When HDL is high (and too high)

For decades, HDL cholesterol has been dubbed the “good cholesterol,” and LDL cholesterol the “bad cholesterol.” In some ways this is true - a high number of LDL particles results in cholesterol build-up, whereas HDL particles aid in cholesterol excretion. Elevated HDL has been associated with a decreased risk of heart disease in several population studies, and so the thought that more HDL is always better has become a pervasive part of medical lore. However, as with most things in medicine, the reality appears to be much more nuanced. Recent studies demonstrate that a high HDL may not always decrease our risk for heart disease and raising it may not improve our heart health. So, what is the optimal level of HDL? Can it still be considered “good cholesterol”? And can it get too high that it is no longer protective?

What is HDL? 

As I’ve written about previously here, high-density lipoprotein (HDL) particles are a type of lipoprotein - a particle that can transport cholesterol in the body. HDL assists with cholesterol excretion, and it accomplishes this task by picking up excess cholesterol in the arteries and transporting it to the liver where it can be metabolized and eventually removed from the body. Research has also shown that HDL has anti-inflammatory, antioxidant, and anti-clotting effects. 

The current 2018 cholesterol guidelines from the American College of Cardiology and American Heart Association consider low HDL < 50 mg/dl in women and < 40 mg/dl in men, with the recommended goal HDL levels anywhere above that threshold but typically over 60 mg/dl.

What impacts your HDL level? 

The amount of HDL in your body is mostly driven by your genetics as well as age, height, and sex. It can be mildly impacted by lifestyle, on the order of 5 – 10%. The biggest lifestyle factors that influence LDL are as follows

1. Smoking - smokers have lower HDL levels, and smoking cessation increases HDL

2. Diet

   • Trans fats, sugar, soda, and refined grains like white rice all lower HDL

   • Fiber-rich foods, omega-3 fats and monounsaturated fats increase HDL

3. Exercise - aerobic exercise, like walking, swimming, running, and cycling, can increase HDL levels

4. Alcohol (especially wine) - increases HDL levels, but overall may impact health negatively so this is not a reason to consume any more than a moderate amount. You can read more here

5. Weight loss - individuals that are above their ideal body weight typically have low HDL levels.  Rapid weight loss has also been shown to temporarily decrease HDL levels, while weight stabilization at a healthy weight is associated with normalized HDL levels

Medications that are associated with a change in HDL level include

1. Niacin can increase HDL by 15 – 30% but with limited patient tolerability

2. Fibrates, such as fenofibrate can increase HDL by 10 – 20%

3. Statins can increase HDL by 5 – 10%

4. Beta blockers, such as metoprolol can lower HDL by 5 – 10%

HDL and Heart Disease

Previous observational studies have repeatedly shown a linear, inverse relationship between HDL and heart disease - said another way, the higher the HDL level, the lower the risk. This has been attributed to the presumed atheroprotective effects from decreased cholesterol in arteries and the anti-inflammatory and antioxidant properties.

The standard lipid panel measures the amount of HDL cholesterol within these particles. It does *not* examine the HDL particle functionality.

We need both proper amount and proper functioning HDL particles to efficiently excrete excess cholesterol.

HDL particles require various enzymes to find, pick up, transport, and deliver cholesterol, and if an enzyme is missing or broken, HDL cannot do its job. Thus, HDL particles may contain elevated amounts of HDL cholesterol - appearing cardioprotective - but in fact, these particles are dysfunctional. As a result, an elevated HDL cholesterol does not always translate to protection from heart disease. 

Can HDL be too high?

Several recent studies have shown that a plateau may exist for HDL, where no further heart disease risk reduction is provided after a certain HDL level is reached. Other studies have found that medications that increase HDL levels do not result in a reduced heart disease risk, even with a higher HDL-c. 

There is even a recent suggestion of increased risk in those with an extremely high HDL level. Initial studies suggested that those with extremely high HDL-c levels and without heart disease may have an increased risk of developing heart disease. A recent study found that in individuals with established heart disease, those with very high HDL levels (> 80 mg/dl) have a higher risk of death compared to those with normal HDL levels, independent of other cardiovascular risk factors. This mortality risk is like those with very low HDL levels (< 40 md/dl). Another study found the risk to begin to increase once HDL reached >97 mg/dl for men and >116 mg/dl for women. The current European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines note that the risk of heart disease appears to increase when HDL-C is above 90 mg/dL.

It is not yet entirely clear why a very high HDL-c level may increase the risk of heart disease and death, but it may be driven by heterogenous functionality of the HDL particles with some actually becoming dysfunctional as described above. Regardless, it seems that the previously widely accepted inverse relationship between HDL and heart disease may not hold true for all levels of HDL-c, with very high levels of HDL-c possibly becoming harmful. 

Is HDL still “good cholesterol”?

All things considered, HDL particles can still be considered the overall “good” guys as long as the mechanism of reverse transport is intact. The numerous studies correlating a lower risk of heart disease in those with normal HDL levels should not be ignored. However, HDL may not be as protective from heart disease as once thought, and it certainly does not negate an elevated LDL cholesterol. 

The optimal level of HDL cholesterol is likely still around 60 mg/dL, but caution is advised if the HDL becomes markedly elevated, particularly above 90 mg/dL.

In my practice, I focus much more on the healthy habits that lower LDL cholesterol. When needed, we also work to improve insulin resistance and the accompanying dyslipidemia (ie most common modifiable cause of low HDL), thereby targeting the root cause rather than one of the end results (elevated HDL-c).

Interested in working with Dr Harkin to optimize your cholesterol?