The guide

When it's your genes: FH, Lp(a) and ApoB

By GyroscopeUpdated November 14, 20264 sources

Some high cholesterol comes mostly from genes. Familial hypercholesterolemia (FH) affects about 1 in 250 to 300 people, and up to 9 in 10 of them don’t know. An LDL of 190 mg/dL or more is where doctors look for it. A separate particle, Lp(a), is set almost entirely by your genes, and every adult should have it tested once.

Why people miss it

High cholesterol gets talked about as a lifestyle problem, so people with a high number blame their plate and try harder. A slim runner with an LDL of 210 assumes it’s the cheese. Family history gets lost too, since a grandfather’s heart attack at 50 was decades ago and nobody called it genetic.

The numbers show how often this happens. The 2026 US guideline says FH affects 1 in 250 to 300 people and that as many as 90% of them haven’t been diagnosed. As many as 20% of adults who have a heart attack young have the FH pattern.

What FH is

FH is an inherited fault in the system that clears LDL. Michael Brown and Joseph Goldstein won the 1985 Nobel Prize for showing that people with FH lack working LDL receptors, the drain that pulls LDL out of the blood (how it works). Inherit one faulty copy, from one parent, and your cholesterol runs two to three times normal from birth. Inherit two, which is rare, and it can be five times normal, with heart attacks in the teens.

Because the LDL is high from birth, the years pile up fast. People with FH have two to four times the risk of heart disease at a young age. General risk calculators underestimate risk in FH, so the guideline says not to use them for it.

Like a slow drain you were born with

Picture two sinks with the same tap. One has a normal drain and one has a drain half blocked from the day it was built. You can turn the tap down in the second sink, and it still fills higher than the first. That’s FH. Food changes help, and at FH levels the guideline recommends medicine as well.

The 190 line

An LDL of 190 mg/dL (4.9 mmol/L) or more is “severe hypercholesterolemia” in the guideline. At that level, doctors check for causes like an underactive thyroid, look for FH and recommend a statin, whatever the 10-year risk score says. If you’re on your own trying to figure out a 190, book the doctor first.

Not everyone with an LDL of 190 has a single FH gene. Among adults with an LDL that high, the guideline says about 2.5% have a known disease-causing FH variant on a genetic test. The rest usually have many small gene effects added together, or another cause. The guideline recommends treatment at 190 either way.

Testing your family

When one person is found, the guideline recommends testing their family. Relatives of someone with FH or with early heart disease can be checked with a single cholesterol panel from age 2. That means parents, brothers and sisters, children, and further out, grandparents, aunts and uncles. Family history alone misses a lot, since up to half of children with a high LDL have no family history anyone reports.

Lp(a): the test to have once

Lp(a), said “L P little a”, is a particle like LDL with an extra protein attached. Its level is set almost entirely by your genes and stays about the same your whole life. Food, exercise and weight barely change it, and statins don’t lower it.

It’s like your height. It was mostly settled before you were born, and nothing you eat will change it much. Knowing it still helps, because it tells your doctor how hard to push on the things you can change.

Levels are highest on average in people of African or South Asian ancestry, though a given level carries the same added risk in everyone. The two units count different things, so they don’t convert exactly. The guideline treats 125 nmol/L and 50 mg/dL as the same line.

The 2026 guideline says every adult should have Lp(a) measured at least once. One test is enough for most people, unless something like menopause, pregnancy, or kidney, liver or thyroid disease could have shifted it. If yours is high, the guideline asks doctors to control LDL, blood pressure and blood sugar more tightly, and to test your close family. What is Lp(a)? has more.

ApoB, in one paragraph

Every particle that can clog an artery (LDL, the triglyceride-carrying particles and Lp(a)) carries exactly one ApoB protein, so an ApoB test counts particles while LDL cholesterol weighs what they carry. The two usually agree. They can disagree when triglycerides are high or with diabetes, and then ApoB is the better guide. The guideline counts an ApoB of 120 mg/dL or more as a risk enhancer, and calls the test reasonable for people already on treatment once their LDL and non-HDL goals are met, especially with high triglycerides or diabetes. ApoB or LDL: which should I trust? goes further.

The genes that protect

Genes work the other way too. About 2.6% of Black participants in one 15 year US study carried a broken copy of PCSK9, a gene for a protein that destroys LDL receptors. They had 28% lower LDL and 88% less coronary heart disease (why LDL is a lifetime number). Drugs that block the same protein now lower LDL on purpose, and they’re one of the options a doctor may add for FH.