Is High Cholesterol Genetic? ApoB & Lp(a)

High cholesterol can be inherited. Familial hypercholesterolaemia (FH) is a genetic condition that keeps LDL (low-density lipoprotein) cholesterol high from birth, and lipoprotein(a), or Lp(a), is a largely inherited risk factor that routine cholesterol tests leave out. If heart disease runs in your family, your doctor may consider whether tests such as ApoB or Lp(a) are appropriate.

At a glance

• A normal cholesterol result does not rule out inherited heart risk.
• Lp(a) is mostly inherited, and international guidelines suggest measuring it at least once in adulthood.
• If FH is found, close relatives, including children, may need their cholesterol checked.

To understand where your own risk sits, start with a doctor-led cardiovascular disease prevention consultation that looks at your personal risk of heart disease and stroke.

Is High Cholesterol Genetic or Caused by Lifestyle?

It can be both. Genes and lifestyle shape most people's cholesterol, but in familial hypercholesterolaemia an inherited gene change reduces how well the body clears LDL cholesterol, so levels are high from birth.

How Is FH Inherited?

FH is inherited in a dominant pattern, so one affected parent can pass it on. A 2013 European Atherosclerosis Society (EAS) consensus statement [1] notes that roughly half the close relatives of someone with a known FH gene change will have inherited it, and that untreated FH typically causes coronary heart disease before 55 in men and 60 in women.

How Common Is Familial Hypercholesterolaemia in South Africa?

South African researchers [2] note that FH affects about 1 in 80 people of Afrikaner ancestry, because of "founder" gene changes inherited from a few shared ancestors. It is also a major contributor to early heart disease in South Africans of Jewish and Indian descent, and occurs in Black South Africans too [2].

In a Cape Town study of 1,031 people with FH at a hospital lipid clinic [3], the average age at presentation was 44, and 43% had ischaemic heart disease (reduced blood flow to the heart muscle). These clinic patients were likely at the more severe end, and the authors describe FH as treatable [3], so early recognition matters.

Signs That May Point to an Inherited Cholesterol Problem

The EAS [1] recommends screening adults, children and families for FH when there is:

• A relative already diagnosed with FH
• Total cholesterol of 8 mmol/L or higher in an adult, or 6 mmol/L or higher in a child
• Early heart disease in you or a close relative, or a sudden early cardiac death in the family
• Tendon xanthomas: firm cholesterol deposits in tendons, often at the heel or over the knuckles

These deposits become more common with age [3], so their absence does not rule FH out.

Can You Have Heart Disease With Normal Cholesterol?

Yes. Blood pressure, smoking, diabetes, age and family history all affect heart risk, and a routine cholesterol test does not include Lp(a), which a 2022 EAS consensus statement [4] describes as a risk factor even when LDL cholesterol is very low.

The amount of cholesterol in each particle also varies [5], so the number of cholesterol-carrying particles can be higher than LDL cholesterol suggests. Our companion guide explains what a routine biomarker panel tests for, from LDL and HDL cholesterol to triglycerides.

"Normal" also depends on your overall risk. The 2018 South African dyslipidaemia guideline [6] sets lower LDL cholesterol targets as risk rises, from below 3 mmol/L to below 1.8 mmol/L.

Is ApoB Better Than LDL Cholesterol?

ApoB does not replace LDL cholesterol, but it can add useful information. Apolipoprotein B (ApoB) sits on each particle that can deposit cholesterol in artery walls, one molecule per particle, so it counts these particles.

A 2019 narrative review in JAMA Cardiology [5] argued that ApoB may capture this risk more accurately than LDL or non-HDL cholesterol (total cholesterol minus HDL, the "good" cholesterol).

The American College of Cardiology and American Heart Association guideline [7] uses ApoB selectively, suggesting it may help assess remaining risk in type 2 diabetes, high triglycerides, cardiometabolic disease or known cardiovascular disease once LDL and non-HDL cholesterol goals are met. Targets vary by risk, so there is no universal "normal" ApoB.

If blood sugar or triglycerides are a concern, consider a metabolic disease prevention consultation that reviews glucose metabolism, lipid balance and family history together.

What Is a Normal Lp(a) Level?

There is no single normal Lp(a) level. The 2022 EAS consensus statement [4] suggests Lp(a)-related risk is unlikely below 30 mg/dL or 75 nmol/L, and increased above 50 mg/dL or 125 nmol/L, with values in between read alongside other risk factors. Risk rises gradually rather than at one cut-off [4].

Lp(a) is an LDL-like particle whose level is more than 90% genetically determined, near adult levels by about age 5, and little changed by lifestyle [4]. Above 180 mg/dL or 430 nmol/L, lifetime risk is similar to untreated FH [4].

Why nmol/L and mg/dL Results Don't Convert Simply

Laboratories report Lp(a) in nmol/L or mg/dL, and the EAS [4] advises against a fixed conversion factor because tests vary. Guidelines differ too: the EAS and American guideline pair 50 mg/dL with 125 nmol/L [4,7], while the European Society of Cardiology (ESC) and EAS update uses 105 nmol/L [8].

Should Everyone Test Lp(a) Once?

European and American guidelines support testing Lp(a) at least once in adulthood [4,7,8]. The earlier 2018 South African guideline [6] uses the same 50 mg/dL or 125 nmol/L risk threshold, but suggests testing mainly for people at higher risk, such as those with FH or a family history of early heart disease.

