基于潜在类别分析对使用ARNI的HFpEF患者临床特征及预后影响因素研究

贺文超; 朱慕诚; 苏全斌; 张琦; 曾文宝; 姚思琪; 张正义

doi:10.16766/j.cnki.issn.1674-4152.003835

基于潜在类别分析对使用ARNI的HFpEF患者临床特征及预后影响因素研究

doi: 10.16766/j.cnki.issn.1674-4152.003835

1.
兰州大学第二医院(第二临床医学院)全科医学科，甘肃兰州 730000
2.
兰州大学第二医院心内科，甘肃兰州 730000
3.
兰州市临夏路街道社区卫生服务中心，甘肃兰州 730000

基金项目:

甘肃省科技计划项目 23YFFFA0039

详细信息

通讯作者:
张正义，E-mail：zhangzhengyi11@lzu.edu.com

中图分类号: R541.6
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出版历程
- 收稿日期: 2024-07-18
- 网络出版日期: 2025-02-13

A study on clinical characteristics and prognostic factors of HFpEF patients using ARNI based on latent class analysis

1.
Department of General Practice, the Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu 730000, China

摘要

摘要: 目的应用潜在类别分析方法，观察血管紧张素受体脑啡肽酶抑制剂(ARNI)在射血分数保留的心衰(HFpEF)患者中的疗效，分析影响患者预后的因素及相关不同特征亚型。方法收集2018年12月—2023年6月在兰州大学第二医院住院并使用ARNI的HFpEF患者的临床数据，并进行1年随访。采用LASSO回归筛选变量，通过潜在类别分析(LCA)探索患者亚组，确定最佳聚类数，比较各表型组间临床特征及预后的差异。结果 HFpEF住院患者1年死亡率为37.9%(85例)。与未死亡组比较，死亡组患者年龄更大，肌酐、N末端B型利钠肽原(NT-proBNP)、血糖、尿素氮更高，BMI、淋巴细胞计数、血钙、白蛋白较低。LCA确定4个表型：表型1为肾功能较好、合并肺动脉高压和心房颤动的超重中老年患者，预后较好；表型2为肾功能差、NT-proBNP最高、合并多种疾病的高龄患者，预后较差；表型3为年龄最小、肾功能最好、心力衰竭症状轻、营养条件佳、合并症少，预后最好；表型4为BMI、血糖、血清白蛋白最低，肾功能最差，合并肺动脉高压、慢性阻塞性肺疾病的高龄患者，预后最差。结论高龄、营养状态差、肾功能不全、合并肺动脉高压是HFpEF患者死亡的影响因素。本研究发现4种具有不同特征及预后差异的HFpEF患者表型，为HFpEF患者应用ARNI提供了新的依据。
- 射血分数保留型心力衰竭 /
- 血管紧张素受体脑啡肽酶抑制剂 /
- 潜在类别分析
Abstract: Objective This study applied the potential category analysis method with the aim of observing the efficacy of angiotensin receptor enkephalinase inhibitors in patients with HFpEF and analyzing the factors affecting the prognosis of the patients and the related different characteristic subtypes. Methods Clinical data of HFpEF patients hospitalized in the Second Hospital of Lanzhou University with ARNI from December 2018 to June 2023 were collected with a one-year follow-up. LASSO regression was used to screen variables, and patient subgroups were explored by latent class analysis (LCA) to determine the optimal number of clusters and to compare the differences in clinical characteristics and prognosis between phenotype groups. Results The 1-year mortality rate for patients hospitalized with HFpEF was 37.9% (85 cases). Compared with patients in the nonfatal group, deceased patients were older, had higher creatinine, NT-proBNP, glucose, and urea nitrogen; and had lower BMI, lymphocytes, blood calcium, and albumin. LCA identified 4 phenotypes: phenotype 1 for overweight middle-aged and elderly patients with better renal function and comorbid pulmonary hypertension and atrial fibrillation, with a better prognosis; and phenotype 2 for elderly patients with poor renal function, the highest NT-proBNP, and comorbidities, with poor prognosis; phenotype 3 with the youngest age, the best renal function, mild symptoms of heart failure, good nutritional condition, and fewer comorbidities, with the best prognosis; and phenotype 4 with the lowest BMI, glucose, and serum albumin, the worst renal function, and a combination of pulmonary arterial hypertension, chronic obstructive pulmonary disease, with the poorest prognosis. Conclusion Advanced age, poor nutritional status, renal insufficiency, and combined pulmonary hypertension are influential factors in the mortality of patients with HFpEF. The discovery of four HFpEF patient phenotypes with different characteristics and prognostic differences provides a new basis for the application of ARNI in HFpEF patients.
- Heart failure with preserved ejection /
- Angiotensin receptor-neprilysin inhibitor /
- Latent class analysis

