Sanders-van Wijk Sandra, Masson Serge, Milani Valentina, Rickenbacher Peter, Gorini Marco, Tavazzi Luigi T, Tobler Daniel, Rickli Hans, Latini Roberto, Brunner-La Roccaenen Hans-Peter
Maastricht University Medical Center, Maastricht, the Netherlands;
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy;
Clin Chem. 2016 Apr;62(4):605-16. doi: 10.1373/clinchem.2015.246850. Epub 2016 Mar 2.
Galectin-3 predicts prognosis in heart failure (HF) and may help to select HF patients in need of intensified therapy.
This retrospective post hoc analysis included 219 patients from the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure (TIME-HF) and 631 patients from Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) with HF who had reduced ejection fraction and available galectin-3 plasma concentrations. The interaction between galectin-3, β-blockers, renin-angiotensin system (RAS) blockade, and spironolactone on outcome was evaluated in TIME-CHF and validated in GISSI-HF. End points were all-cause mortality and the composite of mortality with HF hospitalization or any hospitalization.
High galectin-3 concentrations were associated with adverse outcome in both cohorts and remained significantly associated with death after multivariate adjustment [hazard ratio 2.42 (95% CI 1.17-5.01), P = 0.02, in TIME-CHF; 1.47 (1.02-2.10), P = 0.04, in GISSI-HF). In TIME-CHF, patients with low galectin-3 plasma concentrations had a better prognosis when β-blockers were up-titrated, whereas patients with high galectin-3 plasma concentrations did not (interaction P < 0.05 for mortality and death with or without hospitalization). Opposite trends were seen for RAS blockade but were not statistically significant. Patients with high galectin-3 plasma concentrations had neutral prognosis when receiving spironolactone, whereas patients with low galectin-3 plasma concentrations had worse prognosis when receiving spironolactone (interaction P < 0.10 for death with or without hospitalization). In the GISSI-HF validation cohort, these interactions were confirmed for β-blockers (P < 0.05 for all end points) and consistent for RAS blockade (P < 0.10 for death with or without hospitalization), but inconsistent for spironolactone.
Galectin-3 is a mediocre prognostic marker, and galectin-3 concentrations interact with the treatment effect of β-blockers and possibly RAS blockade in patients with systolic HF.
半乳糖凝集素-3可预测心力衰竭（HF）的预后，并可能有助于筛选需要强化治疗的HF患者。
这项回顾性事后分析纳入了219例来自老年充血性心力衰竭强化与标准药物治疗试验（TIME-HF）的患者以及631例来自意大利心力衰竭生存研究组（GISSI-HF）的HF患者，这些患者射血分数降低且有可用的半乳糖凝集素-3血浆浓度。在TIME-CHF中评估了半乳糖凝集素-3、β受体阻滞剂、肾素-血管紧张素系统（RAS）阻滞剂和螺内酯对结局的相互作用，并在GISSI-HF中进行了验证。终点为全因死亡率以及死亡率与HF住院或任何住院的复合结局。
在两个队列中，高半乳糖凝集素-3浓度均与不良结局相关，多变量调整后仍与死亡显著相关[在TIME-CHF中，风险比为2.42（95%CI 1.17-5.01），P = 0.02；在GISSI-HF中为1.47（1.02-2.10），P = 0.04]。在TIME-CHF中，血浆半乳糖凝集素-3浓度低的患者在增加β受体阻滞剂剂量时预后较好，而血浆半乳糖凝集素-3浓度高的患者则不然（死亡率以及有无住院的死亡情况的相互作用P < 0.05）。RAS阻滞剂呈现相反趋势，但无统计学意义。血浆半乳糖凝集素-3浓度高的患者接受螺内酯时预后中性，而血浆半乳糖凝集素-3浓度低的患者接受螺内酯时预后较差（有无住院的死亡情况的相互作用P < 0.10）。在GISSI-HF验证队列中，β受体阻滞剂的这些相互作用得到确认（所有终点P < 0.05），RAS阻滞剂一致（有无住院的死亡情况P < 0.10），但螺内酯不一致。
半乳糖凝集素-3是一个中等的预后标志物，在收缩性HF患者中，半乳糖凝集素-3浓度与β受体阻滞剂以及可能与RAS阻滞剂的治疗效果相互作用。
