We’ve all seen this patient – the one with a normal cholesterol level and no apparent cardiovascular risk factors who gets admitted with a myocardial infarction at age 50. For years, we had no explanation for why someone so healthy would get such bad coronary artery disease. But now, we do – that explanation is lipoprotein (a). And now, we have treatments that can lower lipoprotein (a) levels and reduce the chances of a heart attack or stroke later in life.
Lipoprotein (a) is composed of an LDL particle with a large glycoprotein called apo(a) wrapped around it. The concentration of lipoprotein (a) in the blood is controlled by the LPA gene on chromosome 6. Heritable variations in this gene result in higher or lower lipoprotein (a) levels. As a result, if a person inherits a certain variation of the LPA gene, that person will have high blood concentrations of lipoprotein (a). About 20 – 30% of humans have elevated lipoprotein (a) levels and these persons are at increased risk of atherosclerosis. People of African descent typically have 2-3 times higher blood levels of lipoprotein (a) than people of European or Asian descent.
Lipoprotein (a) is produced by the liver and then released into the blood. It is excreted or metabolized by the kidney with the result that kidney disease causes the lipoprotein (a) blood levels to increase and liver disease causes levels to decrease. A diet low in saturated fats can also decrease lipoprotein (a) blood levels, but only modestly.
Historically, blood test screening for cardiovascular risk assessment consisted of measuring total and LDL cholesterol levels. People with high LDL levels are usually recommended to start statin medications to reduce their blood cholesterol and thus reduce their risk of atherosclerosis. But it appears that lipoprotein (a) levels may be just as important as LDL levels when it comes to cardiovascular risk. However, most primary care physicians have not been routinely screening patients for elevated lipoprotein (a) levels. This needs to change and I believe that every American should have their lipoprotein (a) level tested once in their life, preferably in their 20’s or earlier, before the onset of atherosclerosis.
What do you do with a patient with a high lipoprotein (a) level?
Statins are great at reducing LDL cholesterol levels but they have a minimal effect on lipoprotein (a) levels. In the past, that was a major reason why physicians did not regularly do screening lipoprotein (a) levels – the thought was: “If I can’t do anything about it, why test for it?” But there are compelling reasons to test patients because there is something we can do about it and those treatment options will be increasing in the near future. Here are some of the things you can do for your patients with high lipoprotein (a) levels:
- Have a lower threshold for starting statins. Currently, statins are recommended for any adult with an LDL cholesterol level above 190 mg/dL. For those with other cardiovascular risk factors putting them at high risk, the LDL cholesterol threshold for statins is 70 mg/dL. The lipoprotein (a) level should be included as one of these other cardiovascular risk factors and patients should be started on a statin if their LDL cholesterol is above 70 mg/dL and also have a lipoprotein (a) level above 50 mg/dL. The statin may not lower lipoprotein (a) levels but by reducing LDL cholesterol levels, the statin can reduce one’s cardiovascular risk.
- Have a lower threshold for starting anti-hypertensive medications. Currently, an out-of-office daytime blood pressure ≥135 mmHg systolic or ≥85 mmHg diastolic is considered indications for starting medication for hypertension. Lower blood pressure thresholds are used if patients have additional cardiovascular risk factors such as diabetes, kidney disease, or age over 65. Consider starting anti-hypertensive medications in patients with an out-of-office daytime blood pressure ≥130 mmHg systolic or ≥80 mmHg diastolic if their lipoprotein (a) level is greater than 50 mg/dL.
- Stronger lifestyle modification recommendations. Some people can get away with being obese, smoking, or a high saturated fat diet. Those with a high lipoprotein (a) level are not these people and need to be told that stopping smoking, keeping their BMI below 30, and eating a diet low in saturated fats is essential to avoiding cardiovascular disease.
- Screen the family. Because lipoprotein (a) levels are determined by inherited genes, if one family member has high levels, it is likely that other family members do also. Advise patients that they have a genetic condition that increases the risk of cardiovascular disease and that they should tell their first degree relatives to get their own lipoprotein (a) level tested.
- PCSK9 inhibitors. Recently, drugs that can reduce lipoprotein (a) levels by 25% have been approved. These include the monoclonal antibodies, evolucumab (Repathа) and alirocumab (Praluent). These drugs have their FDA indications for secondary prevention of atherosclerosis and for familial hypercholesterolemia so treatment of elevated lipoprotein (a) levels is currently considered an off-label indication. This can make insurance coverage difficult by some health insurance companies.
- Lipoprotein apheresis. This is the only FDA-approved treatment for elevated lipoprotein (a) levels and can reduce those levels by 75%. However, aphaeresis must be performed weekly, making it both inconvenient and very expensive for the patient. My suspicion is that most health insurance companies if given a choice between paying $2,500 per week for apheresis or paying $340 every two weeks for Repatha will approve off-label use of Repatha in order to avoid paying for apheresis.
- Pelacarsen. This is an investigational anti-sense medication that targets messenger RNA for lipoprotein (a) and can reduce levels by 50%. Phase 3 studies are underway and FDA approval could come later this year.
Don’t wait… screen everyone
Because a person’s lipoprotein (a) level remains constant throughout life after age 5-years-old, there is no reason to wait until patients are elderly or already have heart disease. Instead, consider testing patients in their 20’s or even earlier in order to encourage a life-time of heart healthy lifestyle changes. The only caveat is that is best to screen patients when they are healthy and not during periods of inflammation, kidney disease, or liver disease since these conditions can affect lipoprotein (a) levels. Most commercial labs will perform lipoprotein (a) tests for $30 – $50 without an order from a person’s doctor. Physician-ordered tests that are run through a patient’s insurance may be even less expensive.
Many physicians rely on the United States Preventive Services Task Force (USPSTF) recommendations when deciding what patients should be screened for what diseases. Currently, the USPSTF has no recommendations about screening patients for elevated lipoprotein (a) levels. But other organizations do have recommendations. For example, the National Lipid Association recommends measuring lipoprotein (a) at least once in every adult. The European Atherosclerosis Society also recommends testing all adults at least once. The American College of Cardiology recommends testing all individuals with risk factors for cardiovascular disease once in a lifetime. The USPSTF generally bases its guidelines on recommendations from specialty societies, it is likely that the USPSTF will include recommendations for lipoprotein (a) screening in the future. But as I see it, there is no reason to wait for the USPSTF, go ahead and start screening all patients now.
February 13, 2025
