scholarly journals Integrated Polygenic Tool Substantially Enhances Coronary Artery Disease Prediction

2021 ◽  
Vol 14 (2) ◽  
Author(s):  
Fernando Riveros-Mckay ◽  
Michael E. Weale ◽  
Rachel Moore ◽  
Saskia Selzam ◽  
Eva Krapohl ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Score ◽  
Disease Risk ◽  
The United States ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Artery Disease

Background: There is considerable interest in whether genetic data can be used to improve standard cardiovascular disease risk calculators, as the latter are routinely used in clinical practice to manage preventative treatment. Methods: Using the UK Biobank resource, we developed our own polygenic risk score for coronary artery disease (CAD). We used an additional 60 000 UK Biobank individuals to develop an integrated risk tool (IRT) that combined our polygenic risk score with established risk tools (either the American Heart Association/American College of Cardiology pooled cohort equations [PCE] or UK QRISK3), and we tested our IRT in an additional, independent set of 186 451 UK Biobank individuals. Results: The novel CAD polygenic risk score shows superior predictive power for CAD events, compared with other published polygenic risk scores, and is largely uncorrelated with PCE and QRISK3. When combined with PCE into an IRT, it has superior predictive accuracy. Overall, 10.4% of incident CAD cases were misclassified as low risk by PCE and correctly classified as high risk by the IRT, compared with 4.4% misclassified by the IRT and correctly classified by PCE. The overall net reclassification improvement for the IRT was 5.9% (95% CI, 4.7–7.0). When individuals were stratified into age-by-sex subgroups, the improvement was larger for all subgroups (range, 8.3%–15.4%), with the best performance in 40- to 54-year-old men (15.4% [95% CI, 11.6–19.3]). Comparable results were found using a different risk tool (QRISK3) and also a broader definition of cardiovascular disease. Use of the IRT is estimated to avoid up to 12 000 deaths in the United States over a 5-year period. Conclusions: An IRT that includes polygenic risk outperforms current risk stratification tools and offers greater opportunity for early interventions. Given the plummeting costs of genetic tests, future iterations of CAD risk tools would be enhanced with the addition of a person’s polygenic risk.

Abstract 264: Utilizing Risk Scoring for Prescribing Statins to Hospitalized Patients to Primarily Prevent Coronary Artery Disease

2020 ◽  
Vol 13 (Suppl_1) ◽  
Author(s):  
Muhammed Atere ◽  
William Lim ◽  
Vishnuveni Leelaruban ◽  
Bhavya Narala ◽  
Stephanie Herrera ◽  
...  
Keyword(s):  
United States ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
High Risk ◽  
Disease Risk ◽  
The United States ◽  
Intermediate Risk ◽  
Peripheral Artery ◽  
Artery Disease

Background: Cardiovascular disease is the leading cause of mortality in the United States. Approximately 25% of total deaths in the United States are attributed to cardiovascular diseases. Modification of risk factors has been shown to reduce mortality and morbidity in people with coronary artery disease. Medications such as statins are well known for reducing risks and recent data has shown that statins are beneficial in the primary prevention of coronary artery disease. The purpose of this study is to assess whether statins are being prescribed on discharge to patients who are identified as intermediate to high risk using the ACC/AHA Pooled Cohort Equations. Methodology: We reviewed and analyzed the charts of hospitalized patient’s ages 40 to 79 years who were discharged under the service of Internal Medicine at Richmond University Medical Center from September 2018 to August 2019. Exclusion criteria included: patients that expired before discharge or were admitted to the intensive or coronary care units, pregnancy, previous diagnosis of coronary/peripheral artery disease or stroke, already on statins or lipid-lowering medications, allergic to statins, discharged on statins for coronary/peripheral artery disease or stroke, and patients with liver disease or elevated liver enzymes. We used the ACC/AHA Pooled Cohort Equations risk to calculate the 10-year coronary artery disease risk for each patient. Results: The 10-year risk is grouped as low risk (<5%), borderline risk (5% to 7.4%), intermediate risk (7.5% to 19.9%) and high risk (≥20%). Among 898 patients, 10% had intermediate and high risk that were not discharged with statins. Among the 10%, about 6.6% were intermediate risk and 3.4% were high risk. Conclusions: A significant number of intermediate and high-risk patients were discharged without statins, although a CT coronary calcium may be helpful in further classifying the risk in some of them. We believe that a lipid profile should be checked in all hospitalized patients 40 years and older in order to calculate their atherosclerosis cardiovascular disease risk score and to possibly initiate statins after discussing the benefits and side effects, particularly in the intermediate risk group. The continuation of statins would be followed up by their primary care physicians. We plan to liaise with the information technology department in our facility to provide a link to the risk calculator in the electronic medical record so that the risk can be calculated and statins initiated as necessary. We will conduct a follow up review to assess for effectiveness.

