Hypertension最新文献

Background: Hypertension is a major cardiovascular risk factor, yet traditional care often results in suboptimal blood pressure (BP) control at the population level. We implemented a remote hypertension management program that monitored home BP and titrated medications per algorithm. This study assessed the program's long-term effects by examining participants' office BP up to 42 months post-enrollment.

Methods: Participants of the remote hypertension program were categorized into 4 groups: (1) enrolled-maintenance (achieved goal home BP of ≤130/80 mm Hg), (2) enrolled-early exit (left before achieving goal BP), (3) education-only (lifestyle modifications and medications compliance), and (4) white coat hypertension group (high office BP but normal home BP). Office BP readings of participants were collected up to 42 months post-enrollment. A linear mixed-effects regression model estimated mean BP levels and studied factors associated with above-goal systolic BP in the maintenance group.

Results: Office BP readings from 3601 participants (mean age, 61±11 years; 57% female; 60% white; 52% atherosclerotic cardiovascular disease) were extracted from electronic health records and analyzed. All groups sustained office BP below their qualifying values (P<0.001) over 42 months. In the maintenance group, 89.7% of participants maintained systolic BP at goal, compared with 63.5% in the early exit group, 69.4% in the education-only group, and 90.7% in the white coat hypertension group. Age >50 years was associated with above-goal systolic BP in the maintenance group.

Conclusions: Participants who achieved BP control through the remote hypertension program maintained goal systolic BP in 90% of cases up to 42 months post-enrollment. These findings highlight the long-term benefits of remote, intensive management programs for effective hypertension control.

The term early life stress encompasses traumatic events occurring before the age of 18 years, such as physical abuse, verbal abuse, household dysfunctions, sexual abuse, childhood neglect, child maltreatment, and adverse childhood experiences. Adverse psychological experiences in early life are linked to enduring effects on mental and physical health in adulthood. In this review, we first describe the effects and potential mechanisms of early life stress on the components of the vasculature. Next, we dive into the impact of early life stress on the vasculature across the lifespan through alterations of the epigenetic landscape. Finally, we consolidate the critical gaps in knowledge for focusing future research including the potential for resilience in combatting the impact of early life stress on vascular health.

Background: Severe preeclampsia (sPE) is a serious condition posing risks to both maternal and fetal health. Based on mass spectrometry analysis, we identified a key protein, PSME3 (proteasome activator subunit 3), an 11S proteasome activator, whose protein level was significantly downregulated in sPE placentas and whose function in sPE remains unknown.

Methods: PSME3 protein levels in human placental tissue were detected using Western blot, and PSME3 concentration in serum was detected by ELISA assay. The human preeclampsia-like phenotypes of Psme3^-/- pregnant mice were examined. Trophoblast cell apoptosis was detected by flow cytometry. Pregnant mice were treated with 9.5% O₂ to construct a preeclampsia mouse model for detecting placental Psme3 expression. The regulation of PSME3 expression by hypoxia was detected in trophoblast cell lines treated with 21% O₂ or 1% O₂.

Results: PSME3 protein levels were significantly downregulated in sPE placentas and serum. Pregnant mice with Psme3^-/- embryos and placentas spontaneously presented human preeclampsia-like symptoms, including hypertension and proteinuria, increased serum soluble fms-like tyrosine kinase 1 concentration, fetal growth restriction, and increased cellular apoptosis. Mechanically, PSME3 knockdown promoted the apoptosis of trophoblast cells by repressing the degradation of UBE2V2 (ubiquitin conjugating enzyme E2 V2). Moreover, the placentas of hypoxia-induced preeclampsia mice presented significantly reduced Psme3 protein levels and elevated Ube2v2 protein levels. Hypoxia-inducible factor-1α functioned as a transcriptional repressor of PSME3.

Conclusions: In sPE placentas, hypoxia of the placenta may lead to the transcriptional inhibition of PSME3. PSME3 deficiency promotes the accumulation of UBE2V2, thereby inducing trophoblast cell apoptosis. Our study provides a new perspective for elucidating the pathogenesis of sPE.

