亚临床甲状腺功能减退与慢性收缩性心力衰竭患者预后关系的meta分析

doi:10.3969/j.issn.1004-583X.2022.10.004

摘要/Abstract

摘要：

目的系统性评价亚临床甲状腺功能减退对慢性收缩性心力衰竭患者预后的影响。方法计算机检索Pubmed、Embase、Web of Science、Cochrane Library、中国生物医学文献数据库、中国知网、万方、维普数据库,检索时限为建库至2022年5月,依据纳入排除标准筛选亚临床甲状腺功能减退与慢性收缩性心力衰竭预后关系的文献,提取资料,应用纽卡斯尔-渥太华评价量表(NOS)评价纳入文献的质量。采用Stata 12.0进行统计分析,计数资料采用风险比(HR)及其95%可信区间(95%CI)为效应量。结果共纳入9篇文献,总计21 723例慢性收缩性心力衰竭患者(其中亚临床甲状腺功能减退组1 225例,甲状腺功能正常组19 120例)被纳入meta分析。结果显示:与甲状腺功能正常组相比,亚临床甲状腺功能减退是慢性收缩性心力衰竭患者全因死亡(HR=1.58,95%CI:1.30~1.92)、心脏事件和(或)再住院(HR=1.42,95%CI:1.16~1.73)的风险因素。亚组分析中亦显示亚临床甲状腺功能减退是慢性收缩性心力衰竭患者不良预后的因素。其中,随访时间小于24个月与慢性收缩性心力衰竭全因死亡的相关性最强(HR=2.50),亚洲人群与慢性收缩性心力衰竭心脏事件和(或)再住院风险的相关性最强(HR=1.59)。结论亚临床甲状腺功能减退可能是慢性收缩性心力衰竭患者全因死亡、心血管事件和(或)再住院的风险因素。

关键词: 甲状腺功能减退症, 心力衰竭, 收缩性, 预后, meta分析

Abstract:

Objective To systematically evaluate the effect of subclinical hypothyroidism (SCH) on prognosis of patients with chronic systolic heart failure (CSHF). Methods A computer search was conducted in Web of Science, Cochrane Library, Chinese Biomedical Database (CBM), China National Knowledge Internet (CNKI), Wanfang, VIP database up to May 2022. The literatures regarding SCH-related prognosis of CSHF patients were extracted based on predefined inclusion/exclusion criteria. The Newcastle-Ottawa scale (NOS) was performed to evaluate the relevant data extracted, a Meta-analysis was conducted using STATA 12.0 statistical software, and the hazard ratio (HR) and its 95% confidence interval (95%CI) were used as the effect quantities. Results Eligible 9 literatures representing 21 723 CSHF patients (hypothyroidism in 1 225; euthyroidism in 19 120) were included in the meta-analysis. Meta-analysis results showed that all-cause mortality (HR=1.58, 95%CI: 1.30-1.92), cardiovascular adverse event and (or) re-hospitalization (HR=1.42, 95%CI: 1.16-1.73) were risk factors for hypothyroidism as compared to euthyroidism. SCH was associated with poor prognosis of CSHF patients in subgroup analysis. The less than 24 months follow-ups were most strongly associated with all-cause mortality (HR=2.50), Asian CSHF patients were most strongly associated with cardiovascular adverse event and (or) re-hospitalization(HR=1.59). Conclusion SCH might be associated with the risk factors for all-cause mortality, cardiovascular events, and/or hospitalization of CHF patients.

Key words: hypothyroidism, systolic heart failure, prognosis, meta-analysis

中图分类号:

左秀秀, 侯天华, 王宏祥. 亚临床甲状腺功能减退与慢性收缩性心力衰竭患者预后关系的meta分析[J]. 临床荟萃, 2022, 37(10): 905-911.

