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.