{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:28:53Z","timestamp":1787318933593,"version":"build-2736575974"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>In individuals with type 2 diabetes with cardio-renal disease but no known heart failure (HF), elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), a marker of heart stress, signals higher risk of HF and cardio-kidney complications. This analysis assesses canagliflozin impact on heart stress and outcomes using age-adjusted NT-proBNP thresholds from two major trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>This analysis included 5281 participants from the CANVAS and CREDENCE trials without HF at baseline. NT-proBNP was measured at baseline and year 1, with heart stress defined using age-adjusted NT-proBNP thresholds. Outcomes included a primary composite (end-stage kidney disease, doubling of serum creatinine, kidney or cardiovascular death), kidney composite, HF hospitalization, cardiovascular death, all-cause death, and HF hospitalization or cardiovascular death composite. Multivariable Cox models assessed heart stress, outcomes, and canagliflozin effects. At baseline, 45% of participants had heart stress. Heart stress independently predicted increased risks for all outcomes, with the highest risks in those with persistent or rising NT-proBNP at baseline and year 1. Rising NT-proBNP by year 1 was associated with higher risk as well. Canagliflozin significantly reduced risks in individuals with heart stress, including the primary composite (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62\u20130.84), kidney composite (HR 0.65, 95% CI 0.53\u20130.79), and HF hospitalization (HR 0.68, 95% CI 0.54\u20130.85). Benefits were less pronounced in those without heart stress.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Age-adjusted NT-proBNP thresholds effectively predict cardio-kidney events in at-risk type 2 diabetes individuals without HF. Canagliflozin offers strong cardiovascular and kidney protection, with the greatest benefits in those with heart stress, emphasizing the need for early identification and intervention.<\/jats:p>\n                    <jats:p>Clinical Trial Registrations: CANVAS (NCT01032629), CREDENCE (NCT02065791).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3786","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T12:15:01Z","timestamp":1753100101000},"page":"2887-2896","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Impact of Canagliflozin on Heart Stress and Outcomes: Pooled Insights from CREDENCE and CANVAS"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3044-197X","authenticated-orcid":false,"given":"Antoni","family":"Bayes-Genis","sequence":"first","affiliation":[{"name":"Heart Institute, Hospital Universitari Germans Trias I Pujol, CIBERCV , Badalona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anping","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hypertension Research Laboratory, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambarish","family":"Pandey","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center , Dallas, TX 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