Impact of Statins on Serial Coronary Calcification in Atheroma
Impact of Statins on Serial Coronary Calcification in Atheroma
Table 1 describes baseline demographics, clinical characteristics, and medication use in each of the treatment groups. Significant trends for between-group differences were noted across certain baseline variables. The no-statin group was of older age, more likely female, had a higher body mass index, and had a higher incidence of diabetes mellitus, hypertension, peripheral arterial disease, and nitrate use compared with the HIST and LIST groups.
Table 2 describes baseline, follow-up, and changes in laboratory biochemical measures within each treatment group. Significant trends for between-group differences were noted across various baseline laboratory variables. Patients receiving HIST had the highest baseline LDL-C levels (119.5 ± 34 mg/dl) but the lowest CRP levels (1.8 mg/l). The no-statin group had the lowest baseline high-density lipoprotein cholesterol levels (41.7 ± 14 mg/dl) but the highest triglyceride (158 [106 to 228]mg/dl) and CRP levels (3.1 [1.4 to 6.4] mg/l). At follow-up, patients receiving HIST had the lowest levels of LDL-C, non–high-density lipoprotein cholesterol, triglycerides, and CRP comparedwith the LIST and no-statin groups (LDL-C, 70.8 ± 26 mg/dl vs. 89.1 ± 25 mg/dl vs. 107.2 ± 31 mg/dl, respectively; non–high-density lipoprotein cholesterol, 96.6 ± 29 mg/dl vs. 117.2 ± 31 mg/dl vs. 138.8 ± 34 mg/dl, respectively; triglycerides, 118 [90 to 159]mg/dl vs. 130 [94 to 177] mg/dl vs. 151 [105 to 216] mg/dl, respectively; CRP, 1.8 [0.6 to 2.8] mg/l vs. 2.0 [0.9 to 4.4] mg/l vs. 2.6 [1.1 to 5.1] mg/l, respectively).
Table 3 describes baseline and changes in PAV and TAV of each treatment group, and pairwise comparisons for changes in atheroma volume following propensity-weighting. Baseline PAV was 36.9 ± 8.9%, 38.0 ± 9.0%, and 37.2 ± 9.0% in the HIST, LIST, and no-statin groups, respectively. The HIST group had significantly lower PAV at baseline compared with the LIST group (p = 0.002). At follow-up, the HIST group demonstrated significant PAV regression from baseline (−0.6 ± 0.1%; p < 0.001), whereas both the LIST and no-statin groups each demonstrated significant PAV progression (+0.8 ± 0.1% and +1.0 ± 0.1%; p < 0.001 from baseline, respectively). These changes in PAV differed significantly for pairwise comparisons between the HIST versus LIST (p < 0.001) and the HIST versus no-statin groups (p < 0.001) (Figure 1A).
(Enlarge Image)
Figure 1.
Statins and Coronary Plaque Calcification: Changes in Coronary Atheroma Volume and Calcium Indices According to Therapy
(A) Percent atheroma volume (PAV) adjusted model, depicting corresponding changes in PAV and calcium index (CaI). (B) Total atheroma volume (TAV) adjusted model depicting corresponding changes in TAV and CaI. Changes in PAV and TAV (blue boxes) are reported as least squares mean ± standard error of the mean, whereas the changes in CaI (salmon boxes) are reported as median (interquartile range). CI = confidence interval; HIST = high-intensity statin therapy; LIST = low-intensity statin therapy.
Baseline TAV was similar across all treatment groups, with no significant between-group differences. At follow-up, both the HIST and LIST groups demonstrated significant TAV regression from baseline (−6.6 ± 0.6 mm and −2.1 ± 0.6 mm; p < 0.001 from baseline, respectively), whereas the no-statin group demonstrated significant TAV progression (+3.0 ± 0.7 mm; p < 0.001). Differences in the magnitude of TAV regression were significant for pairwise comparisons among the HIST versus LIST (p < 0.001), HIST versus no-statin (p < 0.001), and LIST versus no-statin (p = 0.006) groups (Figure 1B).
Table 4 describes baseline and changes in CaI between treatment groups, pairwise comparisons for changes in CaI following propensity-weighting and further adjustment for clinical trial, and baseline measures of plaque burden and calcium. When adjusting for PAV in the statistical model, no significant differences in pairwise comparisons were noted for baseline CaI. However, the TAV-adjusted model yielded significantly greater baseline CaI for the LIST versus no-statin (p = 0.002) and HIST versus no-statin (p = 0.001) pairwise comparisons.
