Originally thought to be a respiratory disease, COVID-19 is now known to attack the body from head to foot, causing everything from strokes and heart attacks to deep vein thrombosis, pulmonary embolism and even painfully red or purple “Covid toes.” All of these potential complications of the new coronavirus have something in common: They stem from vascular disorders, such as blood clots, blood-vessel inflammation and/or impaired blood circulation. What’s more, about 40 percent of COVID-19 fatalities are linked to cardiovascular complications.

There is a rapidly growing body of evidence that SARS-CoV-2, the virus that causes COVID-19, may infect the blood vessels and circulate throughout the body, perhaps explaining why the disease can affect a wide range of organs, including the brain, heart, lungs, kidneys, liver and GI tract. In addition, as reported in the May 2020 BaleDoneen Method Scientific Update for healthcare providers, certain medications used to treat arterial disease may also reduce risk for COVID-19 complications or may be potential therapies. Here are some of the latest discoveries and what they mean for patients with cardiovascular disease (CVD).

The First Proof that SARS-CoV-2 Attacks Blood Vessels

A new report in Lancet demonstrates that cells in the blood vessel lining (endothelium) play a direct role in severe complications of the new coronavirus. Sometimes called the “brains” of the blood vessels, the endothelium acts as a smart barrier between your blood and your blood vessels, controlling the transmission of fluids and other substances between the two. Dysfunction of the endothelium is what leads to coronary heart disease (plaque deposits in artery walls). The endothelium, which is only one cell thick but ranks as the largest organ in the body, also helps regulate blood pressure, as well as the release of enzymes involved in blood clotting, immune function and platelet adhesion (stickiness).

The report’s authors describe “endothelial cell involvement across vascular beds of different organs” in three patients with COVID-19, including two who died from multisystem failure. Post-mortem tests revealed “viral inclusion structures” in the endothelial cells of one patient’s kidney, and “inflammatory cells associated with [the] endothelium” in his heart, small bowel and lungs. In the other patient, a 58-year-old woman, endothelial involvement was detected in the lung, heart, kidney, liver and small intestine. She also suffered a heart attack. A third patient who survived, after suffering respiratory collapse and GI complications requiring surgery, was found to have endothelial involvement of the gut.

Summing up their findings, the researchers state that in each case, “We found evidence of direct viral infection of the endothelial cell and diffuse endothelial inflammation.” They also add that “the development of this disease seems to be that it utilizes the ACE2 receptors as an entry way to a range of cells causing destruction. … This explains why the disease has such a variety of presentations and makes it potentially more dangerous.” Angiotensin-converting enzyme 2 (ACE2) is a protein found on the surface of many types of cells and tissues, including the heart, lungs, kidneys, liver, GI tract and the endothelium.

 “The concept that’s emerging is that this is not a respiratory illness alone, this is a respiratory illness to start with, but it is actually a vascular illness that kills people through its involvement of the vasculature,” study coauthor Mandeep Mehra, MD, medical director of the Brigham and Women’s Hospital Heart and Vascular Center, told Medium.

Could ACE Inhibitors Be a Potential Treatment for COVID-19?

Millions of Americans take medications called ACE inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) to treat high blood pressure, diabetes or heart disease. As we reported in a BaleDoneen Method white paper released in March, there is some evidence that these medications, which the BaleDoneen Method has long used to treat patients with CVD, may also help protect against serious complications in people with COVID-19.

Examples of ACE-I include Accupril (quinapril), Aceon (perindopril), Altace (ramipril), Capoten (captopril), Mavik (fosinopril) and Vasotec (enalapril). ARB medications include Benecar (Olmesartan) or Diovan (valsartan). ACE-I and ARBs fall into a class of medications called renin-angiotensin-aldosterone system (RAAS) inhibitors.

Since then, a rapidly growing body of evidence, as well as position papers from cardiology groups, have revealed that these medications may have a protective — or even lifesaving — effect. For example, a multi-center study of 1,128 patients with high blood pressure who were diagnosed with COVID-19 found that those who were taking ACE-I or ARBs had a 70 percent lower risk of death than those who were taking other types of blood pressure medication. The findings were published in the American Heart Association’s journal Circulation Research in April.

