Clinical Implications of Monogenic Versus Polygenic Hypercholesterolemia: Long‐Term Response to Treatment, Coronary Atherosclerosis Burden, and Cardiovascular Events
Background Familial hypercholesterolemia (FH) may arise from deleterious monogenic variants in FH‐causing genes as well as from a polygenic cause. We evaluated the relationships between monogenic FH and polygenic hypercholesterolemia in influencing the long‐term response to therapy and the risk of a...
| প্রধান লেখক: | , , , , , , , , , , , , , , , |
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| বিন্যাস: | প্রবন্ধ |
| ভাষা: | English |
| প্রকাশিত: |
Wiley
2021-05-01
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| মালা: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| বিষয়গুলি: | |
| অনলাইন ব্যবহার করুন: | https://www.ahajournals.org/doi/10.1161/JAHA.120.018932 |
| _version_ | 1831813319511506944 |
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| author | Laura D’Erasmo Ilenia Minicocci Alessia Di Costanzo Giovanni Pigna Daniela Commodari Fabrizio Ceci Anna Montali Francesca Brancato Ilaria Stanca Antonio Nicolucci Andrea Ascione Nicola Galea Iacopo Carbone Marco Francone Marianna Maranghi Marcello Arca |
| author_facet | Laura D’Erasmo Ilenia Minicocci Alessia Di Costanzo Giovanni Pigna Daniela Commodari Fabrizio Ceci Anna Montali Francesca Brancato Ilaria Stanca Antonio Nicolucci Andrea Ascione Nicola Galea Iacopo Carbone Marco Francone Marianna Maranghi Marcello Arca |
| author_sort | Laura D’Erasmo |
| collection | DOAJ |
| description | Background Familial hypercholesterolemia (FH) may arise from deleterious monogenic variants in FH‐causing genes as well as from a polygenic cause. We evaluated the relationships between monogenic FH and polygenic hypercholesterolemia in influencing the long‐term response to therapy and the risk of atherosclerosis. Methods and Results A cohort of 370 patients with clinically diagnosed FH were screened for monogenic mutations and a low‐density lipoprotein‐rising genetic risk score >0.69 to identify polygenic cause. Medical records were reviewed to estimate the response to lipid‐lowering therapies and the occurrence of major atherosclerotic cardiovascular events during a median follow‐up of 31.0 months. A subgroup of patients (n=119) also underwent coronary computed tomographic angiography for the evaluation of coronary artery calcium score and severity of coronary stenosis as compared with 135 controls. Two hundred nine (56.5%) patients with hypercholesterolemia were classified as monogenic (FH/M+), 89 (24.1%) as polygenic, and 72 (19.5%) genetically undefined (FH/M−). The response to lipid‐lowering therapy was poorest in monogenic, whereas it was comparable in patients with polygenic hypercholesterolemia and genetically undetermined. Mean coronary artery calcium score and the prevalence of coronary artery calcium >100 units were significantly higher in FH/M+ as compared with both FH/M− and controls. Finally, after adjustments for confounders, we observed a 5‐fold higher risk of incident major atherosclerotic cardiovascular events in FH/M+ (hazard ratio, 4.8; 95% CI, 1.06–21.36; Padj=0.041). Conclusions Monogenic cause of FH is associated with lower response to conventional cholesterol‐lowering therapies as well as with increased burden of coronary atherosclerosis and risk of atherosclerotic‐related events. Genetic testing for hypercholesterolemia is helpful in providing important prognostic information. |
| first_indexed | 2024-12-22T21:52:24Z |
| format | Article |
| id | doaj.art-89970b51b4b849c68ecb0e2543b9295c |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-22T21:52:24Z |
| publishDate | 2021-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-89970b51b4b849c68ecb0e2543b9295c2022-12-21T18:11:20ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802021-05-0110910.1161/JAHA.120.018932Clinical Implications of Monogenic Versus Polygenic Hypercholesterolemia: Long‐Term Response to Treatment, Coronary Atherosclerosis Burden, and Cardiovascular EventsLaura D’Erasmo0Ilenia Minicocci1Alessia Di Costanzo2Giovanni Pigna3Daniela Commodari4Fabrizio Ceci5Anna Montali6Francesca Brancato7Ilaria Stanca8Antonio Nicolucci9Andrea Ascione10Nicola Galea11Iacopo Carbone12Marco Francone13Marianna Maranghi14Marcello Arca15Department of Translational and Precision Medicine "Sapienza" University of Rome Rome ItalyDepartment of Translational and Precision Medicine "Sapienza" University of Rome Rome ItalyDepartment of Translational and Precision Medicine "Sapienza" University of Rome Rome ItalyDepartment of Translational and Precision Medicine "Sapienza" University of Rome Rome ItalyDepartment of Translational and Precision Medicine "Sapienza" University of Rome Rome ItalyDepartment of Experimental Medicine "Sapienza" University of Rome Rome ItalyDepartment of Translational