Dept. of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany; Agaplesion Bethesda Hospital, Geriatric Research Unit, Ulm University and Geriatric Center Ulm/Alb-Donau, Ulm, Germany;
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany;
Clin Chem. 2016 Jul;62(7):982-92. doi: 10.1373/clinchem.2016.254755. Epub 2016 May 19.
This study considered whether baseline concentrations and 12-month changes of growth differentiation factor 15 (GDF-15) are associated with subsequent cardiovascular events (CVEs) and total mortality in patients with stable coronary heart disease.
Baseline GDF-15 serum concentrations were measured in 1073 participants in a cardiac rehabilitation program (median follow-up 10 years). GDF-15 associations with subsequent CVE and total mortality were evaluated by Cox-proportional hazards models adjusting for well-established cardiovascular risk factors (Model 2), plus N-terminal probrain natriuretic peptide, high-sensitivity (hs) CRP, and hs cardiac troponin T (Model 3).
In our study population [84.7% men, mean age 59 years, median baseline GDF-15 1232 ng/L (interquartile range, 916, 1674)] we observed 190 CVE and 162 deaths. Compared to participants with GDF-15 <1200 ng/L, increased risk for death was found in participants with GDF-15 ≥1200 and ≤1800 ng/L [hazard ratio (HR) 1.68 (95% CI, 1.08-2.62)] and with GDF-15 >1800 ng/L [HR 1.73 (1.02-2.94)], even in Model 3. The 12-month relative median change was -16.7%. As compared to participants with 12-month relative changes between -20% and 20%, GDF-15 increments >20% were associated with: a) an HR of 1.84 (1.04-3.26) for CVE in Model 2, but found nonsignificant in Model 3; (b) an HR of 2.26 (1.32-3.86) for death even in Model 3.
GDF-15 at baseline is independently associated with subsequent CVE and 10-year total mortality. Twelve-month relative changes remained associated with subsequent CVE when adjusting for well-established cardiovascular risk factors, and with total mortality even after further adjustment for established cardiac biomarkers.
本研究旨在探讨生长分化因子 15（GDF-15）的基线浓度和 12 个月变化与稳定型冠心病患者随后发生心血管事件（CVE）和总死亡率之间的关系。
在心脏康复计划中的 1073 名参与者中测量了基线 GDF-15 血清浓度（中位随访时间为 10 年）。通过 Cox 比例风险模型评估 GDF-15 与随后的 CVE 和总死亡率之间的关系，该模型调整了公认的心血管危险因素（模型 2），外加 N 端脑利钠肽前体、高敏（hs）C 反应蛋白和 hs 心肌肌钙蛋白 T（模型 3）。
在我们的研究人群中[84.7%为男性，平均年龄 59 岁，中位数基线 GDF-15 为 1232ng/L（四分位距，916，1674）]，我们观察到 190 例 CVE 和 162 例死亡。与 GDF-15<1200ng/L 的参与者相比，GDF-15≥1200 且≤1800ng/L[风险比（HR）1.68（95%置信区间，1.08-2.62）]和 GDF-15>1800ng/L[HR 1.73（1.02-2.94）]的参与者死亡风险增加，即使在模型 3中也是如此。12 个月相对中位数变化为-16.7%。与 12 个月相对变化在-20%至 20%之间的参与者相比，GDF-15 增加>20%与以下情况相关：a）模型 2中 CVE 的 HR 为 1.84（1.04-3.26），但在模型 3中无统计学意义；（b）即使在模型 3中，死亡的 HR 也为 2.26（1.32-3.86）。
基线时的 GDF-15 与随后的 CVE 和 10 年总死亡率独立相关。在调整公认的心血管危险因素后，12 个月的相对变化仍与随后的 CVE 相关，即使在进一步调整了既定的心脏生物标志物后，也与总死亡率相关。
