Journal of The American Society of Hypertension最新文献

American Indian communities are at greater risk of hypertension and cardiovascular disease than the general US population and are exposed to greater cadmium levels. However, cadmium's effect on blood pressure is unclear. This study assesses the association between baseline urinary cadmium and longitudinal changes in blood pressure in American Indian communities. Cadmium was measured in 3047 baseline urine samples from Strong Heart Study participants from three geographic areas. Longitudinal changes in blood pressure across three study visits (1989–1999) were modeled using linear mixed models by baseline log urinary cadmium to creatinine ratio. Hypertension risk was evaluated using interval-censored survival analysis. Higher levels of urinary cadmium at baseline were associated with faster rates of increase in diastolic and systolic blood pressure (P [trend] = .001 and .02, respectively). The estimated change in diastolic and systolic blood pressures per year was 0.18 mm Hg (0.05–0.31) and 0.62 mm Hg (0.37–0.87) in the upper quintile of cadmium level compared with −0.11 mm Hg (−0.24 to 0.02) and 0.21 mm Hg (−0.04 to 0.46) in the lowest, respectively. A one-unit increase in log-transformed urinary cadmium was associated with 10% greater hypertension risk (95% confidence interval: 1.01–1.20). In conclusion, blood pressure of individuals with greater baseline levels of urinary cadmium increased at a faster rate relative to those with lower levels.

In recent years, microvesicles (MVs) derived from mesenchymal stem cells (MSCs) have been proved to be able to improve the outcome of pulmonary arterial hypertension (PAH) in many respects, but the underlying mechanisms of it still remain unclear. Because the renin-angiotensin system (RAS) has been found to be closely related to PAH, the present study was designed to investigate whether the effect of MSC-derived MVs on PAH was correlated with RAS. MVs were isolated and purified from bone marrow MSCs. PAH rat models were established by a single intraperitoneal injection of 1% monocrotaline (MCT, 50 mg/Kg). In vivo study, after 3 weeks of MCT exposure, Nor group and PAH group were injected with 0.5 mL saline every 2 days through tail vein, whereas MVs group was injected with 0.5 mL saline containing 30μg MVs and A-779 + MVs group injected with 0.5 mL saline containing 120μg A-779 and 30μg MVs until 5 weeks of MCT exposure. Whereafter all the groups were analyzed for hemodynamic evaluation, right ventricular hypertrophy index, pulmonary vessel wall thickness index and pulmonary vessel lumen area index, the inflammation score, the collagen fiber volume fraction, the levels of Ang-(1-7) and Ang-Ⅱin plasma and lung tissue, and the mRNA levels of ACE2 and ACE in the lung tissue. MVs derived from MSCs relieved the pulmonary artery pressure, right ventricular hypertrophy index, pulmonary vessel wall thickness index, pulmonary vessel lumen area index, the inflammation score, and the collagen fiber volume fraction. Moreover, in MVs group, ACE2 mRNA in the lung tissues and plasma levels of Ang-(1-7) were both upregulated compared with PAH group. On the contrary, ACE and Ang-II were decreased compared with PAH group. However, the enhanced protective effects observed in MVs group were diminished by the use of A-779, an inhibitor of Mas receptor in ACE2-Ang-(1-7)-Mas axis. MVs derived from bone marrow MSCs can exert beneficial effects against MCT-induced PAH in vivo, meanwhile shifting the balance from ACE-Ang-II-AT1R axis toward the ACE2-Ang-(1–7)-Mas axis, which might be one of the possible therapeutic mechanisms for MVs subcellular treatment.

The vascular endothelial growth factor (VEGF) signaling pathway (VSP) fulfills a cardinal role in endothelial cells and its inhibition has profound cardiovascular impact. This is true not only for the normal vasculature but also for the tumor vasculature when VSP inhibitors are used as anti-angiogenic therapies. Generalized endothelial dysfunction predisposes to vasoconstriction, atherosclerosis, platelet activation, and thrombosis (arterial more than venous). All of these have been reported with VSP inhibitors and collectively give rise to vascular toxicities, the most concerning of which are arterial thromboembolic events (ATE). VSP inhibitors include antibodies, acting extracelluarly on VEGF, such as bevacizumab and tyrosine kinases inhibitors, acting intracellularly on the kinase domain of VEGF receptors, such as sunintib and sorafenib. The addition of bevacizumab and VSP tyrosine kinase inhibitor therapy to the cancer treatment regimen is associated with a 1.5–2.5-fold and 2.3–4.6-fold increase risk of ATEs, respectively. Risk factors for ATEs while on VSP inhibitor therapy include age older than 65 years, previous thromboembolic events, history of atherosclerotic disease, and duration of VSP inhibitor therapy. In clinical practice, hypertension remains the most commonly noted vascular manifestation of VSP inhibition. Optimal blood pressure goals and preferred therapeutic strategies toward reaching these goals are not defined at present. This review summarizes current data on this topic and proposes a more intensive management approach to patients undergoing VSP inhibitor therapy including Systolic Blood PRessure Intervention Trial (SPRINT) blood pressure goals, pleiotropic vasoprotective agents such as angiotensin converting enzyme inhibitors, amlodipine, and carvedilol, high-dose statin therapy, and aspirin.

