This issue could not be timelier, as two cholesterol drugs are available over the counter in England and will likely soon be available over the counter in the U.S. In addition, drug studies are in the spotlight. Recently, a number of drugs approved by the FDA, such as Vioxx, have proven more dangerous than previously thought.
Cardiovascular disease is primarily a blood vessel disease. Atherosclerosis has previously been described as “hardening of the arteries.” We now understand that it involves much more than just gradual build-up of plaque. The insides of blood vessels are very active and can become inflamed, which can lead to blood clot formation and subsequently a total obstruction heart attack, stroke or sudden death. Cholesterol, which is a normal component of cells in the body, is a key component in atherosclerosis and is carried in the body by particles known as lipoproteins, which are classified by their density. It is well known that an elevated low-density lipoprotein, LDL (“bad” cholesterol) predisposes to both gradual and acute obstruction of arteries due to plaque build-up and most importantly, inflammation of the inner portion of the arterial wall. High-density lipoproteins, HDL, (“good” cholesterol) have a protective effect on blood vessels. Approximately half of all cardiovascular events, such as heart attacks and strokes, occur in people with normal or low LDL levels.
STATIN FACTS
In 2005, a number of chemically different classes of cholesterol drugs are prescribed. The most effective of these are the statins. These include fluvastatin (lescol), lovastatin (mevacor), pravastatin (pravachol), simvastatin (zocor), atorvastatin (lipitor) and most recently approved rosuvastatin (crestor).
Most of one’s cholesterol comes from liver metabolism. A poor diet does contribute to a high cholesterol level, but genetically determined liver metabolism plays a far larger role. If your parents have high cholesterol, you will most likely have it as well, even with an excellent diet. Statins work in the liver by decreasing production of cholesterol and enhancing absorption of cholesterol.
Statins play an anti-inflammatory role in the inner aspect of blood vessel walls. They decrease artery irritability and, hence, the risk of clot formation and obstruction. The original intention of statins was simple: lower LDL means less plaque build-up. This is true, but much more important, is the discovery that these drugs also have an anti-inflammatory effect on the inner lining of the blood vessel. This blood vessel “smoothing” or stabilizing effect is now recognized as the predominant mechanism for statin’s benefit. Here is the coolest part; they do this even in people with normal cholesterol levels. This is huge, as it implies that even people with normal cholesterol levels glean significant benefit. Last month, two trials published in the New England Journal of Medicine showed statins reduced levels of the inflammatory marker, C-reactive protein (CRP). CRP is associated with cardiac events and reduction of CRP with statin’s lowered cardiac-event rates independent of the LDL level.
Statins as a class of cholesterol-lowering drugs are not new. As a class of drugs they have been available for many years and no group of drugs has been more rigorously studied. More than a million patients have been enrolled in statin studies over the past 10 years. The benefits of statin therapy in high-risk patients are scientifically certain and this huge risk reduction far outweighs the small risk. It has been estimated that statins will save many more lives than penicillin did in the previous century. Even patients at high risk with normal or low cholesterol levels benefit. It is now appropriate in high risk patients to start statins independent of the cholesterol level. Statins are much more than just cholesterol-lowering agents.
ARE STATINS SAFE?
The massive amount of data collected over many years has allowed for a very clear picture of the statin’s favorable safety profile. There are two major concerns with statins. First are abnormalities of liver tests (enzymes). When statins are given in high doses the risk of liver-enzyme rise is only 1-2 percent per year. The good news here is that the test abnormalities are reversible when the drug is stopped. The rumors about liver damage are not true. Statins have never been confirmed to cause a single case of liver failure.
A much more rare side effect, occurring in 1 in 1,000-2,000 patients is inflammation of the muscle, called myopathy. Myopathy is associated with elevations of a muscle enzyme called CK. Patients with high levels of CK and severe muscle pain warrant discontinuation of the drug. These two toxicities are different than the most common side effect, which is minor low-grade muscle aches occurring in approximately 5 percent of patients. Interestingly, in most of the major statin studies minor aches and muscle/liver enzyme abnormalities occur as frequently with placebo as they do with active drug.
FINAL RECOMMENDATIONS: WHAT TO DO?
First, consider one’s risk. Cardiovascular risk is calculated using the known risk factors. These are a positive family history (parent or sibling with heart disease at a young age, <60 years old), smoking, diabetes, high LDL or low HDL, high blood pressure, obesity, inactivity or atherogenic diet (trans-fat and animal/saturated fat). The current recommendations for statins assume that at any level of risk, TLC (therapeutic lifestyle changes) is paramount. The high risk individual with three or more risks is easy.
The answer is statins are absolutely indicated regardless of the LDL. Other than stopping smoking, no intervention or drug could be more valuable for a high-risk individual. With none of the above risks, 10-year event is so low that statin treatment would not provide any statistical benefit and probably is not worth even a small risk. As the number of risks mounts the statin benefit rises. With two or more risks the benefits are large. Keep in mind that statins are under-utilized. The preponderance of the data suggests when in question, lean towards the use of statins. Optimal LDL levels are changing frequently; presently a level of 70 is optimal for individuals with risk and <100 in low-risk patients. There appears to be no lower limit of LDL. In summary, the answer to the question of whether “healthy” people can benefit from statins depends on how “healthy” you are.
John Mandrola, M.D. is a cardiac electrophysiologist (doctor who treats heart rhythm disorders). He is private practice with Cardiovascular Associates. He is active in bike racing and is a member of the Indiana Masters Cycling Team. John is also a member of Kentuckiana HealthFitness Magazine’s Editorial Advisory Board.
