Eau Claire, Wis. — Most people have heard of heart attacks occurring because of a blocked coronary artery. But the body has two types of artery systems: the coronary artery system, which relates to the heart, and peripheral artery system, which involves the arteries carrying oxygenated blood to the arms, legs, brain and the rest of the body.

"Just like coronary arteries, peripheral arteries can become diseased," says Michel Barsoum, M.B., Ch.B., a cardiologist and vascular medicine specialist at Mayo Clinic Health System in Chippewa Falls, Eau Claire and Rice Lake, Wisconsin. "This condition, called peripheral artery disease, or PAD, narrows arteries and reduces blood flow due to a buildup of fatty and calcium deposits on the artery walls."

This can cause claudication, which is muscle pain and cramping when a person is active but usually disappears after a few minutes of rest.

Risk factors for peripheral artery disease

"So who is at risk of peripheral artery disease? People who smoke or have diabetes at any age are at the greatest risk," says Dr. Barsoum.

Other risk factors include:

• Body mass index over 30.
• Family history of PAD, heart disease or stroke.
• High blood pressure.
• High cholesterol.
• Increasing age, especially if you are 65 or older.
  

Symptoms include:

• Aching or cramping in the arms when knitting, writing or performing other manual tasks.
• Change in the color of your leg or arm.
• Coldness of the lower leg or foot even after walking in a warm weather.
• Sores on the toes, feet or leg that don't heal.
• Weakening pulse in the foot.
• Erectile dysfunction in men.
• Hair loss on the legs.
  

"If neck arteries to your brain are affected, symptoms may include difficulty talking, weakness in the arms and legs, or loss of vision," says Dr. Barsoum. "If you experience any of these symptoms, make an appointment with a vascular medicine specialist, who will conduct a physical exam and record your health history."

The exam will include finding a pulse in the affected neck artery and comparing it with the pulse in the unaffected neck artery. Vascular medicine specialists have a wide range of tools available, depending on the degree of your symptoms, to help you return to the activities you love.

For example, if you can walk a few blocks with only mild pain, they may prescribe medications such as aspirin, statins or blood thinners. They also may discuss ways you can modify your risk factors, including quitting smoking; controlling blood pressure, cholesterol and diabetes; and increasing your activity level.

If you have more significant symptoms, such as not being able to tolerate the pain when walking, a vascular medicine specialist typically will order an ultrasound or a CT scan with contrast, or even an angiogram to determine the location and degree of the blockage. Your care team will discuss a variety of surgical options to deal with the blockage.

"Prevention of peripheral artery disease is always the best treatment," says Dr. Barsoum. "Quit smoking, eat a heart-healthy diet, exercise regularly, keep your blood sugar in check if you have diabetes, maintain a healthy weight, and manage your blood pressure and cholesterol levels."

In addition, if you have one or more risk factors, avoid certain over-the-counter cold remedies that contain pseudoephedrine. These medications constrict your blood vessels and might worsen your symptoms.

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About Mayo Clinic Health System
Mayo Clinic Health System has a physical presence in 44 communities and consists of 53 clinics, 16 hospitals and other facilities that serve the healthcare needs of people in Iowa, Minnesota and Wisconsin. The community-based healthcare professionals, paired with the resources and expertise of Mayo Clinic, enable patients in the region to receive the highest-quality physical and virtual healthcare close to home.

Media contact:

• Amanda Dyslin, Mayo Clinic Health System Communications Department, newsbureau@mayo.edu

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• Take heart murmurs seriously

The post Peripheral artery system at risk of disease due to family history, lifestyle appeared first on Mayo Clinic News Network.

The body has two types of artery systems: the coronary artery system, which relates to the heart, and peripheral artery system, which involves the arteries carrying oxygenated blood to the arms, legs and brain.

Just like coronary arteries, peripheral arteries can become diseased. This condition, called peripheral artery disease, or PAD, narrows arteries and reduces blood flow due to a buildup of fatty deposits on the artery walls. This can cause claudication, which is muscle pain and cramping when a person is active but usually disappears after a few minutes of rest.

