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MSGene: Derivation and validation of a multistate model for lifetime risk of coronary artery disease using genetic risk and the electronic health record.

ABSTRACT: Currently, coronary artery disease (CAD) is the leading cause of death among adults worldwide. Accurate risk stratification can support optimal lifetime prevention. We designed a novel and general multistate model (MSGene) to estimate age-specific transitions across 10 cardiometabolic states, dependent on clinical covariates and a CAD polygenic risk score. MSGene supports decision making about CAD prevention related to any of these states. We analyzed longitudinal data from 480,638 UK Biobank participants and compared predicted lifetime risk with the 30-year Framingham risk score. MSGene improved discrimination (C-index 0.71 vs 0.66), age of high-risk detection (C-index 0.73 vs 0.52), and overall prediction (RMSE 1.1% vs 10.9%), with external validation. We also used MSGene to refine estimates of lifetime absolute risk reduction from statin initiation. Our findings underscore the potential public health value of our novel multistate model for accurate lifetime CAD risk estimation using clinical factors and increasingly available genetics.

SUBMITTER: Urbut SM

PROVIDER: S-EPMC10659503 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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MSGene: Derivation and validation of a multistate model for lifetime risk of coronary artery disease using genetic risk and the electronic health record.

Urbut Sarah M SM Yeung Ming Wai MW Khurshid Shaan S Cho So Mi Jemma SMJ Schuermans Art A German Jakob J Taraszka Kodi K Fahed Akl C AC Ellinor Patrick P Trinquart Ludovic L Parmigiani Giovanni G Gusev Alexander A Natarajan Pradeep P

medRxiv : the preprint server for health sciences 20231108

Currently, coronary artery disease (CAD) is the leading cause of death among adults worldwide. Accurate risk stratification can support optimal lifetime prevention. We designed a novel and general multistate model (MSGene) to estimate age-specific transitions across 10 cardiometabolic states, dependent on clinical covariates and a CAD polygenic risk score. MSGene supports decision making about CAD prevention related to any of these states. We analyzed longitudinal data from 480,638 UK Biobank pa ...[more]

PMID: 37986972

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Project description:BackgroundPostoperative delirium is an important problem for surgical inpatients and was the target of a multidisciplinary quality improvement project at our institution. We developed and tested a semiautomated delirium risk stratification instrument, Age, WORLD backwards, Orientation, iLlness severity, Surgery-specific risk (AWOL-S), in 3 independent cohorts from our tertiary care hospital and describe its performance characteristics and impact on clinical care.MethodsThe risk stratification instrument was derived with elective surgical patients who were admitted at least overnight and received at least 1 postoperative delirium screen (Nursing Delirium Screening Scale [NuDESC] or Confusion Assessment Method for the Intensive Care Unit [CAM-ICU]) and preoperative cognitive screening tests (orientation to place and ability to spell WORLD backward). Using data pragmatically collected between December 7, 2016, and June 15, 2017, we derived a logistic regression model predicting probability of delirium in the first 7 postoperative hospital days. A priori predictors included age, cognitive screening, illness severity or American Society of Anesthesiologists physical status, and surgical delirium risk. We applied model odds ratios to 2 subsequent cohorts ("validation" and "sustained performance") and assessed performance using area under the receiver operator characteristic curves (AUC-ROC). A post hoc sensitivity analysis assessed performance in emergency and preadmitted patients. Finally, we retrospectively evaluated the use of benzodiazepines and anticholinergic medications in patients who screened at high risk for delirium.ResultsThe logistic regression model used to derive odds ratios for the risk prediction tool included 2091 patients. Model AUC-ROC was 0.71 (0.67-0.75), compared with 0.65 (0.58-0.72) in the validation (n = 908) and 0.75 (0.71-0.78) in the sustained performance (n = 3168) cohorts. Sensitivity was approximately 75% in the derivation and sustained performance cohorts; specificity was approximately 59%. The AUC-ROC for emergency and preadmitted patients was 0.71 (0.67-0.75; n = 1301). After AWOL-S was implemented clinically, patients at high risk for delirium (n = 3630) had 21% (3%-36%) lower relative risk of receiving an anticholinergic medication perioperatively after controlling for secular trends.ConclusionsThe AWOL-S delirium risk stratification tool has moderate accuracy for delirium prediction in a cohort of elective surgical patients, and performance is largely unchanged in emergent/preadmitted surgical patients. Using AWOL-S risk stratification as a part of a multidisciplinary delirium reduction intervention was associated with significantly lower rates of perioperative anticholinergic but not benzodiazepine, medications in those at high risk for delirium. AWOL-S offers a feasible starting point for electronic medical record-based postoperative delirium risk stratification and may serve as a useful paradigm for other institutions.