Genome-wide association studies have identified >3500 associated single nucleotide polymorphisms and over 1000 independent loci associated with hypertension. These individually have small effect sizes, and few associated loci have been experimentally tested for causal roles in hypertension using animal models or in humans. Thus, methods to prioritize and maximize the relevance of identified single nucleotide polymorphisms and associated loci are critical to determine their importance in hypertension. We propose several approaches to aid in these efforts, including: (1) integration of genome-wide association study data with multiomic data sets, including proteomics, transcriptomics, and epigenomics, (2) utilizing linked clinical and genetic data sets to determine genetic contributions to hypertension subphenotypes with distinct drivers, and (3) performing whole exome/genome sequencing on cohorts of individuals with severe hypertension to enrich for rare variants with larger effect sizes. Rather than creating longer lists of hypertension-associated single nucleotide polymorphisms, these approaches are needed to identify key mediators of hypertension pathophysiology.

Background: Persistently high blood pressure remains the leading risk factor for mortality worldwide. This study aims to identify potential drug targets for hypertension.

Methods: Mendelian randomization was used to identify therapeutic targets for hypertension. Genome-wide association study summary statistics were obtained from the UK Biobank and FinnGen study. Cis-expression quantitative trait loci from the eQTLGen Consortium served as genetic instruments. Colocalization analysis evaluated the likelihood of shared causal variants between single-nucleotide polymorphisms influencing hypertension and gene expression. Survival analysis of UK Biobank data assessed hypertension and mortality risks across participants with different gene alleles.

Results: Mendelian randomization analysis identified 190 drug targets in the discovery cohort and 65 in the replication cohort after multiple testing correction. Colocalization analysis identified 14 hypertension-related drug targets, including angiotensin-converting enzyme, AIMP1, CDC25A, EHMT2, FES, GPX1, GRK4, HSD3B7, NEK4, PTPN12, SIK2, SLC22A4, SLC2A4, and TNFSF12. Survival analysis revealed individuals with the A allele at rs4308 in the angiotensin-converting enzyme gene had a higher incidence of hypertension, while those with the T allele at rs11242109 in the SLC22A4 gene showed a lower hypertension-specific mortality rate.

Conclusions: Drug target Mendelian randomization studies offer new directions for hypertension treatment, providing insights into its mechanisms and robust targets for developing antihypertensive drugs.

Background: In 2024, the World Health Organization released a report on Priorities for Research on Hypertension Care Delivery. This article provides its executive summary.

Methods: The World Health Organization and its technical experts formed a leadership team, developed a scope and objectives, created a thematic framework, developed a survey for each theme, and identified research priorities. The 5 themes included (1) Health care workforce for hypertension care delivery, (2) Service delivery system/models, (3) Patient retention/adherence, (4) Financing the care delivery system, and (5) Research gaps identified in the World Health Organization 2021 Hypertension Guideline. The leadership team received feedback from diverse experts through webinars and online surveys. The final report was peer-reviewed by external experts.

Results: According to postwebinar surveys, we identified 5 to 7 research priorities within each theme, totaling 29 research priorities. The 10 highest priorities were (1) Cost-effectiveness of combination therapy in low/middle-income countries, (2) A system allowing hypertension care closer to home, (3) Health system reform allowing trained community health workers to refill/initiate/titrate antihypertensive medications, (4) Health system reform allowing nurses to diagnose and treat hypertension, (5) Gaps in the medication supply chain, (6) New approaches integrating the management of hypertension and other diseases, (7) Digital approaches for improving medication adherence, (8) Optimal approaches to train health care workers, (9) Approaches to finance hypertension control programs, and (10) Implementation research on task-sharing approaches.

Conclusions: These research priorities provide guidance to researchers, with immediate implications for substantially improve hypertension care and prevent its sequelae. We urge governments, funding agencies, and organizations to consider supporting these research topics.

