Evidence map›Paper›PMID 39724785›Full record

ArticleEBioMedicine2025

Simplifying coronary artery disease risk stratification: development and validation of a questionnaire-based alternative comparable to clinical risk tools.

Michail Kokkorakis, Pytrik Folkertsma, Filippos Anagnostakis, Nicole Sirotin, Manyoo Agarwal, Ronney Shantouf, Robert H Henning, Hanno Pijl, Bruce H R Wolffenbuttel, Jeroen J Bax and 4 more

Abstract read
In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Michail KokkorakisDepartment 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. Electronic address: m.kokkorakis@umcg.nl.
Pytrik FolkertsmaDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Filippos AnagnostakisCenter 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, Italy.
Nicole SirotinDepartment of Preventive Medicine, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.
Manyoo AgarwalHeart, Vascular and Thoracic Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.
Ronney ShantoufHeart, Vascular and Thoracic Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.
Robert H HenningDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Hanno PijlDepartment of Endocrinology, Leiden University Medical Center, Leiden, Netherlands.
Bruce H R WolffenbuttelDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Jeroen J BaxDepartment of Cardiology, Leiden University Medical Center, Leiden, Netherlands.
Douwe E AtsmaDepartment 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, Netherlands.
José Castela ForteDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Christos S MantzorosDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA.
Sipko van DamDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.

Funding

Harvard Clinical and Translational Science CenterUM1TR004408 · NCATS · HARVARD MEDICAL SCHOOL · PI Lindsey Robert Baden, Lee Marshall Nadler · 2023 to 2026
$43.3M
NCATS NIH HHS UM1 TR004408
6 · The paper itself

Abstract

backgroundCoronary 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.

methodsCox 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.

findingsIn 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.

interpretationQUES-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.

fundingUniversity Medical Center Groningen.

Indexed as

Coronary Artery DiseaseAgedFemaleHumansMaleMiddle AgedProportional Hazards ModelsReproducibility of ResultsRisk AssessmentRisk FactorsSurveys and QuestionnairesCoronary artery diseaseData-driven predictionDiscriminative abilitiesMachine learningPopulation screeningRisk stratification

Identifiers

PMID39724785
PMCPMC11732493

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.