Understanding Cholesterol: LDL, HDL and Non-HDL Explained

What is cholesterol?

Cholesterol is a waxy substance used by the body for important functions, including:

• —cell membranes
• —steroid-hormone production
• —bile-acid production.

Because fats do not dissolve easily in blood, cholesterol and triglycerides travel through the circulation packaged inside particles called lipoproteins.

Different lipoproteins have different roles and associations with cardiovascular disease.

What is LDL cholesterol?

LDL stands for: low-density lipoprotein.

LDL particles transport cholesterol around the body.

When the concentration of LDL-containing atherogenic particles is too high, particles can enter the artery wall and contribute to development of atherosclerotic plaque.

The evidence linking LDL to atherosclerotic cardiovascular disease is exceptionally strong. Genetic studies, epidemiological studies and randomised clinical trials consistently demonstrate that higher cumulative exposure to LDL increases atherosclerotic cardiovascular risk and that lowering LDL reduces cardiovascular events.^[3,4]

This is why LDL is often referred to as: “bad cholesterol.”

That phrase is easy to understand, although technically LDL is a lipoprotein particle rather than cholesterol itself.

Does LDL actually cause heart disease?

Yes.

This is stronger than simply saying LDL is “associated” with heart disease.

A major European Atherosclerosis Society consensus review examined genetic, epidemiological and clinical-trial evidence involving millions of participants and concluded that LDL is a causal factor in atherosclerotic cardiovascular disease.^[3]

The relationship also appears cumulative: both how high LDL is and how long someone is exposed to elevated LDL matter.

This is one reason cardiovascular prevention should ideally begin before significant disease develops.

What is HDL cholesterol?

HDL stands for: high-density lipoprotein.

HDL has traditionally been called: “good cholesterol.”

Higher HDL levels are associated observationally with lower cardiovascular risk.

However, the biology is more complicated than: “The higher my HDL, the healthier I am.”

Human genetic and randomised-trial evidence has challenged the idea that simply increasing the concentration of HDL cholesterol necessarily reduces cardiovascular events.^[5,6]

So while HDL remains useful as part of cardiovascular-risk assessment, raising HDL itself is not generally the central therapeutic target in the way lowering LDL-containing atherogenic particles is.

So is HDL not important?

It is still useful.

A very low HDL level can be associated with an adverse metabolic and cardiovascular-risk profile.

But you should not interpret a high HDL as cancelling out:

• —high LDL
• —smoking
• —high blood pressure
• —diabetes
• —obesity
• —other cardiovascular risks.

Likewise, trying to artificially increase an HDL number is not equivalent to treating the underlying causes of cardiovascular risk.

What is non-HDL cholesterol?

Non-HDL cholesterol is calculated very simply: Total cholesterol − HDL cholesterol = non-HDL cholesterol.

It represents cholesterol carried in the range of atherogenic lipoproteins that can contribute to plaque formation.

This includes:

• —LDL
• —very-low-density lipoproteins
• —intermediate-density lipoproteins
• —remnant particles
• —lipoprotein(a).

This is why non-HDL cholesterol can be particularly useful. It captures a broader range of atherogenic cholesterol than LDL cholesterol alone.

Why does NICE use non-HDL cholesterol?

Current NICE guidance uses non-HDL cholesterol in several important ways.

For people receiving statins for primary prevention, NICE recommends aiming for a greater than 40% reduction in non-HDL cholesterol.^[2]

Non-HDL therefore provides a practical way to measure the overall response of atherogenic cholesterol to treatment.

Evidence also supports non-HDL cholesterol as an important marker of cardiovascular risk.^[7,8]

What is total cholesterol?

Total cholesterol is the combined cholesterol contained within several different lipoprotein fractions.

It is useful, but by itself gives an incomplete picture.

Two people could have the same total cholesterol but very different:

• —HDL
• —non-HDL
• —LDL
• —triglycerides
• —overall cardiovascular risks.

This is why clinicians increasingly look at a full lipid profile rather than total cholesterol alone.

What are triglycerides?

Triglycerides are another form of fat carried within the blood.

They are influenced by factors including:

• —diet
• —alcohol
• —body weight
• —diabetes
• —genetics
• —certain medications.

Very high triglyceride levels can create additional medical risks, while more moderate elevations may accompany an adverse metabolic and cardiovascular profile.

They should be interpreted alongside the rest of the lipid profile.

What cholesterol numbers are considered healthy?

For generally healthy adults, the NHS currently provides guide values including:

• —total cholesterol: below 5 mmol/L
• —HDL: above 1.0 mmol/L in men and above 1.2 mmol/L in women
• —non-HDL: below 4 mmol/L.^[1]

Someone who has already had a heart attack, stroke or established coronary artery disease will usually require a more intensive risk-reduction strategy than a young person with otherwise very low cardiovascular risk.

Is a cholesterol of 6 mmol/L dangerous?

A total cholesterol value cannot answer that question by itself.

Doctors would want to know:

• —LDL
• —HDL
• —non-HDL
• —triglycerides
• —age
• —blood pressure
• —smoking status
• —diabetes status
• —kidney function
• —family history
• —other health conditions
• —whether cardiovascular disease is already present.

That information can then be incorporated into an overall cardiovascular-risk assessment.

What is QRISK3?