All treatment groups demonstrated significant progression of coronary calcium from baseline, measured as a change in CaI (HIST, +0.044 [0.0 to 0.12]; LIST, +0.038 [0.0 to 0.11]; no-statin, +0.02 [0.0 to 0.10]; p < 0.001 for all treatment groups). In a PAVadjusted model, pairwise comparisons demonstrated that the change in CaI was significantly greater in the LIST versus no-statin groups (p = 0.03) and the HIST versus no-statin groups (p = 0.007), but not for the HIST versus LIST comparison (p =0.18) (Figure 1A). In a TAV-adjusted model, similar results were found, with pairwise comparisons demonstrating the change in CaI to be significantly greater in the LIST versus no-statin groups (p = 0.01) and the HIST versus no-statin groups (p = 0.004), but not for the HIST versus LIST comparison (p = 0.35) (Figure 1B).
Table 5 describes changes in plaque volume and CaI stratified according to whether patients exhibited plaque progression (defined as change in PAV or TAV >0) or nonprogression/regression (change in PAV or TAV ≤0). Those with plaque progression demonstrated an overall +2.7 ± 0.05% and +7.5 ± 0.5 mm change in PAV and TAV, respectively, whereas nonprogressors/regressors demonstrated an overall −2.2 ± 0.06% and −13.1 ± 0.5 mm change in PAV and TAV, respectively. Changes in CaI were significantly greater in those with plaque progression compared with those with nonprogression/regression irrespective of whether adjusted for by changes in PAV (0.045 [0.00 to 0.12] vs. 0.034 [0.00 to 0.11]; p = 0.002) or changes in TAV (0.045 [0.00 to 0.12] vs. 0.034 [0.00 to 0.11]; p < 0.001).
Table 6 describes correlations between changes in CaI and average on-treatment lipoprotein and CRP levels among patients receiving HIST and no-statin therapy. No significant correlations were found between HISTmediated changes in lipoprotein or CRP levels and changes in CaI. Similarly, no significant associations were found between changes in lipoprotein and CRP levels and changes in CaI in those patients receiving no-statin therapy.
Results
Clinical Characteristics of the Study Population
Table 1 describes baseline demographics, clinical characteristics, and medication use in each of the treatment groups. Significant trends for between-group differences were noted across certain baseline variables. The no-statin group was of older age, more likely female, had a higher body mass index, and had a higher incidence of diabetes mellitus, hypertension, peripheral arterial disease, and nitrate use compared with the HIST and LIST groups.
Baseline and Changes in Laboratory Measures
Table 2 describes baseline, follow-up, and changes in laboratory biochemical measures within each treatment group. Significant trends for between-group differences were noted across various baseline laboratory variables. Patients receiving HIST had the highest baseline LDL-C levels (119.5 ± 34 mg/dl) but the lowest CRP levels (1.8 mg/l). The no-statin group had the lowest baseline high-density lipoprotein cholesterol levels (41.7 ± 14 mg/dl) but the highest triglyceride (158 [106 to 228]mg/dl) and CRP levels (3.1 [1.4 to 6.4] mg/l). At follow-up, patients receiving HIST had the lowest levels of LDL-C, non–high-density lipoprotein cholesterol, triglycerides, and CRP comparedwith the LIST and no-statin groups (LDL-C, 70.8 ± 26 mg/dl vs. 89.1 ± 25 mg/dl vs. 107.2 ± 31 mg/dl, respectively; non–high-density lipoprotein cholesterol, 96.6 ± 29 mg/dl vs. 117.2 ± 31 mg/dl vs. 138.8 ± 34 mg/dl, respectively; triglycerides, 118 [90 to 159]mg/dl vs. 130 [94 to 177] mg/dl vs. 151 [105 to 216] mg/dl, respectively; CRP, 1.8 [0.6 to 2.8] mg/l vs. 2.0 [0.9 to 4.4] mg/l vs. 2.6 [1.1 to 5.1] mg/l, respectively).
Baseline and Changes in Coronary Atheroma Volume According to Therapy
Table 3 describes baseline and changes in PAV and TAV of each treatment group, and pairwise comparisons for changes in atheroma volume following propensity-weighting. Baseline PAV was 36.9 ± 8.9%, 38.0 ± 9.0%, and 37.2 ± 9.0% in the HIST, LIST, and no-statin groups, respectively. The HIST group had significantly lower PAV at baseline compared with the LIST group (p = 0.002). At follow-up, the HIST group demonstrated significant PAV regression from baseline (−0.6 ± 0.1%; p < 0.001), whereas both the LIST and no-statin groups each demonstrated significant PAV progression (+0.8 ± 0.1% and +1.0 ± 0.1%; p < 0.001 from baseline, respectively). These changes in PAV differed significantly for pairwise comparisons between the HIST versus LIST (p < 0.001) and the HIST versus no-statin groups (p < 0.001) (Figure 1A).
