Overview

Hyperlipidaemia is a condition that describes an abnormality in how your body stores, transports, or clears lipids (fats). It can be caused by genetic factors (primary hyperlipidaemia) or by lifestyle choices and other medical conditions such as diabetes, polycystic ovary syndrome (PCOS), and hypertension (secondary hyperlipidaemia).  

While often asymptomatic, it significantly increases the risk of cardiovascular disease (CVD) by contributing to atherosclerosis (plaque buildup in arteries) and raising the risk of heart attack and stroke. In 2019, about 4.4 million deaths were attributed to hyperlipidaemia, particularly high low-density lipoprotein (LDL).^1,2

This article provides a comprehensive and up-to-date overview of hyperlipidaemia management to understand the underlying mechanisms behind each type (primary vs secondary) and how treatment is approached in each case. 

Introduction to hyperlipidaemia

Hyperlipidaemia means having high levels of fats in your blood. These fats include low-density lipoprotein (LDL) or “bad” cholesterol, high-density lipoprotein (HDL) or “good” cholesterol, triglycerides, and total cholesterol. 

LDL can build up in your arteries, forming plaques that increase your risk of heart disease, while HDL helps remove excess cholesterol and protect your blood vessels. 

You may be diagnosed with hyperlipidaemia if your fat levels fall outside the normal ranges:²

• HDL (“good” cholesterol): Which is below 40 mg/dL in men or 50 mg/dL in women
• LDL (“bad cholesterol”): Which is above 100 mg/dL
• Triglycerides: That is over 150 mg/dL
• Total cholesterol: Which is higher than 200 mg/dL

Understanding lipids and their role in the body

Lipids

Lipids are the chemical name for fats and are vital for your body. Your muscles get energy from them, and all your cells need them to work properly. Key lipids include cholesterol, triglycerides, and lipoproteins.

Cholesterol

Cholesterol is in every cell and plays several key roles. It helps with digestion (as part of bile acids), builds cells, makes vitamin D, and supports hormone production.³

Triglycerides

Triglycerides are a type of fat stored in your body's fat cells to provide energy when needed. When you eat, your body uses what it needs for energy and the excess is converted into triglycerides and stored in fat cells.

Lipoproteins

Lipoproteins are combinations of fats and proteins that carry fats through your mostly watery blood. They act like delivery trucks, taking cholesterol and triglycerides where they are needed. The main types are LDL, HDL, very low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL).⁴

Apolipoproteins

Apolipoproteins are proteins on the surface of lipoproteins. They help lipoproteins maintain their shape and direct their movement within the body. You can think of them like keys that fit into locks on cells, allowing fats to enter or leave as needed.

There are several types, including apo A, apo B-48, apo B-100, apo C, and apo E. Each one has a role. For example, apo B-100 is on VLDL and LDL. If there is too much apo B-100, more LDL circulates in the blood, which increases the risk of fatty plaques forming in your arteries, a process known as atherosclerosis.

The process of lipid metabolism

After eating, the fat from your food is formed into chylomicron particles made of triglycerides, cholesterol, and proteins. These chylomicrons travel through your blood, delivering fatty acids to your muscles for energy and to fat tissue for storage. The remaining chylomicron remnants are taken up by the liver.

The liver also produces VLDL to transport triglycerides, which gradually transform into IDL and then into LDL as it delivers fat to tissues. In contrast, HDL collects excess cholesterol from tissues and lipoproteins, returning it to the liver for reuse or removal in a process known as reverse cholesterol transport. 

This delicate balance can be disrupted by factors like poor diet, hormonal imbalances, type 2 diabetes, or genetic conditions, potentially leading to high cholesterol and triglycerides.⁵

Mechanism behind primary hyperlipidaemia

Primary hyperlipidaemia happens because of genetic changes that you inherit from your family. These changes affect the way your body handles fats, and they usually show up in three main ways:

Storage and breakdown of fats

In some people, genes such as LIPE and USF1 are involved. LIPE controls an enzyme that helps break down stored fat when your body needs energy. If this gene does not work properly, fat breakdown slows, leaving more triglycerides in the blood. USF1 helps regulate both fat and sugar metabolism, and certain variants of it can also raise fat levels.⁶

Production of lipoproteins

The liver sometimes produces too many fat-carrying particles, called VLDL. A gene called GCKR influences how the liver processes sugar and fat. When this gene is faulty, the liver tends to make more fat than it should, which pushes up triglyceride and LDL levels.⁶

Clearance of lipoproteins

LDL particles carry a protein called apo B-100, which helps them bind to receptors in the liver so they can be cleared from the blood. If the receptors do not function properly, LDL builds up. This is one of the main reasons LDL cholesterol stays high in people with primary hyperlipidaemia.⁶

On their own, these genetic changes increase your risk. But when combined with other conditions like diabetes, hypertension, or obesity and with environmental factors such as diet and lifestyle, the chances of complications become much higher. That is when problems like atherosclerosis, heart disease, or stroke often start to appear.^6, 7

Management of primary hyperlipidaemia

If you have primary hyperlipidaemia, the main objective is to reduce your risk of atherosclerotic cardiovascular disease (ASCVD),  which encompasses heart attacks, strokes, and other conditions caused by plaque buildup in arteries.