QRISK3 is a UK risk calculator that estimates a person's probability of developing cardiovascular disease over the next 10 years.

It incorporates cholesterol together with many other factors.

This means two people with identical cholesterol results may have very different estimated cardiovascular risk.

Related article: What Is QRISK3 and What Does Your Cardiovascular Risk Mean?

When are statins recommended?

For primary prevention in the UK, NICE recommends offering atorvastatin 20 mg to many people whose QRISK3 10-year cardiovascular risk is 10% or greater, following appropriate discussion.^[2]

Treatment can also be appropriate in other situations, including when the calculated risk may underestimate someone's true risk.

People with established cardiovascular disease are managed differently because they are already known to be at high cardiovascular risk.

How much does lowering LDL help?

A major Cholesterol Treatment Trialists' Collaboration meta-analysis involving approximately 170,000 participants across 26 randomised trials found that further LDL reduction produced further reductions in major vascular events.^[4]

The benefit is related to:

• —the amount LDL is lowered
• —the individual's baseline cardiovascular risk
• —duration of treatment.

This is why the same cholesterol reduction may produce a larger absolute benefit in someone at high baseline risk than in someone at very low risk.

Does everyone with high cholesterol need medication?

No.

Treatment depends on the person's overall risk and circumstances.

Management may include:

• —lifestyle change alone
• —lifestyle change plus medication
• —investigation for an underlying cause
• —assessment for an inherited lipid disorder.

NICE recommends optimising modifiable lifestyle and cardiovascular risk factors as part of primary prevention, while recognising that medication may also provide substantial benefit when indicated.^[2]

What lifestyle changes help cholesterol?

Reduce saturated fat

Replacing some saturated fats with unsaturated fats can improve the lipid profile.

Increase fibre

Foods rich in soluble fibre can help lower LDL cholesterol.

Exercise regularly

Physical activity improves cardiovascular health even when changes in cholesterol itself are relatively modest.

Maintain a healthy weight

Where appropriate, weight reduction can improve several cardiovascular and metabolic risk factors.

Do not smoke

Smoking dramatically increases cardiovascular risk independently of cholesterol.

Manage diabetes and blood pressure

Cardiovascular risk factors frequently occur together. The goal is therefore not simply to “fix cholesterol” while ignoring everything else.

What about eggs?

For most people, blood LDL concentration is influenced more substantially by the overall dietary pattern, genetics and saturated-fat intake than by avoiding individual cholesterol-containing foods alone.

Dietary recommendations should therefore focus on the whole eating pattern rather than labelling one food as universally “good” or “bad”.

People with specific lipid disorders may need individualised advice.

What is familial hypercholesterolaemia?

Familial hypercholesterolaemia (FH) is an inherited condition that causes markedly raised LDL cholesterol from a young age.

Because the arteries are exposed to high LDL for many years, untreated FH substantially increases premature cardiovascular risk.

NICE recommends considering the full lipid profile, clinical findings and family history when deciding whether an inherited lipid disorder may be present.^[2]

Current NICE guidance recommends specialist assessment in people with particularly extreme lipid levels, including total cholesterol above 9.0 mmol/L or non-HDL cholesterol above 7.5 mmol/L, even without a first-degree family history of premature coronary disease.^[2]

What is lipoprotein(a)?

Lipoprotein(a), or Lp(a), is another atherogenic lipoprotein whose concentration is largely genetically determined.

It is not included routinely in every standard lipid profile.

Testing may be useful in selected people, particularly where there is premature cardiovascular disease or a strong family history.

A future Live, Onward article will explain Lp(a) in more detail.

Should I worry about cholesterol if I exercise and feel healthy?

Being fit is extremely beneficial.

But fitness does not make somebody immune to:

• —genetic lipid disorders
• —hypertension
• —diabetes
• —coronary atherosclerosis.

Likewise, somebody can feel completely well while cardiovascular risk factors develop silently.

This is why prevention focuses on identifying modifiable risk before a heart attack or stroke occurs.

Can cholesterol plaque be seen on a scan?

Yes.

Imaging can sometimes demonstrate the consequences of atherosclerotic cholesterol-containing plaque.

For example:

• —Coronary calcium CT — shows calcified coronary atherosclerosis.
• —CT coronary angiography — can demonstrate calcified and non-calcified coronary plaque and assess narrowing of the coronary arteries.

However, imaging and blood tests answer different questions.

A normal scan today does not mean cardiovascular risk factors should be ignored indefinitely.

Questions to ask when you get a cholesterol result

Rather than asking only: “Is my cholesterol high?” consider asking:

• —What is my LDL cholesterol?
• —What is my non-HDL cholesterol?
• —What are my triglycerides?
• —What is my QRISK3 score?
• —What is my blood pressure?
• —Is my family history important?
• —Could this represent familial hypercholesterolaemia?
• —Would lifestyle changes be enough?
• —What would I gain from medication?
• —What target or percentage reduction are we aiming for?

The key message

LDL and other atherogenic lipoproteins matter because they contribute directly to the development of atherosclerosis.

But good cardiovascular prevention is about much more than one cholesterol result.

The goal is to understand: your cholesterol + your blood pressure + your lifestyle + your medical history + your overall cardiovascular risk — and then reduce the risks that can be changed.