We’ve all heard the standard advice: To reduce high cholesterol, don’t smoke, stay away from fatty foods, and watch your weight. But lifestyle and diet aren’t always the cause of high cholesterol, a hallmark risk factor of cardiovascular disease. And standard screening may not give your healthcare team all the information they need to intervene early to prevent a heart attack or stroke.
That’s where advanced lipid testing comes in. These tests, which aren’t a routine part of a standard cholesterol test, or lipid test, can detect underlying genetic conditions that could be causing your body to naturally produce too much cholesterol.
The 411 on Cholesterol
Cholesterol is a waxy substance that your body uses to make hormones and digest fats. There are two types of cholesterol: high-density lipoprotein (HDL), the so-called “good” cholesterol, which is protective against heart disease, and low-density lipoprotein (LDL) cholesterol, which is often considered the “bad” cholesterol. Although LDL cholesterol is not inherently bad, too much of it can build up as plaque and stick to your arteries, causing problems like atherosclerosis.
About 40 percent of adults in the United States have high cholesterol, according to the 2020 Heart Disease and Stroke Statistics report from the American Heart Association (AHA). The Centers for Disease Control and Prevention (CDC) recommends everyone ages 20 years and older get screened every five years. People who are at high risk or who have high cholesterol should be screened more frequently, and may require more advanced testing.
A basic lipid test checks HDL and LDL levels as well as triglycerides, the most common type of fat in the blood. A lipid test will also show total cholesterol, which includes both HDL and LDL, as well as a non-HDL number, which is your LDL cholesterol minus your HDL cholesterol.
“We still get the majority of our cardiovascular risk from a standard lipid test, but for people who have already had early cardiovascular disease, other tests can be helpful to find the cause of this early disease,” says Luke Laffin, MD, the codirector of the center for blood pressure disorders at the Cleveland Clinic in Ohio.
Early Detection Can Help Manage Genetically High Cholesterol
While it’s common knowledge that you can get high cholesterol from a poor diet, obesity, lack of exercise, or smoking, in some cases, people can have high cholesterol because it runs in their family. Familial hypercholesterolemia (FH) is a genetic condition in which a person produces too much LDL cholesterol in their blood. Getting screened for these conditions early can help your doctor better manage your risk for cardiovascular disease.
“There are lots of other lipid tests besides the standard test that can help refine your risk of heart disease and gauge responses to different therapies,” says Charles German, MD, a cardiologist at the University of Chicago Medicine in Illinois.
Even if someone isn’t genetically predisposed to having high cholesterol, advanced lipid tests can paint a more accurate picture of just how much LDL cholesterol is in the blood, which could inform care and help with early intervention.
“If someone is on the fence about starting cholesterol medications even though guidelines recommend it, these advanced lipid tests can push us one way or the other,” says Dr. Laffin.
What You Need to Know About Advanced Lipid Testing
If you’ve had a stroke or heart attack as a young person or have consistently high cholesterol, especially if it can’t be explained by your lifestyle or diet, your doctor may decide you’re a candidate for advanced lipid testing.
According to Laffin, advanced lipid testing, just like regular lipid tests, requires a blood sample. Some advanced tests look for genetic disorders like FH, while others produce more comprehensive assessments of a person’s LDL cholesterol, which could help a doctor decide whether it’s time to start you on medication.
Your doctor will determine which advanced tests are needed. Below is a list of conditions your doctor might look for.
FH has gotten more attention from the cardiovascular community in recent years, and for good reason. The disorder “is one of the most prevalent and underdiagnosed genetic abnormalities within cardiology,” says Dr. German.
Experts recognize FH is underdiagnosed; it’s estimated that about 1 in 250 people worldwide have FH. Finding and treating FH early may reduce the risk of heart disease by about 80 percent, according to the CDC.
There are two types of FH: heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH).
A blood test can detect whether you carry the FH gene. If the test comes back positive, the next step would be testing immediate blood relatives, especially children, says German.
