It appears that in some cases, high-density lipoprotein (HDL) cholesterol, the so-called “good” cholesterol, does not protect against heart disease, and may even be harmful. A new study suggests a subclass of HDL that carries a particular protein is bad for the heart.
Previous studies have shown that high levels of HDL cholesterol are strongly linked to low risk of heart disease. But trials where people have been given drugs to increase their levels of HDL cholesterol have yielded inconsistent results: leading to the idea that HDL cholesterol may actually have protective and non-protective elements.
Now, researchers at the Harvard School of Public Health (HSPH) have found that when the surface of HDL cholesterol bears a small protein called apolipoprotein C-III (apoC-III), there is an increase in the risk of heart disease, and when it is absent, HDL cholesterol is especially heart protective.
They write about their study, the first to show this effect, in a recent online issue of the Journal of the American Heart Association.
Senior author Frank Sacks is professor of cardiovascular disease prevention at HSPH. He told the press:
“This finding, if confirmed in ongoing studies, could lead to better evaluation of risk of heart disease in individuals and to more precise targeting of treatments to raise the protective HDL or lower the unfavorable HDL with apoC-III.”
ApoC-III is a proinflammatory protein that resides on the surface of some lipoproteins, including HDL and LDL (low-density lipoprotein, or “bad”) cholesterol.
For their investigation, Sacks and colleagues examined blood samples from 18,225 men and 32,826 women who took part in the Health Professionals Follow-up Study, and the Brigham and Women’s Hospital-based Nurses’ Health Study between 1989 and 1995.
They wanted to see whether apoC-III made a difference to the heart-protective qualities of HDL cholesterol: they wondered if there were two subclasses of HDL cholesterol, one that protected against heart disease and one that did not, depending on the presence of apoC-III.
The study participants had been followed for 10 to 14 years, during which time 634 of them developed coronary heart disease. Sacks and colleagues matched these participants with controls who had the same demographic status (eg age and gender), smoking status, and whose blood samples were drawn at the same time.
They compared the blood samples in several different ways: they looked at total HDL, HDL with apoC-III, and HDL without apoC-III, and assessed these concentrations against coronary heart disease (CHD) risk.
They also adjusted the results so as to eliminate, as far as possible, effects from other factors that impact CHD risk, such as age, smoking status, diet and lifestyle.
The results showed that after taking these potential influencers into account, two subclasses of HDL cholesterol appear to have opposite effects on risk of CHD in men and women.
A minor subclass, accounting for around 13% of HDL cholesterol, carries apoC-III and this was linked to a higher risk of future CHD.
The major subclass of HDL cholesterol is one that does not carry apoC-III, and this was linked to a lower risk of future CHD.
The analysis showed the participants with plasma HDL apoC-III concentrations in the highest 20% of the population had a 60% increased risk of CHD.
The researchers suggest rather than simply measuring total HDL, it might be better to measure HDL with and without apoC-III to provide a more reliable gauge of heart disease risk, or the protective capacity of HDL.
Jensen also proposed that:
“Reduction in HDL-apoC-III by diet or drug treatments may become an indicator of efficacy.”
Funds from The National Institutes of Health and the Villum Kann Rasmussen Foundation in Denmark helped pay for the study.
This is not the only study recently to doubt the heart-protective benefit of HDL cholesterol. A paper by Sekar Kathiresan of Massachusetts General Hospital in Boston, and colleagues, published in the The Lancet on 17 May, questions the idea that raising blood HDL cholesterol translates into reduced risk of heart attack.
Written by Catharine Paddock PhD