Instability of high polygenic risk classification and mitigation by integrative scoring

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 12, 2025

Polygenic risk scores (PRS) continue to improve with novel methods and expanding genome-wide association studies. Healthcare commercial laboratories are increasingly deploying PRS reports patients, but it is unknown how the classification of high polygenic changes across individual PRS. Here, we assess performance cataloged for three complex traits. We chronologically order all trait-related publications (Pubn) identify single Best(Pubn) each Pubn that has strongest target outcome. While demonstrates generally consistent population-level strengths associations, individuals in top 10% distribution varies widely. Using PRSmix framework, which integrates information several prediction, generate corresponding ChronoAdd(Pubn) combine from up including Pubn. When compared Best(Pubn), demonstrate more high-risk amongst themselves. This integrative scoring approach provides stable reliable an adaptable framework into new can be incorporated as they introduced, integrating easily current implementation strategies. Variability exists classifying diseases. Here authors show improves consistency overall toward clinical applications.

Язык: Английский

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Guideline-Directed Application of Coronary Artery Calcium Scores for Primary Prevention of Atherosclerotic Cardiovascular Disease

JACC. Cardiovascular imaging, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

The 2018 ACC (American College of Cardiology)/AHA Heart Association) and 2021 ESC (European Society Cardiology)/EAS Atherosclerosis Society) guidelines recommend coronary artery calcium (CAC) score for risk refinement in primary prevention atherosclerotic cardiovascular disease (ASCVD). study sought to compare CAC utility as a risk-refining tool following the ACC/AHA guideline using pooled cohort equations (PCE) or PREVENT (Predicting Risk EVENTs) ESC/EAS SCORE2 (Systematic COronary Evaluation 2). A total 1,903 statin-naive participants 55 75 years age, free ASCVD diabetes, with low-density lipoprotein cholesterol <190 mg/dL from prospective population-based Rotterdam Study were included. Per guidelines, we determined proportions scan-eligible reclassified men women, incidence rates, numbers needed treat 10 (NNT10y). By (PCE), 18.3% 11.9% by (PREVENT), 13.4% 3.4% women eligible scan. ESC/EAS, 46.6% 44.9% eligible. Proportions uprisked derisked individuals varied per guideline. Among CAC-eligible individuals, rates ranged 9.3 23.8 1,000 person-years, estimated NNT10y prevent 1 event, based on high-intensity statin use, 11 26. differ selection application ASCVD. Guideline-directed middle-aged apparently healthy population improved stratification at an acceptable both guidelines.

Язык: Английский

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Statins for Primary Prevention of Cardiovascular Disease—With PREVENT, What’s a Clinician to Do?

JAMA, Год журнала: 2024, Номер 332(12), С. 961 - 961

Опубликована: Июль 29, 2024

This Viewpoint explores decision thresholds and the evidence that informs them as well how clinicians may respond to an updated risk estimation model, such Predicting Risk of cardiovascular disease EVENTs equations.

Язык: Английский

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A Framework for Considering the Value of Race and Ethnicity in Estimating Disease Risk

Annals of Internal Medicine, Год журнала: 2024, Номер unknown

Опубликована: Дек. 2, 2024

Accounting for race and ethnicity in estimating disease risk may improve the accuracy of predictions but also encourage a racialized view medicine.

Язык: Английский

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OPPORTUNISTIC ASSESSMENT OF CARDIOVASCULAR RISK USING AI-DERIVED STRUCTURAL AORTIC AND CARDIAC PHENOTYPES FROM NON-CONTRAST CHEST COMPUTED TOMOGRAPHY

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

ABSTRACT Background Primary prevention of cardiovascular disease relies on accurate risk assessment using scores such as the Pooled Cohort Equations (PCE) and PREVENT. However, necessary input variables for these are often unavailable in electronic health record (EHR), information from routinely collected data (e.g., non-contrast chest CT) may further improve performance. Here, we test whether a prediction model based structural features heart aorta CT has added value to existing clinical algorithms predicting major adverse events (MACE). Methods We developed LASSO predict fatal MACE over 12 years follow-up radiomics describing cardiac chamber segmentations 13,437 lung cancer screening CTs National Lung Screening Trial. compared this PCE PREVENT an external testing set 4,303 individuals who had at Mass General Brigham site no history diabetes, prior MACE, or statin treatment. Discrimination incident was assessed concordance index. used binary threshold determine rates patients were statin-eligible ineligible by PCE/PREVENT (≥7.5% risk) score (≥5.0% risk). Results stratified all available calculate scores. In (n = 4,303; mean age 61.5 ± 9.3 years; 47.1% male), 8.0% median 5.1 follow-up. The significantly improved discrimination beyond (c-index 0.653 vs. 0.567, p < 0.001) performed similarly missing inputs. Those both 2.6-fold higher incidence than those eligible alone (29.5 [20.5, 39.1] 11.2 [8.0, 14.4] per 1,000 person-years among PCE-eligible individuals). inputs, 1.8-fold statin-ineligible [21.9, 37.6] 16.7 [14.3, 19.0] 1000 person-years). Similar results found when comparing score. Left ventricular volume short axis length most predictive myocardial infarction, while left atrial sphericity surface-to-volume ratio stroke. Conclusions Based single CT, shape-based predicted demonstrated similar performance inputs standard calculators. Patients high-risk benefit intensified primary prescription).