If this sounds familiar, take a few minutes to learn more about PAD.

Who's at risk for PAD

People who smoke or have diabetes at any age are at the greatest risk for this condition. Other risk factors include:

• Body mass index over 30
• Family history of PAD, heart disease or stroke
• High blood pressure
• High cholesterol
• Increasing age, especially if you are age 65 or older

Recognizing PAD symptoms

In addition to claudication, other symptoms of PAD include:

• Aching or cramping in the arms when knitting, writing or performing other manual task.
• Change in the color of your leg or arm
• Coldness of the lower leg or foot
• Sores on the toes, feet or leg that don't heal
• Weakening pulse in the foot
• Erectile dysfunction in men
• Hair loss

If arteries in your brain are affected, symptoms may include dizziness, weakness in the arms and legs, or loss of consciousness.

If you experience any of these symptoms, make an appointment with a cardiologist, who will conduct a physical exam and record your health history. The exam will include finding a pulse in the affected limb and comparing it with the pulse in the unaffected limb.

PAD treatment options

Cardiologists have a wide range of tools available, depending on the degree of your symptoms, to help you return to the activities you love. For example, if you can walk a few blocks with only mild pain, they may prescribe medications including aspirin, statins or blood thinners. They also may discuss ways you can modify your risk factors, such as quitting smoking; controlling blood pressure, cholesterol and diabetes; and increasing your activity level.

If you have more significant symptoms, such as not being able to tolerate the pain when walking, a cardiologist typically will order a CT scan with contrast, an ultrasound or an angiogram to determine the location and degree of the blockage.

To relieve the blockage, your cardiologist may refer you to a vascular medicine specialist or proceduralist who will conduct an arterial angioplasty. In this procedure, a tiny balloon is inserted into the artery and expanded, pushing the blockage into the arterial wall. At the same time, the balloon can leave behind a stent, which acts as a support for keeping the artery open. The stent itself may contain a drug that helps keep the artery open.

To break up a blockage, the vascular proceduralist also may inject a clot-dissolving drug into the artery where the clot is located.

An untreated blockage can progress and completely interrupt the flow of blood to the affected limb. This loss of blood supply can lead to severe pain even when a person is resting, ulcers, gangrene — and eventually could require amputation.

Prevention is the best treatment

If you have one or more risk factors, you can take action to prevent or stop the progression of PAD.

The best way is to adopt a healthy lifestyle by:

• Avoiding certain over-the-counter cold remedies that contain pseudoephedrine. These medications, which include Advil Cold and Sinus and Aleve-D Sinus and Cold, constrict your blood vessels and can increase your symptoms.
• Not smoking or quitting if you do smoke.
• Eating the rainbow by consuming a plentiful array of colorful fruits and vegetables.
• Exercising regularly, aiming for 30 to 45 minutes several times a week.
• Keeping your blood sugar under control if you have diabetes.
• Maintaining a healthy weight.
• Managing your blood pressure and cholesterol levels.

Next steps:

• Find a cardiologist near you.
• Find a vascular medicine specialist near you.
• Discover how cardiac rehabilitation can improve your vascular health.

Michel Barsoum, M.B., Ch.B., is a cardiologist and vascular medicine specialist in Chippewa Falls, Eau Claire and Rice Lake, Wisconsin.

This article first appeared on the Mayo Clinic Health System blog.

The post PAD: The other arterial disease appeared first on Mayo Clinic News Network.

Peripheral artery disease, or PAD, affects almost 10 million people in the U.S. Approximately one-third of patients will die within five years of a peripheral artery disease diagnosis, and 20% will experience a heart attack or stroke. 

What is it?

Peripheral artery disease usually involves pain in the lower limbs caused by reduced blood flow due to narrowing of the arteries. Its symptoms, like reduced ability to walk due to leg pain, often are brushed off as signs of aging. While age is a factor, younger people with diabetes or who smoke also should be checked for the disease.

"If you have risk factors for lower-extremity PAD — diabetes, tobacco use, high cholesterol, high blood pressure, as well as age — it's really important to have those conversations with your provider about your ability to exercise or walk if you are having any limitation," explains Dr. Amy Pollak, a Mayo Clinic cardiologist.