An even newer study, published in May in New England Journal of Medicine, examined the relationship of CVD, medication use, and rates of in-hospital death among 8,810 patients with COVID-19. Similar to earlier studies, the researchers found the highest mortality risk was for people who were over 65 or had such comorbidities as coronary artery disease, congestive heart failure, heart arrhythmia or COPD (chronic obstructive pulmonary disease). Factors linked to higher rates of survival included:

  • Female sex
  • Use of ACE-I
  • Use of statins

Because this was an observational study — not a randomized, placebo-controlled clinical trial — the study cannot prove a cause-and-effect relationship between taking these medications and lower risk for dying from COVID-19. Nor should patients take these, or any other medications, unless prescribed by their healthcare provider.

Do Heart and Blood Pressure Medications Protect Against Getting COVID-19?

Other new studies do not provide any evidence of an independent relationship between taking ACE-I and ARBs and susceptibility to COVID-19 infection. Three studies examining the effects of these medications on patients with COVID-19 were published in NEJM in May. Subsequently, NEJM published an editorial  “expression of concern” about the quality and reliability of the data used for one of the studies, “Cardiovascular Disease, Drug Therapy and Mortality in Covid-19” because the study drew on medical records from a controversial international database.

The editorial urged readers to instead consult the other two studies, which used completely different, independent data from other sources. In one of these studies, researchers from New York University Grossman School of Medicine analyzed records from 12,594 patients who were tested for the virus, 17 percent of who had developed severe COVID-19. More than one-third of the patients had high blood pressure. The study found no increased risk for testing positive for the virus in people — or for developing severe illness — in people who took any of the common types of blood pressure medication. The other study reported no independent link between taking RAAS inhibitors and susceptibility to COVID-19.

Instead, the latest research suggests that RAAS inhibitors, statins and low-dose aspirin (three of the cornerstones of the BaleDoneen Method’s evidence-based treatment plan to help people with CVD avoid heart attacks, strokes, dementia and other complications of arterial disease) may change the progression of COVID-19, potentially reducing its severity. Here are some research findings demonstrating why these treatments — when combined with an optimal lifestyle — might help lower risk for severe complications of the virus:

  • Along with decreasing blood pressure, RAAS medications also decrease inflammation, oxidative stress and endothelial dysfunction.
  • ACE inhibitors reduce inflammation and blood clotting and improve the functioning of the endothelium, heart and kidneys.
  • Low-dose aspirin helps prevent blood clots that can lead to heart attacks, strokes and damage to other organs. About 30 percent of people with COVID-19 develop blood clots.
  • Aspirin can also improve the prognosis of people with sepsis, a potentially life-threatening complication of severe COVID-19. In ICU patients overall, sepsis is the primary cause of death, although this has not been confirmed in COVID-19 patients.
  • Uncontrolled inflammatory reactions and dysfunctional blood clotting are among the primary pathologies underlying sepsis. Therefore antiplatelet therapies, such as low-dose aspirin, is predicted to become a line of treatment for sepsis in the future.
  • SARS-CoV-2 enters the cells mainly through ACE2 receptors and can trigger an intense inflammatory reaction called cytokine storm.
  • Statins have powerful anti-inflammatory effects and also influence the immune system response in several ways, including cytokine production. Statins also improve the functioning and efficacy of the endothelium.
  • In people with certain inflammatory autoimmune disorders, such as rheumatoid arthritis, multiple sclerosis, and lupus, statins have been shown to be beneficial as an add-on therapy.
  • Statins have also been shown to improve outcomes in people with community-acquired pneumonia/sepsis.
  • During the 2009 H1N1 flu pandemic, a link between statin use and reduced disease severity in hospitalized patients was demonstrated. In 2019, researchers advocated statin use as an immunomodulatory therapy for viral infections with potential benefits during epidemics and pandemics.
  • Statins are also known to influence ACE2 expression

What’s the Bottom Line on Blood-Vessel Health and COVID-19?

About 50 percent of American adults have some form of CVD, including coronary heart disease and high blood pressure. It is now well-established that these patients have worse outcomes overall if they develop COVID-19 and a higher risk of death from the virus. People with CVD are also at increased risk for heart attacks, strokes, dementia and many other complications of vascular disease.

Combined with the optimal lifestyle that forms the fourth cornerstone of the BaleDoneen Method’s treatment plan for people with arterial disease, these therapies have been shown in two recent peer-reviewed studies to halt and even reverse arterial disease, helping people avoid heart attacks, strokes and other devastating complications.

As evidence grows that RAAS inhibitors, statins and low-dose aspirin may play a role in helping people who have CVD avoid the most severe complications of the virus if they become infected, it is essential for patients to find out if they have CVD — and if so, to get the best available, personalized therapies to protect and stabilize their arterial and endothelial health.