Well then create exact protocols to address the problem. Guidelines like control hypertension are not good enough.What objective level do you start at? What dose do you prescribe? What level do you get to?
Cardiologists have ‘big role’ to play in preventing decline in brain health
In recent years it has become clear that heart health and brain health are linked.
Data from various studies have indicated that tighter BP control is associated with improved cognitive outcomes.
Source: Rush University System for Health. Reprinted with permission.
“We learn more and more about the connection between the heart and brain every day — I always tell my patients that what is good for your heart is good for your brain,” Jeff D. Williamson, MD, MHS, chief of the section of gerontology and geriatric medicine in the department of internal medicine at Wake Forest School of Medicine in Winston-Salem, North Carolina, told Cardiology Today. “We know for certain that controlling blood pressure reduces the risk for heart disease and heart failure and reduces the risk for heart attack and death from heart attack. During the past few years, emerging science has shown this same heart-healthy behavior, controlling blood pressure, is also good for the brain. Preventing and treating hypertension reduces the risk for early dementia and certainly reduce the chance for stroke dramatically. There is a strong connection here.”
In the SPRINT MIND study, patients assigned intensive BP control had a significant reduction in risk for mild cognitive impairment compared with those assigned standard BP control (18.3 cases per 1,000 person-years vs. 14.6 cases per 1,000 person-years; HR = 0.81; 95% CI, 0.69-0.95). The same was observed in the risk for combined rate of either probable dementia or mild cognitive impairment (24.1 cases per 1,000 person-years vs. 20.2 cases per 1,000 person-years; HR = 0.85; 95% CI, 0.74-0.97).
Other data from the PESA cohort showed that hypertension and other CV risk factors were associated with cognitive impairment in patients with atherosclerosis.
Several societies, including the American Heart Association and the American Stroke Association, have devoted funding in recent years to further study the connections between heart health and brain health.
Carl J. Pepine, MD, MACC, Cardiology Today Chief Medical Editor, added that participating NIH Institutes and Centers are inviting applications to expand existing awards that are not currently focused on Alzheimer’s disease and its related dementias (AD/ADRD) to allow the research to develop such a focus. This represents a considerable investment of public funds, he said. Multiple health determinants (social, environmental, biological/genetic/epigenetic, psychosocial, economic, health care, etc) contribute to AD/ADRD risk, incidence, age of onset, morbidity and mortality among cohorts with CVD and health disparity populations. Just how these contribute to CVD and AD/ADRD risk, resilience and adverse outcomes in these various populations across the life course is critically important, Pepine said.
Cardiology Today spoke with cardiologists and neurologists about how heart health and brain health are connected, the impact on counseling patients, and what this connection means for future collaborations between the cardiology and neurology communities.
The connection explained
The connection between heart health and brain health is not a new concept, but experts said there is still much more to be learned.
“As scientists and clinicians, we shouldn’t be surprised by the connection. Mechanisms that impact the risk for heart disease, such as circulatory function and epithelial integrity in blood vessels, are exactly the same mechanisms that helps us preserve brain function from both stroke and dementia,” Williamson said.
The AHA Stroke Council issued a scientific statement in June to aid primary care physicians in identifying and assessing modifiable risk factors for cognitive decline, including factors that also affect the heart such as hypertension, diabetes, lack of physical activity, obesity, poor diet, hyperlipidemia, smoking and excessive alcohol use.
Annabelle Santos Volgman, MD, FACC, FAHA, professor of medicine and senior attending physician at Rush Medical College and Rush University Medical Center and medical director of the Rush Heart Center for Women, and others have done work showing how the same preventive measures that improve heart health can also improve brain health.
“I have been practicing cardiology for more than 30 years and am also an electrophysiologist by training. During my career, I have diagnosed many patients with arrhythmias, especially atrial fibrillation,” Volgman, who is also a member of the Cardiology Today Editorial Board, said in an interview. “In the beginning of this work, we noticed there were a lot of men and women with atrial fibrillation, which is associated with the risk for stroke. My mother had a stroke, and it ruined her life and altered our family life, which is what led me to be passionate about decreasing the risk for stroke in every individual. We know that stroke leads to cognitive impairment, but it also goes above and beyond stroke.”
Volgman said her patients who never experienced a stroke would complain of cognitive impairment.
“They thought it was the medications that I had prescribed them that was causing it,” Volgman said. “We would perform genetic testing on patients at the Rush Heart Center for Women, and if genetic tests were negative, we would then perform APOE genotyping testing. We know that an isoform of APOE is a marker for early predisposition to Alzheimer’s disease. When we began receiving positive results, I worried that these patients were not just at risk for heart disease but also for Alzheimer’s disease, and so I started referring these patients to my colleague, Neelum T. Aggarwal, MD, FAMWA, and we became entrenched in this field together.”
