It is not well known which lesions are progressed or regressed in patients with angina pectoris who use statins. We assessed the impact of plaque components on plaque progression in patients with angina pectoris who used rosuvastatin 10 mg/day using virtual histology plus intravascular ultrasound. Sixty-six patients who underwent baseline and 9-month follow-up virtual histology plus intravascular ultrasound for nonintervened intermediate coronary stenosis were grouped according to plaque progression (increase of plaque plus media area, n = 22) or plaque regression (decrease of plaque plus media area, n = 44) at baseline minimum lumen area (MLA) site at follow-up and compared the various parameters including baseline plaque components between the 2 groups. Follow-up low-density lipoprotein cholesterol was not significantly different between the progression and regression groups (85 ± 30 vs 82 ± 24 mg/dl, p = 0.6). Baseline percent necrotic core (NC) area was significantly larger (26.1 ± 10.9% vs 17.6 ± 10.8%, p = 0.004) and baseline percent fibrofatty area was significantly smaller (8.1 ± 6.2% vs 14.2 ± 12.1%, p = 0.008) at the MLA site in the progression group compared to the regression group. Thin-cap fibroatheroma was observed more frequently in the progression group compared to the regression group (32% vs 9%, p = 0.020). Change of plaque plus media area from baseline to follow-up at the MLA site correlated with baseline percent NC area (r = 0.375, p = 0.002), baseline percent fibrofatty area (r = −0.388, p = 0.001), and baseline percent fibrotic area (r = −0.242, p = 0.050). Baseline percent NC area at the MLA site was an independent predictor of plaque progression at follow-up (odds ratio 1.265, 95% confidence interval 1.069 to 1.497, p = 0.006). In conclusion, NC is associated with plaque progression in patients when low-density lipoprotein cholesterol level is around 80 mg/dl at 9-month follow-up in patients with angina pectoris on rosuvastatin 10 mg/day.
No study has examined the relation between baseline plaque components and plaque progression, especially in patients on statin therapy. Therefore, the aim of this study was to assess the impact of baseline plaque components on plaque progression in nonintervened coronary segments in patients with angina pectoris who used a usual dose of rosuvastatin using virtual histology plus intravascular ultrasound.
Methods
This study was a prospective, single-center study. Sixty-six patients who underwent baseline and 9-month follow-up virtual histology plus intravascular ultrasound for nonintervened intermediate coronary stenosis (30% to 70% diameter stenosis by qualitative coronary angiography) were grouped according to plaque progression (n = 22) or plaque regression (n = 44) from baseline to follow-up at the baseline intravascular ultrasound minimum lumen area (MLA) site. All patients presented with stable or unstable angina and received rosuvastatin 10 mg/day from baseline to follow-up. The protocol was approved by the institutional review board. Hospital records of patients were reviewed to obtain information on clinical demographics.
Plaque progression was defined as increase of plaque plus media area ( Figure 1 ); conversely, plaque regression was defined as decrease of plaque plus media area from baseline to follow-up at the baseline intravascular ultrasound MLA site ( Figure 1 ). A 20-MHz, 2.9Fr intravascular ultrasound imaging catheter (Eagle Eye, Volcano Corp., Rancho Cordova, California) was advanced >10 mm beyond the lesion, and automated pullback was performed at a speed of 0.5 mm/s. The same anatomic image slices were analyzed at baseline and at follow-up using axial landmarks and the known pullback speed of the transducer. Volumetric data were generated by software using the Simpson method. Virtual histologic intravascular ultrasound analysis classified the color-coded tissue into 4 major components: green (fibrotic [FT]), yellow-green (fibrofatty [FF]), white (dense calcium [DC]), and red (necrotic core [NC]); thin-cap fibroatheroma was defined as focal NC-rich (≥10% of cross-sectional area) plaques in contact with the lumen with a plaque burden ≥40% in consecutive >3 frames. Virtual histologic intravascular ultrasound analysis was reported in absolute amounts and as percent plaque area or volume.
SPSS 15.0 for Windows (SPSS, Inc., Chicago, Illinois) was used for all analyses. Continuous variables were presented as mean ± 1 SD; comparisons were conducted by Student’s t test or Wilcoxon rank-sum test if normality assumption was violated. Discrete variables were presented as percentages and frequencies; comparisons were conducted by chi-square statistics or Fisher’s exact test as appropriate. Pearson correlation was used to evaluate the correlation between baseline plaque components and change of plaque plus media area at the MLA site. Multivariable logistic regression analysis was performed to identify independent predictors of plaque progression. A p value <0.05 was considered statistically significant.
