Atherosclerosis is a condition characterized by the growth of fatty lesions, atheromas, in blood vessel walls. This narrows and weakens blood vessels, leading to heart disease, and then ultimately the fatal rupture or blockage of a major vessel that causes a heart attack or stroke. This degeneration of the arteries is a universal process. It occurs to various degrees in every older person, and kills perhaps a sixth of humanity at the present time. The only reason that it doesn’t kill everybody is that other degenerative process of aging manage to get in first, that data suggesting that this is most likely only a matter of a few years of difference. We are as old as our arteries, as they say.
The pace at which atherosclerosis progresses is strongly driven by chronic inflammation. Excessive and constant inflammation is a feature of aging, with some people much worse off than others, and this variation in inflammatory burden goes a long way towards determining who will die, earlier than might otherwise be the case, due to the consequences of atherosclerosis. To understand why inflammation is important to this age-related condition, one needs to know something about the underlying processes that cause atherosclerotic lesions to form.
Atherosclerosis is, in essence, a condition of dysfunctional macrophages. These immune cells are responsible for clearing out unwanted, excessive, or damaged lipids, such as cholesterols, from blood vessel walls. Those lipids are handed off to HDL particles to be returned to the liver for disposal. This works just fine in youth. With age, however, a greater fraction of circulating lipids become oxidized, and macrophages do not handle oxidized lipids well at all. They become dysfunctional foam cells, packed with lipids, and issuing inflammatory signals that draw in more macrophages to suffer the same fate. An atherosclerotic lesion is a macrophage graveyard, seeded by oxidized lipids, and growing via a feedback loop of inflammatory signaling and failing, dying macrophages.
If there is greater systemic inflammation in the body, more macrophages will be drawn to lesions. It is also the case that macrophages attempting to clean up those lesions will be more prone to adopt an unhelpful inflammatory state if greater inflammatory signaling is present in the environment. Further, inflammation and excessive amounts of oxidizing molecules go hand in hand: more inflammation will thus tend to mean more oxidized cholesterols in circulation. This all contributes to a more rapid pace of progression for atherosclerosis.
What causes one older person to have a greater level of chronic inflammation than another? One important variation between individuals is the status of chronic infection. Is there a greater burden of, to pick one important example, herpesviruses such as cytomegalovirus that cannot be cleared unaided by the human immune system and that corrode the immune system over time? Another feature is the one examined in today’s research materials, the health of gums. A range of evidence suggests that the localized inflammation of gum disease does not stay localized, and in fact spreads chronic inflammation throughout the body, harming the heart and the brain – and accelerating the progression of atherosclerosis, thus raising the risk of suffering a stroke.
Two studies raise the possibility that treating gum disease alongside other stroke risk factors might reduce the severity of artery plaque buildup and narrowing of brain blood vessels that can lead to a new or a recurrent stroke. However, these two studies could not conclusively confirm a cause-and-effect relationship between gum disease and artery blockage or stroke risk. “Gum disease is a chronic bacterial infection that affects the soft and hard structures supporting the teeth and is associated with inflammation. Because inflammation appears to play a major role in the development and worsening of atherosclerosis, or ‘hardening’ of blood vessels, we investigated if gum disease is associated with blockages in brain vessels and strokes caused by atherosclerosis of the brain vessels.”
In the first study, researchers examined 265 patients (average age of 64) who experienced a stroke between 2015 and 2017, analyzing whether gum disease was associated with specific types of stroke. They found that large artery strokes due to intracranial atherosclerosis were twice as common in patients with gum disease as in those without gum disease. Further, patients with gum disease were three times as likely to have a stroke involving blood vessels in the back of the brain, which controls vision, coordination, and other vital bodily functions. Gum disease was more common in patients who had a stroke involving large blood vessels within the brain, yet not more common among those who had a stroke due to blockage in blood vessels outside the skull.
The second study focused on 1,145 people who had not experienced a stroke, selected from the Dental Atherosclerosis Risk in Communities (DARIC) Study. Researchers used two magnetic resonance images to measure blockages in arteries inside the brain. Participants were an average age of 76. Periodontal examinations were used to classify the presence and severity of gum disease. Researchers found that arteries in the brain were severely blocked (50% or more) in 10% of participants, and people with gingivitis, inflammation of the gums, were twice as likely to have moderately severe narrowed brain arteries from plaque buildup compared to those with no gum disease. After adjusting for risk factors such as age, high blood pressure, and high cholesterol, people with gingivitis were 2.4 times as likely to have severely blocked brain arteries.