Article information
Resumen
Se entiende como marcador biológico cualquier característica que puede ser objetivamente medida y evaluada como indicadora de un proceso biológico normal, un proceso patogénico o una respuesta farmacológica a una intervención terapéutica. En el terreno de la hipertensión arterial pulmonar (HAP), además de los marcadores habituales (hemodinámicos y funcionales), se cuenta con un número creciente de biomarcadores que permiten un acercamiento cada vez más completo al conocimiento de la susceptibilidad y al establecimiento del diagnóstico, pronóstico y respuesta al tratamiento. Estos marcadores pueden ser tanto constitutivos (genéticos) como reactivos a la enfermedad (relacionados con el fallo ventricular derecho, como BMP/NT-proBNP, con la disfunción endotelial, como la endotelina-1, o con la inflamación, como determinadas citocinas y quimiocinas). Los nuevos descubrimientos en genómica y proteómica permiten augurar avances fundamentales en este campo.
Palabras clave:
Hipertensión pulmonar
Biomarcadores
NT-proBNP
Genética
Abstract
A biological marker can be defined as any substance that can be objectively measured and evaluated as an indicator of a normal biological process, a pathogenic process or pharmacological responses to a therapeutic intervention. In pulmonary hypertension (PH), in addition to routine markers (hemodynamic and functional), there are a growing number of biomarkers that allow an increasingly comprehensive approach to knowledge of susceptibility to this disease and to diagnosis, prognosis and treatment response. These markers can be both constitutive (genetic) and disease-related (related to right ventricular failure, such as BMP/NT-proBNP, endothelial dysfunction, such as endothelin-1, or inflammation, such as certain cytokines and chemokines). Novel insights in genomics and proteomics may allow major advances in this field.
Keywords:
Pulmonary hypertension
Biomarkers
NT-proBNP
Genetics
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Bibliografía
[1.]
A.J. Atkinson, W.A. Colburn, V.G. DeGruttola, D.L. DeMets, G.J. Downing, D.F. Hoth, et al.
Biomarkers and surrogate endpoints: preferred definitions and conceptual framework.
Clin Pharmacol Ther, 69 (2001), pp. 89-95
[2.]
C. Rhodes, J. Wharton, M. Wilkins.
Biomarkers in pulmonary hypertension.
PVRI Rev, 1 (2009), pp. 28-30
[3.]
M.E. Van Albada, F.G. Loot, R. Fokkema, M.T.R. Roofthooft, R.M.F. Berger.
Biological serum markers in the management of pediatric pulmonary arterial hypertension.
Pediatr Res, 63 (2008), pp. 321-327
[4.]
S. Rafeq, A.M. Shah, I.R. Preston.
Biomarkers in pulmonary arterial hypertension.
Int J Clin Pract, 63Suppl (2009), pp. 36-41
[5.]
E.D. Austin, J.E. Loyd, J.A. Phillips.
Genetics of pulmonary arterial hypertension.
Semin Respir Crit Care Med, 30 (2009), pp. 386-398
[6.]
S.L. Archer, E.K. Weir, M.R. Wilkins.
Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies.
Circulation, 121 (2010), pp. 2045-2066
[7.]
J. Wipff, P. Dieudé, M. Guedj, B. Ruiz, G. Riemekasten, J.L. Cracowski, et al.
Association of a KCNA5 gene polymorphism with systemic sclerosis–associated pulmonary arterial hypertension in the european caucasian population.
Arthritis Rheum, 62 (2010), pp. 3093-3100
[8.]
J. Wipff, A. Kahan, E. Hachulla, J. Sibilia, J. Cabane, O. Meyer, et al.
Association between an endoglin gene polymorphism and systemic sclerosis-related pulmonary arterial hypertension.
Rheumatology (Oxford), 46 (2007), pp. 622-625
[9.]
