Clonal hematopoiesis is associated with cardiovascular events in patients with stable coronary artery disease
Summary: Clonal hematopoiesis (CH) is a risk factor for atherosclerotic cardiovascular disease, but the impact of smaller clones and the effect on inflammatory parameters is largely unknown. Using ultrasensitive single-molecule molecular inversion probe sequencing, we evaluated the association betwe...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422400693X |
| _version_ | 1797248316451323904 |
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| author | Mihaela I. Dregoesc Helin Tercan Adrian B. Țigu Siroon Bekkering Leo AB. Joosten Mihai G. Netea Rosanne C. van Deuren Alexander Hoischen Niels P. Riksen Adrian C. Iancu |
| author_facet | Mihaela I. Dregoesc Helin Tercan Adrian B. Țigu Siroon Bekkering Leo AB. Joosten Mihai G. Netea Rosanne C. van Deuren Alexander Hoischen Niels P. Riksen Adrian C. Iancu |
| author_sort | Mihaela I. Dregoesc |
| collection | DOAJ |
| description | Summary: Clonal hematopoiesis (CH) is a risk factor for atherosclerotic cardiovascular disease, but the impact of smaller clones and the effect on inflammatory parameters is largely unknown. Using ultrasensitive single-molecule molecular inversion probe sequencing, we evaluated the association between CH and a first major adverse cardiovascular event (MACE) in patients with angiographically documented stable coronary artery disease (CAD) and no history of acute ischemic events. CH was associated with an increased rate of MACE at four years follow-up. The size of the clone predicted MACE at an optimal cut-off value of 1.07% variant allele frequency (VAF). Mutation carriers had no change in monocytes subsets or cytokine production capacity but had higher levels of circulating tissue factor, matrilysin, and proteinase-activated receptor-1. Our study identified CH driver mutations with a VAF as small as 1.07% as a residual cardiovascular risk factor and identified potential biomarkers and therapeutic targets for patients with stable CAD. |
| first_indexed | 2024-04-24T20:12:39Z |
| format | Article |
| id | doaj.art-f86bcc0f47134c969cae7c331a450621 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-24T20:12:39Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-f86bcc0f47134c969cae7c331a4506212024-03-23T06:25:43ZengElsevieriScience2589-00422024-04-01274109472Clonal hematopoiesis is associated with cardiovascular events in patients with stable coronary artery diseaseMihaela I. Dregoesc0Helin Tercan1Adrian B. Țigu2Siroon Bekkering3Leo AB. Joosten4Mihai G. Netea5Rosanne C. van Deuren6Alexander Hoischen7Niels P. Riksen8Adrian C. Iancu9“Iuliu Hatieganu” University of Medicine and Pharmacy, Department of Cardiology –“Niculae Stăncioiu” Heart Institute, 19-21 Calea Moților, 400001 Cluj-Napoca, RomaniaRadboud University Medical Center, Department of Internal Medicine and Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, the NetherlandsMEDFUTURE Research Center for Advanced Medicine, Department of Translational Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 4-6 Louis Pasteur, 400349 Cluj-Napoca, RomaniaRadboud University Medical Center, Department of Internal Medicine and Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, the NetherlandsRadboud University Medical Center, Department of Internal Medicine and Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, the Netherlands; Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, 4-6 Louis Pasteur, 400349 Cluj-Napoca, RomaniaRadboud University Medical Center, Department of Internal Medicine and Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, the Netherlands; Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Carl-Troll-Str. 31, 53115 Bonn, GermanyRadboud University Medical Center, Department of Human Genetics, Geert Grooteplein Zuid 855, 6525 GA Nijmegen, the NetherlandsRadboud University Medical Center, Department of Internal Medicine and Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, the Netherlands; Radboud University Medical Center, Department of Human Genetics, Geert Grooteplein Zuid 855, 6525 GA Nijmegen, the Netherlands; Radboud Expertise Center for Immunodeficiency and Autoinflammation and Radboud Center for Infectious Disease (RCI), Radboud University Medical Center, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, the NetherlandsRadboud University Medical Center, Department of Internal Medicine and Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, the Netherlands; Corresponding author“Iuliu Hatieganu” University of Medicine and Pharmacy, Department of Cardiology –“Niculae Stăncioiu” Heart Institute, 19-21 Calea Moților, 400001 Cluj-Napoca, Romania; Corresponding authorSummary: Clonal hematopoiesis (CH) is a risk factor for atherosclerotic cardiovascular disease, but the impact of smaller clones and the effect on inflammatory parameters is largely unknown. Using ultrasensitive single-molecule molecular inversion probe sequencing, we evaluated the association between CH and a first major adverse cardiovascular event (MACE) in patients with angiographically documented stable coronary artery disease (CAD) and no history of acute ischemic events. CH was associated with an increased rate of MACE at four years follow-up. The size of the clone predicted MACE at an optimal cut-off value of 1.07% variant allele frequency (VAF). Mutation carriers had no change in monocytes subsets or cytokine production capacity but had higher levels of circulating tissue factor, matrilysin, and proteinase-activated receptor-1. Our study identified CH driver mutations with a VAF as small as 1.07% as a residual cardiovascular risk factor and identified potential biomarkers and therapeutic targets for patients with stable CAD.http://www.sciencedirect.com/science/article/pii/S258900422400693XHealth sciencesCardiovascular medicine |
| spellingShingle | Mihaela I. Dregoesc Helin Tercan Adrian B. Țigu Siroon Bekkering Leo AB. Joosten Mihai G. Netea Rosanne C. van Deuren Alexander Hoischen Niels P. Riksen Adrian C. Iancu Clonal hematopoiesis is associated with cardiovascular events in patients with stable coronary artery disease iScience Health sciences Cardiovascular medicine |
| title | Clonal hematopoiesis is associated with cardiovascular events in patients with stable coronary artery disease |
| title_full | Clonal hematopoiesis is associated with cardiovascular events in patients with stable coronary artery disease |
| title_fullStr | Clonal hematopoiesis is associated with cardiovascular events in patients with stable coronary artery disease |
| title_full_unstemmed | Clonal hematopoiesis is associated with cardiovascular events in patients with stable coronary artery disease |
| title_short | Clonal hematopoiesis is associated with cardiovascular events in patients with stable coronary artery disease |
| title_sort | clonal hematopoiesis is associated with cardiovascular events in patients with stable coronary artery disease |
| topic | Health sciences Cardiovascular medicine |
| url | http://www.sciencedirect.com/science/article/pii/S258900422400693X |
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