DID YOU KNOW... Lipoprotein (a) is associated with Increased Risk of Heart Attack or
Myocardial Infarction?

Prepared by John. A. Sawdon M.Sc. Public Education & Special Projects Director,
Cardiac Health Foundation of Canada

Ok, So What is Lipoprotein (a)

Lipoprotein (a) is a molecule that contains both proteins and (cholesterol)lipids. Many enzymes, transporters, structural proteins, antigens and toxins are lipoproteins. Examples include high density and low density lipoproteins of the blood. When LDL cholesterol combines with apoliprotein (a) the result is a compound known as Lp(a). This is a low density lipoprotein that has another form of protein called glycoprotein bonded to it that is known as apolipoprotein (a).1 Lipoprotein is made in your liver which then enters the bloodstream and has been shown to build up under the inner lining of arteries. Essentially it is a small, dense, highly inflammatory lipoprotein. Lp(a) levels are strongly influenced by genetics. The amount your body makes is inherited from your parents and thereby determined by the genes passed on to you at birth2.Lipoprotein does not change much from birth except for women who enter menopause. As estrogen are reduced levels of lipoprotein increase. It is a subclass of LDL but it’s more atherogenic which means it promotes formation of fatty plaques within the interior walls of the arteries. Thus it is linked to a higher risk of heart disease than LDL itself. The production of Lp(a) is controlled by a specific gene. Thus, if you have a mutated version of that gene it can lead to higher Lp(a) levels. Higher levels of Lp(a) are more common in African Canadians/ Afro-Caribbean and less common in Caucasians. Because it is gene related lifestyle change in terms of diet, exercise has little effect in terms of whether you have high Lp(a) levels. A high level of lipoprotein (a) which is a type of lipoprotein/cholesterol is a risk factor for cardiovascular disease. This type of lipoprotein produces small sticky particles that bind to macrophages that then promote foam cells and cholesterol which enter the inner walls of the arteries. This has also been associated with aortic valve stenosis through build-up of calcified deposits that block blood from circulating to the body. These build up as a fatty plaque that eventually leads to both inflammation and thrombosis. Lp(a) interferes with plasminogen, a plasma protein that dissolves blot clots when activated Lp(a) contributes to formation of thrombosis. Coronary thrombosis which occurs in a coronary artery will block part of the blood supply to the heart muscle and cause severe myocardial infarction.


Figure 1

Figure 1 Lp(a) has been found to be a risk factor for myocardial infarction & stroke Cerebral thrombosis occurs in the cerebral arteries, blocking blood supply to the brain and results in strokes. This process also occurs in peripheral artery disease whereby blood clots form in the legs blocking blood supply to the femoral artery and lower legs.

Figure 2 below illustrates apolipoprotein or Lp(a)


Figure 2

Approximately 20% of the general population are affected by high levels of Lp(a) 4 5 This is largely based on genetic factors from their parents and most of these individuals do not know they have elevated levels. Rates are equally high for African Caribbean/African Canadian and south Asian populations. Studies are inconclusive in correlating cardiovascular disease and high levels of Lp(a) in African Canadian/African Caribbean populations. As high levels of this serum Lp(a) travel through the blood stream, they can narrow arteries to the heart, brain and kidneys as well as the legs. This ultimately will lead to blood clots, heart attacks, strokes and peripheral arterial disease as well as calcified aortic stenosis.


Figure 3

Figure 3: above demonstrates the effect of High Lp(a) on the aortic valve

Approximately 13% of the population is affected by high levels of Lp(a) and calcified aortic valve disease. This occurs mainly in people over 60 years of age with slightly higher rates among whites although prevalence rates are similar across various ethno-racial populations. 8

Testing and Treatment Options

When you see your Doctor ask that this test to be included in your cholesterol blood work. It is a simple test but usually is not included when you test for cholesterol levels. Levels of Lp(a) are often reported in in different units, either mg/dl or nmols/L. Chris Kresser of Revolution Health Radio suggests mg/dl is a weight based measurement and shouldn’t be used. He suggests using nmols/L because lipoproteins come in small denser sizes and also large fluffy sizes. He argues that larger fluffy particles weigh more and thus nmols/L is not influenced by weight, He also suggest normal levels are below 35 nmols/L, borderline is 35-75nmols/L, high is 75-125nmols/L and very high over 125nmols/L. The Lipoprotein a Foundation indicates that normal is less than 30mg/dl or 75nmols/L with men younger than 55 and women 65 often experiencing increased risk of heart attack, stroke, and narrowed arteries supplying blood to vital organs. Nordestgaard and colleagues 9 combined with the Lipoprotein (a) Foundation suggests the following groups should request testing from your Heath Care Provider:

