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Lipoprotein(a): the Other ‘Bad’ Cholesterol
There’s a simple blood test your doctor can order to detect Lp(a).
YOU’VE PROBABLY HEARD about low-density lipoprotein, or “bad cholesterol,” but did you know there’s another cholesterol that may be equally bad? Called lipoprotein(a), or Lp(a) – L-p-little-a – for short, it’s a cause of heart attacks, strokes, aortic valve disease, peripheral vascular disease and blood clots. And it’s not picked up by standard cholesterol tests you may receive at a doctor’s office. So, what’s the good news? There is a simple blood test your doctor can order to detect Lp(a), and there are potential treatment options if your level is high. Here’s what you need to know about Lp(a).
What Is Lp(a) and Why Is it Important?
Lp(a) is structurally similar to LDL or “bad cholesterol.” Like LDL, it’s a small protein carried in the bloodstream that transports cholesterol, fats and proteins to organs in the body. At high levels, Lp(a) may deposit in blood vessels and cause atherosclerosis, or plaque buildup, in vessel walls. Plaque buildup causes blood vessel narrowing and reduces the blood supply to vital organs such as the heart, kidneys and brain. Lp(a) may also get in the way of other molecules in the body that help break up clots. As a result, people with high Lp(a) levels are more prone to developing blood clots that may manifest as heart attacks and strokes.
The standard cholesterol/lipid panel of tests taken at a doctor’s office doesn’t include an Lp(a) blood test. They measure total cholesterol, high-density lipoprotein (HDL) – or “good” cholesterol – and fats called triglycerides. LDL is typically calculated from these values. Historically, clinicians have focused on LDL because high levels were shown to cause heart attacks and strokes. Like Lp(a), LDL enters blood vessel walls and may cause significant atherosclerosis. However, recent studies have discovered that other cholesterol particles, such as Lp(a), may also independently cause heart disease irrespective of LDL values.
According to the Lipoprotein(a) Foundation, nearly 63 million Americans and approximately 1 billion people globally have high Lp(a) values. Nearly 1 in every 5 people have elevated Lp(a). With cardiovascular disease remaining the No. 1 killer of Americans, identifying all risk factors, including Lp(a), that lead to cardiovascular disease is critical.
What Are the Risk Factors, and Who Should Be Screened?
Lp(a) is inherited – the value is determined primarily by genes passed along from both parents. People with high Lp(a) levels have a 50 percent chance of passing on high Lp(a) to their children. Other factors such as age, sex and medical conditions such as diabetes and high blood pressure don’t appear to affect Lp(a) value. Without treatment, Lp(a) values tend to remain constant throughout life.
Lp(a) may be measured by a simple blood test, which is offered by most major laboratories across the U.S. Values are reported in two ways: either in milligrams per deciliter or nanomoles per liter, with milligrams per deciliter indicating the mass or amount of Lp(a) proteins in circulation and nanomoles per liter reflecting the concentration of all Lp(a) particles present in the blood. Typically, values above 50 milligrams per deciliter or above 125 nanomoles per liter are considered high, but these may vary slightly depending on the lab.
Experts advise that the following people may particularly benefit from Lp(a) testing:
Those with premature heart disease or a family history of early heart disease, defined as a heart attack or stroke in men under age 55 or women under age 65.
People with a condition called familial hypercholesterolemia, in which LDL levels are very high (often above 190 milligrams per deciliter) beginning at birth.
People with a family history of elevated Lp(a), since Lp(a) is genetically inherited.
People with progression of heart disease despite being treated with cholesterol drugs such as statins.
People with more than 10 percent 10-year heart attack and stroke risk according to U.S. guidelines – a recent study in the Journal of the American College of Cardiology found that in women, Lp(a) was more associated with heart disease in those with high cholesterol.
People with premature aortic valve calcification or peripheral vascular disease.
If a person is found to have high Lp(a), first-degree family members (parents, siblings and children) are encouraged to undergo screening as well because of the inheritance risk of Lp(a). As an important recognition that elevated Lp(a) is a specific disease-causing entity, there are now new International Classification of Diseases-10 diagnosis codes for elevated Lp(a) (E78.41) and a family history of elevated Lp(a) (Z83.430) that will go into effect in October of this year. ICD-10 codes are used in health care to classify all diagnoses, symptoms and procedures as a way of recording and identifying health conditions.
What Are the Treatment Options?
While diet and exercise are recommended overall as part a healthy lifestyle to reduce cardiovascular disease, and they can improve other components of a person’s lipid panel, unfortunately lifestyle choices seem to have little effect on explicitly reducing Lp(a) levels. Even statins, which are used to reduce the amount of plaque caused by LDL, have no impact on Lp(a).
No specific medication is commercially available to specifically lower Lp(a). If Lp(a) levels are high, a prescription version of the dietary supplement niacin (vitamin B3) may be considered to lower Lp(a) values by as much as 40 percent, however evidence for this approach isn’t conclusive. In severe cases, an option is weekly plasmapheresis, a procedure similar to dialysis in which a machine can help filter out Lp(a) particles from the blood.
Research has been promising in the development of drugs specifically targeted for reducing Lp(a). In a 2015 landmark article published in The Lancet, volunteers with elevated Lp(a) levels were randomized into three groups to be administered the new drug ISIS-APO(a)Rx, which specifically targets the genetic material encoding for Lp(a). People in the group receiving the highest dose of this drug experienced an average decrease of nearly 78 percent in Lp(a) values after 30 days. According to a recent article in JAMA Cardiology, it was found that large reductions in Lp(a) are likely needed to produce meaningful benefit in reducing the heart disease risk. With these results, more clinical trials to test the safety and efficacy of these new agents are eagerly awaited.
For now, if a person is diagnosed with high Lp(a), experts recommend lifestyle changes and therapies to decrease the overall cardiovascular disease risk attributable to other modifiable risk factors. Strategies may include focusing on lowering blood pressure, eating a heart-healthy diet, losing weight, increasing physical activity, quitting smoking and reducing LDL levels. Aspirin, a platelet blocking drug, can be considered to prevent clots. An individualized plan should be made with a clinician trained in treating elevated Lp(a).
Lipoprotein(a), or Lp(a), is another “bad” cholesterol that increases your risk for heart disease and stroke, even when other cholesterol numbers are normal.
Lp(a) isn’t measured in a standard cholesterol/lipid blood test, but blood tests are available to measure a person’s Lp(a) level.
Patients at unusually high risk for cardiovascular disease should ask their doctors about measuring Lp(a). These patients include those with early heart disease or a family history of premature heart disease, familial hypercholesterolemia, a family history of elevated Lp(a) and progressive cardiovascular disease despite optimal medical management.
While we await clinical trials testing the safety and efficacy of new Lp(a) drugs, current treatment revolves around using established therapies to reduce modifiable cardiovascular risk factors.
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