Awareness

Peripheral artery disease is detectable and treatable, but it's often not diagnosed early enough. This means patients are often not treated with the most aggressive therapies. Health disparities play a big role, with the highest rates of peripheral artery disease occurring in Black men and women.

"There is an amputation epidemic," says Dr. Pollak. "And I don't use that word epidemic lightly. In today's climate, I use it intentionally. Depending upon where you live in our country, you may be at a higher risk of having an amputation for lower-extremity PAD, and not always be offered a revascularization procedure. So there is a lot of work that needs to be done to raise awareness of PAD, both for patients and health care providers."

Into Action

A new PAD Action Plan spearheaded by the American Heart Association is hoping to do just that.

The plan serves as a roadmap for reducing the burden of peripheral artery disease by improving the awareness, diagnosis and treatment of PAD. The plan also highlights the many gaps and opportunities in PAD research to further reduce preventable complications and deaths for future generations.

"The incidence of PAD is set to triple in the United States in the coming years," says Dr. Pollak, who is a co-chair of the PAD Action Plan. "So we have an important opportunity to not only prevent that from happening, but to prevent heart attacks and strokes to help people live longer lives with a greater degree of functional ability by diagnosing and treating PAD. When it comes to the health disparities, we need to be doing even more outreach to populations that have been historically not focused on with that important information about what PAD is, how it can present, and what treatment options there are."

On the Mayo Clinic Q&A podcast, Dr. Pollak discusses the importance of early diagnosis of PAD to reduce the risk of amputation, heart attack and stroke.

Related posts:

• "Mayo Clinic Minute: How is peripheral artery disease diagnosed?"
• "Peripheral artery disease can signal cardiovascular trouble for heart, brain and legs." 

Watch: Dr. Pollak discusses PAD.

Read the full transcript.

For the safety of its patients, staff and visitors, Mayo Clinic has strict masking policies in place. Anyone shown without a mask was either recorded prior to COVID-19 or recorded in a nonpatient care area where social distancing and other safety protocols were followed.

The post Mayo Clinic Q&A podcast: Early diagnosis of peripheral artery disease reduces risk of amputation, heart attack and stroke appeared first on Mayo Clinic News Network.

Dr. Amy Pollak, a Mayo Clinic cardiologist, explains how physicians identify peripheral artery disease and why an early diagnosis can reduce the risk of amputation, heart attack and stroke.

Watch: The Mayo Clinic Minute

Journalists: Broadcast-quality video pkg (1:00) is in the downloads at the end of the post. Please courtesy: "Mayo Clinic News Network." Read the script.

Peripheral artery disease involves cholesterol buildup in arteries or blood vessels of the legs. The condition can restrict blood flow and lead to complications.

"Peripheral artery disease not only influences our ability to walk, but it puts us at a risk for amputation," says Dr. Pollak. "And that also ties in with heart attack and stroke because of systemic cholesterol buildup."

Diagnosing peripheral artery disease starts by checking circulation to the feet.

"Taking off the shoes and socks, doing a foot exam, feeling the pulses, and then, if you have somebody who either has symptoms that are concerning or an abnormal pulse exam, the next diagnostic test is something that's straightforward to do," says Dr. Pollak.

An ankle-brachial index test can identify circulation issues by comparing blood pressure in a person's ankle to that in their arm before and after exercise. Tests and time with a health care team can promote conversations about the most appropriate medical treatment.

"Not only do we typically think of cholesterol medications, such as statins or the role of aspirin, but some of the other medications to help reduce that future risk," says Dr. Pollak.

Related post:

• "Peripheral artery disease can signal cardiovascular trouble for heart, brain and legs." 

For the safety of its patients, staff and visitors, Mayo Clinic has strict masking policies in place. Anyone shown without a mask was recorded prior to COVID-19 or recorded in an area not designated for patient care, where social distancing and other safety protocols were followed.

The post Mayo Clinic Minute: How is peripheral artery disease diagnosed? appeared first on Mayo Clinic News Network.

