Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.
Comprehensive Heart Failure Center, University Hospital and University of Würzburg, Würzburg, Germany.
Eur J Heart Fail. 2017 Mar;19(3):314-323. doi: 10.1002/ejhf.706. Epub 2016 Dec 18.
Psychopathologies may occur in heart failure (HF) and can be associated with adverse outcomes. Amongst neuropeptide S receptor gene functional sequence variants, the T-allele [asparagine(107)isoleucine, NPSR1 rs324981] has been identified as a risk factor for increased anxiety/overinterpretation of bodily symptoms. We investigated all-cause death and re-hospitalization (composite primary endpoint, CPEP) and healthcare utilization in patients hospitalized for decompensated systolic HF with the TT vs. the AT/AA genotype.
Participants in the Interdisciplinary Network Heart Failure programme were eligible if consenting to genetic testing (n = 924) and randomization to usual care (UC, n = 464) or nurse-co-ordinated disease management (DM, n = 460). Follow-up was 180 days (100% complete). Compared with AT/AA carriers (n = 726), TT genotype carriers (n = 198) had more CPEP events [47% vs. 39%, hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.01-1.61, P = 0.044] and were more frequently re-hospitalized (43% vs. 35%, HR 1.31, 95% CI 1.02-1.67, P = 0.033); mortality rate was similar in both groups (HR 1.11, 95% CI 0.68-1.81, P = 0.664). In subjects undergoing DM, CPEP and re-hospitalization occurred more often in TT (51% and 47%) than in AT/AA carriers (36% and 33%; HR 2.14, 95% CI 1.44-3.19, and HR 2.29, 95% CI 1.52-3.44, genotype/treatment interaction both P = 0.007). Furthermore, TT genotype carriers undergoing DM visited cardiologists and other specialists more often than AT/AA carriers (P = 0.009 and P = 0.005). With UC, event rates did not differ between genotype subgroups.
We identified a psychogenetic determinant of clinical outcomes and healthcare utilization after acute HF, which was modulated by the type of care. Future investigations need to clarify whether NPSR1 genotyping might further enhance the concept of 'personalized' medicine in HF.
ISRCTN23325295.
心理病理学可能发生在心力衰竭（HF）中，并与不良结局相关。在神经肽 S 受体基因功能序列变异体中，T 等位基因[天冬酰胺（107）异亮氨酸，NPSR1 rs324981]已被确定为增加焦虑/过度解释身体症状的风险因素。我们研究了所有原因的死亡和再住院（复合主要终点，CPEP）以及因失代偿性收缩性 HF 住院的患者的医疗保健利用情况，T 等位基因 TT 与 AT/AA 基因型相比。
如果同意进行基因检测（n = 924）并随机分配至常规护理（UC，n = 464）或护士协调的疾病管理（DM，n = 460），则符合条件的患者可参加跨学科网络心力衰竭计划。随访时间为 180 天（100%完整）。与 AT/AA 携带者（n = 726）相比，TT 基因型携带者（n = 198）发生 CPEP 事件的频率更高[47% vs. 39%，风险比（HR）1.27，95%置信区间（CI）1.01-1.61，P = 0.044]，再住院的频率也更高[43% vs. 35%，HR 1.31，95% CI 1.02-1.67，P = 0.033]；两组的死亡率相似（HR 1.11，95% CI 0.68-1.81，P = 0.664）。在接受 DM 治疗的患者中，TT 比 AT/AA 携带者（HR 2.14，95% CI 1.44-3.19 和 HR 2.29，95% CI 1.52-3.44，基因型/治疗相互作用均 P = 0.007）更频繁地发生 CPEP 和再住院。接受 DM 的 TT 基因型携带者比 AT/AA 携带者更频繁地就诊于心内科医生和其他专家（P = 0.009 和 P = 0.005）。在 UC 组中，基因型亚组之间的事件发生率没有差异。
我们确定了急性 HF 后临床结局和医疗保健利用的心理遗传学决定因素，该因素受治疗类型的调节。未来的研究需要阐明 NPSR1 基因分型是否可以进一步增强 HF 中“个体化”医学的概念。
ISRCTN23325295。
