Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden;
Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden; Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Clin Chem. 2016 Mar;62(3):485-93. doi: 10.1373/clinchem.2015.246876. Epub 2016 Jan 14.
There is increasing interest in measurements of cardiovascular (CV) biomarker concentrations for risk prediction in the general population. We investigated the prognostic utility of a panel of novel CV biomarkers including biomarker changes over time.
We measured concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional proadrenomedullin, high-sensitivity cardiac troponin I, growth-differentiation factor-15 (GDF-15), soluble ST2 (sST2), and galectin-3 at baseline and 5 years later in 1016 elderly individuals participating in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Assessed outcomes included all-cause mortality and fatal and nonfatal CV events (in participants without CV disease at baseline) during 10 years of follow-up.
GDF-15 exhibited the strongest association with all-cause mortality (n = 158) with a hazard ratio (HR) per 1-SD increase in standardized ln GDF-15 of 1.68 (95% CI, 1.44-1.96). NT-proBNP was the only biomarker to predict CV events (n = 163; HR 1.54 [95% CI, 1.30-1.84]). GDF-15 and NT-proBNP also improved metrics of discrimination and reclassification of the respective outcomes. Changes in GDF-15 concentrations between 70 and 75 years predicted all-cause mortality whereas changes in NT-proBNP predicted both outcomes. The other biomarkers and their temporal changes provided only moderate prognostic value apart from sST2 which had a neutral relationship with adverse events.
Evaluation of temporal changes in GDF-15 and NT-proBNP concentrations improves risk prediction in an elderly population. These findings are of considerable interest given the emphasis on biomarkers as tools to identify and monitor at-risk individuals with preclinical and potentially modifiable stages of CV disease.
人们对心血管（CV）生物标志物浓度的测量越来越感兴趣，以便在普通人群中进行风险预测。我们研究了包括随时间变化的生物标志物变化在内的一组新型 CV 生物标志物的预后效用。
我们在 Prospective Investigation of the Vasculature in Uppsala Seniors（PIVUS）研究中测量了 1016 名参与研究的老年人基线时和 5 年后的 N 末端脑利钠肽前体（NT-proBNP）、中区域前肾上腺髓质素、高敏心肌肌钙蛋白 I、生长分化因子 15（GDF-15）、可溶性 ST2（sST2）和半乳糖凝集素 3 的浓度。评估的结果包括 10 年随访期间的全因死亡率和致命及非致命性 CV 事件（在基线时无 CV 疾病的参与者中）。
GDF-15 与全因死亡率的相关性最强（n = 158），标准化 ln GDF-15 每增加 1-SD，风险比（HR）为 1.68（95%CI，1.44-1.96）。NT-proBNP 是唯一能预测 CV 事件的生物标志物（n = 163；HR 1.54 [95%CI，1.30-1.84]）。GDF-15 和 NT-proBNP 也改善了各自结局的判别和重新分类的指标。70 至 75 岁之间 GDF-15 浓度的变化预测全因死亡率，而 NT-proBNP 的变化预测两种结局。除 sST2 外，其他生物标志物及其时间变化仅提供了适度的预后价值，sST2 与不良事件之间呈中性关系。
评估 GDF-15 和 NT-proBNP 浓度的时间变化可改善老年人群的风险预测。鉴于将生物标志物作为识别和监测处于临床前和潜在可改变阶段的 CV 疾病高危人群的工具的重要性，这些发现具有相当大的意义。