Results
Plaque was progressed in 22 patients (33%) and was regressed in 44 patients (67%). Baseline characteristics are presented in Table 1 . There were no significant differences in baseline characteristics except for lower glucose level in the plaque progression group.
| Variables | Plaque Progression (n = 22) | Plaque Regression (n = 44) | p Value |
|---|---|---|---|
| Age (years) | 63 ± 10 | 64 ± 9 | 0.5 |
| Men | 13 (59%) | 27 (61%) | 0.9 |
| Clinical presentation | 0.15 | ||
| Stable angina pectoris | 6 (27%) | 20 (46%) | |
| Unstable angina pectoris | 16 (73%) | 24 (55%) | |
| Diabetes mellitus | 3 (14%) | 14 (32%) | 0.11 |
| Smoker | 4 (18%) | 6 (14%) | 0.5 |
| Ejection fraction (%) | 65 ± 5 | 67 ± 6 | 0.3 |
| White blood cells (10 3 /mm 3 ) | 6.4 ± 1.4 | 6.7 ± 1.7 | 0.5 |
| Hemoglobin (g/dl) | 13.8 ± 1.6 | 13.3 ± 2.1 | 0.3 |
| Platelet count (10 3 /mm 3 ) | 229 ± 44 | 235 ± 51 | 0.6 |
| Glucose (mg/dl) | 112 ± 19 | 135 ± 51 | 0.011 |
| Creatine kinase-MB (U/dl) | 4.7 ± 1.7 | 4.4 ± 1.9 | 0.6 |
| Troponin I (ng/ml) | 0.09 ± 0.22 | 0.02 ± 0.03 | 0.2 |
| Creatinine (mg/dl) | 0.9 ± 0.2 | 0.8 ± 0.3 | 0.8 |
| Fibrinogen (mg/dl) | 279 ± 50 | 275 ± 51 | 0.8 |
| High-sensitivity C-reactive protein (mg/dl) | 0.30 ± 0.66 | 0.17 ± 0.38 | 0.4 |
| N-terminal pro-B type natriuretic peptide (pg/ml) | 119 ± 136 | 116 ± 126 | 0.9 |
| Total cholesterol (mg/dl) | 187 ± 30 | 185 ± 37 | 0.8 |
| Triglyceride (mg/dl) | 126 ± 65 | 117 ± 53 | 0.5 |
| Low-density lipoprotein cholesterol (mg/dl) | 121 ± 30 | 123 ± 32 | 0.8 |
| High-density lipoprotein cholesterol (mg/dl) | 45 ± 10 | 48 ± 11 | 0.3 |
| Apoprotein A1 (mg/dl) | 120 ± 13 | 127 ± 18 | 0.089 |
| Apoprotein B (mg/dl) | 98 ± 22 | 96 ± 21 | 0.7 |
| Apoprotein B/A1 | 0.83 ± 0.25 | 0.77 ± 0.25 | 0.4 |
| Lipoprotein (a) (mg/dl) | 30 ± 24 | 40 ± 49 | 0.3 |
Arterial segments used for analysis were 4 left main coronary arteries, 23 left anterior descending coronary arteries, 15 left circumflex arteries, and 23 right coronary arteries (p = 0.4, plaque progression vs regression groups). There were no significant differences in lesion location (p = 0.9), reference diameter and minimal lumen diameter (1.67 ± 0.44 vs 1.79 ± 0.54 mm, p = 0.4), and percent diameter stenosis (49 ± 10% vs 48 ± 11%, p = 0.7) by qualitative coronary angiography between the plaque progression and regression groups.
There were no significant differences in the gray-scale intravascular ultrasound parameters at the proximal and distal references and largest NC site between the plaque progression and regression groups. At the MLA site, plaque plus media areas were 8.8 ± 2.9 mm 2 in the plaque progression group and 10.3 ± 3.6 mm 2 in the plaque regression group (p = 0.10), plaque burdens were 60 ± 7% in the plaque progression group and 60 ± 7% in the plaque regression group (p = 0.9), and there was no significant difference in plaque structure between groups (p = 0.4). Intravascular ultrasound lesion length was not different significantly between groups (p = 0.7). Total atheroma volumes were 126 ± 85 mm 3 in the plaque progression group and 148 ± 93 mm 3 in the plaque regression group (p = 0.3), and percent atheroma volumes were 48 ± 6% in the plaque progression group and 49 ± 6% in the plaque regression group (p = 0.6).
Baseline virtual histologic intravascular ultrasound findings are presented in Table 2 . At the proximal reference, absolute FF area was significantly smaller in the plaque progression group compared to the regression group. At the distal reference, absolute FT and FF areas were significantly smaller in the plaque progression group compared to the regression group. At the MLA site, relative NC area was significantly larger in the plaque progression group compared to the regression group; conversely, absolute FT and FF areas were significantly smaller and relative FF area was significantly smaller in the plaque progression group compared to the regression group. At the largest NC site, relative NC area was significantly larger in the plaque progression group compared to the regression group; conversely, absolute and relative FF areas were significantly smaller in the plaque progression group compared to the regression group. By volumetric analysis, absolute and relative FF volumes were significantly smaller in the plaque progression group compared to the regression group, and there were trends toward larger relative NC and DC volumes in the plaque progression group compared to the regression group. Thin-cap fibroatheroma was observed more frequently in the plaque progression group compared to the regression group.
