High-density lipoprotein cholesterol (HDL cholesterol) is commonly measured to assess the risk of heart disease.
If you’ve had a blood sample drawn for assessment of lipid panel you probably already know if your cholesterol level is acceptable or not. You might also recall something about good and bad cholesterol and the ratio between these two.
Of course, there is only one type of cholesterol. The “good” and “bad” has to do with the lipoproteins that carry cholesterol molecules in our blood stream.
A standard lipid panel provides information about total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL cholesterol) and HDL cholesterol.
LDL cholesterol is often termed “the bad cholesterol” because high levels are associated with increased risk of heart disease.
On the other hand, HDL cholesterol is usually nicknamed “the good cholesterol” because high blood levels are associated with less risk of heart disease whereas low levels are correlated with increased risk.
In other words; there is an inverse relationship between HDL cholesterol and the risk of heart disease. It is believed that HDL’s act as scavengers, picking up excess cholesterol in the blood and transporting it to the liver where it’s broken down.
Atherosclerosis and Heart Disease
Atherosclerosis is the hallmark of coronary artery disease. It may be described as a chronic inflammation of the arterial wall.
Atherosclerosis leads to the formation of lesions or plaques that protrude into the lumen of the artery causing arterial narrowing, which can disturb blood flow. If this occurs in the coronary arteries, it may cause chest pain often termed angina pectoris.
The coronary arteries supply blood to the heart muscle. Acute heart attack (myocardial infarction) occurs when there is a sudden disruption of blood flow in a coronary artery. A sudden blockage is usually caused by a rupture of an atherosclerotic plaque in the vessel wall, with subsequent formation of a blood clot (thrombosis) at the rupture site. The sudden disruption of blood flow causes the death of heart muscle cells (infarction), and may impair the function of the heart muscle.
In 1961, the Framingham Study reported that high blood levels of cholesterol and high blood pressure were associated with increased risk of coronary artery disease and acute heart attack. This lead to the term “coronary risk factors” being defined.
Cigarette smoking, various fractions of cholesterol, insulin resistance, diabetes, obesity, physical activity, mental stress and depression are all examples of modifiable risk factors which, if present increase the risk of heart attack. However, although many risk factors have been identified, coronary heart disease remains a common disorder. Despite extensive research, our understanding of the mechanisms behind this disease is incomplete.
Lipids and Lipoproteins
Lipids, like cholesterol and triglycerides, are essential substances for the human body. They are used by cells for energy utilization, hormone production, bile acid formation and much more.
Because lipids are insoluble in blood, they are carried by lipoproteins that transport them to various tissues and organs. Lipoproteins consist of cholesterol, triglycerides, phospholipids and protein. The lipoproteins act as carriers transporting important fat substances to the organs of the body.
There are five major types of lipoproteins; chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL).
HDL and LDL lipoprotein particles have very different roles. Therefore, measuring the amount of cholesterol within these particles tells two different stories.
Elevated levels of LDL cholesterol are associated with increased risk of heart disease, but high levels of HDL cholesterol are associated with low risk. HDL particles seem to be involved in clearing and removing cholesterol from arteries and atherosclerotic plaques while LDL particles appear directly involved in the atherosclerotic process.
It is important to understand that measurements of HDL cholesterol only provide information about the amount of cholesterol carried by HDL particles. HDL particles differ in size and function, and there are many types, both small and large.
HDL particle number can be measured by NMR (Nuclear Magnetic Resonance). Studies have shown that such measurements are more strongly associated with atherosclerosis than measurements of HDL cholesterol.
Recent studies have shown that simple measurements of HDL cholesterol may not always reflect HDL function. Thus, there is growing evidence that HDL function may sometimes be impaired although measurements of HDL cholesterol are normal. Therefore, measuring HDL cholesterol may not be the best method to assess HDL function.
Although incomplete, HDL cholesterol is still the most widely used measurement to assess HDL.
Other metrics that are currently being tested include HDL particle number, average HDL size, specific HDL subclasses, and HDL functional properties.
HDL Cholesterol and Heart Disease
An inverse relationship exists between HDL cholesterol and the development of coronary artery disease. In other words, high levels are associated with low risk of heart disease, and low levels are linked to high risk.
Based on data from the Framingham Heart Study the risk of heart attack increases about 25 percent for every 5 mg/dl (0.13 mmol/L) decrement in blood levels of HDL cholesterol. However, whether HDL cholesterol is a causal risk factor or merely a marker of risk is still intensely debated.
The most widely accepted hypothesis regarding the protective properties of HDL when it comes to atherosclerosis is that it promotes the uptake of cholesterol from tissues, including the vascular wall, and returns the cholesterol to the liver from where it is excreted. This process is often termed “reverse cholesterol transport.”
