Cholesterol and Lipoproteins: A GP’s Guide for an Informed Patient

When discussing cholesterol with a patient there is often a mixture of concern and confusion. Understanding what cholesterol and lipoproteins are, why their levels matter, and how to interpret blood tests can empower you to make informed decisions about your health.  In this guide, we’ll explore cholesterol in depth, the nuances of blood tests like non-HDL cholesterol, and strategies for prevention and treatment. We won’t shy away from complexity and aim to bring you the most up to date information.

What is cholesterol and what are lipoproteins?

Cholesterol is a waxy, fat-like substance found in every cell of your body. It’s essential for producing hormones, vitamin D, and bile acids that help digest fat. Your body produces most of the cholesterol it needs, and the rest comes from dietary sources like meat, dairy and eggs.

However, cholesterol doesn’t travel freely in the blood because it’s not water-soluble. It needs carriers called lipoproteins. These are particles made of fat (lipid) and protein that transport cholesterol and triglycerides (another type of fat) through your bloodstream.

The main types of lipoproteins are:

1. Low-Density Lipoprotein (LDL): Often labelled the “bad” cholesterol, LDL delivers cholesterol to tissues. Excess LDL can deposit cholesterol in artery walls, leading to atherosclerosis.
2. High-Density Lipoprotein (HDL): Historically, known as the “good” cholesterol, HDL helps remove excess cholesterol from the bloodstream and carries it back to the liver for disposal. However, recent research suggests that very high HDL levels may not always be protective and could even be associated with increased cardiovascular risk.
3. Very-Low-Density Lipoprotein (VLDL): This carries triglycerides and is a precursor to LDL.
4. Non-HDL Cholesterol: This includes all lipoproteins except HDL, providing a broader measure of harmful cholesterol types like LDL and VLDL. Increasingly this is seen as the value to focus on!

Why are lipoproteins and cholesterol important?

Cholesterol and lipoprotein imbalances are major risk factors for cardiovascular disease (CVD), including heart attacks and strokes. Excess LDL can form plaques in artery walls, narrowing blood flow and increasing the risk of clots. Conversely, high HDL levels can be protective by helping clear cholesterol—although, as noted earlier, this is now being reassessed.

Certain conditions amplify these risks, such as:

• Familial Hypercholesterolemia: A genetic condition causing very high LDL levels from birth.
• Metabolic Syndrome: A cluster of factors (high blood pressure, high triglycerides, low HDL, abdominal obesity and insulin resistance) that increase CVD risk.
• Type 2 Diabetes: Often associated with high triglycerides, low HDL, and small, dense LDL particles, which are more atherogenic.

What do blood tests measure?

A standard lipid panel includes:

1. Total Cholesterol: The sum of LDL, HDL, and VLDL cholesterol.
2. LDL Cholesterol: The primary target in most guidelines for lowering cardiovascular risk.
3. HDL Cholesterol: Higher levels are generally better, but not too high.
4. Triglycerides: Elevated levels can indicate a higher risk of CVD and may require specific interventions.
5. Non-HDL Cholesterol: Calculated as total cholesterol minus HDL. It’s a comprehensive measure of atherogenic (heart disease causing) particles and may be more predictive of heart disease risk than LDL alone.

How do I interpret my results?

Here’s a simplified breakdown of desirable levels (values in mmol/L):

• Total Cholesterol: Below 5.0
• LDL Cholesterol: Below 3.0 (or below 1.8 for high-risk individuals)
• HDL Cholesterol: Above 1.0 in men, above 1.2 in women, but less than 2.3
• Triglycerides: Below 1.7
• Non-HDL Cholesterol: Below 3.4 (or 2.6 for high-risk individuals)

Your doctor will interpret these results alongside your overall risk profile, considering factors like age, family history, smoking, blood pressure, and diabetes.

How can I prevent high cholesterol?