The 2025 ESC/EAS update notes that at least 20% of people have levels above 50 mg/dL [8]. Because Lp(a) is largely stable, repeat testing is generally unnecessary [7], unless there is a specific reason such as kidney or liver disease, an acute infection, or a first test in childhood [4].

Heart Disease Runs in My Family: What Tests Should I Do?

Start with a detailed family history, a routine cholesterol test, and blood pressure and glucose checks. Your doctor can then consider whether tests such as ApoB or Lp(a), or genetic assessment, would help.

Cholesterol can be checked on its own or within a doctor-selected comprehensive biomarker panel that looks at lipid metabolism alongside inflammation, insulin regulation and organ function, and our guide explains which checks, including cholesterol and your family history of cardiovascular disease, are worth discussing in your 30s, 40s and 50s.

What Counts as "Premature" Heart Disease?

Definitions vary. The Dutch Lipid Clinic Network FH criteria [1] count heart disease as premature if a first-degree relative (parent, sibling or child) developed it before 55 in a man or 60 in a woman.

The South African guideline [6] advises cholesterol screening from age 20 if a male first-degree relative was affected at 55 or younger, or a female relative at 65 or younger.

Should Children and Other Relatives Be Tested?

When FH is diagnosed, guidelines recommend cascade screening: testing relatives step by step through the family [1,6].

The South African guideline [6] advises screening children of affected families from around age 8, or within six months of birth if both parents have FH. Lp(a) testing may also be reasonable if a parent or sibling has markedly raised Lp(a) [4]. Ask your doctor when your children should be tested.

What Happens If Your ApoB or Lp(a) Result Is High?

A raised result is a reason for a fuller risk assessment, not a diagnosis of heart disease.

A high ApoB is read alongside your other lipid results and overall risk [7]. For raised Lp(a), the EAS [4] recommends early, intensive management of other risk factors, such as:

• Blood pressure and blood glucose control
• Stopping smoking
• Activity, nutrition and weight
• Cholesterol-lowering medication to reduce LDL cholesterol, where appropriate

Lifestyle barely shifts Lp(a) itself [4], so the aim is to lower your overall risk. If FH is suspected, your doctor may refer you for further assessment.

Chest pain or pressure, sudden breathlessness, fainting, or stroke signs such as facial drooping, arm weakness or slurred speech need emergency care immediately, not a booked appointment.

Book a Cardiovascular Disease Prevention Consultation in Cape Town

If heart disease came early in your family, or your cholesterol has always run high, one of our doctors can help you decide which tests are relevant and what your results may mean for your relatives.

Fluid Medical is a multidisciplinary medical centre in Cape Town, with doctors across General Healthcare for Men & Women, Preventative & Longevity Medicine, Sports & Exercise Medicine and Aesthetics Treatments. It is care that doesn't start over every visit: doctor-led, from consultation to treatment.

For a longer-term view, consider a longevity consultation that brings your genetics, medical history and risk factors for age-related disease into one personalised plan. You can also book a cardiovascular disease prevention consultation at our medical centre in Gardens, or call 021 200 2121.

This article is general health information and does not replace a consultation with a doctor.

References

1. Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478-90a. doi:10.1093/eurheartj/eht273. https://pubmed.ncbi.nlm.nih.gov/23956253/
2. Raal FJ, Bahassi EM, Stevens B, Turner TA, Stein EA. Cascade screening for familial hypercholesterolemia in South Africa: the Wits FIND-FH program. Arterioscler Thromb Vasc Biol. 2020;40(11):2747-55. doi:10.1161/ATVBAHA.120.315040. https://pubmed.ncbi.nlm.nih.gov/32878475/
3. Firth JC, Marais AD. Familial hypercholesterolaemia: the Cape Town experience. S Afr Med J. 2008;98(2):99-104. https://pubmed.ncbi.nlm.nih.gov/18350202/
4. Kronenberg F, Mora S, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925-46. doi:10.1093/eurheartj/ehac361. https://pubmed.ncbi.nlm.nih.gov/36036785/
5. Sniderman AD, Thanassoulis G, Glavinovic T, Navar AM, Pencina M, Catapano A, et al. Apolipoprotein B particles and cardiovascular disease: a narrative review. JAMA Cardiol. 2019;4(12):1287-95. doi:10.1001/jamacardio.2019.3780. https://pubmed.ncbi.nlm.nih.gov/31642874/
6. Klug E, Raal FJ, Marais AD, Smuts CM, Schamroth C, Jankelow D, et al. South African dyslipidaemia guideline consensus statement: 2018 update. A joint statement from the South African Heart Association (SA Heart) and the Lipid and Atherosclerosis Society of Southern Africa (LASSA). S Afr Med J. 2018;108(11b):973-1000. doi:10.7196/SAMJ.2018.v108i11.13383. https://pubmed.ncbi.nlm.nih.gov/30421699/
7. Blumenthal RS, Morris PB, Gaudino M, Johnson HM, Anderson TS, Bittner VA, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of dyslipidemia: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2026;87(19):2624-757. doi:10.1016/j.jacc.2025.11.016. https://pubmed.ncbi.nlm.nih.gov/41824590/
8. Mach F, Koskinas KC, Roeters van Lennep JE, Tokgözoğlu L, Badimon L, Baigent C, et al. 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2025;46(42):4359-78. doi:10.1093/eurheartj/ehaf190. https://pubmed.ncbi.nlm.nih.gov/40878289/

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