M. Manetti, Y. Allanore, L. Revillod, C. Fatini, S. Guiducci, G. Cuomo.
A genetic variation located in the promoter region of the UPAR (CD87) gene is associated with the vascular complications of systemic sclerosis.
Arthritis Rheum, 63 (2011), pp. 247-256
[10.]
S.K. Agarwal, P. Gourh, S. Shete, G. Paz, D. Divecha, J.D. Reveille, et al.
Association of Interleukin 23 receptor polymorphisms with anti-topoisomerase-I positivity and pulmonary hypertension in systemic sclerosis.
J Rheumatol, 36 (2009), pp. 2715-2723
[11.]
B. Rueda, O. Broen, O. Torres, C. Simeon, N. Ortego-Centeno, M.M. Schrijvenaars, et al.
The interleukin 23 receptor gene does not confer risk to systemic sclerosis and is not associated with systemic sclerosis disease phenotype.
Ann Rheum Dis, 68 (2009), pp. 253-256
[12.]
N. Nagaya, T. Nishikimi, Y. Okano, M. Uematsu, T. Satoh, S. Kyotani, et al.
Plasma brain natriuretic peptide levels increase in proportion to the extent of right ventricular disfunction in pulmonary hypertension.
J Am Coll Cardiol, 31 (1998), pp. 202-208
[13.]
N. Nagaya, T. Nishikimi, M. Uematsu, T. Satoh, S. Kyotani, F. Sakamaki, et al.
Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension.
Circulation, 102 (2000), pp. 865-870
[14.]
H.H. Leuchte, M. Holzapfel, R.A. Baumgartner, C. Neurohr, M. Vogeser, J. Behr.
Characterization of brain natriuretic peptide in long-term follow-up of pulmonary arterial hypertension.
Chest, 128 (2005), pp. 2368-2374
[15.]
G.A. Heresi.
Clinical perspective: biomarkers in pulmonary arterial hypertension.
Int J Clin Pract, 65 (2011), pp. 5-7
[16.]
M.R. Wilkins, G.A. Paul, J.W. Strange, N. Tunariu, W. Gin-Sing, W. Banya, et al.
Sildenafil versus endothelin receptor antagonist for pulmonary hypertension (SERAPH) study.
Am J Respir Crit Care Med, 171 (2005), pp. 1292-1297
[17.]
V.V. McLaughlin, R.L. Benza, L.J. Rubin, R.N. Channick, R. Voswinckel, V.F. Tapson, et al.
Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial.
J Am Coll Cardiol, 55 (2010), pp. 1915-1922
[18.]
A. Ortiz, M. Ronquillo, F. Gª Hernández, J.E. López, C. Ocaña, J. Sánchez Román, et al.
Determinación de péptidos natriuréticos como marcador de riesgo para el desarrollo precoz de hipertensión pulmonar.
Rev Esp Cardiol, 63 (2010), pp. 36
[19.]
Y. Allanore, D. Borderie, J. Avouac, D. Zerkak, C. Meune, E. Hachulla, et al.
High N-terminal pro-brain natriuretic peptide levels and low diffusing capacity for carbon monoxide as independent predictors of the occurrence of precapillary pulmonary arterial hypertension in patients with systemic sclerosis.
Arthritis Rheum, 58 (2008), pp. 284-291
[20.]
A. Torbicki, M. Kurzyna, P. Kuca, M. Fijalkowska, J. Sikora, M. Florczyk, et al.
Detectable serum cardiac troponin T as a marker of poor prognosis among patients with chronic precapillary pulmonary hypertension.
Circulation, 108 (2003), pp. 844-848
[21.]
M. Lankeit, C. Dellas, A. Panzenbock, N. Skoro-Sajer, D. Bonderman, M. Olschewski, et al.
Heart-type fatty acidbinding protein for risk assessment of chronic thromboembolic pulmonary hypertension.
Eur Respir J, 31 (2008), pp. 1024-1029
[22.]
