Reduction of low-density lipoprotein cholesterol to below 100 milligrams/ deciliter reversed the accumulation of atherosclerotic plaque, according to a study in the September 24th rapid access issue of Circulation.

In the U.S., patients with known heart disease or a major cardiovascular risk factor are generally counseled to reduce their low-density lipoprotein cholesterol to a blood level less than 100 milligrams/deciliter (mg/dL). The goal for patients whose only risk factor is high cholesterol is usually below 130 mg/dL. Statin drugs are commonly used to lower total and low-density cholesterol.

Recently, the question has been raised whether more aggressive low-density cholesterol reduction would confer an even greater benefit, says lead author Allen J. Taylor, M.D. In addition, there is a question of whether factors other than cholesterol reduction are reflected in the overall benefit from statin therapy. Statin agents may also affect levels of inflammation or the degree of artery thickening.

"This is the first comparison of two statin drugs in a general population that looked at more than their cholesterol-lowering abilities," says Taylor.

Researchers recruited 161 patients (average age 60 years, 71 percent men) who were candidates for statin therapy. About half had known cardiovascular disease. Of these patients, 138 completed the study in which they received either 40 mg of the natural drug pravastatin or 80 mg of a relatively new synthetic statin called atorvastatin.

After 12 months, the patients receiving pravastatin treatment had a 27.5 percent drop in their low-density cholesterol compared with a 48.5 percent reduction in low-density cholesterol for patients treated with the higher dose of atorvastatin. The pravastatin group's low-density cholesterol was reduced to 110 mg/dL, whereas the atorvastatin group's level was 76 mg/dL.

Researchers used ultrasound to compare the thickness of the carotid arteries at baseline, after six months, and after one year of therapy. They found that many patients had a net decrease in carotid artery thickness --- 54 percent of atorvastatin patients and 39 percent of pravastatin patients.

Patients who received moderate treatment with pravastatin showed a slight progression in the thickness of the atherosclerosis in their carotid arteries from an average of 0.615 mm at baseline to an average of 0.640 mm thickness at 12 months. People who received atorvastatin treatment had a decrease from an average of 0.625 mm to an average of 0.591 mm.

"Atherosclerosis is a progressive disease that takes years to develop and continues to get worse over time unless treated," Taylor explains. "Previous studies found that patients in whom plaque stabilized - or stopped progressing - had the lowest risk of heart attacks and other cardiovascular disease problems. In general, past studies have shown that regression is uncommon."

"We need to carefully define at what point lower low-density lipoprotein cholesterol values have the greatest benefit in lowering the risk of heart disease. This study would suggest that values much lower than 100 mg/dL appears better than a value of around 100," he says.

In an accompanying editorial, Prediman K. Shah, M.D., says, "The data provided by Taylor are of potential interest and could have significant implications for clinical practice. However, before we conclude that more low-density cholesterol lowering means less atherosclerosis progression or clinical events, more in-depth research is necessary."

Shah points to several large-scale trials that are measuring the effect of moderate versus aggressive cholesterol lowering on coronary plaque and cardiac events that should provide additional valuable information in the near future.