If you have not heard of peripheral artery disease, or PAD, you are not alone. While clinicians and health organizations have made headway in raising awareness that heart disease is the No. 1 cause of death worldwide, PAD — despite being part of cardiovascular disease — is not as well-known.  

PAD affects 8–10 million people in the U.S., most over the age of 65. But it also affects younger people who have additional risk factors, such as diabetes, smoking, obesity,  and high blood pressure. 

Peripheral artery disease involves the lower limbs, but it has its basis in atherosclerosis — a vascular disease where cholesterol plaque builds up in artery walls. This narrows the arteries, restricting circulation and possibly resulting in plaque breaking loose and forming a blood clot. Most patients with PAD will have vascular disease in more than one defined area, increasing the chances of serious complications.  
Watch: Dr. Amy Pollak talks about peripheral artery disease.

Journalists: Broadcast-quality soundbites are available in the downloads at the bottom of the post. Please courtesy: "Mayo Clinic News Network." Read the script.

Unfortunately, peripheral artery disease has not traditionally been diagnosed early enough, and patients are often not treated with the most aggressive therapies. Addressing the issue of awareness and education in clinicians and patients is a key focus area in the new PAD National Action Plan spearheaded by the American Heart Association. This plan was developed in collaboration with 25 organizations and national leaders.  

Dr. Amy Pollak, a Mayo Clinic cardiologist, co-chairs the effort to bring the plan to fruition, along with Dr. Aruna Pradhan of Brigham and Women's Hospital and Dr. Naomi Hamburg of Boston Medical Center.  

The plan outlines goals to: 

• Increase awareness of PAD for patients and health care providers  
• Improve detection, treatment and ultimately health outcomes 
• Reduce amputations related to peripheral artery disease through public health initiatives 
• Increase and sustain research 
• Advance advocacy efforts  

"Lower-extremity PAD has not been prioritized the same way as cardiovascular disease or stroke. But there are several important points to consider," says Dr. Pollak. "If you have polyvascular disease — meaning cholesterol buildup that affects more than one area of the body, such as the heart, brain or leg — then you are at very high risk of heart attack, stroke, death or limb loss related to amputation. Patients with polyvascular disease and diabetes are at the highest PAD risk. We must ask about symptoms, treat these patients with aggressive medical therapy and follow them more closely." 
 

 Awareness and health disparities 

Awareness is important because it opens the door to discuss prevention and treatment. Dr. Pollak notes that within the area of cardiovascular disease, the prevalence of PAD in the American population far surpasses all other types of cardiovascular and circulatory diseases, such as ischemic heart disease, stroke or atrial fibrillation.  

"The American Heart Association did a survey that found that around 90% of people were aware of heart attack and stroke risks. But even in this group educated about heart disease and stroke, most people had not heard of PAD," says Dr. Pollak. "They did not know that you could have cholesterol buildup that involved blood vessels to your leg that could impact your ability to walk and be associated with limb loss. There are critical health disparities in patient education that we need to address because Black Americans are less aware of PAD."  

Thirty percent of Black Americans will develop PAD, compared to 20% of non-Hispanic white Americans. Hispanic people and Native Americans have a similar 20% prevalence of PAD, but they tend to be diagnosed at a later stage of the disease. 

The effects of health disparities regarding peripheral artery disease in Black Americans are stark. These patients often have more severe disease due to later diagnosis and are less likely to receive the best medical therapy. They have a higher risk of death due to cardiovascular events, such as a heart attack or stroke.  

Black Americans are less likely to have procedures such as revascularization that can salvage a circulation-damaged limb. In turn, this leads to more nontraumatic amputations. The rate of amputations due to peripheral artery disease is markedly higher in the Southeast and Texas than the rest of the U.S.  
 

Symptoms and diagnosis of PAD 

As arteries leading to the legs develop significant cholesterol buildup that restricts blood flow, symptoms of PAD may appear. Some symptoms, such as lower leg cramps when walking, may be mild, severe or somewhere in between, but worsen as the disease progresses. Other symptoms may involve changes in the legs, such as coldness in one leg but not the other; shiny skin on the legs; slow growth of toenails and leg hair; sores on toes, feet or legs that do not heal; and no pulse or a weak pulse in legs. People may think some of these symptoms are just signs of aging, so it is important to address them with a health care professional. The most common symptom of PAD is a decreased ability to walk. Patients with PAD may not have any pain. 

