As reported by The Hartford Courant, June 22, 2004.

Statins' Promise

By William Hathaway

For months Joleen Richard adamantly refused to take statins, a class of cholesterol-lowering drugs her doctor said would dramatically reduce her risk of a heart attack.

"I put up a pretty big fight," Richard says. "I felt fine. I didn't want to take more drugs."

For 26 years, the Bolton resident, now 46, has battled diabetes, a disease that puts her at three times greater risk of heart disease than non-diabetics. Her LDL - low-density lipoprotein, or so-called "bad cholesterol" - had crept up to a worrisome level of 175.

Her doctor, Dr. Nicholas Abourizk, an endocrinologist at St. Francis Hospital and Medical Center, told her that a recent study showed statins could essentially eliminate the heightened risk of heart disease that diabetics have.

"Data from the Heart Protection study are incredible," he says.

Abourizk also told Richard that the fat content in her blood made an eye condition potentially dangerous. She finally relented four months ago and began taking Crestor, one of the new generation of statins.

"He didn't give me a choice," Richard says.

"Statins are doing for heart disease what penicillin did for infectious diseases," Abourizk says.

A slew of studies of statins have found they have beneficial health effects for a wide variety of ailments, findings that suggest that millions more people will be urged to take the drugs, already one of the most widely used medications in the United States.

Cardiologists have long been sold on statins, the name for a class of drugs that block the liver's ability to make LDL cholesterol. They includeatorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor) and rosuvastatin (Crestor).

The evidence is rock-solid that statins prevent heart attacks in people with heart disease and people who have high cholesterol. Statins are now officially indicated for people with heart disease or with LDL levels of 190 or above; or LDL levels of 160 or above for people with two or more heart disease risk factors, including a family history of heart disease, being overweight, smoking or being a diabetic. Age - 45 and older for a man; 55 and up for a woman - also is considered a risk factor.

But statins also have been shown to have protective effects for people with average or slightly elevated levels of cholesterol, and doctors now routinely prescribe the drug for diabetics.

In a 2003 study of more than 5,000 people with three risk factors for heart disease - but on average only mildly elevated cholesterol levels - those whose took statins instead of a placebo had 36 percent fewer heart attacks. In addition, the group taking statins had 27 percent fewer strokes.

With varying degrees of conclusiveness, recent studies also suggest that statins may have a protective effect against a wide variety of other diseases - stroke, Alzheimer's disease, glaucoma, multiple sclerosis, osteoporosis and even some forms of cancer.

Estimates vary, but about 13 million Americans now receive some form of statin therapy. Federal guidelines issued in 2001 say that as many as 35 million people could benefit from taking statins.

Statins work by acting on an enzyme in the liver, blocking its ability to make cholesterol; they also help the liver remove LDL cholesterol. The U.S. Food and Drug Administration first approved statins for use in 1987.

Most doctors say the overall safety profile of the drugs is excellent, although the statin Baycol was withdrawn from the market when it was associated with an unusual number of muscle wasting cases. Muscle aches and problems with the liver do occur rarely but are not dangerous if the patient is carefully monitored, doctors say.

So why don't more people take them?

New generation statins can cost up to $1,500 a year and some patients aren't covered by insurance or can't pay, says Dr. David Silverman, associate professor of medicine and director of lipid disorders at the University of Connecticut Health Center.

Silverman adds that patients are reluctant for psychological reasons as well.

"They don't want to take a pill day after day when they feel fine," he says.

Exercise and diet regimen changes remain the first course of treatment for heart patients but can only go so far in helping people reach healthy cholesterol levels, Silverman says. New evidence strongly suggests that optimum LDL cholesterol levels for heart patients should be below 100, he says. And in most cases such a reduction can only be achieved through statins, he says.

"Lifestyle interventions, as much as we talk about it, are never going to do the trick," Silverman says. "A lot of doctors will begin to demand a lower [cholesterol] standard for our patients."

Statins also provide health benefits independent of their ability to lower cholesterol. Studies released this month alone have found that statins appear to cut the risk of colon and prostate cancer by about half among people taking the drug long term, and to significantly reduce the risk of glaucoma and rheumatoid arthritis.

But scientists still don't know why statins appear to offer protection against diseases like cancer.

One theory is that statins reduce inflammation, which may play a role in cancer as well as in the onset of diseases like dementia and multiple sclerosis. It has been known for a decade that statins seem to suppress the expression of a cancer-causing gene, says Timothy Hla, a vascular biologist at the UConn Health Center. It could be that by stopping the formation of cholesterol, statins set off a sort of chain reaction that offers additional protective benefits, he says.

Hla and other scientists say the evidence thus far does not justify the use of statins solely to prevent diseases such as cancer or Alzheimer's. Hla also notes that no studies have been conducted to determine whether statin use is safe over a period of decades.

But there is a growing sentiment among medical professionals that cholesterol should not be the sole criterion for putting people on statins.

When people reach middle age, many are slightly overweight, have mildly elevated blood pressure or cholesterol levels, or may show early signs of insulin resistance, says Dr. Christie Ballantyne, director for the center for cardiovascular disease prevention at Baylor College of Medicine in Houston.

Individually, each warning signal of heart disease would not concern doctors, he says. But collectively, they can add up to danger.

"It turns out that we have been focused too much on cholesterol levels," Ballantyne says. "People can be misled if they are told their levels aren't terrible. The problem is, if you have four or five borderline things, that is too many. We have to change the way we consider risk and assess the whole patient."

For Joleen Richard, at least, statins seem to be working wonders. Her doctor says her LDL is down to 90, and her HDL - her good cholesterol - is up.