An analysis of data from four clinical trials suggests that statin therapy is associated with regression of coronary atherosclerosis when low-density lipoprotein cholesterol (LDL-C or "bad" cholesterol) is substantially reduced and high-density lipoprotein cholesterol (HDL-C or "good" cholesterol) is increased, but it remains to be determined whether this degree of atherosclerosis regression will translate to meaningful reductions in cardiovascular events, according to a study published in the February 7 issue of JAMA.
According to background information in the study, a large body of evidence supports a central role for lowering levels of LDL-C in the prevention of atherosclerotic cardiovascular disease. "Randomized controlled trials have established that statin-mediated reductions in LDL-C have a favorable effect on the incidence of cardiovascular events. As a result, LDL-C lowering has become an integral component of therapeutic strategies in the prevention of cardiovascular disease. In particular, the use of statins has become widespread."
Stephen J. Nicholls, M.B.B.S., Ph.D., and colleagues from the Cleveland Clinic, "investigated the relationship between changes in lipoprotein levels and atheroma volume [lipid deposits in the inner lining of the artery that can obstruct blood flow] in patients with coronary artery disease (CAD) who were treated with statins." The researchers investigated the role of statin-induced reductions in atherogenic lipoproteins such as LDL-C and increases in HDL-C on the rate of atheroma progression. A total of 1,455 patients from four clinical trials were included. The patients underwent serial assessment of atheroma burden using intravascular ultrasonography. The average age of the patients was 57.6 years; 73 percent were men; 92 percent were white; the average body mass index was 30; 24 percent were current smokers; 76 percent had a history of hypertension; and 19 percent had a history of diabetes.
"The lipid changes translated to a mean [average] reduction in LDL-C of 23.5 percent and an increase in HDL-C by 7.5 percent, resulting in a reduction in LDL-C/HDL-C ratio of 26.7 percent. Changes in all lipid parameters, except lipoprotein(a), with statin therapy were significant," the authors found. "Substantial atheroma regression (5 percent or more reduction in atheroma volume) was observed in patients with levels of LDL-C less than the mean (87.5 milligrams per deciliter) during treatment and percentage increases of HDL-C greater than the mean (7.5 percent). No significant differences were found with regard to clinical events."
"These findings may have important implications for the management of a patient with symptomatic atherosclerotic cardiovascular disease. The finding that the beneficial effect of statins on the rate of plaque progression is derived from both reducing LDL-C and increasing HDL-C complements the previous reports that the benefit of statins on both plaque progression and clinical events may be derived in part by anti-inflammatory properties. The findings also provide further evidence to support the atheroprotective properties of HDL-C and therapeutic interventions that increase its levels," the authors write.
"Although it remains to be determined whether the atherosclerotic regression associated with changes in lipid levels observed in this study will translate to meaningful reductions in clinical events, the findings suggest that modifying the levels of both detrimental and protective lipids should be an important objective in the management of patients with established CAD," the authors conclude.
(JAMA. 2007;297:499-508. Available pre-embargo to the media at www.jamamedia.org.)
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