Introduction 

Over the past decade, the number of adults with an increased level of cholesterol in the blood (hyperlipidaemia) has risen at a drastic pace. According to WHO data from 2008, nearly half of adults in the United States (47.7%) and more than half in Europe (53.7%) were diagnosed with hyperlipidaemia.^1,2 These numbers send a serious warning to healthcare throughout the whole world, as hyperlipidaemia is a chronic and progressive condition that significantly increases the risk of cardiovascular disease and premature death. 

Treating it isn’t simple. It often requires lifelong lifestyle changes and strict adherence to medication throughout one's whole life.¹

At the same time, lipids themselves are not the “bad guys”. They are essential for making hormones, building cell membranes, and providing energy. The problem arises when there are too many of them in the body. 

So, why has hyperlipidaemia become so common in recent years? Is it simply our diets, or are we diagnosing it more effectively than before? In this article, we’ll explore the answers to these questions more deeply.

Understanding lipoproteins

Lipids can’t move by themselves in the bloodstream, they need some assistance, a transport system. That’s where lipoproteins come in. Lipoproteins (LPs) are complex structures. So let’s break it down into an easier analogy. 

Imagine, lipoproteins are like delivery trucks that move through roads and highways (blood vessels) of the body to different buildings, stores, or warehouses (different parts of the body). 

The cargo (a core part of LP) itself consists of: 

• Triglycerides are the "product" that provides energy to the tissues
• Cholesterol serves as the "box" or "bag" into which the "product" (cell membranes) is placed

Every truck (LP) has its labeling and a tracking number, these are the apolipoproteins (apoLP) in LPs, which guide where the truck should go and how to unload the goods.

There are different types of trucks for different jobs:

• Chylomicrons are big cargo trucks bringing products from the “import docks” (intestines)
• Very Low Density LPs (VLDL) are the trucks from the “central warehouse” (liver) delivering to stores (tissues)
• Low-Density LPs (LDL) are smaller vans that deliver cholesterol to local shops or specific customers (cells)
• Intermediate-Density LPs (IDLs)
• High-Density LPs (HDL) are recycling trucks that pick up unused goods and return them to the warehouse (liver)

The differences between these classes of LPs depend on the size of the molecule, its lipid content, and the type of apolipoprotein. 

Pathways of lipoprotein metabolism

So how does this transportation system work? And does what we eat really affect our cholesterol levels? To answer these questions, we need to look at the three main pathways of lipoprotein (LP) movement:³ 

1. Exogenous pathway, transport of fats from food
2. Endogenous pathway, transport of fats from the liver
3. Reverse cholesterol transport, recycling and removal of excess cholesterol

Transport of fats from food (exogenous)

When we eat foods that contain fat, special enzymes called lipases in the small intestine break them down into smaller pieces like cholesterol and fatty acids. These are then absorbed by the cells lining the intestine.

Inside these cells, the fats are rebuilt into larger molecules, triglycerides and cholesteryl esters, which are then transported by LPs, mostly chylomicrons. 

Chylomicrons enter the bloodstream and go to the tissues like muscle and fat, where the enzyme lipoprotein lipase (LPL) unloads fatty acids. These can be burnt immediately for energy or stored for later use. After delivering their goods, the “empty” chylomicrons return to the liver, where they are processed and removed from the blood within about 12 hours after eating. ⁴

Transport of fats from the liver (endogenous)

During fasting, stored fats in body fat tissue are broken down into fatty acids and sent to the liver. The liver can also make new fatty acids from scratch. These fatty acids are turned into triglycerides and packaged with cholesterol, vitamin E, and proteins to form VLDL (very-low-density lipoproteins). As VLDL travels through the bloodstream, LPL removes much of its triglyceride to supply muscle, heart, and fat tissue. The leftover particles, IDL (intermediate-density lipoproteins), go back to the liver.

