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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Calcific aortic stenosis &#40;CAS&#41; is a clinical entity with an increasing prevalence in developed countries as populations age&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> The prevalence of CAS and its initial stage&#44; aortic sclerosis&#44; is reaching epidemic proportions&#44; affecting 2-7&#37; of the general population and 30&#37; of adults aged over 65&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">After becoming symptomatic&#44; CAS patients have an increased risk of sudden death and a mean survival of 2-3 years&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> and so prompt aortic valve replacement &#40;AVR&#41; is recommended&#46; AVR is currently the only definitive treatment available with proven benefits in symptom relief and improved survival&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> However&#44; the diagnostic criteria for CAS and the optimal timing for AVR are the subject of debate&#44; mainly because symptom severity is often misjudged or masked by aging and the presence of other comorbidities&#46; Studies have consistently shown that mortality in CAS patients awaiting surgery is higher than in those referred for isolated coronary surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">3</span></a> Additionally&#44; even after successful valve replacement&#44; at least 15&#37; of patients die within one year and another 20&#37; experience a serious event&#46; Therefore&#44; there is a need for biomarkers that can monitor the severity&#44; progression and prognosis of CAS&#44; since they could improve risk stratification and clinical decisions&#44; particularly with regard to the optimal timing for AVR&#44; since plasma markers can be accurately measured in the laboratory to give robust&#44; cost-effective and rapid results&#46; However&#44; the value of the available markers is debatable&#44; and none have yet been translated into clinical practice or incorporated into the guidelines&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The pathophysiology of CAS involves various biological processes and has not been completely elucidated&#46; Briefly&#44; CAS is triggered by mechanical stress on the aortic valve in conjunction with atherosclerotic risk factors&#44; leading to endothelial dysfunction and valve leakage&#44; followed by deposition and oxidation of lipids and other compounds in the subendothelium&#46; Monocytes infiltrate the valve tissue and phagocytize the modified lipids&#44; becoming foam cells&#46; T lymphocytes secrete cytokines&#44; which promote inflammation and remodeling of the extracellular matrix&#46; Fibroblasts transdifferentiate into valvular myofibroblasts with an osteoblast-like phenotype&#46; These events underlie subsequent changes involving extracellular matrix remodeling and neovascularization&#44; ultimately leading to active calcification&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a> Given the multiple biological pathways underlying the pathophysiology of CAS&#44; there are many potential biomarkers that could be clinically valuable to diagnose CAS and monitor its progression and prognosis&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Most of the markers studied so far have been used to assess the presence and severity of CAS but are less useful for monitoring progression or prognosis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46; An exception seems to be B-type natriuretic peptide &#40;BNP&#41; and its prohormone&#44; NT-proBNP&#44; released by cardiomyocytes on stretching&#46; Increased BNP levels are associated with low-flow CAS&#44; impaired left ventricular &#40;LV&#41; longitudinal strain and myocardial fibrosis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46; BNP appears to be an independent predictor of prognosis in patients with CAS&#44; particularly in those with severe stenosis and low transvalvular gradient&#46; In CAS&#44; patients with higher BNP or NT-proBNP levels display significantly lower one-year survival and higher probability of developing symptoms&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Markers of endothelial dysfunction such as asymmetric dimethylarginine &#40;ADMA&#41;&#44; enzyme tissue plasminogen activator &#40;tPA&#41; and homocysteine have shown modest results&#46; While high plasma levels of both ADMA and tPA are independently linked to a diagnosis of CAS&#44; the latter was found not to be a predictor of CAS&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">4&#44;6</span></a> Subsequent studies with smaller number of patients have shown contradictory results&#44; highlighting the weaknesses of these biomarkers&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Markers of oxidative stress&#44; such as malondialdehyde&#44; 8-hydroxy-2-deoxyguanosine&#44; cysteine&#44; homocysteine&#44; cysteinylglycine and glutathione&#44; have also been evaluated&#46; Among these&#44; only malondialdehyde has proved promising&#44; predicting adverse outcomes during 30-day and 1-year follow-up in high-risk patients