Associations of Serum Urate and Cardiovascular Events in a Clinical Trial of Interleukin-1β Blockade
Background: Serum urate (SU) associates with cardiovascular (CV) events, mortality, and gout. Objectives: The purpose of this study was to assess whether SU predicts CV risk in a trial of interleukin (IL)-1β inhibition with canakinumab, and whether IL-1β blockade, kidney function, or gout alter thes...
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Elsevier
2025-03-01
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| Series: | JACC: Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772963X24008640 |
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| author | Nicholas H. Adamstein, MD Jean G. MacFadyen, BA Brittany N. Weber, MD, PhD Peter Libby, MD Daniel H. Solomon, MD, MPH Paul M Ridker, MD, MPH |
| author_facet | Nicholas H. Adamstein, MD Jean G. MacFadyen, BA Brittany N. Weber, MD, PhD Peter Libby, MD Daniel H. Solomon, MD, MPH Paul M Ridker, MD, MPH |
| author_sort | Nicholas H. Adamstein, MD |
| collection | DOAJ |
| description | Background: Serum urate (SU) associates with cardiovascular (CV) events, mortality, and gout. Objectives: The purpose of this study was to assess whether SU predicts CV risk in a trial of interleukin (IL)-1β inhibition with canakinumab, and whether IL-1β blockade, kidney function, or gout alter these associations. Methods: This study is a subanalysis of the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS), which randomized 10,061 patients with prior myocardial infarction and elevated high-sensitivity C-reactive protein to 3 doses of canakinumab or placebo. SU was measured at baseline. Cox proportional hazards models compared major adverse cardiovascular events (MACE), CV death, and all-cause mortality among those with SU ≤6.8 mg/dL (normal), 6.8 to 9.0 mg/dL (elevated), and ≥9.0 mg/dL (markedly elevated). Cox regressions were repeated within subgroups, including canakinumab vs placebo, estimated glomerular filtration rate ≥60 vs <60 mL/min, and gout vs no gout. Results: Markedly elevated SU associated with MACE (HR: 1.66 [95% CI: 1.38-1.99]; P < 0.0001), CV death (HR: 2.52 [95% CI: 1.98-3.21]; P < 0.0001), and all-cause mortality (HR: 2.43 [95% CI: 2.01-2.94]; P < 0.0001) compared to normal SU. After multivariable adjustment for a minimal set of potential confounders, SU independently predicted all 3 endpoints. Associations were unchanged after IL-1β blockade with canakinumab. For normal estimated glomerular filtration rate, SU associated with CV and all-cause mortality, but not MACE. Participants with gout had higher event rates independent of SU. Conclusions: In over 10,000 patients with coronary artery disease, individuals with markedly elevated SU have elevated CV risk despite aggressive treatment. IL-1β blockade did not modify these associations. Baseline kidney function and monosodium urate deposition may function as effect modifiers. |
| format | Article |
| id | doaj-art-702c9a4c2a674a03bcbb65f168163ccc |
| institution | Kabale University |
| issn | 2772-963X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
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| series | JACC: Advances |
| spelling | doaj-art-702c9a4c2a674a03bcbb65f168163ccc2025-01-26T05:05:24ZengElsevierJACC: Advances2772-963X2025-03-0143101583Associations of Serum Urate and Cardiovascular Events in a Clinical Trial of Interleukin-1β BlockadeNicholas H. Adamstein, MD0Jean G. MacFadyen, BA1Brittany N. Weber, MD, PhD2Peter Libby, MD3Daniel H. Solomon, MD, MPH4Paul M Ridker, MD, MPH5Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA; Address for correspondence: Dr Nicholas H. Adamstein, Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, 900 Commonwealth Avenue, Boston, Massachusetts 02215, USA.Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USADivision of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USADivision of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USADivision of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USACenter for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USABackground: Serum urate (SU) associates with cardiovascular (CV) events, mortality, and gout. Objectives: The purpose of this study was to assess whether SU predicts CV risk in a trial of interleukin (IL)-1β inhibition with canakinumab, and whether IL-1β blockade, kidney function, or gout alter these associations. Methods: This study is a subanalysis of the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS), which randomized 10,061 patients with prior myocardial infarction and elevated high-sensitivity C-reactive protein to 3 doses of canakinumab or placebo. SU was measured at baseline. Cox proportional hazards models compared major adverse cardiovascular events (MACE), CV death, and all-cause mortality among those with SU ≤6.8 mg/dL (normal), 6.8 to 9.0 mg/dL (elevated), and ≥9.0 mg/dL (markedly elevated). Cox regressions were repeated within subgroups, including canakinumab vs placebo, estimated glomerular filtration rate ≥60 vs <60 mL/min, and gout vs no gout. Results: Markedly elevated SU associated with MACE (HR: 1.66 [95% CI: 1.38-1.99]; P < 0.0001), CV death (HR: 2.52 [95% CI: 1.98-3.21]; P < 0.0001), and all-cause mortality (HR: 2.43 [95% CI: 2.01-2.94]; P < 0.0001) compared to normal SU. After multivariable adjustment for a minimal set of potential confounders, SU independently predicted all 3 endpoints. Associations were unchanged after IL-1β blockade with canakinumab. For normal estimated glomerular filtration rate, SU associated with CV and all-cause mortality, but not MACE. Participants with gout had higher event rates independent of SU. Conclusions: In over 10,000 patients with coronary artery disease, individuals with markedly elevated SU have elevated CV risk despite aggressive treatment. IL-1β blockade did not modify these associations. Baseline kidney function and monosodium urate deposition may function as effect modifiers.http://www.sciencedirect.com/science/article/pii/S2772963X24008640serum urateatherosclerosismajor adverse cardiovascular eventsinflammationcytokinesgout |
| spellingShingle | Nicholas H. Adamstein, MD Jean G. MacFadyen, BA Brittany N. Weber, MD, PhD Peter Libby, MD Daniel H. Solomon, MD, MPH Paul M Ridker, MD, MPH Associations of Serum Urate and Cardiovascular Events in a Clinical Trial of Interleukin-1β Blockade JACC: Advances serum urate atherosclerosis major adverse cardiovascular events inflammation cytokines gout |
| title | Associations of Serum Urate and Cardiovascular Events in a Clinical Trial of Interleukin-1β Blockade |
| title_full | Associations of Serum Urate and Cardiovascular Events in a Clinical Trial of Interleukin-1β Blockade |
| title_fullStr | Associations of Serum Urate and Cardiovascular Events in a Clinical Trial of Interleukin-1β Blockade |
| title_full_unstemmed | Associations of Serum Urate and Cardiovascular Events in a Clinical Trial of Interleukin-1β Blockade |
| title_short | Associations of Serum Urate and Cardiovascular Events in a Clinical Trial of Interleukin-1β Blockade |
| title_sort | associations of serum urate and cardiovascular events in a clinical trial of interleukin 1β blockade |
| topic | serum urate atherosclerosis major adverse cardiovascular events inflammation cytokines gout |
| url | http://www.sciencedirect.com/science/article/pii/S2772963X24008640 |
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