How Good is ‘Good Cholesterol?’


At first we thought all cholesterol was bad. Then, some time ago, there was this idea of “good cholesterol” — the kind that protects the heart by removing the bad stuff from our arteries, and carrying it back to the liver, where it’s broken down and passed from the body.

How Good is 'Good Cholesterol?'

Low-density lipoprotein (LDL) (the bad cholesterol) is found in high levels in 33.5% of American adults, according to the Centers for Disease Control and Prevention (CDC). High levels of high density lipoprotein (HDL) (the good cholesterol) are believed to provide anti-inflammatory protection in the arteries.

But now research presented at the American College of Cardiology 2016 Scientific Sessions in Chicago suggests that high levels of that “good cholesterol” are unlikely to protect people from heart disease if their bloodstream also contains high levels of a newly identified biomarker of inflammation in the arteries.

Inflammation of the artery walls raises the risk of a heart attack or stroke because it increases the chance of plaque on the arterial walls rupturing.

Researchers used a test called NMR spectroscopy to measure lipoprotein particles and glycoprotein acetylation, or GlycA, in 2,848 patients. Participants were average age 63; 66% were male, and 65% had coronary artery disease.

Findings revealed a higher risk of heart attack or stroke among those with high levels of the biomarker GlycA. These results indicate that an interaction may occur between GlycA and small HDL particles, restricting the capacity of HDL to act as an anti-inflammatory, and increasing the chance of a heart attack or stroke.

So good cholesterol is still good, but its effectiveness can be compromised by GlycA levels – which may now become a more reliable predictor of life-threatening adverse events.

What Doctors Got Wrong About ‘Good’ Cholesterol


A new genetic study published in the journal Science suggests that contrary to the conventional wisdom, high levels of good cholesterol aren’t necessarily heart-protective for everyone.

“Twenty years ago, if you had high bad cholesterol and high good cholesterol, doctors said don’t worry about it — one offsets the other,” Dr. Scott Wright, a cardiologist at the Mayo Clinic, who wasn’t involved in the study, told The Huffington Post.”I never really bought that, and time has proven my skepticism to be correct. You can have a heart attack despite having a high level of good cholesterol.”

Doctors have long assumed that high levels of good cholesterol were intrinsically heart-protective, in recent years companies have focused on developing medications that boost these levels, with decidedly underwhelming results. Instead, according to this latest research, some people with naturally high good cholesterol due to a genetic mutation are at an increased risk of heart disease.

“It challenges our conventional wisdom about whether ‘good’ cholesterol is protecting people from heart disease or not,” study author Adam Butterworth, a researcher at the University of Cambridge, told BBC. Drugs “trying to raise HDL may not be that useful,” he said.

The difference between good and bad cholesterol

In general, high levels of bad (LDL) cholesterol leads to build up of the fatty, wax-like substance throughout the body, and good (HDL) cholesterol picks up those LDL deposits and clears them out of the body via the digestive tract. You would think that a stronger waste-management system (read: high levels of good cholesterol) would mean the body is running efficiently and you’re healthier, but the new Science study shows that in some cases, that’s not true.

The study analyzed 1,000 people with a SCARB1 gene mutation, which leads to naturally elevated good cholesterol levels, and found — surprisingly — that those individuals were at an 80 precent increased risk for heart disease.

Of course, this doesn’t mean that everyone with high levels of good cholesterol is at an increased risk. The SCARB1 gene mutation is rare, only affecting 1 out of every 1,700 people. For the rest of the naturally high, good cholesterol folks, who don’t have the SCARB1 gene mutation, good cholesterol could still offer them some degree of protection against heart disease.

Nearly all of the study participants with the SCARB1 gene mutation were of Ashkenazi Jewish descent (a group that’s already at risk for other genetically linked conditions, including Gaucher disease, Parkinson’s disease and breast and ovarian cancers). Still, it’s important to note that SCARB1 gene mutations aren’t limited to Ashkenzai Jews.

You can improve your health, even if you have ‘bad’ genes

“It’s never too early to start with a good family health history,” Dr. Charis Eng, a cancer geneticist at the Cleveland Clinic, previously told HuffPost. She advised sitting down with the family member who knows your extended family’s health the best, and using that information to draw up family health blueprint (which you should update periodically).

And if you have both high good cholesterol and a family history of heart disease, which kills more than 600,000 Americans every year, you should talk to your health care provider about lowering your risk, according to Wright.

