Deepak Voora1, Adrian Coles2, Kerry L Lee2, Udo Hoffmann3, James A Wingrove4, Brian Rhees4, Lin Huang4, Susan E Daniels4, Mark Monane4, Steven Rosenberg4, Svati H Shah5, William E Kraus6, Geoffrey S Ginsburg7, Pamela S Douglas5. 1. Duke Center for Applied Genomics & Precision Medicine, Duke University School of Medicine, Durham, NC; Department of Medicine, Duke University School of Medicine, Durham, NC. Electronic address: Deepak.voora@duke.edu. 2. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC. 3. Massachusetts General Hospital, Harvard Medical School, Boston, MA. 4. CardioDx, Inc., Redwood City, CA. 5. Department of Medicine, Duke University School of Medicine, Durham, NC; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC. 6. Department of Medicine, Duke University School of Medicine, Durham, NC. 7. Duke Center for Applied Genomics & Precision Medicine, Duke University School of Medicine, Durham, NC; Department of Medicine, Duke University School of Medicine, Durham, NC.
Abstract
BACKGROUND: Identifying predictors of coronary artery disease (CAD)-related procedures and events remains a priority. METHODS: We measured an age- and sex-specific gene expression score (ASGES) previously validated to detect obstructive CAD (oCAD) in symptomatic nondiabetic patients in the PROMISE trial. The outcomes were oCAD (≥70% stenosis in ≥1 vessel or ≥50% left main stenosis on CT angiography [CTA]) and a composite endpoint of death, myocardial infarction, revascularization, or unstable angina. RESULTS: The ASGES was determined in 2370 nondiabetic participants (47.5% male, median age 59.5 years, median follow-up 25 months), including 1137 with CTA data. An ASGES >15 was associated with oCAD (odds ratio 2.5 [95% CI 1.6-3.8], P<.001) and the composite endpoint (hazard ratio [HR] 2.6 [95% CI 1.8-3.9], P<.001) in unadjusted analyses. After adjustment for Framingham risk, an ASGES >15 remained associated with the composite endpoint (P=.02); the only component that was associated was revascularization (adjusted HR 2.69 [95% CI 1.52-4.79], P<.001). Compared to noninvasive testing, the ASGES improved prediction for the composite (increase in c-statistic=0.036; continuous net reclassification index=43.2%). Patients with an ASGES ≤15 had a composite endpoint rate no different from those with negative noninvasive test results (3.2% vs. 2.6%, P=.29). CONCLUSIONS: A blood-based genomic test for detecting oCAD significantly predicts near-term revascularization procedures, but not non-revascularization events. Larger studies will be needed to clarify the risk with non-revascularization events.
BACKGROUND: Identifying predictors of coronary artery disease (CAD)-related procedures and events remains a priority. METHODS: We measured an age- and sex-specific gene expression score (ASGES) previously validated to detect obstructive CAD (oCAD) in symptomatic nondiabeticpatients in the PROMISE trial. The outcomes were oCAD (≥70% stenosis in ≥1 vessel or ≥50% left main stenosis on CT angiography [CTA]) and a composite endpoint of death, myocardial infarction, revascularization, or unstable angina. RESULTS: The ASGES was determined in 2370 nondiabeticparticipants (47.5% male, median age 59.5 years, median follow-up 25 months), including 1137 with CTA data. An ASGES >15 was associated with oCAD (odds ratio 2.5 [95% CI 1.6-3.8], P<.001) and the composite endpoint (hazard ratio [HR] 2.6 [95% CI 1.8-3.9], P<.001) in unadjusted analyses. After adjustment for Framingham risk, an ASGES >15 remained associated with the composite endpoint (P=.02); the only component that was associated was revascularization (adjusted HR 2.69 [95% CI 1.52-4.79], P<.001). Compared to noninvasive testing, the ASGES improved prediction for the composite (increase in c-statistic=0.036; continuous net reclassification index=43.2%). Patients with an ASGES ≤15 had a composite endpoint rate no different from those with negative noninvasive test results (3.2% vs. 2.6%, P=.29). CONCLUSIONS: A blood-based genomic test for detecting oCAD significantly predicts near-term revascularization procedures, but not non-revascularization events. Larger studies will be needed to clarify the risk with non-revascularization events.
Authors: Burcu Gul; Alexandra Lansky; Matthew J Budoff; David Sharp; Bruce Maniet; Lee Herman; Jane Z Kuo; Lin Huang; Mark Monane; Joseph A Ladapo Journal: J Womens Health (Larchmt) Date: 2019-01-17 Impact factor: 2.681
Authors: Emily R Ko; Ricardo Henao; Katherine Frankey; Elizabeth A Petzold; Pamela D Isner; Anja K Jaehne; Nakia Allen; Jayna Gardner-Gray; Gina Hurst; Jacqueline Pflaum-Carlson; Namita Jayaprakash; Emanuel P Rivers; Henry Wang; Irma Ugalde; Siraj Amanullah; Laura Mercurio; Thomas H Chun; Larissa May; Robert W Hickey; Jacob E Lazarus; Shauna H Gunaratne; Daniel J Pallin; Guruprasad Jambaulikar; David S Huckins; Krow Ampofo; Ravi Jhaveri; Yunyun Jiang; Lauren Komarow; Scott R Evans; Geoffrey S Ginsburg; L Gayani Tillekeratne; Micah T McClain; Thomas W Burke; Christopher W Woods; Ephraim L Tsalik Journal: JAMA Netw Open Date: 2022-04-01
Authors: Jonathan D Newman; Pamela S Douglas; Ilya Zhbannikov; Maros Ferencik; Borek Foldyna; Udo Hoffmann; Svati H Shah; Geoffrey S Ginsburg; Michael T Lu; Deepak Voora Journal: Am Heart J Date: 2022-05-21 Impact factor: 5.099