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The Journal of heart valve disease 07/2012; 21(4):473-5. · 0.81 Impact Factor
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ABSTRACT: The study aims were to test the effect of rosuvastatin on the progression of left ventricular (LV) diastolic function in patients with aortic stenosis (AS), and to evaluate the use of beta-natriuretic-peptide (BNP) as a marker of diastolic dysfunction in this condition.
Sixty-one hypercholesterolemic, consecutive new referrals with moderate AS were administered rosuvastatin (Crestor) 20 mg/day for 18 months, while a further 60 subjects with normal cholesterol levels remained untreated. The LV diastolic function was determined using conventional Doppler echocardiography, tissue Doppler imaging (TDI); BNP plasma levels were monitored when subjects entered the study and then assessed prospectively at six-month intervals until the study end.
After an 18-month (mean 73 +/- 24 weeks) period of treatment with rosuvastatin (Tx group), patients showed a significantly better diastolic function than untreated subjects (uTx group), as indicated by an isovolumic relaxation time (IVRT) (Tx 102.0 +/- 42.8 versus 97.2 +/- 19.1; p < 0.001; uTx 99.7 +/- 21.7 versus 95.2 +/- 21.8 ms; p = 0.032), E/A ratio (Tx 1.0 +/- 0.6 versus 0.9 +/- 0.3, p = 0.52; uTx 1.2 +/- 0.40 versus 0.9 +/- 0.30 versus, p = 0.006), and E/E' ratio (Tx 11.4 +/- 1.5 versus 11.4 +/- 1.8, p = 0.19; uTx 15.4 +/- 1.2 versus 12.3 +/- 1.5, p < 0.001). Similarly, at study end, plasma levels of BNP were significantly lower in the Tx group than in the uTx group [median (1st-3rd quartiles): 37.0 pg/ml (20.1-65.2 pg/ml) versus 57.1 pg/ml (46.9-98.2 pg/ml); p = 0.017].
The results of this prospective follow up study of asymptomatic patients showed that rosuvastatin treatment delays the progression of diastolic dysfunction in moderate AS when assessed using hemodynamic echocardiographic parameters or by the release of plasma physiological markers. Hence, the benefits of statin treatment in AS, which are known to affect the valve endothelium, also extend to changes affecting myocardial function itself.
The Journal of heart valve disease 07/2012; 21(4):463-72. · 0.81 Impact Factor
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ABSTRACT: After hypertension and coronary artery disease (CAD), aortic stenosis (AS) is the most prevalent form of cardiovascular disease in the Western world (1-3). It is usually caused by either the degenerative calcifica-tion of a trileaflet valve or the progressive stenosis of a congenital bicuspid valve (4). Calcific aortic valve disease is a progressive condition for which patients are usually referred to a tertiary care center at a late stage in the disease process (1,5,6). Although aortic valve calcification was once thought to be a passive process, recent insights into its pathogenesis have suggested an inflammatory process similar to that of atherosclerosis (7,8). While statins were considered first-line candidates for slowing the progress of AS (9), and despite promising results being obtained with animal models and retrospective studies (10-16) and also from one prospective non-randomized trial (13), the results of recent randomized clinical tri-als have failed to confirm the expected benefit (17-19). In fact, the suggestion that a lack of benefit from statins therapy in calcific AS may be due to the presence of extensive calcification indicates that early treatment with statins might be more beneficial.
The Journal of heart valve disease 01/2012; 21:463. · 0.81 Impact Factor
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ABSTRACT: Paraoxonases may exert anti-atherogenic action by reducing lipid peroxidation. Previous studies examined associations between polymorphisms in the paraoxonase 1 (PON1) gene and development of coronary artery disease (CAD), with inconsistent results. Given the similarities in clinical and pathophysiological risk factors of CAD and calcific aortic valve stenosis (CAVS), we postulated a link between PON1 alleles and CAVS progression.
We investigated the association between PON1 55 and 192 single nucleotide polymorphisms (SNPs), their enzyme activity, and CAVS progression assessed by aortic valve area and transvalvular peak velocity in 67 consecutive patients with moderate CAVS and 251 healthy controls.
PON1 paraoxonase activity was higher in CAVS patients (P<0.001). The PON1 genotype Q192R SNP (P=0.03) and variant allele (R192) (P=0.01) frequencies differed between CAVS patients and controls. Significant association existed between PON1 enzyme activity, phenotypic effects of PON1 192 genotype polymorphisms, and CAVS progression, but not between PON1 55 and high-density lipoprotein (P=0.44) or low-density lipoprotein cholesterol (P=0.12), between 192 genotype and high-density lipoprotein (P=0.24) or low-density lipoprotein cholesterol (P=0.52).
The PON1 genotype Q192R SNP has an important effect on CAVS disease progression. This study helps outline a genotype-phenotype relationship for PON1 in this unique population.
American journal of cardiovascular disease. 01/2012; 2(2):123-32.
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ABSTRACT: At present, no medical therapy is known to affect the progression of rheumatic mitral stenosis (MS). We sought to assess the effect of statin treatment on long-term progression of MS in a large population.
