AbstractEndothelial dysfunction is acknowledged as a marker for subclinical target organ damage (STOD) in hypertension, though its therapeutic potential has not yet been clarified. This study assessed whether early endothelial function improvement (EEFI) reduced STOD in patients with essential hypertension (EH).

摘要内皮功能障碍被认为是高血压亚临床靶器官损伤（STOD）的标志物，尽管其治疗潜力尚未阐明。本研究评估了早期内皮功能改善（EEFI）是否降低了原发性高血压（EH）患者的STOD。

We conducted a retrospective cohort analysis of 456 EH patients initially free from STOD. Endothelial function was assessed using brachial artery flow-mediated dilation (FMD), with values ≤ 7.1% indicating dysfunction. Patients were initially categorized by endothelial status (dysfunction: n = 180, normal: n = 276), and further divided into improved or unimproved groups based on changes within three months post-enrollment.

我们对456名最初没有STOD的EH患者进行了回顾性队列分析。使用肱动脉血流介导的扩张（FMD）评估内皮功能，值≤7.1%表示功能障碍。患者最初按内皮状态分类（功能障碍：n=180，正常：n=276），并根据入组后三个月内的变化进一步分为改善组或未改善组。

During a median follow-up of 25 months, 177 patients developed STOD. The incidence of STOD was significantly higher in patients with initial dysfunction compared to those with normal function. Kaplan–Meier analysis indicated that the improved group had a lower cumulative incidence of STOD compared to the unimproved group (p < 0.05).

在中位随访25个月期间，177名患者出现了STOD。。Kaplan-Meier分析表明，与未改善组相比，改善组的STOD累积发生率较低（p<0.05）。

Multivariable Cox regression confirmed EEFI as an independent protective factor against STOD in EH patients (p < 0.05), regardless of their baseline endothelial status, especially in those under 65 years old, non-smokers, and with low-density lipoprotein cholesterol levels ≤ 3.4 mmol/L. In conclusion, EEFI significantly reduces STOD incidence in EH patients, particularly in specific subgroups, emphasizing the need for early intervention in endothelial function to prevent STOD..

多变量Cox回归证实EEFI是EH患者抵抗STOD的独立保护因素（p<0.05），无论其基线内皮状态如何，特别是在65岁以下，不吸烟者和低密度脂蛋白胆固醇水平≤3.4 mmol/L的患者中。总之，EEFI显着降低EH患者的STOD发病率，特别是在特定亚组中，强调需要早期干预内皮功能以预防STOD。。

IntroductionHypertension affects roughly one billion individuals worldwide, making it a prevalent chronic disease1. As a major risk factor for cardiovascular diseases, it poses a threat to public health globally2. Current treatment strategies focus on comprehensive risk management beyond mere blood pressure control, emphasizing target organ protection and clinical event reduction3.

引言高血压影响全球约10亿人，使其成为一种普遍的慢性疾病1。。目前的治疗策略侧重于全面的风险管理，而不仅仅是血压控制，强调靶器官保护和临床事件减少3。

Endothelial dysfunction is crucial in hypertension development, serving as both an early biomarker of elevated blood pressure and a warning for future cardiovascular events4,5. However, limited evidence exists on how early endothelial function improvement (EEFI) can prevent the progression of subclinical target organ damage (STOD) in hypertensive patients.Flow-mediated dilation (FMD), a non-invasive technique, assesses endothelial function and accurately reflects vascular health.

内皮功能障碍在高血压发展中至关重要，既是血压升高的早期生物标志物，也是未来心血管事件的警告4,5。然而，关于早期内皮功能改善（EEFI）如何预防高血压患者亚临床靶器官损伤（STOD）进展的证据有限。血流介导的扩张（FMD）是一种非侵入性技术，可评估内皮功能并准确反映血管健康。

Using this technology, our prior research6,7,8,9,10 has investigated the link between endothelial function and hypertension, demonstrating that endothelial dysfunction correlates with a heightened risk of progression and complications in essential hypertension (EH). Based on these findings, we hypothesized that EEFI would reduce the incidence of STOD in EH patients.

