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论文题名(中文):

 血浆醛固酮和肾素与高血压表型的相关性研究    

姓名:

 周展扬    

论文语种:

 chi    

学位:

 硕士    

学位类型:

 学术学位    

学校:

 北京协和医学院    

院系:

 北京协和医学院阜外医院    

专业:

 临床医学-内科学    

指导教师姓名:

 张宇清    

校内导师组成员姓名(逗号分隔):

 张宇辉 翟玫 毛懿    

论文完成日期:

 2025-05-07    

论文题名(外文):

 Correlation Between Plasma Aldosterone, Renin, and Blood Pressure Phenotypes    

关键词(中文):

 高血压表型 醛固酮 血浆肾素活性 醛固酮-肾素比值 肥胖    

关键词(外文):

 Hypertension phenotypes Aldosterone Plasma renin activity Aldosterone-to-renin ratio Obesity    

论文文摘(中文):

第一部分:高血压人群血浆醛固酮、肾素与血压表型的相关性分析

背景:高血压是全球范围内重要的公共卫生问题,不同高血压表型可能由不同的病理生理机制调控。鉴于肾素-血管紧张素-醛固酮系统(Renin-Angiotensin-Aldosterone System, RAAS)在血压调控中的重要作用,本研究基于中国内分泌性高血压筛查队列,探讨血浆醛固酮(Plasma Aldosterone Concentration,PAC)、血浆肾素活性(Plasma Renin Activity,PRA)及醛固酮-肾素比值(Aldosterone-to-Renin Ratio,ARR)在不同高血压表型中的分布特征及其对血压控制的关联性。

方法:本研究纳入 4641 名受试者,采用液相色谱-串联质谱法测定PAC、PRA并计算 ARR。根据诊室血压水平将受试者分为单纯收缩期高血压(Isolated Systolic Hypertension,ISH)、单纯舒张期高血压(Isolated Diastolic Hypertension,IDH)和收缩舒张期高血压(Systolic Diastolic Hypertension,SDH)。并进一步依据身体质量指数(Body Mass Index,BMI)、性别、年龄分亚组进行多因素分析,考察不同 RAAS 指标与血压表型的关系,以及使用不同降压药后 RAAS 指标与血压控制的变化。

结果:(1) 本研究共纳入 4641 名受试者,平均年龄 60.2 岁,女性占 42.7%,PAC 与 PRA 中位数分别为 3.89 ng/dL 和 0.45 ng/mL/h,平均血压为 148/88 mmHg。(2)整体人群中,PAC、PRA与舒张压(Diastolic Blood Pressure,DBP)正相关(r1 = 0.042, r2 = 0.03)。分组后发现:未用药人群中,PAC与收缩压(Systolic Blood Pressure,SBP)(r=0.048)、DBP (r=0.064) 均呈微弱正相关,PRA与DBP呈负相关(r=-0.07, P=0.001),ARR与DBP呈微弱负相关(r=-0.05, P=0.01);而在用药人群中,PRA 与 SBP 呈微弱负相关 (r=-0.12, P=0.04)。(3) 在未用药人群中,根据 ARR>20 且 PAC>10 ng/dL 筛出可疑原发性醛固酮增多症(Primary Aldosteronism,PA)患者。结果显示:可疑PA组 PAC 与 SBP、DBP 的相关性更高 ( SBP: r=0.306, P=0.001)。多因素分析校正协变量后,非可疑PA组PAC、PRA、ARR 与血压的关联均减弱 (P>0.05)。(4)高血压人群的表型分析显示:ISH组低肾素,IDH 组为高肾素。SDH 则随年龄不同而呈现不同 RAAS 状态,年轻者常见高肾素高醛固酮,老年者则常见低肾素高醛固酮。(5)亚组分析显示在使用 RAAS 抑制剂的人群中,PAC水平未被有效抑制的个体, 这组ARR 较高,血压控制难度也显著增加。限制性立方样条分析提示,当PAC <4.2 ng/dL 时,PAC越低,血压越难控制;当PAC>4.2 ng/dL 时,PAC越高,血压控制亦更困难。