“Never assume you’re completely protected just because your good cholesterol is high,” he said. “You always need to be paying attention to the other risks and living a healthy lifestyle to try to reduce your risk of heart disease.”

Perhaps most importantly, the study shouldn’t be interpreted as demonizing good cholesterol. The classic nutrition advice still holds: Quit smoking, try to maintain a healthy weight, exercise and focus on eating a healthful diet of lean proteins, lots of produce and healthy fats.

“Anything we do with diet and exercise to raise or improve our good cholesterol is healthy and not harmful,” Wright said, who tells his own patients to get their weight in a healthy range and practice interval training to boost their good cholesterol and protect against heart disease.

In general, the U.S. Centers for Disease Control and Prevention recommends that adults get their cholesterol checked every five years, with an eye toward an ideal LDL cholesterol lower than 100 mg/dL and an HDL cholesterol higher than 60 mg/dL. The American Heart Association says people looking to lower their bad cholesterol should limit their sodium and sugar intake, and reduce the amount of fatty and red meats, fried foods and baked goods they consume.

Would-be drug mimics ‘good’ cholesterol .


A new drug candidate designed to mimic the body’s “good” cholesterol shows a striking ability in mice to lower cholesterol levels in the blood and dissolve artery-clogging plaques. What’s more, the compound works when given orally, rather than as an injection. If the results hold true in humans—a big if, given past failures at transferring promising treatments from mice—it could provide a new way to combat atherosclerosis, the biggest killer in developed countries.

Although doctors already have effective cholesterol-lowering agents, such as statins, at their disposal, there’s room for improvement. Statins have significant side effects in some people and don’t always reduce cholesterol enough in others. “There is still plenty of heart disease out there even among people who take statins,” says Godfrey Getz, an experimental pathologist at the University of Chicago in Illinois.

For that reason, researchers around the globe are searching for novel drugs that affect cholesterol levels in one of two ways. The first has been to reduce levels of low-density lipoprotein (LDL), commonly known as bad cholesterol, which has been associated with higher heart disease risk. This is the goal of statins, which block an enzyme involved in cholesterol production. The second strategy is to increase levels of good cholesterol, or high-density lipoprotein (HDL), which seems to boost heart health in people who have a lot of it. But producing HDL-raising drugs that prevent heart disease has proven difficult. In the body, a large protein called apolipoprotein A-I (apoA-I) wraps around fatty lipid molecules to create HDL particles that sop up LDL and ferry it to the liver where it is eliminated. So for several decades researchers have been designing and testing small protein fragments called peptides to see if they could mimic the behavior of apoA-I. One such peptide, known as 4F, did not reduce serum cholesterol levels, but it did shrink arterial plaques in mice, rabbits, and monkeys. And in an early clinical trial by researchers at Bruin Pharma Inc. in Beverly Hills, California, that was designed only to measure its safety in people, 4F didn’t appear to show any beneficial effect.

Multiple copies of a four-armed peptide wrap around lipids to create particles that mimic the behavior of HDL, the "good" cholesterol.

M. Reza Ghadiri, a chemist at the Scripps Research Institute in San Diego, California, and his colleagues took a slightly different tack, creating a peptide that mimics another part of the apoA-I protein than 4F does. Initial in vitro studies suggested the peptide formed HDL-like particles and sopped up LDL, an encouraging result that prompted them to push it further. Ghadiri and his Scripps colleagues have now tested their compound in mice that develop artery clogging plaques when fed a Western-style high-fat diet. One group of animals received the peptide intravenously. For another group, the researchers simply added the compound to the animals’ water, a strategy they considered unlikely to work, because the gut contains high amounts of proteases designed to chop proteins apart. To their surprise, in both groups, serum cholesterol levels dropped 40% from their previous levels within 2 weeks of starting to take the drug. And by 10 weeks, the number of artery-clogging lesions had been reduced by half, the team reports in the October issue of the Journal of Lipid Research. What remains puzzling, however, is that Ghadiri and his colleagues did not detect their peptides in the blood of their test animal. Ghadiri says this suggests that the new peptide may work by removing cholesterol precursors in the gut before they enter the bloodstream.

“It’s a very interesting result,” Getz says. But he cautions that the work has been tested only in animals, and many therapies—including the closely related 4F peptide—fail to transfer to humans. That said, Getz notes that some of the initial promising results with this peptide and other apoA-I mimics offer hope that researchers may soon come up with novel drugs capable of dissolving artery-clogging plaques before they can wreak their havoc.