Zuo Xiuxiu, Hou Tianhua, Wang Hongxiang. Effect of subclinical hypothyroidism on prognosis of patients with chronic systolic heart failure: A meta-analysis[J]. Clinical Focus, 2022, 37(10): 905-911.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: http://www.lchc.cn/CN/10.3969/j.issn.1004-583X.2022.10.004

http://www.lchc.cn/CN/Y2022/V37/I10/905

图/表 6

参考文献 31

[1]	Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the heart failure society of America[J]. Circulation, 2017, 136(6):e137-e161.
[2]	Ning N, Gao D, Triggiani V, et al. Prognostic role of hypothyroidism in heart failure: A meta-analysis[J]. Medicine (Baltimore), 2015, 94(30):e1159. doi: 10.1097/MD.0000000000001159 URL
[3]	Bielecka-Dabrowa A, Godoy B, Suzuki T, et al. Subclinical hypothyroidism and the development of heart failure: An overview of risk and effects on cardiac function[J]. Clin Res Cardiol, 2019, 108(3):225-233. doi: 10.1007/s00392-018-1340-1 pmid: 30091084
[4]	杨宜恒, 郑振中. 亚临床甲状腺功能减退对心力衰竭患者预后影响的Meta分析[J]. 实用心脑肺血管病杂志, 2021, 29(5):70-74.
[5]	Yang G, Wang Y, Ma A, et al. Subclinical thyroid dysfunction is associated with adverse prognosis in heart failure patients with reduced ejection fraction[J]. BMC Cardiovasc Disord, 2019, 19(1):83. doi: 10.1186/s12872-019-1055-x URL
[6]	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses[J]. Eur J Epidemiol, 2010, 25(9):603-605. doi: 10.1007/s10654-010-9491-z pmid: 20652370
[7]	Iacoviello M, Guida P, Guastamacchia E, et al. Prognostic role of sub-clinical hypothyroidism in chronic heart failure outpatients[J]. Curr Pharm Des, 2008, 14(26):2686-2692. doi: 10.2174/138161208786264142 URL
[8]	Sato Y, Yoshihisa A, Kimishima Y, et al. Subclinical hypothyroidism is associated with adverse prognosis in heart failure patients[J]. Can J Cardiol, 2018, 34(1):80-87. doi: S0828-282X(17)31110-8 pmid: 29275887
[9]	Kannan L, Shaw PA, Morley MP, et al. Thyroid dysfunction in heart failure and cardiovascular outcomes[J]. Circ Heart Fail, 2018, 11(12):e005266. doi: 10.1161/CIRCHEARTFAILURE.118.005266 URL
[10]	Frey A, Kroiss M, Berliner D, et al. Prognostic impact of subclinical thyroid dysfunction in heart failure[J]. Int J Cardiol, 2013, 168(1):300-305. doi: 10.1016/j.ijcard.2012.09.064 pmid: 23041000
[11]	Wang W, Guan H, Gerdes AM, et al. Thyroid status, cardiac function, and mortality in patients with idiopathic dilated cardiomyopathy[J]. J ClinEndocrinol Metab, 2015, 100(8):3210-3218. doi: 10.1210/jc.2014-4159 URL
[12]	Li X, Yang X, Wang Y, et al. The prevalence and prognostic effects of subclinical thyroid dysfunction in dilated cardiomyopathy patients: A single-center cohort study[J]. J Card Fail, 2014, 20(7):506-512. doi: 10.1016/j.cardfail.2014.05.002 pmid: 24858054
[13]	刘凯, 陈英, 郑杨, 等. 亚临床甲状腺功能减退对老年心力衰竭病人预后的影响[J]. 实用老年医学, 2019, 33(11):1108-1112.
[14]	Rhee CM, Curhan GC, Alexander EK, et al. Subclinical hypothyroidism and survival: The effects of heart failure and race[J]. J Clin Endocrinol Metab, 2013, 98(6):2326-2336. doi: 10.1210/jc.2013-1039 pmid: 23720788
[15]	Shuichi K, Shohei K, Hiroo S, et al. Subclinical hypothyroidism is a useful predictor of adverse events in heart failure patients with reduced left ventricular ejection fraction[J]. J CARD FAIL, 2015, 21(10):S187.
[16]	Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: The Whickham survey[J]. Clin Endocrinol (Oxf), 1977, 7(6):481-493. doi: 10.1111/j.1365-2265.1977.tb01340.x URL
[17]	Canaris GJ, Manowitz NR, Mayor G, et al. The Colorado thyroid disease prevalence study[J]. Arch Intern Med, 2000, 160(4):526-534. doi: 10.1001/archinte.160.4.526 pmid: 10695693
[18]	Kannan L, Shaw PA, Morley MP, et al. Thyroid dysfunction in heart failure and cardiovascular outcomes[J]. Circ Heart Fail, 2018, 11(12):e005266. doi: 10.1161/CIRCHEARTFAILURE.118.005266 URL
[19]	Lam CS, Lyass A, Kraigher-Krainer E, et al. Cardiac dysfunction and noncardiac dysfunction as precursors of heart failure with reduced and preserved ejection fraction in the community[J]. Circulation, 2011, 124(1):24-30. doi: 10.1161/CIRCULATIONAHA.110.979203 pmid: 21670229
[20]	Biondi B. Mechanisms in endocrinology: Heart failure and thyroid dysfunction[J]. Eur J Endocrinol, 2012, 167(5):609-618. doi: 10.1530/EJE-12-0627 pmid: 22956554
[21]	Martínez-Sellés M, García Robles JA, Prieto L, et al. Hospitalized congestive heart failure patients with preserved versus abnormal left ventricular systolic function[J]. Rev Esp Cardiol, 2002, 55(6):579-586. pmid: 12113716
[22]	Ilic S, Tadic M, Ivanovic B, et al. Left and right ventricular structure and function in subclinical hypothyroidism: The effects of one-year levothyroxine treatment[J]. Med Sci Monit, 2013, 19:960-968. doi: 10.12659/MSM.889621 URL
[23]	Tadic M, Ilic S, Kostic N, et al. Subclinical hypothyroidism and left ventricular mechanics: A three-dimensional speckle tracking study[J]. J Clin Endocrinol Metab, 2014, 99(1):307-314. doi: 10.1210/jc.2013-3107 pmid: 24187401
[24]	Mousa S, Hemeda A, Ghorab H, et al. Arterial wall stiffness and the risk of atherosclerosis in egyptian patients with overt and subclinical hypothyroidism[J]. Endocr Pract, 2020, 26(2):161-166. doi: 10.4158/EP-2019-0322 pmid: 31557076
[25]	Saif A, Mousa S, Assem M, et al. Endothelial dysfunction and the risk of atherosclerosis in overt and subclinical hypothyroidism[J]. Endocr Connect, 2018, 7(10):1075-1080. doi: 10.1530/EC-18-0194 pmid: 30352390
[26]	Swaid B, Kheiri B, Sundus S, et al. The effect of levothyroxine treatment in individuals with subclinical hypothyroidism on surrogate markers of atherosclerosis: A meta-analysis of randomized controlled trials[J]. J Community Hosp Intern Med Perspect, 2019, 9(4):305-309.
[27]	Sengupta S, Jaseem T, Ambalavanan J, et al. Homeostatic model assessment-insulin resistance (HOMA-IR 2) in mild subclinical hypothyroid subjects[J]. Indian J Clin Biochem, 2018, 33:214-217. doi: 10.1007/s12291-017-0647-4 URL
[28]	Treister-Goltzman Y, Yarza S, Peleg R. Lipid profile in mild subclinical hypothyroidism: Systematic review and meta-analysis[J]. Minerva Endocrinol (Torino), 2021, 46(4):428-440.
[29]	Hueston WJ, Pearson WS. Subclinical hypothyroidism and the risk of hypercholesterolemia[J]. Ann Fam Med, 2004, 2(4):351-355. pmid: 15335135
[30]	Jayasingh IA, Puthuran P. Subclinical hypothyroidism and the risk of hypercholesterolemia[J]. J Family Med Prim Care, 2016, 5(4):809-816. doi: 10.4103/2249-4863.201177 pmid: 28348996
[31]	Papadopoulou AM, Bakogiannis N, Skrapari I, et al. Thyroid dysfunction and atherosclerosis: A systematic review[J]. In Vivo, 2020, 34(6):3127-3136. doi: 10.21873/invivo.12147 pmid: 33144416

