Low HDL-cholesterol: Not quantity, but quality

Cholesterol is a major risk factor for heart disease. Elevated LDL-cholesterol, commonly known as the 'bad cholesterol,' is associated with the increased risk of heart disease while HDL-cholesterol, the 'good cholesterol', is associated with decreased risk.

During the past few years, approximately 40 regions in the genome have been associated with plasma HDL-cholesterol levels. In a recent publication, the genetic background of low HDL-cholesterol was studied by research groups from the University of Helsinki, Finland. The study subjects were Finnish individuals with either extremely high or extremely low HDL-cholesterol.

The scientists discovered several new genes which predispose low HDL-cholesterol levels. They also observed that many of the genes regulating inflammation and immune response of the body were also associated with low HDL-cholesterol levels in the circulation. The results thus validate the strong link between inflammation and low HDL-cholesterol.

"The results of the study tell us that some individuals are genetically more prone to inflammation than others, especially in the adipose tissue and blood vessels. The inflammation may block the transport of cholesterol from vessel walls to circulation leading to lower HDL-cholesterol levels in the circulation," says Dr. Pirkka-Pekka Laurila.

'Good' is not always that good

The researchers also showed that the quality of HDL particle can vary considerably. In individuals, whose HDL-cholesterol levels were low, the quality of HDL particles was also impaired; they contained smaller amounts of lipid molecules which are known to be antioxidant and thus protective to arteries. In individuals with high HDL-cholesterol levels in the circulation, the lipid composition of the HDL particle was more beneficial regarding heart disease risk.

Based on this Finnish study, and earlier ones, the terms 'HDL-cholesterol' and 'HDL particle' should not be confused to indicate heart disease risk. The term 'good cholesterol' appears to be misleading as the cholesterol molecules is exactly the same in both 'good' HDL and 'bad' LDL particles. It is likely that molecules other than cholesterol -- the lipid and protein molecules on the surface of the HDL particle -- are responsible for the protective effects of HDL particles against heart disease.

This study was conducted in collaboration with research groups led by Professors Marja-Riitta Taskinen, Matti Jauhiainen, Matej Orešič, and Samuli Ripatti.

Cholesterol is a molecule which is transported in the circulation by its carriers, the HDL particles and LDL particles. HDL particles remove cholesterol from the blood vessel walls and transport it to the liver to be excreted from the body via bile. LDL particles transport cholesterol to the organs of the body from the blood stream. If LDL-cholesterol levels are elevated in the blood stream, cholesterol will accumulate in the vessel wall leading to plaque formation in the vessels (atherosclerosis).