服用含噻嗪类利尿剂单片复方制剂发生低钾血症的高血压住院患者中重度低钾血症的影响因素

Factors associated with moderate-to-severe hypokalemia in hospitalized hypertensive patients with thiazide-containing single-pill combination-induced hypokalemia

摘要

目的 探究服用含噻嗪类利尿剂单片复方制剂（SPC）的低钾血症高血压住院患者发生中重度低钾血症的危险因素。方法 采用回顾性分析方法，收集2013年1月1日至2023年12月31日在南京医科大学附属淮安第一医院因低钾血症住院且服用含噻嗪类利尿剂SPC的原发性高血压患者资料。根据纳入患者的血钾水平将研究人群分为轻度低钾血症组（血钾水平3.0～＜3.5 mmol/L）和中重度低钾血症组（血钾水平<3.0 mmol/L）。采用多因素logistic模型分析中重度低钾血症的影响因素，并进行亚组分析。结果 最终纳入研究对象261例，平均年龄（66.62±11.13）岁，女性占54.79%（143例）。轻度低钾血症组165例，中重度低钾血症组96例。中重度低钾血症组服用传统SPC比例[51.04%（49/96）比34.55%（57/165），χ²=6.847，P=0.009]、吸烟比例（χ²=3.977，P=0.046）、饮酒比例（χ²=4.072，P=0.044）高于轻度低钾血症组，血氯（Z=–2.707，P=0.007）、血钙（Z=–2.025，P=0.043）及血磷（Z=–3.097，P=0.002）水平低于轻度低钾血症组。多因素logistic回归分析结果显示，服用传统SPC药物（OR=1.917，95%CI：1.102～3.333，P=0.021），血氯水平（OR=0.940，95%CI：0.900～0.981，P=0.004）为中重度低钾血症的影响因素。亚组分析结果显示，年龄、性别、是否合并糖尿病、是否合并冠心病、是否吸烟、是否饮酒、估算的肾小球滤过率（eGFR）水平这些因素与服用含噻嗪类利尿剂SPC的类型交互作用无统计学意义（均P_交互＞0.05）。结论 在服用含噻嗪类利尿剂SPC发生低钾血症的高血压住院患者中，服用传统SPC和血氯水平是中重度低钾血症的影响因素。

Abstract

Objective To explore the risk-factors for moderate to severe hypokalemia in hospitalized hypertensive patients with hypokalemia who are taking single-pill combination (SPC) containing thiazide diuretics. Methods A retrospective analysis was conducted. Data were collected from patients with essential hypertension who were hospitalized for hypokalemia at Huai'an First People's Hospital, Nanjing Medical University, between January 1, 2013, and December 31, 2023, and who were taking thiazide-containing SPC. Based on serum potassium levels, the subjects were divided into a mild hypokalemia group (serum potassium level: 3.0 to ＜3.5 mmol/L) and a moderate-to-severe hypokalemia group (serum potassium leve: <3.0 mmol/L). Multivariate logistic model was used to analyze the factors related to moderate-to-severe hypokalemia and subgroup analysis was conducted. Results A total of 261 subjects were included, with a mean age of (66.62 ± 11.13) years, and 54.79% (143 cases) were female. Among them, 165 were in the mild hypokalemia group, and 96 were in the moderate-to-severe hypokalemia group. Compared with patients in the mild hypokalemia group, patients in the moderate-to-severe hypokalemia group had a significantly higher proportion of taking traditional SPC (51.04% [49/96]vs 34.55% [57/165],χ² = 6.847, P = 0.009), smokers (χ²= 3.977, P = 0.046), and alcohol consumers (χ²= 4.072, P = 0.044). Additionally, serum chloride (Z = –2.707, P = 0.007), calcium (Z = –2.025, P = 0.043), and phosphorus (Z = –3.097, P = 0.002) levels were significantly lower in the moderate-to-severe hypokalemia group. Multivariate logistic regression analysis showed that taking traditional SPC (OR = 1.917, 95%CI: 1.102 to 3.333, P = 0.021) and serum chloride levels (OR = 0.940, 95%CI: 0.900 to 0.981, P = 0.004) were influencing factors for moderate-to-severe hypokalemia. Subgroup analysis results showed that, the interactions between factors such as age, sex, comorbid diabetes, comorbid coronary heart disease, smoking, alcohol consumption, and estimated glomerular filtration rate (eGFR) level with the type of SPC containing thiazide diuretics were not statistically significant (all P for interaction ＞ 0.05). Conclusion The traditional SPC and serum chloride levels are influencing factors for the moderate-to-severe hypokalemia in hospitalized hypertensive patients taking SPC containing thiazide diuretics.

