Statins may have stabilising, procalcific effects on atheroma plaque
Impact of Statins on Serial Coronary Calcification During Atheroma Progression and Regression
Puri R, Nicholls SJ, Shao M, et al.,
J Am Coll Cardiol. 2015 Apr 7;65(13):1273-82. doi: 10.1016/j.jacc.2015.01.036
BackgroundIn the most recent US guidelines, high-intensity statin therapy (HIST) is advocated in all individuals with known atherosclerosis, regardless of baseline lipoprotein levels , since statins can regress atherosclerosis and lower cardiovascular event rates.
Coronary arterial calcification (CAC) scoring using computed tomography (CT) is considered a reliable surrogate measure of coronary atheroma volume, and CAC at baseline strongly associated with incident CV events . It can be postulated that the effects of statin therapy on both plaque and its calcific component may be concordant. Prior serial CT evaluations of the effect of statins on CAC have, however, yielded conflicting results.
Mechanistic studies have shown potential procalcific effects of statins in vitro . This study set out to test the hypothesis that statin therapy is associated with concordant changes of both coronary atheroma volume and plaque calcification, using serial coronary intravascular ultrasound (IVUS). The observed changes were compared between patients receiving HIST, low-intensity statin therapy (LIST) and no-statin therapy. Patients participating in 8 clinical IVUS trials (REVERSAL, SATURN, AQUARIUS, NORMALIZE, ACTIVATE, ILLUSTRATE, STRADIVARIUS, PERISCOPE) were included.
- At follow-up, patients on HIST had the lowest LDL-c levels (70.8+26 mg/dL vs. 119.5 +34 mg/dL at baseline), as compared with those on LIST (89.1+25 mg/dl) and the no-statin group (107.2+31 mg/dL). Non-HDL cholesterol, triglyceride and CRP levels were also lowest in patients on HIST at follow-up.
- The HIST group showed significantly lower percent atheroma volume (PAV) at baseline than the LIST and no-statin group. At follow-up, the HIST group showed significant PAV regression from baseline (-0.6+0.1%, P<0.001), while the LIST and no-statin groups both showed significant PAV progression (0.8+0.1% and 1.0+0.1%, P<0.001 from baseline, respectively).
- TAV regression from baseline was seen in both the HIST and LIST groups (-6.6+0.6 mm3 and -2.1+0.6 mm3, P<0.001), and progression in the no-statin group (3.0+0.7 mm3, P<0.001).
- All treatment groups showed significant progression of coronary calcium, monitored as change in Calcium Index (CaI, HIST: 0.044 [0.0-0.12], LIST: 0.038 [0.0-0.11], no-statin: 0.02 [0.0-0.10], P<0.001 for all groups).
In a PAV-adjusted model, both statin-treated groups showed a significantly greater change in CaI than the no-statin group.
- Patients showing plaque progression had an overall change of +2.7+0.05% in PAV and +7.5+0.5 mm3 in TAV, while nonprogressors/regressors showed an overall -2.2+0.06% in PAV and -13.1+0.5 mm3 in TAV. Changes in CaI were significantly greater in those with plaque progression (0.045 [0.00-0.12]) than in nonprogressors/regressors (0.034 [0.00-0.11], irrespective of adjustment for changes in PAV or TAV.
- No significant correlations were observed between HIST-mediated changes in lipoproteins or CRP levels and changes in CaI, nor between these aspects in patients not on statins.
ConclusionIn this study, serial coronary IVUS revealed the significant pro-calcific effects of both HIST and LIST, as well as the calcific nature of coronary atheroma progression in patients not on statins. This analysis shows a dominant influence of statins on changes in plaque calcification, irrespective of net plaque progression or regression. The greatest increases in calcium were seen in patients on HIST who also showed significant plaque regression, while statin-naïve patients demonstrated the smallest increase in plaque calcification over time, coinciding with atheroma progression. The possible procalcific effects of statins are consistent with potential plaque-stabilising effects, in addition to their effects on atheroma volume.
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