Background

NT-proBNP and hs-cTnT are associated with cardiovascular outcomes and are recommended for measurement in type 2 diabetes (T2D). However, the effects of an intensive lifestyle intervention (ILI) targeting weight loss on cardiac biomarkers and the prognostic association of changes in these biomarkers with risk of adverse cardiovascular outcomes in T2D are not well-established.

Objectives

To evaluate the effects of an ILI on cardiac biomarkers and the association of changes in cardiac biomarkers with risk of cardiovascular outcomes in T2D.

Methods

Participants of the LookAHEAD trial underwent NT-proBNP and hs-cTnT measurement at baseline (N=3,984), 1- and 4-years. The effects of the ILI (vs. diabetes support and education [DSE]) on cardiac biomarkers were assessed using adjusted linear mixed-effect models and summarized as geometric mean ratios (GMR). Associations of longitudinal changes in cardiac biomarkers with risk of cardiovascular outcomes were assessed using adjusted Cox models.

Results

Average baseline NT-proBNP and hs-cTnT was 77 and 10.7 ng/L, respectively. The ILI (vs. DSE) led to an increase in NT-proBNP at 1-year (GMR[95% CI]: 1.14[1.08-1.20]), but this difference was attenuated by 4-years (GMR[95% CI]: 1.01[0.96-1.07]). The ILI (vs. DSE) led to lower hs-cTnT at 1-year (GMR[95% CI]: 0.94[0.91-0.97]) and 4-years (GMR[95% CI]: 0.93 [0.90-0.96]). Participants with meaningful weight loss by 1-year (≥5% vs. <5%) had a significant increase in NT-proBNP in the short-term (year-1) which attenuated in the long-term follow-up (year-4). Meaningful 1-year weight loss was significantly associated with reduction in hs-cTnT in the long-term. In adjusted Cox-models, increase in NT-proBNP was significantly associated with higher risk of the composite ASCVD outcome and HF independent of baseline measure of the cardiac biomarker and changes in risk factors. In contrast, longitudinal increase in hs-cTnT was significantly associated with higher risk of the composite ASCVD outcome but not HF in the most adjusted model.

Conclusions

Among adults with T2D, an ILI led to a significant reduction in hs-cTnT on follow-up but a transient increase in NT-proBNP levels at 1-year that attenuated over time. Longitudinal assessment of NT-proBNP and hs-cTnT provide prognostic information for ASCVD risk while only changes in NT-proBNP predicted HF risk.

中文翻译：

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糖尿病的强化生活方式干预、心脏生物标志物和心血管结局：LookAHEAD 心脏生物标志物辅助研究

 背景

NT-proBNP 和 hs-cTnT 与心血管结局相关，推荐用于 2 型糖尿病 （T2D） 的测量。然而，针对体重减轻的强化生活方式干预 （ILI） 对心脏生物标志物的影响以及这些生物标志物变化与 T2D 不良心血管结局风险的预后关联尚未得到充分证实。

 目标

评估 ILI 对心脏生物标志物的影响以及心脏生物标志物变化与 T2D 心血管结局风险的关联。

 方法

LookAHEAD 试验的参与者在基线 （N=3,984）、1 年和 4 年接受了 NT-proBNP 和 hs-cTnT 测量。使用调整后的线性混合效应模型评估 ILI （vs. 糖尿病支持和教育 [DSE]）对心脏生物标志物的影响，并总结为几何平均比 （GMR）。使用调整后的 Cox 模型评估心脏生物标志物纵向变化与心血管结局风险的关联。

 结果

平均基线 NT-proBNP 和 hs-cTnT 分别为 77 和 10.7 ng/L。ILI （vs. DSE） 导致 1 年 NT-proBNP 增加 （GMR[95% CI]： 1.14[1.08-1.20]），但这种差异在 4 年后减弱 （GMR[95% CI]： 1.01[0.96-1.07]）。ILI （vs. DSE） 导致 1 年 （GMR[95% CI]： 0.94[0.91-0.97]）和 4 年 （GMR[95% CI]： 0.93 [0.90-0.96]） hs-cTnT 降低。到 1 年体重显著减轻的参与者 （≥5% vs. <5%） 在短期 （第 1 年） 内 NT-proBNP 显著增加，在长期随访 （第 4 年） 中减弱。有意义的 1 年体重减轻与长期 hs-cTnT 的降低显着相关。在调整后的 Cox 模型中，NT-proBNP 的增加与复合 ASCVD 结局和 HF 的较高风险显著相关，与心脏生物标志物的基线测量和危险因素的变化无关。相比之下，在调整最多的模型中，hs-cTnT 的纵向增加与复合 ASCVD 结局的较高风险显著相关，但与 HF 无关。

 结论

在患有 T2D 的成人患者中，ILI 导致随访时 hs-cTnT 显着降低，但 1 年时 NT-proBNP 水平短暂增加，并随着时间的推移而减弱。NT-proBNP 和 hs-cTnT 的纵向评估为 ASCVD 风险提供预后信息，而只有 NT-proBNP 的变化可预测 HF 风险。