2024年 · 第10卷第02期

高血压是一个主要的公共卫生问题，也是全球死亡的主要风险因素，可归因死亡人数从1990年的680万增加到2019年的1080万。^1,2根据世界卫生组织的数据，高血压的年龄标准化患病率估计为33%，2019年全球约有13亿30-79岁的成年人受到影响，比1990年翻了一番。³除了沉重的疾病负担，与高血压相关的经济负担也相当可观，约占全球医疗保健支出的10%。⁴此外，尽管诊断和治疗能力有所提高，但高血压护理状况仍然不理想，特别是在低收入和中等收入国家。例如，在中国，2019年高血压的知晓率、治疗率和控制率分别为38.3%、34.6%和12.0%。⁵越来越多的证据要求对高血压进行更全面、更有效的预防和管理。

Exercise and medication have similar benefits in reducing blood pressure (BP); however, hypertension management initiatives primarily focus on medicines. This is due to scarce research on the effectiveness of implementation strategies for optimal exercise adoption and adherence. Smartphones were found to be effective in delivering hypertension care and increase exercise adherence. Despite this, only a small number of research projects in India have used smartphones as a strategy for managing hypertension.

We hypothesized that smartphone application-based care would lead to higher exercise adherence among adults (30-79 years) with hypertension compared to those who receive usual care. It will be a multicentric, randomized controlled, parallel-design, superiority clinical trial. The outcome assessor and data analyst will be blinded to group allocation. Participants in the intervention group will receive mobile application-based care for 6 weeks. Participants in the usual care group will receive a standard intervention. Both groups will receive the same number of follow-ups.

The primary outcome is the difference in the proportion of people adherent to the recommended level of physical activity evaluated using an exercise adherence rating scale in the intervention group and the control group. Exercise adoption will be measured as the percentage of eligible participants in each study setting willing to initiate the exercise program. The secondary outcome includes differences in systolic and diastolic BP and self-management (evaluated using the Hypertension Self-Care Profile). The trial outcome will be accompanied by a process evaluation.

This research will inform about the comparative effectiveness of conventional and m-health interventions for exercise adoption and adherence in people with hypertension in resource-constrained settings.

Hypertension (HTN) involves genetic variability in the renin-angiotensin system and influences antihypertensive response. We previously reported that angiotensinogen (AGT) messenger RNA (mRNA) is endogenously bound by miR-122-5p and rs699 A > G decreases reporter mRNA in the microRNA functional-assay PASSPORT-seq. The AGT promoter variant rs5051 C > T is in linkage disequilibrium (LD) with rs699 A > G and increases AGT transcription. The independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C > T counterbalances AGT decreased by rs699 A > G, and when these variants occur independently, it translates to HTN-related phenotypes.

We used in silico, in vitro, in vivo, and retrospective models to test this hypothesis.

In silico, rs699 A > G is predicted to increase miR-122-5p binding affinity by 3%. Mir-eCLIP results show rs699 is 40-45 nucleotides from the strongest microRNA-binding site in the AGT mRNA. Unexpectedly, rs699 A > G increases AGT mRNA in an AGT-plasmid-cDNA HepG2 expression model. Genotype-Tissue Expression (GTEx) and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A > G occurs independently from rs5051 C > T. However, GTEx and the in vitro experiments suggest rs699 A > G confers cell-type-specific effects on AGT mRNA abundance, and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A > G associations with HTN.

We found that rs5051 C > T and rs699 A > G significantly associate with systolic blood pressure in Black participants in the UK Biobank, demonstrating a fourfold larger effect than in White participants. Further studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C > T or rs699 A > G. Studies like this will help clinicians move beyond the use of race as a surrogate for genotype.

Genome-wide association studies (GWAS) have identified more than a thousand loci for blood pressure (BP). Functional genes in these loci are cell-type specific. The aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms (RNAm-SNPs).

Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium, we identified associations between RNAm-SNPs and BP. The association between RNAm-SNPs, gene expression, and BP were examined.

A total of 355 RNAm-SNPs related to m⁶A, m¹A, m⁵C, m⁷G, and A-to-I modification were associated with BP. The related genes were enriched in the pancreatic secretion pathway and renin secretion pathway. The BP GWAS signals were significantly enriched with m⁶A-SNPs, highlighting the potential functional relevance of m⁶A in physiological processes influencing BP. Notably, m⁶A-SNPs in CYP11B1, PDE3B, HDAC7, ACE, SLC4A7, PDE1A, FRK, MTHFR, NPPA, CACNA1D, and HDAC9 were identified. Differential methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were detected. RNAm-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection (AD) cases and controls. In scRNA-seq study, we identified ARID5A, HLA-DPB1, HLA-DRA, IRF1, LINC01091, MCL1, MLF1, MLXIPL, NAA16, NADK, RERG, SRM, and USP53 as differential expression genes for AD in aortic cells.

