Hypertension最新文献

Background: The latest updated 2025 and 2017 American College of Cardiology and the American Heart Association guidelines lowered the diagnostic threshold for hypertension to 130/80 mm Hg. Whether the new classification for hypertension has implications for reproductive outcomes remains uncertain.

Methods: This retrospective cohort study was conducted at the Reproductive Medicine Center of Shandong University in China. Women who underwent the initial embryo transfer of their first in vitro fertilization cycle were categorized into the normal blood pressure (BP), elevated BP, stage 1 hypertension, and stage 2 hypertension groups based on BP levels measured just before in vitro fertilization treatment. We examined associations of prepregnancy BP and reproductive outcomes.

Results: This study included 43 629 women who received in vitro fertilization treatment. The rate of live birth was lower in women with stage 1 and stage 2 hypertensions (46.1% and 41.4%, respectively) compared with women with normal BP (49.2%), with the adjusted relative ratios of 0.97 (95% CI, 0.937-0.996; P=0.027) and 0.91 (95% CI, 0.85-0.98; P=0.009), respectively. Compared with normal BP, both stage 1 and stage 2 hypertension were associated with higher risks of pregnancy loss, preeclampsia, and preterm delivery. Elevated BP was associated with a higher risk of gestational hypertension. Optimal BP cutoffs for adverse reproductive outcomes were consistent with the diagnostic threshold for stage 1 hypertension.

Conclusions: Compared with normal BP, prepregnancy stage 1 and stage 2 hypertension were associated with a lower rate of live birth after in vitro fertilization treatment and increased risks of pregnancy complications.

Background: This study aims to develop a prediction model to identify individuals at risk of hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, by integrating epigenetic biomarkers and clinical factors in the first trimester of pregnancy.

Methods: A 2-stage nested case-control study, matched by age and body mass index, was conducted with 618 pregnant women in China, with peripheral blood samples collected in the first trimester to evaluate the average methylation levels of differentially methylated regions (DMRs) between controls and HDP cases. In stage 1 (discovery set), 24 controls and 27 cases were used to identify the differential DMRs. In stage 2, 294 controls and 273 cases were used to validate the previously identified DMRs. DMRs selected from the intersectional results of lasso regression, XGBoost, random forest, and Shapley Additive Explanations models were further combined with women's clinical risk factors to construct prediction models using logistic regression.

Results: In stage 1, 52 differential DMRs were identified with a false-positive rate <0.05. In stage 2, 12 differential DMRs were consistently observed, and 3 DMRs located in the CTSA, HMGB1, and miR1908/FADS2 genes were selected to construct a prediction model for HDPs. After combining the selected DMRs with clinical factors, the model achieved an area under the curve of 0.863 (95% CI, 0.826-0.901) in the training set and 0.757 (95% CI, 0.686-0.828) in the test set.

Conclusion: Findings of this study offer potential opportunities to identify high-risk patients with HDP in early pregnancy through DMRs identified in peripheral blood and provide new insights into the epigenetic cause of HDP.

Background: Home blood pressure (BP) monitoring (HBPM) is increasingly used as an alternative to office BP. However, factors influencing agreement between office and home BP among very old adults remain unclear.

Methods: During ARIC (Atherosclerosis Risk in Communities) visit 10, participants underwent 3 automated office BP (AOBP) measurements using an Omron HEM-907XL and performed HBPM twice daily for 8 days using an Omron BP7450. Discordance was defined as a systolic BP difference of ±10 mm Hg between mean AOBP and HBPM. Multivariable regression models evaluated demographic, anthropometric, and clinical factors associated with discordance.

Results: Among 792 participants (58% female; mean age, 84±3.7 years), mean systolic BP was 130.6 mm Hg (AOBP) and 129.6 mm Hg (HBPM). Despite a minimal average difference (1.0±15.7 mm Hg), 49% had ≥10 mm Hg systolic BP discordance. Higher AOBP was associated with greater discordance. Compared with females, males had lower AOBP relative to HBPM (-4.69 mm Hg [95% CI, -6.86 to -2.51]). Smaller arm circumference was associated with higher discordance (β=14.4 mm Hg [95% CI, 4.78-24.04]). Frail adults had lower AOBP relative to HBPM (β, -5.1 mm Hg [95% CI, -11.0 to 0.9]). Baseline AOBP systolic BP ≥140 mm Hg strongly predicted discordance ≥+10 mm Hg (odds ratio, 8.27 [95% CI, 5.52-12.40]). Participants aged 91 to 100 years had lower AOBP than those aged 78 to 80 years (β, -5.0 mm Hg [95% CI, -10.06 to 0.001]).

Conclusions: Among very old adults, substantial BP discordance between AOBP and HBPM was common and influenced by higher BP, age, male sex, arm circumference, and frailty.

