Association Between Circulating GDF‐15 and Cardio‐Renal Outcomes and Effect of Canagliflozin: Results From the CANVAS Trial
Background Studies have suggested that sodium glucose co‐transporter 2 inhibitors exert anti‐inflammatory effects. We examined the association of baseline growth differentiation factor‐15 (GDF‐15), a marker of inflammation and cellular injury, with cardiovascular events, hospitalization for heart fa...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-12-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.121.021661 |
| _version_ | 1797942663923630080 |
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| author | Taha Sen Jingwei Li Brendon L. Neuen Clare Arnott Bruce Neal Vlado Perkovic Kenneth W. Mahaffey Wayne Shaw William Canovatchel Michael K. Hansen Hiddo J. L. Heerspink |
| author_facet | Taha Sen Jingwei Li Brendon L. Neuen Clare Arnott Bruce Neal Vlado Perkovic Kenneth W. Mahaffey Wayne Shaw William Canovatchel Michael K. Hansen Hiddo J. L. Heerspink |
| author_sort | Taha Sen |
| collection | DOAJ |
| description | Background Studies have suggested that sodium glucose co‐transporter 2 inhibitors exert anti‐inflammatory effects. We examined the association of baseline growth differentiation factor‐15 (GDF‐15), a marker of inflammation and cellular injury, with cardiovascular events, hospitalization for heart failure (HF), and kidney outcomes in patients with type 2 diabetes in the CANVAS (Canagliflozin Cardiovascular Assessment Study) and determined the effect of the sodium glucose co‐transporter 2 inhibitor canagliflozin on circulating GDF‐15. Methods and Results The CANVAS trial randomized 4330 people with type 2 diabetes at high cardiovascular risk to canagliflozin or placebo. The association between baseline GDF‐15 and cardiovascular (non‐fatal myocardial infarction, non‐fatal stroke, cardiovascular death), HF, and kidney (40% estimated glomerular filtration rate decline, end‐stage kidney disease, renal death) outcomes was assessed using multivariable adjusted Cox regression models. During median follow‐up of 6.1 years (N=3549 participants with available samples), 555 cardiovascular, 129 HF, and 137 kidney outcomes occurred. Each doubling in baseline GDF‐15 was significantly associated with a higher risk of cardiovascular (hazard ratio [HR], 1.2; 95% CI, 1.0‒1.3), HF (HR, 1.5; 95% CI, 1.2‒2.0) and kidney (HR, 1.5; 95% CI, 1.2‒2.0) outcomes. Baseline GDF‐15 did not modify canagliflozin’s effect on cardiovascular, HF, and kidney outcomes. Canaglifozin treatment modestly lowered GDF‐15 compared with placebo; however, GDF‐15 did not mediate the protective effect of canagliflozin on cardiovascular, HF, or kidney outcomes. Conclusions In patients with type 2 diabetes at high cardiovascular risk, higher GDF‐15 levels were associated with a higher risk of cardiovascular, HF, and kidney outcomes. Canagliflozin modestly lowered GDF‐15, but GDF‐15 reduction did not mediate the protective effect of canagliflozin. |
| first_indexed | 2024-04-10T20:12:13Z |
| format | Article |
| id | doaj.art-458987ece31e41058173b90f40c068fb |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-10T20:12:13Z |
| publishDate | 2021-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-458987ece31e41058173b90f40c068fb2023-01-26T10:36:40ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802021-12-01102310.1161/JAHA.121.021661Association Between Circulating GDF‐15 and Cardio‐Renal Outcomes and Effect of Canagliflozin: Results From the CANVAS TrialTaha Sen0Jingwei Li1Brendon L. Neuen2Clare Arnott3Bruce Neal4Vlado Perkovic5Kenneth W. Mahaffey6Wayne Shaw7William Canovatchel8Michael K. Hansen9Hiddo J. L. Heerspink10Department of Clinical Pharmacy and Pharmacology University of Groningen The NetherlandsThe George Institute for Global HealthUNSW Sydney Sydney AustraliaThe George Institute for Global HealthUNSW Sydney Sydney AustraliaThe George Institute for Global HealthUNSW Sydney Sydney AustraliaThe George Institute