Why do some patients become severely ill with COVID-19 while others have milder cases or no symptoms at all? A new peer-reviewed BaleDoneen publication proposes an intriguing theory. Published in Medical Hypotheses in June, the paper suggests that the people who are hardest hit by the new coronavirus may also have a very common — and often undiagnosed — underlying health problem that makes them much more vulnerable to severe or fatal COVID-19 infection: microvascular disease (MVD).
Authored by Bradley Bale, MD, Amy Doneen, DNP and Dave Vigerust, PhD, the publication argues that MVD impairs the body’s innate immunity, leaving people who have it less able to mount a vigorous immune system defense against SARS-CoV-2, the virus that causes COVID-19. As a result, people with MVD may fall prey to the most severe complications of COVID-19, which is now known to attack the body from head to foot, causing everything from heart attacks and strokes to pneumonia, chronic kidney disease, blood clots and even “Covid toes.” Here is a closer look at the new research and you need to know about the potential link between MVD and COVID-19.
What is microvascular disease?
Although MVD is very common, many patients have never heard of it. Over the years, it’s had more aliases than a career criminal, including “small vessel disease,” “Syndrome X,” “microvascular dysfunction” and “nonobstructive artery disease.” As discussed more fully in the new BaleDoneen publication, “Microvascular disease confers additional risk to COVID-19 infection,” MVD is a disorder of the small arteries, such as arterioles and capillaries. By some estimates, there are up to 45,000 miles of these vessels in the body, some of which are too tiny to see.
MVD is found at higher rates in older adults, as well as those with diabetes, high blood pressure and cardiovascular disease (CVD). These are the same patients who face a much higher threat of severe or fatal outcomes if they catch the new coronavirus. A common denominator of this high-risk group is that they frequently have atherosclerosis (plaque in the arteries). Research has shown that the extent of atherosclerosis is directly related to the extent of MVD. Therefore, there is a high probability that the patients with higher mortality rates from COVID-19 have MVD.
Unlike coronary artery disease, MVD is not caused by plaque buildup. Instead, the endothelium, which acts as a smart barrier between your blood and the arterial wall, becomes dysfunctional. This leads to reduced flow of oxygen- and nutrient-rich blood to the tissues in the body’s organs, including the brain, heart, lungs, liver and kidneys, all of which can be damaged by COVID-19 complications. Moreover, the number and total volume of the tiniest vessels — capillaries — is decreased in people with MVD, as compared to people without it.
What’s the potential link between MVD and COVID-19?
In response to injury or infection, cells in the affected area mobilize immune system troops to battle the invading pathogen by releasing signaling molecules as a call to arms, along with chemical attractants. These substances summon the body’s defenders, including neutrophils, to the affected area, launching an immune system response called the inflammatory cascade.
Normally, neutrophils are one of the first responders. These immune cells fight infection in two ways: by gobbling up microorganisms and by spraying them with toxins. This includes the release of the enzyme myeloperoxidase (MPO), which combines with hydrogen peroxidase (H2O2) to create hypochlorous acid (HOCl), a powerful virus-killer that plays a key role in innate immunity. However, to do their job, neutrophils must first travel to the infection site via the arterial system.
As reported in the BaleDoneen paper, recent evidence from COVID-19 patients shows that on average, in those with severe disease, levels of neutrophils are significantly higher than in those with mild disease. However, MVD in the lung can impede HOCl production by neutrophils in several ways. First, MVD reduces tissue perfusion of the lung, potentially decreasing the number of these immune system soldiers that actually reach the battleground of diseased tissue. Second, microvascular endothelial cells produce H2O2, which is the primary substance regulating expansion of blood vessels to increase flow. MVD can result in decreased H2O2 production, leaving less of this compound available to combine with MPO to create virus-killing HOCl.
Why does COVID-19 cause some people to have heart attacks?
The BaleDoneen hypothesis also suggests that some of the MPO released by neutrophils would not have any H2O2 with which to combine. Moreover, the higher level of neutrophils in severely ill patients may result in higher levels of MPO in their blood. A number of studies have shown that elevated blood levels of MPO are an independent predictor of increased risk for heart attacks.
Rates of heart attacks and acute cardiac injury are reportedly higher in the same group of COVID-19 patients who have the highest risk for severe illness or death: older adults and those with certain co-morbidities. Some of that elevated cardiovascular risk may result from higher cardiometabolic demand in patients with coronary MVD. In other words, decreased flow of oxygen- and nutrient- rich blood to the heart muscle may raise these patients’ heart attack risk.
This hypothesis also aligns with the observation that children are at low risk for COVID-19 complications, while early observations report increased risk in people ages 40 to 69. As we recently reported, rates of heart attacks and strokes are on the rise in younger adults (those under age 55). Some of the main culprits are America’s increasingly unhealthy lifestyle and the obesity epidemic. As rates of CVD are rising in younger people, so too is MVD, since the two conditions often occur in tandem and have similar risk factors.
What can I do to avoid developing microvascular disease?
The same optimal lifestyle measures advised by the BaleDoneen Method to protect the health of your heart, brain and large arteries will also help safeguard your smaller ones. To learn more, read our blog posts, “5 Healthy Lifestyle Steps that Lower Stroke Risk 90%,” “10 Lifestyle Moves that Could Lower Your Dementia Risk by 35 Percent” and “AHA for Life: A Proven Plan to Prevent Heart Attacks, Strokes and Dementia.” Also discuss your risk factors and ways to reduce them with your healthcare provider.