关键词

单片复方制剂 / 高血压 / 利尿剂 / 低钾血症

Key words

single-pill combination / hypertension / diuretics / hypokalemia

参考文献

[1] 国家心血管病中心, 中国心血管健康与疾病报告编写组, 胡盛寿 . 中国心血管健康与疾病报告2024概要[J]. 中国循环杂志， 2025， 40（6）： 521-559.

[2] 中国高血压防治指南修订委员会, 高血压联盟(中国), 中国医疗保健国际交流促进会高血压病学分会, 等 . 中国高血压防治指南(2024年修订版)[J]. 中华高血压杂志(中英文)， 2024， 32（7）： 603-700.

[3] Cappello B, Chowdhury N, Dorji G, et al. Guideline for the pharmacological treatment of hypertension in adults [Internet][M]. Geneva: World Health Organization, 2021: 11-15.

[4] William MJ, McCarthy Cian P, Maria BR, et al. 2024 ESC guidelines for the management of elevated blood pressure and hypertension[J]. Eur Heart J， 2024， 45（38）： 3912-4018.

[5] 陈丹翔, 谢舒, 汪丽, 等 . 江苏省淮安市社区高血压患者单片复方制剂使用情况及其影响因素分析[J]. 中华全科医师杂志， 2024， 23（5）： 457-462.

[6] Zhao X, Dahal A, Yang Q, et al. Comparison of efficacies of commonly used hypertension treatment modalities: a retrospective study of 1900 participants in a hypertension clinic[J]. Med Sci Monit， 2020， 26： e921211.

[7] 谢舒, 陈丹翔, 汪丽, 等 . 江苏省淮安市社区高血压患者利尿剂使用情况及影响因素的混合研究[J]. 中华高血压杂志(中英文)， 2024， 32（12）： 1141-1148.

[8] 陈丹翔, 谢舒, 汪丽, 等 . 全科医师开具单片复方制剂降压药物处方影响因素的质性研究[J]. 中华全科医师杂志， 2025， 24（2）： 150-155.

[9] Adamczak M, Chudek J, Zejda J, et al. Prevalence of hypokalemia in older persons: results from the PolSenior national survey[J]. Eur Geriatr Med， 2021， 12（5）： 981-987.

[10] Nilsson E, Gasparini A, Ärnlöv J, et al. Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system[J]. Int J Cardiol， 2017， 245： 277-284.

[11] Lin Z, Cheung BMY, Tang V, et al. Incidence of severe hypokalaemia in patients taking indapamide[J]. Intern Emerg Med， 2023， 18（2）： 549-557.

[12] 湖北省基层医学联盟, 朱元州, 尚游, 等 . 高危低钾血症患者加速治疗专家共识(东湖共识)[J]. 中华卫生应急电子杂志， 2023， 9（4）： 193-198.

[13] 中华医学会糖尿病学分会 . 中国糖尿病防治指南(2024版)[J]. 中华糖尿病杂志， 2025， 17（1）： 16-139.

[14] Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease: a report of the American Heart Association/American College of Cardiology joint committee on clinical practice guidelines[J]. Circulation， 2023， 148（9）： e9-e119.

[15] Garimella PS, Tighiouart H, Sarnak MJ, et al. Tubular secretion of creatinine and risk of kidney failure: the modification of diet in renal disease (MDRD) study[J]. Am J Kidney Dis， 2021， 77（6）： 992-994.

[16] 李威, 王德征, 薛晓丹, 等 . 2010—2019年天津市死亡居民吸烟率变化趋势及主要死亡原因构成分析[J]. 中华健康管理学杂志， 2022， 16（8）： 529-534.

[17] 李浩然, 付胜奇, 邢海英, 等 . 三酰甘油葡萄糖指数与动脉硬化性脑小血管病患者情感障碍的相关性研究[J]. 中国脑血管病杂志， 2023， 20（11）： 730-739.

[18] Castro D, Sharma S . Hypokalemia[M]. In: StatPearls. Treasure Island(FL): StatPearls Publishing, 2025: 1-2.