The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs, gene expression, and BP. The identified BP-associated genes in aortic cells were associated with AD.

The correlation between metals and hypertension, such as sodium, zinc, potassium, and magnesium, has been confirmed, while the relationship between aluminum and hypertension is not very clear. This study aimed to evaluate the correlation between plasma aluminum and hypertension in electrolytic aluminum workers by the Bayesian networks (BN).

In 2019, 476 male workers in an aluminum factory were investigated. The plasma aluminum concentration of workers was measured by inductively coupled plasma mass spectrometry. The influencing factors on the prevalence of hypertension were analyzed by the BN.

The prevalence of hypertension was 23.9% in 476 male workers. The risk of hypertension from plasma aluminum in the Q2, Q3, and Q4 groups was 5.20 (1.90-14.25), 6.92 (2.51-19.08), and 7.33 (2.69-20.01), respectively, compared with that in the Q1 group. The risk of hypertension from the duration of exposure to aluminum of >10 years was 2.23 (1.09-4.57), compared without aluminum exposure. Area under the curve was 0.80 of plasma aluminum and the duration of exposure to aluminum was based on covariates, indicating that aluminum exposure had important predictive value in the prevalence of hypertension in the occupational population. The results of the study using the BN model showed that if the plasma aluminum of all participants was higher than Q4 (≥47.86 µg/L) and the participants were drinking, smoking, diabetes, central obesity, dyslipidemia, and aged >50 years, the proportion of hypertension was 71.2%.

The prevalence of hypertension increased significantly with the increase of plasma aluminum level.

Growth differentiation factor-15 (GDF-15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF-15 and pre-eclampsia (PE).

The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF-15 were measured by using enzyme-linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF-15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs).

MOM of GDF-15 in PE participants was higher compared with controls (1.588 vs. 1.000, p < 0.001). In the logistic model, pregnant women with higher MOM of GDF-15 (>1) had a 4.74-fold (95% CI= 2.23-10.08, p < 0.001) increased risk of PE, adjusted by age, preconceptional body mass index, gravidity, and parity.

These results demonstrated that higher levels of serum GDF-15 were associated with PE. GDF-15 may serve as a biomarker for diagnosing PE.

美国心脏病学会/美国心脏协会将顽固性高血压（RH）定义为服用三种抗高血压药物（包括肾素-血管紧张素系统抑制剂、钙通道阻滞剂（CCB）和耐受剂量良好的利尿剂）的患者的临床血压（BP）读数>130/80 mmHg。^1,2据多项基于人群的调查报道，在美国，在诊断为高血压的成年人中，RH患病率约为12%-15%。²一项前瞻性研究表明，20%被诊断为RH的人患有原发性醛固酮增多症。^3,4RH除经典的三种降压药外，还给予螺内酯和盐皮质激素。然而，关于螺内酯的安全性概况，据报道其具有几种副作用，例如睾酮产生低、月经不调和血清钾水平过度升高，使得该药物不适合治疗RH的纵向治疗目的。⁵

高血压是过早死亡的重要原因，在全球范围内导致近1000万人死亡和超过2亿人残疾。¹近年来，高血压治疗的重点不仅转移到平均血压，还转移到血压变异性（BPV），根据发生的时间段分为非常短期、短期和长期BPV。^2,3长期BPV具有临床意义，研究表明，与短期变异性相比，其在预测长期心血管事件、卒中和死亡率方面具有优越性。鉴于其与肾前功能下降有关，降低血压波动势在必行。

对小编来说，

亲爱的编辑，全世界大约有10亿人患有高血压。其中，95%患有原发性高血压，这是一种未确诊的高血压。¹血压（BP）的调节涉及许多信号通路。其中，肾素血管紧张素系统是众所周知的。所有这些途径都通过调节肾脏盐处理和血管平滑肌（VSM）组织的张力来调节。这些机制中的任何一个都可能出现故障并改变阻力动脉的VSM张力，从而升高血压。然而，由于PH的确切起源及其病理生理学是未知的，因此效果较差，并且使用通用治疗。²在美国，超过50%的高血压患者的血压没有得到很好的控制，这一事实就说明了这一点。抗高血压治疗耐药性影响另外500万人，定义为尽管联合使用至少三种抗高血压药物仍无法调节血压。³