(Enlarge Image)
Figure 1.
Statins and Coronary Plaque Calcification: Changes in Coronary Atheroma Volume and Calcium Indices According to Therapy
(A) Percent atheroma volume (PAV) adjusted model, depicting corresponding changes in PAV and calcium index (CaI). (B) Total atheroma volume (TAV) adjusted model depicting corresponding changes in TAV and CaI. Changes in PAV and TAV (blue boxes) are reported as least squares mean ± standard error of the mean, whereas the changes in CaI (salmon boxes) are reported as median (interquartile range). CI = confidence interval; HIST = high-intensity statin therapy; LIST = low-intensity statin therapy.
Baseline TAV was similar across all treatment groups, with no significant between-group differences. At follow-up, both the HIST and LIST groups demonstrated significant TAV regression from baseline (−6.6 ± 0.6 mm and −2.1 ± 0.6 mm; p < 0.001 from baseline, respectively), whereas the no-statin group demonstrated significant TAV progression (+3.0 ± 0.7 mm; p < 0.001). Differences in the magnitude of TAV regression were significant for pairwise comparisons among the HIST versus LIST (p < 0.001), HIST versus no-statin (p < 0.001), and LIST versus no-statin (p = 0.006) groups (Figure 1B).
Baseline and Changes in CaI According to Therapy
Table 4 describes baseline and changes in CaI between treatment groups, pairwise comparisons for changes in CaI following propensity-weighting and further adjustment for clinical trial, and baseline measures of plaque burden and calcium. When adjusting for PAV in the statistical model, no significant differences in pairwise comparisons were noted for baseline CaI. However, the TAV-adjusted model yielded significantly greater baseline CaI for the LIST versus no-statin (p = 0.002) and HIST versus no-statin (p = 0.001) pairwise comparisons.
All treatment groups demonstrated significant progression of coronary calcium from baseline, measured as a change in CaI (HIST, +0.044 [0.0 to 0.12]; LIST, +0.038 [0.0 to 0.11]; no-statin, +0.02 [0.0 to 0.10]; p < 0.001 for all treatment groups). In a PAVadjusted model, pairwise comparisons demonstrated that the change in CaI was significantly greater in the LIST versus no-statin groups (p = 0.03) and the HIST versus no-statin groups (p = 0.007), but not for the HIST versus LIST comparison (p =0.18) (Figure 1A). In a TAV-adjusted model, similar results were found, with pairwise comparisons demonstrating the change in CaI to be significantly greater in the LIST versus no-statin groups (p = 0.01) and the HIST versus no-statin groups (p = 0.004), but not for the HIST versus LIST comparison (p = 0.35) (Figure 1B).
Changes in Coronary Atheroma Volume and CaI According to Plaque Progression/Regression
Table 5 describes changes in plaque volume and CaI stratified according to whether patients exhibited plaque progression (defined as change in PAV or TAV >0) or nonprogression/regression (change in PAV or TAV ≤0). Those with plaque progression demonstrated an overall +2.7 ± 0.05% and +7.5 ± 0.5 mm change in PAV and TAV, respectively, whereas nonprogressors/regressors demonstrated an overall −2.2 ± 0.06% and −13.1 ± 0.5 mm change in PAV and TAV, respectively. Changes in CaI were significantly greater in those with plaque progression compared with those with nonprogression/regression irrespective of whether adjusted for by changes in PAV (0.045 [0.00 to 0.12] vs. 0.034 [0.00 to 0.11]; p = 0.002) or changes in TAV (0.045 [0.00 to 0.12] vs. 0.034 [0.00 to 0.11]; p < 0.001).
Relationships Between Changes in CaI and On-treatment Lipoproteins and CRP
Table 6 describes correlations between changes in CaI and average on-treatment lipoprotein and CRP levels among patients receiving HIST and no-statin therapy. No significant correlations were found between HISTmediated changes in lipoprotein or CRP levels and changes in CaI. Similarly, no significant associations were found between changes in lipoprotein and CRP levels and changes in CaI in those patients receiving no-statin therapy.
