Marked low-density lipoprotein cholesterol reduction below current national cholesterol education program targets provides the greatest reduction in carotid atherosclerosis.

BACKGROUND: Current National Cholesterol Education Program (NCEP) guidelines recognize low-density lipoprotein cholesterol (LDL-C) below 100 mg/dl as an optimal level. Evidence supporting this is scant. Both LDL-C and C reactive protein (CRP) are known correlates of atherosclerosis progression.

HYPOTHESIS: We examined the effect of final LDL-C and CRP obtained with statin therapy on carotid intima-media thickness (CIMT), a valid surrogate for clinical benefit of lipid-lowering therapies.

METHODS: In a randomized, single-center trial, 161 patients were assigned to statin therapy of different potencies (pravastatin 40 mg, n = 82; atorvastatin 80 mg, n = 79). The effects on CIMT were assessed in relationship to LDL-C and CRP levels obtained after 12 months of therapy.

RESULTS: Changes in CIMT were directly related to the final LDL-C level obtained on statin therapy after 12 months (R = 0.219, p = 0.015). Carotid intima-media thickness regression was seen in 61% of the subjects in the lowest quartile of final LDL-C (< 70 mg/dl) versus 29% of the subjects with the highest quartile of final LDL-C (> or = 114 mg/dl, p = 0.008). No threshold value was seen, with more favorable effects on absolute change in CIMT with lower values of LDL-C (decrease in CIMT of 0.06 +/- 0.17 mm in the lowest quartile compared with an increase of 0.06 +/- 0.09 in the highest quartile of LDL-C, p = 0.008). On-treatment LDL and CRP concentrations both below the group median values were associated with the greatest likelihood of CIMT regression.

CONCLUSIONS: Regression of carotid atherosclerosis is directly related to the absolute LDL-C level on statin therapy. The greatest regression was obtained with an LDL-C < 70 mg/dl, supporting marked LDL-C reduction to levels below current NCEP guidelines.