Fewer than 2% of eligible patients are screened for primary aldosteronism, despite evidence that early detection and targeted therapy are associated with lower cardiovascular and kidney morbidity. Recent updates to major hypertension and endocrine guidelines reflect growing recognition that primary aldosteronism is far more prevalent than previously understood and that broader, more practical screening approaches are needed. These recommendations increasingly extend screening beyond resistant hypertension to adults with stage 2 hypertension and even to all individuals with hypertension. They also aim to lower barriers to testing through more flexible guidance on antihypertensive medication management, reaffirm the aldosterone-to-renin ratio as the preferred initial test, and provide more standardized criteria for interpretation. Supporting evidence includes epidemiological data demonstrating a continuum of renin-independent aldosterone production across blood pressure categories, strong associations between untreated primary aldosteronism and adverse cardiovascular and kidney outcomes independent of blood pressure, and favorable cost-effectiveness of screening even in lower-risk groups. Implementation remains the principal challenge, with obstacles spanning patient, clinician, and health system levels. Emerging electronic health record strategies, including electronic phenotyping and integrated clinical decision support, have shown early promise in increasing screening uptake and streamlining diagnostic pathways. Collectively, contemporary guideline updates and implementation innovations represent a shift toward earlier and broader detection of primary aldosteronism, with the potential to reduce preventable cardiorenal disease across the hypertensive population.

Background: Preeclampsia is a severe hypertensive disorder of pregnancy associated with low SIRT1 (sirtuin 1) levels in trophoblasts. Single-cell sequencing showed abnormal activation of trophoblast Rarres2 (retinoic acid receptor responder 2) and macrophage Cmklr1 (chemokine-like receptor 1) at the maternal-fetal interface in systemic Sirt1 heterozygous knockout mice. This study investigated how low SIRT1 in trophoblasts increases RARRES2 expression, affecting macrophage polarization and preeclampsia pathogenesis.

Methods: We conducted coculture experiments to analyze trophoblast RARRES2 and macrophage CMKLR1 interactions, performed luciferase and chromatin immunoprecipitation assays to validate transcription factors for RARRES2 in trophoblasts, and utilized mass spectrometry and immunoprecipitation to identify transcriptional coregulators. cKO (trophoblast-specific Sirt1 knockout) mice were generated and treated with Rarres2 knockout or progesterone supplementation to validate the role of the SIRT1/RARRES2 axis in preeclampsia pathogenesis and prevention by progesterone. Finally, we measured RARRES2 and SIRT1 levels in the plasma of patients with preeclampsia.

Results: Low-SIRT1 expression in trophoblasts promoted M1-type macrophage polarization and inhibited trophoblast invasion, mediated by the RARRES2-CMKLR1 interaction. SIRT1 regulated RARRES2 expression in trophoblasts by recruiting NCOR2 (nuclear receptor corepressor 2). cKO mice showed preeclampsia-like symptoms and RARRES2-CMKLR1 activation at the maternal-fetal interface, which were reversed by Rarres2 knockout or progesterone supplementation. Notably, RARRES2 levels were higher and were a risk factor, whereas SIRT1 levels were lower and were a protective factor for preeclampsia in early pregnancy.

Conclusions: This study highlights SIRT1's potential role in regulating abnormal trophoblast-macrophage interactions at the maternal-fetal interface in preeclampsia and offers a new strategy for its early prediction and prevention.

Background: Circular RNAs have emerged as key regulators of vascular remodeling and promising therapeutic targets, yet their specific contributions to pulmonary hypertension (PH) remain largely unknown.

Methods: We identified a PH-related circular RNA, circMFN2, generated from the MFN2 (mitofusin-2) locus, which was significantly downregulated in the peripheral blood of patients with PH and in pulmonary arteries of Sugen/hypoxia-induced PH mice. Functional studies were performed in human pulmonary artery smooth muscle cells under hypoxic conditions and in Sugen/hypoxia mice treated intranasally with R8-circMFN2 (R8-peptide-modified liposomal circMFN2). Transcriptomic profiling, RNA-protein interaction assays, and mitochondrial function analyses were used to define the downstream mechanisms.

Results: circMFN2 overexpression significantly attenuated hypoxia-induced human pulmonary artery smooth muscle cell proliferation, migration, and mitochondrial dysfunction. RNA sequencing after circMFN2 knockdown revealed activation of gene networks associated with respiratory system diseases. Mechanistically, circMFN2 directly bound the RNA-binding protein IGF2BP3 (insulin-like growth factor 2 mRNA-binding protein 3), thereby blocking its stabilization of PDK4 (pyruvate dehydrogenase kinase 4) mRNA. This circMFN2-IGF2BP3-PDK4 regulatory axis limited PDK4-mediated metabolic reprogramming, restored mitochondrial fusion, reduced reactive oxygen species, and normalized oxidative phosphorylation. In Sugen/hypoxia mice, therapeutic intranasal delivery of R8-circMFN2 significantly improved pulmonary hemodynamics, reduced vascular remodeling, and downregulated PDK4 expression.

Conclusions: circMFN2 functions as a hypoxia-responsive regulator that preserves mitochondrial homeostasis by restraining the IGF2BP3-PDK4 axis. Intranasal delivery of R8-circMFN2 establishes a translational potential for noninvasive circular RNA-based therapy to reverse pulmonary vascular remodeling and hemodynamic impairment in PH.

