DID YOU KNOW...
That Inflammation Might be the Real Cause of Heart Attacks?

Prepared by : John A. Sawdon, M.Sc., Public Education & Special Projects Director

Cardiovascular Disease remains the leading cause of death throughout the Western World and the second most common cause in Canada. Despite the obsessive focus on Cholesterol levels as a major modifiable risk factor for cardiovascular disease death, we need to be mindful that half of all coronary events occur in persons with low levels of total cholesterol and LDL-C bad cholesterol. The medical field agrees that plenty of other factors also contribute to cardiovascular disease including tobacco use, psychosocial stress, obesity, physical activity levels, and genetic predispositions. The search for new and better predictors of risk has led researchers to a better understanding of inflammation in atherosclerosis and thrombosis. (1)

As we know the body needs cholesterol which is a soft, waxy sterol to help digest fats, strengthen and repair cell membranes, insulate nerves, manufacture vitamin D and make hormones. Because it’s a fatlike substance, cholesterol can’t dissolve in our water-based blood and flows directly to the cells. Instead it needs to be carried by lipoproteins, the two most notable being LDL or low density lipoproteins and HDL or high density lipoproteins. The LDL’s deliver cholesterol to the cells on an as need basis and the heavier HDL’s act as scavengers, picking up excess cholesterol even scraping it off artery walls and transporting it to the liver for processing and elimination. Within this context both HDL and LDL are good cholesterol because each performs a critical function for the body. Although we have declared war on bad cholesterol, this premise overlooks the body’s critical need for low density lipoproteins and the fact that LDL only turns bad when free radicals oxidize it which essentially destabilizes it. Once oxidized the tiny particles of cholesterol become sticky and attach to the artery wall which starts an inflammatory cascade that leads to heart attack causing blood clots. (2)


Figure 1: Types of Chronic Inflammation & Types of Illnesses

When thinking of inflammation we associate this with an injury or infection whereby the body releases chemicals, and infection fighting white blood immune cells to aide in the body’s healing process. Inflammation can also be chronic as in a long term problem whereby the body releases these same blood chemicals, often in response to being overweight, not being physically active or having too high of levels of blood sugar in the form of glucose. Although not formally proven yet that inflammation causes cardiovascular diseases, we know that low grade chronic inflammation is closely linked to all stages of atherosclerosis, a disease that underlies heart attack, stroke and peripheral artery disease. (3)

Atherosclerosis occurs when the artery wall thickens as a result of an invasion and accumulation of white blood cells (foam Cells) and a proliferation of intimal-smooth-muscle cells creating a fibrofatty plaque which continues to build as we age. Coronary artery disease refers to atherosclerosis of the blood vessels that supply blood to the heart muscle, but can also affect other arteries in the body such as those that supply blood to the brain, the legs, arms and the gut. The triggering event of atherosclerosis is the movement of low density cholesterol into the innermost layer of the vessel wall. LDL cholesterol is quickly followed by white blood cells and thus begins the process of plaque formation, consisting mainly of cholesterol, fatty substances and waste products of cells. This leads to inflammation of the walls of the blood vessels resulting in continuous damage and growth of plaques. This plaque formation starts decades earlier and as they grow in size they start to narrow the artery which then reduces blood flow and oxygen to the heart muscle. This leads to angina or chest pain. Plaques can be either stable or unstable, with unstable plaques causing the problems. Stable atherosclerotic plaques which tend to be asymptomatic (without symptoms) are rich in smooth muscle cells. On the other hand, unstable plaques are full of macrophages and foam cells and extracellular matrix separating the lesion from the arterial lumen or fibrous cap which becomes weakened and is prone to rupture.(4) When this cap becomes weakened and ruptures, this is the process we believe leads to the heart attack. When this layer of cells is damaged the inflamed plaque becomes exposed to the blood stream which leads to an overreaction within the body and a triggering of a blood clot within the artery. This then leads to either a partial or full blockage of blood-flow within the artery to the heart muscle causing heart damage. Although the exact sequence of events is not yet fully understood, it is thought that chronic inflammation of the artery walls leads to plaques becoming more vulnerable to rupturing. This same process can occur within an artery leading to the brain resulting in a stroke. Another common occurrence in advanced disease is insufficient blood supply to the legs. This is called peripheral artery disease or PAD.


Figure 2: Impact of c-reactive protein and inflammation on the walls of the arteries

The search for new and better predictions of risk has led to an in-depth understanding of inflammation in atherogenesis and thrombosis. Inflammation plays a role in all stages of atherothrombosis which is the underlying cause of approximately 80% of all sudden cardiac deaths (5). Recently the role of several markers including C - reactive protein in the prediction of coronary events has been studied in healthy men and women. C-Reactive Protein (CRP) is an acute phase reactant that has been shown in prospective cohort studies worldwide to be a reliable measure of underlying systemic inflammation and a strong predictor of Myocardial infarction (Heart Attack) and stroke. In several large scale prospective studies HsCRP has been shown to have predictive value for peripheral artery disease and for heart attack and stroke. (6) HsCRP levels increase with acute infection and trauma. The body produces CRP during the general process of inflammation. Therefore CRP is a marker for inflammation that indicates increased presence of inflammation in the body. CRP levels seem to predict cardiovascular risk at least as well as cholesterol levels do. (7) Data from the Physicians Health study, a clinical trial involving 18,000 doctors, found that elevated levels of CRP were associated with a threefold increase in the risk of heart attack. In the Harvard Women’s Health Study results of CRP test were more accurate than cholesterol levels in predicting heart problems. After three years CRP was the strongest predictor of risk. Women in the group with the highest CRP levels were more than four times as likely to have died or have had a heart attack compared to those with low levels of inflammation. Doctors can test your blood for CRP. It is a simple blood test that can be done at the same time you get your cholesterol checked. One test is the high sensitivity C-reactive protein (hs-CRP). The rating scale used to determine levels is as follows:

• Less than 1.0mg/LLow
• 1.0-2.9mg/LIntermediate
• Greater than 3.0mg/LHigh

It is important to note that inflammation due to other conditions such as infection, autoimmune diseases, illness or arthritis can raise CRP levels. Tell your Doctor all of your symptoms before having your CRP levels checked. It is only recommended that you have your CRP levels checked if you are at risk for heart disease. These risk factors that place you at higher risk for heart disease include:

  • A previous heart attack or stroke
  • A family history of heart disease
  • Elevated levels of total and LDL cholesterol;
  • Low HDL levels Below 40
  • High Blood Pressure
  • Being male or postmenopausal women
  • Cigarette smoker
  • Uncontrolled diabetes
  • Physical inactivity
  • Obesity and being overweight

What can you do about High C - reactive protein levels?

Exactly the same things you would do if you are at risk for heart disease:

  • Eat heart healthy diets including the Mediterranean diet including lots of antioxidants and olive oil, low salt, low sugar and reduced saturated fats
  • Reducing high cholesterol levels
  • Maintaining a healthy weight
  • Exercising regularly
  • Managing Diabetes and High Blood Pressure
  • Stop smoking
  • Reduce Alcohol consumption
  • Both aspirin and Statins have been effective in reducing c-reactive protein levels in cohort studies

The 2013 American College of Cardiology and the American Heart Association have developed a new tool to measure the risk of atherosclerotic cardiovascular disease. This tool helps the Doctor in consultation with the patient to estimate the risk of a heart attack or stroke within ten years by estimating a risk score. For patients falling into a high risk score, often doctors will prescribe statins as a way of managing the risk.


Figure 3: The role of statins in reducing inflammation and C - reactive protein levels

If your scores or risk for heart disease is high, talk with your Doctor about ways of reducing your risk including the potential of testing your C-reactive protein levels.

Our intention in this article is to raise awareness of the role of inflammation and C - reactive protein. We hope this article piques your curiosity and motivates you to do additional research. We would love to hear your thoughts on the value of this and other heart healthy articles. Write to us and share you thoughts including topical areas you would like us to write about. You can send comments to jsawdon@cardiachealth.ca

References:

  1. Willerson,James T. M.D.;Ridker, PaulM. M.D. MPH Inflammation as Cardiovascular risk factor .2004 American Heart Association , http://www.circulationaha.org http://circ.ahajournals.org
  2. Keough,James Inflammation, Not Cholesterol may cause Heart Disease February 26, 2014 https://yogainternational.com/article/view/inflammation-not-high-cholesterol-may-cause-heart-disease
  3. Griffin, Jan M.D. MPH John Hopkins University School of Medicine. Inflammation and Heart Disease: What is C-Reactive Protein? Who Might Benefit from testing? April 6. 2016 http://health.usnews.com/health-news/patient-advice/articles/2016-04-06/inflammation-and-heart-disease-what-is-c-reactive-protein-who-might-benefit-from-testing.
  4. Atherosclerosis – Wikipedia
  5. Williams, James T. M.D., Ridker, Paul M. M.D. MPH Inflammation as a Cardiovascular Risk Factor, University of Texas, Houston Health Science Centre, Houston, Texas 77225 2004 American Heart Association http://www.circulationaha.org
  6. Ridker, Paul M. High Sensitivity C-Reactive Protein: Potential Adjunct for Global Risk Assessment in the Primary Prevention of Cardiovascular Disease, April 3, 2001 http://circ.ahajournals.org/content/103/13/1813
  7. Ridker, Paul M. Inflammation, C-Reactive Protein and Cardiovascular Disease: Moving past the Marker versus Mediator Debate; Circulation Research: 2014; 114:594-595 http://circres.aha.journals.org/content/114/4/594
  8. Griffin Jan M.D., Michos Erin M.D. M.H.S. Inflammation and Heart Disease: What is C-Reactive Protein? Who might benefit from Testing? April 6, 2016 , http://health.usnews.com/health-news/patient-advice/articles/2016-04-06/inflammation-and-heart-disease-what-is-c-reactive-protein-who-might-benefit-from-testing
  9. Sissons, Mark How Might Inflammation Cause Heart Disease? January 18, 2012 http://www.marksdailyapple.com/how-might-inflammation-cause-heart-disease/print/
  10. Shrivasta Amit Kumar, Singh Harsh Vardhan, Raizada Arun , Singh Sanjeev Kumar C-Reactive Protein, Inflammation and Coronary Heart Disease The Egyptian Heart Journal 2015 67, 89-97 http://www.journals.elsevier.com/the-egyptian-heart-journalhttp://creativecommons.org/licences /by-ne-nd/3.0/
  11. Cholesterol Levels of Canadians, 2009 to 2011 Statistics Canada Government of Canada, http://www.statcan.gc.ca/pub/82-625-x/2012001/article/11732-eng.htm

The articles, on the Cardiac Health Foundation of Canada website, are presented with the understanding that the Foundation is providing information only and not rendering medical advice. Please check with your family physician, specialist or health care professional before implementing any of the ideas expressed in these articles.