For unclear reasons, only about 40% of patients with calcific aortic stenosis also have coronary

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1 Αθηροσκλήρωση και ασβεστοποιός στένωση της αορτικής βαλβίδας. Οµοιότητες και διαφορές Ν. Μεζίλης Κλινική «Άγιος Λουκάς»

2 Ασβεστοποιός στένωση της αορτικής βαλβίδας: Μία ακόµα µορφή αθηρωµάτωσης;

3 Some observations For unclear reasons, only about 40% of patients with calcific aortic stenosis also have coronary artery disease, and most people with coronary artery disease do not have calcific aortic stenosis. Hypertension, smoking, and diabetes mellitus have consistently been linked to the development of aortic stenosis. Endothelial injury or other processes that contribute to coronary disease may play a similar role in calcific aortic stenosis In observational studies, aortic stenosis progressed at a slower rate in patients who received statin drugs than in those who did not.

4 Aortic Stenosis Reumatic Congenital bicuspid Calcific

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7 The lesion of calcific aortic stenosis shares histologic similarities with atheromatous coronary artery disease, and its development and progression are linked to various traditional risk factors for atherosclerosis.

8 Gross specimen of minimally diseased aortic valve (left) and severely stenotic aortic valve (right). Freeman R V, and Otto C M Circulation. 2005;111: Gross specimen of minimally diseased aortic valve (left) and severely stenotic aortic valve (right). In the severely stenotic valve, there are prominent lipocalcific changes on aortic side of valve cusps (arrow), with sparing of commissures.

9 Cellular architecture of the aortic valve. Leopold J A Circ Cardiovasc Interv. 2012;5:

10 On gross inspection, the diseased aortic valve has areas of irregular thickening and calcification on the aortic side. Microscopically, the diseased aortic valve leaflets reveal disruption of the endothelium on the aortic side. Macrophage Calcifications Lipids

11 Figure 2. Potential pathways depicting calcific aortic valve disease. Freeman R V, and Otto C M Circulation. 2005;111: Similarities to atherosclerosis are present in these lesions, with prominent accumulation of atherogenic lipoproteins, including LDL and lipoprotein(a), evidence of LDL oxidation, an inflammatory cell infiltrate, and microscopic calcification

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14 Allison M A et al. Arterioscler Thromb Vasc Biol. 2004;24: A, Prevalence of calcium per vascular pattern in women. B, Prevalence of calcium per vascular pattern in men.

15 There was a significant correlation between the annualized progression of coronary and aortic valve calcification (r0.42, P0.001)

16 There was a significant influence of serum LDL cholesterol levels on the progression both of aortic valve and coronary calcifications

17 Box plots of the annualized progression of coronary calcifications and of aortic valve calcifications in the two patient groups divided according to their LDL cholesterol level. Box plots display median, 25th and 75th percentile, and the extreme values.

18 In Vivo Aortic Valve Thermal Heterogeneity in Patients With Nonrheumatic Aortic Valve Stenosis: The First In Vivo Experience in Humans. Toutouzas et al. J Am Coll Cardiol Representative Photomicrographs of HE Staining in Examined Specimens of Aortic Valves (A) Hematoxylin and eosin (HE) staining in aortic valve stenosis showing intense inflammation ( 200). (B) The HE staining in aortic valve insufficiency showing normal valvular stroma with sparse cellularity ( 200).

19 From: In Vivo Aortic Valve Thermal Heterogeneity in Patients With Nonrheumatic Aortic Valve Stenosis: The First In Vivo Experience in Humans J Am Coll Cardiol. 2008;52(9): doi: /j.jacc

20 Significant difference in local inflammatory activation within aortic valve leaflets as well as between the leaflets of the same stenotic valve From: In Vivo Aortic Valve Thermal Heterogeneity in Patients With Nonrheumatic Aortic Valve Stenosis: The First In Vivo Experience in Humans J Am Coll Cardiol. 2008;52(9): doi: /j.jacc

21 Thermal heterogeneity is increased in AVS and correlates with inflammatory mononuclear cell infiltration, expression of pro-inflammatory cytokines and neoangiogenic factors

22 Genetics Vitamin D receptor polymorphisms The receptor B allele is more frequent among patients with AS Polymorphism in the estrogen receptor gene might facilitate aortic stenosis through dyslipidemia.

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24 Statins but Not Angiotensin-Converting Enzyme Inhibitors Delay Progression of Aortic Stenosis ACEIs do not appear to slow AS progression. However, statins significantly reduce the hemodynamic progression of both mild-to-moderate and severe AS, an effect that may not be related to cholesterol lowering. R. Rosenhek et al, Circulation 2004

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27 Overall effect of statin on annualized increase of peak transaortic pressure gradient

28 Overall effect of statin on annualized decrease of aortic valve area.

29 A Randomized Trial of Intensive Lipid- Lowering Therapy in Calcific Aortic Stenosis S. Joanna Cowell, B.M., David E. Newby, M.D., Robin J. Prescott, Ph.D., Peter Bloomfield, M.D., John Reid, M.B., Ch.B., David B. Northridge, M.D., and Nicholas A. Boon, M.D. for the Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression (SALTIRE) Investigators N Engl J Med 2005;

30 double-blind, placebo-controlled trial, patients with calcific aortic stenosis were randomly assigned to receive either 80 mg of atorvastatin daily or a matched placebo

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32 SEAS Trial, 2008

33 Guidelines on the management of valvular heart disease (version 2012) The Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Statin therapy should not be used in AS patients where their only purpose is to slow progression. On the other hand, modification of atherosclerotic risk factors must be strongly recommended, following the guidelines of secondary prevention in atherosclerosis

34 Take home messages Stratify patient in low or high risk for rapid progression o AS Intense treatment for patients with risk factors