American Journal of Hypertension
ISSN / EISSN: 08957061 / 19417225
Published by: Oxford University Press (OUP)
Total articles ≅ 17,593
Latest articles in this journal
Published: 30 November 2022
American Journal of Hypertension; https://doi.org/10.1093/ajh/hpac128
Blood pressure (BP) variability (BPV) is an emerging risk factor for cognitive impairment and dementia, but relationships with cognition in the context of antihypertensive strategies remain unclear. We examined whether visit-to-visit BPV relates to cognitive change based on antihypertensive treatment type. In this post hoc analysis of the SPRINT MIND trial, 2348 participants underwent 4 BP measurements over a 9-month period after treatment randomization (standard vs intensive BP lowering) and ≥ 1 neuropsychological evaluation thereafter. BPV was calculated as tertiles of BP SD. Participants underwent cognitive testing at baseline and every two years during the planned 4-year follow-up. Cognitive composite scores were calculated for global cognition, memory, language, executive function, and processing speed. Linear mixed models investigated relationships between BPV, antihypertensive treatment group, and time on cognitive composite scores. Elevated BPV was associated with the fastest decline in processing speed (ß = -.07 [95% CI -.12, -.01]; p = .02) and executive function (ß = -.08 [95% CI -.16, -.006]; p = .03) in the standard treatment group only. BPV was not related to cognitive change in the intensive treatment group. Mean/minimum/maximum BP was not associated with cognitive composite scores over time in either antihypertensive treatment group. Elevated BPV remains a risk for cognitive decline despite strictly controlled BP levels, in the standard treatment group. Specific declines were observed in processing speed and executive function, domains often impacted by cerebrovascular disease and may underpin risk for dementia and cerebrovascular disease associated with BPV.
Published: 16 November 2022
American Journal of Hypertension; https://doi.org/10.1093/ajh/hpac126
Published: 6 November 2022
American Journal of Hypertension; https://doi.org/10.1093/ajh/hpac125
Parag Goyal, MD, MSc, Ian M Kronish, MD, MPH; N-of-1 trials for pediatric hypertension? A promising approach to increasing the precision of antihypertensive tre
Published: 4 November 2022
American Journal of Hypertension; https://doi.org/10.1093/ajh/hpac124
Steroidal mineralocorticoid-receptor-antagonists (MRAs), such as spironolactone and eplerenone, are guideline-directed therapies in patients with heart failure with reduced ejection fraction or resistant hypertension. However, the associated risk of hyperkalemia and hormonal side effects limit their broad use and downstream cardiorenal protection in high-risk patients with type 2 diabetes mellitus (T2DM) and moderate-to-advanced chronic kidney disease (CKD). The critical unmet need to improve long-term cardiorenal outcomes in such patients with CKD has sparked considerable efforts to the discovery and development of a new class of compounds. Finerenone is a novel, non-steroidal MRA that has recently received regulatory approval with the indication of cardiorenal protection in patients with CKD associated with T2DM. Two landmark phase 3 clinical trials, FIDELIO-DKD and FIGARO-DKD, demonstrated that among patients with T2DM and a broad spectrum of CKD, finerenone reduced the risk of “hard” cardiovascular and kidney failure outcomes as compared with placebo, with a minimal risk of hyperkalemia. Subgroup analyses of these trials also provided preliminary evidence that the efficacy and safety profile of finerenone was similar and irrespective of background therapy with other guideline-directed therapies, such as sodium-glucose co-transporter type 2 (SGLT-2) inhibitors and glucagone-like peptide 1 receptor agonists. Whether the combination of finerenone with a SGLT-2 inhibitor is more beneficial in patients with T2DM and CKD as compared with either therapy alone is a crucial research question that is currently under investigation in an ongoing clinical trial.
Published: 2 November 2022
American Journal of Hypertension; https://doi.org/10.1093/ajh/hpac123
Objective: Identifying potential pathways through which adverse childhood experiences (ACEs) impact health and health behavior remains important, given ACE survivors’ increased risk for cardiovascular disease and poor cardiovascular health behaviors. This study examines whether modifiable variables - depression and patient activation – explain the relationship between adverse childhood experiences and medication adherence. Methods: Using baseline data from a pragmatic trial designed to decrease disparities in hypertension control, we conducted regression analyses to examine whether depression and patient activation mediated the association between ACEs and medication adherence. Data were collected between August 2017 and October 2019 (n = 1818). Results: Participants were predominantly female (59.4%) and Black or African American (57%) with uncontrolled blood pressure (mean – 152.3/85.5 mm Hg). Most participants reported experiencing at least one ACE (71%) and approximately 50% reported being adherent to their blood pressure medication. A significant indirect effect between ACEs and medication adherence was found for depression symptoms (Sobel test z = -5.46, p <.001). Patient activation was not a mediator in these relationships. Conclusions: Experiencing more depression symptoms significantly accounted for the association between adverse childhood experiences and medication adherence in a diverse sample of adults with uncontrolled blood pressure. Addressing depression symptoms, which may result from experiences with ACEs and other current stressors, could translate to better medication adherence and, potentially, better blood pressure control among this high-risk group. Given the serious lifetime health implications of ACEs, continued efforts are needed for primary prevention of childhood adversities.
