Why Treat Cholesterol?

Some things that influence the development of heart disease and stroke are not within your control. You can't change your sex, your race, or your genes, each of which has a substantial impact on whether you will or won't have heart trouble (see Figure 5). In a small percentage of people, genetic factors are so dominant that heart disease develops regardless of any protective factors. For most of us, though, what we eat, what we do, and what we don't do interact with a mild genetic predisposition toward atherosclerosis and can end up as full-blown heart disease.

Figure 5: Who has high LDL or low HDL?   Who has high LDL or low HDL? Americans with high LDL   Percentage of Americans ages 20 and older with LDL cholesterol 130 mg/dL or higher (borderline high)   Who has high LDL or low HDL? Americans with low HDL   Percentage of Americans ages 20 and older with HDL cholesterol lower than 40 mg/dL (increased risk of coronary heart disease) Source: American Heart Association, Heart Disease and Stroke Statistics, 2006 Update.

The good news is that almost anyone can change or control most of the things that hasten the development of heart disease — things such as high blood pressure, high blood sugar, physical inactivity, obesity, and smoking, as well as high cholesterol. Working on these factors — whether by modifying your diet, taking medication, exercising, or quitting smoking — should provide a potent benefit. As the Framingham Heart Study suggests, it's best to look at the whole heart disease forest before focusing too much on the single tree of cholesterol reduction. You may need an all-out assault on many fronts, a kind of physical spring cleaning, to keep heart disease from appearing or getting worse. Then again, less drastic adjustments may be in order. In any case, you will probably reap the greatest benefit from attacking as many risk factors as possible, a strategy that has always been central to the NCEP's message.

Benefits of Lowering Your Cholesterol

There's no doubt that lowering the amount of LDL cholesterol sliding through your bloodstream can reduce your odds of having a heart attack. Data from dozens of studies indicate that the chance of having a heart attack drops 20%–30% for each 10% drop in cholesterol. As we push cholesterol levels even lower with newer drugs, that ratio changes. For example, in the PROVE-IT study of more than 4,000 men and women, the group of participants who lowered their LDL levels from about 100 to 62 (close to a 40% decline) had a heart disease rate about 16% lower than that of people whose LDL levels fell only to the low 90s (see "How low should you go?"). No matter which statistic you look at, the bottom line is the same: Although taking a cholesterol-lowering medication will not guarantee you protection from heart attack or stroke, it can substantially improve your odds.

In early studies of the potential benefits of cholesterol-lowering strategies, the best therapies available could bring about only modest reductions in cholesterol. Using a combination of diet and drugs that lowered blood cholesterol levels by binding cholesterol-rich compounds in the intestine and preventing their absorption, volunteers in these early studies reduced their cholesterol levels by 5%–10% and had 20%–30% fewer heart attacks than volunteers who took placebos.

Starting in the 1990s, studies that used newer, more powerful cholesterol-lowering drugs called statins (see Table 7) changed the thinking about the benefits of drug therapy for high cholesterol and who might benefit from it. The first of these studies, called the Scandinavian Simvastatin Survival Study, involved 4,444 men and women, ages 35–70, who had pre-existing heart disease and high total cholesterol levels. Half took the cholesterol-lowering drug simvastatin for five years, and half took placebo tablets. By the end of the trial, LDL levels in the treatment group had fallen by 35% and total cholesterol had dropped by 25%, while no change took place in the placebo group. The lower cholesterol levels translated to a 30% lower chance of dying during the trial and a 34% lower chance of having a major coronary event, such as a nonfatal heart attack.

This was the first study to show that lowering cholesterol truly saved and prolonged lives. Other studies followed in relatively short order, each with a different target population, extending the value of cholesterol-lowering drug therapy to new groups. Together these large studies marshaled powerful evidence of the value of statin drugs in lowering cholesterol. They demonstrated that statins reduce the risk of having a heart attack or other major coronary event for almost everyone — people with and without pre-existing heart disease and those with high cholesterol, borderline high cholesterol, and even normal cholesterol.

Newer studies have indicated that lowering cholesterol even further through high doses of statins provides even more benefit to the heart. For example, the Heart Protection Study, published in 2002, found that high-risk people with LDL levels long considered normal benefit from statin therapy as much as others. The study evaluated 20,536 British people 40–80 years old who had been diagnosed with coronary artery disease, other forms of atherosclerosis, or diabetes. A substantial number of them had normal cholesterol levels. The subjects were randomly assigned to receive either 40 mg of simvastatin per day or a placebo. Over the next five years, statin therapy was dramatically beneficial. It reduced the risk of nonfatal heart attacks and cardiac deaths by about 25% each, and it produced similar reductions in the risk of stroke and in the need for artery-opening procedures. Statin therapy was equally effective in all age groups, including people over 70, who were previously considered too old to benefit. Plus, the statin produced similar benefits regardless of cholesterol level, including in people with total cholesterol levels below 193 mg/dL and LDL levels below 116 — levels once considered entirely normal and not requiring treatment. This study confirmed statin drugs as a major weapon in the fight against heart disease.

A cluster of studies involving thousands of people have driven the point home even further: The lower the LDL cholesterol levels, the better. These studies, with names like REVERSAL, IDEAL, and ASTEROID, have shown that using statins to lower LDL levels significantly can prevent heart attacks and — when coupled with an increase in HDL levels — may actually reverse the process of atherosclerosis (see "How low should you go?").

Statins appear to have other benefits as well. Studies have also highlighted the possibilities that statins may decrease the risk for osteoporosis, multiple sclerosis, Alzheimer's, and some types of cancer. While doctors won't prescribe statins for anything other than lowering cholesterol, the potential protection against other diseases is a welcome side effect.

What are the Risks of Treatment?

There is virtually no downside to lowering LDL and total cholesterol levels with a healthier diet and a program of regular exercise. And there are many benefits to this type of lifestyle — reaching well beyond cholesterol and heart disease to better weight management and even cancer prevention. It's worth the effort to select foods lower in saturated fat and trans fat and to boost your daily consumption of fruits and vegetables.

Regular exercise does raise your risk for minor injuries, such as shin splints or sprains and strains. But if you choose a low-impact activity, take it slowly at first, and very gradually increase the intensity of your program, the benefits — lower total and LDL cholesterol, lower triglycerides, higher HDL, lower blood pressure, better control of blood sugar, a stronger heart that pumps blood more efficiently, even a better mood — far outweigh the risks.

On the other hand, using medication to lower cholesterol can produce some unwanted consequences. Statins are generally free from side effects, although they make some people drowsy, constipated, or nauseous — and, in rare cases, have caused liver and muscle damage. The older but still widely used types of cholesterol-lowering drugs also have side effects, including constipation, heartburn, and a bloated feeling.

Is Treatment Worth the Trouble or The Cost?

While the statin trials have shown a clear and very important benefit to patients who use them to aggressively lower their LDL cholesterol, the way that the results of these studies are reported inflates the impact of cholesterol-lowering therapy. If a treatment has little or no cost, such as lowering high cholesterol with diet and exercise, then it makes sense to treat everyone (particularly because diet and exercise have so many other benefits beyond improving cholesterol levels). But when the therapy is costly, as is the case with cholesterol-lowering therapy, experts must consider whether treating large groups of people is cost-effective. That is why a panel of experts was convened by the National Heart, Lung, and Blood Institute to recommend guidelines for cholesterol treatment. It is important to remember that these recommendations leave room for patients and doctors to make individualized decisions.