'Good' cholesterol not so good at preventing heart disease

It is a widely held belief that we should keep levels of the "bad" cholesterol in check, while "good" cholesterol should be high in order to protect against heart disease and other cardiovascular conditions. But new research challenges this belief.

High-density lipoprotein (HDL) cholesterol "is 'good' cholesterol," write the American Heart Association (AHA). "Think of it as the 'healthy' cholesterol, so higher levels are better," they add.

In light of this widely accepted belief, an increasing number of studies have been trying out various therapeutic ways to increase HDL cholesterol levels.

The hope has also been that testing such different therapies may also shed some light on the mechanisms by which HDL seemingly prevents heart disease. Such mechanisms are still unclear, as most of the belief that HDL protects against heart disease rests on observational evidence.

One such therapeutic strategy has been to block the activity of a protein called cholesterol ester transfer protein (CETP).

But now a new study, published in the journal JAMA Cardiology, shows that raising levels of the so-called good cholesterol by blocking this protein does not do much to protect against heart disease.

The research was largely genetic — analyzing the genetic variants of more than 150,000 adults in China — and it was led by a team from University of Oxford in the United Kingdom in collaboration with scientists at the Peking University and Chinese Academy of Medical Sciences, both in Beijing, China.

The lead author of the paper is Dr. Iona Millwood, from the Nuffield Department of Population Health at the University of Oxford.

Studying the effect of blocking CETP

The CETP protein is tasked with transferring HDL cholesterol to certain lipoproteins in exchange for triglycerides, which are a type of fat found in the blood.

As Dr. Millwood and her colleagues explain, certain genetic variants can have the same effect on the CETP protein as a drug would.

Therefore, the team analyzed the CETP-altering genetic variants of 151,217 individuals in order to evaluate the potential benefits and risks of using a CETP-inhibiting treatment.

The participants were clinically followed for more than 10 years. By the end of this period, more than 5,700 of them had developed coronary heart disease, and more than 20,000 had had a stroke.

Dr. Millwood and colleagues found that a higher number of CETP genetic variants did increase levels of HDL cholesterol, but it did not lower the risk of coronary heart disease and stroke.

Additionally, the research did not find any effect on the risk of atherosclerosis or other diseases, such as diabetes and kidney disease. The study's lead author summarizes the findings.

"Our research has helped clarify the role of different types of cholesterol, and suggests that raising levels of HDL [cholesterol] by blocking CETP activity, without also lowering LDL [cholesterol], does not confer any major benefits for cardiovascular disease."

Dr. Iona Millwood

Study co-author Zhengming Chen, a professor at the University of Oxford, adds, "This study demonstrates the value of large prospective biobank studies with genetic data linked to health records, carried out in diverse global populations, to predict the potential benefits or harms of new drug treatments."

The researchers are planning to use the same genetic approach to elucidate the potential effects of other drug targets.