Published: 1 November 2022
American Journal of Hypertension, Volume 35, pp 964-964; https://doi.org/10.1093/ajh/hpac033
To investigate the role and mechanism of microRNA-7a-5p (miR-7a-5p) in paraventricular nucleus on sympathetic overactivity in the spontaneously hypertensive rats (SHR). Wistar-Kyoto (WKY) rats and SHR aged 12 weeks were randomly divided into recombinant adeno-associated virus (rAAV) overexpressing miR-7a-5p mimic, miR-7a-5p negative control (NC), antimiR-7a-5p, or NC of antimir-7a-5p treatment groups (n = 6 per group). In addition, WKY rats and SHR aged 12 weeks were randomly divided into rAAV overexpressing GABRA1, GABRA1 NC, GABRA1 shRNA, or NC of GABRA1 shRNA treatment groups (n = 6 per group). Four weeks later, hemodynamic parameters, renal sympathetic nerve activity (RSNA), and plasma norepinephrine levels were observed. Four weeks after injection of rAAV into the paraventricular nucleus, overexpression of miR-7a-5p mimic increased RSNA and mean arterial pressure (MAP) in WKY and SHR (all P < 0.05). The number of FosB positive neurons in paraventricular nucleus was significantly upregulated (all P < 0.01) while the number of GABRA1 positive neurons in paraventricular nucleus was significantly downregulated (all P < 0.01). Overexpression of GABRA1 in hypothalamic paraventricular nucleus decreased RSNA and MAP in WKY and SHR (all P < 0.05). Compared with WKY, the overexpression or knockdown of miR-7a-5p/GABRA1 had more significant effect on RSNA and MAP in SHR (all P < 0.05). The expression of miR-7a-5p in hypothalamic paraventricular nucleus in SHR was significantly upregulated (P < 0.01) while GABRA1 protein levels were significantly downregulated (P < 0.01). miR-7a-5p mimic transfection in primary brain neurons or NG108 cells resulted in significant downregulation of GABRA1 protein expression. TargetScan prediction showed that there was sequence binding at the 3′UTR end of GABRA1 mRNA by miR-7a-5p. Dual luciferase reporter assay confirmed that miR-7a-5p can target GABRA1 gene. miR-7a-5p in hypothalamic paraventricular nucleus increases RSNA by inhibiting GABRA1 expression, and may contribute to the development of hypertension.
Published: 1 November 2022
American Journal of Hypertension, Volume 35, pp 964-965; https://doi.org/10.1093/ajh/hpac062
To assess the effects of telmisartan on susceptibility of atrial fibrillation (AF) in pressure overload rats, and to probe the underlying molecular mechanism and signal pathways. Forty-nine 12-week-old male SD rats were randomly divided into sham operation (n = 15), abdominal aorta coarctation (AAC, n = 17), and AAC with telmisartan treatment groups (n = 17). Telmisartan 10 mg/(kg d) was administered by gavage for 4 weeks after AAC. Four weeks after operation, the indexes of echocardiography, hemodynamics, and cardiac electrophysiology including left atrial conduction time (LACT) and interatrial conduction time (IACT) were assessed. The mRNAs were extracted from left atrial tissues and analyzed by next generation sequencing. Systolic left ventricular pressure, systolic aortic pressure, left atrial diameters, and interventricular septal thickness in AAC rats were higher than those in sham rats (all P < 0.05), all of which were lowered by telmisartan treatment (all P < 0.05). LACT and IACT were significantly increased in AAC rats and ameliorated by telmisartan treatment. In isolated perfused heart, duration of AF induced by burst electrical stimulation was longer in AAC rats, which was shortened by telmisartan treatment. A total of 897 genes were downregulated by AAC but upregulated by telmisartan treatment (down/up 897 gene set). Also, 1,542 genes were upregulated by AAC but downregulated by telmisartan treatment (up/down 1,542 gene set). Venn and GO enrichment analyses showed that 5 target genes in the down/up 897 gene set were the key rate limiting enzymes of fatty acid oxidation while 5 target genes in the up/down 1,542 gene set were involved in Wnt/β-catenin signal pathway and type I and II collagen components. Telmisartan lowers AF susceptibility via suppressing the left atrial enlargement and shortening atrial conduction time. Possible molecular mechanisms may be related to the improvement of fatty acid oxidation and downregulation of the Wnt/β-catenin pathway and collagen expression.