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图 1 LASSO回归模型最佳惩罚系数(λ)变化过程

Figure 1. The evolution of the optimal penalty coefficient (λ) in the LASSO regression model

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图 2 各亚组LCA分析结果

Figure 2. Results of LCA analysis for each subgroup

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表 1 2组HFpEF患者一般资料及实验室指标比较

Table 1. Comparison of general information and laboratory indicators between two groups of HFpEF patients

项目	合计(n=224)	死亡组(n=85)	未死亡组(n=139)	统计量	P值
年龄[M(P₂₅, P₇₅), 岁]	72.5(64.0, 81.0)	80.0(71.0, 84.0)	68.0(54.0, 77.0)	-5.808^a	< 0.001
18~34岁[例(%)]	4(1.8)	0	4(2.9)
35~59岁[例(%)]	45(20.1)	7(8.2)	38(27.3)
60~74岁[例(%)]	76(33.9)	22(25.9)	54(38.9)
75岁以上[例(%)]	99(44.2)	56(65.9)	43(30.9)
性别[例(%)]				0.059^b	0.809
男性	111(49.5)	43(50.6)	68(48.9)
女性	113(50.5)	42(49.4)	71(51.1)
民族[例(%)]				1.483^b	0.830
汉族	190(84.8)	74(87.0)	116(83.5)
回族	23(10.3)	8(9.4)	15(10.8)
藏族	6(2.7)	1(1.2)	5(3.6)
其他	5(2.2)	2(2.4)	3(2.1)
脉搏(x±s, 次/min)	82.4±20.7	84.0±23.5	81.3±18.9	-0.928^c	0.354
收缩压(x±s, mmHg)	136.1±25.3	136.1±23.6	136.2±26.3	0.032^c	0.974
舒张压(x±s, mmHg)	79.0±17.9	78.1±15.6	79.6±19.1	0.625^c	0.532
BMI(x±s)	24.9±4.9	22.9±4.2	26.1±4.9	4.948^c	< 0.001
Ly(x±s, ×10⁹/L)	1.25±0.55	1.11±0.52	1.34±0.55	3.106^c	0.002
GLU[M(P₂₅, P₇₅), mmol/L]	6.3(5.3, 7.8)	7.2(5.5, 8.8)	5.9(5.1, 7.8)	-2.711^a	0.007
BUN[M(P₂₅, P₇₅), mmol/L]	7.8(5.9, 9.6)	8.5(6.3, 10.4)	7.3(5.7, 8.8)	-2.604^a	0.009
Cr[M(P₂₅, P₇₅), μmol/L]	88.0(70.8, 101.2)	95.6(71.4, 119.3)	86.0(70.0, 99.9)	-2.061^a	0.039
Ca²⁺(x±s, mmol/L)	2.23±0.15	2.20±0.14	2.24±0.15	2.214^c	0.028
ALB(x±s, g/L)	37.21±4.56	35.90±4.30	38.01±4.55	3.435^c	0.001
NT-proBNP[M(P₂₅, P₇₅), pg/mL]	1 724(728, 3 760)	2 295(1 010, 5 030)	1 497(633, 2 993)	-3.374^a	0.001
注：^a为Z值，^b为χ²值，^c为t值。1 mmHg=0.133 kPa。Ly为淋巴细胞计数(lymphocyte count)，GLU为血清葡萄糖(glucose)，BUN为血尿素氮(blood urea nitrogen)，Cr为血肌酐(creatinine)。

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表 2 LCA各亚组HFpEF患者一般资料、实验室指标及合并症比较

Table 2. Comparison of general information, laboratory indicators, and comorbidities in HFpEF patients across LCA subgroups