It has also been postulated that HDL’s may promote normal function of the endothelium, the innermost layer of the arteries. Furthermore, HDL’s may reduce inflammation, protect against oxidation of LDL, and positively affect blood clotting (thrombosis).
HDL Cholesterol – Normal Range
The table below shows the reference values;
|HDL cholesterol (mg/dL)
(U.S. and some other countries)
|HDL cholesterol (mmol/L
(Canada and most of Europe)
|Below 40 mg/dL (men)
Below 50 mg/dL (women)
|Below 1.0 mmol/L (men)
Below 1.3 mmol/L (women)
|40-49 mg/dL (men)
50-59 mg/dL (women)
|1-1.3 mmol/L (men)
1.3-1.5 mmol/L (women)
|60 mg/dL and above||1.6 mmol/L and above||Very good|
Levels above 60 mg/dl (1.6 mmol/L) are associated with low risk of coronary heart disease. This is more likely to be seen among women than men.
HDL cholesterol below 40 mg/dL (1.0 mmol/L) is considered too low and appears to be an independent risk factor for coronary artery disease. Furthermore, the definition of metabolic syndrome includes low HDL cholesterol as one of the five criteria for classification. Low HDL cholesterol is one of the most common phenotypes seen in persons with premature heart disease.
HDL cholesterol in the range of 20-40 (0.5-1.0 mmol/L) may appear in isolation but is often associated with high triglyceride concentration, insulin resistance and increased risk of type 2 diabetes. Furthermore, some drugs, such as beta-blockers may lower HDL cholesterol. Anabolic steroids can markedly reduce HDL cholesterol and should be suspected particularly in healthy young men with unexpectedly low HDL cholesterol levels.
Levels of less than 20 mg/dL (0.5 mmol/L) are uncommon and can sometimes be attributed to very high triglycerides. It may also be due to rare genetic mutations, such as Tangier disease and fish-eye disease.
Individuals with high HDL cholesterol often have large LDL particles. They are also likely to have low LDL particle number (LDL-P). LDL-P is a reliable marker of risk for coronary artery disease.
Measuring apolipoprotein B or LDL-P may help to estimate risk among individuals with high levels of both LDL-and HDL cholesterol. Calculating non-HDL cholesterol may also be useful to assess risk under these circumstances. Assessing the triglyceride/HDL cholesterol ratio may provide further information.
How Can HDL Cholesterol Be Influenced?
HDL cholesterol can be influenced by lifestyle modification.
Smoking reduces HDL cholesterol and smoking cessation is associated with moderately increased levels.
Regular aerobic exercise can modestly increase HDL cholesterol. This increase is related to the frequency and intensity of physical activity, with greatest increases occurring with frequent, low-intensity exercise, such as five 30-minute sessions per week.
Obesity is associated with low HDL cholesterol levels and high triglyceride levels. A negative correlation exists between HDL cholesterol and body-mass index (BMI), meaning that HDL cholesterol tends to be lower with increasing BMI. Weight loss usually raises HDL cholesterol.
Dietary choices affect HDL cholesterol. If the intake of fat is reduced, levels of LDL- and HDL cholesterol both decline. In one study comparing calorically balanced diets, those who consumed a low-fat diet had lower HDL-cholesterol than those who were fed a high-fat diet.
Intake of saturated fats usually increases both LDL- and HDL cholesterol. Substituting monounsaturated fat for saturated fatty acids may improve the ratio between these tow subfractions of cholesterol.
Limiting intake of simple carbohydrates is usually helpful, in particular, if triglycerides are elevated. This is often the case in obese people and those with metabolic syndrome.
A diet rich in n–3 polyunsaturated fatty acids (omega-3) – sources include oils (olive, canola, soy, flaxseed), nuts (almonds, peanuts, walnuts, pecans), cold-water fish (salmon, mackerel), and shellfish — with limited carbohydrates, such as those found in ready-to-eat cereals, potatoes, white bread, and snack foods, is often recommended.
Moderate alcohol consumption raises HDL cholesterol but is usually not recommended for that purpose.
Several classes of medications increase HDL cholesterol levels; these include niacin and fibrates, and, to a lesser degree, statins. With the exception of statins, drug therapy that elevates HDL cholesterol has not been shown to improve outcome or reduce the risk of coronary events.
The 2013 American College of Cardiology/American Heart Association Guidelines for the Treatment of Blood Cholesterol to Reduce Cardiovascular Risk do not make a recommendation to add therapy to raise low HDL cholesterol in patients who are on maximal statin therapy.