Abstract 5055: The SANDS Trial: Does Aggressive Lowering of LDL-C and Non-HDL-C in Diabetes Decrease the Plasma ApoB and LDL-C Particle Number?
Background: Concern has been raised that aggressive lowering of LDL-C may not be accompanied by reductions in particle number or apoB lipoprotein concentrations. The SANDS trial demonstrated that a group treated for 3 years to aggressive (AGG) targets of LDL-C ≤ 70 mg/dL and non-HDL-C ≤ 100 mg/dL had a decrease in atherosclerosis, as measured by regression of carotid intimal medial thickness (CIMT) and decreased mean arterial mass, compared with a standard group (STD) treated to LDL-C and non-HDL-C of 100 and 130 mg/dL, respectively.
Methods: Participants were 499 type 2 diabetic men and women (average age 56 y) with no previous CVD events; 426 had all baseline and 36-mo lipoprotein variables. Mean baseline BMI (33kg/m2), A1c (8.0%), and HDL-C (46mg/dl) did not change during the study. A standardized algorithm for lipid lowering was used in both groups; the number of hypolipidemic drugs (mean [SD]) was 1.5 [.75] and 1.2 [.73] in the AGG and STD groups, respectively. At baseline and 36 months, lipoprotein particle number (LDL-P and VLDL-P) was quantified by nuclear magnetic resonance, and plasma apoB by immunoassay.
Results: There were significant decreases in apoB, LDL-P, VLDL-P, and VLDL size but not LDL size in the AGG vs STD groups. The decrease in LDL-P was reflected in all LDL fractions. In an ordered logit analyses, the probability of a decrease in CIMT was significantly related to decrease in LDL-C and separately to non-HDL-C (p <.005), but not significantly related to the decrease in apoB (p =.19) and LDL-P (p =.055).
Conclusion: Aggressively lowering LDL-C and non-HDL-C to targets of 70 and 100 mg/dL, respectively, was accompanied by a significant decrease in LDL-P and VLDL-P and a decline in total plasma apoB; changes in LDL-C and non-HDL-C were separately the best predictors of IMT decrease. The relationship of the associated decrease in carotid atherosclerosis to CVD events awaits longer term observation.