Sliding scale for LDL: How low should you go?

Content provided by the Faculty of the Harvard Medical School

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.

Current LDL targets

Aim for an LDL below 100 mg/dL (your doctor may recommend under 70 mg/dL) if you are at high risk (a calculated risk* greater than 20%) of having a heart attack or stroke over the next 10 years. This generally includes individuals who have had a heart attack, stroke, or mini-stroke; who have angina (chest pain with activity or stress); who have had bypass surgery, angioplasty, or a procedure to open a narrowed artery in the neck; who have peripheral artery disease, narrowed carotid arteries, or an abdominal aortic aneurysm; who have diabetes; or who have two or more major risk factors for heart disease.

Aim for an LDL below 130 mg/dL (your doctor may recommend under 100 mg/dL) if your risk is below 20% and you don't have any of the conditions listed above.

Aim for an LDL below 160 mg/dL if you have zero or one risk factor for cardiovascular disease.

*To calculate your risk, talk with your doctor or do it online at www.health.harvard.edu/147.

Reference: Cholesterol section on Better Medicine


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