HDL metabolism and reverse cholesterol transport

Every cell in the body can make cholesterol, but only the liver and intestine can effectively remove it. The liver sends cholesterol into bile, which helps digest fats, while the intestine can release cholesterol into the gut. If there is too much of cholesterol, the body uses a reverse cholesterol transport to the liver for disposal. HDL (high-density lipoprotein) plays the main role here, which is why it’s been nicknamed “good cholesterol”.

Hyperlipidaemia: Definition and types

Hyperlipidaemia is a disorder in which the levels of lipids (fats) in the blood are elevated. 

There are two main types of hyperlipidaemia:¹

1. Primary (familial) - linked to genetic disorders, mutations in the specific genes that regulate lipid metabolism;
2. Secondary (acquired) - starts as a result of other health conditions, such as hypothyroidism, diabetes, or as a side effect of certain medications (amiodarone, glucocorticoids), or a specific lifestyle regime, like an unhealthy diet or lack of physical activity.¹ 

Dysregulation Mechanisms

Hyperlipidaemia occurs when the balance between lipid transport and clearance is disrupted.⁵ 

And this, in turn, can happen through several mechanisms: 

1. Overproduction of LPs
   • The liver can release too much VLDL due to high intake of saturated fats, refined carbohydrates, or metabolic conditions like obesity, diabetes, or hypothyroidism
   • Genetic disorders that can cause the liver to produce VLDL and LDL particles, even on a normal diet
2. Impaired disposal of LPs
   • Problems with LDL receptors or apolipoprotein E (apoE) can reduce the body’s ability to remove LDL from the blood
   • Deficiency in lipoprotein lipase (LPL) or its cofactors can slow down triglyceride breakdown, leaving chylomicrons and VLDL circulating for longer periods
3. Lipid accumulation
   • Excess LDL can infiltrate the endothelium (the inner layer of blood vessels), especially when it’s damaged by high blood pressure, smoking, or oxidative stress. This may cause inflammation, leading to atherosclerotic plaque formation
     

In most cases, hyperlipidaemia results from a mix of factors, usually it is predisposed by genetic factors and worsened by diet or obesity. In other words, both internal processes and excessive food consumption contribute to hyperlipidaemia.⁵ 

Laboratory tests

If your doctor wants to check your lipid metabolism, the most important laboratory test would be checking the fasting lipid profile, which includes LDL, HDL, triglycerides, and total cholesterol.⁶ 

Sometimes additional markers might be added, including VLDL, total cholesterol-to-HDL, and LDL-to-HDL ratios. Usually, it is advised not to eat or drink anything (except for water) for 9 to 12 hours beforehand, because triglyceride levels might be affected by food.⁶ 

Your doctor may also order liver function tests. This helps determine whether any lipid abnormalities are linked to liver problems.

Health consequences of hyperlipidaemia

High cholesterol doesn’t usually cause symptoms you can feel, but over time, it quietly damages your blood vessels.¹ Think of it like slow rust building up inside pipes, the more and longer the buildup, the harder it is for water (blood in the case of the vessels) to flow. 

It can lead to clogged arteries, heart attacks, strokes, and poor circulation in the legs. And if cholesterol levels stay high for years, the risks increase.¹ Plaques in the arteries can grow slowly, causing chest pain or breathlessness, or suddenly burst, forming a clot that can block blood flow in seconds. 

The good news is that the hyperlipidaemia could be managed. 

Regular check-ups with your doctor are important, and while medication may sometimes be needed, lifestyle changes, such as a healthy diet, regular exercise, and avoiding smoking, are the foundation of treatment.

Summary

Lipoproteins are essential molecules that regulate lipid transport and metabolism. Without them, the cells wouldn’t get the necessary fat and energy, nor build molecules and hormones and other vital compounds. 

When the balance of this transport system is disrupted due to genetics, diet, or certain health conditions, fats could build up in the blood and cause serious complications like atherosclerosis, leading to an increased risk of heart diseases and stroke. 

Laboratory tests could help identify which lipoproteins are involved and whether the transport system is working properly. Based on these results, your doctor can recommend the most effective treatment plan. 

Maintaining healthy lifestyle habits and checking your cholesterol levels regularly are key steps in protecting your heart and blood vessels.