Simplifying coronary artery disease risk stratification: development and validation of a questionnaire-based alternative comparable to clinical risk toolsResearch in context

Summary: Background: Coronary artery disease (CAD) comprises one of the leading causes of morbidity and mortality both in the European population and globally. All established clinical risk stratification scores and models require blood lipids and physical measurements. The latest reports of the Eu...

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Main Authors: Michail Kokkorakis, Pytrik Folkertsma, Filippos Anagnostakis, Nicole Sirotin, Manyoo Agarwal, Ronney Shantouf, Robert H. Henning, Hanno Pijl, Bruce H.R. Wolffenbuttel, Jeroen J. Bax, Douwe E. Atsma, José Castela Forte, Christos S. Mantzoros, Sipko van Dam
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Language:English
Published: Elsevier 2025-01-01
Series:EBioMedicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352396424005541
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author Michail Kokkorakis
Pytrik Folkertsma
Filippos Anagnostakis
Nicole Sirotin
Manyoo Agarwal
Ronney Shantouf
Robert H. Henning
Hanno Pijl
Bruce H.R. Wolffenbuttel
Jeroen J. Bax
Douwe E. Atsma
José Castela Forte
Christos S. Mantzoros
Sipko van Dam
author_facet Michail Kokkorakis
Pytrik Folkertsma
Filippos Anagnostakis
Nicole Sirotin
Manyoo Agarwal
Ronney Shantouf
Robert H. Henning
Hanno Pijl
Bruce H.R. Wolffenbuttel
Jeroen J. Bax
Douwe E. Atsma
José Castela Forte
Christos S. Mantzoros
Sipko van Dam
author_sort Michail Kokkorakis
collection DOAJ
description Summary: Background: Coronary artery disease (CAD) comprises one of the leading causes of morbidity and mortality both in the European population and globally. All established clinical risk stratification scores and models require blood lipids and physical measurements. The latest reports of the European Commission suggest that attracting health professionals to collect these data can be challenging, both from a logistic and cost perspective, which limits the usefulness of established models and makes them unsuitable for population-wide screening in resource-limited settings, i.e., rural areas. Therefore, the aim of this study was to develop and externally validate a questionnaire-based risk stratification model on a population scale at minimal cost, i.e., the Questionnaire-Based Evaluation for Estimating Coronary Artery Disease (QUES-CAD) to stratify the 10-year incidence of coronary artery disease. Methods: Cox proportional hazards (CoxPH) and Cox gradient boosting (CoxGBT) models were trained with 10-fold cross-validation using combinations of ten questionnaire variables on the White population of the UK Biobank (n = 448,818) and internally validated the models in all ethnic minorities (n = 27,433). The Lifelines cohort was employed as an independent external validation population (n = 97,770). Additionally, we compared QUES-CAD's performance, containing only questionnaire variables, to clinically established risk prediction tools, i.e., Framingham Coronary Heart Disease Risk Score, American College of Cardiology/American Heart Association pooled cohort equation, World Health Organization cardiovascular disease risk charts, and Systematic Coronary Risk Estimation 2 (SCORE2). We conducted partial log-likelihood ratio (PLR) tests and C-index comparisons between QUES-CAD and established clinical prediction models. Findings: In the external validation set, QUES-CAD exhibited C-index values of CoxPH: 0.692 (95% Confidence Interval [CI]: 0.673–0.71) and CoxGBT: 0.699 (95% CI: 0.681–0.717) for the male population and CoxPH: 0.771 (95% CI: 0.748–0.794) and CoxGBT: 0.759 (95% CI: 0.736–0.783) for the female population. The addition of measurement-based variables and variables that require a prior medical examination (i.e., insulin use, number of treatments/medications taken, prevalent cardiovascular disease [other than CAD, and stroke diagnosed by a doctor]) and the further addition of biomarkers/other measurements (i.e., high-density lipoprotein [HDL] cholesterol, total cholesterol, and glycated haemoglobin) did not significantly improve QUES-CAD's performance in most instances. C-index comparisons and PLR tests showed that QUES-CAD performs and fits the data at least as well as the clinical prediction models. Interpretation: QUES-CAD performs comparably to established clinical prediction models and enables a population-wide identification of high-risk individuals for CAD. The model developed and validated herein relies solely on ten questionnaire variables, overcoming the limitations of existing models that depend on physical measurements or biomarkers. Funding: University Medical Center Groningen.
