BACKGROUND: Recent trials have demonstrated better outcomes with intensive than with moderate statin treatment. Intensive treatment produced greater reductions in both low-density lipoprotein(LDL)cholesterol and C-rea...BACKGROUND: Recent trials have demonstrated better outcomes with intensive than with moderate statin treatment. Intensive treatment produced greater reductions in both low-density lipoprotein(LDL)cholesterol and C-reactive protein(CRP), suggesting a relationship between these two biomarkers and disease progression. METHODS: We performed intravascular ultrasonography in 502 patients with angiographically documented coronary disease. Patients were randomly assigned to receive moderate treatment(40 mg of pravastatin orally per day)-or intensive treatment(80 mg of atorvastatin orally per day). Ultrasonography was repeated after 18 months to measure the progression of atherosclerosis. Lipoprotein and CRP levels were measured at baseline and followup. RESULTS: In the group as a whole, the mean LDL cholesterol level was reduced from 150.2 mg per deciliter(3.88 mmol per liter)at baseline to 94.5 mg per deciliter(2.44 mmol per liter)at 18 months(P< 0.001), and the geometric mean CRP level decreased from 2.9 to 2.3 mg per liter(P< 0.001). The correlation between the reduction in LDL cholesterol levels and that in CRP levels was weak but significant in the group as a whole(r=0.13, P=0.005), but not in either treatment group alone. In univariate analyses, the percent change in the levels of LDL cholesterol, CRP, apolipoprotein B-100, and nonhigh-density lipoprotein cholesterol were related to the rate of progression of atherosclerosis. After adjustment for the reduction in these lipid levels, the decrease in CRP levels was independently and significantly correlated with the rate of progression. Patients with reductions in both LDL cholesterol and CRP that were greater than the median had significantly slower rates of progression than patients with reductions in both biomarkers that were less than the median(P=0.001). CONCLUSIONS: For patients with coronary artery disease, the reduced rate of progression of atherosclerosis associated with intensive statin treatment, as compared with moderate statin treatment, is significantly related to greater reductions in the levels of both atherogenic lipoproteins and CRP.展开更多
Background: Inhibiting the enzyme acyl-CoA:cholesterol acyltransferase(ACAT) has beneficial effects on foam cell formation and therefore has the potential to favorably influence the progression of coronary atheroscler...Background: Inhibiting the enzyme acyl-CoA:cholesterol acyltransferase(ACAT) has beneficial effects on foam cell formation and therefore has the potential to favorably influence the progression of coronary atherosclerosis. The aim of this study is to determine whether ACAT inhibition, when added to usual medical care, reduces atheroma progression in subjects with coronary artery disease. Methods: Five hundred thirty-four subjects with established coronary artery disease on angiography were randomized to receive the experimental ACAT inhibitor, pactimibe, 100 mg daily or matching placebo for 18 months. The primary efficacy parameter will be the nominal change in percent atheroma volume determined by analysis of pullback intravascular ultrasound(IVUS) images of matched coronary artery segments acquired at baseline and 18-month follow-up. In addition, the effect of pactimibe on plasma lipids and inflammatory markers and the incidence of clinical cardiovascular events will also be assessed. Conclusion: Serial IVUS has emerged as a sensitive imaging modality to assess the impact that novel antiatherosclerotic strategies have on the arterial wall. In this study, IVUS will be used to assess whether ACAT inhibition modifies progression of atherosclerotic plaque.展开更多
Aims: On the basis of the evidence from autopsy studies, it is accepted that compensatory enlargement(remodelling) of coronary arteries during progression of atherosclerosis diminishes once atheroma burden(cross-secti...Aims: On the basis of the evidence from autopsy studies, it is accepted that compensatory enlargement(remodelling) of coronary arteries during progression of atherosclerosis diminishes once atheroma burden(cross-sectional area stenosis) reaches ~40%. Our aim was to evaluate whether atheroma burden is a limiting factor for coronary arterial remodelling using in vivo serial intravascular ultrasound(IVUS). Methods and results: From the cohort of the Reversal of Atherosclerosis with Aggressive Lipid Lowering(REVERSAL) trial, we identified 210 focal coronary lesions at baseline IVUS. Of these, 128 lesions that had an increase in atheroma area at the 18-month follow-up IVUS were included in the analysis. Lesions were matched at baseline and follow-up. The increase in external elastic membrane(EEM) area for each mm2 increase in atheroma area was not significantly different in lesions with< 40 and ≥40%atheroma burden at baseline(1.62 vs. 1.28 mm2, P=0.30). There were no correlations between atheroma burden at baseline and change in EEM(r=0.02, P=0.86) or change in lumen(r=0.04, P=0.64) areas. Conclusion: Assessment of coronary arterial remodelling by serial IVUS revealed that compensatory remodelling is not limited by atheroma burden. Atheroma burden is not a determinant of arterial enlargement during the progression of atherosclerosis.展开更多
