HDL Cholesterol – Not Always Healthy

When it comes to HDL cholesterol, most people think, “more is better.” After all, it’s been drilled into us that HDL (“good”) cholesterol removes LDL (“bad”) cholesterol from the blood vessels so that it can be excreted from the body, thereby protecting against heart disease and stroke.

The relationship between HDL and heart disease is now known to form a U-shaped curve. Too little OR too much is associated with heart disease, cancer, and premature death. The ideal range for HDL is not >40 mg/dl as most of us have been told; it’s 40-60 mg/dl.

In a study of 5,500 high-risk individuals, there was a positive association with all-cause mortality if the HDL was >80 mg/dl. Two population-based cohorts in Copenhagen of over 100,000 people showed that all-cause mortality increased significantly in women with an HDL of >135 and men with an HDL of >97.

In some studies, the link between high HDL and the increased risk of death or cardiovascular disease is much more pronounced in women than men, which is interesting, because women are regularly told that their HDL level should be higher than men’s. In fact, among 1,400 postmenopausal women, those with the most elevated HDL were more likely to have plaques in their carotid arteries.

Dysfunctional HDL is pro-inflammatory and contributes to the narrowing of arteries because it  causes the buildup of cholesterol in the blood. Conditions such as diabetes or systemic inflammation are believed to alter HDL from a cardioprotective particle to one that promotes inflammation and LDL oxidation. The problem is that there hasn’t been a ton of research on how to determine if HDL is dysfunctional.

HDL is not just one type of particle, but instead a family of particles with different sizes, shapes, and compositions. Small HDL particles decrease the risk of atherosclerosis, while large particles increase the risk in certain individuals. For example, these large HDL particles appear to increase the risk of heart disease in women who’ve just entered menopause, and then protect them once they’ve been in menopause for a while. It’s tricky stuff.

Only one percent of the population has an HDL level >80 mg/dl, while half of us have an HDL level that is too low, below the threshold of 40 mg/dl needed for protection against heart disease. If your HDL is >60, hang tight if all of your other numbers are at target, and you don’t have heart disease and aren’t at risk for developing heart disease. The appropriate management of too-high HDL is unknown at this time.

It’s important not to think, “My LDL is high, but my high HDL cancels it out, so it doesn’t matter.” LDL is still the number one predictor of heart disease, and no one should be hanging their hat on the idea that HDL is protecting them. In fact, HDL can be useful, harmful, or neutral. There are more than 60 different proteins associated with HDL, but most particles will only carry a few. No one knows which proteins confer which properties.

Medications taken solely to raise low HDL levels are unlikely to be helpful in the long run; they can lead to the loss of some surface proteins essential to cardioprotection. Some physicians will order an HDL particle number measurement if a patient has high LDL and very high HDL. These assays that measure HDL efflux capacity better predict cardiovascular events than HDL levels alone. Calcium scoring, which is a non-invasive CT scans of the heart, can also be helpful in these situations and will determine your risk of developing heart disease by measuring the amount of calcified plaque in your coronary arteries.