Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCE
Abstract Background Obesity is an independent risk factor for cardiovascular disease (CVD) in patients with type 2 diabetes (T2D). However, it is not known to what extent weight fluctuations might be associated with adverse outcomes. We aimed at assessing the associations between extreme weight chan...
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-023-01832-5 |
| _version_ | 1797836655005007872 |
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| author | Giulia Ferrannini Carol Pollock Andrea Natali Yshai Yavin Kenneth W. Mahaffey Ele Ferrannini |
| author_facet | Giulia Ferrannini Carol Pollock Andrea Natali Yshai Yavin Kenneth W. Mahaffey Ele Ferrannini |
| author_sort | Giulia Ferrannini |
| collection | DOAJ |
| description | Abstract Background Obesity is an independent risk factor for cardiovascular disease (CVD) in patients with type 2 diabetes (T2D). However, it is not known to what extent weight fluctuations might be associated with adverse outcomes. We aimed at assessing the associations between extreme weight changes and cardiovascular outcomes in two large randomised controlled trials of canagliflozin in patients with T2D and high cardiovascular (CV) risk. Methods In the study populations of the CANVAS Program and CREDENCE trials, weight change was evaluated between randomization and week 52–78, defining subjects in the top 10% of the entire distribution of weight changes as gainers, subjects in the bottom 10% as losers and the remainder as stable. Univariate and multivariate Cox proportional hazards models were used to test the associations between weight changes categories, randomised treatment and covariates with heart failure hospitalisation (hHF) and the composite of hHF and CV death. Results Median weight gain was 4.5 kg in gainers and median weight loss was 8.5 kg in losers. The clinical phenotype of gainers as well as that of losers were similar to that of stable subjects. Weight change within each category was only slightly larger with canagliflozin than placebo. In both trials, gainers and losers had a higher risk of hHF and of hHF/CV death compared with stable at univariate analysis. In CANVAS, this association was still significant by multivariate analysis for hHF/CV death in both gainers and losers vs. stable (hazard ratio – HR 1.61 [95% confidence interval - CI: 1.20–2.16] and 1.53 [95% CI 1.14–2.03] respectively). Results were similar in CREDENCE for gainers vs. stable (adjusted HR for hHF/CV death 1.62 [95% CI 1.19–2.16]) Conclusions Extremes of weight gain or loss were independently associated with a higher risk of the composite of hHF and CV death. In patients with T2D and high CV risk, large changes in body weight should be carefully assessed in view of individualised management. Trials registration CANVAS ClinicalTrials.gov number: NCT01032629. CREDENCE ClinicalTrials.gov number: NCT02065791 |
| first_indexed | 2024-04-09T15:13:30Z |
| format | Article |
| id | doaj.art-fce672c1b3eb4cc994ec7692bc3da35a |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-04-09T15:13:30Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-fce672c1b3eb4cc994ec7692bc3da35a2023-04-30T11:06:37ZengBMCCardiovascular Diabetology1475-28402023-04-0122111010.1186/s12933-023-01832-5Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCEGiulia Ferrannini0Carol Pollock1Andrea Natali2Yshai Yavin3Kenneth W. Mahaffey4Ele Ferrannini5Department of Medicine Solna, Karolinska InstitutetKolling Institute of Medical Research, Sydney Medical School, University of SydneyDepartment of Clinical and Experimental Medicine, University of PisaJanssen Research & Development, LLC, Welsh & McKean RdsStanford Center for Clinical Research, Department of Medicine, Stanford University School of MedicineCNR Institute of Clinical PhysiologyAbstract Background Obesity is an independent risk factor for cardiovascular disease (CVD) in patients with type 2 diabetes (T2D). However, it is not known to what extent weight fluctuations might be associated with adverse outcomes. We aimed at assessing the associations between extreme weight changes and cardiovascular outcomes in two large randomised controlled trials of canagliflozin in patients with T2D and high cardiovascular (CV) risk. Methods In the study populations of the CANVAS Program and CREDENCE trials, weight change was evaluated between randomization and week 52–78, defining subjects in the top 10% of the entire distribution of weight changes as gainers, subjects in the bottom 10% as losers and the remainder as stable. Univariate and multivariate Cox proportional hazards models were used to test the associations between weight changes categories, randomised treatment and covariates with heart failure hospitalisation (hHF) and the composite of hHF and CV death. Results Median weight gain was 4.5 kg in gainers and median weight loss was 8.5 kg in losers. The clinical phenotype of gainers as well as that of losers were similar to that of stable subjects. Weight change within each category was only slightly larger with canagliflozin than placebo. In both trials, gainers and losers had a higher risk of hHF and of hHF/CV death compared with stable at univariate analysis. In CANVAS, this association was still significant by multivariate analysis for hHF/CV death in both gainers and losers vs. stable (hazard ratio – HR 1.61 [95% confidence interval - CI: 1.20–2.16] and 1.53 [95% CI 1.14–2.03] respectively). Results were similar in CREDENCE for gainers vs. stable (adjusted HR for hHF/CV death 1.62 [95% CI 1.19–2.16]) Conclusions Extremes of weight gain or loss were independently associated with a higher risk of the composite of hHF and CV death. In patients with T2D and high CV risk, large changes in body weight should be carefully assessed in view of individualised management. Trials registration CANVAS ClinicalTrials.gov number: NCT01032629. CREDENCE ClinicalTrials.gov number: NCT02065791https://doi.org/10.1186/s12933-023-01832-5Weight changeObesityHeart failure hospitalizationCardiovascular deathCanagliflozinType 2 diabetes |
| spellingShingle | Giulia Ferrannini Carol Pollock Andrea Natali Yshai Yavin Kenneth W. Mahaffey Ele Ferrannini Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCE Cardiovascular Diabetology Weight change Obesity Heart failure hospitalization Cardiovascular death Canagliflozin Type 2 diabetes |
| title | Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCE |
| title_full | Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCE |
| title_fullStr | Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCE |
| title_full_unstemmed | Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCE |
| title_short | Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCE |
| title_sort | extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death evidence from the canvas program and credence |
| topic | Weight change Obesity Heart failure hospitalization Cardiovascular death Canagliflozin Type 2 diabetes |
| url | https://doi.org/10.1186/s12933-023-01832-5 |
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