chronic inflammation

Chronic Inflammation and Cardiovascular Disease

All of the following discussion is taken from an excellent review paper: The Role of Inflammation in Cardiovascular Disease. It is not easy reading, so I’m going translate it into language that’s simpler for non-physicians to understand.

The cells that line the arteries in the body, including the arteries in the heart are called the vascular endothelium. In normal people, the endothelium has anti-inflammatory and antithrombotic (anti-clot forming) properties. It controls which molecules can cross it and which cannot. The endothelium also controls the smooth muscle contraction and relaxation which dilates or constricts the arteries. This takes place through the balance between the release of substances which dilate the arteries, such as nitric oxide (NO), and substances that constrict the arteries such as endothelin.

Effects of chronic inflammation on endothelium

Chronic inflammation from any cause reduces nitric oxide and endothelin, resulting in damage to the junctions between the endothelial cells. This allows larger molecules, like cholesterol to cross into the endothelial cells. When chronic inflammation is present, LDL (bad cholesterol) metabolism is shifted from large- and medium-size LDL particles towards small and dense LDL particles. These particles cause more atherosclerosis than larger ones because they are not cleared as well by the liver LDL receptors. They thus tend to persist in the circulation. These small dense LDL particles accumulate underneath the endothelium. These particles induce a local inflammatory response. White blood cells called macrophages engulf the LDL particles and release inflammatory cytokines. Many of these macrophages die forming a necrotic core. This stimulates the the formation of a fibrous collagen cap in the wall of the arteries over the LDL particles and dead macrophages.

From systemic inflammation to focal atherosclerosis

Even though inflammation is systemic, atheromatous plaques are focal. They tend to occur where arteries branch or on side branches because these areas are exposed to disturbed blood flow.

Stable vs unstable plaques

The plaques with the fibrous collagen caps when initially formed are stable. If chronic inflammation stops, then they remain stable and do not cause narrowing of the coronary arteries. If chronic inflammation persists then more macrophages continue to release inflammatory cytokines. These inflammatory molecules start to thin some of the fibrous caps making them unstable and prone to rupture.

What happens when a plaque ruptures?

When a plaque ruptures it exposes the interior of the plaque to the bloodstream. This activates the blood clotting system and a clot forms that can obstruct the artery. If it completely obstructs the artery it causes a classic heart attack, also called a STEMI (ST elevation myocardial infarction). The ST refers to a part of an electrocardiogram called the ST segment. In a classic heart attack there is elevation of the ST segments on the electrocardiogram. The elevation makes the electrocardiogram look like firemen’s hats. Here is an example of an electrocardiogram with marked elevation of the ST segments.

If the clot does not completely obstruct the artery the ST segments do not show elevation, but some damage to the heart muscle still happens. The symptoms of this kind of heart attack are similar to a classic heart attack with chest pain radiating to the arm or neck. This kind of heart attack is called an NSTEMI (Non-ST Elevation MI. It is usually detected by measuring enzymes that are released by the injured heart muscle.

Plaques that partially obstruct arteries

Even plaques that are stable and not in danger of rupture can get large enough to partially obstruct arteries in the heart. When these plaques obstruct more than 50% of the diameter of the artery they can cause symptoms. When a person exercises the heart muscle needs more blood and the obstruction limits the blood flow. In this case a person may get chest pain with exercise (angina) that goes away when they sit down and rest.

Strokes

Chronic inflammation causes exactly the same kind of changes in the carotid arteries and other arteries in the brain. Rupture of a plaque in these vessels can cause a stroke. Sometimes platelets adhere to a ruptured plaque in an artery that causes a transient obstruction of the artery that is then washed away by the blood stream. That results in temporary stroke symptoms that resolve in 5-10 minutes. This is called a TIA (Transient Ischemic Attack). A TIA can be a warning signal of risk of a bigger stroke. People who have TIA’s should be immediately evaluated for risk of a bigger stroke.

Treatment of vascular inflammation

Statins are a class of medicine that we used to think work primarily by lowering LDL cholesterol. It was later found that statins have a powerful anti-inflammatory effect. This may well be the major reason that statins reduce the risk of heart attack and stroke.

Bottom Line

Chronic inflammation results in changes in the endothelium of arteries in the heart and brain. These changes allow LDL cholesterol to accumulate in the endothelium causing fibrous plaques. Continued inflammation causes these plaques to become unstable and prone to rupture. Ruptured plaques cause blood clots to form which can lead to heart attacks and strokes. Statins have a powerful anti-inflammatory effect which may be the main reason they reduce the risk of heart attacks and strokes.

Inflammation: Pathway to Chronic Diseases

Inflammation is activation of the immune system in response to threat or injury to the body. Acute inflammation mobilizes the immune system to repair an injury or fight an infection. Once healing takes place the immune system goes back to baseline. Chronic inflammation, however, involves long term activation of the immune system caused by some ongoing stress to the body. More and more, researchers are beginning to show that chronic inflammation is the common pathway to many diseases. There are multiple causes of chronic inflammation. In this post I will write about the causes of chronic inflammation. I will also do a series of posts about the many diseases that chronic inflammation causes. These posts will be based on the structure of an excellent book: Inflamed – Deep Medicine and the Anatomy of Injustice. It is not easy to read because it is disturbing but I highly recommend it. I will also write about a test to measure chronic inflammation. I will write about things you can do to decrease chronic inflammation if you have it and how to prevent it if you don’t. There are many causes of chronic inflammation that have to do with the structure of our society. These are things an individual cannot control. These societal causes will take ongoing efforts by all of us to change some of the toxic structures of society.

