HMG-CoA reductase inhibitor (Statin) therapy and coronary atherosclerosis in Japanese subjects: role of high-density lipoprotein cholesterol.
The level of serum low-density lipoprotein cholesterol (LDL-C) achieved and change in serum LDL-C level in response to HMG-CoA reductase inhibitor (statin) therapy may not be reflected in coronary plaque regression in Japanese subjects, and plaque regression has occurred in many cases in the absence of any marked decrease in serum LDL-C level. We hypothesized that the indicators of coronary plaque regression in response to statin therapy in a Japanese population are different from the indicators in Western populations.
The purpose of this study was to investigate the predictors of coronary plaque regression in Japanese patients with coronary artery disease (CAD) using a receiver-operating-characteristic (ROC) analysis.
A 6-month prospective observational study to identify predictors of regression of coronary plaque as assessed by volumetric intravascular ultrasound was conducted on 113 CAD patients receiving usual doses of pravastatin at Nihon University Surugadai Hospital, Tokyo, Japan.
The mean pravastatin dose was 12.5 ± 3.2 mg/day. After 6 months of therapy, the average change in plaque volume was -9.9% (p < 0.0001 vs baseline). Body mass index (BMI) before pravastatin therapy was significantly lower in the plaque regression group than in the plaque progression group (23.5 ± 2.8 kg/m2 vs 25.3 ± 2.5 kg/m2, p < 0.01). Furthermore, significant increases in serum levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo) A-1, and decreases in LDL-C/HDL-C, apoB/apoA-1, and monocyte count were observed in the plaque regression group (n = 90) in comparison with the plaque progression group (n = 23), while there were no differences in achieved LDL-C levels between the groups (101 ± 25 mg/dL vs 101 ± 24 mg/dL). The changes in plaque volume correlated with the changes in serum levels of HDL-C (r = -0.496, p < 0.0001), LDL-C/HDL-C (r = 0.361, p < 0.0001), apoA-1 (r = -0.362, p = 0.0005), apoB/apoA-1 (r = 0.314, p = 0.0003), monocyte count (r = 0.325, p = 0.0004), and with baseline BMI (r = 0.278, p = 0.003), but not with the change in LDL-C level (r = 0.023, p = 0.860). Moreover, an ROC analysis showed that the change in HDL-C level was better than any other parameter in terms of evaluating the predictor of plaque regression because it had a larger area under the ROC curve (0.751; sensitivity: 76.9%; specificity: 60.9%; cut off value: ±0%).
Even with modest LDL-C lowering to maintain the serum LDL-C level at only 100 mg/dL, we demonstrated that reduction of the coronary plaque volume can be achieved by elevation of the serum HDL-C. The results suggest that the ameliorating action of statins on lipid metabolism and sensitivity to their inhibitory effect on the progression of coronary plaque may be different in Japanese and Western populations.
Department of Cardiology, Nihon University Surugadai Hospital, Tokyo, Japan. firstname.lastname@example.org
SourceAmerican journal of cardiovascular drugs : drugs, devices, and other interventions 11:6 2011 Dec 1 pg 411-7
Area Under Curve
Coronary Artery Disease
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Sensitivity and Specificity
Pub Type(s)Journal Article