Statins Revolutionize Heart Disease Care

For a remarkable percentage of patients, the number one killer of both men and women in the United States has met its match in statins. The family of heart disease drugs identified as statins are technically the “3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.” But what do they do, exactly, and how do they work?

“Statins work, basically, by blocking cholesterol synthesis,” said Karen L. Fickel, MD, Medical College of Wisconsin Assistant Clinical Professor of Internal Medicine. “They do that in two ways. They ‘up-regulate’ receptors for the bad cholesterol, increasing the number of receptors to pull the bad cholesterol out of the bloodstream.

“Statins also block the actual cholesterol production in the liver. They work by stopping the active enzyme, HMG-CoA reductase, which is the rate-limiting step in cholesterol synthesis.” In fact, some health care practitioners consider statins “the new aspirin” because, like aspirin, they show such widespread benefits with minimal side effects.

Studies of the impact of statins have all reached similar conclusions: statin treatment consistently results in significantly lower cholesterol levels and dramatically reduces the incidence of coronary heart disease and vascular events such as heart attack and stroke.

A Two Way Street: LDL and HDL
Cholesterol has long been identified as a critical component in the risk for heart disease. The two types of cholesterol form a sort of two-way street in the bloodstream. Just like oil and water, cholesterol, which is fatty, and blood, which is watery, do not mix. In order to be able to travel in the bloodstream, the cholesterols made in the liver combine with protein to make particles called lipoproteins. These lipoproteins then carry the cholesterol through the bloodstream.

Low-density lipoprotein (LDL) is often referred to as "bad" cholesterol because it carries cholesterol into the blood, where it can do harm. LDL plays the lead role in causing fatty buildup in the arteries, raising the risk of heart disease.

High-density lipoprotein (HDL), the "good" cholesterol, carries blood cholesterol back to the liver where it can be disposed of. HDL also serves the body well in a variety of critical processes such as producing hormones, building cell walls and digesting dietary fats.

When LDL levels are high the bad cholesterol can be very bad indeed, with results as described in the Food and Drug Administration publication FDA Consumer: “This circulating cholesterol can injure arteries, especially the coronary ones that supply the heart. This leads to accumulation of cholesterol-laden "plaque" in vessel linings, a condition called atherosclerosis.

“When blood flow to the heart is impeded, the heart muscle becomes starved for oxygen, causing chest pain (angina). If a blood clot completely obstructs a coronary artery affected by atherosclerosis, a heart attack (myocardial infarction) or death can occur.” In other words, high LDL levels greatly increase risk while normal HDL levels can decrease risk. This is where statins have come into play in a big way, but not just because of their direct impact on cholesterol levels.

Confusing? Just remember, when it comes to cholesterol, you want to keep your low (LDL) low, and your high (HDL) high.

Spectacular Effects
“There’s a lot we don’t know about how statins work,” said Dr. Fickel. “It’s a really exciting field of research. We think statins have implications beyond cholesterol management. We know they lower LDL, which is their main effect, in big numbers that are anywhere from 20% to 50% in an average person. It’s phenomenal.

“We also think statins reduce coronary events and vascular events such as stroke and heart attack. They reduce mortality from those incidents by 20% to 40%. That’s huge. We think they’re marvelous drugs and use them frequently with really good results on an individual level.”

The other effects of statins, about which less is known, may be equally spectacular. “We think they probably have anti-platelet activity, maybe even anti-ischemic activity and anti-thrombotic activity, meaning they would help prevent stroke more directly by working on the lining of the blood vessel itself. On a cellular level, we think statins might stabilize some of the plaque that can flake off and cause strokes and heart attacks,” says Dr. Fickel.

According to the National Heart, Lung, and Blood Institute, 99.5 million adults in the US – about half of the adult population – have elevated total cholesterol levels. Heart disease kills more than 500,000 people each year in the US, more deaths than by any other cause. After cancer, stroke is the third leading cause of death.

Studies indicate that statins are saving thousands of people from premature heart disease and stroke death each year. Research published in a 1998 issue of the journal Circulation found that the risk of death from heart disease dropped 15% for every 10 percentage points of cholesterol reduction. The long-term controlled trials completed to date indicate that certain statins reduce the occurrence of coronary heart disease anywhere from 20% to more than 40%.

Several statins are currently approved or being studied for approval for use in the US, and studies show varied effects for each. Continuing research that compares members of the statin family is helping doctors prescribe the right statin at the best cost depending on the individual patient.

Those statins now on the market are generally considered to have excellent safety profiles, with the most common adverse effects being muscle aches and gastrointestinal symptoms. According to a study reported in the March 2003 American Heart Journal, liver toxicity has been observed in less than 1% of patients on high doses of statins and is even more rare at low doses. Still, statins are absolutely contraindicated in patients with liver disease.

Diet and Exercise No Less Important
Even though statins are proving effective, dietary changes and lifestyle modifications remain the first line of treatment for high cholesterol. Diet, smoking, heredity, weight, exercise regimen, gender, age and stress levels can all be direct or indirect factors in elevating cholesterol levels and/or causing heart disease.

How and when to use statins are among the basic issues raised by the emergence of this powerful treatment. “One of the hot topics today is trying to answer the question ‘what is a normal LDL number,’” said Dr. Fickel. “We used to say we could just look at the total cholesterol numbers. Now we’re much more specific about looking at the individual components in the cholesterol panel.”

“I usually look at the overall risk factor profile,” said Dr. Fickel. “If you’ve had a heart attack, if you have known coronary disease or if you have diabetes, we’d want to keep your LDL under 100 (milligrams per deciliter, the number used to measure cholesterol). For other patients, if there’s high blood pressure, family history or some other of those factors that aren’t quite as obvious, I count up how many risk factors the there are and generally if patients have two or more they should keep their LDL at least under 130.

“But I also try to emphasize diet and exercise. Even though you’re taking statin medication that’s still not a license to eat anything you want or skip the exercise. I’ll start by recommending appropriate diet and exercise for six to 12 months. My experience is that very few people at high-risk levels are able to achieve their goal level with just diet and exercise, so I might suggest we try a statin for about a month.

One thing that’s very encouraging to people is that when they come in for the next cholesterol check they’ll often see a big reduction in their LDL number. That’s a great motivator for them to continue with the overall program and to continue taking their medication.”

Dan Ullrich
HealthLink Contributing Writer

This article includes information from the National Heart, Lung and Blood Institute and the US Food and Drug Administration.

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.