Cholesterol, a waxy, pale-yellow fat, travels through the bloodstream in tiny, protein-covered
particles called lipoproteins that mix easily with blood. You need cholesterol to create cell
membranes, make hormones, and synthesize vitamin D, among other things. But if you’re trying
to avoid heart disease, you should keep tabs on your blood cholesterol values — especially
your low-density lipoprotein (LDL), or “bad” cholesterol. Too much LDL in the bloodstream helps
to create artery-clogging plaque, raising your risk of a heart attack.
Your cholesterol report (also called a lipid profile or lipid panel) also includes your high-density
lipoprotein (HDL); see the table below for recommended values. HDL has long been referred to
as “good” cholesterol, based on observational studies dating back decades showing that people
with high HDL levels are less likely to develop cardiovascular disease.
However, the scientific understanding of HDL has evolved in the ensuing years, and many
cardiologists now believe that HDL may be more of a bystander rather than a “good guy” that
helps lower heart disease risk. “Higher HDL levels are closely linked with behaviors like eating a healthy diet and getting regular exercise,” says Dr. Stephen Wiviott, a cardiologist at Harvardaffiliated Brigham and Women’s Hospital.
Researchers have also discovered that the way HDL functions and its role in the body are more
complex that once believed.
“The analogy that’s often used to describe HDL is a garbage truck, because it picks up extra
cholesterol, or garbage, from the bloodstream and the arteries and then transports it to the liver,
where it’s recycled or disposed,” says Dr. Wiviott. That was the rationale behind the creation of
experimental drugs that raised HDL levels dramatically — between 60% and 100%.
Over the past decade, large clinical trials tested five of these drugs (known as CEPT inhibitors) in people with low HDL levels. But while the drugs reliably raised HDL levels, they didn’t achieve
the most important goal: preventing heart attacks, strokes, and other complications from
clogged arteries. Maybe, the thinking went, it wasn’t the number of garbage trucks that mattered
but how good they were at picking up trash. That is, maybe the drugs increased the wrong kind
of HDL cholesterol.
It turns out that HDL comes in different shapes and sizes. Some types are spherical, while others
are doughnut shaped. Some types of HDL are great at plucking excess cholesterol from LDL
and artery walls (a process referred to as reverse cholesterol transport), while some are not.
What if you had an HDL-based drug specifically designed to improve reverse cholesterol
transport? Think of it as an empty garbage truck with a better trash compactor. But when
investigators tested four weekly infusions of this type of experimental drug on more than 18,200
recent heart attack survivors, it was no better than a placebo in preventing heart attack, stroke,
or death, as detailed in a study published May 2, 2024, in The New England Journal of Medicine.
“It’s yet another point of reference to suggest that targeting HDL with medications may not be
helpful,” says Dr. Wiviott.
But these findings shouldn’t distract you from focusing on the factors you can control — namely,
making sure your LDL is below 100 milligrams per deciliter, or even lower if you have heart
disease. That’s true even if you have a high HDL level, which shouldn’t be considered overly
reassuring or a reason to ignore an elevated LDL value, says Dr. Wiviott
