness levels in our study, which is reassuring, especially for older individuals or those with medical conditions that may prohibit higher levels of exertion. There is also ample evidence from other studies that higher step counts are associated with a host of favorable health outcomes. So, I would not want to dissuade people from following their step counts.
However, if your goal is to improve your fitness level, or to slow down the inescapable decline in fitness that occurs with aging, performing at least a moderate level of exertion [through intentional exercise] is over three times more efficient than just walking at a relatively low cadence.
Where is that line? When does exercise go from moderate to rigorous, for people who might be wondering if they are doing enough? We used definitions from prior studies that categorized a cadence of 60–99 steps/minute as low-level exertion, while 100–129 steps/minute is generally considered to be indicative of moderate physical activity and greater than 130 steps/minute is considered vigorous. These step counts may need to be a bit higher in younger individuals. The Physical Activity Guidelines for Americans recommend 150–300 minutes/week of moderate intensity or 75–150 minutes/ week of vigorous intensity exercise. However, this upper limit is really a guidance meant to encourage people to exercise. In our study, we did not observe any evidence of a threshold beyond which higher levels of activity were no longer associated with greater fitness.
Can you explain in some detail how the results of your study were achieved, studying participants in the Framingham Heart Study? Thank you for this question and for the opportunity to thank the Framingham Heart Study participants. It is only through their voluntary participation over three generations now that studies such as ours are possible. For our study, we analyzed data from participants of the Third Generation cohort (literally the grandchildren of the original participants, in many cases) and the multiracial sample. At the most recent study visit in 2016–2019, we performed cardiopulmonary exercise tests (CPETs) on stationary cycles for comprehensive fitness evaluations. CPETs are the “gold standard” assessment of fitness and involve exercise testing with a face mask or mouthpiece to measure the oxygen that is breathed in and the carbon dioxide that’s breathed out during exercise. You may have seen professional endurance athletes (such as cyclists) performing similar tests during training sessions. Participants also took home accelerometers, which were worn on belts around their waist for eight days after their study visit. Accelerometers were worn at the recent study visit and at the prior visit eight years earlier, and information was compared.
Matthew Nayor, MD, MPH
Boston Medical Center cardiologist and assistant professor of medicine
Do you have your own exercise routine, where you are consciously thinking of moderate versus rigorous, and trying to find that balance? Well, I’m certainly not a competitive athlete, but I try to stay active. One aspect of our results that I keep coming back to is the finding that higher levels of sedentary time can be offset by dedicated exercise. I find this reassuring—especially during the pandemic when many of us are spending even more time seated in front of a computer—that my daily run or Peloton class is serving to at least preserve my fitness level. n
New Online Prediction Tool Could Reduce Breast Cancer Deaths Among Black Women
BU researchers have developed a breast cancer risk model to meet critical gap in identifying the cancer earlier in Black women
In the United States, Black women are more likely to have breast cancer at earlier ages and with a worse prognosis than white women. Despite this, there is a critical gap in breast cancer risk prediction models for Black women. Breast cancer risk prediction tools are used by clinicians to identify women at higher-than-average risk of breast cancer for early or more frequent screening by mammography and other modalities. But until now, there’s been a lack of prediction tools tailored to Black women.
That’s finally poised to change. Researchers at Boston University’s School of Public Health (BUSPH) and Slone Epidemiology Center have developed and evaluated a risk prediction model for breast cancer in Black women, suitable for use in primary care settings in the United States. The researchers described and evaluated the model in a recent report published in the Journal of Clinical Oncology.
“Because US Black women have a disproportionately high rate of breast cancer deaths, improvement in early detection of breast cancer in this population is critical, especially in young Black women who have not yet reached the ages at which mammographic screening is typically begun,” says study corresponding author Julie Palmer, ScD, a BUSPH professor of epidemiology, director of BU’s Slone Epidemiology Center, and the Karin Grunebaum Professor in Cancer Research at the BU School of Medicine.
Palmer and colleagues used epidemiologic data from three case-control studies of Black women from various regions of the United States to build a new risk prediction model. They tested the model using 15 years of follow-up data from 51,798 participants in BU’s Black Women’s Health Study and found that it was well calibrated. Discriminatory accuracy, which reflects how well a model predicts risk for an individual woman, was similar to that of the most frequently used questionnaire-based breast cancer risk prediction models for white women—and was most accurate for women under age 40.
The researchers say the online tool is simple to use through a website, and all the information required can be obtained from the women themselves with a few questions.
“This new tool for personalized prediction of breast cancer risk in Black women can be easily used by primary care providers to guide screening recommendations and/or referral for genetic testing, particularly for young Black women, thus leading to earlier diagnosis and reduced mortality,” says Palmer.
Women can also use the tool themselves and input their own information to calculate their five-year breast cancer risk, says study senior author Ludovic Trinquart, a BUSPH adjunct associate professor of biostatistics and director of the Center for Clinical Trials at Tufts Medical Center.
“We believe that it’s best to discuss breast cancer risk and screening with a healthcare provider, and our tool could help women have a part in shared decisionmaking,” Trinquart says. n “Because US Black women have a disproportionately high rate of breast cancer deaths, improvement in early detection of breast cancer in this population is critical, especially in young Black women who have not yet reached the ages at which mammographic screening is typically begun.”