Hypertension presents the largest modifiable public health challenge due to its high prevalence, its intimate relationship to cardiovascular diseases, and its complex pathogenesis and pathophysiology. Low awareness of blood pressure elevation and suboptimal hypertension diagnosis serve as the major hurdles in effective hypertension management. Advances in artificial intelligence in hypertension have permitted the integrative analysis of large data sets including omics, clinical (with novel sensor and wearable technologies), health-related, social, behavioral, and environmental sources, and hold transformative potential in achieving large-scale, data-driven approaches toward personalized diagnosis, treatment, and long-term management. However, although the emerging artificial intelligence science may advance the concept of precision hypertension in discovery, drug targeting and development, patient care, and management, its clinical adoption at scale today is lacking. Recognizing that clinical implementation of artificial intelligence-based solutions need evidence generation, this opinion statement examines a clinician-centric perspective of the state-of-art in using artificial intelligence in the management of hypertension and puts forward recommendations toward equitable precision hypertension care.

Background: The cardio-ankle vascular index (CAVI) and heart-thigh β index (htβ) assess arterial stiffness by correcting pulse wave velocity for blood pressure to achieve less dependency on blood pressure variations. Normative data for these markers among US communities are lacking. We aimed to assess the determinants and normative values of CAVI and htβ.

Methods: MESA (Multi-Ethnic Study of Atherosclerosis) participants with CAVI and htβ measurements were included (n=2950). A subgroup selected to define normative values included only participants without previous cardiovascular disease, diabetes, smoking, antihypertensive use, and with blood pressure <140/90 mm Hg, body mass index <35 kg/m², and creatinine <1.5 mg/dL. Associations were assessed by multivariable linear regressions. All continuous variables were standardized.

Results: Among 2950 participants (mean age, 73.6 years; 47.2% male), older age (β for CAVI=0.39, P<0.001 and htβ=0.41, P<0.001), and male sex (β for CAVI=0.30, P<0.001 and htβ=0.11, P<0.001) were associated with higher arterial indices. Participants with higher blood pressure, height, and diabetes exhibited higher CAVI and htβ. A higher waist circumference was associated with lower CAVI and htβ. Among the normative value subgroup (n=676), the mean CAVI was 8.7 (2 Z score range, 6.5-11.2), and the mean htβ was 8.9 (2 Z score range, 4.3-13.6). Among participants without cardiovascular disease, higher CAVI and htβ were associated with higher predicted 10-year cardiovascular risk estimated by pooled cohort equations (per SD of CAVI=3.6%, P<0.001 and htβ=3.3%, P<0.001).

Conclusions: We report determinants and normative values of CAVI and htβ in a multiethnic community-based US population. Future studies should focus on the prognostic utility of CAVI and htβ.

Background: ATP citrate lyase (ACLY) is a key enzyme in de novo lipogenesis that generates acetyl-CoA from citrate. Although fatty acids are required for energy production and biomass synthesis in the heart, the regulatory mechanisms of ACLY-mediated de novo lipogenesis in pathological cardiac fibroblasts remain unknown. The aim of this study was to investigate the biological role of ACLY in cardiac remodeling.

Methods: Adeno-associated virus serotype 9-mediated shRNA targeting Acly was intravenously injected into C57BL/6J male mice. The mice were subsequently continuously infused with a mixture of angiotensin II and phenylephrine. Cardiac phenotypes were evaluated via histological staining. Cell proliferation assays, stable isotope tracing with 13C-labeled glucose, and chromatin immunoprecipitation assays were performed using human cardiac fibroblasts.

Results: ACLY expression was upregulated in the heart sections of mice treated with angiotensin II/phenylephrine, in particular in fibrotic areas. Masson trichrome staining revealed that Acly gene silencing significantly reduced cardiac fibrosis in these mice. Both siRNA-mediated ACLY knockdown and pharmacological ACLY inhibition suppressed the proliferation and expression of fibrous proteins in cultured human cardiac fibroblasts stimulated with transforming growth factor-β. Mechanistically, ACLY inhibition reduced de novo lipogenesis, limiting the fatty acid supply essential for cellular growth and proliferation. It also decreased H3K9 and H3K27 acetylation, in addition to the presence of acetylated H3K9 and H3K27 at the promoter regions of fibrotic genes.

Conclusions: Our findings demonstrate that ACLY plays an important role in maladaptive cardiac fibrosis. ACLY could be a novel therapeutic target to prevent the development of heart failure.