scholarly journals B-PO02-164 GENOME-WIDE POLYGENIC RISK SCORE PREDICTS SUDDEN ARRHYTHMIC DEATH IN PATIENTS WITH CORONARY ARTERY DISEASE

Heart Rhythm ◽  
2021 ◽  
Vol 18 (8) ◽  
pp. S164-S165
Author(s):  
Roopinder K. Sandhu ◽  
Jacqueline Dron ◽  
Yunxian Liu ◽  
Manickavasagar Vinayagamoorthy ◽  
Nancy R. Cook ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Arrhythmic Death ◽  
Genome Wide ◽  
Artery Disease

scholarly journals A Polygenic Risk Score for Coronary Artery Disease Improves the Prediction of Early-Onset Myocardial Infarction and Mortality in Men

2021 ◽  
Author(s):  
Hasanga D. Manikpurage ◽  
Aida Eslami ◽  
Nicolas Perrot ◽  
Zhonglin Li ◽  
Christian Couture ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Score ◽  
Predictive Accuracy ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Artery Disease ◽  
Genetically Determined

ABSTRACTBackgroundSeveral risk factors for coronary artery disease (CAD) have been described, some of which are genetically determined. The use of a polygenic risk score (PRS) could improve CAD risk assessment, but predictive accuracy according to age and sex is not well established.MethodsA PRSCAD including the weighted effects of >1.14 million SNPs associated with CAD was calculated in UK Biobank (n=408,422), using LDPred. Cox regressions were performed, stratified by age quartiles and sex, for incident MI and mortality, with a median follow-up of 11.0 years. Improvement in risk prediction of MI was assessed by comparing PRSCAD to the pooled cohort equation with categorical net reclassification index using a 2% threshold (NRI0.02) and continuous NRI (NRI>0).ResultsFrom 7,746 incident MI cases and 393,725 controls, hazard ratio (HR) for MI reached 1.53 (95% CI [1.49-1.56], p=2.69e-296) per standard deviation (SD) increase of PRSCAD. PRSCAD was significantly associated with MI in both sexes, with a stronger association in men (interaction p=0.002), particularly in those aged between 40-51 years (HR=2.00, 95% CI [1.86-2.16], p=1.93e-72). This group showed the highest reclassification improvement, mainly driven by the up-classification of cases (NRI0.02=0.199, 95% CI [0.157-0.248] and NRI>0=0.602, 95% CI [0.525-0.683]). From 23,982 deaths, HR for mortality was 1.08 (95% CI [1.06-1.09], p=5.46e-30) per SD increase of PRSCAD, with a stronger association in men (interaction p=1.60e-6).ConclusionOur PRSCAD predicts MI incidence and all-cause mortality, especially in men aged between 40-51 years. PRS could optimize the identification and management of individuals at risk for CAD.

scholarly journals POLYGENIC RISK SCORE FOR CORONARY ARTERY DISEASE ASSOCIATES WITH INCIDENCE OF CALCIFIC AORTIC STENOSIS

