The Controversial Link Between Chronic Infections and Heart Disease

Problematic research has long linked chronic infections to heart disease, opening new paths for combating the world's number one killer

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For over a century, cardiovascular disease has consistently been the number one cause of death worldwide. Today, various manifestations of the disease claim about 18 million lives each year. That’s nearly double the death toll of cancer, which is the world’s second leading cause of death.

It’s clear that cardiovascular problems are at epidemic proportions. But before the 20th century, it was far more common to die from infections and cardiovascular disease wasn’t nearly the issue it is today.

It was the rise of smoking and the modern lifestyle that proved to be so hard on the heart. By the 1960s, heart disease had reached its all time high. As the death toll climbed, the medical establishment began to wise up to a number of definite causes through the aid of autopsy studies.

Think about the risk factors that contribute to heart disease and you probably picture what those studies revealed: that things like stress, diabetes, and cigarette smoking lead to cardiovascular damage. This is why preventative measures to mitigate these factors are regularly promoted by experts.

But we rarely hear about another potential risk factor that has been observed in the literature for over 40 years. Research shows that chronic infections may also contribute to cardiovascular disease. And the impact it has on public health could be considerable.

The Infection Conundrum

Since the 1970s, evidence began accumulating that various bacterial and viral infections may play a role in atherosclerosis, otherwise known as hardening of the arteries. The idea is known as the infection hypothesis.

While there are no symptoms associated with atherosclerosis itself, it is considered to be a major cause of all other forms of heart disease. This inherently inflammatory condition is believed to be the underlying cause in about 50 percent of all deaths in the modern industrialized world.

If chronic infections are indeed a culprit of atherosclerosis, it would help shed light on a medical mystery—one which finds that as many as 50 percent of atherosclerosis patients lack all the well-established risk factors. Medical science has learned a lot about the cardiovascular system over the last century, but with so many cases still left unexplained, significant unknowns remain.

While cardiovascular damage from chronic infections is often referred to as merely a theory, many scientists say there’s enough evidence to take it seriously. In a review of the literature published in a 2016 edition of the journal ARYA Atherosclerosis, researchers said that, “it is so clear that some microbes and infectious agents can be involved in the process of atherosclerosis.”

The review concluded that controlling infections, especially among people who already exhibit traditional risk factors for atherosclerosis, should be taken into account for reducing the risk of heart disease.

Problems Finding a Treatment

Everyone agrees that inflammation harms the cardiovascular system, and all the established risk factors are inflammatory in nature. Infections are likewise inflammatory, because inflammation is how the immune system combats infections. Researchers have also found microorganisms in the blood and arterial plaque that are linked to infections. 

Still, critics say the hypothesis lacks clarity, because there is no firm grasp of how it works exactly. Many studies have demonstrated that certain pathogens seem to exacerbate atherosclerosis development in animal models. However, no study has been able to identify a clear causal relationship between infection and arterial damage.

Another research review in the November 2017 edition of the European Heart Journal spells out the specific bone of contention: despite years of evidence for the infection hypothesis, the lack of understanding for the mechanism behind it leaves doctors with no reliable strategy to fight it. 

“Identifying the appropriate target pathway has been the Achilles heel in our efforts to mitigate the atherosclerotic response. Is it the microorganism per se or the myriad of signaling pathways that are activated in chronic infection that are pro-atherogenic?” researchers wrote.

With this murky understanding, clinical trials evaluating various antibiotics and other treatment regimens to address the coronary impact of chronic infections have repeatedly failed, and researchers admit enthusiasm toward designing more clinical trials is dwindling.

Infections of Concern

Even if researchers still can’t pinpoint the exact mechanism infections use to damage the circulatory system, they have at least revealed paths to explore.

For example, infectious bacteria and viruses have been shown to have a direct effect on vascular tissue, and an indirect effect on the body’s release of cytokines (immune cells), which both contribute to heart disease. Infectious agents that have been identified in this process include chlamydia, herpes, Helicobacter pylori, influenza A, hepatitis C, cytomegalovirus, and HIV.

The latest virus of concern connected to cardiovascular events is COVID-19. SARS-CoV-2 is notorious for attacking the lungs, but an article in the August 2022 edition of the journal Nature looks at several pieces of evidence which suggest that the cardiovascular system is vulnerable to the virus, as well. And the problem is believed to persist several months after the infection resolves.

In one study from 2022, researchers looked at records from the US Department of Veterans Affairs (VA) and found that people faced substantially increased risks for 20 different cardiovascular conditions in the year following a COVID infection. Conditions included heart attack, stroke, swelling of the heart, and heart inflammation.

Of course, how it works specifically is still not clear. Some researchers suggest that COVID-19’s effect on the heart could be related to the ACE2 protein that the virus uses to enter cells. Another presumes that plaques may accumulate where the immune response has damaged the lining of the blood vessels, leaving these areas vulnerable to problems. Whatever the case, the coronary risk of post-COVID infection is another reason experts recommend taking the vaccine promoted to protect against the virus.

Unfortunately, the COVID vaccine itself has been implicated in numerous cardiovascular events. According to the latest figures from the Vaccine Adverse Events Reporting System (VAERS), over 18,000 heart attacks are linked to the jab, and 26,000 cases of myocarditis or pericarditis (inflammation of the heart or of the sack surrounding the heart).

Before the COVID shot, these inflammatory cardiac events were considered rare, but now they have become increasingly common—particularly among young people—and cardiology experts warn they could have long-term consequences.

Yet other experts insist that, despite these side effects, the vaccine still does more good than harm. A recent study published online in the journal JAMA Pediatrics  identifying cases of myocarditis and pericarditis post-vaccination concluded that the shot needs “to be considered in the context of the reduced risk of COVID-19 infection and associated outcomes as a result of protection from vaccination.”

Plans for a New Shot

Because cardiovascular disease fueled by atherosclerosis impacts more than 82 million Americans, it’s clear that this is a public health issue that demands to be addressed. And many researchers are confident that another vaccine may be the answer.

While scientists have been routinely stumped in devising a drug protocol to prevent infection-induced cardiovascular damage, there is growing interest in an atherosclerosis vaccine that might do the job. In developing such a treatment, researchers believe they can avoid some of the pitfalls of other prevention proposals, and may offer new strategies to target the various signaling pathways related to infections.

However, even experts who are excited by the prospect say the idea is still in its infancy, according to an article published in a 2018 edition of the journal Circulation Research titled, “In Pursuit of an Atherosclerosis Vaccine: Chasing the Holy Grail.”

“Many challenging questions, such as vaccine formulation, route of delivery, schedule and durability of vaccination, proper patient selection for testing, and monitoring of efficacy endpoints or safety issues remain to be answered in ongoing preclinical and clinical testing,” researchers wrote.

Despite the challenges that must still be overcome, researchers concluded that it “has the potential to transform cardiovascular prevention.”