Intensive, but not moderate, statin therapy lowers epicardial adipose tissue

15/05/2013

Reduction of EAT volume in postmenopausal women by atorvastatin 80 mg could be a unsuspected mechanism through which statins improve clinical outcome.

Effect of Intensive Versus Moderate Lipid-Lowering Therapy on Epicardial Adipose Tissue in Hyperlipidemic Post-Menopausal Women: A Substudy of the BELLES Trial (Beyond Endorsed Lipid Lowering with EBT Scanning) 
Literature - Alexopoulos N, Melek BH, Arepalli CD, et al. - J Am Coll Cardiol. 2013 May 14;61(19):1956-61.

Alexopoulos N, Melek BH, Arepalli CD, et al.
J Am Coll Cardiol. 2013 May 14;61(19):1956-61. doi: 10.1016/j.jacc.2012.12.051

Background

Epicardial adipose tissue (EAT) is thought to contribute to the pathogenesis of coronary plaque formation in a paracrine fashion, and is therefore considered a novel marker of coronary atherosclerosis risk [1,2]. It is associated with some features of vulnerability of atherosclerotic plaques [3-5].
Intensive versus moderate lipid-lowering therapy did not show a different effect on progression of coronary artery calcium (CAC) in hyperlipidemic post-menopausal women in the BELLES study [6]. This analyses van de BELLES trial aimed to investigate whether intensive versus moderate lipid-lowering therapy has differential effects on EAT.
430 post-menopausal hyperlipidemic women were randomised to either atorvastatin 80 mg/day and matching pravastatin placebo (194 patients) or pravastatin 40 mg/day and matching atorvastatin placebo (226 patients). A baseline CT scan was performed as well as a follow-up CT-scan 12 months after randomisation.

Main results

  • EAT was larger in hypertensive, as opposed to normotensive patients (median ( range): 113 (35-307) vs. 98 (36-272) ml, P<0.001), as well as in diabetic in comparison to nondiabetic patients (119 (71-248) vs 102 (35-307) ml, P<0.001).
  • Patients on atorvastatin showed a greater percent decrease after follow-up than the pravastatin group in total cholesterol (median: -39.2% vs. -19.6%, P<0.001), LDL-C (-53.3% vs. -28.3%, P<0.001), triglycerides (-28.2% vs. -13.6%, P<0.001) and non-HDL-C (-49.7% vs. -25.5%, P<0.001).
  • EAT was more reduced in the atorvastatin group than in pravastatin-treated patients (-3.38% vs. -0.83%, P=0.025). EAT change from baseline was not statistically significant in the pravastatin group.
  • No significant correlations were found between reduction in total cholesterol, LDL-C, non HDL-C, triglycerides and EAT reduction in either treatment arm.

Conclusion

Intensive lipid-lowering treatment with atorvastatin for 1 year is associated with a significant reduction in EAT volume in postmenopausal women, while moderate statin treatment did not show such an effect. Although the extent of EAT has been associated with subclinical atherosclerosis and adverse outcomes, the prognostic value of EAT regression is currently unknown and deserves future study.  EAT modulation could be an unsuspected and easy to measure mechanism by which statins influence clinical outcome.  

References

1. Iacobellis G, Sharma AM. Epicardial adipose tissue as new cardiometabolic risk marker and potential therapeutic target in the metabolic syndrome. Curr Pharm Des 2007;13:2180–4.
2. McLean DS, Stillman AE. Epicardial adipose tissue as a cardiovascular risk marker. Clin Lipidol 2009;4:55– 62.
3. Alexopoulos N, McLean DS, Janik M, et al. Epicardial adipose tissue and coronary artery plaque characteristics. Atherosclerosis 2010;210:150–4.
4. Oka T, Yamamoto H, Ohashi N, et al. Association between epicardial adipose tissue volume and characteristics of non-calcified plaques assessed by coronary computed tomographic angiography. Int J Cardiol
2012;161:45–9.
5. Schlett CL, Ferencik M, Kriegel MF, et al. Association of pericardial fat and coronary high-risk lesions as determined by cardiac CT. Atherosclerosis 2012;222:129 –34.
6. Raggi P, Davidson M, Callister TQ, et al. Aggressive versus moderate lipid-lowering therapy in hypercholesterolemic postmenopausal women: Beyond Endorsed Lipid Lowering with EBT Scanning
(BELLES). Circulation 2005;112:563–71.


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