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Tuesday, July 24, 2007

Low Cholesterol Levels And Cancer

Low Cholesterol Levels And Cancer


Millions of Americans take statins to lower their cholesterol, but how low should you go" A number of scientific studies support the benefits of lowering low-density lipoprotein (LDL) cholesterol, and achieving low LDL cholesterol levels is one of the most important steps in preventing heart disease. New research, however, provides evidence for an association between low LDL levels and cancer risk.

The authors of the study, reported in the July 31, 2007, issue of the Journal of the American College of Cardiology (JACC), set out to understand how and why statins cause side effects, especially damage to the liver and muscle cells. The study findings support taking multiple medications rather than high-dose statins to minimize those side effects. The scientists did not expect to find the increased cancer risk (one additional incident per 1,000 patients) from low LDL levels, and additional studies have already begun to investigate this potential risk further. A key component in future studies will be to confirm the risk and to identify whether the risk may be a side effect of statins or just low LDL.

This analysis doesnt implicate the statin in increasing the risk of cancer, said lead author Richard H. Karas, M.D., F.A.C.C., professor of medicine at Tufts University School of Medicine. The demonstrated benefits of statins in lowering the risk of heart disease remain clear; however, certain aspects of lowering LDL with statins remain controversial and merit further research.

The scientists found one additional incident of cancer per 1,000 patients with low LDL levels when in comparison to patients with higher LDL levels. In their evaluation of randomized controlled statin trials published before November 2005, the scientists looked at 13 therapy arms consisting of 41,173 patients.

Scientists assessed absolute change and percentage of change in LDL reduction and the resulting achieved LDL levels in relation to rates of newly diagnosed cancer in each therapy arm. They also looked at the relationship between low, intermediate and high doses of statins and rates of newly diagnosed cancer. Eventhough they did not find a relationship between percent of change and absolute change in LDL levels, they observed higher rates of newly diagnosed cancer among patients with lower achieved LDL levels. In addition, the new cancers were not of any specific type or location.

Recent data from large-scale statin trials have shown that more intensive LDL lowering can provide significant cardiovascular benefits to higher-risk patients. In response to these findings, recent national guidelines have advocated for lower LDL goals and higher doses of statins to reach them. However, informal observations linking intensive LDL lowering and higher occurence rate of reported health problems, including liver and muscle toxicity and cancer, has introduced some concern over the safety of such therapys.

These concerns in part prompted the current study. However, the current findings are not definitive, as limitations of the study show. Scientists performed their analysis from summary data taken directly from published manuscripts of each trial. An analysis based on data for each individual patient would have yielded more specific and potentially more compelling results, said Dr. Karas.

These current findings provide insufficient evidence that there is any problem with LDL lowering that outweighs its significant benefits on vascular disease, said John C. La Rosa, M.D., who wrote an accompanying editorial in the July 31 issue of JACC. However, we must continue to be vigilant in ensuring that its benefit clearly outweighs its risk.

Eventhough the cancer risk was surprising, the scientists primarily sought to determine how and why statins cause side effects, especially damage to the liver and muscle cells. For this portion of the study, scientists analyzed 23 statin therapy arms that included 75,317 patients with a combined 309,506 years of follow up. A link between LDL lowering and liver or muscle irritation was not found. However, liver toxicity levels increased with higher statin dosage. Based on their findings, the scientists concluded that moderate-dose treatment with multiple medications including statins may prove to be preferable to high-dose treatment with statins alone. Dr. Karas emphasized that patients are advised to continue their statin therapys and, as always, consult their doctor before discontinuing use of any medication.

While these results raise important new questions about statin use, they do not demonstrate a causal relationship between statins and cancer, said James Dove, M.D., F.A.C.C., president of the American College of Cardiology. This study is hypothesis-generating, not hypothesis-proving.

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