| Variables | Plaque Progression (n = 22) | Plaque Regression (n = 44) | p Value |
|---|---|---|---|
| Absolute plaque area | |||
| Fibrotic area (mm 2 ) | |||
| Proximal reference | 1.60 ± 1.34 | 2.25 ± 1.52 | 0.094 |
| Distal reference | 0.93 ± 0.82 | 1.67 ± 1.64 | 0.020 |
| Minimum lumen area site | 2.77 ± 1.46 | 3.93 ± 2.13 | 0.013 |
| Largest necrotic core site | 2.59 ± 1.35 | 3.43 ± 1.96 | 0.078 |
| Fibrofatty area (mm 2 ) | |||
| Proximal reference | 0.37 ± 0.44 | 0.69 ± 0.74 | 0.039 |
| Distal reference | 0.26 ± 0.34 | 0.55 ± 0.67 | 0.024 |
| Minimum lumen area site | 0.44 ± 0.43 | 1.08 ± 1.21 | 0.003 |
| Largest necrotic core site | 0.36 ± 0.32 | 0.81 ± 0.97 | 0.008 |
| Dense calcium area (mm 2 ) | |||
| Proximal reference | 0.15 ± 0.21 | 0.22 ± 0.33 | 0.4 |
| Distal reference | 0.14 ± 0.15 | 0.16 ± 0.35 | 0.8 |
| Minimum lumen area site | 0.79 ± 0.79 | 0.66 ± 0.53 | 0.4 |
| Largest necrotic core site | 0.97 ± 0.79 | 0.75 ± 0.52 | 0.19 |
| Necrotic core area (mm 2 ) | |||
| Proximal reference | 0.31 ± 0.39 | 0.41 ± 0.55 | 0.4 |
| Distal reference | 0.23 ± 0.28 | 0.30 ± 0.54 | 0.5 |
| Minimum lumen area site | 0.79 ± 0.79 | 0.66 ± 0.53 | 0.4 |
| Largest necrotic core site | 1.72 ± 1.16 | 1.43 ± 0.92 | 0.3 |
| Relative plaque area | |||
| Fibrotic area (%) | |||
| Proximal reference | 61.6 ± 18.5 | 60.8 ± 20.5 | 0.9 |
| Distal reference | 54.5 ± 23.1 | 56.7 ± 23.4 | 0.7 |
| Minimum lumen area site | 50.8 ± 16.2 | 56.7 ± 11.6 | 0.094 |
| Largest necrotic core site | 46.4 ± 15.9 | 52.3 ± 12.5 | 0.10 |
| Fibrofatty area (%) | |||
| Proximal reference | 13.7 ± 12.7 | 16.6 ± 12.6 | 0.4 |
| Distal reference | 16.7 ± 18.7 | 18.8 ± 19.2 | 0.7 |
| Minimum lumen area site | 8.1 ± 6.2 | 14.2 ± 12.1 | 0.008 |
| Largest necrotic core site | 6.1 ± 5.2 | 11.6 ± 10.3 | 0.005 |
| Dense calcium area (%) | |||
| Proximal reference | 7.6 ± 10.3 | 5.3 ± 7.5 | 0.3 |
| Distal reference | 6.9 ± 7.9 | 4.9 ± 8.3 | 0.4 |
| Minimum lumen area site | 15.1 ± 10.8 | 11.5 ± 9.7 | 0.18 |
| Largest necrotic core site | 17.1 ± 10.8 | 13.0 ± 9.1 | 0.11 |
| Necrotic core area (%) | |||
| Proximal reference | 12.7 ± 10.6 | 10.1 ± 9.1 | 0.3 |
| Distal reference | 12.4 ± 11.5 | 10.4 ± 11.5 | 0.5 |
| Minimum lumen area site | 26.1 ± 10.9 | 17.6 ± 10.8 | 0.004 |
| Largest necrotic core site | 30.2 ± 11.0 | 23.2 ± 11.8 | 0.023 |
| Volumetric analysis | |||
| Absolute plaque volume | |||
| Fibrotic volume (mm 3 ) | 36.5 ± 27.2 | 49.9 ± 38.6 | 0.15 |
| Fibrofatty volume (mm 3 ) | 6.3 ± 5.2 | 13.9 ± 18.1 | 0.012 |
| Dense calcium volume (mm 3 ) | 10.1 ± 13.6 | 7.9 ± 7.5 | 0.4 |
| Necrotic core volume (mm 3 ) | 14.2 ± 15.6 | 12.1 ± 9.5 | 0.5 |
| Relative plaque volume | |||
| Fibrotic area (%) | 55.8 ± 11.8 | 59.1 ± 8.4 | 0.2 |
| Fibrofatty area (%) | 10.1 ± 7.1 | 15.5 ± 11.1 | 0.045 |
| Dense calcium area (%) | 13.7 ± 9.2 | 9.8 ± 7.4 | 0.064 |
| Necrotic core area (%) | 20.3 ± 8.1 | 15.8 ± 9.5 | 0.063 |
| Thin-cap fibroatheroma | 7 (32%) | 4 (9%) | 0.020 |
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