Rethinking HDL cholesterol

Earlier article retained

Cholesterol, a waxy, pale-yellow fat, travels through the bloodstream inside tiny protein-coated particles called lipoproteins that mix readily with blood. Your body needs cholesterol to build cell membranes, make hormones, and synthesize vitamin D, among other tasks. But if you want to avoid heart disease, it pays to watch your blood cholesterol values, especially your low-density lipoprotein (LDL), the "bad" cholesterol. Too much LDL in the bloodstream helps form artery-clogging plaque, raising the risk of a heart attack.

Your cholesterol report, also called a lipid profile or lipid panel, also lists your high-density lipoprotein (HDL); the table below shows recommended values. HDL has long been called "good" cholesterol, based on decades of observational studies finding that people with high HDL levels are less likely to develop cardiovascular disease.

Scientific understanding of HDL has evolved since then, and many cardiologists now believe HDL may be more of a bystander than a "good guy" that actively lowers heart disease risk. "Higher HDL levels are closely linked with behaviors like eating a healthy diet and getting regular exercise," notes one cardiologist.

Rethinking what HDL does

Researchers have also found that how HDL functions, and its role in the body, is more complex than 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," the cardiologist explains. That idea was the rationale behind experimental drugs that raised HDL levels dramatically, by 60% to 100%.

Over the past decade, large clinical trials tested five of these drugs (known as CEPT inhibitors) in people with low HDL. The drugs reliably raised HDL levels but failed the most important test: preventing heart attacks, strokes, and other complications of clogged arteries. Perhaps, the thinking went, it was not the number of garbage trucks that mattered but how good they were at picking up trash. In other words, the drugs may have increased the wrong kind of HDL.

It turns out HDL comes in different shapes and sizes. Some particles are spherical, others doughnut-shaped. Some types are excellent at plucking excess cholesterol from LDL and artery walls (a process called reverse cholesterol transport), while others are not.

Lipid lowdown: What numbers are best?

The desirable values below are for people without known heart disease.

TOTAL CHOLESTEROL: Less than 200 mg/dL = desirable; 200 to 239 mg/dL = borderline high; 240 mg/dL and above = high.

LDL CHOLESTEROL: Less than 100 mg/dL = optimal; 100 to 129 mg/dL = near or above optimal; 130 to 159 mg/dL = borderline high; 160 to 189 mg/dL = high; 190 mg/dL and above = very high.

HDL CHOLESTEROL: Less than 40 mg/dL = low (a risk factor); 60 mg/dL and above = high (protective).

TRIGLYCERIDES: Less than 150 mg/dL = normal; 150 to 199 mg/dL = borderline high; 200 to 499 mg/dL = high; 500 mg/dL and above = very high.

A better garbage truck?

What if you had an HDL-based drug designed specifically to improve reverse cholesterol transport? Picture an empty garbage truck fitted with a better trash compactor. But when investigators tested four weekly infusions of this experimental drug in more than 18,200 recent heart attack survivors, it proved no better than a placebo at preventing heart attack, stroke, or death, according to a study published May 2, 2024, in a leading medical journal. "It's yet another point of reference to suggest that targeting HDL with medications may not be helpful," the cardiologist says.

These findings should not distract you from the factors you can control: making sure your LDL is below 100 milligrams per deciliter, or even lower if you have heart disease. That holds true even if your HDL level is high, which should never be taken as overly reassuring or as a reason to ignore an elevated LDL value, he adds.