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Posted on Saturday September 28, 2024 in Naked Heart
An article written by Dr Edward Leatham, Consultant Cardiologist
Tags: Cholesterol, Coronary heart disease, LDL, NH1 search website using Tags to find related stories.
When people think of cholesterol, most immediately associate it with something bad. However, cholesterol is an essential molecule required by every cell in our body. It plays a key role in the production of hormones, the structure of cell membranes, and other vital functions. But like many things in the body, it’s all about balance. And when it comes to cholesterol, the balance between “good” and “bad” cholesterol, particularly low-density lipoprotein (LDL) cholesterol, is critical for our health.
LDL cholesterol, often referred to as “bad cholesterol,” is the principle cause of the buildup of plaque in the coronary arteries, which leads to coronary heart disease (CHD). This type of heart disease can result in heart attacks, strokes, and other cardiovascular events. In fact, studies have shown that elevated LDL cholesterol is one of the most significant risk factors for heart disease.
In this article, we will explore what determines your LDL cholesterol levels, the role of the liver in cholesterol production, and how genetic and lifestyle factors influence cholesterol levels and heart disease risk.
LDL (low-density lipoprotein) is the primary vehicle that transports cholesterol through the bloodstream. While our cells need some cholesterol to function properly, too much LDL can lead to a dangerous accumulation in the walls of arteries. Over time, this buildup, known as atherosclerosis, can restrict blood flow and increase the risk of heart attacks and strokes.
For years, the focus on reducing LDL levels was centered on dietary changes. It was believed that lowering the intake of saturated fats and cholesterol in food would reduce blood cholesterol levels and, in turn, lower the risk of heart disease. However, modern research has revealed that while diet may be important in some people, the liver’s role in producing cholesterol is even more significant in most. This explains the saying ‘90% of your cholesterol is made by the liver and only 10% is from what you eat’.
Cholesterol is such a vital molecule that our bodies have a sophisticated system to ensure its continuous supply. There are two main sources of cholesterol in the body:
The liver is the central hub for cholesterol production, responsible for synthesizing about 90% of the cholesterol in the blood. The enzyme HMG-CoA reductase plays a key role in this process, and this is the target for cholesterol-lowering medications like statins.
In addition to producing cholesterol, the liver regulates cholesterol levels in the bloodstream by removing LDL particles from the blood through LDL receptors (LDLRs). These receptors are located on the surface of liver cells and act as a clearing mechanism for LDL cholesterol. When LDL receptors are numerous and active, more LDL cholesterol is removed from the blood, leading to lower blood cholesterol levels.
LDL receptors are critical for maintaining healthy cholesterol levels. These receptors latch onto LDL particles in the bloodstream and bring them into liver cells, where the cholesterol can be used or stored. The more active LDL receptors you have, the more efficient your body is at clearing cholesterol from the blood.
For individuals with highly active LDL receptors, LDL cholesterol levels tend to remain low, regardless of dietary fat intake. Conversely, individuals with fewer or less efficient LDL receptors will have higher LDL levels, which increases the risk of plaque buildup in the arteries and coronary heart disease.
PCSK9 is a protein that plays a key role in cholesterol regulation. It influences how many LDL receptors are available to remove LDL cholesterol from the bloodstream. PCSK9 binds to LDL receptors and marks them for destruction, reducing the number of receptors available to clear LDL particles.
When PCSK9 activity is high, fewer LDL receptors are available, and LDL cholesterol levels rise. This process explains why some people have high cholesterol levels even with a healthy diet. In recent years, PCSK9 inhibitors have emerged as a new class of cholesterol-lowering medications. These drugs prevent PCSK9 from inactivating LDL receptors, allowing more LDL to be cleared from the blood, thus significantly lowering cholesterol levels.
While diet and lifestyle factors are important, genetic mutations also play a significant role in determining LDL cholesterol levels. One well-known genetic condition is familial hypercholesterolemia (FH), which affects approximately 1 in 250 people. Individuals with FH have defective or absent LDL receptors, leading to extremely high LDL cholesterol levels from birth. Without treatment, FH can lead to premature coronary heart disease.
In addition to FH, there are numerous other genetic mutations that affect cholesterol regulation, particularly in the PCSK9 pathway. Many people have mutations that cause overactive PCSK9, leading to fewer LDL receptors and higher cholesterol levels. These genetic mutations are relatively common and contribute to the wide variation in cholesterol levels observed in the general population.
It’s interesting to consider the evolutionary roots of high LDL cholesterol. Some theories suggest that elevated LDL levels may have provided an advantage in early human history. LDL cholesterol has been shown to bind to and neutralize certain bacteria, which might have helped our ancestors survive infections. Before the 1800s, when infections were a leading cause of death and most people didn’t live past the age of 30, higher LDL levels may have been protective.
However, in modern times, where people are living longer, these same genetic traits that once conferred survival advantages are now contributing to higher rates of coronary heart disease.
As we age, cholesterol regulation becomes less efficient. LDL receptor activity tends to decline, and cholesterol levels naturally rise. This increase in LDL cholesterol with age is one reason why heart disease becomes more prevalent in older adults. Even individuals who had normal cholesterol levels in their youth may see a rise in cholesterol as they reach middle age and beyond.
This age-related rise in LDL cholesterol underscores the importance of regular cholesterol screenings, especially for those with additional risk factors like a family history of heart disease.
For many people, due to their genetic makeup, even a strict vegetarian and diary free diet fails to lower LDL sufficiently to slow the progression of plaque build up . Most patients find that dietary changes can lower LDL by no more than 10% therefore medication is recommended as a result. Fortunately, modern medicine offers several effective strategies for managing high cholesterol levels those at risk who are unable to achieve sufficient LDL reduction by dietary means. Statins, the most widely prescribed class of cholesterol-lowering drugs, work by inhibiting the HMG-CoA reductase enzyme in the liver. This reduction in cholesterol synthesis triggers the liver to produce more LDL receptors, which in turn lowers LDL cholesterol levels in the blood.
For individuals who cannot tolerate statins or for those with genetic mutations affecting PCSK9, newer treatments such as PCSK9 inhibitors are available. These medications, administered as injections, can lower LDL cholesterol by 50-60%, providing an effective option for those at high risk of coronary heart disease.
In summary, while diet does play a role in cholesterol levels, the liver’s production and regulation of cholesterol are the primary determinants of LDL cholesterol levels in most individuals. The body’s intricate system of cholesterol synthesis, LDL receptor activity, and PCSK9 regulation works together to maintain cholesterol balance.
As we age, the decline in LDL receptor activity can lead to rising cholesterol levels, increasing the risk of coronary heart disease. Regular cholesterol monitoring and preventive treatments like statins or PCSK9 inhibitors can help manage cholesterol levels and reduce the risk of heart disease. Understanding the genetic and physiological factors that influence cholesterol levels allows us to take a proactive approach to heart health, ensuring a longer and healthier life.
When it comes to coronary heart disease, LDL Cholesterol is considered to be the main determinant of the build up in coronary plaque that occurs in about 50% of our population by the age of 60. Plaque is the first of four processes that lead to a heart attack, each featured in stories overt the next few months.
For other stories related to cholesterol, coronary heart disease, and LDL, explore the archives by entering a tag under the search function above.
Next up: ‘let’s talk about salt’ . Due for release 8/10/24.
The Naked Heart is an educational project owned and operated by Dr Edward Leatham. It comprises a series of blog articles, videos and reels distributed on Tiktok, Youtube and Instagram aimed to help educate both patients and healthcare professionals about cardiology related issues.
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