Did you know there are several factors that can contribute to atherosclerotic cardiovascular disease (ASCVD) which can cause heart attacks or stroke? These factors include age, sex, high blood pressure, smoking, diabetes, obesity, elevated levels of low-density lipoprotein cholesterol (LDL-C) and/or lipoprotein(a) (Lp(a)), and genetic conditions such as familial hypercholesterolemia.1

For some, these ASCVD events can strike even in the absence of any well-known risk factors. The reason for this could lie in a little-known particle found in the body called Lp(a), which is pronounced L-p-little-a. Lp(a) can deal a triple blow to heart and blood vessel (cardiovascular) health by narrowing arteries, fanning the flames of inflammation, and enhancing the risk of blood clots.2 To shed further light on Lp(a), we’re answering some of the most important questions about this little-known form of a bad cholesterol.

What is Lp(a)?

A lipoprotein is a fat and protein molecule that carries cholesterol in the blood.3 Cholesterol has a bad reputation in the world of health, but at the correct levels, it is a vital component to building healthy cells and hormones.3 The two most well-known types of lipoprotein are low-density lipoprotein (LDL), sometimes known as “bad cholesterol,” and high-density lipoprotein (HDL), or “good cholesterol”.3,4

Produced in the liver, Lp(a) is another type of lipoprotein that carries cholesterol, fats and proteins in the blood.5,6 Unfortunately, Lp(a) can cause problems if levels are elevated in the body. People who may otherwise appear healthy can develop ASCVD, which can cause heart attacks, stroke and other related conditions.7-10 Lp(a) levels are primarily – up to 90% – determined by a person’s genes.2

Visualization of the impact of Lp(a)

Coronary arteries supply blood, oxygen and nutrients to the heart.11 Here we can see a narrowing of the coronary artery due to the buildup of a fatty deposit – an atherosclerotic plaque.11 If the atherosclerotic plaque ruptures, it can cause an ASCVD event such as a heart attack or stroke.11 Elevated levels of Lp(a) cause atherosclerotic plaques to form, and also increase inflammation (which may promote the growth and loosening of plaques) and the risk of blood clots.5,12

Are elevated levels of Lp(a) bad for health?

It is normal to have Lp(a) in the blood. At normal levels, it assists in the natural clotting of blood and wound healing.13 But having elevated levels is a known independent risk factor that causes ASCVD.7,14 Living with ASCVD means fatty deposits are building up in the arteries in a process called atherosclerosis.15 This is problematic because atherosclerotic plaques (the name for the fat buildup in the arteries) can rupture and cause a cardiovascular event such as a heart attack or stroke.15 Lp(a) also increases inflammation, which in turn may promote the growth and loosening of plaques, and the risk of blood clots.2,14,16,17 People with elevated Lp(a) have twice the risk of experiencing an ASCVD event compared to those who not have elevated Lp(a).5,12

Well-recognized risk factors for ASCVD include age, sex, high blood pressure, high cholesterol, diabetes and smoking.10,16 Having elevated levels of Lp(a) means people are also more likely to experience ASCVD in the future.12,18

While having elevated levels of Lp(a) may increase a person’s likelihood of ASCVD, this does not guarantee they will develop it. People who have multiple risk factors are at higher risk of developing ASCVD, however.16 And, unfortunately, despite increasing the risk of ASCVD events by a similar amount to high LDL-C (“bad” cholesterol), most people aren’t aware of their Lp(a) levels.19-27

“Elevated ” Lp(a) levels: what are they and what causes them?

Lab equipment

Normal Lp(a) levels in the blood are less than 30 milligrams (mg) per deciliter (dL), or 75 nanomoles (nmol) per liter (L). Levels higher than this are believed to increase the risk of developing ASCVD, and levels greater than 50 mg/dL or 125 nmol/L are considered elevated.1,12,28 People with elevated Lp(a) over 93 mg/dL are 1.6 times more likely to experience stroke than individuals with low Lp(a) of 10 mg/dL or below.18,29-32

Around 20–30% of the global population – that’s about 1.4 billion people! – have elevated Lp(a) levels, but many people who appear healthy may not know they are at risk.12

Lp(a) levels are usually genetically determined.2 If one of a person’s parents has elevated Lp(a) levels, they may have a 1 in 2 chance of also having elevated Lp(a) levels.2,33 Elevated Lp(a) levels can affect anyone but are more common in certain ethnic groups, including people of African origin.34

Levels do not change very much over one’s lifetime, though they can vary in women.2,14,34,35 This is because Lp(a) levels increase as estrogen levels naturally decline during menopause.2,14,34,35

How are Lp(a) levels tested?

