What is Low HDL Cholesterol?
High-density lipoproteins (HDL) are a type of particle in our bodies with a range of characteristics and functions. Scientists have used many methods to sort these HDL particles into different groups. The first methods sorted them by size and density using a process called ‘ultracentrifugal flotation rate’ in a high salt solution, followed by grouping based on the number of lipoprotein particles, which are tiny packages that carry fats around the body.
Another method, called ‘gel electrophoresis’, divided HDL further into five categories – 2a, 2b, 3a, 3b, and 3c. This was based on the composition of ‘apolipoprotein AI’, which is a major component of HDL. Even more accurate methods like ‘Nuclear magnetic resonance (NMR) spectroscopy’ and ‘ion mobility’ have been used to count HDL particles.
What makes HDL important is its ability to protect against atherosclerosis, a disease that narrows and hardens the arteries. HDL does this in a few ways, including moving cholesterol out of the cells in the artery walls and helping remove it from the body through the liver, acting as an antioxidant, fighting inflammation, and helping the cells lining our blood vessels (known as ‘endothelial cells’) work properly.
What Causes Low HDL Cholesterol?
Having low levels of ‘good’ cholesterol, also called HDL (High-Density Lipoprotein), could be due to a variety of reasons. It could be caused by certain medications, genetic disorders, or it may be part of a bigger health issue known as the metabolic syndrome.
There are some genetic conditions, such as Fish Eye disease and Tangier disease, that can lead to low HDL. In some families, these conditions could pass genetically from parents to children. One such generational condition is called familial hypoalphalipoproteinemia, which occurs due to unusual changes in the genes related to a particular protein, resulting in low HDL. Another is familial HDL deficiency, which is a common reason for low HDL.
Tangier disease, identified about 40 years ago in siblings living on Tangier Island, is an inherited condition in which the person has extremely low or no HDL in the body. It can lead to early heart disease, peripheral neuropathy (a term for diseases that lead to damage in your peripheral nerves), and enlarged organs like the liver and spleen. This disease also causes changes in the skin and eyes due to the buildup of certain fats, alongside enlarged tonsils and lymph nodes.
Another uncommon inherited condition is familial combined hypolipidemia, defined by low levels of all fats in the bloodstream including HDL. In this condition, a protein known as Cholesterol Ester Transfer Protein (CETP) plays a vital role. CETP helps in the movement of cholesterol from HDL to other fatty proteins. Higher levels of this protein might help reduce the risk of heart problems related to cholesterol buildup in your arteries while lower levels could increase the risk.
The enzyme lipoprotein lipase helps to move cholesterol to HDL from other fats in the body, reducing the levels of harmful fats. If there are changes in the genes responsible for this enzyme, it could lead to early heart disease in some cases.
Another enzyme called hepatic triglyceride lipase can also affect HDL levels. It breaks down fats from HDL, resulting in lower blood levels of HDL.
There’s also an enzyme called Lecithin Cholesterol Acyltransferase (LCAT), which helps to change free cholesterol into cholesterol esters and HDL cholesterol. Genetic problems with LCAT can lead to very low levels of HDL. A condition called Fish-eye syndrome is caused by LCAT deficiency due to genetic mutations, resulting in severe eye-related symptoms and potentially kidney disease.
Finally, low HDL cholesterol can also be a component of the metabolic syndrome. This syndrome includes insulin resistance, type 2 diabetes, obesity, high blood pressure, marginally high levels of ‘bad’ cholesterol (LDL), and a spike in certain harmful fats present in your blood.
Risk Factors and Frequency for Low HDL Cholesterol
Many hereditary causes of low HDL, a type of cholesterol, are considered rare and their prevalence isn’t well-known. However, it’s estimated that mutations in the apo A-I gene, which can contribute to low HDL, occur in 6% and 0.3% of the general population.
Signs and Symptoms of Low HDL Cholesterol
Low HDL, or “good” cholesterol levels, can have many causes. In most cases, there aren’t obvious signs or symptoms to give us clues. However, several distinct conditions can provide key symptoms or findings that help in making a quick diagnosis.
- Conditions associated with high LDL (“bad” cholesterol) and triglyceride levels often lead to skin changes, such as xanthomas (fatty deposits under the skin) and xanthelasmas (yellowish deposits of fat on or around the eyelids).
