Hypertension最新文献

Background: The aortic-femoral arterial stiffness gradient, calculated as the ratio of lower-limb pulse-wave velocity (PWV) to central (aortic) PWV, is a promising tool for assessing cardiovascular disease (CVD) risk, but whether it predicts incident CVD is unknown.

Methods: We examined the association of the aortic-femoral arterial stiffness gradient measures carotid-femoral stiffness gradient (femoral-ankle PWV divided by carotid-femoral PWV) and the heart-femoral stiffness gradient (femoral-ankle PWV divided by heart-femoral PWV), as well as PWV, with incident CVD (coronary disease, stroke, and heart failure) and all-cause mortality among 3109 participants of the Atherosclerosis Risk in Communities Study cohort (age, 75±5 years; carotid-femoral PWV, 11.5±3.0 m/s), free of CVD. Cox regression was used to estimate hazard ratios (HR) and 95% CIs.

Results: Over a median 7.4-year follow-up, there were 322 cases of incident CVD and 410 deaths. In fully adjusted models, only top quartiles of carotid-femoral stiffness gradient (quartile 4: HR, 1.43 [95% CI, 1.03-1.97]; and quartile 3: HR, 1.49 [95% CI, 1.08-2.05]) and heart-femoral stiffness gradient (quartile 4: HR, 1.77 [95% CI, 1.27-2.48]; and quartile 3: HR, 1.41 [95% CI, 1.00-2.00]) were significantly associated with a greater risk of incident CVD. Only high aortic stiffness in combination with low lower-limb stiffness was significantly associated with incident CVD (HR, 1.46 [95% CI, 1.06-2.02]) compared with the referent low aortic stiffness and high lower-limb stiffness. No PWVs were significantly associated with incident CVD. No exposures were associated with all-cause mortality.

Conclusions: The aortic-femoral arterial stiffness gradient may enhance CVD risk assessment in older adults in whom the predictive capacity of traditional risk factors and PWV are attenuated.

Hypertension requires increased systemic vascular resistance. Thus far, Mendelian hypertension-related genes are related to salt retention, an indirect regulatory effect. With the identification of mutated, overactive, PDE3A (phosphodiesterase 3A), we have uncovered a more direct vasoconstrictive mechanism. The autosomal-dominant syndrome features another specific phenotype, brachydactyly type E. Hypertension and the bony phenotype invariably occur together. We distinguished between these phenotypes by examining individual pedigrees. We implicated the gene encoding the parathyroid hormone-related peptide in the brachydactyly. We identified the hypertensive mechanisms as involving regulatory-region, gain-of-function, exon 4 rare pathogenic variants, in the cAMP-cGMP-catabolizing enzyme, PDE3A. We generated rodent models that recapitulate all human phenotypes. Comparisons not only allowed pathogenic insights into the human condition but also provided intervention models. Moreover, we identified rare pathogenic variants in exon 13 encoding the enzymatic pocket. These patients had identical phenotypes, also corroborated in a rodent model, which produced the same human phenotypes. These data could allow the differentiation between a target organ and blood pressure phenotype. The research allows visualization of enzymatic processes at the intracellular nanodomain level. The scope of this project has elucidated genetic mechanisms important to cartilage development, possibly cancer metastases, and findings relevant to cardiovascular regulation via systemic vascular resistance. For our team, the project was an educational/scientific adventure over a professional lifetime.

Background: Primary aldosteronism (PA), the most common curable salt-dependent form of arterial hypertension, features renal K⁺ loss and enhanced Na⁺ reabsorption. We investigated whether the electrolyte, water, and TonEBP (tonicity-responsive enhancer binding protein)/NFAT5 (nuclear factor of activated T cells 5) content is altered in the skin of patients with PA and corrected by surgical cure.

Methods: We obtained skin biopsies from 80 subjects: 49 consecutive patients with PA, optimally treated with a mineralocorticoid receptor antagonist; 6 essential hypertensives; and 25 normotensive controls. We measured Na⁺, K⁺, water content with atomic absorption spectroscopy after ashing, and NFAT5 mRNA with digital droplet polymerase chain reaction. The patients with PA were retested after adrenalectomy.