"We know that a history of tobacco use, or diabetes, are major risk factors for developing PAD. Other traditional risk factors, such as high blood pressure, high cholesterol and age, also increase the risk of PAD. We need to ask our patients with these risk factors if they have any symptoms that could be related to PAD and check their pulses in their feet. If they have concerning symptoms or an abnormal pulse exam, the next step is often doing a noninvasive ABI (ankle-brachial index) test," Dr. Pollak explains. 

A physical exam can uncover symptoms that a patient may not be aware of or had simply attributed to something else. Dr. Pollak says it is important to remove socks and check the legs and feet of patients who fit the risk profile, even if they are younger. Clinicians can ask patients what sort of activities they can comfortably do to identify problems. And blood tests to check for diabetes and measure cholesterol also should be up to date. 

Diagnostic tests, such as the ankle-brachial index test that compares blood pressure in a patient's ankle to that in their arm before and after exercise, can identify circulation issues in the legs. This test is a noninvasive way to identify the presence and severity of peripheral artery disease.  

Angiograms use imaging technologies to home in on blockages and can be done with CTs or MRI. Catheter angiograms allow for treatment to open the arteries at the same time. When initiated early enough, revascularization in lower limbs restores blood flow and prevents the need for amputation. Losing mobility can affect a person's ability to work, making it more difficult to stay active and independent.  

The stakes are high for patients and the health care system that cares for them. Approximately one-third of patients will die within five years of a peripheral artery disease diagnosis, and 20% will experience a heart attack or stroke.  

"As a higher percentage of the U.S. population becomes older in the coming decades, progressive cardiovascular diseases like PAD will be relevant to even more people," notes Dr. Pollak. "Improving awareness, diagnosis and guideline-based treatment of PAD by 2025 is a crucial step to improve cardiovascular health and reduce nontraumatic amputations in the future." 

The post Peripheral artery disease can signal cardiovascular trouble for heart, brain and legs  appeared first on Mayo Clinic News Network.

DEAR MAYO CLINIC: I am in my early 50s, and I enjoy hiking and biking. I was active until leg pain brought me to my doctor. I was diagnosed with a blockage of the artery behind my right knee. What is this condition, and what treatments are available?

ANSWER: Your condition, called peripheral artery disease, is a common problem in which narrowed arteries reduce the amount of blood that reaches the limbs. The type of blocked artery you describe can be treated in several ways. The specific treatment you need depends on the severity of your symptoms and the extent of the blockage.

The most frequent cause of peripheral artery disease is a buildup of fat and calcium deposits on artery walls. Over time, this buildup, which is known as atherosclerosis or plaque, can limit blood flow through the artery and lead to serious problems, including tissue death and amputation of the affected limb.

When plaque begins to form, it doesn't cause symptoms. But it can be detected during a physical exam when blood pressure in an ankle or leg is compared to blood pressure in an arm. Normally, blood pressure is higher in the legs than in the arms. As a blockage develops, though, blood pressure in the leg falls.

Factors that increase risk for plaque buildup include cigarette smoking, diabetes, kidney failure, high blood pressure and high cholesterol.

If these factors are not controlled, plaque continues to build and symptoms begin to appear. The most common symptom, called "claudication," is leg pain or cramp with walking. Depending on how advanced the disease is, the pain may be mild or severe. As the disease progresses, the distance you can walk without pain gets shorter. The first approach to treat this disease is to take part in physical activity or a walking program for 30–40 minutes three to four times per week.

If nothing is done to treat the risk factors, peripheral artery disease can progress to its most serious stage, which is when blood flow to the limb is dramatically decreased. A telltale symptom of this stage is leg pain at resting, particularly at night when the leg is raised on a bed. Often patients must get out of bed or dangle their foot outside the bed to relieve symptoms.