- ‘Fish-eye disease’ leads to severe cloudy patches on the cornea, prompting its name.
- People with a condition called ‘Tangier disease’ often experience peripheral neuropathy, a nerve disorder that affects the arms and legs.
- A physical check-up of a patient with Tangier disease might reveal an enlarged liver or spleen, bigger tonsils or lymph nodes, a whitish-grey ring around the cornea (arcus corneae), xanthomas, and xanthelasma.
- Those who suffer from metabolic syndrome could develop a skin condition called acanthosis nigricans, usually associated with insulin resistance. This condition causes dark, velvety patches in the folds of your skin.
Testing for Low HDL Cholesterol
If your doctor thinks you might have a condition called fish-eye disease, they’ll take a few tests to check how your body is doing. One of these tests involves checking your HDL cholesterol levels. HDL is a type of ‘good’ cholesterol in your blood. Fasting lipid panel is the test used to measure this.
Another test is called NMR. This stands for Nuclear Magnetic Resonance, and it counts the number of certain particles in your blood. But, there isn’t currently a reliable, standard method to analyze these measurements.
Fish-eye disease can cause protein in your urine (proteinuria) and kidney damage (nephropathy), so your doctor will want to take a look at how your kidneys are working. A basic anabolic panel is a group of tests that check for different substances in your blood, including those which give information about your kidney function. A urine test is conducted to check for protein in your urine.
All these measurements would help your doctor get a better idea of what’s going on in your body and confirm whether or not fish-eye disease is causing your symptoms.
Treatment Options for Low HDL Cholesterol
Contrary to common belief, research does not support the idea that increasing the level of ‘good’ cholesterol (known as HDL cholesterol) in the body has beneficial health effects. For example, in 2009, a study looking at over 100 different medical trials found no link between increasing HDL cholesterol levels through treatment and a lower risk of heart disease, heart-related deaths or overall deaths.
While the medications niacin and gemfibrozil can increase the amount of HDL cholesterol in the blood by 15-30%, their efficacy in reducing heart disease is questionable. One study found that adding niacin to a common group of cholesterol-lowering drugs called statins didn’t provide any extra benefits, despite a significant increase in HDL cholesterol levels.
Another study, known as the VA HIT trial, looked at patients with heart disease who had low HDL cholesterol, balanced LDL cholesterol – ‘bad’ cholesterol, and moderate level of fats called triglycerides. Patients were randomly split into two groups – one treated with gemfibrozil, the other given a placebo. The study found that those in the gemfibrozil group had fewer heart attacks and heart-related deaths over five years. This was linked to the increase in HDL cholesterol and not changes to other types of fats in their blood.
Studies have also tested infusing a protein, known as apolipoprotein A-I (ApoA1), to see if it can reduce the risk of heart disease. Animal studies have shown promise, with ApoA1 reducing the amount of ‘bad’ cholesterol and harmful thickening of artery walls. However, major clinical trials in humans are needed to definitively determine whether this treatment can reduce heart disease events.
The potential benefits of injecting reconstituted HDL – ‘remade’ good cholesterol – has also been explored. However, the trial had to be stopped early because of increased abnormal liver test results in patients receiving higher doses. Follow-up scans didn’t show any significant differences in the amount of artery-clogging plaques between patients who did and didn’t receive the treatment.
Other compounds, such as CETP inhibitors, have been investigated for their potential to increase HDL cholesterol levels. Despite promising results in increasing HDL levels, several trials had to be stopped early because they did not reduce the risk of heart disease events or were unsafe.
Lastly, heart disease patients with low HDL cholesterol levels were found to have the same amount of risk reduction when treated with common cholesterol-lowering drugs, regardless of their baseline HDL levels. So, raising that level may not provide significant benefits.
So, for people at higher risk of developing heart disease with low levels of HDL cholesterol, a healthy diet, regular exercise, maintaining a healthy weight, and quitting smoking have been shown to improve HDL cholesterol levels and lower the risk of heart disease. In some cases, certain medications might lower HDL cholesterol. Despite this, it’s not usually recommended to stop these medications as they are crucial in treating other health conditions.
