Updated Comments: August 2017 publication in EHJ shows very high HDL predicts an increased mortality risk (see more details below...)

As shown in older studies (AIM-HIGH & HPS2-THRIVE), HDL-C increase alone cannot be associated to cardiovascular benefits, especially when LDL-C is very low. HDL-C remains a marker to assess cardiovascular risk but not a Risk Factor: meaning that raising HDL-C is not proven to provide benefit.

A recent data analysis published on August 2017 in the European Heart Journal by Madsen et al. (Eur Heart J 2017;38:2478–2486) referring to the Copenhagen City Heart Study and the Copenhagen General Population Study has shown that the presence of an extremely high concentration of HDL cholesterol is predictive of an increase in all-cause mortality in both men and women. This analysis included 52.268 men and 64.240 women and shows a U-shaped relationship between HDL cholesterol concentration and mortality, with an increased risk observed at both low levels and very high levels of HDL cholesterol. The lowest mortality was observed with HDL cholesterol levels of 73.5mg/dL (1.9 mmol/L) in men and 92.8mg/dL (2.4 mmol/L) in women.

Complexity of HDL-C functions does not allow simplifications such as to determine CV Benefit just from HDL-C concentration (eg: mg/dL) modifications. Number and size of HDL-C particles, concentration of Apo-A1, and the actual Reverse Cholesterol Efflux need to be considered. More trials are underway to finally conclude on this matter.

LDL-C remains the primary treatment target (recent guidelines also mention non-HDL and Apo-B as secondary targets).

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