{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:13:05Z","timestamp":1789409585026,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Disease-related anorexia-cachexia is associated with poor prognosis of patients with cardiovascular disease (CVD) or cancer. Growth differentiation factor-15 (GDF-15) has emerged as a central regulator of appetite and body weight. However, the exact role of GDF-15 in lean patients has not been elucidated.<\/jats:p><jats:p><jats:bold>Aim:<\/jats:bold> Our aim is to evaluate whether the association of GDF-15 with mortality, including cancer death, differs according to body mass index (BMI) level.<\/jats:p><jats:p><jats:bold>Methods and Results:<\/jats:bold> We collected blood samples from 4,061 patients with CV risk factors who were enrolled in the nationwide practice-based J-HOP (Japan Morning Surge-Home Blood Pressure) study. Serum GDF-15 levels were determined by immunoassay analysis. During a mean follow-up period of 6.6 years, we observed 174 (6.7\/1000 person-year) all-cause deaths, 68 (2.6\/1000 person-year) cancer deaths, and 56 (2.2\/1000 person-year) CV deaths. Patients were stratified according to the cut-points of GDF-15 at 1,200 ng\/L and BMI at 22.5 and 25.0 kg\/m<jats:sup>2<\/jats:sup>. The association between the GDF-15\/BMI based study groups and each outcome was evaluated by Cox-proportional hazard models with adjustment for established risk factors. The multivariate Cox regression model showed that patients with elevated GDF-15 (\u22651,200 ng\/L) and low BMI (&amp;lt;22.5 kg\/m<jats:sup>2<\/jats:sup>) were significantly associated with increased risk of all outcomes [all-cause death, hazard ratio (HR) 3.15, 95% confidence interval (CI) 1.85\u20135.34, <jats:italic>p<\/jats:italic> &amp;lt; 0.001; cancer death, HR 3.52, 95%CI 1.64\u20137.57, <jats:italic>p<\/jats:italic> = 0.001; CV death, HR 2.88, 95%CI 1.20\u20136.92, <jats:italic>p<\/jats:italic> = 0.018, respectively] compared to a reference group with non-elevated GDF-15 and normal BMI (22.5\u201325.0 kg\/m<jats:sup>2<\/jats:sup>). In analyses of a subgroup with low BMI (&amp;lt;22.5 kg\/m<jats:sup>2<\/jats:sup>), patients with elevated GDF-15 had 4.79-fold increased risk of cancer death and 11-fold greater risk of CV death when compared with patients with non-elevated GDF-15 (&amp;lt;1,200 ng\/L) after adjustment for established risk factors.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> In patients with CV risk factors, GDF-15 was associated with all-cause, cancer, and CV death. This relationship was especially remarkable in patients with low BMI. The serum GDF-15 levels in patients with low BMI might be a useful marker to identify the potential for anorexia-cachexia associated with CVD and cancer.<\/jats:p>","DOI":"10.3389\/fcvm.2021.660317","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T04:54:27Z","timestamp":1622782467000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Growth Differentiation Factor 15 Predicts Cancer Death in Patients With Cardiovascular Risk Factors: The J-HOP 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