项目	表型1(n=90)	表型2(n=23)	表型3(n=61)	表型4(n=50)	统计量	P值
年龄^a[M(P₂₅, P₇₅), 岁]	70.5(64.0, 76.0)	80.0(67.0, 82.0)	66.0(50.5, 79.0)	81.0(71.8, 84.3)	33.629^b	< 0.001
18~34岁[例(%)]	2(2.22)	0	2(3.28)	0
35~59岁[例(%)]	17(18.89)	2(8.70)	23(37.70)	3(6.00)
60~75岁[例(%)]	46(51.11)	4(17.39)	13(21.31)	13(26.00)
75岁以上[例(%)]	25(27.78)	17(73.91)	23(37.70)	34(68.00)
脉搏^a(x±s, 次/min)	91.5±22.0	85.2±26.9	73.8±13.9	74.9±14.9	13.427^c	< 0.001
Ly(x±s, ×10⁹/L)	1.28±0.57	1.14±0.42	1.45±0.56	0.99±0.44	7.392^c	< 0.001
BMI^a(x±s)	25.95±4.88	23.48±3.26	26.39±4.54	21.72±4.49	12.564^c	< 0.001
GLU^a[M(P₂₅, P₇₅), mmol/L]	7.7(5.4, 10.4)	7.8(6.3, 7.8)	5.5(5.0, 6.2)	5.9(5.1, 7.8)	29.307^b	< 0.001
BUN^a[M(P₂₅, P₇₅), mmol/L]	6.8(5.6, 8.8)	8.8(8.8, 9.8)	6.5(5.5, 8.8)	9.2(8.1, 15.5)	45.578^b	< 0.001
Cr[M(P₂₅, P₇₅), μmol/L]	83.3(67.4, 99.9)	99.9(94.0, 100.0)	80.0(66.9, 95.5)	99.9(76.6, 136.6)	23.668^b	< 0.001
K^+a[M(P₂₅, P₇₅), mmol/L]	3.5(3.2, 3.9)	4.0(3.9, 4.2)	4.0(3.8, 4.3)	4.0(3.8, 4.7)	52.533^b	< 0.001
Na⁺[M(P₂₅, P₇₅), mmol/L]	138.9(137.3, 140.9)	138.3(136.0, 138.3)	138.5(136.4, 141.0)	137.0(133.9, 139.1)	13.306^b	0.004
Ca²⁺(x±s, mmol/L)	2.21±0.16	2.20±0.11	2.30±0.12	2.18±0.15	8.004^c	< 0.001
Cl^-(x±s, mmol/L)	100.57±5.61	101.68±4.05	103.38±4.43	101.49±5.05	3.775^c	0.011
ALB^a(x±s, g/L)	36.58±4.55	36.76±3.61	40.30±2.97	34.79±4.69	17.997^c	< 0.001
NT-proBNP[M(P₂₅, P₇₅), pg/mL]	1 767(848, 3 572)	3 235(843, 6 341)	945(309, 2 131)	2 291(1 033, 4 810)	21.496^b	< 0.001
高血压[例(%)]	56(62.22)	18(78.26)	43(70.49)	20(40.00)	14.535^d	0.002
脑血管病^a[例(%)]	13(14.44)	17(73.91)	5(8.20)	0	71.180^d	< 0.001
肺动脉高压^a[例(%)]	38(42.22)	3(13.04)	10(16.39)	26(52.00)	22.725^d	< 0.001
呼吸道感染[例(%)]	23(25.56)	6(26.09)	3(4.92)	15(30.00)	13.444^d	0.004
心房颤动[例(%)]	39(43.33)	11(47.83)	17(27.87)	18(36.00)	4.774^d	0.189
2型糖尿病[例(%)]	16(17.78)	6(26.09)	6(9.84)	6(12.00)	4.343^d	0.227
慢性阻塞性肺疾病^a[例(%)]	9(10.00)	6(26.09)	0	31(62.00)	74.999^d	< 0.001
胸腔积液[例(%)]	22(24.44)	3(13.04)	3(4.92)	17(34.00)	16.547^d	0.001
腹腔积液^a[例(%)]	4(4.44)	0	0	1(2.00)	3.949^d	0.267
1年内死亡[例(%)]	32(35.56)	13(56.52)	11(18.03)	29(58.00)	22.401^d	< 0.001
注：^a指纳入潜在类别分析的变量。^b为H值，^c为F值，^d为χ²值。

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