Apolipoprotein B (APOB)

What is Apolipoprotein B (APOB)?

Apolipoproteins are the major protein components of the lipid-transporting lipoproteins. Apolipoproteins maintain the structural integrity and functionality of lipoproteins.

Apolipoprotein B (ApoB) is present in LDL cholesterol, also known as “bad” cholesterol. ApoB is important for transporting cholesterol and other fats in the blood to the tissues and arteries. However, too much LDL cholesterol can lead to a build-up of fatty deposits in the artery walls, a condition called atherosclerosis, which increases the risk of heart attacks and strokes^[1].

Measuring your ApoB levels can give you a better idea about your cardiovascular disease risk than measuring LDL levels alone because it tells you how many atherosclerosis-causing particles are circulating in your blood.

Why is APOB Important?

A study published in The Lancet found that people who had a raised ApoB level have a higher risk of developing coronary artery disease even if their LDL cholesterol levels are normal^[2].

ApoB is an important biomarker for predicting cardiovascular disease risk because it reflects the total number of potentially harmful lipoprotein particles in the blood. The number of ApoB-containing particles that become trapped in the artery walls depends on how many are currently in circulation.

Smaller ApoB particles are more likely to stick to the artery walls because they bind strongly to glycosaminoglycans, causing plaque build up, leading to cardiovascular disease. However, larger ApoB have a higher cholesterol-carrying potential. This means that all types of ApoB particles contribute to the development of atherosclerosis and heart disease. Therefore, measuring ApoB levels can give you a clearer picture of cardiovascular risk than your LDL cholesterol levels alone.

How is ApoB Measured?

ApoB is measured using a blood test, but it isn’t a standard test in the NHS and is limited to hospital specialists. It’s usually measured if you have a family history of heart disease, high blood fat levels, or your doctor wants to find out your risk of developing heart disease.

Compared to LDL cholesterol measurements alone, ApoB is thought to be a more accurate predictor of cardiovascular disease because it measures the number of “bad” cholesterol particles circulating in your blood^[3].

ApoB can be measured alongside APOA to give an ApoB:APOA ratio which can tell you how balanced your apolipoproteins are. A high ApoB:APOA ratio can suggest you are at a higher risk for developing heart disease.

What Are Normal ApoB Levels?

The reference ranges for ApoB can differ depending on the testing laboratory. A normal ApoB range is shown in the table below according to age and sex:

Because research suggests that the higher your ApoB:APOA ratio the higher your risk of developing cardiovascular disease, a cut off value of ≥0.9 for men and ≥0.8 for women has been suggested^[5]. If your ApoB:APOA ratio is above this, then it suggests you are at a high risk of a heart attack, stroke, or heart cardiovascular complications^[6].

What Do ApoB Results Mean?

ApoB levels are usually linked to LDL cholesterol levels, although this isn’t always the case. That means that many of the factors that lead to high LDL levels, also increase ApoB. High ApoB levels are usually associated with an increased risk of developing cardiovascular disease.

The most common cause of abnormal ApoB levels are genetic or inherited disorders, such as:

• Familial combined hyperlipidaemia – causes high cholesterol and triglyceride levels in the blood
• Abetalipoproteinemia – causes unusually low ApoB levels

Several underlying conditions and lifestyle choices can also cause high ApoB levels, including:

• diets high in saturated fat and cholesterol
• diabetes
• an underactive thyroid (hypothyroidism)
• certain medications (androgens, beta blockers, diuretics, synthetic progesterone, corticosteroids)
• kidney disease
• pregnancy
• Cushing’s syndrome

If you have a condition that affects lipoprotein production, it can lower the concentration of ApoB in your blood. Secondary causes of low ApoB levels are:

• certain medications (oestrogen, statins, thyroxine)
• an overactive thyroid (hyperthyroidism)
• malnutrition
• Reye’s syndrome
• weight loss
• liver cirrhosis
• surgery^[7]

Although different laboratories have different reference ranges, a typical Apolipoprotein level is 0.4 to 1.20 g/L for anyone over 19 years old^[8].

How to Manage ApoB Levels

There are several things you can do to help lower your ApoB levels on your own or with medical help.

Some of the ways you can lower ApoB levels include:

1. Follow a heart healthy diet

A heart healthy diet, like the Mediterranean diet, can help to reduce your ApoB levels^[9]. The diet focuses on mainly plant-based foods, healthy fats, and animal products are consumed moderately, with the preferred animal protein coming from fish and seafood. There is an emphasis on eating foods such as:

• Whole grains such as oats and barley are linked to a lower risk of cardiovascular disease and all cause mortality^[10] because they are rich in fibre, including beta-glucan that slows digestion and reduces the absorption of cholesterol and sugar^[11].
• Olive oil is rich in healthy, monounsaturated fats, like oleic acid, which has anti-inflammatory properties and heart health benefits. Studies suggest that replacing saturated fats with healthier alternatives, like olive oil, can lower cholesterol, inflammation, and your risk of heart disease^[12].
• Fruit and vegetables provide fibre, essential nutrients, and antioxidants which can lower the risk of heart disease further^[13].
• Beans and legumes are natural sources of plant stanols and sterols that have anti-atherosclerotic effects, such as reducing nitric oxide and plaque formation^[14]. Some research indicates that for each 5g of soluble fibre, ApoB levels reduced by 44.9 mg/L^[15].
• Nuts are rich in healthy fats, fibre, and other nutrients that are linked to a 19% lower risk of heart disease and 25% lower risk of cardiovascular related death^[16].
• Herbs and spices such as garlic have been shown to improve blood pressure and cholesterol levels, while cinnamon can improve blood glucose levels, and turmeric has anti-inflammatory properties. Research has shown that curcumin lowers ApoB-100 levels and may be helpful for reducing atherogenic lipoproteins and preventing atherosclerosis^[17].