结论:PAC、PRA及ARR与血压相关性弱,但在可疑原醛人群中相关性增加。使用RAAS抑制剂后PAC水平更高人群血压更难以控制。

 

第二部分:难治性高血压患者的临床特征与血压监测差异分析

背景:难治性高血压(Resistant Hypertension, RH)是临床管理的难点,本研究旨在基于难治性高血压患者队列,系统分析其人群特征、血压测量方式差异及RAAS指标的临床价值。

方法:本研究纳入就诊于阜外医院的74例难治性高血压患者,收集其诊室血压、动态血压(Ambulatory Blood Pressure,ABP)、家庭血压(Home Blood Pressure,HBP)等数据,并分析其代谢特征、靶器官损害及RAAS 相关指标参数。比较患者不同年龄、BMI 及血压表型组间各变量的差异。

结果:(1)在难治性高血压人群中老年患者(≥60岁)血压表型以ISH为主(71.4% vs. 37.0%, P=0.01),诊室SBP显著高于年轻组(<60岁)(161.93±21.32 vs. 151.61±16.90 mmHg, P=0.024),家庭SBP也显著高于年轻组(141.22 ± 13.09 vs.147.39±11.96mmHg,p=0.046)。而年轻组血压表型中IDH比例更高,且诊室DBP(97.76±10.96 vs. 84.25±10.51 mmHg, P<0.001)及动态DBP(90.30±8.09 vs. 80.79±9.58 mmHg, P<0.001)均显著升高;(2)肥胖(BMI≥28 kg/m²)患者DBP水平更高(96.37±13.30 vs. 84.50±10.37 mmHg, P<0.05),且甘油三酯水平显著升高(1.90 vs. 1.48 mmol/L, P=0.039);(3)动态血压监测显示,诊室SBP显著高于24小时平均SBP(155.5±19.2 vs.136.9 ± 13.3mmHg, P<0.001),诊室DBP也高于24小时平均DBP(92.6±12.6 vs. 86.7±9.8mmHg,P<0.001)且非杓型高血压占79.7%;(4)PAC、PRA、ARR水平与血压表型无显著关联(P>0.05)。

结论:难治性高血压人群老年、肥胖人群比例高,诊室血压可能高估真实血压负荷,需结合动态血压以优化诊断及治疗策略。

 

 

论文文摘(外文):

Part I: Correlation Between Plasma Aldosterone, Renin, and Blood Pressure Phenotypes in Hypertensive Populations

Background: Hypertension is a major global public health challenge, and different blood pressure (BP) phenotypes may be mediated by distinct physiological mechanisms. Given the critical role of the renin-angiotensin-aldosterone system (RAAS) in BP regulation, this study, based on a Chinese Endocrine Hypertension Screening Cohort, aimed to explore the distribution of plasma aldosterone concentration (PAC), plasma renin activity (PRA), and the aldosterone-to-renin ratio (ARR) across various hypertension phenotypes and their impact on BP control.

Methods: A total of 4,641 participants were enrolled. PAC and PRA were measured using liquid chromatography-tandem mass spectrometry, and ARR was calculated. Participants were categorized into isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH) based on office BP. Furthermore, subgroups were defined by body mass index (BMI), sex, and age. Multivariate analyses were performed to assess the association between RAAS markers and hypertension phenotypes, as well as the effect of different antihypertensive regimens on RAAS markers and BP control.

