scholarly journals Use of a Polygenic Risk Score Improves Prediction of Myocardial Injury After Non-Cardiac Surgery

2020 ◽  
Vol 13 (4) ◽  
Author(s):  
Nicholas J. Douville ◽  
Ida Surakka ◽  
Aleda Leis ◽  
Christopher B. Douville ◽  
Whitney E. Hornsby ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Odds Ratio ◽  
Myocardial Injury ◽  
Risk Index ◽  
Cardiac Risk ◽  
Noncardiac Surgery ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Artery Disease

Background: While postoperative myocardial injury remains a major driver of morbidity and mortality, the ability to accurately identify patients at risk remains limited despite decades of clinical research. The role of genetic information in predicting myocardial injury after noncardiac surgery (MINS) remains unknown and requires large scale electronic health record and genomic data sets. Methods: In this retrospective observational study of adult patients undergoing noncardiac surgery, we defined MINS as new troponin elevation within 30 days following surgery. To determine the incremental value of polygenic risk score (PRS) for coronary artery disease, we added the score to 3 models of MINS risk: revised cardiac risk index, a model comprised entirely of preoperative variables, and a model with combined preoperative plus intraoperative variables. We assessed performance without and with PRSs via area under the receiver operating characteristic curve and net reclassification index. Results: Among 90 053 procedures across 40 498 genotyped individuals, we observed 429 cases with MINS (0.5%). PRS for coronary artery disease was independently associated with MINS for each multivariable model created (odds ratio=1.12 [95% CI, 1.02–1.24], P =0.023 in the revised cardiac risk index-based model; odds ratio, 1.19 [95% CI, 1.07–1.31], P =0.001 in the preoperative model; and odds ratio, 1.17 [95% CI, 1.06–1.30], P =0.003 in the preoperative plus intraoperative model). The addition of clinical risk factors improved model discrimination. When PRS was included with preoperative and preoperative plus intraoperative models, up to 3.6% of procedures were shifted into a new outcome classification. Conclusions: The addition of a PRS does not significantly improve discrimination but remains independently associated with MINS and improves goodness of fit. As genetic analysis becomes more common, clinicians will have an opportunity to use polygenic risk to predict perioperative complications. Further studies are necessary to determine if PRSs can inform MINS surveillance.

scholarly journals Polygenic Risk Score-enhanced Risk Stratification of Coronary Artery Disease in Patients with Stable Chest Pain

2021 ◽  
Author(s):  
Morten Krogh Christiansen ◽  
Simon Winther ◽  
Louise Nissen ◽  
Bjarni Jóhann Vilhjálmsson ◽  
Lars Frost ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Stratification ◽  
Lipid Lowering ◽  
Polygenic Risk Score ◽  
Fractional Flow ◽  
Coronary Cta ◽  
Polygenic Risk ◽  
Artery Disease ◽  
Clinical Potential

Background - Polygenic risk scores (PRSs) are associated with coronary artery disease (CAD), but the clinical potential of using PRSs at the single-patient level for risk stratification has yet to be established. We investigated whether adding a PRS to clinical risk factors (CRFs) improves risk stratification in patients referred to coronary computed tomography angiography (CTA) on a suspicion of obstructive CAD. Methods - In this prespecified diagnostic substudy of the Dan-NICAD trial we included 1617 consecutive patients with stable chest symptoms and no prior history of CAD referred for coronary CTA. CRFs used for risk stratification were age, sex, symptoms, prior or active smoking, antihypertensive treatment, lipid-lowering treatment, and diabetes. In addition, patients were genotyped and their PRSs were calculated. All patients underwent coronary CTA. Patients with a suspected ≥50% stenosis also underwent invasive coronary angiography (ICA) with fractional flow reserve (FFR). A combined endpoint of obstructive CAD was defined as a visual ICA stenosis >90%, FFR <0.80, or a quantitative coronary analysis stenosis >50% if FFR measurements were not feasible. Results - The PRS was associated with obstructive CAD independent of CRFs (adjusted OR 1.8 [95%CI 1.5-2.2] per SD). The PRS had an area under the curve (AUC) of 0.63 (0.59-0.68), which was similar to that for age and sex. Combining the PRS with CRFs led to a CRF+PRS model with AUC of 0.75 (0.71-0.79), which was 0.04 more than the CRF model ( P =0.0029). By using pre-test probability (PTP) cutoffs at 5% and 15%, a net reclassification improvement of 15.8% ( P =3.1e-4) was obtained, with a down-classification of risk in 24% of patients (211/862) in whom the PTP was 5%-15% based on CRFs alone. Conclusions - Adding a PRS improved risk stratification of obstructive CAD beyond CRFs, suggesting a modest clinical potential of using PRSs to guide diagnostic testing in the contemporary clinical setting.