Aggarwal, a cognitive neurologist in the department of neurological sciences at Rush Alzheimer’s Disease Center at Rush University Medical Center, said she sees many women who are diagnosed with Alzheimer’s disease who also have CVD.
“This connection piqued my interest, and when Dr. Volgman referred these patients to me, I had it in the back of my mind that if we could control their CV risk factors, then maybe we could prevent the development of dementia,” she said.
Aggarwal later joined the Rush Heart Center for Women, serves as the Center’s Research Director, and began formally screening cardiology patients with memory concerns.
“This collaboration has allowed us to introduce concepts to our patients about the link between brain health and heart health and introduce these patients to clinical trials, which are so important,” Aggarwal said.
“Through the SPRINT MIND clinical trial, researchers found that when blood pressure was lowered and intensely monitored, the white matter hyperintensities, that we often see on scans and monitor in neurology, were less, which is a good indicator that we can modify the negative effects from the brain through blood pressure management.
“Through SPRINT MIND, we are also continuing to learn that changes in cognition can be modified if we intensely modify blood pressure management in these patients,” she added. “SPRINT MIND in itself has been pivotal for how we are thinking about blood pressure and cognition, and it gives the practicing clinician, and especially the cardiologist and the primary care physician, good reason to consider it and to consider talking about brain health when they’re talking about blood pressure management with their patients.”
Collaboration is key
The heart-brain connection necessitates collaboration between cardiologists and neurologists, Deborah A. Levine, MD, MPH, associate professor of medicine and director of the Cognitive Health Services Research Program at University of Michigan in Ann Arbor, told Cardiology Today.
“Many vascular risk factors can cause problems with both brain health and heart health. For example, atrial fibrillation increases the risk for cognitive decline. Through collaboration between cardiologists and neurologists, we can make larger strides in improving patient care and research then we would without collaboration,” Levine said. “Cardiologists could include the goal of maintaining brain health as one of the motivating factors to diagnose and treat vascular risk factors in their patients, to exercise regularly and to eat healthy, in addition to maintaining cardiovascular health and avoiding the risk for cardiovascular events such as stroke and heart attack.”
In the PESA study, researchers examined the association between cerebral metabolism with CV risk factors and atherosclerotic plaque burden in carotid and femoral arteries among 547 asymptomatic participants with evidence of subclinical atherosclerosis (mean age, 50 years; 82% men).
Results showed global brain 18F-fluorodeoxyglucose uptake had an inverse correlation with 30-year Framingham Risk Score, which researchers determined was mainly driven by the presence of hypertension. Additionally, carotid plaque burden was inversely associated with global brain 18F-fluorodeoxyglucose uptake, even after adjustment for 30-year Framingham Risk Score.
“The more we learn that the same behaviors and interventions in heart health can reduce the risk for loss of brain health, then the more powerful our message becomes,” Williamson said. “Cardiologists should discuss with their patients that what is being done for their heart is also good for their brain and can reduce their risk for Alzheimer’s disease and related dementia in the future. Similarly, neurologists, family practitioners and general internists should relay to their patients that what they are doing to lower their chance for dementia and Alzheimer’s disease is also good for their heart. We all need to be giving the same messages to patients, which will add an incentive to our patients to be even more careful in following risk prevention strategies.”
Alan S. Maisel, MD, emeritus professor of medicine at the University of California, San Diego, and a co-founder of the Evermore Medical Foundation, said clinicians should tell their patients that “if they want to live into their 70s and 80s and not experience issues with brain health, then they better start paying attention to good blood pressure control.”
“We know how difficult it can be to get our middle-aged or older-aged patients to take their blood pressure medicine. But now, we can definitively tell them that we know that uncontrolled blood pressure will hasten cognitive decline and even possibly lead to dementia or other diseases, like Parkinson’s disease,” Maisel said. “This information may lead to better compliance with taking their medications. We must be aware of the ever-growing importance between heart health and brain health as neurologists and cardiologists.”
Volgman agreed but said that in a busy cardiologist’s office, discussions about the link between heart and brain health may be missed.
“Some do not realize the connection is something that we should be addressing,” Volgman said. “Unfortunately, right now, we do not have very many good trials on this, which is why Dr. Aggarwal and I are involved in a variety of different trials on the topic.”
One ongoing NIH-funded trial is comparing physical activity or brain health games, physical activity alone, brain health games alone or neither intervention (usual care) among 250 women at Rush Heart Center for Women.
“We will follow participants for 6 months and test their memory function. We are currently halfway through the study, and I am excited about this work,” Volgman said. “This could give us ammunition if the data are positive for physical activity because we know that observational studies have shown that physical activity is associated with less cognitive dysfunction, but this has never been tested in a randomized controlled study. Hopefully, we will get interesting results so that we can emphasize to our patients the importance of physical activity on cognitive function.”