Results:
(1) The mean age of the participants was 60.2 years, with 42.7% being female. The median PAC and PRA were 3.89 ng/dL and 0.45 ng/mL/h, respectively, and the average BP was 148/88 mmHg.
(2) The Overall correlations between RAAS markers and BP were weak. In the untreated group, PAC was weakly positively correlated with both systolic BP (SBP) and diastolic BP (DBP) (P<0.05), whereas PRA showed a mild negative correlation with DBP (r=-0.07, P=0.001), and ARR also correlated negatively with DBP (r=-0.05, P=0.01). In the treated group, PRA was negatively correlated with SBP (r=-0.12, P=0.04), but PAC had no significant association with BP.
(3) Among the untreated participants, those meeting ARR>20 and PAC>10 ng/dL criteria were identified as potentially having primary aldosteronism (PA). PAC was more strongly correlated with BP in this “suspected PA” subgroup (e.g., SBP: r=0.306, P=0.001) but showed weaker correlations in the non-PA group. After adjusting for confounders, the associations of PAC, PRA, and ARR with BP were largely non-significant (P>0.05).
(4) Phenotypic analyses in the general hypertensive population revealed that ISH was characterized by low renin, IDH by high renin, and SDH varied with age (low-renin/high-PAC in older SDH vs. high-renin/high-PAC in younger SDH). In individuals receiving RAAS inhibitors, persistent aldosterone elevation was linked to higher ARR and poorer BP control. Restrictive cubic spline analysis indicated that when PAC was <4.2 ng/dL, lower PAC levels were associated with greater difficulty in BP control, whereas PAC >4.2 ng/dL were associated with poorer blood pressure control.
(5) Overweight/obese individuals tended to exhibit more metabolic disorders and specific RAAS profiles, making BP control more difficult. Persistent elevation of aldosterone despite RAAS blockade suggests aldosterone escape and a potential risk of PA.

Conclusion: Distinct RAAS features underlie different hypertension phenotypes, underscoring the need to consider aldosterone and renin levels, along with age and metabolic factors, in the personalized management of hypertension. Aldosterone escape or suspected PA should be considered in those whose aldosterone levels remain elevated after RAAS inhibition. These findings provide new evidence for precision therapy and RAAS-targeted management in hypertensive patients.

 

Part2:Analysis of Clinical Characteristics and Blood Pressure Monitoring Discrepancies in Patients with Resistant Hypertension

Background:Resistant hypertension (RH) poses a significant challenge in clinical management due to the heterogeneity in its diagnostic criteria and epidemiological findings. This study aims to systematically analyze the population characteristics, differences in blood pressure (BP) measurement methods, and the clinical value of renin-angiotensin-aldosterone system (RAAS) indicators based on a cohort of RH patients.

Methods:A total of 74 RH patients who visited Fuwai Hospital were enrolled in this study. Data on office BP, ambulatory blood pressure monitoring (ABPM), and home blood pressure monitoring (HBPM) were collected, along with metabolic characteristics, target organ damage, and RAAS system parameters. Statistical analyses were performed to compare clinical differences among patients with different age groups, body mass index (BMI), and BP phenotypes, and to explore the clinical characteristics of RH and the diagnostic value of different BP measurement methods.

Results:Elderly patients (≥60 years) predominantly had isolated systolic hypertension (ISH) (71.4% vs. 37.0%, P=0.01), with significantly higher office systolic blood pressure (SBP) compared to younger patients (161.93±21.32 vs. 151.61±16.90 mmHg, P=0.024). In contrast, younger patients (<60 years) had a higher prevalence of isolated diastolic hypertension (IDH) and exhibited significantly higher office diastolic blood pressure (DBP) (97.76±10.96 vs. 84.25±10.51 mmHg, P<0.001) and ambulatory DBP (90.30±8.09 vs. 80.79±9.58 mmHg, P<0.001). Patients with obesity (BMI≥28 kg/m²) had significantly higher DBP (96.37±13.30 vs. 84.50±10.37 mmHg, P<0.05) and elevated triglyceride levels (1.90 vs. 1.48 mmol/L, P=0.039). Office SBP was significantly higher than the 24-hour ambulatory SBP (Δ=18.6 mmHg, P<0.001), and 79.7% of patients exhibited a non-dipping BP pattern, indicating an impaired nocturnal BP regulation.RAAS system characteristics: Aldosterone levels were not significantly associated with BP phenotypes (P>0.05). However, findings support the RAAS system as a potential therapeutic target.

Conclusion:ABPM plays a crucial role in the accurate diagnosis of resistant hypertension. Targeted interventions are necessary for elderly ISH patients and those with obesity-related diastolic hypertension. Limitations of this study include a small sample size and the lack of long-term prognostic data. Future studies should expand the cohort to validate aldosterone-targeted therapies and metabolic regulation strategies.

 

开放日期:

 2025-06-05    

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