{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T14:13:28Z","timestamp":1765808008881,"version":"3.40.5"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Congenital heart defects (CHDs) affect 40\u2009000 US births per year, half of which require surgical intervention. Individual differences in surgical outcomes including mortality and complications are not well understood but may be due to genetic variability. We hypothesized that polygenic risk scores (PRSs) for blood pressure in adults are associated with treatments and postsurgical outcomes in children with CHD, as CHD survivors are at higher risk of negative cardiometabolic disease.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              We used imputed genotype data from pediatric participants requiring surgery for CHD (median age at surgery, 201 days; n\n              <jats:sub>max<\/jats:sub>\n              =2498). Base data for the systolic and diastolic blood pressure PRSs (n\n              <jats:sub>max<\/jats:sub>\n              =760\u2009226) came from published genome-wide association study. The blood pressure PRSs were tested for association with postsurgical outcomes. All effects presented are per SD increase in PRS and adjusted for age, sex, body mass index, surgical complexity score, and first 10 principal components of ancestry.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              A higher diastolic blood pressure PRS was associated with decreased in-hospital mortality risk (odds ratio, 0.57 [0.39\u20130.82];\n              <jats:italic>P<\/jats:italic>\n              =0.0022). Additional analyses suggest an interaction between diastolic blood pressure PRS and vasopressor dose. Those with a diastolic blood pressure PRS 1 SD above the mean, receiving a vasopressor dose in the top tertile, were estimated to have 52% (32%\u201366%) lower risk of in-hospital mortality compared with those with a vasopressor dose in the bottom tertile.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>These results suggest a genetically determined postsurgical survival advantage for CHD patients with blood pressure increasing alleles. Further study may reveal novel mechanisms contributing to postoperative morbidity and mortality, and this approach may assist in early identification of children at risk for adverse postoperative outcomes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.121.319842","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T10:00:17Z","timestamp":1645696817000},"page":"1030-1037","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Diastolic Blood Pressure Alleles Improve Congenital Heart Defect Repair Outcomes"],"prefix":"10.1161","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6179-0515","authenticated-orcid":true,"given":"Joseph H.","family":"Breeyear","sequence":"first","affiliation":[{"name":"Vanderbilt Genetics Institute (J.H.B., S.L.V.D., P.J.K., T.L.E.), Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6371-7530","authenticated-orcid":true,"given":"Jacob M.","family":"Keaton","sequence":"additional","affiliation":[{"name":"Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD (J.M.K.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric S.","family":"Torstenson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics (E.S.T.), Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew H.","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Cardiac Critical Care Medicine, Johns Hopkins All Children\u2019s Hospital, St. Petersburg, FL (A.H.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4636-5780","authenticated-orcid":true,"given":"Derek","family":"Klarin","sequence":"additional","affiliation":[{"name":"Veterans Affairs Boston Healthcare System, MA (D.K., P.N.)."},{"name":"Center for Genomic Medicine (D.K., P.N.), Massachusetts General Hospital, Harvard Medical School, Boston."},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (D.K., P.N.)."},{"name":"Division of Vascular Surgery and Endovascular Therapy, University of Florida School of Medicine, Gainesville (D.K.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8009-1632","authenticated-orcid":true,"given":"Scott M.","family":"Damrauer","sequence":"additional","affiliation":[{"name":"Corporal Michael Crescenz VA Medical Center, Philadelphia, PA (S.M.D.)."},{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia (S.M.D.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8402-7435","authenticated-orcid":true,"given":"Pradeep","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Veterans Affairs Boston Healthcare System, MA (D.K., P.N.)."},{"name":"Center for Genomic Medicine (D.K., P.N.), Massachusetts General Hospital, Harvard Medical School, Boston."},{"name":"Cardiovascular Research Center (P.N.), Massachusetts General Hospital, Harvard Medical School, Boston."},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (D.K., P.N.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2580-1405","authenticated-orcid":true,"given":"Sara L.","family":"Van Driest","sequence":"additional","affiliation":[{"name":"Vanderbilt Genetics Institute (J.H.B., S.L.V.D., P.J.K., T.L.E.), Vanderbilt University Medical Center, Nashville, TN."},{"name":"Department of Pediatrics, Center for Pediatric Precision Medicine (S.L.V.D., J.G.W., P.J.K.), Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey G.","family":"Weiner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Pediatric Precision Medicine (S.L.V.D., J.G.W., P.J.K.), Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1529-9872","authenticated-orcid":true,"given":"Prince J.","family":"Kannankeril","sequence":"additional","affiliation":[{"name":"Vanderbilt Genetics Institute (J.H.B., S.L.V.D., P.J.K., T.L.E.), Vanderbilt University Medical Center, Nashville, TN."},{"name":"Department of Pediatrics, Center for Pediatric Precision Medicine (S.L.V.D., J.G.W., P.J.K.), Vanderbilt University Medical Center, Nashville, 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