DID YOU KNOW...
Exploring Dyslipidemia (High Cholesterol) and Hypercholesterolemia Including New Treatment Methods

By: John A. Sawdon M.Sc. Public Education & Special Project Director, Cardiac Health Foundation of Canada

Atherosclerosis is a common form of heart disease in which plaques of cholesterol and other substances form in the artery walls and eventually restrict blood flow. This restriction leads to less oxygen in the blood and results in chest or shoulder pain following exercise and or excitement. This chest pain is usually associated with Angina. This limiting of oxygen forces the heart muscle to work harder to the point of failure which is what happens when we experience a heart attack or myocardial infarction. In 1948 Dr. William Castelli identified the factors that influenced heart disease through the Framingham, Massachusetts study. Castelli’s study identified that “individuals with levels of cholesterol below 150 milligrams per decilitre had the lowest coronary artery disease risk”. (1)

Cholesterol which is not the same as fat, looks like a waxy substance. The liver manufactures cholesterol and sends it out to other parts of the body for the production of hormones and cell membranes. Cholesterol is essential for healthy cell membranes, hormone production and vitamin storage. It is critical to the normal function of every cell in the body. However, it also contributes to the development of atherosclerosis, a condition in which cholesterol-containing plaques form within the arteries. These plaques block arteries and when plaques rupture, a blood clot forms on the artery thereby reducing the flow of blood.(2) As mentioned previously and illustrated in Figure 1 below, if it’s the heart we experience angina, if it’s the brain then the result is a stroke. If blood is reduced in the arteries of our legs, we experience pain while walking that indicates our arteries are blocked.


Figure 1

Types of Cholesterol

When cholesterol is transported in the bloodstream it is packed into low-density lipoproteins (LDL) that is often referred to as “Bad Cholesterol”. Although LDL is necessary to transport cholesterol throughout the body, high LDL levels dramatically increases your risk for atherosclerosis and eventually a heart attack. When cholesterol is released from dead cells it is picked up for disposal by high-density lipoprotein the “Good Cholesterol”. (3) Figure 2 below illustrates the difference between a healthy artery and a plaque filled artery.


Figure 2

The Link between High Cholesterol and Atherosclerosis

Dr. Jung San Huang Professor of Biochemistry and Molecular Biology Saint Louis School of Medicine and his team discovered that cholesterol limits the activity of a key protective protein called transforming growth factor-beta (TGF-beta). TGF-beta serves a number of important functions within the body; it protects the heart including the aorta and other vessels from damage caused by a variety of factors including hypertension (high blood pressure) and high blood cholesterol levels. Cholesterol suppresses the responsiveness of cardiovascular cells to TGF-beta and its protective qualities- thus allowing atherosclerosis to develop. Similarly, the research discovered that statin drugs lower cholesterol levels, enhance the responsiveness of cardiovascular cells to the protective actions of TGF-beta, thus helping to prevent the development of atherosclerosis and heart disease. (4)

The use of Statins and PCSK9 Inhibitors in Treating High Levels LDL-C “Bad” Cholesterol including Familial Hypercholesterolemia

Statins are a class of medicines that are used to lower blood cholesterol levels. The drugs are able to block the action of a chemical in the liver that is necessary for making cholesterol. By reducing blood cholesterol levels, statins lower the risk of chest pain (angina), heart attack and stroke. (5)

Several types of statins exist which are known through their brand names in brackets including atorvastatin(Lipitor), cerivastatin (Baycol), fluvastatin( Lescol), lovastatin(Mevacor, Altoprev, Advicor, Altocor), mevastatin( the first statin drug), pitavastatin(Livalo), Pravastatin ( Pravachol), rosuvastatin (Crestor) and Simvastatin (Zocor).

Mevastatin is a naturally occurring statin that is found in red yeast rice. (6)

Statins on average reduce LDL-C or bad cholesterol in the range of 21 to approximately 38%. The following table provides a summary on the pharmacology of statins(7):

Drug Reduction LDL-C % Increase HDL-C % Reduction in Total C %
Atorvastatin 20 to 60% 5-13% 25-45%
Lovastatin 21 to 41% 2-10% 16 to 34%
Simvastatin 26 to 47% 8-16% 19-36%
Fluvastatin 22-36% 3-11% 16-27%
Rosuvastatin 45-63% 8-14% 33-46%
Pravastatin 22-34% 2-12% 16-25%