[19] Mobley CM, Bryan AS, Moran AE, et al. Fixed—dose combination medication use among US adults with hypertension: a missed opportunity[J]. J Am Heart Assoc， 2023， 12（4）： e027486.

[20] 陈丹翔, 谢舒, 汪丽, 等 . 社区高血压患者单片复方降压药物服药依从性及血压控制情况的影响因素研究[J]. 中国全科医学， 2025， 28（28）： 3566-3572, 3582.

[21] Huffman MD, Baldridge AS, Lazar D, et al. Efficacy and safety of a four—drug, quarter—dose treatment for hypertension: the QUARTET USA randomized trial[J]. Hypertens Res， 2024， 47（6）： 1668-1677.

[22] Sanuade OA, Jacobson TA, Quintana A, et al. Process evaluation of a double—blind randomized controlled trial to assess the efficacy and safety of a quadruple ultra—low—dose treatment for hypertension within a federally qualified health center network (QUARTET USA)[J]. J Am Heart Assoc， 2024， 13（1）： e032236.

[23] 中国医疗保健国际交流促进会高血压专业委员会, 《基层医疗机构规范高血压用药管理项目》专家组 . 单片复方制剂降压药物在基层医疗机构中的临床应用专家建议[J]. 中华老年心脑血管病杂志， 2020， 22（8）： 810-815.

[24] Hoorn EJ, Bovée DM, Geerse DA, et al. Diet—exercise—induced hypokalemic metabolic alkalosis[J]. Am J Med， 2020， 133（11）： e667-e669.

[25] Little R, Ellison DH . Modifying dietary sodium and potassium intake: an end to the 'salt wars'?[J]. Hypertension， 2024， 81（3）： 415-425.

[26] Wilcox CS, Testani JM, Pitt B . Pathophysiology of diuretic resistance and its implications for the management of chronic heart failure[J]. Hypertension， 2020， 76（4）： 1045-1054.

[27] Suzumoto Y, Zucaro L, Iervolino A, et al. Kidney and blood pressure regulation—latest evidence for molecular mechanisms[J]. Clin Kidney J， 2023， 16（6）： 952-964.

[28] Dominguez Rieg JA, Rieg T . New functions and roles of the Na⁺—H⁺—exchanger NHE3 [J]. Pflugers Arch， 2024， 476（4）： 505-516.

[29] Banken C, Harris AN, Conway R, et al. Correlation of serum chloride concentrations with components of the renin—angiotensin—aldosterone system in a dog with congestive heart failure[J]. J Vet Intern Med， 2024， 38（6）： 3255-3260.

[30] Adin D, Kurtz K, Atkins C, et al. Role of electrolyte concentrations and renin—angiotensin—aldosterone activation in the staging of canine heart disease[J]. J Vet Intern Med， 2020， 34（1）： 53-64.

[31] Stone MS, Martyn L, Weaver CM . Potassium intake, bioavailability, hypertension, and glucose control[J]. Nutrients， 2016， 8（7）： 444.

[32] Rangaswami J, Bhalla V, Blair JEA, et al. Cardiorenal syndrome: classification, pathophysiology, diagnosis, and treatment strategies: a scientific statement from the American Heart Association[J]. Circulation， 2019， 139（16）： e840-e878.

[33] Hendriksen LC, van der Linden PD, Lagro—Janssen ALM, et al. Sex differences associated with adverse drug reactions resulting in hospital admissions[J]. Biol Sex Differ， 2021， 12（1）： 34.

[34] Luo Y, Hao J, Su Z, et al. Prevalence and related factors of hypokalemia in patients with acute ischemic stroke[J]. Int J Gen Med， 2024， 17： 5697-5705.

[35] Gao J, Akbari A, Wang T . Green tea could improve elderly hypertension by modulating arterial stiffness, the activity of the renin/angiotensin/aldosterone axis, and the sodium—potassium pumps in old male rats[J]. J Food Biochem， 2022， 46（12）： e14398.

[36] Sun H, Weaver CM . Rising trend of hypokalemia prevalence in the us population and possible food causes[J]. J Am Coll Nutr， 2021， 40（3）： 273-279.

[37] Hunter RW, Bailey MA . Hyperkalemia: pathophysiology, risk factors and consequences[J]. Nephrol Dial Transplant， 2019， 34（Suppl 3）： iii2-iii11.

基金资助

淮安市自然科学生命健康专项软课题(2023KX0007)