Are existing and emerging biomarkers associated with cardiorespiratory fitness in patients with chronic heart failure?
Are existing and emerging biomarkers associated with cardiorespiratory fitness in patients with chronic heart failure?
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DOI：
10.1016/j.ahj.2019.11.006
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发表时间：
2020-02-01
影响因子：
4.8
通讯作者：
Felker, G. Michael
中科院分区：
文献类型：
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作者：
Fudim, Marat;Kelly, Jacob P.;Felker, G. Michael
研究背景呼吸适应性（CRF）与心力衰竭（HF）患者的健康状况和临床结局密切相关。我们的目的是测试是否生物标志物可以反映CRF及其随时间的变化。方法此事后分析使用的数据从门诊队列的心力衰竭射血分数降低（HFrEF）（IRONOUT）和心力衰竭保留射血分数（HFpEF）（RELAX）。在基线和16周或24周随访时（分别针对IRONOUT和RELAX）测量了心率运动试验、6分钟步行距离（6 MWD）和血清生物标志物。生物标志物包括N末端B型利钠肽原（NT-proBNP）、可溶性ST 2、生长分化因子-15和半乳糖凝集素-3。基线峰值VO 2、VE/VCO 2斜率和6 MWD显示与HFrEF和HFpEF中所有4种检测生物标志物的加倍轻度相关。多变量校正（包括所有生物标志物）后，生物标志物变化与HFrEF功能参数之间唯一显著相关的是NT-proBNP变化和VE/VCO 2斜率变化（每加倍增加3.596%，95% CI 0.779-6.492，P = 0.012）。在HFpEF中，峰值VO 2降低与NT-proBNP升高相关（-0.726 mL/min/kg/加倍，95% CI -1.100至-0.353，P < .001），6 MWD降低与生长分化因子-15升高相关结论在这些非卧床试验队列中，NT-proBNP与基线和HFrEF和HFpEF的CRF变化相关。相比之下，新型生物标志物似乎不适合作为HF患者运动能力系列评估的可靠替代物，因为除了传统风险因素和NT-proBNP外，与CRF缺乏一致的独立关联。
Background Cardiorespiratory fitness (CRF) is closely linked to health status and clinical outcomes in heart failure (HF) patients. We aimed to test whether biomarkers can reflect CRF and its change over time.Methods This post hoc analysis used data from ambulatory cohorts of heart failure with reduced ejection fraction (HFrEF) (IRONOUT) and heart failure with preserved ejection fraction (HFpEF) (RELAX). Cardiopulmonary exercise testing, 6-minute walk distance (6MWD), and serum biomarkers were measured at baseline and 16- or 24-week follow-up (for IRONOUT and RELAX respectively). Biomarkers included N-terminal pro-B type natriuretic peptide (NT-proBNP), soluble ST2, growth differentiation factor-15, and Galectin-3.Results Analysis included 225 patients with HFrEF and 216 with HFpEF. Baseline peak VO2, VE/VCO2 slope, and 6MWD showed a mild correlation with the doubling of all 4 tested biomarkers in HFrEF and HFpEF. Following multivariable adjustment (including all biomarkers), the only significant association between change in biomarker and functional parameter in HFrEF was change in NT-proBNP and change in VE/VCO2 slope (3.596% increase per doubling, 95% CI 0.779-6.492, P = .012). In HFpEF, a decrease in peak VO2 was associated with an increase in NT-proBNP (-0.726 mL/min/kg per doubling, 95% CI -1.100 to -0.353, P < .001), and a decrease in 6MWD was associated with an increase in growth differentiation factor-15 (-31.606 m per doubling, 95% CI -61.404 to -1.809, P = .038).Conclusions In these ambulatory trial cohorts, NT-proBNP was associated with baseline and change in CRF in HFrEF and HFpEF. In contrast, novel biomarkers do not appear suitable as a reliable surrogate for serial assessment of exercise capacity in HF patients given lack of consistent independent association with CRF beyond traditional risk factors and NT-proBNP.