作者	年份	国家	总人数/甲状腺正常人数/亚临床甲减人数	TSH界值(mIU/L)		随访时间(月)	平均年龄(岁)	男性占比(%)	结局	调整因素
作者	年份	国家	总人数/甲状腺正常人数/亚临床甲减人数	对照组	试验组	随访时间(月)	平均年龄(岁)	男性占比(%)	结局	调整因素
Iacoviello等^[7]	2008	意大利	338/304/34	>0.35	>5.5	16	64	77	心脏事件全因死亡住院率	年龄,糖尿病,NYHA分级,平均动脉压,心率,心房颤动,左室射血分数,左室舒张末期内径、心肌梗死、肾小球滤过率,血红蛋白,钠离子,NT-proBNP、ACEI或ARB药物的缺乏治疗
Sato等^[8]	2018	日本	1100/911/132	>0.4	>4	36	67	73	心脏事件全因死亡	年龄,性别,体重指数,收缩压,心率,NYHA分级,是否有缺血性因素,高血压、糖尿病、慢性肾脏病,贫血,心房颤动,吸烟史,钠离子,C反应蛋白,BNP,左室射血分数
Kannan等^[9]	2018	美国	1365/1006/74	>0.45	>4.51	50	56.6	65	心脏事件全因死亡	年龄,性别,种族,体重指数,缺血性病因,胺碘酮的使用,甲状腺药物使用
Frey等^[10]	2013	德国	758/628/34	>0.3	>4.0	37	68	71	全因死亡	年龄
Wang等^[11]	2015	中国	458/353/41	>0.55	>4.78	17	51	71	住院率心脏事件全因死亡	年龄,性别,贫血,肾脏功能障碍,高脂血症,吸烟,糖尿病
Li等^[12]	2014	中国	963/816/79	>0.35	>5.5	42	52.1	73.7	全因死亡	年龄,性别,高血压史,心房颤动,室性心动过速,饮酒吸烟,左室直径,左房直径,左室射血分数,FT3,T3,T4,亚临床甲亢,亚临床甲减
刘凯等^[13]	2019	中国	1100/911/132	>0.4	>4	36.6	71.3	55.8	心脏事件全因死亡	年龄、性别、体重指数、收缩压,心率,NYHA分级,缺血性心脏病,高血压,糖尿病,血脂水平,慢性肾病,贫血,心房颤动,吸烟史,血钠,C-反应蛋白、BNP和左室射血分数
Rhee等^[14]	2013	美国	15570/14130/691	>0.39	>4.6	429	46.7	46.5	全因死亡	年龄,性别,种族,糖尿病,吸烟,高血压,高胆固醇血症,BMI,既往脑卒中,心肌梗死
Shuichi等^[15]	2015	日本	71/61/8	>0.35	>5.5	无	无	无	住院率	无