Treatment varies based on the severity of the disease. When peripheral artery disease is diagnosed in the early stages of the disease, lifestyle changes often are enough to treat it. Quitting smoking; eating a healthier diet; and controlling high blood pressure, high cholesterol or diabetes — along with a daily walking program — can help. These steps typically slow or stop progression of the disease because they allow the body to develop other channels for blood to bypass the blockage. Exercise can help condition muscles to get oxygen from blood more efficiently, so the muscles can work better despite reduced blood flow.

If lifestyle changes are not enough to slow the disease's progress, or if severely limited blood flow threatens the viability of the leg, additional treatment may be necessary.

One treatment possibility is bypass surgery performed by a vascular surgery team. A blood vessel from another part of the body or an artificial blood vessel is placed around the blockage in the leg, so blood can flow around the affected artery.

A less invasive approach involves endovascular treatment, which includes options such as angioplasty, stents and plaque removal. In angioplasty, a small hollow tube, called a catheter, is threaded through a blood vessel to the blocked artery. A small balloon on the tip of the catheter is inflated to expand the artery, flatten the blockage and stretch the artery open to increase blood flow. A mesh metal framework, called a stent, may be placed in the artery to keep it open. Some catheters also can be used to remove plaque. The plaque buildup can be physically removed from the artery, either by scraping it out with a blade or drill, or using a laser to destroy it.

For a person in your situation, a conservative approach to treatment is usually an appropriate first step. Medical intervention typically is not necessary, unless peripheral artery disease has advanced to the point that the health of the limb is threatened.

My recommendation is to follow up with a vascular expert for a more thorough review of your situation to determine the best treatment for you. — Dr. Young Erben, Vascular Surgery, Mayo Clinic, Jacksonville, Florida

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This month’s feature highlights four articles, three of which focus on COVID-19, that appear in the current issue of Mayo Clinic Proceedings. These articles are also featured on the Mayo Clinic Proceedings’ YouTube Channel.

A Paradigm and Program for Administering Anti-Spike Monoclonal Antibodies to Eligible Patients With COVID-19

Infection with SARS-CoV-2 leads to polymorphic clinical presentations that encompass a spectrum ranging from an entirely asymptomatic state to a severe, life-threatening illness. The former is managed by quarantine while the latter necessitates care in the intensive care unit with therapies that may include remdesivir and dexamethasone. For individuals with mild to moderate disease and concomitant risk factors for disease escalation and the need for hospitalization, the Food and Drug Administration (FDA), via emergency use authorization (EUA), approved the use of several spike-neutralizing monoclonal antibodies that may be intravenously administered in the outpatient setting. Such authorization for use by the FDA was based on encouraging data from early phase clinical trials demonstrating that the use of these antibodies, as compared with placebo, reduced viral load and the risk for disease progression.

In the present issue of Mayo Clinic Proceedings, Razonable et al discuss in-depth the development and current functioning of the outpatient program at Mayo Clinic that administers these antibodies to eligible, high-risk patients with mild to moderate COVID-19.

Their article begins by detailing the challenges in developing such a program and these include, among others:

1. The need to establish facilities, separate from existing outpatient infusion centers, such that non-infected patients receiving non-COVID-19-related treatment in these infusion centers are not exposed to patients with COVID-19 administered anti-spike monoclonal antibody;
2. The relative lack of awareness by patients and providers of the availability of such therapeutic options; and
3. The fact that such use of neutralizing antibodies is not currently sanctioned by relevant medical societies.

An additional challenge in initiating this program was that it was introduced at a time when Mayo Clinic, like other health care systems, concurrently faced the dual demands of dealing with a surge situation in the number of COVID-19 cases, and yet concomitantly was preparing for the implementation of vaccination programs. Razonable et al describe the infrastructure underpinning the success of this program, an infrastructure that includes not only the needed physical space and facilities where these antibodies are administered, but also an essential electronic network.