Results: We discovered a higher dry weight of the skin biopsy specimen at surgery than at follow-up (P<0.001) and a direct correlation with electrolyte and water content (all P<0.01), indicating the need for dry weight adjustment of electrolyte and water data. Surgical cure of PA markedly increased skin dry weight-adjusted K⁺ (from 1.14±0.1 to 2.81±0.27 µg/mg; P<0.001) and water content (from 2.92±1.4 to 3.85±0.23 mg/mg; P<0.001), but left dry weight-adjusted skin Na⁺ content unaffected. In patients with PA, NFAT5 mRNA was higher (P=0.031) than in normotensive controls and decreased after surgery (P=0.035).

Conclusions: Despite mineralocorticoid receptor antagonist treatment ensuring normokalemia, the patients with PA had a skin cell K⁺ depletion that was corrected by adrenalectomy. The activated NFAT5/TonEBP pathway during mineralocorticoid receptor antagonist administration suggests enhanced skin Na⁺ lymphatic drainage and can explain the lack of overt skin Na⁺ accumulation in patients with PA. Its deactivation after surgical cure can account for the lack of skin Na⁺ decrease postadrenalectomy.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06090617.

Background: Blood-brain barrier (BBB) integrity is presumed to be impaired in hypertension, resulting from cerebral endothelial dysfunction. Hypertension precedes various cerebrovascular diseases, such as cerebral small vessel disease, and is a risk factor for developing neurodegenerative diseases for which BBB disruption is a preceding pathophysiological process. In this cross-sectional study, we investigated the relation between hypertension, current blood pressure, and BBB leakage in human subjects.

Methods: BBB leakage was determined in 22 patients with hypertension and 19 age- and sex-matched normotensive controls (median age [range], 65 [45-80] years; 19 men) using a sparsely time-sampled contrast-enhanced 7T magnetic resonance imaging protocol. Structural cerebral small vessel disease markers were visually rated. Multivariable regression analyses, adjusted for age, sex, cardiovascular risk factors, and cerebral small vessel disease markers, were performed to determine the relation between hypertension status, systolic and diastolic blood pressure, mean arterial pressure, drug treatment, and BBB leakage.

Results: Both hypertensive and normotensive participants showed mild scores of cerebral small vessel disease. BBB leakage did not differ between hypertensive and normotensive participants; however, it was significantly higher for systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the cortex, and diastolic blood pressure and mean arterial pressure in the gray matter. Effectively treated patients showed less BBB leakage than those with current hypertension.

Conclusions: BBB integrity in the total and cortical gray matter decreases with increasing blood pressure but is not related to hypertension status. These findings show that BBB disruption already occurs with increasing blood pressure, before the presence of overt cerebral tissue damage. Additionally, our results suggest that effective antihypertensive medication has a protective effect on the BBB.

Registration: URL: https://trialsearch.who.int/; Unique identifier: NL7537.

Background: In many practices, the screening for primary aldosteronism relies on a single-blood draw for plasma aldosterone concentration (PAC) and plasma renin activity (PRA) to establish an aldosterone-to-renin ratio (ARR). ARR levels vary between expert centers and repeated assays in the same individual, emphasizing the potential variability of this screening approach. A suppressed PRA to <1 ng/mL per h has been proposed as an alternative test to the ARR.

Methods: We compared 2 potential screening approaches to identify probable primary aldosteronism (ARR≥30 or ARR≥20 versus PRA suppressed below 1 ng/mL per h) in a cohort of 94 829 paired PRA and PAC samples submitted by clinicians to evaluate the presence of primary aldosteronism.

Results: Of 94 829 patients, 20.3% tested positive based on ARR≥20 (95% CI, 20.0%-20.5%), 13.9% based on ARR≥30 (95% CI, 13.6%-14.1%), versus 45.9% based on suppressed PRA (<1 ng/mL per minute [95% CI, 45.5%-46.2%]). In the PRA group, a range of aldosterone levels was observed: 5.5% had PAC >15 ng/dL, 25.2% had PAC 5 to 15 ng/dL, and 15.2% had PAC <5 ng/dL, compared with 6%, 12.7%, and 1.6% in the ARR≥20 group and 4.7%, 8.5%, and 0.7% in the ARR≥30 group.

Conclusions: In this cohort of individuals being screened for primary aldosteronism, substantially more individuals were identified using criteria focused on suppression of renin activity compared with using the aldosterone renin ratio as a screening tool.