Sliding scale for LDL: How low should you go?

The target for the safest amount of "bad" cholesterol continues to drift downward.

In 1986, a "desirable" blood level of low-density lipoprotein (LDL, the so-called bad cholesterol) was 130 milligrams per deciliter (mg/dL). Today, information from medical anthropologists and some high-powered clinical trials suggests the new "desirable" should be half that. This has guideline writers, doctors, and the rest of us wondering: how low should we go with LDL?

LDL and arteries

Low-density lipoprotein particles are small, relatively buoyant spheres made up of lipids (fats) and proteins. In the right amount, LDL is good — necessary, actually. It ferries insoluble cholesterol through the bloodstream to the nerves and other tissues that need it. LDL turns "bad" when there's too much of it in circulation, due to a diet rich in saturated fats, one with too many calories, or a genetic problem.

Some of the excess LDL ends up in the inner lining of arteries, where it undergoes a chemical transformation known as oxidation. White blood cells called macrophages sense oxidized LDL as foreign or harmful, and gobble it up. As macrophages fill with oxidized LDL and die off, they send chemical signals that cause inflammation in the artery wall. This steady, low-grade inflammation contributes to artery damage.

The body tries to wall off the growing pool of LDL-stuffed macrophages and other debris by growing tissue around it. This new tissue, called plaque, is an outward sign of atherosclerosis, the disease process at the root of heart attacks, strokes, peripheral artery disease, and other problems.

Plaque can narrow a coronary artery, reducing blood flow and causing the chest pain known as angina. If a plaque bursts, the clot that forms to seal off the break can completely block blood flow, causing a heart attack or potentially deadly rhythm problem. If plaque bursts in a blood vessel nourishing the brain, it causes a stroke.

Redefining desirable

Although the average LDL among Americans is now down to about 120 mg/dL, that doesn't necessarily make this number healthy or desirable. Our hunter-gatherer ancestors probably had LDLs in the 50 to 75 mg/dL range, like modern hunter-gatherers such as the Hazda, Maasai, and Inuit peoples. Strict vegetarians often have LDLs below 90 mg/dL. In all of these groups, rates of heart disease are substantially lower than they are among most Americans.

Findings from clinical trials support the idea that reducing LDL well below 100 mg/dL can have positive payoffs. Trials with acronyms such as PROVE-IT, REVERSAL, ASTEROID, and JUPITER have shown that using powerful statins such as atorvastatin (Lipitor) or rosuvastatin (Crestor) to lower LDL to 70 mg/dL or below halted or even reversed the steady spread of atherosclerotic plaque and also reduced the rate of heart attack and stroke.

Is this safe? In PROVE-IT, the average LDL fell to 65 mg/dL; some participants achieved LDLs under 40. Yet side effects such as muscle problems were no more common among those with LDLs under 60 than in those with higher LDLs.

New guidelines on the horizon

Some of the country's top cholesterol experts are now at work revising the guidelines that doctors use to identify and treat cholesterol problems. Ask these experts what they want their LDLs to be, and the odds are good that many will say 70 or so. Whether they will ratchet down the LDL target for everyone, though, is up in the air. For one thing, there is still relatively little information from randomized controlled trials on the balance of benefits and risks of drastically lowering LDL. For another, such a recommendation could conceivably put millions more American adults on a cholesterol-lowering statin.

The panel's report is due out in 2012. It will be interesting to see if it further lowers the bar for a desirable LDL. Until then, a prudent course of action is to aim for the LDL target that's appropriate for you (see "Current LDL targets"), and to have a conversation with your doctor about getting there.