{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T12:40:33Z","timestamp":1786711233810,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,12]]},"group-title":"Genetic and Genomic Medicine","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Severe hypercholesterolemia has four primary causes: monogenic familial hypercholesterolemia (FH), polygenic hypercholesterolemia (PRS), severely elevated Lp(a) concentration, and hypercholesterolemia due to environmental\/lifestyle\/behavioral factors (i.e., no known genetic etiology). Here, we explore patient and clinician perspectives about the identification and management of each of these causes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Patients with severe hypercholesterolemia with a primary language of English or Spanish and clinicians (primary care, genetic counseling, cardiology) across two health systems (Geisinger, Mount Sinai) participated in semi-structured interviews. Analysis was completed using an\n                    <jats:italic>a priori<\/jats:italic>\n                    codebook informed by Proctor\u2019s implementation outcomes to identify themes influencing the identification and management of the underlying causes of severe hypercholesterolemia.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 28 patients and 25 clinicians participated. Patients emphasized the importance of receiving results directly from their clinician, requested take-home resources that mirrored the information from their clinician, were motivated to seek multidisciplinary care, and anticipated all results would be actionable, but that high-risk PRS and elevated Lp(a) may require more support (e.g., specialists, education) to act on. Clinicians stressed the importance of integrating workflows (e.g., test ordering) with the electronic health record, highlighted LDL-C levels and multidisciplinary care coordination as key to management, explained how they would tailor care to individual patients, and expressed a more limited understanding of Lp(a) and PRS result types based on their clinical experiences and, therefore, hesitation about the recommended clinical actions.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Patients and clinicians identified complementary determinants influencing the identification and management of the underlying cause of severe hypercholesterolemia. Participants welcomed risk information and requested a higher level of informational support and specialty expertise to appropriately manage high Lp(a) and PRS results. Integrating genomic information into risk assessments will require a partnership between general practitioners and specialists to provide a multidisciplinary approach to the identification and management of the underlying causes of severe hypercholesterolemia.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.10.26360146","type":"posted-content","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T22:35:14Z","timestamp":1786574114000},"source":"Crossref","is-referenced-by-count":0,"title":["Designing to Implement Genomics Informed ASCVD Risk Assessment: Patient and Clinician Perspectives about Identifying and Managing the Underlying Causes of Severe Hypercholesterolemia"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9670-5947","authenticated-orcid":false,"given":"Kelly M.","family":"Morgan","sequence":"first","affiliation":[{"name":"Department of Genomic Health, Geisinger, Danville, PA 17822, United 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Danville, PA 17822, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Carr","sequence":"additional","affiliation":[{"name":"Department of Genomic Health, Geisinger, Danville, PA 17822, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ceballos","sequence":"additional","affiliation":[{"name":"Institute for Genomic Health, Icahn School of Medicine, New York, NY 10029, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8557-7225","authenticated-orcid":false,"given":"Samuel S.","family":"Gidding","sequence":"additional","affiliation":[{"name":"Department of Genomic Health, Geisinger, Danville, PA 17822, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9198-759X","authenticated-orcid":false,"given":"Eimear E.","family":"Kenny","sequence":"additional","affiliation":[{"name":"Institute for Genomic Health, Icahn School of Medicine, New York, NY 10029, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7400-5507","authenticated-orcid":false,"given":"Amy R.","family":"Kontorovich","sequence":"additional","affiliation":[{"name":"Institute for Genomic Health, Icahn School of Medicine, New York, NY 10029, United States"},{"name":"Cardiovascular Research Institute, Icahn School of Medicine, New York, NY 10029, United States"},{"name":"Fuster Heart Hospital, Icahn School of Medicine, New York, NY 10029, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Naib","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Icahn School of Medicine, New York, NY 10029, United States"},{"name":"Fuster Heart Hospital, Icahn School of Medicine, New York, NY 10029, United 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