American Journal of Hypertension最新文献

Background: Extracellular volume (ECV) overload and endothelial cell dysfunction are mortality risk factors in hemodialysis (HD) patients. Endothelin-1 (ET-1), an endothelium-derived vasoconstrictive peptide, is associated with poor outcomes in HD patients. We hypothesized there would be associations between ET-1 and ECV overload in hypertensive HD patients.

Methods: We obtained pre-HD ET-1, ECV/weight (bioimpedance spectroscopy), pre-HD hemodynamics, and ambulatory blood pressure (BP) in an HD cohort. Following appropriate transformations, we conducted correlation and linear regression analyses idendifying associations between ET-1, ECV overload, total peripheral resistance index (TPRI), cardiac index (CI), and ambulatory BP.

Results: Among 66 patients, median ET-1 was 1.93 (1.49-2.56) pg/ml. Median pre-HD ECV/weight, median TPRI, mean CI, and mean systolic ambulatory BP were 0.25 (0.22-0.30) l/kg, 3,161 (2,711-3,642) dynes × s/cm-5/m2, 2.92 (0.6) l/min/m2, and 143 (14) mm Hg, respectively. After reciprocal-transformation, ET-1 correlated with reciprocal-transformed ECV/weight (r = 0.3, P = 0.01), log-transformed TPRI (r = -0.3, P = 0.006), CI (r = 0.3, P = 0.009), and ambulatory BP (r = -0.3, P = 0.02). These associations persisted in linear regression analysis (β = 0.15, P = 0.002; β = -0.8, P = 0.002; β = 0.2, P = 0.002; β = -19, P = 0.03).

Conclusions: In hypertensive HD patients, ET-1 associates with ECV overload higher TPRI and ambulatory BP, and lower CI. Further research is necessary to determine if ECV reduction lowers ET-1 or if pharmacologic ET-1 antagonism can improve outcomes in HD patients with refractory ECV overload.

Background: Hypertension is a risk factor for atrial fibrillation (AF), and brain and muscle arnt-like protein 1 (Bmal1) regulate circadian blood pressure and is implicated in several fibrotic disorders. Our hypothesis that Bmal1 inhibits atrial fibrosis and susceptibility to AF in salt-sensitive hypertension (SSHT) and our study provides a new target for the pathogenesis of AF induced by hypertension.

Methods: The study involved 7-week-old male Dahl salt-sensitive that were fed either a high-salt diet (8% NaCl; DSH group) or a normal diet (0.3% NaCl; DSN group). An experimental model was used to measure systolic blood pressure (SBP), left atrial ejection fraction (LAEF), left atrial end-volume index (LAEVI), left atrial index (LAFI), AF inducibility, AF duration, and atrial fibrosis pathological examination and the expression of Baml1 and fibrosis-related proteins (TNF-α and α-SMA) in left atrial tissue.

Results: DSH increased TNF-α and α-SMA expression in atrial tissue, level of SBP and LAESVI, atrial fibrosis, AF induction rate, and AF duration, and decreased Bmal1 expression in atrial tissue, the circadian rhythm of hypertension, and level of LAEF and LAFI. Our results also showed that the degree of atrial fibrosis was negatively correlated with Bmal1 expression, but positively correlated with the expression of TNF-α and α-SMA.

Conclusions: We demonstrated that a high-salt diet leads to circadian changes in hypertension due to a reduction of Bmal1 expression, which plays a crucial role in atrial fibrosis and increased susceptibility to AF in SSHT rats.

Background: High salt (HS) intake induces an augmented hypertensive response to nitric oxide (NO) inhibition, though it causes minimal changes in blood pressure (BP) in NO intact condition. The cause of such augmentation is not known. HS induces tumor necrosis factor-alpha (TNFα) production that causes natriuresis via activation of its receptor type 1 (TNFR1). We hypothesized that NO deficiency reduces renal TNFR1 activity, leading to enhanced sodium retention and hypertension.

Methods: We examined the changes in renal TNFR1 protein expression (Immunohistochemistry analyses) after HS (4% NaCl) intake in wild-type mice (WT, C57BL6) treated with a NO synthase (NOS) inhibitor, nitro-l-arginine methyl ester (L-NAME; 0.05 mg/min/g; osmotic mini-pump), as well as in endothelial NOS knockout mice (eNOSKO) and compared the responses in WT mice with normal salt (NS; 0.3% NaCl) intake. BP was measured with tail-cuff plethysmography and 24-hour urine collections were made using metabolic cages.

Results: HS alone did not alter mean BP in untreated mice (76 ± 3 to 77 ± 1 mm Hg) but induced an augmented response in L-NAME treated (106 ± 1 vs. 97 ± 2 mm Hg) and in eNOSKO (107 ± 2 vs. 89 ± 3 mm Hg) mice. The percentage area of TNFR1 expression in renal tissue was higher in WT + HS (4.1 + 0.5%) than in WT + NS mice (2.7 ± 0.6%). However, TNFR1 expression was significantly lower in L-NAME treated WT + NS (0.9 ± 0.1%) and in eNOSKO + NS (1.4 ± 0.2%) than in both WT + NS and WT + HS mice.

Conclusions: These data indicate that TNFR1 activity is downregulated in NO deficient conditions, which facilitates salt retention leading to augmented hypertension during HS intake.

