Science of high cholesterol still mystifying top scientists

You might think that scientists have high cholesterol pretty much worked out given that millions of North Americans take cholesterol-lowering drugs. But you'd be wrong. This oily molecule, which lines our cell membranes and provides raw material for our hormones, continues to mystify top scientists.

Here's what we know for sure: Too much cholesterol is bad for you and drugs to lower it can help. While the body needs cholesterol to survive, most adults have far too much of it. That translates into an increased risk of heart attacks, because cholesterol collects as plaque in the arteries. These can become inflamed and deposits can suddenly break off, causing heart attack and stroke.

Statins, the class of cholesterol drugs that includes simvastatin (generic Zocor), Lipitor and Crestor, have been proved to prevent heart attacks and strokes in numerous studies involving 90,000 patients. Exercise and weight loss can also help lower bad cholesterol levels and heart risk. Eating large amounts of certain foods such as oats and salmon may also help.

"We know an awful lot," says Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic. "If you look at what's happened to cardiovascular rates in the past couple of decades, we certainly know enough to know one class of drugs, statins, has had a very big impact. If you give these drugs to susceptible individuals, you can reduce their risk by 25 per cent. The problem is we are kind of stuck in a rut. We haven't had a new class of drugs since 1987 that has had proven benefits. That's not a very good track record, so obviously there's still a lot we don't know."

One unresolved question is whether all methods of lowering cholesterol are created equal. Most of the cholesterol in the body is made from fat in the liver. Statins work by short-circuiting this process. They may also cut levels of inflammation. But the cholesterol drug Zetia (not soldin Canada), from Merck, works by a totally different mechanism, one that has not been proven to prevent heart attacks. It works by blocking absorption of cholesterol from food. In two trials, the drug failed to prevent clogged arteries. Merck is only now conducting a big trial to see if it prevents heart attacks.

In medicine, absolute certainty is always elusive. Even after tens of thousands of patients have been followed for years in clinical trials, some worry there are side effects of statins that still haven't turned up.

A related controversy, brought up in an analysis in the Annals of Internal Medicine last month, is whether doctors are using statins the right way. Doctors currently use drugs to try to get patients' LDL down to a specific target for most people the target is 120 milligrams per deciliter. But Yale cardiologist Harlan Krumholz and University of Michigan internist Rodney Hayward say this is unnecessarily complicated. Instead, they recommend doctors estimate people's total cardiovascular risk using a multiple risk factors like high blood pressure and age. People with a 15 per centor higher 10-year risk of suffering a heart attack should get a healthy dose of Lipitor (40 mg); everyone else should take generic simvastin, also at a 40 mg dose. Krumholz and Hayward calculate this method would prevent more heart attacks than bothering with numerical targets, while allowing patients to take lower doses of drugs.

Another debate is whether it is worth it to take drugs that lower blood levels of fatty particles called triglycerides. Some doctors are big believers in lowering triglycerides, which has made Abbott Laboratories' TriCor drug (notsold in Canada)a $1 billion US product. But the drug has not really proven its heart-protecting benefit in a big trial. One is due next month at the annual meeting of the American College of Cardiology. Fish oil supplements containing certain omega-3 fatty acids can lower triglyceride levels and may protect the heart in other ways as well.

One more big question is whether drugs that raise good cholesterol (HDL) can benefit people. People with naturally high levels of HDL are somewhat protected against heart disease, but most attempts to raise HDL with drugs have flopped. One HDL-raising drug out there is the B-vitamin niacin, also sold by Abbott under the brand name Niaspan. Major trials of its effectiveness are due in the next couple of years.

New research into the human genetic code is yielding new questions about how the body regulates cholesterol levels and clues to new potential drugs. One apparently supercharged version of HDL is in clinical trials already. Another promising lead is a gene called PCSK9. People with certain variants of this gene seem to be protected from developing high cholesterol and heart disease.

In medicine, absolute certainty is always elusive. Even after tens of thousands of patients have been followed for years in clinical trials, some worry there are side effects of statins that still haven't turned up. But a link to cancer has been disproved, and cardiologists insist these are some of the safest medicines around. Some researchers speculate they might have benefits in diseases like Alzheimer's or in preventing tumors, but again, this evidence is murky.

The bottom line: Cardiologists don't know much as much as you might think about high cholesterol. But they do know that you should watch your diet and exercise. If you are still at risk of a heart attack, consider taking a statin drug.