Most individuals are placed on statins because of high levels of cholesterol. In our previous article on Did You Know we highlighted Familial Hypercholesterolemia in which individuals have very high levels of total cholesterol. The group of statins highlighted above have simply not been powerful enough to make a difference in the lives of these individuals. The new PCSK9-inhibitor drug class has now become a game changer. (8) This class of drugs which includes Amgen’s brand name Repatha or evolocumab and Sanofi’s Praluent or alirocumab were approved by Health Canada as adjunct additions with statins in treating those individuals with Familial Hypercholesterolemia. These game changers now have reduced readings in the 400 to 1000 levels by 60%. (9)Both of these drugs are taken via injections either once or twice a month.

Though reduction of cholesterol is important, heart disease is complex and inflammation appears to also play a role in atherosclerosis and heart disease. Thirty-five percent of individuals who develop heart attacks do not have high levels of cholesterol, yet most of these individuals have atherosclerosis. This means that high levels of cholesterol are not always necessary for atherosclerosis. The goal of cholesterol treatment is the reduction of cholesterol to normal levels.

If you have concerns about your Cholesterol level or if you are on a statin and have questions, you should always consult your Doctor for answers and advice on medications. You should also consult with your Doctor first before considering stopping statins if they have been prescribed for you. Unfortunately, a number of studies have revealed that any time a negative news story appears in the media about statins, often the result is that many individuals stop taking their statin medications. (10)Statins which also reduce inflammation reduce the risk for heart attacks and strokes. Figure 3 demonstrates the impact of statins on atherosclerosis.

Statins also create some side effects for some individuals. If you experience any side effects, you should consult with your Doctor as soon as possible. The United States Food and Drug Agency has published public alerts for people taking statins that can be accessed at FDA’s Consumer update page (/forconsumers/consumerupdates/default.htm)(11). The Canadian Women’s Health Network has also published “Evidence for caution: Women and statin use” at www.cwhn.ca . (12)


Figure 3

Statins and the new PCSK9-Inhibitors are game changers in assisting individuals to get their blood cholesterol levels to manageable levels. Figure 3 illustrates the effect of these potential game changers on atherosclerosis and inflammation. For further information, research our references, consult with your Doctors and the Health Canada website.


References:

  1. Physicians Committee for Responsible Medicine 2014/11/03; Washington D.C. 20016, Cholesterol and Heart Disease; www.physicanscommittee.org
  2. MacGill, Markus M. D,, Webberley Helen M.D., 30/12/2015 Cholesterol: Causes, Symptoms and Treatments http://www.medicalnewstoday.com/articles/9152.php
  3. Davis Katheleen M.D.18/06/2015; Hyperlipidemia: Causes, Dignosis and Treatments http://medicalnewstoday.com/articles/295385.php.
  4. Huang Jung San Ph.D; 21/09/2007; Science Daily; The Link Between Cholesterol and Heart Disease Explained; http://www.sciencedaily.com/releases/2007/09/070918100608.htm
  5. MedicineNet.com 2/3/2015; What are Statins and How do they Work? http://www/medicinenet.com/script/main/art.asp?articlekey=18510
  6. Crosta, Peter M.A. 2/07/2015, Knowledge Center; What are Statins? How statins work and side effects of statins; http://www/medicinenewstoday.com/articles/8274.htp
  7. Wikepedia ; Discovery and development of statins; https://en.wikipedia.org/w/index.php? Title=discovery_and_development_of_statins&oldid=718813977
  8. UT Southwestern Medical Centre, 26/02/2016 Science Daily; PCSK9-inhibitor drug class becomes a game changer for patient with extremely high cholesterol https://wwwsciencedaily.com/releases/2016/02/160226081621.htm
  9. Wysong,Pippa The Medical Post News 24/11/2015; Treating Dyslipidemia: Change is coming;
  10. Nielson Sune Fallgaard. Nordestgaard Borge Gronne European Heart Journal 6/11/2015 Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: a nationwide prospective cohort study European Heart Journal doi:10.1093/eurheartj/ehv641
  11. U.S. Food and Drug Administration Protecting and promoting Your Health 31/01/2014 FDA Expands Advice on Statin Risks
  12. Rosenberg Harriet Ph.D, Allard Daniel M.A., Canadian Women’s Health Network, Evidence for Caution: Women and statin use http://www.cwhn.ca/en/node/39417

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.