From our 20-year database, we identified all patients with rheumatic MS with > or =2 echocardiographies > or =1 year apart. Exclusion criteria were previous intervention on the mitral valve, more than moderate aortic regurgitation, or symptoms at first examination. The study sample included 315 patients (mean age, 61+/-12 years; 224 women); 35 patients (11.1%) were treated with statins, and 280 (88.9%) were not. Mean follow-up period was 6.1+/-4.0 years (range, 1 to 20). The rate of decrease in mitral valve area was significantly lower in the statin group compared with the untreated group (0.027+/-0.056 versus 0.067+/-0.082 cm(2)/y; P=0.005). The annualized change in mean transmitral gradient was lower in statin-treated patients (0.20+/-0.59 versus 0.58+/-0.96 mm Hg/y; P=0.023). The prevalence of fast MS progression (annual change in mitral valve area >0.08 cm(2)) was significantly lower in the statin group (P=0.008). An increase in systolic pulmonary artery pressure of >10 mm Hg was found in 17% of patients in the statin group versus 40% of untreated patients (P=0.045).
Our study shows a significantly slower progression of rheumatic MS in patients treated with statins. These findings could have an important impact in the early medical therapy of patients with rheumatic heart disease.
Circulation 05/2010; 121(19):2130-6. · 14.74 Impact Factor
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Luis M Moura
The Journal of heart valve disease 09/2009; 18(5):562-4. · 0.81 Impact Factor
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ABSTRACT: Valvular heart disease (VHD) is characterized by an ongoing, inflammatory cellular response which results in a left ventricular hemodynamic stress change in response to valvulopathy. The current inflammatory hypothesis suggests that as the heart valve disease progresses the inflammatory cytokine response is activated causing continuation of deleterious effects on the heart and vasculature. This can lead to progression of heart failure and left ventricular dysfunction. Over the last 10 years, a number of biologically active molecules, termed biomarkers, have been discovered in VHD. These can be used to detect the progression and pathogenesis of heart failure and to assess the severity of inflammation (e.g., C-reactive protein). Brain natriuretic peptide (BNP) can diagnose underlying cardiac systolic and diastolic dysfunction. In high-risk patients BNP is also considered to be a useful tool for assisting in the diagnosis and monitoring the progression of VHD. Patients with symptomatic VHD benefit from aortic valve surgery; however, management in the absence of symptoms remains challenging. While the lack of symptoms can delay aortic valve replacement, unselected premature aortic valve replacement may be associated with unbalanced risks of cardiac surgery. This review summarizes the current and emerging clinical and potential research application of specific biomarkers of VHD.
Expert Review of Cardiovascular Therapy 09/2008; 6(7):945-54.
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ABSTRACT: This review article will discuss aortic stenosis, the evolving studies defining the cellular mechanisms and the potential for medical therapies for the treatment of this disease.
Currently, the only therapy for these patients is surgical valve replacement. In the past decade there has been a change in the paradigm towards our understanding of the cellular biology of this disease process. Studies in laboratories across the world have demonstrated that this disease has an active biology and that this biology may be targeted with medical therapies similar to that of vascular atherosclerosis.
Calcific aortic stenosis is the third most common form of cardiovascular disease in the USA. It has replaced rheumatic heart disease in prevalence in western countries due to improved access to healthcare and the widespread use of antibiotics.
Current Opinion in Cardiology 12/2007; 22(6):572-7. · 2.33 Impact Factor
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ABSTRACT: The objective of this study was to test the effect of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor on the progression of moderate to severe aortic stenosis as measured by echocardiography.
Recent retrospective studies support the hypothesis that statins slow the progression of aortic stenosis.
We performed an open-label, prospective study evaluating 121 consecutive patients with asymptomatic moderate to severe aortic stenosis (aortic valve area > or = 1.0 cm2; mean age 73.7 +/- 8.9 years; 57 men and 64 women), treated with and without rosuvastatin according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Echocardiographic, serum lipid, and inflammatory markers were measured at baseline and every 6 months for 18 months.
Sixty-one patients (50.4%) with elevated LDL (159.7 +/- 33.4 mg/dl), aortic valve velocity (3.65 +/- 0.64 m/s), and aortic valve area (1.23 +/- 0.42 cm2) received rosuvastatin (20 mg/day), and 60 (49.6%) with a normal LDL (118.6 +/- 37.4 mg/dl), aortic valve velocity (3.62 +/- 0.61 m/s), and aortic valve area (1.20 +/- 0.35 cm2) received no statin. During a mean follow-up of 73 +/- 24 weeks, the change in aortic valve area in the control group was -0.10 +/- 0.09 cm2/year versus -0.05 +/- 0.12 cm2/year in the rosuvastatin group (p = 0.041). The increase in aortic valve velocity was 0.24 +/- 0.30 m/s/year in the control group and 0.04 +/- 0.38 m/s/year in the rosuvastatin group (p = 0.007). There was significant improvement in serum lipid and echocardiographic measures of aortic stenosis in the statin group.
Prospective treatment of aortic stenosis with rosuvastatin by targeting serum LDL slowed the hemodynamic progression of aortic stenosis. This is the first prospective study that shows a positive effect of statin therapy for this disease process. (Rosuvastatin Affecting Aortic Valve Endothelium; http://www.clinicaltrials.gov/ct/show/NCT00114491?order = 1; NCT0014491).
Journal of the American College of Cardiology 02/2007; 49(5):554-61. · 14.16 Impact Factor