Preventing high cholesterol involves maintaining a healthy balance of lipoproteins. Here are evidence-based lifestyle interventions:

1. Diet

• Reduce Saturated and Trans Fats: Found in fatty meats, butter, and processed foods, these fats raise LDL levels.
• Increase Unsaturated Fats: Found in olive oil, avocados, nuts and fatty fish, these can lower LDL and raise HDL.
• Eat Soluble Fiber: Foods like oats, beans, lentils and fruits reduce LDL by binding cholesterol in the gut.
• Incorporate Plant Sterols: Found in fortified foods like margarine, plant sterols block cholesterol absorption in the gut.

2. Physical Activity

• Regular exercise increases HDL, lowers LDL and triglycerides, and improves overall cardiovascular health. Aim for at least 150 minutes of moderate aerobic activity per week.

3. Weight Management

• Losing even 5-10% of body weight can significantly improve your lipid profile, especially triglycerides and HDL.

4. Avoid Smoking and Limit Alcohol

• Smoking lowers HDL and damages blood vessels. Excess alcohol can raise triglycerides and contribute to weight gain.

What drug treatments are available?

For some, lifestyle changes may not be enough. Medication can be a critical component of managing cholesterol levels, especially for individuals with high cardiovascular risk or specific conditions like familial hypercholesterolemia.

1. Statins

• Statins are the first-line treatment for lowering LDL. They work by inhibiting an enzyme in the liver responsible for cholesterol production.
• Examples: Atorvastatin, Rosuvastatin.
• They are generally well tolerated and work well

2. Ezetimibe

• This medication reduces cholesterol absorption in the intestines and can be added to statins for further LDL reduction.

3. PCSK9 Inhibitors

• These injectable drugs significantly lower LDL by enhancing the liver’s ability to remove cholesterol from the blood.
• They are often injected every fortnight.
• Examples include: Evolocumab, Alirocumab.

4. Inclisiran

• A newer injectable medication, inclisiran, works by targeting RNA to reduce PCSK9 production in the liver, thereby lowering LDL levels.  It is administered twice yearly, it offers a convenient option for long-term LDL control, though its expense limits its availability.

5. Bempedoic Acid

• Bempedoic acid is an oral medication that inhibits cholesterol synthesis in the liver, targeting the same pathway as statins but at a different step. It’s particularly useful for individuals who cannot tolerate high-dose statins due to side effects. It can also be combined with ezetimibe for enhanced LDL-lowering effects.

6. Fibrates

• Primarily used to lower triglycerides and increase HDL. Less commonly prescribed for LDL reduction.

7. Omega-3 Fatty Acids

• Prescription-strength omega-3s can lower triglycerides, though they don’t affect LDL or HDL significantly.

8. Lipoprotein(a) Lowering Therapies

• Lipoprotein(a), or Lp(a), is a genetic variant of LDL associated with increased cardiovascular risk. Recent studies published in JAMA highlight emerging therapies targeting Lp(a) directly, including antisense oligonucleotides. These therapies show promise in reducing Lp(a) levels and are currently under investigation for their impact on cardiovascular outcomes.

Why is non HDL cholesterol important?

Non-HDL cholesterol is gaining attention as a more comprehensive marker of cardiovascular risk than LDL alone. By including all atherogenic (heart disease causing) particles (VLDL, IDL, and LDL), it reflects the total burden of harmful cholesterol. For patients with high triglycerides or diabetes, non-HDL cholesterol may be more predictive of risk.

Additionally, particle size matters. Small, dense LDL particles are more harmful than larger, buoyant ones because they’re more likely to penetrate artery walls and oxidize. Advanced lipid testing (like ApoB or LDL particle number) can provide further insights, especially for high-risk individuals.

What are the key takeaways?

• Cholesterol and lipoproteins are essential for health but need to be balanced to prevent cardiovascular disease.
• Blood tests like the lipid panel and non-HDL cholesterol offer valuable insights into your risk.
• Lifestyle changes, including diet, exercise and smoking cessation, are foundational for prevention and treatment.
• Medications like statins, PCSK9 inhibitors, inclisiran, bempedoic acid, and emerging Lp(a)-lowering therapies play a vital role for those at high risk.

Your lipid profile is just one piece of the puzzle. It’s essential to assess your overall cardiovascular risk and work with your GP to develop a personalised plan. By understanding these concepts, you’re taking a critical step toward proactive health management.

To book an appointment click here or call us on 0207 245 9333.