  • Having Familial Hypercholesterolemia, an inherited high LDL cholesterol levels
  • Strong family history of cardiovascular disease including heart attack, stroke and narrowed arteries involving males under 55 and females under 65 years of age
  • Personal history of premature cardiovascular disease
  • Someone in your family has high Lp(a) levels. This is mostly an inherited condition, thus if an adult has it there is a one in two chance the children will also have it. All members of the family should then be tested.
  • .
  • Heart attack or stroke with no other known risk factors such as smoking, high LDL or bad cholesterol, diabetes or obesity. 50% of individuals who have had heart attacks have normal levels of LDL cholesterol
  • High LDL levels along with cardiovascular disease even though taking statins and or other cholesterol lowering medications

Approximately 30% of individuals with Familial Hypercholesterolemia have high Lp(a) levels and most are not routinely tested for this 10. If members of your family have high levels of Lp(a), be persistent in having your Doctor order this test. Currently the European Society of Cardiology, the European Atherosclerosis Society, the National Lipid Association and the Canadian lipid guidelines recommend Lp(a) testing for those at intermediate or high risk for CVD, strong family history, recurrent CVD, and for those unresponsive to guideline recommended therapies. 11

Treatment Options:

Unlike elevated LDL-C, elevated Lp(a) is resistant to both lifestyle modification and statin treatment. Although statins only decrease Lp(a) modestly, Dr. Stanley Hazen of the Cleveland Clinic which reviewed Lp(a) levels with 5,000 patients suggested higher dosage of statins should be prescribed as a means of reducing inflammation and myocardial infarction and ischemic stroke. He contended which was borne out by their study that Lp(a) which rides on LDL particles will ultimately do less damage if LDL particles are not available to attach to. In their study they were able to reduce rising mortality rates due to high levels of Lp(a) through reducing LDL-C levels. This approach they believe will ultimately reduce the risk for recurrent myocardial infarction and or stroke. 12

In patients with Familial Hypercholesterolemia statins have been shown to reduce Lp(a) levels by 17 to 22%. Niacin either alone or in combination with statins appears to be most effective in lowering Lp(a) levels by up to 40%.

Lipoprotein apheresis is the most effective way to both lower cholesterol and Lp(a) levels. Originally introduced to treat Familial Hypercholesterolemia 40 years ago its use has been expanded to include patient with progressive CVD due to heterozygous FH and raised levels of Lp(a). There is evidence that apheresis completed weekly or biweekly coupled with statins prolongs life expectancy of homozygotes and reduces cardiovascular events in heterozygotes. There is also evidence that apheresis also arrests progressive CHD and reduces events in patients with raised Lp(a).13

Other agents that have had minor success in lowering Lp(a)(less than 10%) levels include 81mg aspirin, estrogen, thyroxine replacement, and fish oil. The (PCSK9i) protein convertase subtilisin/kexin-type 9 inhibitor such as Repatha and cholesterol ester transfer protein (CETP) inhibitor are two compounds that reduce Lp(a) by 40% and 17% respectively.14 15 Currently none of the new medications have been approved as Lp(a) lowering indications. We do know that some newer pharmaceutical medications are within clinical trials; however these results are still a few years out.

If you suspect you have high levels of Lp(a) consult with your Doctor and ask for the blood test to determine your levels. If you are found to have high levels, have the rest of your family tested. Do not take niacin over the counter unless consulting with your Doctor.

The National Heart, Lung, and Blood Institute has developed an agenda for future research and action on raised levels of Lp(a). Some of this includes educating Doctors, Health Care practitioners, Individuals and Families about the role of Lp(a) and cardiovascular disease. Additionally, there is a recommendation to conduct more testing of individuals in identifying prevalence rates and reducing risk for myocardial infarction, strokes, peripheral artery disease and aortic stenosis. Equally future research into Lp(a) as a risk factor for CVD, the effect of PCSK9i on reducing Lp(a) and whether this medication which si taken as an injection ultimately reduces CVD risk.