Measurements of 24-hour urinary sodium (24hrUNa) and potassium (24hrUK) excretion are useful in hypertensives but 24-hour urine collection may be difficult or unreliable. We compared three formulas (Tanaka, Kawasaki, Pan American Health Organization [PAHO]) proposed to estimate 24hrUNa and 24hrUK based on spot urine measurements. We studied 382 patients admitted to a hypertension unit. Sodium, potassium, and creatinine levels were measured using standard laboratory methods in a morning urine sample, followed by 24-hour urinary collection. Agreement between estimated and measured 24hrUNa and 24hrUK was evaluated using the Pearson correlation and Bland-Altman plots. Measured 24hrUNa was 158 ± 75 mmol/d and 24hrUK was 54 ± 24 mmol/d. The correlation coefficient was r = 0.53 for estimated versus measured 24hrUNa, r = 0.69–0.73 for estimated versus measured 24hrUK (all P < .001). The mean bias for 24hrUNa was significantly smaller for Tanaka (10.5 mmol/d) and PAHO (11.5 mmol/d) compared with Kawasaki formula (−29.9 mmol/d). The mean bias for 24hrUK was significantly smaller for Kawasaki (7.3 mmol/d) and PAHO (8.3 mmol/d) compared with Tanaka formula (16.5 mmol/d). Using a single morning urine sample, we found the PAHO formula to be the best for predicting mean 24hrUK and 24hrUNa in hospitalized hypertensive patients. However, precision and accuracy of all the evaluated formulas was inadequate.

Hypertension, obesity, and old age are major risk factors for left ventricular (LV) diastolic dysfunction (LVDD), but easily applicable screening tools for people at risk are lacking. We investigated whether HF1, a urinary biomarker consisting of 85 peptides, can predict over a 5-year time span mildly impaired diastolic LV function as assessed by echocardiography. In 645 white Flemish (50.5% women; 50.9 years [mean]), we measured HF1 by capillary electrophoresis coupled with mass spectrometry in 2005–2010. We measured early (E) and late (A) peak velocities of the transmitral blood flow and early (e') and late (a') mitral annular peak velocities and their ratios in 2009–2013. In multivariable-adjusted analyses, per 1-standard deviation increment in HF1, e' was −0.193 cm/s lower (95% confidence interval: −0.352 to −0.033; P = .018) and E/e' 0.174 units higher (0.005–0.342; P = .043). Of 645 participants, 179 (27.8%) had LVDD at follow-up, based on impaired relaxation in 69 patients (38.5%) or an elevated filling pressure in the presence of a normal (74 [43.8%]) or low (36 [20.1%]) age-specific E/A ratio. For a 1-standard deviation increment in HF1, the adjusted odds ratio was 1.37 (confidence interval, 1.07–1.76; P = .013). The integrated discrimination (+1.14%) and net reclassification (+31.7%) improvement of the optimized HF1 threshold (−0.350) in discriminating normal from abnormal diastolic LV function at follow-up over and beyond other risk factors was significant (P ≤ .024). In conclusion, HF1 may allow screening for LVDD over a 5-year horizon in asymptomatic people.

The study aimed to explore the association of visceral fat index (VFI) with untreated hypertension in different genders and evaluate the practicability of VFI as a marker for discriminating untreated hypertension in Chinese rural population. A total of 12,536 eligible participants aged 35 years and older were derived from the RuralDiab study in China. VFI was assessed with bioelectrical impendence methods and divided into sex-specific quartiles. Logistic regression and restricted cubic spline regression were performed. Receiver operating characteristic curve was applied to analyze the discriminating performance of VFI. Meanwhile, a meta-analysis was conducted to validate the result of this study.

Compared with the lowest VFI quartile, the adjusted odds ratios (ORs) and 95% confidence interval (95% CI) in the highest VFI quartile were 3.68 (2.91–4.66) in male and 2.63 (2.12–3.25) in female (P_trend < .01). Nonlinear increasing trends about the risk of untreated hypertension were observed with the continuously increasing VFI in both genders (P_linearity < .01). The sensitivity and specificity in the optimal cutoff values for VFI were 58.37% and 62.26% in male, and 49.09% and 66.67% in female. The area under the curves (95% CI) were 0.64 (0.63–0.66) in male and 0.61 (0.60–0.62) in female. Meta-analysis results displayed the pooled odds ratios (95% CI) of 2.65 (1.79–3.93) in male and 2.27 (1.74–2.95) in female. VFI was significantly positively correlated with the risk of untreated hypertension, and dose-response relationships were observed in both genders in Chinese rural population. However, VFI as a marker had limited potential for discriminating untreated hypertension.

It has been demonstrated that bone morphogenetic protein-9 (BMP-9) may have an important role in vascular development and stability. However, the association of circulating BMP-9 with essential hypertension (HTN) has not been established in humans. The objective of this study is to observe the changes of circulating BMP-9 levels in patients with HTN and to investigate the association of circulation BMP-9 and insulin resistance (IR) in a cross-sectional study. Two hundred twenty-five individuals, including 132 patients with hypertension, and 93 healthy controls, were included in the present study. Circulating BMP-9 concentrations were measured with an ELISA kit. The association of circulating BMP-9 with other parameters was analyzed. When compared with healthy subjects, circulating BMP-9 concentrations were markedly lower in HTN patients (46.20 [31.85–62.80] vs. 77.21 [39.33–189.15], P < .01) and correlated negatively with blood pressure and the homeostasis model assessment of insulin resistance (P < .05 or P < .01). Decreasing levels of BMP-9 were independently and markedly related to HTN. In a multiple linear regression analysis, only systolic blood pressure and free fatty acid concentrations were independently associated with circulating BMP-9. Our findings suggest that BMP-9 may be a serum biomarker for HTN and IR.