What else can Low HDL Cholesterol be?
Certain medications used to manage high blood pressure, also known as anti-hypertensive medications, can alter levels of a certain type of cholesterol known as HDL in the blood. These medications include:
- Diuretics: These drugs can increase all types of cholesterol and triglycerides (a type of fat), especially in African Americans. The effect is proportional to the dosage. However, in diabetics taking diuretics, the HDL level may decrease.
- Beta-blockers: These drugs can lower HDL levels because they increase triglycerides. However, selective beta-blockers, especially in diabetic patients, have a smaller effect on raising triglycerides.
- Alpha-blockers: They have the opposite effect of beta-blockers. They decrease triglycerides and increase HDL levels.
- Central sympathomimetics: They decrease HDL and other types of cholesterol.
- Vasodilators: These drugs increase HDL while reducing LDL (bad cholesterol) and total cholesterol.
Being aware of these effects can help in managing blood cholesterol levels while treating high blood pressure.
What to expect with Low HDL Cholesterol
According to research from the Framingham heart study, myocardial infarction, which is also known as a heart attack, increases by about 25% for every 5 mg/dL decrease in HDL cholesterol serum levels below average values. HDL cholesterol, often referred to as ‘good cholesterol’, helps remove other forms of cholesterol from your bloodstream.
Further studies have found that a low level of this ‘good cholesterol’ remains a risk factor for heart attacks, even when other known risk factors are taken into account. Research on patients with established heart disease indicated that higher levels of HDL cholesterol can help protect against future heart-related incidents. This was found to be true even when patients were being treated with statin therapy, a type of treatment used to lower cholesterol levels in the blood, as shown in the SMART study.
Possible Complications When Diagnosed with Low HDL Cholesterol
Increasing the level of HDL cholesterol without a significant increase in HDL particles can lead to an overload of cholesterol in the HDL particles. A study conducted in a community showed an acceleration towards carotid atherosclerosis (a type of heart disease). This was measured by the thickening of the carotid artery wall in patients who showed no symptoms and had no underlying heart disease. Certain treatments, such as CETP inhibitors and niacin, can raise HDL cholesterol levels without affecting the functionality or number of HDL particles. This usually tends to increase the number of cholesterol overloaded particles.
- Increase in HDL cholesterol without matching increase in particles can cause cholesterol overload.
- This overload can fast-track progression towards heart disease.
- Some treatments, like CETP inhibitors and niacin, can raise HDL cholesterol but don’t affect the functionality or the number of particles.
- Such treatments may contribute to cholesterol overload.
Preventing Low HDL Cholesterol
Maintaining a healthy diet can be an effective treatment for low levels of HDL (good cholesterol). The Mediterranean diet, often associated with longer life spans and reduced risk of heart disease, is one such example. Yet, it’s crucial to note that what types of fats you include in your diet can affect your HDL levels differently.
For example, replacing just 1% of your meals with trans fats instead of saturated fats, monounsaturated fats, or polyunsaturated fats affects your cholesterol. This mixed kind of diet can raise cholesterol levels by different proportions and increase lipoprotein, a class of fats that includes cholesterol and triglycerides, in your blood.
Aside from monitoring your diet, keeping an eye on your weight and regularly exercising can also help maintain your HDL levels. The type of saturated fats you eat can make a difference too. Saturated fats with 14 (like myristic) and 16 (like palmitic) carbon chain lengths found primarily in dairy products and red meats can increase both good and bad cholesterol while decreasing fats like triglycerides. Conversely, stearic acid with an 18 carbon chain found in beef and cocoa butter has less impact on your cholesterol levels.
Further, while there isn’t a complete agreement on the effects of monounsaturated fats on HDL, replacing polyunsaturated fats (such as those found in some fishes) with monounsaturated fats (found in foods like nuts, avocados, and olive oil) can help reduce insulin resistance – a condition where your body doesn’t use insulin effectively. Since insulin resistance and diabetes can cause low HDL, addressing these issues is also a part of managing your HDL levels.
Lastly, Omega 6 fatty acids, another type of fats found in plant oils like soybean, safflower, sunflower, and corn, can help increase good cholesterol while decreasing bad cholesterol and other fat types like triglycerides in your blood.