title: A New Integrated Clinical-Biohumoral Model to Predict Functionally Significant Coronary Artery Disease in Patients With Chronic Chest Pain.
abstract: BACKGROUND
  In patients with chronic angina-like chest pain, the probability of coronary artery disease (CAD) is estimated by symptoms, age, and sex according to the Genders clinical model. We investigated the incremental value of circulating biomarkers over the Genders model to predict functionally significant CAD in patients with chronic chest pain.
  
  
  METHODS
  In 527 patients (60.4 years, standard deviation, 8.9 years; 61.3% male participants) enrolled in the European Evaluation of Integrated Cardiac Imaging (EVINCI) study, clinical and biohumoral data were collected.
  
  
  RESULTS
  Functionally significant CAD-ie, obstructive coronary disease seen at invasive angiography causing myocardial ischemia at stress imaging or associated with reduced fractional flow reserve (FFR < 0.8), or both-was present in 15.2% of patients. High-density lipoprotein (HDL) cholesterol, aspartate aminotransferase (AST) levels, and high-sensitivity C-reactive protein (hs-CRP) were the only independent predictors of disease among 31 biomarkers analyzed. The model integrating these biohumoral markers with clinical variables outperformed the Genders model by receiver operating characteristic curve (ROC) (area under the curve [AUC], 0.70 [standard error (SE), 0.03] vs 0.58 [SE, 0.03], respectively, P < 0.001) and reclassification analysis (net reclassification improvement, 0.15 [SE, 0.07]; P = 0.04). Cross-validation of the ROC analysis confirmed the discrimination ability of the new model (AUC, 0.66). As many as 56% of patients who were assigned to a higher pretest probability by the Genders model were correctly reassigned to a low probability class (< 15%) by the new integrated model.
  
  
  CONCLUSIONS
  The Genders model has a low accuracy for predicting functionally significant CAD. A new model integrating HDL cholesterol, AST, and hs-CRP levels with common clinical variables has a higher predictive accuracy for functionally significant CAD and allows the reclassification of patients from an intermediate/high to a low pretest likelihood of CAD.
authors.affiliation: Institute of Clinical Physiology, National Research Council, Pisa, Italy. Electronic address: chiara.caselli@ifc.cnr.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Caselli
authors.affiliation: Institute of Clinical Physiology, National Research Council, Pisa, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Rovai
authors.affiliation: Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Lorenzoni
authors.affiliation: Institute of Clinical Physiology, National Research Council, Pisa, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Carpeggiani
authors.affiliation: Institute of Cardiology, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Teresinska
authors.affiliation: Institut Catala de la Salut, Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Aguade
authors.affiliation: Fondazione Toscana G. Monasterio, Pisa, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Todiere
authors.affiliation: Fondazione Toscana G. Monasterio, Pisa, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Gimelli
authors.affiliation: Kliniken des Landkreises Göppingen, Göppingen, Germany.
authors.forename: Stephen
authors.initials: S
authors.lastname: Schroeder
authors.affiliation: Ospedale della Versilia, Lido di Camaiore, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Casolo
authors.affiliation: Ospedale della Versilia, Lido di Camaiore, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Poddighe
authors.affiliation: Centre for Advanced Cardiovascular Imaging, NIHR Cardiovascular Biomedical Research Unit at Barts, William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pugliese
authors.affiliation: APHP, Groupe Hospitalier Bichat-Claude Bernard, Département Hospitalo-Universitaire FIRE and Université Paris Diderot, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Le Guludec
authors.affiliation: Azienda Ospedaliero Universitaria Careggi, Firenze, Italy.
authors.forename: Serafina
authors.initials: S
authors.lastname: Valente
authors.affiliation: Università di Genova, Genoa, Italy.
authors.forename: Gianmario
authors.initials: G
authors.lastname: Sambuceti
authors.affiliation: Università di Napoli Federico II, Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Perrone-Filardi
authors.affiliation: Institute of Clinical Physiology, National Research Council, Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Del Ry
authors.affiliation: Institute of Clinical Physiology, National Research Council, Pisa, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Marinelli
authors.affiliation: Klinikum rechts der Isar der Technischen Universitat Munchen, Munchen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Nekolla
authors.affiliation: University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Pietila
authors.affiliation: Fondazione Toscana G. Monasterio, Pisa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Lombardi
authors.affiliation: Institute of Clinical Physiology, National Research Council, Pisa, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Sicari
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Arthur
authors.initials: A
authors.lastname: Scholte
authors.affiliation: University Hospital Clinico San Carlos, Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Zamorano
authors.affiliation: University Hospital Zurich, Zurich, Switzerland.
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Kaufmann
authors.affiliation: Imperial College London, United Kingdom.
authors.forename: S Richard
authors.initials: SR
authors.lastname: Underwood
authors.affiliation: University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.affiliation: Institute of Clinical Physiology, National Research Council, Pisa, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Giannessi
authors.affiliation: Institute of Clinical Physiology, National Research Council, Pisa, Italy; Fondazione Toscana G. Monasterio, Pisa, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Neglia
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000787:Angina Pectoris / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D001219:Aspartate Aminotransferases / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D002637:Chest Pain / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D008076:Cholesterol, HDL / Q000097:blood*; D002908:Chronic Disease; D015331:Cohort Studies; D017023:Coronary Angiography / Q000379:methods; D003327:Coronary Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D005260:Female; D053805:Fractional Flow Reserve, Myocardial; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D002097:C-Reactive Protein; D001219:Aspartate Aminotransferases