We have been hearing for years that high-density lipoprotein (HDL)—the “good cholesterol”—may not be all it's cracked up to be. Now a new study shows that a certain subclass of HDL may actually be “bad,” increasing the risk of coronary heart disease.

A small protein may be to blame. HDL with a small proinflammatory protein called apolipoprotein C-III (apoC-III) on its surface may nearly double the risk of heart disease in healthy men and women, according to Frank Sacks, professor of cardiovascular disease prevention at the Harvard School of Public Health and senior author on a paper in the April Journal of the American Heart Association. Conversely, Sacks's study found, HDL without apoC-III may be especially heart-protective. A number of studies have shown that LDL (low-density lipoprotein)—the “bad cholesterol”—with apoC-III on its surface is particularly harmful, leading to higher incidence of plaque buildup in artery walls. Yet, Sacks says, this is the first large-scale prospective study with healthy subjects to show that apoC-III on HDL may have similar effects.

The scientists examined blood samples taken from 572 women in the Nurses' Health Study and from 699 men in the Health Professionals Follow-Up Study, two of the largest long-term investigations of factors that affect women's and men's health. Over 10 to 14 years of follow-up, they documented 634 cases of coronary heart disease, which they matched with control subjects for age, smoking status and the date blood was drawn. After adjusting for those and other lifestyle-based cardiovascular risk factors, they found a nearly twofold increase in risk for HDL with apoC-III. The men and women whose levels of HDL with apoC-III were in the top 20 percent had a 60 percent higher risk of developing heart disease than those in the bottom 20 percent.

Sacks says the techniques his team used to measure the levels of the two HDL subclasses, which Harvard is patenting, could lead to more precise tests to evaluate heart disease risk and treatment response. Moreover, the findings, if replicated in his and others' ongoing studies, could spur development of drugs that target HDL subclasses, working to raise HDL without apoC-III and lower HDL with it. “The bottom line is, there's a lot more to be learned about HDL and how it acts,” says Nilesh Samani of the University of Leicester in England and co-author of a paper that found raising HDL levels might not change heart disease risk.

This article was originally published with the title Cholesterol Confusion.

4 Comments

1. 1. tharriss 08:25 AM 9/13/12

   Onward C̶h̶r̶i̶s̶t̶i̶a̶n̶ Science Soldiers? :-)

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2. 2. Archimedes 08:35 AM 9/13/12

   The amino acid, Alanine, inhibits cholesterol biosynthesis. At the same time, Alanine is the only amino acid released by fasting cardiac muscle. This implies a regulatory mechanism exists within the heart muscle with regard to the aforementioned.
   Assuming the same, perhaps Alanine dietary preventive health and treatment modalities should be investigated with regard to cardiac atherosclerosis, dyslipidemia (cholesterol and lipid disorders), and general cardiac health (coronary heart disease).

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3. 3. Stagnaro 11:58 AM 9/13/12

   Unfortunately, all researches "demonstrating" that lipoproteins can bring about CAD are fundamentally biased. As a consequence, also Framingham Heart Study conclusions are biased, as I have emphasised often, even recently in a blog of mine: www.sergiostagnaro.wordpress.com (1-4)
   In a few words, individuals, involved by AMI as well as AMI outcome, of course, independently of environmental risk factors, which may be totally absent, as in my personal case, since birth, are positive for CAD Inherited Real Risk, characterised by type I, subtype b) newborn-pathological Endoarteriolar Blocking Devises in coronary arterioles, according to Hammersen, bedside recognised in one second by means of Caotino's Sign, using a simple stethoscope (5).
   
   References on request
   

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4. 4. BillR 04:23 PM 9/13/12

   Tell me again, why should I believe these studies? They contradict each other so much and the researchers change their conclusions so often that I have no confidence that the medical researches even know what they are talking about. We need to stop jumping to conclusions based on a single study that only gives limited insight onto a limited aspect of a problem. Lets get the cold hard facts straight before pumping out drugs with the promise that this will fix everything only to have it kill you.

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