This electronic network, relying on the electronic health record and informational technology, enables the following: the early identification of patients with newly diagnosed COVID-19 and meeting eligibility criteria to receive these antibodies; assembling relevant electronic order sets; establishing a registry for all eligible patients, including those who were infused and those who declined such infusions; and the ready communication among the diverse personnel involved in this program. The expertise and personnel needed for the success of the program are truly vast, and include the COVID-19 Frontline Care Team; experts from relevant medical specialties, nursing, and pharmacy; primary care providers; infection prevention and control; health care administration; and experts in compliance, legal and ethical aspects, engineering, informatics, and facility management.

The core Monoclonal Antibody Treatment Team (MATRx), serving as a hub that connects with relevant clinical and administrative expertise, established a just system for drug allocation that drew upon guidance from the FDA and relevant Departments of Health and Human Services, and from ethicists and legal experts. The MATRx meets daily, reviews identified and referred patients, and allocates medications according to patient eligibility and the consensus-driven process of allocation. The MATRx engages relevant leaders and experts not only intramurally within Mayo Clinic, but also extramurally. These latter connections enable engagement with regional hospitals, long-term care facilities and nursing homes, and with providers caring for the underrepresented and disadvantaged populations.

Between November 19, 2020, and February 19, 2021, this program at Mayo Clinic administered spike-neutralizing monoclonal antibodies to more than 4,000 patients across Mayo Clinic’s geographically diverse sites in Arizona, Florida, Minnesota, and Wisconsin. Razonable et al point out that the preliminary results of this program are encouraging, and that currently underway are analyses of such outcomes as rates of hospitalization, adverse drug effects, hospital-free days, and mortality in patients in whom spike-neutralizing monoclonal antibodies were administered. Razonable and colleagues are to be commended for envisioning this paradigm for the delivery of anti-spike monoclonal antibodies for eligible patients with COVID-19, for assembling a cohesive network of relevant experts and expertise, and for developing the requisite infrastructure and logistics that effect the essential processes of this promising program.

Razonable RR, Aloia NCE, Anderson RJ, et al. A framework for outpatient infusion of anti-spike monoclonal antibodies to high-risk patients with mild to moderate coronavirus disease-19: the Mayo Clinic model. Mayo Clin Proc. 2021;96(5):1250-1261.

Immune Responses to SARS-CoV-2: Epidemiology and the Basis for a Therapeutic Strategy

Two articles in the present issue of Mayo Clinic Proceedings examine different aspects of immune responses elicited by infection with SARS-CoV-2.

Carter et al assessed the prevalence of antibodies to SARS-CoV-2 among health care personnel at Mayo Clinic, a medical center with clinical sites in five states. Between June 15, 2020, and August 8, 2020, almost 30,000 personnel were screened by a two-stage procedure that involved first a dried blood spot test (obtained by finger stick), which, if reactive, was followed by a confirmatory test based on a total antibody immunoassay on a venous blood sample. The overall seroprevalence rate was 0.60%; when analyses included all previous SARS-CoV-2 tests (such as previous serologies and RT-PCR tests), the prevalence rate was estimated at 1.08%.

These findings are remarkable in that they are appreciably lower than what has been reported for other medical centers, the latter ranging from 3.8% to 13.7%. Such lower prevalence rates at Mayo Clinic sites may reflect several considerations including the following two. First, prevalence rates for SARS-CoV-2 infection in communities surrounding the Mayo Clinic sites, overall, may be lower than elsewhere; indeed, in the analysis by Carter et al prevalence rates were generally higher at Mayo Clinic sites in Arizona and Florida, geographic regions with relatively higher numbers of COVID-19 cases. Second, precautionary measures against viral spread including universal masking requirements for health care personnel were consistently and promptly implemented at Mayo Clinic with the onset of the COVID-19 pandemic.

Also in this issue of Mayo Clinic Proceedings is the study by Klassen et al that undertook a systematic review and meta-analysis of the current literature regarding the use of convalescent plasma as a therapeutic approach in COVID-19. Systemic antibody-based immune responses to SARS-CoV-2 in patients convalescing from COVID-19 are regarded as the effector mechanisms accounting for the putative salutary effects of convalescent plasma in COVID-19.

