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aving high levels of “good” cholesterol is thought to promote heart health, but a 67-year-old Jewish grandmother is helping turn that idea on its head.

The woman carries two copies of a genetic mutation that cause her to have off-the-charts high levels of HDL cholesterol — the good kind — yet her arteries are still as thick and gummed up as an old rusty pipe.

And a new study finds that even one copy of that genetic mutation raises the risk of life-threatening clogged arteries by 79 percent. That makes it as dangerous a risk factor as diabetes or high blood pressure.

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The findings may help explain why drugs that aim to raise HDL don’t seem to help heart health. In some cases, it seems, high levels of HDL can actually be harmful.

“This is the first example where a specific mechanism of increasing HDL is, kind of paradoxically, associated with increased risk” of heart disease, said Dr. Daniel Rader, a lipidologist at the University of Pennsylvania Perelman School of Medicine, who led the team that reported the findings Thursday in the journal Science.

Cholesterol comes in two forms: LDL, the “bad” kind that contributes to plaques; and HDL, the scavenger, which carries bad cholesterol away from the arteries and sends it to the liver for destruction.

The class of drugs known as statins, which are widely prescribed, improve heart health by reducing LDL levels. Pharmaceutical companies for years have tried to find complementary drugs that would raise HDL. Yet none of them has ever been proven to prevent heart attacks or strokes.

One explanation for the frequent pharma failures is that it’s the inner workings of HDL — not the absolute amount — that really matters.

“Boosting HDL concentration alone might not be sufficient” to protect the heart, said Dr. Sanjay Kaul, a cardiologist at the Cedars-Sinai Medical Center in Los Angeles. “HDL functionality might be more important.”

The 67-year-old grandma in Rader’s study had loss-of-function mutations in a gene called SCARB1. This gene encodes a receptor that helps absorb HDL cholesterol into the liver and other tissues. But the woman’s mutation completely inactivates this receptor, the study found. That means instead of settling into tissues, HDL continues to circulate in the blood at high levels.

Despite its abundance, the HDL may not be able to do its job properly, resulting in more plaques accumulating in the arteries.

Rader’s study results closely matched those from a series of experiments on mouse models that, until now, had never been confirmed in human samples.

“When you put it all together, it strongly supports the idea that if you block the flux of cholesterol from arteries back to the liver, it actually is bad,” said Dr. Alan Tall, a cholesterol researcher at the Columbia University Medical Center, who conducted some of those mouse studies.

Rather than blindly raising HDL levels, a few drug companies are now focused on enhancing HDL function. To that end, they are infusing patients who have had heart attacks or other cardiovascular issues with forms of HDL grown in cell culture or purified from human plasma.

The furthest along in development is CSL-112, a reconstituted HDL from CSL Behring. According to spokeswoman Natalie de Vane, the company has completed enrollment on its 1,200-person, Phase 2 trial, and results will be reported in the second half of this year.

Another therapeutic possibility raised by Rader’s findings would be to boost the expression of SCARB1 to improve heart health in the general population. Of course, such a therapy would also lower HDL counts. But, according to Rader, “as the HDL field has evolved, lowering of HDL isn’t necessarily viewed as such a bad thing anymore.”

Tall isn’t so sure. The HDL-is-good-for-you dogma is “pretty embedded” in the medical and patient communities, he said, and so they “may have difficultly swallowing an agent that reduces HDL cholesterol levels.”

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