使用这项技术，我们之前的研究[6,7,8,9,10]研究了内皮功能与高血压之间的联系，证明内皮功能障碍与原发性高血压（EH）进展和并发症风险增加相关。基于这些发现，我们假设EEFI可以降低EH患者STOD的发生率。

We aimed to explore this hypothesis through empirical research. This study sought to explore the potential of EEFI to prevent STOD in EH patients. The findings could enhance the understanding of EH progression and inform prevention and treatment strategies for hypertension.MethodsExperimental protocolThis single-center retrospective cohort study drew from the Hypertension Target Organ Damage and Its Risk Factors—Fuzhou Study database.

我们旨在通过实证研究探索这一假设。本研究旨在探讨EEFI预防EH患者STOD的潜力。这些发现可以增强对EH进展的理解，并为高血压的预防和治疗策略提供信息。方法实验方案这项单中心回顾性队列研究来自福州高血压靶器官损害及其危险因素研究数据库。

Ethical clearance was granted by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University (Ref: .

伦理审查由福建医科大学第一附属医院伦理委员会批准（参考文献：。

Table 1 Clinical characteristics of hypertensives patients with and without initial endothelial impairment.Full size tablePatients were categorized based on initial endothelial function for further analysis. In the impaired group, the improved subgroup had significantly fewer smokers than the unimproved subgroup (p < 0.05), with similar other baseline characteristics.

。根据初始内皮功能对全尺寸表患者进行分类，以进行进一步分析。在受损组中，改善的亚组吸烟者明显少于未改善的亚组（p<0.05），其他基线特征相似。

Despite similar blood pressure control, the improved subgroup used more renin-angiotensin system (RAS) inhibitors and fewer diuretics than the unimproved subgroup (Table 2). In the normal group, those in the improved subgroup were younger with higher eGFR levels than the unimproved subgroup (p < 0.05).

尽管血压控制相似，但与未改善的亚组相比，改善的亚组使用了更多的肾素-血管紧张素系统（RAS）抑制剂和更少的利尿剂（表2）。在正常组中，改善亚组的患者年龄较小，eGFR水平高于未改善亚组（p<0.05）。

There were no significant abnormalities between the groups in terms of initial treatment medications and other baseline data (Table 3)..

就初始治疗药物和其他基线数据而言，两组之间没有显着异常（表3）。。

Table 2 Clinical characteristics of patients with initial endothelial impairment who improved vs. those who did not improve after 3 months of enrollment treatment.Full size tableTable 3 Clinical characteristics of patients with initial normal endothelial function who improved vs. those who did not improve after 3 months of enrollment treatment.Full size tableRelationship between EEFI and the incidence of STOD in EH patientsKaplan–Meier survival curve analysis revealed a significantly higher incidence of STOD in EH patients with endothelial dysfunction than in those with normal function (Log-rank test, p < 0.001), as shown in Fig.

表2初始内皮损伤患者的临床特征在登记治疗3个月后有所改善，而没有改善。。全尺寸表EEFI与EH患者STOD发生率之间的关系Kaplan-Meier生存曲线分析显示，内皮功能障碍EH患者的STOD发生率显着高于功能正常的患者（对数秩检验，p<0.001），如图所示。

S1 (Supplementary Fig. 1). Subsequent subgroup analysis with a cumulative hazard curve indicated that the group with improved endothelial function exhibited a significantly lower STOD incidence than the unimproved group (Log-rank test, p < 0.05) (Fig. 2).Figure 2Cumulative hazard curves for STOD in the improved (dotted line) and unimproved (solid line) groups of EH patients with initial impaired (a) and unimpaired (b) endothelial function.

S1（补充图1）。。图2初始受损（a）和未受损（b）内皮功能的EH患者的改善（虚线）和未改善（实线）组中STOD的累积危险曲线。

EH essential hypertension, STOD subclinical target organ damage.Full size imageCox regression analysis of the incidence of STOD in EH patientsMultivariate Cox regression analysis was conducted with EEFI, factors with significant differences or trends in the univariate analysis, and traditional risk factors (age, gender, BMI, smoking, blood pressure, FSG, and LDL-C) as independent variables to examine their association with STOD incidence.

EH原发性高血压，STOD亚临床靶器官损害。EH患者STOD发病率的全尺寸imageCox回归分析使用EEFI，单因素分析中具有显着差异或趋势的因素以及传统危险因素（年龄，性别，BMI，吸烟，血压，FSG和LDL-C）作为自变量来检查它们与STOD发病率的关系。

In patients with initial endothelial impairment, age, female and LDL-C emerged as independent risk factors for STOD, whereas EEFI (HR = 0.53, 95% CI 0.35–0.79) served as a protective factor (Fig. 3a). Subgroup analysis showed that EEFI significantly reduced the risk of STOD .