Background: Postprandial hypotension (PPH) may contribute to falls among older adults, particularly those taking antihypertensive medication. However, evidence on this association in community-dwelling populations is limited. Since ambulatory blood pressure (BP) monitoring captures BP during daily activities, it may provide accurate assessments of PPH outside the clinic setting.

Methods: This prospective cohort study examined the association between PPH and fall risk among community-dwelling adults aged ≥65 years taking antihypertensive medication. At baseline, participants underwent 24-hour ambulatory BP monitoring; subsequently, they completed monthly fall calendars during a 12-month follow-up. PPH by systolic BP (SBP; systolic PPH) was defined as a postprandial SBP decline, mean SBP during the hour before the meal minus the minimum SBP during the 2 hours after the meal, following any meal of ≥20 mm Hg, or a decrease to SBP ≤90 mm Hg when preprandial SBP was ≥100 mm Hg.

Results: Among 626 participants (mean±SD age, 74.6±6.2 years; 56.1% women), 442 (70.6%) experienced systolic PPH. The mean±SD number of meals was 2.6±0.8 during the ambulatory BP monitoring period. During the 12-month follow-up, falls occurred in 169 of 442 (38.2%) participants with systolic PPH and 70 of 184 (38.0%) participants without systolic PPH. Systolic PPH was not associated with fall risk (adjusted hazard ratio, 0.93 [95% CI, 0.69-1.26]). A restricted cubic spline analysis demonstrated no evidence of an association between the largest postprandial SBP decline across all meals and fall risk.

Conclusions: In this cohort study, PPH identified by ambulatory BP monitoring was common but not associated with risk of falls.

Background: Multifetal pregnancies have increased preeclampsia risk, but the underlying pathogenesis may differ from that of singletons. It remains unclear whether twin placentas show molecular signs of preeclampsia synchronously.

Methods: We performed RNA sequencing on 32 individual placental samples from twin gestations grouped by preeclampsia status: 24 dichorionic twin (DT) and 8 monochorionic twin gestations. Ten singleton placentas from preeclamptic pregnancies were also analyzed. A benchmark data set (GSE203507, GSE114691, and GSE1482410) and a test data set (GSE190973) comprised 71 early onset preeclampsia and 69 control singleton placentas. Differential abundance analysis was conducted, and machine learning was used to derive a novel 98-transcript classification signature (accuracy >0.97 in benchmark and test data sets).

Results: Across 7 groups, 2946 transcripts were differentially modulated (likelihood-ratio test; false discovery rate <0.05). Placental signature scoring distinguished normotensive from early onset preeclampsia in GSE203507 singletons (P<0.0001) although normotensive DTs did not differ from DTs with preeclampsia (Kruskal-Wallis/Dunn). Notably, some twin placentas without clinical preeclampsia exhibited preeclampsia-like profiles. Linear mixed-effects regression, which accounted for intertwin correlation structure, revealed increasing signature scores across singleton and DT groups (all P<0.01): normotensive singletons

Conclusions: These findings highlight the complexity of preeclampsia pathology in twins. In DT pregnancies complicated by preeclampsia, placental involvement may be asymmetrical, suggesting that disease may arise from a single affected placenta; however, these results require replication.

Background: Hypertension is a leading risk factor for negative health outcomes due to end-organ effects that include small vessel disease in the brain. Low-renin hypertension is understudied at the blood pressure (BP), microvascular, and mechanistic level, and in relation to biological sex. This study examined the effects of low-renin hypertension, produced by activation of the brain renin-angiotensin system in a deoxycorticosterone acetate (DOCA) salt model.

Methods: C57BL/6J mice were treated with DOCA (or sham) and given tap H₂O and H₂O with 0.15 mol/L NaCl for 3 to 4 weeks followed by assessment of the microvasculature. Mean arterial pressure and BP variability were measured using radiotelemetry.

Results: Baseline and diurnal changes in mean arterial pressure, increases in mean arterial pressure, and BP variability during DOCA salt, were greater in male than female mice. Compared with sham treatment, endothelial function of cerebral arterioles in vivo was reduced by >70% by DOCA salt in males, dysfunction that could be reversed by local inhibition of AT1R (angiotensin II type 1 receptor), MR (mineralocorticoid receptor), or Rho kinase. DOCA salt increased arteriolar cross-sectional area and wall stiffness in male, but not female mice. In males (but not females), performance on a novel object recognition test was selectively impaired.

Conclusions: Activation of the central renin-angiotensin system has sex-specific effects on BP, diurnal changes in BP, BP variability, arteriolar structure, and stiffness. Marked endothelial dysfunction was present in males (with several contributing mechanisms). These findings provide new insight into BP-related and small vessel disease-related phenotypes, mechanisms that contribute to endothelial dysfunction, and sex-specific differences in BP traits in a preclinical model of low-renin hypertension.