文摘BACKGROUND: Recent trials have demonstrated better outcomes with intensive than with moderate statin treatment. Intensive treatment produced greater reductions in both low-density lipoprotein(LDL)cholesterol and C-reactive protein(CRP), suggesting a relationship between these two biomarkers and disease progression. METHODS: We performed intravascular ultrasonography in 502 patients with angiographically documented coronary disease. Patients were randomly assigned to receive moderate treatment(40 mg of pravastatin orally per day)-or intensive treatment(80 mg of atorvastatin orally per day). Ultrasonography was repeated after 18 months to measure the progression of atherosclerosis. Lipoprotein and CRP levels were measured at baseline and followup. RESULTS: In the group as a whole, the mean LDL cholesterol level was reduced from 150.2 mg per deciliter(3.88 mmol per liter)at baseline to 94.5 mg per deciliter(2.44 mmol per liter)at 18 months(P< 0.001), and the geometric mean CRP level decreased from 2.9 to 2.3 mg per liter(P< 0.001). The correlation between the reduction in LDL cholesterol levels and that in CRP levels was weak but significant in the group as a whole(r=0.13, P=0.005), but not in either treatment group alone. In univariate analyses, the percent change in the levels of LDL cholesterol, CRP, apolipoprotein B-100, and nonhigh-density lipoprotein cholesterol were related to the rate of progression of atherosclerosis. After adjustment for the reduction in these lipid levels, the decrease in CRP levels was independently and significantly correlated with the rate of progression. Patients with reductions in both LDL cholesterol and CRP that were greater than the median had significantly slower rates of progression than patients with reductions in both biomarkers that were less than the median(P=0.001). CONCLUSIONS: For patients with coronary artery disease, the reduced rate of progression of atherosclerosis associated with intensive statin treatment, as compared with moderate statin treatment, is significantly related to greater reductions in the levels of both atherogenic lipoproteins and CRP.
文摘Background: Inhibiting the enzyme acyl-CoA:cholesterol acyltransferase(ACAT) has beneficial effects on foam cell formation and therefore has the potential to favorably influence the progression of coronary atherosclerosis. The aim of this study is to determine whether ACAT inhibition, when added to usual medical care, reduces atheroma progression in subjects with coronary artery disease. Methods: Five hundred thirty-four subjects with established coronary artery disease on angiography were randomized to receive the experimental ACAT inhibitor, pactimibe, 100 mg daily or matching placebo for 18 months. The primary efficacy parameter will be the nominal change in percent atheroma volume determined by analysis of pullback intravascular ultrasound(IVUS) images of matched coronary artery segments acquired at baseline and 18-month follow-up. In addition, the effect of pactimibe on plasma lipids and inflammatory markers and the incidence of clinical cardiovascular events will also be assessed. Conclusion: Serial IVUS has emerged as a sensitive imaging modality to assess the impact that novel antiatherosclerotic strategies have on the arterial wall. In this study, IVUS will be used to assess whether ACAT inhibition modifies progression of atherosclerotic plaque.
文摘Aims: On the basis of the evidence from autopsy studies, it is accepted that compensatory enlargement(remodelling) of coronary arteries during progression of atherosclerosis diminishes once atheroma burden(cross-sectional area stenosis) reaches ~40%. Our aim was to evaluate whether atheroma burden is a limiting factor for coronary arterial remodelling using in vivo serial intravascular ultrasound(IVUS). Methods and results: From the cohort of the Reversal of Atherosclerosis with Aggressive Lipid Lowering(REVERSAL) trial, we identified 210 focal coronary lesions at baseline IVUS. Of these, 128 lesions that had an increase in atheroma area at the 18-month follow-up IVUS were included in the analysis. Lesions were matched at baseline and follow-up. The increase in external elastic membrane(EEM) area for each mm2 increase in atheroma area was not significantly different in lesions with< 40 and ≥40%atheroma burden at baseline(1.62 vs. 1.28 mm2, P=0.30). There were no correlations between atheroma burden at baseline and change in EEM(r=0.02, P=0.86) or change in lumen(r=0.04, P=0.64) areas. Conclusion: Assessment of coronary arterial remodelling by serial IVUS revealed that compensatory remodelling is not limited by atheroma burden. Atheroma burden is not a determinant of arterial enlargement during the progression of atherosclerosis.