Cellular Adhesion Molecules and Adverse Outcomes in Chronic Heart Failure: Findings From the DAPA-HF Randomized Clinical Trial.

Systemic levels of VCAM-1 are associated with incident heart failure (HF).

VCAM-1的系统水平与发生心力衰竭（HF）有关。

Background

To determine if VCAM-1 and ICAM-1 levels are associated with progression of established HF.

确定VCAM-1和ICAM-1水平是否与已建立的心力衰竭（HF）的进展有关。

DESIGN, SETTING, AND PARTICIPANTS: Participants enrolled in the biomarker substudy of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) randomized clinical trial had VCAM-1 and ICAM-1 levels measured at baseline and 12 months.

设计、环境和参与者：在 dapagliflozin 和预防心力衰竭不良结果（DAPA-HF）随机临床试验的生物标志物子研究中注册的参与者在基线和12个月时测量了VCAM-1和ICAM-1水平。

The DAPA-HF trial was conducted at 410 sites in 20 countries.

DAPA-HF试验在20个国家的410个地点进行。

Patients with HF and reduced ejection fraction (HFrEF) in New York Heart Association (NYHA) class II to IV with elevated natriuretic peptides were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019.

招募了心力衰竭且射血分数降低（HFrEF）的患者，这些患者为纽约心脏病协会（NYHA）II至IV级，且心钠肽水平升高，招募时间为2017年2月15日至2018年8月17日，最终随访时间为2019年6月6日。

Data were analyzed from January 2023 to January 2025.

数据分析的时间范围是从2023年1月到2025年1月。

Methods

Dapagliflozin, 10 mg, once daily vs placebo.

达格列净，每日一次10毫克，与安慰剂进行比较。

main_outcomes_and_measures

The primary outcome was the composite of a worsening HF event or cardiovascular death.

主要结果是心力衰竭恶化事件或心血管死亡的复合终点。

The associations between VCAM-1 and ICAM-1 levels at baseline and the primary outcome, its components, and all-cause death were analyzed using Cox proportional hazards regression models adjusted for known prognostic variables including estimated glomerular filtration rate (eGFR), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hs-TnT), as well as high-sensitivity C-reactive protein.

使用Cox比例风险回归模型分析了基线时VCAM-1和ICAM-1水平与主要结果、其组成部分以及全因死亡之间的关联，这些模型已经根据已知的预后变量进行了调整，包括估算的肾小球滤过率(eGFR)、N末端前体B型利钠肽(NT-proBNP)和高敏肌钙蛋白T(hs-TnT)，以及高敏C反应蛋白。

Results

A total of 3051 participants (mean [SD] age, 67.2 [10.5] years; 2386 male [78.2%]) were included in this study.

本研究共纳入3051名参与者（平均年龄[标准差]为67.2[10.5]岁；2386名为男性[占78.2%]）

Mean (SD) follow-up time was 17.6 (5.2) months.

平均随访时间为17.6（标准差5.2）个月。

The median (IQR) baseline VCAM-1 level was 997 (816.7-1218.8) ng/mL.

基线VCAM-1水平的中位数（四分位数间距）为997（816.7-1218.8）ng/mL。

Compared with patients with lower concentrations of VCAM-1, those with higher concentrations of VCAM-1 were older (mean [SD] age T3 vs T1, 69.7 [9.7] years vs 64.1 [10.7] years; P < .001), in worse NYHA class (T3 vs T1, NYHA class III/IV 35.6% [362 of 1017] vs 26.5% [269 of 1017]; P < .001), and had higher NT-proBNP (median [IQR] T3 vs T1, 2018 [1126-3753] pg/mL vs 1118 [693-1830] pg/mL) and hs-TnT (median [IQR] T3 vs T1, 24.7 [17.1-37.5] ng/L vs 16.6 [11.6-24.9] ng/L) concentrations, and lower eGFR (mean [SD] T3 vs T1, 58.4 [17.6] mL/min/1.73 m2 vs 71.7 [18.0] mL/min/1.73 m2).

与VCAM-1浓度较低的患者相比，VCAM-1浓度较高的患者年龄较大（平均[标准差]年龄T3 vs T1，69.7 [9.7]岁 vs 64.1 [10.7]岁；P < .001），纽约心脏病协会（NYHA）心功能分级更差（T3 vs T1，NYHA III/IV级35.6% [362/1017] vs 26.5% [269/1017]；P < .001），NT-proBNP（中位数[四分位数间距]T3 vs T1，2018 [1126-3753] pg/mL vs 1118 [693-1830] pg/mL）和hs-TnT（中位数[四分位数间距]T3 vs T1，24.7 [17.1-37.5] ng/L vs 16.6 [11.6-24.9] ng/L）浓度更高，而估算的肾小球滤过率（eGFR）较低（平均[标准差]T3 vs T1，58.4 [17.6] mL/min/1.73 m2 vs 71.7 [18.0] mL/min/1.73 m2）。

Patients in tertile 3 of VCAM-1, compared with tertile 1, had the highest risk of each outcome (eg, adjusted hazard ratio[HR] for primary outcome 1.40; 95% CI, 1.11-1.77; P = .004).

VCAM-1第三三分位数的患者，与第一三分位数相比，每种结果的风险最高（例如，主要结果的调整后风险比[HR]为1.40；95%置信区间，1.11-1.77；P = .004）。

ICAM-1 level was not associated with an elevated risk of any outcome.

ICAM-1水平与任何结果的增加风险无关。

The benefit of dapagliflozin vs placebo in reducing the risk of the primary outcome was consistent across VCAM-1 tertiles: HR, 0.76 (95% CI, 0.54-1.06), 0.82 (95% CI, 0.59-1.12), and 0.77 (95% CI, 0.61-0.98) for tertiles 1, 2 and 3, respectively (P for interaction = .93).

与安慰剂相比，达格列净降低主要结果风险的益处，在VCAM-1三分位数中是一致的：第一三分位数、第二三分位数和第三三分位数的HR分别为0.76（95% 置信区间, 0.54-1.06）、0.82（95% 置信区间, 0.59-1.12）和0.77（95% 置信区间, 0.61-0.98）（交互作用P值= .93）。

There was no significant change in VCAM-1 level with dapagliflozin at 52 weeks.

在52周时，达格列净对VCAM-1水平没有显著改变。

conclusions_and_relevance

Results of this substudy of the DAPA-HF randomized clinical trial demonstrate that higher VCAM-1 levels, possibly reflecting a distinct inflammatory/immune pathophysiological pathway in HFrEF, were associated with worse outcomes, even after adjustment for conventional prognostic variables.

DAPA-HF随机临床试验的这项子研究结果显示，较高的VCAM-1水平可能反映了HFrEF中一种独特的炎症/免疫病理生理途径，并且与较差的结果相关，即使在调整了传统预后变量后也是如此。

trial_registration

ClinicalTrials.gov Identifier: NCT03036124.

临床试验注册号：NCT03036124。