Determinants of aortic sclerosis progression: implications regarding impairment of nitric oxide signalling and potential therapeutics
| Autor: | Bernard J. Gersh, Doan T.M. Ngo, Aaron L. Sverdlov, John D. Horowitz, Yuliy Y. Chirkov, Wai P.A. Chan, John J McNeil |
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| Přispěvatelé: | Sverdlov, Aaron L, Ngo, Doan TM, Chan, Wai PA, Chirkov, Yuliy Y, Gersh, Bernard J, McNeil, John, Horowitz, John D |
| Rok vydání: | 2012 |
| Předmět: |
Male
Ramipril Aortic valve medicine.medical_specialty ACE-inhibitors/angiotensin receptor blockers Angiotensin-Converting Enzyme Inhibitors Nitric Oxide Angiotensin Receptor Antagonists chemistry.chemical_compound endothelial function nitric oxide Internal medicine medicine Humans Aged Aortic atherosclerosis Sclerosis medicine.diagnostic_test business.industry Aortic valve disorder Aortic Valve Stenosis Middle Aged medicine.disease Echocardiography Doppler medicine.anatomical_structure chemistry ageing inflammation Aortic Valve Aortic valve stenosis Disease Progression Arterial stiffness Cardiology Female Cardiology and Cardiovascular Medicine Lipid profile Asymmetric dimethylarginine business aortic valve sclerosis/calcification Biomarkers medicine.drug |
| Zdroj: | European Heart Journal. 33:2419-2425 |
| ISSN: | 1522-9645 0195-668X |
| Popis: | Aims Aortic valve stenosis (AS) and its precursor, aortic valve sclerosis (ASc), occur frequently in Western populations. Investigations to retard the progression of AS using statins have been unsuccessful. Development of ASc in humans is associated with increased aortic valve backscatter (AVBS) and poor tissue nitric oxide (NO) responsiveness. In an animal model, ramipril retarded AS/ASc development. We have now set out to identify factors associated with the progression of ASc in humans. Methods and results At baseline and after 4 years, 204 randomly selected subjects (age 63 ± 6 years at study entry) underwent echocardiography with the determination of AVBS values, measurements of platelet NO responsiveness, plasma asymmetric dimethylarginine concentrations, lipid profile, high-sensitivity-C-reactive protein, routine biochemistry, and 25-hydroxy-vitamin D levels. During the study period, 68% of subjects had detectable AVBS progression. On multivariate analysis, higher calcium concentrations ( β = 0.22; P = 0.004), poor platelet NO responsiveness ( β = 0.18; P = 0.018), and increased arterial stiffness ( β = 0.15; P = 0.044) were independent predictors of disease progression. The use of angiotensin-converting enzyme-inhibitors/angiotensin II receptor blockers (ACE-I/ARB) predicted the lack of disease progression (assessed categorically) in the overall cohort and in those without ASc at baseline ( n = 159) ( β = 0.8; P = 0.025 and β = 1.3; P = 0.001, respectively). No conventional coronary risk factors were associated with disease progression. Conclusion This study of early aortic valve disease (i) demonstrates that disease progression occurs in the majority of the normal ageing population over a 4-year period; (ii) provides evidence of the importance of the NO signalling cascade in disease development and progression; and (iii) provides additional data linking ACE-I/ARB use with the retardation of ASc. |
| Databáze: | OpenAIRE |
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