Further evidence that high-density lipoprotein is a chameleon-like lipoprotein.

Abstract

This editorial refers to ‘Serum amyloid A: high-density lipoproteins interaction and cardiovascular risk’ by S. Zewinger et al ., doi:10.1093/eurheartj/ehv352. Zewinger et al. 1 studied 3310 patients undergoing coronary angiography in the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study and determined that serum amyloid A (SAA) concentrations predicted all-cause and cardiovascular mortality. Patients with low SAA levels and higher high-density lipoprotein (HDL) cholesterol levels had lower all-cause and cardiovascular mortality. In contrast, patients with high SAA levels and higher HDL cholesterol levels had increased all-cause and cardiovascular mortality. The authors derived a formula to calculate the levels of biologically ‘effective’ HDL cholesterol based on SAA and HDL cholesterol data from the LURIC Study. They validated this approach using two other populations, one with high SAA levels and very high risk for cardiovascular events: 1255 participants with type 2 diabetes on haemodialysis in the German Diabetes and Dialysis Study (4D) and a population-based survey of inhabitants of Augsburg, Germany (KORA S4 Study). In the KORA S4 Study, 4261 participants were recruited; subjects with previous myocardial infarction ( n = 77), stroke ( n = 48) or with missing values for HDL cholesterol or SAA were excluded ( n = 102) as well as those lost to follow-up ( n = 7). In these populations, HDL cholesterol levels did not predict outcomes, but higher levels of the calculated biologically ‘effective’ HDL cholesterol were associated with reduced risk for all-cause mortality as well as reduced cardiovascular endpoints. In vitro studies showed that SAA-supplemented HDL reduced endothelial nitric oxide (NO) production and increased endothelial production of reactive oxygen species, leading to the loss of the ability of the HDL to decrease adhesion of mononuclear cells to TNF-α-treated endothelial cells. The authors concluded that ‘SAA turned HDL into a pro-inflammatory particle’. In 1994, Liao et al. 2 demonstrated that mildly …