Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease

• Published in: Journal of the American College of Cardiology Vol. 70; no. 7; pp. 813 - 826
• Main Authors: Lindholm, Daniel, Lindbäck, Johan, Armstrong, Paul W., Budaj, Andrzej, Cannon, Christopher P., Granger, Christopher B., Hagström, Emil, Held, Claes, Koenig, Wolfgang, Östlund, Ollie, Stewart, Ralph A.H., Soffer, Joseph, White, Harvey D., de Winter, Robbert J., Steg, Philippe Gabriel, Siegbahn, Agneta, Kleber, Marcus E., Dressel, Alexander, Grammer, Tanja B., März, Winfried, Wallentin, Lars
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.08.2017; Elsevier Limited
• Subjects: Acute coronary syndromes; Aged; Arteriosclerosis; Benzaldehydes - therapeutic use; Biomarkers; Biomarkers - blood; Brain natriuretic peptide; Calcium-binding protein; cardiac troponin; Cardiology; Cardiovascular; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Coronary artery disease; Coronary Disease - blood; Coronary Disease - mortality; Coronary Disease - prevention & control; Coronary vessels; Death; Diabetes mellitus; Disease prevention; Female; Follow-Up Studies; Gene expression; Global Health; Health risk assessment; Heart diseases; Heart failure; Humans; Ischemia; Lipids; Lipoproteins; low-density lipoprotein cholesterol; Male; Middle Aged; Mortality; N-terminal pro-B-type natriuretic peptide; Natriuretic Peptide, Brain - blood; Oximes - therapeutic use; Peptide Fragments - blood; Peptides; Phospholipase A2 Inhibitors - therapeutic use; Plasma; Prognosis; Prospective Studies; Risk Assessment - methods; Risk Factors; risk prediction; Secondary Prevention - methods; Smoking; Studies; Survival Rate - trends; Troponin; Troponin T; Troponin T - blood; NT-proBNP; hs-cTnT; LDL-C; cardiac troponin; low-density lipoprotein cholesterol; risk prediction; N-terminal pro–B-type natriuretic peptide; GDF-15; high-sensitivity cardiac troponin T; growth differentiation factor 15
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2017.06.030

Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD). This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD. In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study. During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This “ABC-CHD” model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts. This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903) [Display omitted]