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spelling doaj-art-c4b4a87e90e547a18471aa0b7893b14f2025-08-20T02:39:12ZengElsevierEBioMedicine2352-39642025-01-0111110551810.1016/j.ebiom.2024.105518Simplifying coronary artery disease risk stratification: development and validation of a questionnaire-based alternative comparable to clinical risk toolsResearch in contextMichail Kokkorakis0Pytrik Folkertsma1Filippos Anagnostakis2Nicole Sirotin3Manyoo Agarwal4Ronney Shantouf5Robert H. Henning6Hanno Pijl7Bruce H.R. Wolffenbuttel8Jeroen J. Bax9Douwe E. Atsma10José Castela Forte11Christos S. Mantzoros12Sipko van Dam13Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Corresponding author. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsCenter for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA; Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, ItalyDepartment of Preventive Medicine, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab EmiratesHeart, Vascular and Thoracic Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab EmiratesHeart, Vascular and Thoracic Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab EmiratesDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Endocrinology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Cardiology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Cardiology, Leiden University Medical Center, Leiden, Netherlands; National eHealth Living Lab, Leiden, Netherlands; Department of Design, Organization and Strategy, Faculty of Industrial Design Engineering, Delft University of Technology, Delft, NetherlandsDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Boston VA Healthcare System, Harvard Medical School, Boston, MA, USADepartment of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsSummary: Background: Coronary artery disease (CAD) comprises one of the leading causes of morbidity and mortality both in the European population and globally. All established clinical risk stratification scores and models require blood lipids and physical measurements. The latest reports of the European Commission suggest that attracting health professionals to collect these data can be challenging, both from a logistic and cost perspective, which limits the usefulness of established models and makes them unsuitable for population-wide screening in resource-limited settings, i.e., rural areas. Therefore, the aim of this study was to develop and externally validate a questionnaire-based risk stratification model on a population scale at minimal cost, i.e., the Questionnaire-Based Evaluation for Estimating Coronary Artery Disease (QUES-CAD) to stratify the 10-year incidence of coronary artery disease. Methods: Cox proportional hazards (CoxPH) and Cox gradient boosting (CoxGBT) models were trained with 10-fold cross-validation using combinations of ten questionnaire variables on the White population of the UK Biobank (n = 448,818) and internally validated the models in all ethnic minorities (n = 27,433). The Lifelines cohort was employed as an independent external validation population (n = 97,770). Additionally, we compared QUES-CAD's performance, containing only questionnaire variables, to clinically established risk prediction tools, i.e., Framingham Coronary Heart Disease Risk Score, American College of Cardiology/American Heart Association pooled cohort equation, World Health Organization cardiovascular disease risk charts, and Systematic Coronary Risk Estimation 2 (SCORE2). We conducted partial log-likelihood ratio (PLR) tests and C-index comparisons between QUES-CAD and established clinical prediction models. Findings: In the external validation set, QUES-CAD exhibited C-index values of CoxPH: 0.692 (95% Confidence Interval [CI]: 0.673–0.71) and CoxGBT: 0.699 (95% CI: 0.681–0.717) for the male population and CoxPH: 0.771 (95% CI: 0.748–0.794) and CoxGBT: 0.759 (95% CI: 0.736–0.783) for the female population. The addition of measurement-based variables and variables that require a prior medical examination (i.e., insulin use, number of treatments/medications taken, prevalent cardiovascular disease [other than CAD, and stroke diagnosed by a doctor]) and the further addition of biomarkers/other measurements (i.e., high-density lipoprotein [HDL] cholesterol, total cholesterol, and glycated haemoglobin) did not significantly improve QUES-CAD's performance in most instances. C-index comparisons and PLR tests showed that QUES-CAD performs and fits the data at least as well as the clinical prediction models. Interpretation: QUES-CAD performs comparably to established clinical prediction models and enables a population-wide identification of high-risk individuals for CAD. The model developed and validated herein relies solely on ten questionnaire variables, overcoming the limitations of existing models that depend on physical measurements or biomarkers. Funding: University Medical Center Groningen.http://www.sciencedirect.com/science/article/pii/S2352396424005541Coronary artery diseaseMachine learningData-driven predictionRisk stratificationDiscriminative abilitiesPopulation screening
spellingShingle Michail Kokkorakis
Pytrik Folkertsma
Filippos Anagnostakis
Nicole Sirotin
Manyoo Agarwal
Ronney Shantouf
Robert H. Henning
Hanno Pijl
Bruce H.R. Wolffenbuttel
Jeroen J. Bax
Douwe E. Atsma
José Castela Forte
Christos S. Mantzoros
Sipko van Dam
Simplifying coronary artery disease risk stratification: development and validation of a questionnaire-based alternative comparable to clinical risk toolsResearch in context
EBioMedicine
Coronary artery disease
Machine learning
Data-driven prediction
Risk stratification
Discriminative abilities
Population screening
title Simplifying coronary artery disease risk stratification: development and validation of a questionnaire-based alternative comparable to clinical risk toolsResearch in context
title_full Simplifying coronary artery disease risk stratification: development and validation of a questionnaire-based alternative comparable to clinical risk toolsResearch in context
title_fullStr Simplifying coronary artery disease risk stratification: development and validation of a questionnaire-based alternative comparable to clinical risk toolsResearch in context
title_full_unstemmed Simplifying coronary artery disease risk stratification: development and validation of a questionnaire-based alternative comparable to clinical risk toolsResearch in context
title_short Simplifying coronary artery disease risk stratification: development and validation of a questionnaire-based alternative comparable to clinical risk toolsResearch in context
title_sort simplifying coronary artery disease risk stratification development and validation of a questionnaire based alternative comparable to clinical risk toolsresearch in context
topic Coronary artery disease
Machine learning
Data-driven prediction
Risk stratification
Discriminative abilities
Population screening
url http://www.sciencedirect.com/science/article/pii/S2352396424005541
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