Impact of Statins on Serial Coronary Calcification During Atheroma | Journal Scan
Do statins modulate calcification of human coronary atheroma?
The study compared changes in coronary atheroma volume and calcium indices (CaI) in patients receiving high-intensity statin therapy (HIST), low-intensity statin therapy (LIST), and no-statin therapy. In a post hoc patient-level analysis of eight prospective randomized trials employing serial coronary intravascular ultrasound (IVUS), serial changes in coronary percent atheroma volume (PAV), and CaI were measured across matched single coronary segments in patients with coronary disease. Target vessels for IVUS had no angiographic stenosis >50% within a segment at least 30 mm in length. IVUS was performed on the same vessel at baseline and follow-up, which ranged from 18-24 months. Calcium was identified as echogenic signal brighter than the adventitia in each frame, graded 1-4 by the degree of acoustic shadowing within the circumference, and totaled. Of the eight studies, two were designed to assess the impact of statins, two were novel lipid-altering drugs, two involved antihypertensive drugs in clinical use, one pioglitazone, and the last an endocannibanoid receptor antagonist. HIST was defined as atorvastatin 80 mg or rosuvastatin 40 mg, and LIST was defined as atorvastatin <40 mg, rosuvastatin <20 mg, and standard dosing of first-generation statins.
Mean age was 58 years and about 30% were women. No-statin subjects were older, more often women, and had a larger body mass index, and more diabetes, hypertension, and peripheral arterial disease. At follow-up, those on HIST had the lowest low-density lipoprotein cholesterol (HIST 70.8 vs. 89.1 for LIST vs. 107 mg/dl for no-statin), non–high-density lipoprotein cholesterol, triglycerides, and C-reactive protein (CRP). Following propensity-weighted adjustment for differences in baseline and changes in clinical, laboratory, and ultrasonic characteristics, HIST (n = 1,545) was associated with PAV regression from baseline (-0.6 ± 0.1%, p < 0.001), whereas both LIST (n = 1,726) and no-statin therapy (n = 224) were associated with PAV progression (+0.8 ± 0.1% and +1.0 ± 0.1%, p < 0.001, respectively; p < 0.001 for both HIST vs. LIST and HIST vs. no-statin, p = 0.35 for LIST vs. no-statin). Significant increases in CaI from baseline were noted across all groups (median [interquartile range] HIST: +0.044 [0.0, 0.12]; LIST: +0.038 [0.0, 0.11]; no-statin: +0.020 [0.0, 0.10]; p < 0.001 for all), which could relate to statin intensity (p = 0.03 for LIST vs. no-statin; p = 0.007 for HIST vs. no-statin; p = 0.18 for HIST vs. LIST). No correlations were found between changes in CaI and on-treatment levels of atherogenic and antiatherogenic lipoproteins, and CRP, in either of the HIST or no-statin groups.
Independent of their plaque-regressive effects, statins promote coronary atheroma calcification. These findings provide insight as to how statins may stabilize plaque beyond their effects on plaque progression.
That the no-statin group was much smaller than HIST and LIST, with more women and diabetics and less smokers, may have affected the results. The effect of statins on computed tomography (CT) coronary artery calcium in observational studies has varied from an increase to less than age-predicted increase. The difference may be related to duration and CT assessment of the total calcium score, and IVUS targeting specific mild plaque in one epicardial coronary artery. Among the theoretical value of the findings is that by enhancing calcium in less than significant coronary artery plaques, particularly in those that show regression, statins may be inducing a healing process that results in stabilization of those most prone to rupture. Considering the findings were independent of lipids and CRP, an obvious question is what effect the novel nonstatin lipid-altering agents will have on plaque regression and CaI.
Keywords: Plaque, Atherosclerotic, Adventitia, Antihypertensive Agents, Calcium, Cholesterol, Cholesterol, LDL, Constriction, Pathologic, Coronary Disease, Coronary Vessels, C-Reactive Protein, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipids, Lipoproteins, LDL, Tomography, Ultrasonics, Ultrasonography, Interventional, Prospective Studies, Secondary Prevention
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