AimsThe utility of growth differentiation factor‐15 (GDF‐15) in predicting long‐term adverse outcomes in heart failure (HF) patients is not well established. This study explored the relationship between GDF‐15 levels and adverse outcomes in HF patients across various ejection fraction (EF) phenotypes associated with coronary heart disease (CHD) and evaluated the added prognostic value of incorporating GDF‐15 into the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score‐based model.Methods and resultsThis single‐centre cohort study included 823 HF patients, categorized into 230 (27.9%) reduced EF (HFrEF), 271 (32.9%) mid‐range EF (HFmrEF), and 322 (39.1%) preserved EF (HFpEF) groups. The median age was 68.0 years (range: 56.0–77.0), and 245 (29.8%) were females. Compared with the HFrEF and HFmrEF groups, the HFpEF group had a higher GDF‐15 concentration (P = 0.002) and a higher MAGGIC risk score (P < 0.001). We examined the associations between GDF‐15 levels and the risks of all‐cause mortality and HF rehospitalization using Cox regression models. The C‐index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) metrics were employed to assess the incremental prognostic value. During the 9.4 year follow‐up period, 425 patients died, and 484 were rehospitalized due to HF. Multivariate Cox regression analysis revealed that elevated GDF‐15 levels were significantly associated with an increased risk of all‐cause mortality [hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.20–1.54; P < 0.001] and HF rehospitalization (HR = 1.75, 95% CI: 1.57–1.95; P < 0.001) across all HF phenotypes. This association remained significant when GDF‐15 was treated as a categorical variable (high GDF‐15 group: all‐cause death: HR = 1.73, 95% CI: 1.40–2.14; P < 0.001; HF rehospitalization: HR = 3.37, 95% CI: 2.73–4.15; P < 0.001). Inclusion of GDF‐15 in the MAGGIC risk score‐based model provided additional prognostic value for all HF patients (Δ C‐index = 0.021, 95% CI: 0.002–0.041; IDI = 0.011, 95% CI: 0.001–0.025; continuous NRI = 0.489, 95% CI: 0.174–0.629) and HF rehospitalization (Δ C‐index = 0.034, 95% CI: 0.005–0.063; IDI = 0.021, 95% CI: 0.007–0.032; continuous NRI = 0.307, 95% CI: 0.147–0.548), particularly in the HFpEF subgroup.ConclusionsGDF‐15 is identified as an independent risk factor for adverse outcomes in HF patients across the entire EF spectrum in the context of CHD. Integrating GDF‐15 into the MAGGIC risk score‐based model enhances its prognostic capability for adverse outcomes in the general HF population. This incremental prognostic effect was observed specifically in the HFpEF subgroup and not in other subgroups.

中文翻译：

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生长分化因子-15 对全射血分数表型心力衰竭的预后价值

目的 生长分化因子-15 (GDF-15) 在预测心力衰竭 (HF) 患者长期不良结局方面的效用尚未明确。本研究探讨了与冠心病 (CHD) 相关的各种射血分数 (EF) 表型的心力衰竭 (HF) 患者中 GDF-15 水平与不良结局之间的关系，并评估了将 GDF-15 纳入荟萃分析全球组的附加预后价值方法和结果 这项单中心队列研究纳入了 823 名心力衰竭患者，分为 230 名 (27.9%) EF 降低 (HFrEF) 和 271 名 (32.9%) 中等 EF (HFmrEF) ）和 322 个（39.1%）保留 EF (HFpEF) 组。中位年龄为 68.0 岁（范围：56.0-77.0），其中 245 名（29.8%）为女性。与HFrEF和HFmrEF组相比，HFpEF组的GDF-15浓度更高（磷= 0.002) 和更高的 MAGGIC 风险评分 (磷< 0.001）。我们使用 Cox 回归模型检查了 GDF-15 水平与全因死亡率和心力衰竭再住院风险之间的关联。采用 C 指数、综合辨别改善（IDI）和净重分类改善（NRI）指标来评估增量预后价值。在 9.4 年的随访期间，425 名患者死亡，484 名患者因心力衰竭再次住院。多变量 Cox 回归分析显示，GDF-15 水平升高与全因死亡风险增加显着相关[风险比 (HR) = 1.36，95% 置信区间 (CI)：1.20–1.54；磷< 0.001] 和心衰再住院（HR = 1.75，95% CI：1.57–1.95；磷< 0.001) 涵盖所有 HF 表型。当 GDF-15 被视为分类变量时，这种关联仍然显着（高 GDF-15 组：全因死亡：HR = 1.73，95% CI：1.40-2.14；磷< 0.001；心力衰竭再住院：HR = 3.37，95% CI：2.73–4.15；磷< 0.001）。将 GDF-15 纳入基于 MAGGIC 风险评分的模型中，为所有心力衰竭患者提供了额外的预后价值（Δ C 指数 = 0.021，95% CI：0.002-0.041；IDI = 0.011，95% CI：0.001-0.025；连续NRI = 0.489，95% CI：0.174–0.629）和心力衰竭再住院（Δ C 指数 = 0.034，95% CI：0.005–0.063；IDI = 0.021，95% CI：0.007–0.032；连续 NRI = 0.307，95% CI：0.147-0.548），特别是在 HFpEF 亚组中。结论 GDF-15 被确定为 CHD 背景下整个 EF 谱系 HF 患者不良结局的独立危险因素。将 GDF-15 整合到基于 MAGGIC 风险评分的模型中可以增强其对一般心力衰竭人群不良结果的预测能力。这种增加的预后效应在 HFpEF 亚组中尤其明显，而在其他亚组中则没有。