Lp(a) levels can be tested through a simple blood test. Unfortunately, however, this test is rarely included in standard cholesterol or lipid testing.34

Testing should be considered for people who are at a higher risk of heart disease, such as those with:14,35

Patient with elevated lipoprotein(a) learns about ASCVD
  • A family history of elevated Lp(a) levels
  • A family history of ASCVD at an early age (under 55 years for men and under 65 years for women)
  • Familial hypercholesterolemia (FH)
  • A history of heart attack or stroke with no other associated risk factors, such as smoking, high LDL-C, diabetes or obesity
  • High LDL-C, even when taking medication to bring it down

Only one test is needed to determine Lp(a) levels and whether people are potentially at risk of ASCVD.7,28

Recent clinical guidelines – which are recommendations on how to diagnose, manage and treat a medical condition – from a number of international medical societies that cover ASCVD* have recognized the importance of testing for Lp(a) levels in people with ASCVD.36-39 In fact, there is a growing trend in recent guidelines towards recommending universal Lp(a) screening for everyone (not just those with ASCVD) at least once in their lifetime. Without testing people’s Lp(a) levels, people remain unaware of their CV risk associated with elevated Lp(a) or how it can be managed.40-42

What treatment options are available for people with elevated Lp(a) levels?

There are currently no approved pharmacological treatment options to effectively reduce the levels of Lp(a) in the blood. The standard treatments for high LDL-C have no or only modest effects on Lp(a).2,28

Empty medication dispenser

Knowing that Lp(a) levels are elevated and that there are no specific treatment options can be worrying, but people can still take certain steps to improve their health. General medical advice is to focus on treating the other modifiable risk factors that can contribute to ASCVD, such as high LDL-C, high blood pressure, obesity, smoking and diabetes.10,28 Additionally, there are several Lp(a) medications that are now being tested in clinical trials.2

If a person’s Lp(a) levels are elevated, they can work with their doctor to evaluate their ASCVD risk and devise an appropriate plan of action.

Can lifestyle changes improve Lp(a) levels?

It is now well known that diet and exercise changes will not have a significant effect on Lp(a) levels.2 However, diet and exercise can positively impact other risk factors.10

Novartis continues to lead the way in educating around the triple threat to cardiovascular health presented by elevated levels of Lp(a) and encouraging dialogue around ASCVD and its associated risk factors.

* Such as the European Society of Cardiology (ESC) / European Atherosclerosis Society (EAS), American Association of Clinical Endocrinologist (AACE) / American College of Endocrinology (ACE), and Canadian Cardiovascular Society (CCS).

References:

  1. Mayo Clinic. Heart disease. 2018. Available at: https://www.mayoclinic.org/diseases-conditions/heart-disease/symptoms-causes/syc-20353118.
  2. Dolgin E. Lp(a)-lowering drugs bolster cardiovascular pipeline. Nat Rev Drug Discov. 2020;19(3):154–155.
  3. Harvard Health Publishing. How it’s made: Cholesterol production in your body. 2017. Available at: https://www.health.harvard.edu/heart-health/how-its-made-cholesterol-production-in-your-body.
  4. Mayo Clinic. High cholesterol. 2019. Available at: https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/symptoms-causes/syc-20350800. Last accessed March 2020.
  5. Tsimikas S. A Test in Context: Lipoprotein(a): Diagnosis, Prognosis, Controversies, and Emerging Therapies. J Am Coll Cardiol. 2017;69(6):692–711.
  6. Encore Research Group. Normal Cholesterol Numbers Aren’t Enough? 2019. Available at: https://encoredocs.com/2019/06/11/normal-cholesterol-numbers-arent-enough/.
  7. Clarke R, Peden JF, Hopewell JC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 2009;361(26):2518–2528.
  8. Emerging Risk Factors Collaboration, Erqou S, Kaptoge S, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302(4):412–423.
  9. Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301(22):2331–2339.
  10. Roy S. Atherosclerotic Cardiovascular Disease Risk and Evidence-based Management of Cholesterol. N Am J Med Sci. 2014; 6(5): 191-198.
  11. Mayo Clinic. Coronary artery disease. Available at https://www.mayoclinic.org/diseases-conditions/coronary-artery-disease/symptoms-causes/syc-20350613. Accessed February 2022.
  12. Tsimikas S et al. J Am Coll Cardiol. 2018;71:177–192.
  13. Orsó E & Schmitz G. Clin Res Cardiol Suppl. 2017; 12(Suppl 1): 31–37.
  14. American College of Cardiology. Lipoprotein(a) in Clinical Practice. 2019. Available at: https://www.acc.org/latest-in-cardiology/articles/2019/07/02/08/05/lipoproteina-in-clinical-practice. Last accessed August 2020.
  15. National Institutes of Health: National Heart, Lung and Blood Institute. Atherosclerosis. Available at https://www.nhlbi.nih.gov/health-topics/atherosclerosis. Accessed February 2022.
  16. NHS Atherosclerosis (arteriosclerosis) https://www.nhs.uk/conditions/atherosclerosis. Last accessed July 29, 2020.
  17. John Hopkins Medicine. Fight Inflammation to Help Prevent Heart Disease. Available at: https://www.hopkinsmedicine.org/health/wellness-and-prevention/fight-inflammation-to-help-prevent-heart-disease#:~:text=Inflammation%20may%20promote%20the%20growth,you%20have%20a%20heart%20attack. Last accessed December 2020.
  18. Borén J et al. Eur Heart J. 2020;41:2313–2330.
  19. Nordestgaard BG et al. J Lipid Res. 2016;57:1953–1975.
  20. Kamstrup PR et al. JAMA. 2009;301(22):2331‒2339.
  21. Langsted A et al. J Am Coll Cardiol. 2019;74(1):54–56.
  22. Larsson SC et al. Circulation. 2020;141(22):1826–1828.
  23. Clarke R et al. N Engl J Med. 2009;361(26):2518‒2528
  24. Langsted A & Nordestgaard BG. Curr Opin Lipidol. 2020;31(3):125‒131.
  25. Tsimikas S. Curr Opin Endocrinol Diabetes Obes. 2016;23:157–164.
  26. Albers JJ et al. J Am Coll Cardiol. 2013;62(17):1575‒1579.
  27. Khera AV et al. Circulation. 2014;129:635–642.
  28. Heart UK. Lipoprotein(a). 2020. Available at: https://www.heartuk.org.uk/downloads/factsheets/lipoprotein-a.pdf. Last accessed March 2020.
  29. Libby P et al. Nat Rev Dis Primers. 2019;5(1):56.
  30.  Albers JJ et al. J Am Coll Cardiol. 2013;62(17):1575‒1579.
  31. Khera AV et al. Circulation. 2014;129:635–642.
  32. Nestel PJ et al. Arterioscler Thromb Vasc Biol. 2013;33:2902–2908.
  33. McCormick, S. Lipoprotein(a): Biology and Clinical Importance. Clin Biochem Rev. 2004. 15(1):69-80 (ncbi.nlm.nih.gov/pmc/articles/PMC1853362/).
  34. NAPS. Health Awareness - Heart Disease Risk Even Your Doctor May Not Know About. 2018. Available at: http://naprecis.com/2018/04/05/health-awareness-heart-disease-risk-even-doctor-may-not-know/.
  35. Scientific American. Lipoprotein “Little A” Can Cause More Than a Little Damage to the Heart. 2019. Available at: https://blogs.scientificamerican.com/observations/lipoprotein-little-a-can-cause-more-than-a-little-damage-to-the-heart/.
  36. Mach F et al. Eur Heart J. 2020;41:111–188.
  37. Handelsman Y et al. Endocr Pract. 2020;26:1–29.
  38. Pearson GJ et al. Can J Cardiol. 2021; DOI: https://doi.org/10.1016/j.cjca.2021.03.016.
  39. Rallidis LS et al. Atherosclerosis. 2018;269:29‒34
  40. Thanassoulis G. Circulation. 2019;139:1493–1496.
  41. Dron JS et al. Circ Genom Precis Med. 2021 Feb 1:CIRCGEN120003182. doi: 10.1161/CIRCGEN.120.003182.
  42. Lahoz R et al. Abstract and poster presented at the 88th EAS Congress 2020, Oct 4–7 (Poster 1305).