Your doctor may calculate your ASCVD risk score, which estimates your chance of developing serious heart problems in the next 10 years. This score considers factors such as cholesterol levels, age, sex, blood pressure, smoking history, and the presence of diabetes. 

Lifestyle changes are fundamental for managing primary hyperlipidaemia and reducing cardiovascular risk. These include:

• Reducing intake of saturated and trans fats
• Increasing dietary fibre
• Maintaining a healthy weight
• Exercising regularly
• Avoiding smoking

While these steps may not completely normalise cholesterol in primary hyperlipidaemia, they still help lower your overall risk.

Additionally, medications are often required. Statins are the first choice because they lower LDL cholesterol and reduce the risk of heart events. If statins alone do not reach target levels, other drugs such as ezetimibe or PCSK9 inhibitors may be used. For very high triglycerides, fibrates or omega-3 fatty acids may also be considered.⁶

You also have to take into account that management is long-term. Since primary hyperlipidaemia is inherited, stopping treatment usually causes cholesterol levels to rise again. Regular follow-up with blood tests is recommended to help monitor response to therapy and adjust medications if needed.

Secondary hyperlipidaemia

Secondary hyperlipidaemia is not caused by your genes. Instead, it occurs as a result of lifestyle habits, other health conditions, or certain medications.⁸

Common contributing factors include:

• Lifestyle habits: Smoking, eating a diet high in saturated fats and sugars, and a lack of physical activity
• Health conditions: Type 2 diabetes, polycystic ovary syndrome (PCOS), obesity, hypothyroidism, and kidney disease
• Medications: Corticosteroids, some diuretics, birth control pills, and certain antipsychotics

How these factors lead to high cholesterol and triglycerides

Unhealthy diet and lack of exercise

• Eating too much sugar and unhealthy fat, along with a lack of exercise, causes the liver to release more fat particles (like VLDL) into the blood
• At the same time, levels of HDL (“good” cholesterol) may drop, reducing the body’s ability to clear excess fat

Diabetes and insulin resistance (including in PCOS)

• Insulin resistance disrupts sugar and fat metabolism
• This leads to higher levels of fatty acids, which the liver converts into triglycerides and LDL (“bad “cholesterol), while HDL may decrease
• These fats can become oxidised, increasing plaque formation in arteries and raising heart disease risk

Obesity

• Extra body fat releases more fatty acids into the bloodstream, overloading the liver and increasing triglycerides and LDL
• Fat tissue also releases inflammatory substances, which lower HDL and make LDL more likely to form plaque, increasing heart disease risk

Hypothyroidism

• A slow metabolism reduces how efficiently LDL is cleared and may lower HDL while raising triglycerides
• This imbalance increases the risk of plaque formation in the arteries

Kidney disease

• Damaged kidneys affect how your body processes fats
• The liver may produce more fats, and fat-carrying particles (lipoproteins) do not work properly
• This leads to higher LDL and triglycerides, lower HDL, and increased plaque formation in arteries

Certain medications

• Some drugs, such as corticosteroids, certain diuretics, birth control pills, and some antipsychotics, can cause the liver to produce more triglycerides, slow LDL removal, or reduce HDL
• Over time, these changes increase cholesterol and triglyceride levels and raise the risk of heart disease

Managing secondary hyperlipidaemia

Most cases of high cholesterol and triglycerides are linked to lifestyle habits or other health conditions. By adopting healthier habits, you can positively influence your body's ability to process fats and lower these levels.

Start with your lifestyle habits. Following a Mediterranean-style diet, reducing sugar and unhealthy fats, staying active, maintaining a healthy weight, and avoiding smoking can make a real difference. These changes help lower LDL (“bad” cholesterol) and triglycerides while supporting HDL (“good” cholesterol).

It is also important to manage other health issues. Keeping blood sugar under control if you have diabetes or PCOS, treating hypothyroidism, and supporting kidney health can improve cholesterol levels. If any medications you take contribute to high fats, your doctor may adjust them or suggest alternatives.

Sometimes, lifestyle changes and treating underlying conditions are not enough. In that case, medicines such as statins or other prescribed drugs can help lower LDL and triglycerides. Your doctor will consider your overall ASCVD risk to determine personalised treatment..

Regular check-ups are also important to monitor your cholesterol and triglyceride levels and ensure you stay on track for a healthier heart.^8, 9

Summary

High cholesterol and triglycerides can be inherited (primary) or caused by lifestyle habits and other health conditions (secondary). Management focuses on healthy lifestyle habits, treating underlying conditions, and, when needed, medications such as statins. Regular check-ups help monitor progress and reduce the risk of heart disease and stroke.