Statins and the soul of medicine.

R cholesterol levels saves lives. Statin drugs are effective ways of lowering cholesterol levels. Several large-scale randomized controlled trials have demonstrated that statin drugs can reduce cardiac events and premature death, and they may have additional anti-inflammatory benefits. I prescribe them for patients when indicated. Clearly, though, it would be better if diet and lifestyle changes could accomplish the same goals, because all drugs are costly and have adverse effects, known and unknown. However, many physicians believe that only modest goals can be accomplished in this way, so they might as well give patients statins right away. This view seems to be shared by the recent report of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III). They urge more intensive treatment of elevated plasma cholesterol and other risk factors for coronary artery disease. The diagnosis is right, but the prescription is incomplete. I agree with the ATP III goals of reducing lowdensity lipoprotein (LDL) cholesterol to 100 mg/dl and have been advocating this for many years. However, the panel’s “Therapeutic Lifestyle Changes (TLC)” diet and lifestyle recommendations do not go far enough to reduce LDL cholesterol sufficiently for most patients to avoid lipid-lowering drugs. In tacit acknowledgment of the fact that the ATP III TLC diet has insufficient effect on plasma cholesterol levels, the panel encouraged physicians to simultaneously prescribe cholesterol-lowering drugs for those with LDL 130 mg/dl: “For most patients, an LDL-lowering drug will be required to achieve an LDL cholesterol 100 mg/dl; thus an LDL cholesterol-lowering drug can be started simultaneously with TLC to attain the goal of therapy.” We used to say, “try lowering it with diet first,” but now the committee’s chairman, Scott M. Grundy says, “if your LDL is 130 and you have coronary disease, you should be on drug therapy.” 4 Moderate changes such as a TLC diet or a step 2 diet reduce LDL cholesterol by only about 5% to 10% in most patients. In a recent study, the step 2 diet failed to lower LDL cholesterol significantly unless combined with exercise. In clinical practice, Jones and Smith go to their doctors and are prescribed a step 2 or TLC diet. When they return on their next visit, their LDL cholesterol has not declined very much. Patients are then often told that they “failed diet,” when, in actuality, they just didn’t go far enough. Also, most patients with coronary heart disease who followed a step 1 or 2 diet had overall progression of atherosclerosis when measured by serial arteriography. Many patients, perhaps most, can achieve the therapeutic goal of LDL 100 mg/dl without lipid-lowering drugs if they make changes in diet and lifestyle that are more intensive than the NCEP panel recommends. These intensive changes in diet and lifestyle reduced LDL cholesterol by 40% (from an average LDL of 143.8 to 86.56 mg/dl) after 1 year in ambulatory patients who were not taking cholesterol-lowering drugs. In Asia, where a very low fat diet is the norm, the average LDL in the entire population of 4 billion people is 95 mg/dl. Given these data, it is unfortunate that the panel did not offer more intensive lifestyle changes as a therapeutic option, even for motivated patients. Why were patients not even given the option of making more intensive changes in diet and lifestyle that, for many, can be a safe and effective alternative to a lifetime of cholesterol-lowering drugs? It has been estimated that the new guidelines could triple the sales of these medicines in the United States to nearly $30 billion/year at a time when 48 million Americans cannot afford health insurance. Worldwide sales of statin drugs are estimated to be $300 billion/year. All medications, including lipid-lowering drugs, have side effects, known and unknown. As tens of millions of people take these medications for decades, more long-term side effects may become apparent. (The recent example of cerivastatin being taken off the market is a reminder of this.) In contrast, it costs virtually nothing additional to eat a healthful diet, walk, meditate, and quit smoking, and the only side effects of these behaviors are beneficial ones. The reason why intensive changes in diet and lifestyle have a much greater effect on LDL than a TLC diet is well understood, as Brown and Goldstein elucidated. The level of plasma LDL is regulated by the LDL receptor, a cell surface glycoprotein that removes LDL from plasma by receptor-mediated endocytosis. Most patients with atherosclerosis have plasma LDL cholesterol levels that are many times higher than necessary to saturate the LDL receptor system. For them, a step 2 or TLC diet may still saturate and downregulate the LDL receptor system, thereby leading to further progression of atherosclerosis and little decrease in plasma cholesterol levels. Further reductions in fat and cholesterol resulting From the Preventive Medicine Research Institute and the University of California, San Francisco, San Francisco, California. Manuscript received December 20, 2001; revised manuscript received and accepted February 11, 2002. Address for reprints: Dean Ornish, MD, Founder and President, Preventive Medicine Research Institute, Clinical Professor of Medicine, University of California, San Francisco, 900 Bridgeway, Suite 1, Sausalito, California 94965. E-mail: DeanOrnish@ aol.com.