Published: 1 November 2022
American Journal of Hypertension, Volume 35, pp 965-965; https://doi.org/10.1093/ajh/hpac061
To investigate the relationship between salt taste threshold and hypertensive nephropathy in patients with essential hypertension. A cross-sectional study was conducted in 346 hypertensive patients in Daping Hospital from 2017 to 2019. Among them 94 patients were hypertensive nephropathy and 252 hypertensive patients without renal damage served as controls. The salt taste threshold of patients was measured by taking different concentrations of NaCl solution. The difference in salt taste threshold between the 2 groups of patients was compared, and the correlation between salt taste threshold and hypertensive nephropathy was analyzed. Receiver operating characteristic (ROC) curve was used to analyze the value of salt taste threshold to predict hypertensive nephropathy. The salt taste threshold of the hypertensive nephropathy patients was significantly higher than that in hypertensive patients without renal damage [0.075 (0.050–0.100) vs. 0.050 (0.050–0.100) mol/l, P = 0.010]. As salt taste threshold increased, the renal function decreased gradually, which was manifested by the increase of urine microalbumin to creatinine ratio, blood creatinine, blood urea nitrogen, urine N-acetyl-β-glucosaminidase, and the decrease of estimated glomerular filtration rate. Logistic regression analysis showed that after adjusting for traditional risk factors, a higher salt taste threshold was an independent risk factor for hypertensive nephropathy (odds ratio = 1.299, 95% confidence interval [CI] 1.020–1.655, P = 0.034). The area under ROC curve was 0.586 (95% CI 0.520–0.652). Salt taste threshold correlates with biochemical indicators of renal damage, and a higher salt taste threshold is a risk factor of hypertensive nephropathy in patients with essential hypertension.
Published: 31 October 2022
American Journal of Hypertension; https://doi.org/10.1093/ajh/hpac122
Background: Higher blood pressure variability (BPV) is associated with the development of major vascular diseases, independent of mean blood pressure. However, despite data indicating that serum inflammatory markers are linked to hypertension, the association between serum inflammatory markers and BPV has not been studied in humans. Methods: This is a post hoc analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) study. The study exposure was tertiles of serum level of interleukin-6 (IL-6), C-reactive protein (CRP), d-dimer, plasmin–antiplasmin complex (PAP), fibrinogen antigen, and calibrated Factor VIII (%) at the baseline study visit. The primary outcome was visit-to-visit BPV measured as the residual standard deviation (rSD) of at least 4 study visits (2000–2018). Two logistic regression models were fit to the top tertile of rSD during follow-up: in Model 1, we adjusted for age, sex, and hypertension, and in Model 2, for patient age categories, sex, race/ethnicity, education, hypertension, diabetes, smoking, drinking, body mass index, lipid-lowering medication, and mean systolic blood pressure. Results: Our analysis included 5,483 patients, with a mean (SD) age of 61.4 (10.0) years, 52.9% female, and 40.7% White. In unadjusted analyses, all markers of inflammation were associated with higher BPV, but after adjustment, only IL-6 retained significance (P < 0.001). The odds ratio for the highest tertile of BPV and IL-6 was 1.49 (95% confidence interval [CI] 1.28–1.74, P < 0.001). Conclusions: Baseline serum IL-6 was associated with increased subsequent BPV in a large multiracial cohort. Further investigation is needed to better understand the relationship between chronic inflammation and BPV.
Published: 30 October 2022
American Journal of Hypertension; https://doi.org/10.1093/ajh/hpac121
We investigated the association between ambulatory blood pressure (BP) and the risk of home hypertension in a normotensive population and whether considering ambulatory BP improves the 10-year prediction model for home hypertension risk, which was developed in the previous Ohasama Study. In this prospective study, we followed up 410 participants (83.2% women; age, 53.6 years) without home and ambulatory hypertension in the general population of Ohasama, Japan. The Cox model was used to assess the hazard ratios for home hypertension (home BP ≥135/≥85 mmHg or initiation of antihypertensive treatment) and model improvement. During a mean 14.2-year follow-up, 225 home hypertension incidences occurred. The hazard ratio (95% confidence interval) for home hypertension incidence per 1-standard deviation higher (=6.76 mmHg) 24-h systolic BP was 1.59 (1.33–1.90), after adjustments for possible confounding factors, including baseline home systolic BP. Harrell’s C-statistics increased from 0.72 to 0.73 (P=0.11) when 24-h systolic BP was added to the basic 10-year home hypertension prediction model, which includes sex, age, body mass index, smoking status, office systolic BP, and baseline home systolic BP. Continuous net reclassification improvement (0.53, P<0.0001) and integrated discrimination improvement (0.028, P=0.0014) revealed improvement in the model. 24-h systolic BP could be an independent predictor of future home hypertension. Home BP and 24-h BP can longitudinally influence each other in the long term.