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In the U.S., current thinking about cholesterol is generally that “lower is better.” But there is a growing body of evidence, most recently a study published in the July 2007 Journal of the American College of Cardiology, that suggests very low cholesterol levels are linked to cancer.
This leaves two fundamental questions unanswered: How low is low enough? And might there be dangers from going too low?
The issue is not so cut-and-dry. High cholesterol, especially if accompanied by other...
In the U.S., current thinking about cholesterol is generally that “lower is better.” But there is a growing body of evidence, most recently a study published in the July 2007 Journal of the American College of Cardiology, that suggests very low cholesterol levels are linked to cancer.
This leaves two fundamental questions unanswered: How low is low enough? And might there be dangers from going too low?
The issue is not so cut-and-dry. High cholesterol, especially if accompanied by other risk factors, can lead to very serious cardiovascular problems such as hardened arteries, strokes and heart attacks. And because heart disease is the leading cause of death in the U.S. – claiming over 650,000 lives in 2004 alone, according the Centers for Disease Control and Prevention – there has been a major push from the public health community to fight heart disease head on.
To this end, the Department of Health and Human Services, through the National Cholesterol Education Program (NCEP), has worked since 1985 to “reduc[e] the percentage of Americans with high blood cholesterol” through education programs aimed both at the public and health professionals. The project has been successful in achieving its goals, dramatically increasing blood cholesterol screening and lowering average total cholesterol levels among U.S. adults from 213 mg/dL to 203 mg/dL since 1978. In its most recent guidelines, the NCEP pushed harder for still lower cholesterol levels, suggesting drug therapy for almost all high-risk patients with an LDL-C (“bad” cholesterol) of 100 and over.
But how the new study fits into this traditional treatment of high cholesterol is unclear at this point.
Study causes controversy among editors
The Journal of the American College of Cardiology study was a metaanalysis examining the relationship between lowering LDL-C using statins and the development of cancer.
A meta-analysis, such as the one done for this study, involves combining data from studies already published or completed to see trends that might be missed in any one individual study. In this case, the authors limited their data to the 13 large, randomized, controlled (with a comparison group) trials on statins published up to November 2005 that included data on newly diagnosed cancer. Although in all these studies there was a comparison group that did not receive the statins, those study participants were not included in the meta-analysis. The four statins that met the criteria were lovastatin (MEVACOR), simvastatin (ZOCOR), fluvastatin (LESCOL) and pravastatin (PRAVACHOL).
In their analysis, researchers found a “highly significant inverse relationship between achieved LDL-C levels and rates of newly diagnosed cancer.” In other words, researchers saw more new cases of cancer in patients with the lowest cholesterol levels. However, cancer rates were not related to the degree of LDL-C lowering – that is to say, cancer rates were not linked to how much the cholesterol levels decreased, but how low cholesterol levels became. While it is true that the cholesterol lowering in the meta-analysis was obtained by treatment with statins, similar cholesterol lowering by other methods (diet, exercise or other cholesterol- lowering drugs) might, or might not, have the same effects.
There was some disagreement among the editors of the Journal as to whether to publish the study, which challenges the standard school of thought in U.S. cholesterol management that lower is better. Ideally, a study would give clearer insight as to how doctors and patients should proceed. However, as the editors pointed out, the findings, though provocative, did not provide clear answers and much more research must be done to provide doctors and their patients with a recommendation for the appropriate management of cholesterol levels. The editors chose to publish the article although its practical impact would be unclear, saying: “In the five years that we have been stewards of the Journal, no other manuscript has stimulated such intense scrutiny and discussion.”
New study builds on existing experience
The authors and editors were very concerned by the study’s finding, especially because similar evidence has existed for decades.
An increased incidence in side effects has been associated with low cholesterol since as early as 1971. That year a Japanese report showed a correlation between bleeding in the brain and very low cholesterol levels. This study was followed in the 1970s and 1980s with a number of other studies showing a surprising increase in mortality from noncardiovascular causes (cancer, respiratory, digestive, trauma) as cholesterol levels fell. Those findings caused enough worry at the National Institutes of Health’s National Heart, Lung and Blood Institute (NHLBI) that the agency called a conference to discuss the matter.
The NHLBI conference, held in 1990, examined data from 20 studies, including those from the U.S., Europe, Japan and Scandinavia. Data were pooled to examine outcomes in men and women as a function of their total cholesterol levels. Some studies were observational (no drugs involved); others were tests of cholesterol-lowering drugs. One analysis showed that the chance of death due to cancer, trauma, respiratory and digestive causes was actually increased at low total cholesterol levels. In fact, the only cause of death that decreased as cholesterol levels fell was cardiovascular (45 percent of deaths).
Medical community should recognize potential relationship
With the present study being larger than previous ones and therefore more convincing, there needs to be a more honest acceptance of this “disturbing” potential relationship so that physicians and patients can make more realistic choices between drug risks and benefits.
What You Can Do
Patients undergoing treatment for cholesterol levels should discuss with their physicians how low they are aiming to get their cholesterol levels, bringing to the doctor’s attention concerns about the dangers of very low cholesterols and discussing the differences between the goals for lowering cholesterol for primary and secondary prevention (see box below).
Primary vs. Secondary Prevention of Heart Attacks When it comes to lowering cholesterol, there are two types of heart attack prevention: primary and secondary. Secondary prevention means preventing heart attacks in those with existing cardiovascular disease: those with angina (chest pain) and those who have already suffered heart attacks or other life-threatening cardiovascular outcomes. Primary prevention, on the other hand, refers to treating people who are not known to have cardiovascular disease, many of whom are at very low risk because they do not smoke, do not have high blood pressure, are not diabetic and do not have firstdegree relatives who have had heart attacks or strokes at a young age: younger than 55 for men, 65 for women. For people like this, diet and exercise are the preferable starting points. For secondary prevention, the benefit of LDL-lowering may well outweigh the risk of liver and muscle disease and the possible risk of cancer. However, for primary prevention, especially in those with the lowest risks because of the absence of the above-mentioned risk factors, the benefit/risk balance is quite different. This is because, as far as we know, the drug-induced risks of muscle and liver disease and possible increased risk of cancer are present whether a patient is engaging in primary or secondary prevention, but the benefits for primary prevention are much less clear. Thus, the benefit/risk ratio is much less favorable for this group. This is true, in general, but is magnified by the findings of the present study. |
