Impact of Baseline Lipoprotein and C-Reactive Protein Levels on Coronary Atheroma Regression Following High-Intensity Statin Therapy

Puri R, Nissen SE, Shao M, et al.
Am J Cardiol. 2014 Aug 27. doi: 10.1016/j.amjcard.2014.08.009. [Epub ahead of print]

Background

The prognostic benefits of statin-mediated LDL-c lowering are clear. While European lipid-lowering guidelines recommend an LDL-c target of below 70 mg/dL (or a >50% reduction from baseline LDL-c) [1] for higher risk patients, United States guidelines now advocate the use of high-intensity statin therapy in all adults with documented atherosclerotic CV disease [2]. Treatment guidelines all recommend LDL-c lowering with statins for CV risk reduction.
Evidence is accumulating that change in coronary atheroma volume is associated with incident CV events [3,4]. The impact of potent statin therapy on coronary atheroma progression, depending on baseline lipoprotein levels is, however, unclear.
This study tested the hypothesis that maximally intensive statin therapy would result in equivalent degrees of coronary atheroma regression in patients, independent of baseline lipoprotein and C-reactive protein (CRP) levels. Data of participants of 8 clinical trials (REVERSAL, ASTEROID, SATURN, AQUARIUS, ACTIVATE, ILLUSTRATE, STRADIVARIUS, PERISCOPE) that assessed the impact of medical therapies on serial changes in coronary atheroma burden using intravascular
ultrasound (IVUS) were analysed.

Main results

• On average, switching to high-intensity statin therapy lowered LDL-c by an incremental 38.4%, non-HDL-c levels by 33.6%, triglycerides by 13.1% and CRP by 33.3% (all P<0.001).
  These changes were associated with a net reduction of percent atheroma volume (PAV) of 0.70% and total atheroma volume (TAV) of 8.2mm3 (both P<0.001).  
• A broad range of baseline LDL-c levels was seen (26-251 mg/dL). When stratifying according to quintiles of baseline LDL-c, no significant differences in baseline coronary atheroma volume were seen across the quintiles. No significant differences were seen in changes in PAV and TAV, nor in proportion of patients experiencing disease regression.
• When considering quintiles of baseline HDL-c levels, a trend was seen toward the presence of more extensive coronary disease at baseline in subjects with lower HDL-c. There were, however, no significant differences in changes in PAV and TAV or in the proportion of patients showing disease regression.
• No significant differences were seen between quintiles of baseline non-HDL-c levels either, nor of baseline triglyceride or CRP levels.

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Conclusion

This study shows a similar impact of high-intensity statin therapy on atherosclerotic disease progression rates in all patients, irrespective of their baseline levels of several atherogenic or protective lipoproteins or CRP.
Even though some patients present with seemingly well controlled lipoprotein levels, they may harbour coronary atheromas that appear amenable to further statin-modification and stabilisation. This suggests that a broader group of patients may derive therapeutic benefit from such therapy, in accordance with the latest ACC/AHA lipid treatment guidelines that recommend high-intensity statin therapy in any patient with atherosclerotic CV disease, regardless of baseline lipoprotein levels.

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References

1. Reiner Z, Catapano AL, De Backer G, et al. ESC/EAS guidelines for the management of  dyslipidaemias: the Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769e1818.
2. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2889e2934.
3. Tardif JC, Lesage F, Harel F, et al. Imaging biomarkers in atherosclerosis trials. Circ Cardiovasc Imaging 2011;4:319e333.
4. Nicholls SJ, Hsu A, Wolski K, et al. Intravascular ultrasound-derived measures of coronary atherosclerotic plaque burden and clinical outcome. J Am Coll Cardiol 2010;55:2399e2407.