在初始内皮损伤的患者中，年龄，女性和LDL-C是STOD的独立危险因素，而EEFI（HR=0.53，95%CI 0.35-0.79）是保护因素（图3a）。亚组分析显示，EEFI显着降低了STOD的风险。

Data availability

数据可用性

The datasets generated and analyzed during the current study are not publicly available due to privacy or ethical restrictions but are available from the corresponding author on reasonable request. The data were drawn from the Hypertension Target Organ Damage and Its Risk Factors—Fuzhou Study database..

由于隐私或道德限制，当前研究期间生成和分析的数据集无法公开获得，但可根据合理要求从通讯作者处获得。数据来自福州市高血压靶器官损害及其危险因素研究数据库。。

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Download referencesAcknowledgementsThe authors appreciate the help of Yihua Shen, Tingting Zhou, Xiaoqi Cai, Heling Huang, Didi Huang and all the participants in this study.FundingThis work was supported by the Natural Science Foundation of Fujian Province (Grand No. 2020J011227).Author informationAuthors and AffiliationsDepartment of Emergency, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, ChinaXiaodong Huang, Xianwei Huang, Mandong Pan & Jiyan LinXiamen Key Laboratory for Clinical Efficacy and Evidence-Based Research of Traditional Chinese Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, ChinaXiaodong Huang, Xianwei Huang, Mandong Pan & Jiyan LinDepartment of Geriatrics, Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, ChinaLiangdi XieAuthorsXiaodong HuangView author publicationsYou can also search for this author in.

下载参考文献致谢作者感谢沈怡华，周婷婷，蔡晓琪，黄和玲，黄滴滴以及本研究所有参与者的帮助。资助这项工作得到了福建省自然科学基金（Grand No.2020J011227）的支持。作者信息作者和附属机构厦门大学第一附属医院急诊科，厦门大学医学院，厦门，361003，中国黄晓东，黄贤伟，潘满东和吉林省厦门市中医临床疗效和循证研究重点实验室，厦门大学第一附属医院，厦门，361003，黄晓东，黄贤伟，潘满东和吉林省老年医学系，福建医科大学第一附属医院，福建省福州市茶中路20号在。

PubMed Google ScholarXianwei HuangView author publicationsYou can also search for this author in

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PubMed Google ScholarContributionsXiaodong Huang (X.H.): Conceptualization, Investigation, Data curation, Formal analysis, Writing—original draft, Visualization. Xianwei Huang (X.W.H.), M.P., and J.L.: Investigation, Data curation, Funding acquisition, Writing—review & editing.

PubMed谷歌学术贡献Xiaodong Huang（X.H.）：概念化，调查，数据管理，形式分析，撰写原稿，可视化。黄贤伟（X.W.H.），M.P。和J.L.：调查，数据管理，资金获取，写作评论和编辑。

L.X.: Conceptualization, Methodology, Funding acquisition, Supervision, Project administration, Validation, Writing—review & editing.Corresponding authorCorrespondence to.

五十、 十：概念化、方法论、资金获取、监督、项目管理、验证、写作审查和编辑。。

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Reprints and permissionsAbout this articleCite this articleHuang, X., Huang, X., Pan, M. et al. Effect of early endothelial function improvement on subclinical target organ damage in hypertensives.

转载和许可本文引用本文Huang，X.，Huang，X.，Pan，M。等人。早期内皮功能改善对高血压患者亚临床靶器官损伤的影响。

Sci Rep 14, 16078 (2024). https://doi.org/10.1038/s41598-024-67143-1Download citationReceived: 16 May 2024Accepted: 08 July 2024Published: 12 July 2024DOI: https://doi.org/10.1038/s41598-024-67143-1Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

Sci Rep 1416078（2024）。https://doi.org/10.1038/s41598-024-67143-1Download引文接收日期：2024年5月16日接受日期：2024年7月8日发布日期：2024年7月12日OI：https://doi.org/10.1038/s41598-024-67143-1Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。。

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KeywordsEssential hypertensionSubclinical target organ damageEndothelial functionFlow-mediated dilation

关键词原发性高血压亚临床靶器官损伤内皮功能血流介导的扩张

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