COVID-19 and the brain
When the COVID-19 pandemic hit, much was learned about the impact of the virus on the heart and the brain. An ever-growing amount of research is underway looking into the heart-brain connection among individuals with COVID-19 long-hauler syndrome.
“This is a story that is still to be written and understood. We use the term ‘long-hauler,’ but we haven’t had a long-haul yet, so we really don’t know the long-term impact just yet,” Williamson said. “There is a lot of conjecture and a lot of very important science being done to understand what the long-term effects of COVID-19 are, but we are just entering the cusp of understanding it all. Patients certainly tell me that they are still feeling symptoms from COVID-19, but we are just beginning to understand what the biology of that is, and we need to be careful to not speak before we understand. I can conjecture that just as COVID-19 has had vascular effects on the heart and vascular effects on the kidneys, there are likely vascular effects on the brain as well as is the case for many viral pathogens. This is where the focus of scientific work needs to be in the next 5 years.”
Maisel agreed.
“There is a lot of ongoing research on COVID-19, especially with treatments, but we have to understand the etiology of the ‘long-hauler,’ which we still do not know,” Maisel said.
Maisel and colleagues are conducting an ongoing study examining the use of ivabradine (Corlanor, Amgen) in patients with COVID-19 long-hauler syndrome.
“Ivabradine seems to work in patients with tachycardia, and so we think it will work for individuals with post-COVID-19 tachycardia,” he said. “There are other already available agents that we plan to study as well. We still need to explore the pathophysiologic mechanisms, but we do have treatments to test for these patients.”
The ongoing INSPIRE study is another trial that aims to learn more about the long-term health effects of COVID-19.
“We started to work with a team here at Rush University on the CDC-funded INSPIRE study, which is a multisite trial of patients who had COVID-19 and want to be followed for potential long-hauler syndrome,” Aggarwal said. “The cognitive ‘brain fog’ seems to be one of the bigger issues that people are facing once other symptoms go away.”
Other neurological symptoms observed among COVID-19 long-haulers, including loss of smell and taste, suggest the central nervous system is affected, Volgman said.
“Years ago, when researchers were studying polio, they had no idea the types of negative neurological complications that these individuals would have in the future,” she said. “This is the message that we need to give to people who do not want to get vaccinated. They may not die, but we do not know what neurological or other organ complications they may experience long term.”
‘Prioritizing the connection’
Experts told Cardiology Today that there have recently been greater efforts to address the heart health and brain health connection.
“The American Heart Association is prioritizing the connection between the brain and heart, which will be a good resource for practicing cardiologists going forward,” Levine said. “We still do not know at what age to start treating high blood pressure to prevent dementia, and we also need to know whether intensively lowering blood pressure to optimal levels in adults with low or moderate cardiovascular risk will reduce the risk for cognitive decline and dementia later on in life.”
Knowing this could change patient care and policy, Levine added.
“We do not have evidence that intensive blood pressure lowering can improve cognitive outcomes later in life for low- to moderate-risk groups,” Levine said. “Most adults have low or moderate cardiovascular risk, and it is possible that intensive blood pressure lowering could be beneficial for adults with low or moderate cardiovascular risk to prevent the combined endpoints of cardiovascular events and cognitive decline and dementia. My group is currently working on this research, which could change clinical practice.”
Aggarwal and Volgman will host a session on the connection between heart and brain health at the American College of Cardiology Scientific Session in April.
“We need to start thinking about research models that will put specialists together where we are working collaboratively and where we are able to bring best practices together, because ideas come when we collaborate in close proximity,” Aggarwal said. “We also have to consider the types of trials we are designing. Representation in clinical trials is important, not only with diversity by race and ethnicity but also by sex and gender and making sure that the trials that we embark on are inclusive. If we think about this with our cardiology colleagues and neurology colleagues together, we can design better trials.”
Volgman agreed.
“Research is needed looking into treatments to help decrease cognitive decline progression. This is not something that we as cardiologists will solve alone, but our big role is to ensure that we are treating cardiovascular disease so that it does not affect the brain,” Volgman said. “This includes atherosclerosis and blood pressure control, and we still need to figure all of that out, and then, of course, stroke reduction from the atherosclerosis and atrial fibrillation, which will be our main contribution to decreasing cognitive impairment in our patients. The field is ultimately richer when we work together.”
- References:
- Cortes-Canteli M, et al. J Am Coll Cardiol. 2021;doi:10.1016/j.jacc.2020.12.027.
- Lazar RM, et al. Stroke. 2021;doi:10.1161/STR.0000000000000367.
- Williamson JD, et al. JAMA. 2019;doi:10.1001/jama.2018.21442.
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