2021 ◽  
Vol 77 (18) ◽  
pp. 1725
Author(s):  
Shady Abohashem ◽  
Michael Osborne ◽  
Taimur Abbasi ◽  
Hadil Zureigat ◽  
Tawseef Dar ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Aortic Stenosis ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Calcific Aortic Stenosis ◽  
Polygenic Risk ◽  
Artery Disease

scholarly journals An integrated polygenic and clinical risk tool enhances coronary artery disease prediction

2020 ◽  
Author(s):  
Fernando Riveros-Mckay ◽  
Michael E. Weale ◽  
Rachel Moore ◽  
Saskia Selzam ◽  
Eva Krapohl ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
High Risk ◽  
Predictive Power ◽  
Low Risk ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Integrated Risk ◽  
Artery Disease

AbstractBackgroundThere is considerable interest in whether genetic data can be used to improve standard cardiovascular disease risk calculators, as the latter are routinely used in clinical practice to manage preventative treatment.MethodsThis research has been conducted using the UK Biobank (UKB) resource. We developed our own polygenic risk score (PRS) for coronary artery disease (CAD), using novel and established methods to combine published genomewide association study (GWAS) data with data from 114,196 UK Biobank individuals, also leveraging a large resource of other GWAS datasets along with functional information, to aid in the identification of causal variants, and thence define weights for > 8M genetic variants. We utilised a further 60,000 UKB individuals to develop an integrated risk tool (IRT) that combined our PRS with established risk tools (either the American Heart Association/American College of Cardiology’s pooled cohort equations (PCE) or the UK’s QRISK3) which was then tested in an additional, independent, set of 212,563 UKB individuals. We evaluated prediction performance in individuals of European ancestry, both as a whole and stratified by age and sex.FindingsThe novel CAD PRS showed superior predictive power for CAD events, compared to other published PRSs. As an individual risk factor, it has similar predictive power to each of systolic blood pressure, HDL cholesterol, and LDL cholesterol, but is more predictive than total cholesterol and smoking history. Our novel CAD PRS is largely uncorrelated with PCE, QRISK3, and family history, and, when combined with PCE into an integrated risk tool, had superior predictive accuracy. In individuals reclassified as high risk, CAD event rates were markedly and significantly higher compared to those reclassified as low risk. Overall, 9.7% of incident CAD cases were misclassified as low risk by PCE and correctly classified as high risk by the IRT, in contrast to 3.7% misclassified by the IRT and correctly classified by PCE. The overall net reclassification improvement for the IRT was 5.7% (95% CI 4.4−7.0), but when individuals were stratified into four age-by-sex subgroups the improvement was larger for all subgroups (range 7.7%−17.3%), with best performance in younger middle-aged men aged 40–54yo (17.3%, 95% CI 13.0–21.5). Broadly similar results were found using a different risk tool (QRISK3), and also for cardiovascular disease events defined more broadly.InterpretationAn integrated risk tool that includes polygenic risk outperforms current, clinical risk stratification tools, and offers greater opportunity for early interventions. Given the plummeting costs of genetic tests, future iterations of CAD risk tools would be enhanced with the addition of a person’s polygenic risk.FundingGenomics plc

scholarly journals Predictive Accuracy of a Polygenic Risk Score–Enhanced Prediction Model vs a Clinical Risk Score for Coronary Artery Disease

JAMA ◽  
2020 ◽  
Vol 323 (7) ◽  
pp. 636 ◽  
Author(s):  
Joshua Elliott ◽  
Barbara Bodinier ◽  
Tom A. Bond ◽  
Marc Chadeau-Hyam ◽  
Evangelos Evangelou ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Prediction Model ◽  
Risk Score ◽  
Predictive Accuracy ◽  
Polygenic Risk Score ◽  
Clinical Risk Score ◽  
Polygenic Risk ◽  
Clinical Risk ◽  
Artery Disease
Sign in / Sign up

Export Citation Format

Share Document