with symptomatic&#44; severe CAS treated with transcatheter AVR&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Hypercholesterolemia has also been associated with the pathogenesis of CAS&#44; despite contradictory results from studies assessing the use of lipid-lowering agents in these patients&#46; Thus research on potential CAS markers related to lipid deposition&#44; such as total&#44; LDL and oxidized-LDL cholesterol plasma levels became promising&#46; Disappointingly&#44; several major studies &#40;SEAS&#44; SALTIRE and ASTRONOMER<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">8&#8211;10</span></a>&#41; have shown no direct relationship between the progression of CAS and any cholesterol-related particles&#46; Similarly&#44; leptin levels have been significantly associated with the presence of CAS&#44; although the role of leptin in its pathogenesis and whether it is associated with the progression of CAS remains unclear&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Another potential group of biomarkers is molecules involved in osteoblastic transdifferentiation&#44; such as fetuin&#44; which inhibits calcification and whose plasma levels are inversely associated with the presence of CAS&#44; but only in non-diabetic patients&#46; The relation of fetuin levels with the severity and progression of CAS is unclear&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a> Osteopontin is another potentially interesting marker for CAS&#44; since it is the only molecule directly involved in the ectopic calcification that occurs in the later stages of the disease&#46; Recently a correlation between plasma osteopontin levels and the severity of CAS has been demonstrated&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a> Lastly&#44; calcium-phosphorus product is associated with the severity of CAS in patients with end-stage renal disease&#44; in which it is inversely related to aortic valve area and positively related to both peak and mean transvalvular gradients&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Over the last decade&#44; the concept of CAS as a degenerative disease has changed due to increasing evidence of an active inflammatory process related in many ways to arteriosclerosis&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a> prompting exploration of inflammatory molecules as potential biomarkers of CAS progression&#46; Interventions that reduce the degree of inflammation have been shown to attenuate the progression of valve stenosis&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">12</span></a> In this regard&#44; C-reactive protein &#40;CRP&#41; and high-sensitivity CRP plasma levels have been shown to be elevated in CAS&#44; although with no association with aortic valve area&#44; degree of calcification or aortic jet velocity&#44; and to discriminate patients with and without events&#44; respectively&#46; Regarding disease progression and prognosis&#44; the usefulness of CRP levels is uncertain&#44; mostly due to its non-specific mode of release during most inflammatory processes&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a> Recently&#44; combining growth differentiation factor-15 levels with the logistic Euro-SCORE or EuroSCORE II has led to the identification of patient subgroups with greatly differing outcomes after transcatheter AVR&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">13</span></a> The neutrophil&#47;lymphocyte ratio &#40;NLR&#41; and platelet&#47;lymphocyte ratio have also recently been the subject of interest as predictors of the severity and extent of CAS&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">14&#44;15</span></a> Both ratios significantly correlated with the severity of CAS and the latter also predicted the presence of LV systolic dysfunction&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Another promising disease marker is the lymphocyte&#47;monocyte ratio&#46; In the current issue of the <span class="elsevierStyleItalic">Journal</span>&#44; Efe at al&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">16</span></a> observed a statistically significant inverse relationship between this ratio and severity of CAS&#46; Despite its inherent limitations this study makes an additional and promising contribution to this exciting emerging field and paves the way for future research in this topic&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">It is worth mentioning other potential CAS markers that have been assessed with modest results&#46; Indexes of von Willebrand factor activity have been associated with CAS severity and bleeding and were predictive of cardiovascular outcomes<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">17</span></a>&#59; extracellular matrix proteins&#44; such as MMP-1&#44; MMP-2&#44; MMP-9 and TIMP-1&#44; displayed similar values between CAS patients and controls despite showing univariate correlations with echocardiographic data &#40;LV enlargement and diastolic function&#41;&#59; and inflammatory biomarkers&#44; including interleukin-1 beta&#44; tumor necrosis factor alpha and transforming growth factor beta&#44; correlated