Blocking Inflammation to Prevent Heart Attacks


In what may be the biggest advance in knowledge about the prevention of heart attacks since the discovery of statins, researchers at Harvard Medical School have shown that blocking inflammation helps to prevent heart attacks (New Engl J of Med, August 27, 2017) and cancers (Lancet, August 27, 2017).

You can help to protect yourself from having a heart attack by making lifestyle changes and taking statin drugs to lower cholesterol. However, five years after people who suffer a heart attack have made some lifestyle changes and taken statins, 25 percent will suffer another heart attack. Hundreds of previous research papers point to continuing inflammation as the cause. This breakthrough study shows that giving canakinumab, a drug to block inflammation, reduced second heart attacks in people who had already had a heart attack. This is the first study to show that lowering inflammation without also lowering blood cholesterol levels helps to prevent heart attacks.

The Study
More than 10,000 patients, average age 61, who had had a heart attack and also had positive blood tests for inflammation (high-sensitivity C-reactive protein levels >2 mg/L) were all given high doses of statins. In addition, some were given varying doses of an anti-inflammatory drug, canakinumab, while others were given a placebo. After four years, both groups had the same cholesterol levels but those who took canakinumab had a 15 percent lower rate of second heart attacks, non-fatal heart attacks, fatal heart attacks and strokes, and 30 percent fewer heart surgeries such as bypass surgery or stents. They also had an incredible 50 percent lower death rate from cancer, even though they had the same total death rate.

What is Inflammation?
Your body uses inflammation to protect you from invading germs and to heal injuries. When a germ gets into your body, you make cells and proteins to kill that germ. As soon as the germ is gone, your immunity is supposed to dampen down and stop making large amounts of these cells, antibodies and proteins. Chronic inflammation means that your immunity does not stop working, even though there are no germs that need fighting or injuries that need to be healed. See Inflammation Can Help or Harm

Your immunity stays active and uses the same cells and proteins that kill germs to attack and damage your own cells. Chronic inflammation can lead to:
• Heart attacks: The same immune chemicals that dissolve the outer membranes of bacteria can dissolve the inner linings of your arteries to punch holes in them and start the formation of plaques. A heart attack occurs when a plaque breaks off from the inner lining of an artery leading to your heart, travels down an ever-narrowing artery, and prevents blood from reaching parts of your heart muscle. If you do not die during a heart attack, the part of your heart muscle deprived of oxygen dies and is replaced by scar tissue.
• Strokes: A stroke can occur when plaque breaks off from an artery leading to your brain.
• Diabetes: Type I diabetes can occur when your immunity attacks and kills the beta cells of the pancreas that produce insulin. You develop diabetes because you lack insulin. Type II diabetes can occur when your overactive immunity prevents your cells from responding to insulin, causing very high rises in blood sugar and insulin levels.
• Cancers: An overactive immunity can attack cells to damage the genetic material called DNA. The abnormal DNA that results can turn normal cells into cancerous ones.
• Auto-immune diseases: Specific diseases that appear to be caused by an overactive immunity are grouped together and called auto-immune diseases. Your overactive immunity can cause rheumatoid arthritis to destroy your joints and tendons, lupus to destroy your kidneys and other parts of your body, or other diseases such as dermatomyositis and scleroderma.

Statins Lower Inflammation
Statins help to prevent heart attacks because they prevent inflammation in addition to lowering cholesterol. We have known for more than 15 years that drugs that lower cholesterol but do not reduce inflammation do not prevent heart attacks. For example, ezetimide (Zetia) lowers cholesterol, but does not prevent heart attacks when given alone because it does not reduce inflammation. This new study shows that you can increase heart attack protection by lowering inflammation more, without any further lowering of cholesterol.

Anti-Inflammatory Drugs Can have Serious Side Effects
Canakinumab is an antibody that attaches to and inactivates interleukin-1b, a chemical that brings on inflammation. By blocking interleukin-1b, this antibody markedly reduces the immune response. It has already been approved by the FDA for an auto-immune disease called juvenile idiopathic arthritis. In this study the people receiving canakinumab had a significant reduction in symptoms of inflammatory diseases such as gout, rheumatoid arthritis and osteoarthritis. However, by blocking your immune response, it can also markedly increase your risk for getting serious infections and spreading infections through your body.  In this new study from Harvard, the overall death rate was not reduced in the group taking canakinumab, probably because the reduction in deaths from heart attacks and cancers was  offset by an increase of deaths from infections.

Canakinumab (brand name Ilaryis), made by Novartis, costs about $200,000 a year. A much cheaper anti-inflammatory drug, methotrexate, might help to prevent heart attacks in the same way, but this drug has many known side effects including increased risk for serious infections.

Current Recommendations
Almost all people who have had heart attacks should be taking statins and so should people at high risk for heart attacks. Based on this new study and many previous studies, they should also have a blood test for high sensitivity CRP. If it is greater than 2.0 mg/L, they suffer from chronic inflammation and are at high risk for another heart attack.

However, drugs that block inflammation have the potential to increase risk for infections. Many research papers show that the safest way to reduce inflammation is to follow an anti-inflammatory lifestyle, which includes:
• exercising every day
• losing excess body fat, particularly in the belly
• keeping blood levels of hydroxy vitamin D above 20 ng/ml
• avoiding alcohol
• avoiding smoking and second-hand smoke
• following an anti-inflammatory diet: eating large amounts of fruits, vegetables and nuts and avoiding sugar added foods, sugared drinks including fruit juices, red meat, processed meats and fried foods. See Anti-Inflammatory and Pro-Inflammatory Foods

Checked 5/23/23