T. Nakata, A. Hashimoto, M. Hase, K. Tsuchihashi, K. Shimamoto.
Human heart-type fatty acid-binding protein as an early diagnostic and prognostic marker in acute coronary syndrome.
Cardiology, 99 (2003), pp. 96-104
[23.]
C. Rubens, R. Ewert, M. Halank, R. Wensel, H.D. Orzechowski, H.P. Schultheiss, et al.
Big endothelin-1 and endothelin-1 plasma levels are correlated with the severity of primary pulmonary hypertension.
Chest, 120 (2001), pp. 1562-1569
[24.]
H. Wilkens, M. Bauer, N. Forestier, J. König, A. Eichler, S. Schneider, et al.
Influence of inhaled iloprost on transpulmonary gradient of big endothelin in patients with pulmonary hypertension.
Circulation, 107 (2003), pp. 1509-1513
[25.]
Y. Hiramoto, W. Shioyama, T. Kuroda, M. Masaki, S. Sugiyama, K. Kitaro Okamoto.
Effect of bosentan on plasma endothelin-1 concentration in patients with pulmonary arterial hypertension.
Circ J, 71 (2007), pp. 367-369
[26.]
D. Montani, R. Souza, C. Binkert, W. Fischli, G. Simonneau, M. Clozel, et al.
Endothelin-1/endothelin-3 ratio: a potential prognostic of pulmonary arterial hypertension.
Chest, 131 (2007), pp. 101-108
[27.]
M.T. Collados, J. Sandoval, S. López, F.A. Massó, A. Páez, J.R. Borbolla, et al.
Characterization of von Willebrand factor in primary pulmonary hypertension.
Heart Vessels, 14 (1999), pp. 246-252
[28.]
A. Veyradier, T. Nishikubo, M. Humbert, M. Wolf, O. Sitbon, G. Simonneau, et al.
Improvement of von Willebrand factor proteolysis after prostacyclin infusion in severe pulmonary arterial hypertension.
Circulation, 102 (2000), pp. 2460-2462
[29.]
G. Warwick, P.S. Thomas, D.H. Yates.
Biomarkers in pulmonary hypertension.
Eur Respir J, 32 (2008), pp. 503-512
[30.]
D. Elstein, A. Nir, M. Klutstein, B. Rudensky, A. Zimran.
C-reactive protein and NTproBNP as surrogate markers for pulmonary hypertension in Gaucher disease.
Blood Cells Mol Dis, 34 (2005), pp. 201-205
[31.]
C.J. Rhodes, J. Wharton, L. Howard, J.S.R. Gibbs, A.A. Aldashev, M.R. Wilkins.
Growth differentiation factor-15 as a biomarker in pulmonary arterial hypertension and hypoxia-induced pulmonary hypertension.
Circulation, 120 (2009), pp. S1135
[32.]
E. Soon, A.M. Holmes, C.M. Treacy, N.J. Doughty, L. Southgate, R.D. Machado.
Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension.
Circulation, 122 (2010), pp. 920-927
[33.]
J. Hiremath, S. Thanikachalam, K. Parikh, S. Shanmugasundaram, S. Bangera, L. Shapiro, et al.
Exercise improvement and plasma biomarker changes with intravenous treprostinil therapy for pulmonary arterial hypertension: a placebo-controlled trial.
J Heart Lung Transplant, 29 (2010), pp. 137-149
[34.]
N. Amabile, C. Heiss, V. Chang, F.S. Angeli, L. Damon, E.J. Rame, et al.
Increased CD62e+ endothelial microparticle levels predict poor outcome in pulmonary hypertension patients.
J Heart Lung Transplant, 28 (2009), pp. 1081-1086
[35.]
V.H. Abdul-Salam, J. Wharton, J. Cupitt, M. Berryman, R.J. Edwards, M.R. Wilkins.
Proteomic analysis of lung tissues from patients with pulmonary arterial hypertension.
Circulation, 122 (2010), pp. 2058-2067
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