This analysis by Klassen et al included 10 randomized clinical trials, 20 matched-control studies, 96 case reports/case series, and 2 dose response studies. Based on their comprehensive analysis, Klassen et al conclude that mortality rates were significantly lower in patients treated with convalescent plasma as compared with other treatments, especially so if patients were treated early in their illness with higher titer convalescent plasma.

These two articles are notable for several reasons including the fact that they are linked by the concept that understanding the response to disease and its causes can offer important insights regarding the disease itself and approach to therapy.

The study by Carter et al demonstrates that seroprevalence among health care personnel may be institution-specific, possibly mirroring either viral infection in surrounding communities or the stringency in implementing institutional precautionary measures against viral spread. The study by Klassen et al demonstrates the beneficial effects that can clearly accrue from convalescent plasma – a therapeutic approach to disease that harkens back more than a century as it was the basis for the award of a Nobel Prize to von Behring in 1901 - particularly if administered in high titer and promptly after the onset of COVID-19.

Carter RE, Theel ES, Breeher LE, et al, for the Mayo Clinic Serology Screening Program Operations Team. Prevalence of SARS-CoV-2 antibodies in a multistate academic medical center. Mayo Clin Proc. 2021;96(5):1165-1174.

Klassen SA, Senefeld JW, Johnson PW, et al. The effect of convalescent plasma therapy on mortality of patients with COVID-19: systematic review and meta-analysis. Mayo Clin Proc. 2021;96(5):1262-1275.

Peripheral Arterial Disease Presages Atrial Fibrillation and Ischemic Stroke

The risk of atrial fibrillation (AF) is increased by intrinsic heart disease (ischemic, valvular, hypertensive, congenital, heart failure, cardiomyopathy), disease elsewhere (pneumonia, sleep apnea), systemic diseases (diabetes, chronic kidney disease), endocrinopathies (hyperthyroidism), and personal behavior (smoking, excess/binge alcohol intake). In the present issue of Mayo Clinic Proceedings, Tseng et al examined whether patients with lower extremity peripheral arterial disease (PAD) are more likely to develop AF.

In this large cohort (over 30,000 subjects) retrospective study, PAD was determined by the non-invasive test of ankle-brachial index (ABI, highest ankle systolic blood pressure/highest brachial systolic blood pressure), and the subsequent occurrence of AF assessed over a follow-up of 8.5 years. A low ABI reflects PAD that arises from atherosclerosis as atherosclerotic luminal narrowing lowers the ankle systolic blood pressure and thus the ABI. A high ABI reflects PAD caused by medial arterial calcification, the latter impairing vascular compliance and causing arteries to stiffen; medial arterial calcification occurs in diabetes and chronic kidney disease.

Tseng et al report that after adjusting for relevant comorbidities, and as compared with patients with a normal ABI (1.0 to 1.39), patients who had a low ABI (<1.0) or a high ABI (≥1.4) had an increased risk of incident AF. Moreover, as the ABI progressively decreased below 1.0 (indicating worsening of PAD), the risk for AF increased. Such complications of AF as ischemic stroke, along with all-cause mortality, were both increased in patients with either a low or high ABI. While the basis for increased risk of AF in patients with PAD is uncertain, echocardiographic data in patients with an abnormal ABI in the study by Tseng et al offer a possible explanation. In these patients, low and high ABI were associated with such echocardiographic findings as a higher left atrial volume index, left ventricular mass index, and right ventricular systolic pressure, and a lower left ventricular ejection fraction. Notably, after appropriate adjustment, such alterations in these specific echocardiographic indices were also associated with an increased risk of incident AF. Thus, PAD, possibly through accompanying cardiac abnormalities, predisposes to AF, the latter through embolic events predisposing to ischemic stroke. The study by Tseng et al is an interesting example of how disease may be relayed from region to region, with such recruitment and amplification of disease processes, in turn, setting the stage for increased mortality.

Tseng AS, Girardo M, Firth C, et al. Lower extremity arterial disease as a predictor of incident atrial fibrillation and cardiovascular events. Mayo Clin Proc. 2021;96(5):1175-1183.

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