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 Moving Genomics to Routine Care

2020 ◽  
Vol 13 (5) ◽  
pp. 406-416 ◽  
Author(s):  
Zahra Aryan ◽  
Attila Szanto ◽  
Angeliki Pantazi ◽  
Tejaswini Reddi ◽  
Carolyn Rheinstein ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Clinical Care ◽  
Polygenic Risk Score ◽  
Carrier Status ◽  
Polygenic Risk ◽  
Pathogenic Variants ◽  
Artery Disease ◽  
Cardiovascular Care

Background: Whole-genome sequencing (WGS) costs are falling, yet, outside oncology, this information is seldom used in adult clinics. We piloted a rapid WGS (rWGS) workflow, focusing initially on estimating power for a feasibility study of introducing genome information into acute cardiovascular care. Methods: A prospective implementation study was conducted to test the feasibility and clinical utility of rWGS in acute cardiovascular care. rWGS was performed on 50 adult patients with acute cardiovascular events and cardiac arrest survivors, testing for primary and secondary disease-causing variants, cardiovascular-related pharmacogenomics, and carrier status for recessive diseases. The impact of returning rWGS results on short-term clinical care of participants was investigated. The utility of polygenic risk scores to stratify coronary artery disease was also assessed. Results: Pathogenic variants, typically secondary findings, were identified in 20% (95% CI, 11.7–34.3). About 60% (95% CI, 46.2–72.4) of participants were carriers for one or more recessive traits, most commonly in HFE and SERPINA1 genes. Although 64% (95% CI, 50.1–75.9) of participants carried at least one pharmacogenetic variant of cardiovascular relevance, these were actionable in only 14% (95% CI, 7–26.2). Coronary artery disease prevalence among participants at the 95th percentile of polygenic risk score was 88.2% (95% CI, 71.8–95.7). Conclusions: We demonstrated the feasibility of rWGS integration into the inpatient management of adults with acute cardiovascular events. Our pilot identified pathogenic variants in one out of 5 acute vascular patients. Integrating rWGS in clinical care will progressively increase actionability.

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 Modifies Risk of Coronary Artery Disease Conferred by Low-Density Lipoprotein Cholesterol

2020 ◽  
Author(s):  
Alessandro Bolli ◽  
Paolo Di Domenico ◽  
Roberta Pastorino ◽  
George Busby ◽  
Giordano Bottà
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Polygenic Risk Score ◽  
Lipid Levels ◽  
Polygenic Risk ◽  
Artery Disease ◽  
Cad Risk ◽  
Blood Lipid Levels

AbstractBackgroundAn individual’s lifetime risk of Coronary Artery Disease (CAD) is determined by a combination of genetic and lifestyle factors. Whilst adherence to a healthy lifestyle can help individuals with high genetic risk reduce their lifetime risk of CAD, the extent to which blood lipid levels affect CAD risk in individuals with varying genetic risk remains unknown. To explore how genetics, blood lipids and CAD risk interact, we derived a novel genome-wide polygenic risk score (PRS) for CAD. We then applied the PRS to individuals from the UK Biobank and divided them into Low PRS (bottom 10 percentiles of PRS distribution), Intermediate PRS (PRS in the 10th-90th percentiles), and High PRS (top 10 percentiles), and further stratified individuals by blood lipid levels.ResultsWe found that the elevated CAD risk conferred by high low-density lipoprotein cholesterol (LDL-C) was modified by the interaction with PRS (P-value interaction: <0.005). Individuals with High PRS and whose LDL-C was Borderline (between 130 and 160 mg/dL) had higher CAD relative risk (HR 3.10; 95% CI, 2.55-3.76) than those at Intermediate PRS whose LDL-C were Very High (>190 mg/dL; HR 2.77; 95% CI, 2.33-3.28). Furthermore, individuals with High PRS but whose lipid levels were below the following thresholds did not have a significantly increased risk for incident CAD: LDL-C <130 mg/dL, total Cholesterol (TC) <200 mg/dL, LDL-C:HDL <2.0 and TC:HDL <3.0. In addition, individuals with Low PRS and Very High LDL-C (>190 mg/dl) did not have increased CAD risk, which was comparable to individuals with Intermediate PRS and Optimal LDL-C (<130 mg/dL).ConclusionsOur results have important implications for the primary prevention of coronary artery disease. Currently, healthy individuals with Borderline LDL-C (130-159 mg/dL) are not considered to be at high risk of CAD. Here we demonstrate that the combination of Borderline LDL-C and High PRS results in CAD relative risk which is greater than individuals without high polygenic risk, but whose LDL-C levels are high enough for statins to be recommended (>190 mg/dL). This analysis therefore demonstrates that PRS can identify a proportion of the population who are at high-risk of CAD but who are invisible to current approaches for assessing CAD risk. Moreover, of perhaps greater significance is the evidence that individuals who have a combination of High PRS and Optimal blood lipid levels do not have greater risk of CAD than individuals without high polygenic risk and the same Optimal blood lipid levels. Our results suggest that high polygenic risk for CAD could be overcome by controlling blood lipid levels. We propose that incorporating PRS into CAD risk assessment early in life could allow individuals at high polygenic risk to benefit from tailored blood lipid guidelines and avoid lifetime exposure to potentially damaging PRS-dependent LDL-C levels.

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
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