作者	年份	国家	总人数/甲状腺正常人数/亚临床甲减人数	TSH界值(mIU/L)		随访时间(月)	平均年龄(岁)	男性占比(%)	结局	调整因素
作者	年份	国家	总人数/甲状腺正常人数/亚临床甲减人数	对照组	试验组	随访时间(月)	平均年龄(岁)	男性占比(%)	结局	调整因素
Iacoviello等^[7]	2008	意大利	338/304/34	>0.35	>5.5	16	64	77	心脏事件全因死亡住院率	年龄,糖尿病,NYHA分级,平均动脉压,心率,心房颤动,左室射血分数,左室舒张末期内径、心肌梗死、肾小球滤过率,血红蛋白,钠离子,NT-proBNP、ACEI或ARB药物的缺乏治疗
Sato等^[8]	2018	日本	1100/911/132	>0.4	>4	36	67	73	心脏事件全因死亡	年龄,性别,体重指数,收缩压,心率,NYHA分级,是否有缺血性因素,高血压、糖尿病、慢性肾脏病,贫血,心房颤动,吸烟史,钠离子,C反应蛋白,BNP,左室射血分数
Kannan等^[9]	2018	美国	1365/1006/74	>0.45	>4.51	50	56.6	65	心脏事件全因死亡	年龄,性别,种族,体重指数,缺血性病因,胺碘酮的使用,甲状腺药物使用
Frey等^[10]	2013	德国	758/628/34	>0.3	>4.0	37	68	71	全因死亡	年龄
Wang等^[11]	2015	中国	458/353/41	>0.55	>4.78	17	51	71	住院率心脏事件全因死亡	年龄,性别,贫血,肾脏功能障碍,高脂血症,吸烟,糖尿病
Li等^[12]	2014	中国	963/816/79	>0.35	>5.5	42	52.1	73.7	全因死亡	年龄,性别,高血压史,心房颤动,室性心动过速,饮酒吸烟,左室直径,左房直径,左室射血分数,FT3,T3,T4,亚临床甲亢,亚临床甲减
刘凯等^[13]	2019	中国	1100/911/132	>0.4	>4	36.6	71.3	55.8	心脏事件全因死亡	年龄、性别、体重指数、收缩压,心率,NYHA分级,缺血性心脏病,高血压,糖尿病,血脂水平,慢性肾病,贫血,心房颤动,吸烟史,血钠,C-反应蛋白、BNP和左室射血分数
Rhee等^[14]	2013	美国	15570/14130/691	>0.39	>4.6	429	46.7	46.5	全因死亡	年龄,性别,种族,糖尿病,吸烟,高血压,高胆固醇血症,BMI,既往脑卒中,心肌梗死
Shuichi等^[15]	2015	日本	71/61/8	>0.35	>5.5	无	无	无	住院率	无

