Most of us have had cholesterol levels drawn where the different types of lipoproteins are explained as the bad LDL cholesterol, and the more protective good HDL. This idea came out of the Framingham Heart Study, a primary research project begun in 1948, that identified many risks for cardiovascular disease. But what if the good HDL cholesterol isn’t so good? High levels of low density lipoprotein (LDL) builds up in arterial walls and can cause atherosclerosis increasing ones risk of heart attacks and stroke. High density lipoprotein (HDL) on the other hand can lower overall cholesterol levels by binding with LDL and moving it to the liver, where it is excreted as waste. You can think of HDL as garbage trucks taking cholesterol away from the tissues, whereas LDL and other particles are delivery trucks of cholesterol. The more garbage trucks would mean less build up of cholesterol and fewer cardiovascular events. So a higher level of HDL is better…right?
Recent research reveals that very high HDL levels actually increase the risk of atherosclerotic cardiovascular disease (ASCVD). The authors defined high HDL as >80 mg/dL in men and >100 mg/dL in women. In a study of more than 400,000 people from the general population in the UK., men with HDL levels below 40 or above 80 and women with levels above 100 were at greater risk of both mortality from all causes and cardiovascular death in particular. Two smaller groups surprisingly with coronary disease and HDL levels over 80 had a 96% higher risk of dying overall than those with lower HDL levels.
There are some that are anti-inflammatory and others that can become pro-inflammatory if in an oxidative environment. So the HDL story is not so simple.
Data on HDL can vary on many levels. For example, there are ethnic variations, women have higher HDL levels than men and quitting smoking and moderate alcohol intake can increase HDL levels. Metabolic syndrome or pre-diabetes can lower HDL levels. Further, not all HDL particles are the same. There are some that are anti-inflammatory and others that can become pro-inflammatory if in an oxidative environment. So the HDL story is not so simple. Niacin, commonly used to treat elevated Lp(a) levels can significantly increase HDL levels but has been found to have no reductions in ASCVD. This suggests that there is a U-shaped curve for HDL cholesterol where very low levels are bad and very high levels are also bad. The best solution is the more Goldilocks than the Jekyll and Hyde result which is getting just the right amount of HDL lying between 40-80 mg/dL. But how do we identify how well the HDL family is working? In other words…we want more garbage trucks moving out the garbage (LDL) but we don’t want the garbage trucks stuck in traffic.
One solution would be to measure cholesterol efflux. This was done in the Dallas Heart Study, which was a better predictor of cardiovascular (CV) risk. If you have low cholesterol efflux, then you are at risk. A high efflux means you are good. This marker takes the guess work out of whether high HDL particles are effective and you don’t have to deal with all the different sub-particles in the HDL family.
Unfortunately, we cannot measure cholesterol efflux easily, so the next best thing is to treat what we can control which is high LDL and low HDL. You may have more efficient trucks but not enough of them. People need to know that high HDL is not a universal protective factor for atherosclerosis and puts them actually at higher risk. So lowering LDL through healthy lifestyle changes such as exercise, and a high fiber, low sugar diet is very effective. Estrogen has been shown to be protective for women starting in early menopause. And especially avoid smoking which can raise LDL and lower HDL.
References: Denworth, L. When “Good” Cholesterol Turns Bad. ScientificAmerican.com. The Science of Health. June 2023.
Lin, P. Are higher HDL-C levels really better? Obesity, Metabolic Syndrome, and Prediabetes. Protective Effect of HDL-C Against Cardiovascular Disease. August 01, 2023.