Язык: Английский

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Statin use and cardiovascular risk in young adults in the United States

American Journal of Preventive Medicine, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Evaluation and Comparison of the PREVENT and Pooled Cohort Equations for 10‐Year Atherosclerotic Cardiovascular Risk Prediction

Journal of the American Heart Association, Год журнала: 2025, Номер unknown

Опубликована: Фев. 8, 2025

Background We compared the atherosclerotic cardiovascular disease (ASCVD) risk prediction performance of American Heart Association's Predicting Risk Cardiovascular Disease Events (PREVENT) Base and PREVENT Full equations (includes urine albumin/creatinine ratio, glycated hemoglobin, social deprivation index) with pooled cohort (PCEs). Methods included adults, aged 40 to 75 years, no history ASCVD, diabetes, or statin use in 2009 from Kaiser Permanente Southern California followed up through 2019. ASCVD was defined as myocardial infarction, fatal coronary heart disease, nonfatal ischemic stroke. model discrimination (Harrell C), mean calibration (estimated ratio predicted/observed event rates), curve among overall population stratified by sex race ethnicity. Results Of 559 241 adults (mean age, 54 years; 11% Asian, non‐Hispanic Black, 32% Hispanic), 10 695 developed an (median follow‐up, years). Harrell C 0.741 (95% CI, 0.736–0.745) for Base, 0.743 0.738–0.748) Full, 0.736–0.746) PCEs. Compared PCEs, both improved men but not women, Black other races ethnicities. Both were well calibrated calibration, 0.85–1.36; slope, 0.69–1.27), whereas PCEs overestimated 10‐year 1.80–2.18; 0.32–0.45). Conclusions better predict absolute across racial ethnic groups a contemporary US adult population.

Язык: Английский

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The Role of Risk Equations in Primary Prevention of Atherosclerotic Cardiovascular Disease

Опубликована: Март 1, 2025

Review The Role of Risk Equations in Primary Prevention Atherosclerotic Cardiovascular Disease Rishi Rikhi and Michael D. Shapiro * Center for Disease, Section on Medicine, Department Internal Wake Forest University School Winston-Salem, NC 27157, USA Correspondence: [email protected]; Tel.: +1-(336)-713-7085; Fax: +1-(336)-716-9188 Received: 24 January 2025; Accepted: 11 February Published: 1 March 2025 Abstract: cardiovascular disease (ASCVD) is the leading cause death United States. 2018 American Heart Association (AHA)/American College Cardiology (ACC) blood cholesterol guideline recommends use pooled cohort equations (PCE) assessment 10-year ASCVD risk participants aged 40–75 years without a history or diabetes, low-density lipoprotein-cholesterol (LDL-C) ≥70 mg/dL <190 mg/dL. Recently, AHA released Predicting (CVD) EVENTs (PREVENT) that calculate both 10- 30-year ASCVD, CVD, heart failure (HF) 30–79 years. This review provides an overview primary prevention performance PREVENT compared to PCE. offers enhanced approach by integrating markers cardiovascular, kidney, metabolic health along with social determinants health, providing superior calibration discrimination holds promise refining statin eligibility identifying individuals at ASCVD. However, additional research essential define clinical thresholds evaluate its potential directing emerging preventive therapies.

Язык: Английский

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Performance of PREVENT equations for cardiovascular risk prediction in young patients with myocardial infarction: From the MGB YOUNG-MI Registry

American Journal of Preventive Cardiology, Год журнала: 2025, Номер unknown, С. 100992 - 100992

Опубликована: Апрель 1, 2025

Язык: Английский

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Semaglutide Eligibility Across All Current Indications for US Adults

JAMA Cardiology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 18, 2024

This cross-sectional study uses National Health and Nutrition Examination Survey data to examine the number of US adults eligible for semaglutide across all current indications.

Язык: Английский

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