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Harvard Commentaries
Harvard Commentaries
Reviewed by the Faculty of Harvard Medical School

Healthy Heart, Features Healthy Heart, Features

What Should Your LDL Cholesterol Be?

August 29, 2012

By Thomas H. Lee M.D.

Harvard Medical School

Over the last few years, people have bragged if their LDL cholesterol (the "bad" cholesterol) was less than 100 milligrams per deciliter (mg/dL). However, the publication of two major trials (PROVE-IT and REVERSAL) showed that patients with diagnosed coronary artery disease had fewer heart attacks and deaths and not as many fatty deposits in their arteries when their LDL levels were much lower — about 60 mg/dL. Those studies have kindled a surge of activity and discussion among cardiology experts and between doctors and patients. The debate boils down to a simple question: How low should your LDL cholesterol be?

Getting a simple answer to a simple question is not always as easy as one might expect, but there seems to be growing momentum for defining "optimal" LDL cholesterol as 50 to 70 mg/dL. This target is not "official" — at least not yet. The American Heart Association (AHA) has lowered the LDL goal to less than 70 mg/dL for people at very high risk of a heart attack or sudden death. The goal for everyone else is less than 100 mg/dL. The American College of Cardiology and the National Heart, Lung and Blood Institute endorse the AHA recommendations.

However, ask most physicians, even those at average risk, what they want their LDL to be, and they will give you a number lower than 100. The evidence to support this belief goes beyond PROVE-IT and REVERSAL. If you study "hunter-gatherer" populations still living their indigenous life styles, you find LDLs of 50 to 75 mg/dL, and you find no atherosclerosis. Healthy gorillas and other primates in the wild have LDL levels of 40 to 80 mg/dL, and no atherosclerosis. In fact, modern humans are the only adult mammals with mean LDL levels over 80 mg/dL, and they are the only animals that keel over on a regular basis with heart attacks.

Plenty of research studies show that the lower your LDL level, the less atherosclerosis you have and the lower your heart-attack risk. Most studies only included people with an LDL of 90 mg/dL or higher. That's because until recently it was nearly impossible to find humans in the Western world with lower LDLs. And available drugs couldn't get LDL down to lower levels. Now, however, there are drugs and combinations of drugs that can get LDL to that 50 to 70 mg/dL range in most people. Since it is unlikely that many of us are ready to go back to the hunter-gatherer lifestyle, the real question becomes whether we should be taking these medications with a goal of getting our LDL down to those low ranges.

As a physician, I counsel people based on their risk profile. For my patients with a high risk of a heart attack — such as people with known coronary disease, diabetes, or multiple heart-disease risk factors — I have a very low threshold for prescribing a statin (such as Lipitor, Mevacor, Pravachol, Zocor and others). And I push up the statin dose until the LDL is well below 100 mg/dL. Occasionally, I recommend combining statins with other drugs to get their LDL even lower, or to raise their HDL (the "good" cholesterol). For example, niacin can lower LDL and raise HDL. It is inexpensive and available without a prescription. However, you should only take niacin and a statin together in collaboration with your doctor. Niacin has significant side effects, especially when combined with other cholesterol-lowering drugs.

It is trickier to advise people about taking a statin when they do not have risk factors for heart disease and do not have any signs of atherosclerosis. Statins do have side effects, some of them potentially serious, and they are not cheap. Over the course of a year, they cost patients and society a pretty penny. So for lower-risk people, is the small potential benefit of getting their LDL down greater than the risks of the drug? And is that difference worth the cost of the drugs? The answers to these questions are not completely clear.

Given current available knowledge, I am not pushing medications on low-risk patients unless their LDL is over 160 mg/dL. I consider it when their LDL is 130 to 159 mg/dL, while weighing factors like family history and C-reactive protein levels. The results of a major trial called JUPITER were published in November 2008. They suggested that patients who have low LDL levels but high CRP levels benefit from treatment with the powerful statin rosuvastatin. Experts are considering the impact of these data on treatment guidelines. But the data suggest that CRP can help identify patients with normal or low LDL levels who should be considered for drug therapy. Stay tuned.

Thomas H. Lee, M.D., is the chief executive officer for Partners Community HealthCare Inc. He is a professor of medicine at Harvard Medical School. He is an internist and cardiologist at Brigham and Women's Hospital. Dr. Lee is the chairman of the Cardiovascular Measurement Assessment Panel of the National Committee for Quality Assurance.

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