with fibrotic markers in patients with mild CAS but were unable to discriminate CAS&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">18</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">As a consequence of rising life expectancy&#44; the demand for aortic valve monitoring can be expected to increase in the future&#46; The initial stages of CAS usually remain asymptomatic for a long time&#59; when patients complain the disease has already progressed to an advanced stage&#46; The more information is gathered on the natural course of aortic valve degeneration&#44; the greater the chances of successfully intervening before irreversible valve damage has ensued and surgery becomes urgent&#46; Therefore&#44; instead of using a single plasma marker&#44; there are high hopes for the potential utility of a panel of biomarkers&#44; reflecting diverse pathways involved in CAS&#44; or even a scoring system that combines biomarkers with echocardiographic and&#47;or clinical data to aid in risk stratification of patients with CAS&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Biomarkers of aortic valve stenosis&#46; Ideally a biomarker should be easily measurable&#44; highly reproducible and useful in diagnosing &#40;1&#41;&#44; following the disease progression &#40;2&#41; and predicting its prognosis &#40;3&#41;&#46; Most of the markers studied so far are valuable tools to diagnose and assess the severity of aortic valve stenosis &#40;AVS&#44; ex&#46; CRP and osteopontin&#41; but show poor utility when it comes to monitor AVS progression or prognosis&#46; The exception seems to be B-type natriuretic peptide &#40;BNP&#41; and its prohormone&#44; NT-proBNP&#44; both able to diagnose&#44; assess the severity and prognosis of AVS patients&#46; BNP mechanism of release is triggered by ventricular pressure overload imposed by the stenotic valve as depicted in the heart on the left&#46; ADMA&#44; asymmetric dimethylarginine&#59; CRP&#44; C-reactive protein&#59; GDF-15&#44; growth differentiation factor-15&#59; hs-CRP&#44; high-sensitivity&#59; tPA&#44; enzyme tissue plasminogen activator&#46; Figure was produced using Servier Medical Art&#46;</p>"
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Editorial comment
Biomarkers of aortic valve stenosis: Should we rely on a single one?
Biomarcadores da estenose valvular aórtica: devemos confiar num único?
Inês Falcão-Pires, Adelino F. Leite-Moreira
Corresponding author
amoreira@med.up.pt

Corresponding author.
Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, Universidade do Porto, Porto, Portugal
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    "titulo" => "Biomarkers of aortic valve stenosis&#58; Should we rely on a single one&#63;"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Biomarkers of aortic valve stenosis&#46; Ideally a biomarker should be easily measurable&#44; highly reproducible and useful in diagnosing &#40;1&#41;&#44; following the disease progression &#40;2&#41; and predicting its prognosis &#40;3&#41;&#46; Most of the markers studied so far are valuable tools to diagnose and assess the severity of aortic valve stenosis &#40;AVS&#44; ex&#46; CRP and osteopontin&#41; but show poor utility when it comes to monitor AVS progression or prognosis&#46; The exception seems to be B-type natriuretic peptide &#40;BNP&#41; and its prohormone&#44; NT-proBNP&#44; both able to diagnose&#44; assess the severity and prognosis of AVS patients&#46; BNP mechanism of release is triggered by ventricular pressure overload imposed by the stenotic valve as depicted in the heart on the left&#46; ADMA&#44; asymmetric dimethylarginine&#59; CRP&#44; C-reactive protein&#59; GDF-15&#44; growth differentiation factor-15&#59; hs-CRP&#44; high-sensitivity&#59; tPA&#44; enzyme tissue plasminogen activator&#46; Figure was produced using Servier Medical Art&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Calcific aortic stenosis &#40;CAS&#41; is a clinical entity with an increasing prevalence in developed countries as populations age&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> The prevalence of CAS and its initial stage&#44; aortic sclerosis&#44; is reaching epidemic proportions&#44; affecting 2-7&#37; of the general population and 30&#37; of adults aged over 65&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">After becoming symptomatic&#44; CAS patients have an increased risk of sudden death and a mean survival of 2-3 years&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> and so prompt aortic valve replacement &#40;AVR&#41; is recommended&#46; AVR is currently the only definitive treatment available with proven benefits in symptom relief and improved survival&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> However&#44; the diagnostic criteria for CAS and the optimal timing for AVR are the subject of debate&#44; mainly because symptom severity is often misjudged or masked by aging and the presence of other comorbidities&#46; Studies have consistently shown that mortality in CAS patients awaiting surgery is higher than in those referred for isolated coronary surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">3</span></a> Additionally&#44; even after successful valve replacement&#44; at least 15&#37; of patients die within one year and another 20&#37; experience a serious event&#46; Therefore&#44; there is a need for biomarkers that can monitor the severity&#44; progression and prognosis of CAS&#44; since they could improve risk stratification and clinical decisions&#44; particularly with regard to the optimal timing for AVR&#44; since plasma markers can be accurately measured in the laboratory to give robust&#44; cost-effective and rapid results&#46; However&#44; the value of the available markers is debatable&#44; and none have yet been translated into clinical practice or incorporated into the guidelines&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The pathophysiology of CAS involves various biological processes and has not been completely elucidated&#46; Briefly&#44; CAS is triggered by mechanical stress on the aortic valve in conjunction with atherosclerotic risk factors&#44; leading to endothelial dysfunction and valve leakage&#44; followed by deposition and oxidation of lipids and other compounds in the subendothelium&#46; Monocytes infiltrate the valve tissue and phagocytize the modified lipids&#44; becoming foam cells&#46; T lymphocytes secrete cytokines&#44; which promote inflammation and remodeling of the extracellular matrix&#46; Fibroblasts transdifferentiate into valvular myofibroblasts with an osteoblast-like phenotype&#46; These events underlie subsequent changes involving extracellular matrix remodeling and neovascularization&#44; ultimately leading to active calcification&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a> Given the multiple biological pathways underlying the pathophysiology of CAS&#44; there are many potential biomarkers that could be clinically valuable to diagnose CAS and monitor its progression and prognosis&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Most of the markers studied so far have been used to assess the presence and severity of CAS but are less useful for monitoring progression or prognosis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46; An exception seems to be B-type natriuretic peptide &#40;BNP&#41; and its prohormone&#44; NT-proBNP&#44; released by cardiomyocytes on stretching&#46; Increased BNP levels are associated with low-flow CAS&#44; impaired left ventricular &#40;LV&#41; longitudinal strain and myocardial fibrosis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46; BNP appears to be an independent predictor of prognosis in patients with CAS&#44; particularly in those with severe stenosis and low transvalvular gradient&#46; In CAS&#44; patients with higher BNP or NT-proBNP levels display significantly lower one-year survival and higher probability of developing symptoms&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Markers of endothelial dysfunction such as asymmetric dimethylarginine &#40;ADMA&#41;&#44; enzyme tissue plasminogen activator &#40;tPA&#41; and homocysteine have shown modest results&#46; While high plasma levels of both ADMA and tPA are independently linked to a diagnosis of CAS&#44; the latter was found not to be a predictor of CAS&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">4&#44;6</span></a> Subsequent studies with smaller number of patients have shown contradictory results&#44; highlighting the weaknesses of these biomarkers&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Markers of oxidative stress&#44; such as malondialdehyde&#44; 8-hydroxy-2-deoxyguanosine&#44; cysteine&#44; homocysteine&#44; cysteinylglycine and glutathione&#44; have also been evaluated&#46; Among these&#44; only malondialdehyde has proved promising&#44; predicting adverse outcomes during 30-day and 1-year follow-up in high-risk patients with symptomatic&#44; severe CAS treated with transcatheter AVR&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Hypercholesterolemia has also been associated with the pathogenesis of CAS&#44; despite contradictory results from studies assessing the use of lipid-lowering agents in these patients&#46; Thus research on potential CAS markers related to lipid deposition&#44; such as total&#44; LDL and oxidized-LDL cholesterol plasma levels became promising&#46; Disappointingly&#44; several major studies &#40;SEAS&#44; SALTIRE and ASTRONOMER<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">8&#8211;10</span></a>&#41; have shown no direct relationship between the progression of CAS and any cholesterol-related particles&#46; Similarly&#44; leptin levels have been significantly associated with the presence of CAS&#44; although the role of leptin in its pathogenesis and whether it is associated with the progression of CAS remains unclear&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Another potential group of biomarkers is molecules involved in osteoblastic transdifferentiation&#44; such as fetuin&#44; which inhibits calcification and whose plasma levels are inversely associated with the presence of CAS&#44; but only in non-diabetic patients&#46; The relation of fetuin levels with the severity and progression of CAS