The Top 3 Questions about Lp(a), by Dr. Kahn

By Joel Kahn, MD, FACC

We owe fitness guru and TV host of The Biggest Loser series, Bob Harper, much gratitude for educating the public about his near-death experience in early 2017 from closure of his “widowmaker” heart artery while exercising. He has publicly highlighted his missed warning signs, his recovery in cardiac rehabilitation classes, his ongoing emotional recovery with the support of his fans and his dog, and the use of automatic defibrillators in gyms and other public settings to save lives. All this has received much media attention and undoubtedly has done more to raise awareness of these issues than many prior efforts.

Furthermore, Bob Harper pushed the envelope again by educating the public about a high level of a form of cholesterol he inherited that is neither rare nor benign. Harper indicated that his heart attack was due to an elevated level of Lipoprotein(a), a cholesterol particle related to but different from the better-known LDL cholesterol.

At my preventive cardiology clinic, I care for hundreds of patients with elevated Lipoprotein(a) and I want to share some of that experience with you.

1. What is Lipoprotein(a)? 

 Lipoprotein(a) is also known as Lp(a) or the “sticky cholesterol”. It is a particle in the blood that carries cholesterol, fats and proteins.  Whether it is detectable in your blood depends on whether you inherited the ability to produce it from one or both parents. You can be thin, exercise, and eat a lot of kale and still have a very high level of Lp(a). The level of Lp(a) usually does not change much from childhood on.  Diet, exercise, and statin medications like atorvastatin have little impact on lowering the level of Lp(a).

Lp(a) is a big molecule made in the liver separately from LDL-cholesterol that is a combination of fats, proteins and cholesterol.  High levels in the blood increase the risk of conditions that may alter cardiovascular health and fitness. It is the strongest inherited risk factor for heart disease in otherwise healthy persons. In fact, over 80 million people in the USA alone have elevated levels. It is more commonly inherited in African-Americans and those of Asian background. 

All that is needed to check whether the individuals you see in your practice have inherited Lp(a) from one or both parents is a simple blood test that is widely available and not expensive.

Unfortunately, a measurement of Lp(a) is not included in standard cholesterol panels.  Levels of Lp(a) are reported in different units, either mg/dL or nmol/L.  A normal level is less than 30 mg/dL or less than 75 nmol/L. Some people I treat have Lp(a) levels of over 400 mg/dl!

2. When do you check Lp(a) levels?

Recently, the European Society of Atherosclerosis recommended widespread measurement of Lp(a) one time to determine if someone has a hidden risk for atherosclerosis.

I agree with this recommendation, but in the USA, the current advice¹ is to check Lp(a) blood level if: 

• The individual has a family member with early heart disease or stroke (men younger than 55 years of age and women less than 65 years of age)
• A family member is known to have high Lp(a).  If a parent has high Lp(a), their children have a 1 in 2 chance of being high.
• The individual suffered a heart attack, stroke, or aortic valve stenosis with no other known risk factors.
• The individual’s cholesterol is high despite taking a statin medication.² It might be the LDL cholesterol within Lp(a) is adding to the result; statins do not lower Lp(a) cholesterol.^3-4

3. What can be done about a high Lp(a)? 

As with all cardiovascular risk, lifestyle and reduction of inflammation is essential for individuals with elevated Lp(a). In particular, I always work with individuals to help them to follow a lifestyle known to reduce the overall risk of heart disease, including: 

• Eat a healthy diet.⁵ People with high Lp(a) appear to benefit from a whole food, plant-based diet or a Mediterranean diet emphasizing vegetables, whole fruits, whole grains, and legumes while limited dairy, meats, eggs, added sugars, and refined grains.  
• Exercise 30-60 minutes a day.
• Stop smoking
• Control your weight to keep your waistline thin.
• Lower stress with 7-8 hours of sleep along with relaxation like yoga or meditation.
• Know your blood pressure, blood sugar and LDL-cholesterol numbers and work to manage them to optimal levels.

Currently, there is no approved medication for those with elevated Lp(a). New injectable drugs used to lower cholesterol are now FDA approved and these also lower Lp(a). New medications are in clinical trials to specifically lower Lp(a), but it will be several years before results are available. Unfortunately, statin cholesterol medication does not lower Lp(a) and often raises it. There are two injectable PCSK9 inhibitor medications that often lower both LDL-cholesterol and Lp(a) but they are only approved for lowering LDL-cholesterol and are expensive. Niacin or vitamin B3 lowers Lp(a) and  also lowers LDL-cholesterol and triglycerides while raising HDL-cholesterol. There are no large and long-term studies using niacin in patients with Lp(a), however. 

In peri and post-menopausal women, hormone replacement therapy (HRT) can lower Lp(a) levels. Finally, an advanced treatment called apheresis, similar to hemodialysis, cleanses the blood of Lp(a) through a filter. This is available and approved for use but is used infrequently due to the complexity and expense. 

One other potential intervention is to protect and support the artery wall itself. All the blood vessels are protected by a thin inner lining called the endothelial glycocalyx. One of the main dangers of Lp(a) and other molecules in the blood is that they can adhere to the blood vessel wall, causing damage and inflammation. By protecting and sustaining the blood vessel wall, these particles are less likely to lodge in the subendothelial space and trigger disease.

Thank you Bob Harper, and others, who have worked to make Lp(a) a household word. At present, approximately 1% of physicians routinely measure levels of Lp(a) but the word is getting out. When you see patients with elevated cardiovascular risk, consider who might benefit from Lp(a) testing.

Joel Kahn, MD, FACC

Founder, Kahn Center for Cardiac Longevity

References

1. Wilson DP, Jacobson TA, Jones PH, et al. Use of Lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association. Journal of Clinical Lipidology. 2019;13(3):374-392. doi:10.1016/j.jacl.2019.04.010
2. Willeit P, Ridker PM, Nestel PJ, et al. Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials. The Lancet. 2018;392(10155):1311-1320. doi:1016/S0140-6736(18)31652-0
3. Tsimikas S, Gordts PLSM, Nora C, Yeang C, Witztum JL. Statin therapy increases lipoprotein(a) levels. Eur Heart J. 2020;41(24):2275-2284. doi:10.1093/eurheartj/ehz310
4. Wang X, Li J, Ju J, Fan Y, Xu H. Effect of different types and dosages of statins on plasma lipoprotein(a) levels: A network meta-analysis. Pharmacol Res. 2021;163:105275. doi:10.1016/j.phrs.2020.105275
5. Engler RJM, Brede E, Villines T, Vernalis MN. Lipoprotein(a) Elevation: A New Diagnostic Code with Relevance to Service Members and Veterans. Fed Pract. 2019;36(Suppl 7):S19-S31.

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