Effects of atorvastatin on serum lipids, serum inflammation and plaque morphology in patients with stable atherosclerotic plaques

Abstract

Statin treatment in patients with coronary heart disease is associated with a reduced incidence of short-term adverse events and endpoint cardiac events. However, the effects of statin treatment on atherosclerotic plaques, particularly stable plaques, remain poorly defined. In total, 228 consecutive patients with stable atherosclerotic plaques who had undergone coronary arteriography (CAG) and intravascular ultrasound (IVUS) were randomly assigned to receive placebo (placebo group, n=54) or atorvastatin (ATOR) at a single daily dose of 10 mg (ATOR 10 mg group, n=47), 20 mg (ATOR 20 mg group, n=45), 40 mg (ATOR 40 mg group, n=43) or 80 mg (ATOR 80 mg group, n=39). Endpoints, including serum lipids, serum inflammation, plaque volume and percentage of plaque necrosis were assessed after 3-6 months. At baseline, mean low-density lipoprotein (LDL), high-density lipoprotein (HDL) and high-sensitivity C-reactive protein (hs-CRP) levels, as well as plaque volumes and percentages of plaque necrosis, were similar between all groups. At 6 months of follow-up, the LDL levels in the ATOR groups were below those at their respective baselines (P<0.01). HDL levels in the ATOR 80 mg group following treatment were significantly higher compared with baseline (P=0.001). Additionally, they were significantly higher compared with those in the placebo, ATOR 10, 20 and 40 mg groups (P<0.01, P=0.001, P=0.048, P=0.047, respectively). Hs-CRP levels in the placebo group following treatment were higher compared with baseline levels (6.87±2.62 vs. 5.07±1.80, P<0.01), but hs-CRP levels in the ATOR 80 mg group following treatment were lower compared with baseline (3.59±1.07 vs. 6.10±2.12, P<0.01). According to the virtual histology (VH) of IVUS, the percentages of plaque necrosis following treatment in the placebo and ATOR 10 mg groups rose above baseline levels (15.51±12.56 vs. 7.69±1.31%, 13.54±11.76 vs. 7.83±1.43%, P<0.01) and conformed to the diagnostic criteria for unstable plaques (15.51±12.56, 13.54±11.76%). By contrast, in the ATOR 20, 40 and 80 mg groups, percentages of plaque necrosis remained stable following treatment compared with baseline (P=0.069, 0.846 and 0.643, respectively). Plaque volumes following treatment in the placebo, ATOR 10 and 20 mg groups were similar to baseline levels. However, in the ATOR 40 and 80 mg groups, plaque volumes decreased following treatment compared with baseline plaque volumes (30.69±8.12 vs. 37.09±12.01 mm(3), 24.99±1.01 vs. 36.47±14.68 mm(3), P=0.019, P<0.01, respectively). ATOR (20 mg/day) is able to lower LDL to standard levels while ATOR 40 mg/day was superior to 20 mg/day and had similar effects to 80 mg/day. Only ATOR 80 mg/day was able to increase HDL levels. Hs-CRP in patients without ATOR was higher and ATOR 80 mg/day decreased levels. ATOR ≥20 mg/day is able to stabilize plaques and ATOR 80 mg/day was superior to 20 and 40 mg/day. Thus, ATOR 40-80 mg/day reduces the volume of plaques.

Figure 1.

Study design. ATOR, atorvastatin.

Figure 2

Intravascular ultrasound (IVUS) of two different plaques. (A) Unstable plaque. (B) Stable plaque.

Figure 3

Changes in LDL at baseline and follow-up. LDL, low-density lipoprotein; ATOR, atorvastatin.

Figure 4

Changes in HDL at baseline and follow-up. HDL, high-density lipoprotein; ATOR, atorvastatin.

Figure 5

Changes in hs-CRP at baseline and follow-up. Hs-CRP, high-sensitivity C-reactive protein; ATOR, atorvastatin.

Figure 6

Changes in the relative amount of necrotic tissue at baseline and follow-up. ATOR, atorvastatin.

Figure 7

Changes in plaque volume at baseline and follow-up. ATOR, atorvastatin.