Background: The renal proximal tubule (RPT) plays a pivotal role in regulating sodium reabsorption and thus blood pressure (BP). Transient receptor potential ankyrin 1 (TRPA1) has been reported to protect against renal injury by modulating mitochondrial function. We hypothesize that the activation of TRPA1 by its agonist cinnamaldehyde may mitigate high-salt intake-induced hypertension by inhibiting urinary sodium reabsorption through restoration of renal tubular epithelial mitochondrial function.

Methods: Trpa1-deficient (Trpa1-/-) mice and wild-type (WT) mice were fed standard laboratory chow [normal diet (ND) group, 0.4% salt], standard laboratory chow with 8% salt [high-salt diet (HS) group], or standard laboratory chow with 8% salt plus 0.015% cinnamaldehyde [high-salt plus cinnamaldehyde diet (HSC) group] for 6 months. Urinary sodium excretion, reactive oxygen species (ROS) production, mitochondrial function, and the expression of sodium hydrogen exchanger isoform 3 (NHE3) and Na+/K+-ATPase of RPTs were determined.

Results: Chronic dietary cinnamaldehyde supplementation reduced tail systolic BP and 24-hour ambulatory arterial pressure in HS-fed WT mice. Compared with the mice fed HS, cinnamaldehyde supplementation significantly increased urinary sodium excretion, inhibited excess ROS production, and alleviated mitochondrial dysfunction of RPTs in WT mice. However, these effects of cinnamaldehyde were absent in Trpa1-/- mice. Furthermore, chronic dietary cinnamaldehyde supplementation blunted HS-induced upregulation of NHE3 and Na+/K+-ATPase in WT mice but not Trpa1-/- mice.

Conclusions: The present study demonstrated that chronic activation of Trpa1 attenuates HS-induced hypertension by inhibiting urinary sodium reabsorption through restoring renal tubular epithelial mitochondrial function. Renal TRPA1 may be a potential target for the management of excessive dietary salt intake-associated hypertension.

Background: A novel method for estimating central systolic aortic pressure (cSAP) has emerged, relying solely on the peripheral mean (MBP) and diastolic (DBP) blood pressures. We aimed to assess the accuracy of this Direct Central Blood Pressure estimation using cuff alone (DCBPcuff = MBP2/DBP) in comparison to the use of a generalized transfer function to derive cSAP from radial tonometry (cSAPtono).

Methods: This retrospective analysis involved the International Database of Central Arterial Properties for Risk Stratification (IDCARS) data (Aparicio et al., Am J Hypertens 2022). The dataset encompassed 10,930 subjects from 13 longitudinal cohort studies worldwide (54.8% women; median age 46.0 years; office hypertension: 40.1%; treated: 61.0%), documenting cSAPtono via SphygmoCor calibrated against brachial systolic BP (SBP) and DBP. Our analysis focused on aggregate group data from 12/13 studies (89% patients) where a full BP dataset was available. A 35% form factor was used to estimate MBP = (DBP + (0.35 × (SBP-DBP)), from which DCBPcuff was derived. The predefined acceptable error for cSAPtono estimation was set at ≤ 5 mm Hg.

Results: The cSAPtono values ranged from 103.8-127.0 mm Hg (n = 12). The error between DCBPcuff and cSAPtono was 0.2 ± 1.4 mm Hg, with no influence of the mean. Errors ranged from -1.8 to 2.9 mm Hg across studies. No significant difference in errors was observed between BP measurements obtained via oscillometry (n = 9) vs. auscultation (n = 3) (P = 0.50).

Conclusions: Using published aggregate group data and a 35% form factor, DCBPcuff demonstrated remarkable accuracy in estimating cSAPtono, regardless of the BP measurement technique. However, given that individual BP values were unavailable, further documentation is required to establish DCBPcuff's precision.

Background: Medicare supplement insurance, or Medigap, covers 21% of Medicare beneficiaries. Despite offsetting some out-of-pocket (OOP) expenses, remaining OOP costs may pose a barrier to medication adherence. This study aims to evaluate how OOP costs and insurance plan types influence medication adherence among beneficiaries covered by Medicare supplement plans.

Methods: We conducted a retrospective analysis of the Merative MarketScan Medicare Supplement Database (2017-2019) in Medigap enrollees (≥65 years) with hypertension. The proportion of days covered (PDC) was a continuous measure of medication adherence and was also dichotomized (PDC ≥0.8) to quantify adequate adherence. Beta-binomial and logistic regression models were used to estimate associations between these outcomes and insurance plan type and log-transformed OOP costs, adjusting for patient characteristics.

Results: Among 27,407 patients with hypertension, the average PDC was 0.68 ± 0.31; 47.5% achieved adequate adherence. A mean $1 higher in 30-day OOP costs were associated with a 0.06 (95% confidence intervals [CIs]: -0.09 to -0.03) lower probability of adequate adherence, or a 5% (95% CI: 4%-7%) decrease in PDC. Compared with comprehensive plan enrollees, the odds of adequate adherence were lower among those with point-of-service plans (odds ratio [OR]: 0.69, 95% CI: 0.62-0.77), but higher among those with preferred provider organization (PPO) plans (OR: 1.08, 95% CI: 1.01-1.15). Moreover, the association between OOP costs and PDC was significantly greater for PPO enrollees.

Conclusions: While Medicare supplement insurance alleviates some OOP costs, different insurance plans and remaining OOP costs influence medication adherence. Reducing patient cost-sharing may improve medication adherence.