for Global HealthUNSW Sydney Sydney AustraliaThe George Institute for Global HealthUNSW Sydney Sydney AustraliaDepartment of Medicine Stanford Center for Clinical Research Stanford University School of Medicine Stanford CAJanssen Research & Development, LLC Raritan NJJanssen Global Services, LLC Raritan NJJanssen Research & Development, LLC Spring House PADepartment of Clinical Pharmacy and Pharmacology University of Groningen The NetherlandsBackground Studies have suggested that sodium glucose co‐transporter 2 inhibitors exert anti‐inflammatory effects. We examined the association of baseline growth differentiation factor‐15 (GDF‐15), a marker of inflammation and cellular injury, with cardiovascular events, hospitalization for heart failure (HF), and kidney outcomes in patients with type 2 diabetes in the CANVAS (Canagliflozin Cardiovascular Assessment Study) and determined the effect of the sodium glucose co‐transporter 2 inhibitor canagliflozin on circulating GDF‐15. Methods and Results The CANVAS trial randomized 4330 people with type 2 diabetes at high cardiovascular risk to canagliflozin or placebo. The association between baseline GDF‐15 and cardiovascular (non‐fatal myocardial infarction, non‐fatal stroke, cardiovascular death), HF, and kidney (40% estimated glomerular filtration rate decline, end‐stage kidney disease, renal death) outcomes was assessed using multivariable adjusted Cox regression models. During median follow‐up of 6.1 years (N=3549 participants with available samples), 555 cardiovascular, 129 HF, and 137 kidney outcomes occurred. Each doubling in baseline GDF‐15 was significantly associated with a higher risk of cardiovascular (hazard ratio [HR], 1.2; 95% CI, 1.0‒1.3), HF (HR, 1.5; 95% CI, 1.2‒2.0) and kidney (HR, 1.5; 95% CI, 1.2‒2.0) outcomes. Baseline GDF‐15 did not modify canagliflozin’s effect on cardiovascular, HF, and kidney outcomes. Canaglifozin treatment modestly lowered GDF‐15 compared with placebo; however, GDF‐15 did not mediate the protective effect of canagliflozin on cardiovascular, HF, or kidney outcomes. Conclusions In patients with type 2 diabetes at high cardiovascular risk, higher GDF‐15 levels were associated with a higher risk of cardiovascular, HF, and kidney outcomes. Canagliflozin modestly lowered GDF‐15, but GDF‐15 reduction did not mediate the protective effect of canagliflozin.https://www.ahajournals.org/doi/10.1161/JAHA.121.021661canagliflozinGDF‐15renal and cardiovascular outcomesSGLT2 inhibitor |
| spellingShingle | Taha Sen Jingwei Li Brendon L. Neuen Clare Arnott Bruce Neal Vlado Perkovic Kenneth W. Mahaffey Wayne Shaw William Canovatchel Michael K. Hansen Hiddo J. L. Heerspink Association Between Circulating GDF‐15 and Cardio‐Renal Outcomes and Effect of Canagliflozin: Results From the CANVAS Trial Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease canagliflozin GDF‐15 renal and cardiovascular outcomes SGLT2 inhibitor |
| title | Association Between Circulating GDF‐15 and Cardio‐Renal Outcomes and Effect of Canagliflozin: Results From the CANVAS Trial |
| title_full | Association Between Circulating GDF‐15 and Cardio‐Renal Outcomes and Effect of Canagliflozin: Results From the CANVAS Trial |
| title_fullStr | Association Between Circulating GDF‐15 and Cardio‐Renal Outcomes and Effect of Canagliflozin: Results From the CANVAS Trial |
| title_full_unstemmed | Association Between Circulating GDF‐15 and Cardio‐Renal Outcomes and Effect of Canagliflozin: Results From the CANVAS Trial |
| title_short | Association Between Circulating GDF‐15 and Cardio‐Renal Outcomes and Effect of Canagliflozin: Results From the CANVAS Trial |
| title_sort | association between circulating gdf 15 and cardio renal outcomes and effect of canagliflozin results from the canvas trial |
| topic | canagliflozin GDF‐15 renal and cardiovascular outcomes SGLT2 inhibitor |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.121.021661 |
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