and Precision Medicine "Sapienza" University of Rome Rome ItalyDepartment of Translational and Precision Medicine "Sapienza" University of Rome Rome ItalyDepartment of Translational and Precision Medicine "Sapienza" University of Rome Rome ItalyCORESEARCH Center for Outcomes Research and Clinical Epidemiology Pescara ItalyDepartment of Radiological Sciences, Oncology and Pathology "Sapienza" University of Rome Rome ItalyDepartment of Radiological Sciences, Oncology and Pathology "Sapienza" University of Rome Rome ItalyDepartment of Radiological Sciences, Oncology and Pathology "Sapienza" University of Rome, I.C.O.T. Hospital Latina ItalyDepartment of Radiological Sciences, Oncology and Pathology "Sapienza" University of Rome Rome ItalyDepartment of Translational and Precision Medicine "Sapienza" University of Rome Rome ItalyDepartment of Translational and Precision Medicine "Sapienza" University of Rome Rome ItalyBackground Familial hypercholesterolemia (FH) may arise from deleterious monogenic variants in FH‐causing genes as well as from a polygenic cause. We evaluated the relationships between monogenic FH and polygenic hypercholesterolemia in influencing the long‐term response to therapy and the risk of atherosclerosis. Methods and Results A cohort of 370 patients with clinically diagnosed FH were screened for monogenic mutations and a low‐density lipoprotein‐rising genetic risk score >0.69 to identify polygenic cause. Medical records were reviewed to estimate the response to lipid‐lowering therapies and the occurrence of major atherosclerotic cardiovascular events during a median follow‐up of 31.0 months. A subgroup of patients (n=119) also underwent coronary computed tomographic angiography for the evaluation of coronary artery calcium score and severity of coronary stenosis as compared with 135 controls. Two hundred nine (56.5%) patients with hypercholesterolemia were classified as monogenic (FH/M+), 89 (24.1%) as polygenic, and 72 (19.5%) genetically undefined (FH/M−). The response to lipid‐lowering therapy was poorest in monogenic, whereas it was comparable in patients with polygenic hypercholesterolemia and genetically undetermined. Mean coronary artery calcium score and the prevalence of coronary artery calcium >100 units were significantly higher in FH/M+ as compared with both FH/M− and controls. Finally, after adjustments for confounders, we observed a 5‐fold higher risk of incident major atherosclerotic cardiovascular events in FH/M+ (hazard ratio, 4.8; 95% CI, 1.06–21.36; Padj=0.041). Conclusions Monogenic cause of FH is associated with lower response to conventional cholesterol‐lowering therapies as well as with increased burden of coronary atherosclerosis and risk of atherosclerotic‐related events. Genetic testing for hypercholesterolemia is helpful in providing important prognostic information.https://www.ahajournals.org/doi/10.1161/JAHA.120.018932atherosclerosiscardiovascular diseasegeneticshypercholesterolemiatherapy |
| spellingShingle | Laura D’Erasmo Ilenia Minicocci Alessia Di Costanzo Giovanni Pigna Daniela Commodari Fabrizio Ceci Anna Montali Francesca Brancato Ilaria Stanca Antonio Nicolucci Andrea Ascione Nicola Galea Iacopo Carbone Marco Francone Marianna Maranghi Marcello Arca Clinical Implications of Monogenic Versus Polygenic Hypercholesterolemia: Long‐Term Response to Treatment, Coronary Atherosclerosis Burden, and Cardiovascular Events Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease atherosclerosis cardiovascular disease genetics hypercholesterolemia therapy |
| title | Clinical Implications of Monogenic Versus Polygenic Hypercholesterolemia: Long‐Term Response to Treatment, Coronary Atherosclerosis Burden, and Cardiovascular Events |
| title_full | Clinical Implications of Monogenic Versus Polygenic Hypercholesterolemia: Long‐Term Response to Treatment, Coronary Atherosclerosis Burden, and Cardiovascular Events |
| title_fullStr | Clinical Implications of Monogenic Versus Polygenic Hypercholesterolemia: Long‐Term Response to Treatment, Coronary Atherosclerosis Burden, and Cardiovascular Events |
| title_full_unstemmed | Clinical Implications of Monogenic Versus Polygenic Hypercholesterolemia: Long‐Term Response to Treatment, Coronary Atherosclerosis Burden, and Cardiovascular Events |
| title_short | Clinical Implications of Monogenic Versus Polygenic Hypercholesterolemia: Long‐Term Response to Treatment, Coronary Atherosclerosis Burden, and Cardiovascular Events |
| title_sort | clinical implications of monogenic versus polygenic hypercholesterolemia long term response to treatment coronary atherosclerosis burden and cardiovascular events |
| topic | atherosclerosis cardiovascular disease genetics hypercholesterolemia therapy |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.120.018932 |
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