In people with FH, high cholesterol typically starts in childhood, sometimes even at birth. People with HeFH have a higher risk of heart attack in childhood or adolescence, according to German. “The idea is that the earlier we can identify it, the earlier we can intervene and prevent a heart attack or stroke. Early intervention is key,” he says.
Since FH isn’t caused by things like diet, lack of exercise, or smoking, intervention typically includes medication. A study published in November 2021 found that a combination of three medications that included proprotein convertase subtilisin–kexin type 9 inhibitors, a drug specifically designed to manage high cholesterol in people with FH, was the best method for keeping LDL cholesterol levels below 1.8 millimoles per liter (mmol/L). More than 80 percent of participants were on statins, a commonly used treatment for high cholesterol, and only about 20 percent of people who had been diagnosed with FH were using combined therapies.
“Finding and treating FH early is important because we know that cardiovascular risk is determined by the time averaged LDL cholesterol,” Laffin explains. “If you have had elevated cholesterol levels starting in your teens, which we often see in people with FH, getting aggressive treatment early will be the best thing to prevent an event later down the line.”
Lipoprotein a — Lp(a)
In general, lipoproteins are substances made from fat and protein, and their purpose is to carry cholesterol through the bloodstream.
Lipoprotein(a) is a type of LDL cholesterol. Elevated levels of Lp(a) in the blood — greater than 50 milligrams per deciliter (mg/dL) — puts someone at a higher risk for heart disease and stroke. And although it’s a type of LDL cholesterol, Lp(a) raises heart disease risk independently of total LDL cholesterol levels, according to the American College of Cardiology.
Like FH, elevated Lp(a) can be genetic. A study published in March 2018 concluded that people with FH are more likely than the general public to also have elevated Lp(a), and that having both conditions significantly increases a person’s risk of premature coronary artery disease. The study included 316 people, more than half of whom had premature coronary artery disease. Roughly 4.5 percent of participants had both Lp(a) and FH. The researchers found that elevated Lp(a) alone made someone nearly twice as likely to have premature coronary artery disease, and FH alone made someone more than three times as likely. But having both conditions increased risk more than fivefold.
According to German, like FH, elevated Lp(a) is underdiagnosed. “We think that 20 percent of the population has elevated Lp(a) levels, so we need to do a better job of screening for it,” he says.
Apolipoprotein B-100 — ApoB
Apolipoprotein B-100, or apoB, is a specific protein on the surface of cholesterol, and the main protein found in LDL cholesterol. An apoB reading can give a more accurate measurement of how much LDL cholesterol is in the blood and is a better biomarker of heart disease risk than a standard LDL-C test, according to the 2018 American College of Cardiology/American Heart Association Guidelines on managing cholesterol.
LDL Particles — LDL-P
According to German, basic lipid tests measure the amount of LDL cholesterol (LDL-C) in the blood, but not the LDL particles. LDL-P measures the number of LDL particles, whereas LDL-C is the amount of cholesterol these particles carry. Like apoB, an LDL-P reading can provide a more accurate snapshot of your LDL cholesterol levels, as well as your risk of cardiovascular disease. It’s basically an extra test that can provide more information about how much LDL cholesterol is in your blood. This test is typically used in research and wouldn’t be something your doctor orders for you, but it is a test you may come across in your research, notes German.
C-Reactive Protein — CRP
According to Laffin, this isn’t actually a lipid test, but it can provide some important information about cardiovascular risk and may be part of an advanced lipid test screening. C-reactive protein is a marker of inflammation.
“We know that inflammation is very closely tied to cardiovascular events,” explains Laffin. “If those plaques in the arteries are inflamed, they are more likely to rupture. It’s like a volcano ready to blow.”
If someone has elevated CRP levels in addition to high cholesterol, this could push a medical provider to seek more aggressive treatment for cholesterol control, Laffin says.