The Process of Inflammation

The inflammatory process starts with damage or threat of damage to the body. That can be an infection, a wound, or perceived threat of such. The immune system mobilizes white blood cells called macrophages to the injured area or site of infection. The cells of the immune system also release a cascade of messenger molecules called cytokines that amplify inflammation. These include interleukin 1ß, interleukin- 6 and tumor necrosis factor -α. The liver also releases a protein called c-reactive protein. When the threat is neutralized the immune system helps the body start to heal by releasing anti-inflammatory cytokines including interleukin (IL)-1 receptor antagonist, IL-4, IL-10, IL-11, and IL-13.

In chronic inflammation the pro-inflammatory cytokines continue to predominate and the c-reactive protein continues to be elevated.

Causes of Chronic Inflammation

Causes an individual can do something about

  • Low levels of physical activity.
  • Having a BMI at or above 30 , especially when excess weight is deep within your belly (visceral fat). The best way to measure belly fat is to use a tape measure to measure your waist at the widest point. Increased belly fat is greater than 35 inches for women or greater than 40 inches for men
  • An imbalance of healthy and unhealthy bacteria in your intestine (dysbiosis). Dysbiosis can be caused by antibiotics and by eating foods low in soluble fiber.
  • Regularly eating foods that cause inflammation, especially highly processed foods, or foods high in sugar or salt
  • Inadequate sleep
  • Using tobacco products.
  • Regularly drinking too much alcohol
  • Periodontal disease (gum infection) and tooth decay
  • Perceived stress

Societal Causes

  • Experience of racism (structural or personal)
  • Poverty
  • Homelessness
  • Worry about debt
  • Work stress
  • Exposure to air pollution
  • Exposure to chemicals (pesticides and herbicides for farm workers, glyphosphate (RoundUp) for everyone, microplastics in our bloodstreams for everyone. Every day, we are surrounded by thousands of synthetic chemicals. They are in our food, clothes, tools, furniture, toys, cosmetics and medicines. We know the health effects of only a few of these).

Diseases caused by chronic inflammation

  • Cardiovascular Disease (coronary artery disease, heart attacks, congestive heart failure)
  • Strokes
  • Type 2 diabetes
  • Cancer (multiple types)
  • Inflammatory bowel disease (crohns disease, ulcerative colitis)
  • Rheumatoid Arthritis
  • Lupus and similar autoimmune diseases
  • Asthma
  • COPD
  • Pulmonary fibrosis
  • Depression

Tests to measure chronic inflammation

All of the inflammatory cytokines can be measured but those are expensive tests. A simple inexpensive test that measures inflammation, both acute and chronic is high sensitivity CRP. It will also be high with an acute infection or injury, but will return to normal after the infection or injury have resolved. If it remains elevated when you are not sick or injured it is a sign of chronic inflammation. It may be worth asking your doctor to order this test if you have any of the individual or societal risk factors for chronic inflammation. A normal hs-CRP is less than 0.55 mg/dl in men and less than 1.0 mg/dl in women. If your hs-CRP is high in the absence of acute infection or injury, that can serve as motivation to make lifestyle changes to decrease your chronic inflammation and put you in a population that has less risk of developing any of the diseases associated with chronic inflammation.

Anti-inflammatory lifestyle

  • Exercise regularly. The CDC recommends 30 minutes of moderate exercise (walking briskly) for 30 minutes at least 5 days a week.
  • Eat mostly unprocessed or minimally processed foods and avoid sugary drinks or foods with added sugar or high fructose corn syrup. Also include foods with high soluble fiber such as beans, carrots, sweet potatoes, nuts, berries and most fruits (not fruit juice). Organic foods, while more expensive, have no residual pesticides or herbicides. If you eat meat buy grass fed beef, and pasture raised chicken and pork. Eat more plant-based foods than meat.
  • Avoid taking antibiotics as much as possible
  • Sleep. Average at least 8 hours a night
  • Floss your teeth daily, brush twice a day and see your dentist every 6 months
  • If you don’t smoke, don’t start and if you do smoke quit.
  • It is better not to drink alcohol at all, but if you do limit it to 1 drink a day or less.
  • Learn meditation or self hypnosis to manage stress. There are good books and videos, but an in person course is best if it is available.
  • Drink only filtered water and not bottled water in plastic bottles
  • Gas stoves cause significant indoor air pollution. If possible switch to an electric stove. Induction type burners actually heat more quickly than gas. If you have to use a gas stove, be sure to turn the ventilator fan on and open a window if possible.

Bottom Line

Chronic inflammation is the common pathway for many chronic diseases. There are many individual strategies that reduce or prevent chronic inflammation. Many of these strategies are not possible for people with socioeconomic problems. The stress black people experience from structural and individual racism, homelessness or inadequate housing, anxiety over debt, exposure to environmental synthetic chemicals, and exposure to air pollution are societal problems that we all have a responsibility to address.

My next post will deal with chronic inflammation and cardiovascular disease.