2. Exercise regularly

Getting regular moderate-intensity exercise can significantly lower your ApoB levels and improve the ApoB:APOA ratio^[18]. Further research shows that intense exercise can lower ApoB levels by 5%^[19]. It is important to aim to complete at least 150 minutes of moderate-intensity exercise every week, like brisk walking, swimming, cycling, or even gardening^[20].

3. Maintain a healthy weight

Weight management is a crucial aspect of maintaining healthy ApoB levels. Excess body fat is associated with increased LDL cholesterol and ApoB levels, which increases your risk of heart disease. Research suggests that losing 6 to 12% of you body weight can significantly reduce circulating ApoB^[21].

Using a combination of dietary changes and increasing your activity levels is the preferred method of weight loss. You can help achieve sustainable weight loss by:

• eating fewer calories than you burn to create a calorie deficit
• avoiding fad or crash diets – these can result in rapid weight loss, but you may quickly put it back on. So, focus on long-term lifestyle changes for lasting results
• Incorporating strength training into your exercise programme to help improve your metabolism and support weight loss

4. Reduce alcohol consumption

Alcohol is associated with increased circulating ApoB levels^[22], so to keep your levels within a healthy range it’s important to keep your alcohol consumption low. There is no completely safe level of alcohol, but the NHS recommends drinking no more than 14 units per week^[23]. Check how many units per week you’re drinking with this unit calculator.

5. Give up smoking

Smoking increases ApoB^[24] and the risk of plaque building up in your arteries. Giving up smoking improves your blood fats and can reduce your ApoB levels, reducing your risk of cardiovascular disease.

6. Increase your intake of plant stanols/sterols

Upping your intake of foods that contain plant sterols and stanols may improve your lipid profile and lower your ApoB levels. It is suggested that eating 2g/day can contribute to lowering your LDL cholesterol levels by 10%, alongside other dietary changes^[25]. Foods that naturally contain stanols and sterols include:

• avocados
• apples
• oranges
• bananas
• onion
• spinach
• broccoli
• wholegrains
• nuts and seeds

7. Consider speaking to your doctor about Medications. statins

In some cases, lifestyle changes alone may not be enough to improve your blood fats or lower your ApoB levels. So, your doctor may prescribe cholesterol lowering medications, like statins. However, even if you are prescribed medication, it is still important to continue with your lifestyle modifications to support its function in lowering the amount of fat, including ApoB circulating in your blood.

When it comes to medications for lowering ApoB, several options exist with varying degrees of efficacy, including:

• PCSK9 inhibitors such as evolocumab and alirocumab which have been shown to reduce LDL cholesterol levels by 60 to 70%^[26], making them the most potent for lowering ApoB. They are administered by subcutaneous injection and work by enhancing LDL receptor recycling, leading to lower levels. These are often best for patients with familial hypercholesterolemia or people who cannot tolerate statins.
• High-intensity statins including Atorvastatin (40 – 80 mg) and Rosuvastatin (20 to 40 mg) can reduce LDL cholesterol levels by more than 50%^[27] and work by reducing the amount of cholesterol your liver makes. These are widely prescribed because of their strong cardiovascular benefits.
• Bempedoic acid (Nexletol) is a lipid-lowering medication that can lower LDL cholesterol levels by 15 to 25% and up to 38% when combined with ezetimibe. It works upstream of statins, lowering cholesterol synthesis. It’s most useful for people who cannot tolerate statins.
• Ezetimibe has been shown to lower ApoB levels significantly more than placebo, up to 15%^[28]. It is a cholesterol absorption inhibitor that blocks the absorption of dietary and biliary cholesterol. Ezetimibe is often used as an add-on to statin therapy and is well tolerated with few side effects.
• Icosapent Ethyl is a highly purified prescription form of the omega-3 fatty acid eicosapentaenoic acid (EPA) that works by lowering blood fat levels. It can lower ApoB levels by 5 to 10%, has anti-inflammatory effects, and reduces cardiovascular events beyond just lowering LDL cholesterol.
• Inclisiran is a new small interfering RNA therapy that inhibits the production of the PCSK9 protein. Research shows that it reduces ApoB levels by 35.8% after 510 days^[29]. It has a long-lasting effect and only requires two injections per year.

Choosing the best medication for you will depend on several factors, including:

• Baseline ApoB levels – how high (or low) your starting ApoB levels are will determine the intensity of the treatment you need.
• Cardiovascular risk profile – if your cardiovascular risk is high, you may require a stronger, more potent therapy.
• Medication tolerance – all medications can cause side effects and can affect your ability to continue treatment.
• Comorbidities – if you have any other health conditions, this may determine which types of medication are most suitable for you.
• Patient preference – if you have a fear of needles, for example, you may prefer oral medications to subcutaneous injections.

For patients with very high cardiovascular risk or severely elevated ApoB, combination therapy (typically statin plus one or more additional agents) often provides the most robust reduction in ApoB levels and cardiovascular risk. These should be discussed with your doctor.