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 (≥ 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.