My intention was to introduce you to Lp(a) which is often undiagnosed. I hope I have piqued your interest and if you meet the criteria for testing motivated you to call your Doctor to arrange for testing. If you have questions or comments, we would love to hear from you. Send your questions or comments to jsawdon@cardiachealth.ca. If you have topics you want us to address send us note.

References:

  1. Kresser, Chris Let’s Take back Your Health: RHR: How your Lipoprotein (a) Level affects Your Risk of Heart Disease December 26, 2014 https://chriskresser.com/how-your-lipoproteina-level-affects-your-risk-of-heart-disease/
  2. Lipoprotein(a) Foundation; Understand your Lipoprotein (a) May 30 2017 https://www.lipoproteinafoundation.org/?page=UnderstandLpa
  3. Rosenson, Robert S MD, Stein, James H MD, Durrington Paul MD, Lipoprotein (a) and Cardiovascular Disease, UptoDate Wolters Kluwer https://www.uptodate.com/contents/lipoprotein-a-and-cardiovascular-disease
  4. Saeedi, Ramesh MD, PhD; Li,Min MD PhD; Frohlich MD FRCPC : Lipoprotein(a): Why is it so Important? BC Medical Journal Issue: BMJ, Vol.56, No.4, May 2014, page(s) 180-182 Articles https://www.bcmj.org/print/6498
  5. Ibid Lipoprotein(a) Foundation
  6. Qi, Quibin, Qi, Lu Liopoprotein(a) and cardiovascular disease in diabetic patients Department of Nutrition, Harvard Scholl of Public Health & Channing Laboratory, Department of Medicine, Brigham & Women’s Hospital & Harvard medical School August 2012:7(4): 397-407 doi:10.2217/clp.12.46 National Institute of Health, Clin Lipodol. Available in PMC 2013 June 01
  7. Moll, Jennifer Pharm D; What is Lipoprotein(a)? April 8 2017 Very Well https://www.verywell.com/what-is-lipoproteina-698070?print
  8. Nainggolan, Lisa: Lp(a) Gene Variant Associated with Aortic Stenosis February 6 2013 https://www.medscape.com/viewarticle/778878_print.
  9. Ibid Lipoprotein (a): Why is it so important? BC Medical Journal May 2014
  10. Ibid Lipoprotein(a) Foundation May 30 2017
  11. Graveline, Duane MD, PhD Lipoprotein(a) –Lp(a)- and Heart Disease https://spacedoc.com/articles/lpa-and-heart-disease
  12. Hazen, Stanley MD PhD, Lipoprotein(a)-Treating the Untreatable Health Essentials https://health.clevelandclinic.org/2011/09/do-you-know-your-cholesterol/
  13. Walji,Shahenaz, Neuwirth Claire, Thompson Gilbert R; Lipoprotein Apheresis for the Treatment of Familial Hypercholesterolemia clin lipology 2013:8(5): 573-586 http://www.medscape.com/viewarticle/811660_print
  14. Ibid Lipoprotein (a): Why is it so important? BC Medical Journal May 2014
  15. Eckardstein, Arnold von; Lipoprotein (a) : A refractory risk factor for atherosclerotic and thrombotic vascular diseases; European Heart Journal 2017 38, 1530-1541 https://academic.oup.com/eurheartj/article-abstract/38/20/1530/3836081/lipoprotein-a
  16. Raal, Frederick J MB BCH MMed PhD; Giugliano, Robert P MD SM; Sabatine, Marc S MD MPH; Koren, Michael J MD; Langslet Gisle MD; Bays Harold MD; Blom Dirk PhD MD; Eriksson Mats MD; Dent Ricardo MD; Wasserman Scott M, MD; Huang Fannie MS; Xue Allen PhD; Albizem Moetaz MD; Scott Rob MD; Stein Evan A, MD PhD: Reduction In Lipoprotein (a) with PCSK9 Monocloanl Antibody Evolocumab (AMG 145) Journal of American College of Cardiology 2014 published by Elsevier Vol 63 No 13 2014 ISSN 0735-1097

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.