Project description:BackgroundBinary diagnosis of coronary artery disease does not preserve the complexity of disease or quantify its severity or its associated risk with death; hence, a quantitative marker of coronary artery disease is warranted. We evaluated a quantitative marker of coronary artery disease derived from probabilities of a machine learning model.MethodsIn this cohort study, we developed and validated a coronary artery disease-predictive machine learning model using 95 935 electronic health records and assessed its probabilities as in-silico scores for coronary artery disease (ISCAD; range 0 [lowest probability] to 1 [highest probability]) in participants in two longitudinal biobank cohorts. We measured the association of ISCAD with clinical outcomes-namely, coronary artery stenosis, obstructive coronary artery disease, multivessel coronary artery disease, all-cause death, and coronary artery disease sequelae.FindingsAmong 95 935 participants, 35 749 were from the BioMe Biobank (median age 61 years [IQR 18]; 14 599 [41%] were male and 21 150 [59%] were female; 5130 [14%] were with diagnosed coronary artery disease) and 60 186 were from the UK Biobank (median age 62 [15] years; 25 031 [42%] male and 35 155 [58%] female; 8128 [14%] with diagnosed coronary artery disease). The model predicted coronary artery disease with an area under the receiver operating characteristic curve of 0·95 (95% CI 0·94-0·95; sensitivity of 0·94 [0·94-0·95] and specificity of 0·82 [0·81-0·83]) and 0·93 (0·92-0·93; sensitivity of 0·90 [0·89-0·90] and specificity of 0·88 [0·87-0·88]) in the BioMe validation and holdout sets, respectively, and 0·91 (0·91-0·91; sensitivity of 0·84 [0·83-0·84] and specificity of 0·83 [0·82-0·83]) in the UK Biobank external test set. ISCAD captured coronary artery disease risk from known risk factors, pooled cohort equations, and polygenic risk scores. Coronary artery stenosis increased quantitatively with ascending ISCAD quartiles (increase per quartile of 12 percentage points), including risk of obstructive coronary artery disease, multivessel coronary artery disease, and stenosis of major coronary arteries. Hazard ratios (HRs) and prevalence of all-cause death increased stepwise over ISCAD deciles (decile 1: HR 1·0 [95% CI 1·0-1·0], 0·2% prevalence; decile 6: 11 [3·9-31], 3·1% prevalence; and decile 10: 56 [20-158], 11% prevalence). A similar trend was observed for recurrent myocardial infarction. 12 (46%) undiagnosed individuals with high ISCAD (≥0·9) had clinical evidence of coronary artery disease according to the 2014 American College of Cardiology/American Heart Association Task Force guidelines.InterpretationElectronic health record-based machine learning was used to generate an in-silico marker for coronary artery disease that can non-invasively quantify atherosclerosis and risk of death on a continuous spectrum, and identify underdiagnosed individuals.FundingNational Institutes of Health.

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Project description:BACKGROUND:Deploying accurate computable phenotypes in pragmatic trials requires a trade-off between precise and clinically sensical variable selection. In particular, evaluating the medical encounter to assess a pattern leading to clinically significant impairment or distress indicative of disease is a difficult modeling challenge for the emergency department. OBJECTIVE:This study aimed to derive and validate an electronic health record-based computable phenotype to identify emergency department patients with opioid use disorder using physician chart review as a reference standard. METHODS:A two-algorithm computable phenotype was developed and evaluated using structured clinical data across 13 emergency departments in two large health care systems. Algorithm 1 combined clinician and billing codes. Algorithm 2 used chief complaint structured data suggestive of opioid use disorder. To evaluate the algorithms in both internal and external validation phases, two emergency medicine physicians, with a third acting as adjudicator, reviewed a pragmatic sample of 231 charts: 125 internal validation (75 positive and 50 negative), 106 external validation (56 positive and 50 negative). RESULTS:Cohen kappa, measuring agreement between reviewers, for the internal and external validation cohorts was 0.95 and 0.93, respectively. In the internal validation phase, Algorithm 1 had a positive predictive value (PPV) of 0.96 (95% CI 0.863-0.995) and a negative predictive value (NPV) of 0.98 (95% CI 0.893-0.999), and Algorithm 2 had a PPV of 0.8 (95% CI 0.593-0.932) and an NPV of 1.0 (one-sided 97.5% CI 0.863-1). In the external validation phase, the phenotype had a PPV of 0.95 (95% CI 0.851-0.989) and an NPV of 0.92 (95% CI 0.807-0.978). CONCLUSIONS:This phenotype detected emergency department patients with opioid use disorder with high predictive values and reliability. Its algorithms were transportable across health care systems and have potential value for both clinical and research purposes.

Dataset Information

MSGene: Derivation and validation of a multistate model for lifetime risk of coronary artery disease using genetic risk and the electronic health record.

Publications

MSGene: Derivation and validation of a multistate model for lifetime risk of coronary artery disease using genetic risk and the electronic health record.

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