Abstract: Background Hypertension is a major modifiable risk factor for cardiovascular disease, with its global prevalence continuing to rise. However, the underlying mechanisms remain incompletely understood. Tsukushi (TSK) is a newly identified hepatokine involved in the regulation of glucose and lipid metabolism and has been closely linked to various metabolic disorders that may contribute to the development of hypertension. To date, the relationship between circulating TSK levels and the risk of hypertension remains unclear. Objective To investigate the association between serum TSK levels and hypertension. Methods This cross-sectional study enrolled 143 patients from the Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, between 2018 and 2024 as the hypertension group, and 98 normotensive individuals from the Health Examination Center during the same period as the control group. General clinical data and laboratory parameters were collected. All participants were divided into three groups according to tertiles of serum TSK levels: T1 group ( ≤ 0.8 ng/mL, n=75), T2 group (0.8~1.5 ng/mL, n=87), and T3 group ( ≥ 1.5 ng/mL, n=79). Group comparisons were performed using independent-samples t test, Mann-Whitney U test, and χ2 test. Correlation analysis was used to evaluate the relationships between TSK levels and clinical parameters. Multivariate logistic regression analysis was employed to assess the association between TSK levels and the risk of hypertension. Results Compared with the normotensive group, serum TSK levels were significantly higher in the hypertension group (P<0.01). After adjustment for age, sex, and body mass index, serum TSK levels were positively correlated with systolic blood pressure (r=0.214), diastolic blood pressure (r=0.213), waist circumference (r=0.165), and homeostasis model assessment of insulin resistance (r=0.183), and negatively correlated with high-density lipoprotein cholesterol (r=-0.138) and C-peptide-based β-cell function (HOMA-CP, r=-0.168) (P<0.05). The prevalence of hypertension increased progressively across increasing TSK tertiles, with rates of 48.0%, 57.5%, and 72.2% in the T1, T2, and T3 groups, respectively (P<0.01). Multivariate logistic regression analysis demonstrated that after stepwise adjustment across multiple models, serum TSK levels remained positively associated with the risk of hypertension (OR=1.542, 95%CI=1.054-2.256, P<0.05). Compared with the T1 group, participants in the T3 group had a significantly higher risk of hypertension (OR=2.561, 95%CI=1.017-6.442, P<0.05). Conclusion Elevated serum TSK levels are closely associated with hypertension. Higher serum TSK levels are independently associated with an increased risk of hypertension.

Key words: Hypertension, Tsukushi, Insulin resistance, βcell function, Crosssectional study

摘要： 背景 高血压是心血管疾病的重要危险因素，全球患病率持续升高，但其发病机制仍未完全阐明。Tsukushi（TSK）是一种新兴肝源性分泌蛋白，参与糖脂代谢调控，与多种代谢异常密切相关，而这些异常可能影响高血压发生发展。目前血清TSK水平与高血压患病风险的关系尚不明确。目的 探讨血清Tsukushi（TSK）水平与高血压的相关性。方法 本研究为横断面研究，纳入2018—2024年于江苏大学附属医院内分泌代谢科门诊就诊以及住院的受试者共143例作为高血压组，同期体检中心体检的受试者98例为血压正常组。收集研究对象的一般资料及实验室检查指标，根据TSK水平三分位数将全部研究对象分为3组：T1组（TSK≤0.8 ng/mL，n=75）、T2组（0.8 ng/mL<TSK<1.5 ng/mL，n=87）、T3组（TSK≥1.5 ng/mL，n=79）。采用独立样本t检验、MannWhitney U检验、χ2 检验进行组间比较，采用相关性分析探讨TSK水平与临床指标的相关性，采用多因素Logistic回归分析探讨TSK水平与高血压患病风险的相关性。结果 与血压正常组相比，高血压组的TSK水平显著增高（P<0.01）。校正年龄、性别、BMI后，TSK水平与收缩压（r=0.214）、舒张压（r=0.213）、腰围（r=0.165）、稳态模型评估胰岛素抵抗指数（r=0.183）呈正相关，与高密度脂蛋白胆固醇（r=-0.138）及基于C肽的β细胞功能（r=-0.168）呈负相关（P<0.05）。随着TSK水平升高，高血压患病率呈递增趋势，T1、T2、T3组高血压患病率分别为48.0%、57.5%和72.2%（P<0.01）。多因素Logistic回归分析结果显示，经多模型逐步校正后，血清TSK水平与高血压患病风险呈正相关（OR=1.542，95%CI=1.054~2.256，P<0.05）；以T1组为参照，T3组高血压患病风险显著升高（OR=2.561，95%CI=1.017~6.442，P<0.05）。结论 血清TSK水平升高与高血压密切相关，高TSK水平与高血压患病风险增加独立相关。

关键词: 高血压, Tsukushi, 胰岛素抵抗, β 细胞功能, 横断面研究