作者	暴露组代表性	非暴露组代表性	暴露因素确定	研究时没有要观察的结局指标	是否控制混杂因素	盲法独立	随访时间是否足够长	随访完整性	总分(分)
Iacoviello等^[7]	1	1	1	1	1	1	0	1	7
Sato等^[8]	1	1	1	1	1	1	1	1	8
Kannan等^[9]	1	1	1	1	1	1	1	1	8
Frey等^[10]	1	1	1	1	1	1	1	1	8
Wang等^[11]	1	1	1	1	1	1	0	1	7
Li等^[12]	1	1	1	1	2	1	1	1	9
刘凯等^[13]	1	1	1	0	1	1	1	1	7
Rhee等^[14]	1	1	1	1	1	1	1	1	8
Shuichi等^[15]	1	1	1	0	1	0	0	1	5

作者	暴露组代表性	非暴露组代表性	暴露因素确定	研究时没有要观察的结局指标	是否控制混杂因素	盲法独立	随访时间是否足够长	随访完整性	总分(分)
Iacoviello等^[7]	1	1	1	1	1	1	0	1	7
Sato等^[8]	1	1	1	1	1	1	1	1	8
Kannan等^[9]	1	1	1	1	1	1	1	1	8
Frey等^[10]	1	1	1	1	1	1	1	1	8
Wang等^[11]	1	1	1	1	1	1	0	1	7
Li等^[12]	1	1	1	1	2	1	1	1	9
刘凯等^[13]	1	1	1	0	1	1	1	1	7
Rhee等^[14]	1	1	1	1	1	1	1	1	8
Shuichi等^[15]	1	1	1	0	1	0	0	1	5

亚组	全因死亡					心脏事件和(或)再住院
	文章数量	异质性检验		Meta分析		文章数量	异质性检验		Meta分析
	文章数量	I²(%)	P	HR	95%CI	文章数量	I²(%)	P	HR	95%CI
种族
欧美洲	4	2.7	0.379	1.59	1.29-1.97	2	86.5	0.006	1.11	1.06-1.15
亚洲	4	66.6	0.029	1.56	1.28-1.90	3	60.3	0.081	1.59	1.29-1.96
年龄
≤65岁	5	54.4	0.076	1.74	1.44-2.10	3	89.6	0.000	1.11	1.07-1.16
>65岁	3	0	0.703	1.37	1.09-1.71	2	0	0.976	1.42	1.13-1.79
随访时间
≤24月	2	0	0.347	2.50	1.76-3.56	2	91.7	0.001	1.11	1.06-1.15
>24月	6	0	0.637	1.44	1.23-1.69	3	0	0.532	1.53	1.26-1.86
样本量
≤1 000例	4	70.4	0.017	1.73	1.33-2.24	2	91.7	0.001	1.11	1.06-1.15
>1 000例	4	0	0.729	1.52	1.28-1.80	3	0	0.532	1.53	1.26-1.86