is unclear&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a> Osteopontin is another potentially interesting marker for CAS&#44; since it is the only molecule directly involved in the ectopic calcification that occurs in the later stages of the disease&#46; Recently a correlation between plasma osteopontin levels and the severity of CAS has been demonstrated&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a> Lastly&#44; calcium-phosphorus product is associated with the severity of CAS in patients with end-stage renal disease&#44; in which it is inversely related to aortic valve area and positively related to both peak and mean transvalvular gradients&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Over the last decade&#44; the concept of CAS as a degenerative disease has changed due to increasing evidence of an active inflammatory process related in many ways to arteriosclerosis&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a> prompting exploration of inflammatory molecules as potential biomarkers of CAS progression&#46; Interventions that reduce the degree of inflammation have been shown to attenuate the progression of valve stenosis&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">12</span></a> In this regard&#44; C-reactive protein &#40;CRP&#41; and high-sensitivity CRP plasma levels have been shown to be elevated in CAS&#44; although with no association with aortic valve area&#44; degree of calcification or aortic jet velocity&#44; and to discriminate patients with and without events&#44; respectively&#46; Regarding disease progression and prognosis&#44; the usefulness of CRP levels is uncertain&#44; mostly due to its non-specific mode of release during most inflammatory processes&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a> Recently&#44; combining growth differentiation factor-15 levels with the logistic Euro-SCORE or EuroSCORE II has led to the identification of patient subgroups with greatly differing outcomes after transcatheter AVR&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">13</span></a> The neutrophil&#47;lymphocyte ratio &#40;NLR&#41; and platelet&#47;lymphocyte ratio have also recently been the subject of interest as predictors of the severity and extent of CAS&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">14&#44;15</span></a> Both ratios significantly correlated with the severity of CAS and the latter also predicted the presence of LV systolic dysfunction&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Another promising disease marker is the lymphocyte&#47;monocyte ratio&#46; In the current issue of the <span class="elsevierStyleItalic">Journal</span>&#44; Efe at al&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">16</span></a> observed a statistically significant inverse relationship between this ratio and severity of CAS&#46; Despite its inherent limitations this study makes an additional and promising contribution to this exciting emerging field and paves the way for future research in this topic&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">It is worth mentioning other potential CAS markers that have been assessed with modest results&#46; Indexes of von Willebrand factor activity have been associated with CAS severity and bleeding and were predictive of cardiovascular outcomes<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">17</span></a>&#59; extracellular matrix proteins&#44; such as MMP-1&#44; MMP-2&#44; MMP-9 and TIMP-1&#44; displayed similar values between CAS patients and controls despite showing univariate correlations with echocardiographic data &#40;LV enlargement and diastolic function&#41;&#59; and inflammatory biomarkers&#44; including interleukin-1 beta&#44; tumor necrosis factor alpha and transforming growth factor beta&#44; correlated with fibrotic markers in patients with mild CAS but were unable to discriminate CAS&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">18</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">As a consequence of rising life expectancy&#44; the demand for aortic valve monitoring can be expected to increase in the future&#46; The initial stages of CAS usually remain asymptomatic for a long time&#59; when patients complain the disease has already progressed to an advanced stage&#46; The more information is gathered on the natural course of aortic valve degeneration&#44; the greater the chances of successfully intervening before irreversible valve damage has ensued and surgery becomes urgent&#46; Therefore&#44; instead of using a single plasma marker&#44; there are high hopes for the potential utility of a panel of biomarkers&#44; reflecting diverse pathways involved in CAS&#44; or even a scoring system that combines biomarkers with echocardiographic and&#47;or clinical data to aid in risk stratification of patients with CAS&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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ISSN: 21742049
Original language: English
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Revista Portuguesa de Cardiologia (English edition)
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