Trial of Intensive Blood-Pressure Control in Older Patients with Hypertension.

BACKGROUND: The appropriate target for systolic blood pressure to reduce cardiovascular risk in older patients with hypertension remains unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned Chinese patients 60 to 80 years of age with hypertension to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. RESULTS: Of the 9624 patients screened for eligibility, 8511 were enrolled in the trial; 4243 were randomly assigned to the intensive-treatment group and 4268 to the standard-treatment group. At 1 year of follow-up, the mean systolic blood pressure was 127.5 mm Hg in the intensive-treatment group and 135.3 mm Hg in the standard-treatment group. During a median follow-up period of 3.34 years, primary-outcome events occurred in 147 patients (3.5%) in the intensive-treatment group, as compared with 196 patients (4.6%) in the standard-treatment group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.92; P = 0.007). The results for most of the individual components of the primary outcome also favored intensive treatment: the hazard ratio for stroke was 0.67 (95% CI, 0.47 to 0.97), acute coronary syndrome 0.67 (95% CI, 0.47 to 0.94), acute decompensated heart failure 0.27 (95% CI, 0.08 to 0.98), coronary revascularization 0.69 (95% CI, 0.40 to 1.18), atrial fibrillation 0.96 (95% CI, 0.55 to 1.68), and death from cardiovascular causes 0.72 (95% CI, 0.39 to 1.32). The results for safety and renal outcomes did not differ significantly between the two groups, except for the incidence of hypotension, which was higher in the intensive-treatment group. CONCLUSIONS: In older patients with hypertension, intensive treatment with a systolic blood-pressure target of 110 to less than 130 mm Hg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to less than 150 mm Hg. (Funded by the Chinese Academy of Medical Sciences and others; STEP ClinicalTrials.gov number, NCT03015311.).

The relationship between circadian rhythm of blood pressure and vascular dysfunction in essential hypertension.

OBJECTIVE: This study aimed to explore whether circadian rhythm of blood pressure is associated with brachial-ankle pulse wave velocity (baPWV) and brachial artery flow-mediated dilation (FMD) in patients with essential hypertension. METHOD: This cross-sectional study included 4,217 patients with essential hypertension who completed 24-hour ambulatory blood pressure monitoring, baPWV, and FMD. BaPWV and FMD were measured to evaluate arterial stiffness and endothelial dysfunction. Participants were divided into dipper, non-dipper, and reverse dipping groups according to the nocturnal systolic blood pressure dipping percentage. RESULTS: In this study, baPWV was highest in the reverse dipping groups, followed by non-dipper and dipper groups (1667.11 ± 327.90 vs. 1613.88 ± 325.11 vs. 1577.45 ± 306.15 cm/s, P < .001) and FMD gradually increased (4.41 ± 2.87 vs. 4.70 ± 2.84 vs. 4.92 ± 2.79%, P = .001). baPWV and FMD were significantly associated with declining nocturnal systolic blood pressure (SBP). Interestingly, FMD (ß = 0.042, P = .014) was only positively associated with a drop in nocturnal SBP decline in patients <65 years of age. Whereas baPWV was consistently negatively associated with nocturnal SBP decline regardless of age (ß = -0.065, P < .001, age <65 years; ß = -0.149, P = .002, age ≥ 65). Receiver operating characteristics (ROC) curves analysis showed areas under the curve (AUC) of baPWV/FMD for predicting circadian rhythm of blood pressure are 0.562/0.554 with a sensitivity of 51.7%/53.9% and specificity of 56.4%/53.4. CONCLUSION: Impairment of baPWV and FMD were correlated with abnormal circadian rhythm of blood pressure in essential hypertension, suggesting a decrease in nighttime SBP may associate with endothelial function and arterial stiffness.

The Correlation of Fibroblast Growth Factor 23 with Cardiac Remodeling in Essential Hypertension with Normal Renal Function.

BACKGROUND: Fibroblast growth factor 23 (FGF23), a glycoprotein-regulating calcium and phosphorus homeostasis, has been linked to cardiovascular diseases. We aimed to evaluate the correlation of FGF23 levels and cardiac remodeling (left atrial [LA] enlargement and left ventricular hypertrophy [LVH]) in essential hypertension (EH) with normal renal function and explore the diagnostic values of FGF23 and B-type natriuretic peptide (BNP) in cardiac remodeling. METHODS AND RESULTS: We enrolled 40 healthy control subjects (group I) and 146 EH patients (group II). Plasma FGF23 concentration was measured in all subjects. In this study, FGF23 level was significantly higher in group II (660.77 [446.26, 1,001.72]) pg/mL compared with the controls (73.23 [52.92, 103.69]) pg/mL (p < 0.001). Logistic regression analysis revealed that FGF23 was independently correlated to LVH and LA enlargement. Receiver operating characteristic (ROC) curve indicated FGF23 had an optimal cutoff of 834.63 pg/mL for LVH (area under ROC curve [AUC], 0.913; 95% CI: 0.863-0.963) and 497.06 pg/mL for LA enlargement (AUC, 0.694; 95% CI: 0.612-0.768). The DeLong test was performed to compare AUCs of FGF23 and BNP, and the AUC of FGF23 (0.913) was statistically higher compared to AUC of BNP (0.661) (DeLong test: p < 0.001) in the diagnosis of LVH. CONCLUSION: Plasma FGF23 level elevated in EH, increased with the progress of cardiac remodeling, and was independently related to LVH and LA enlargement. The diagnostic value of FGF23 in cardiac remodeling, especially for LVH, was superior to BNP.

Effectiveness of Levoamlodipine Maleate for Hypertension Compared with Amlodipine Besylate: a Pragmatic Comparative Effectiveness Study.

PURPOSE: Antihypertensive treatment is the most important method to reduce the risk of cardiovascular events in hypertensive patients. However, there is scant evidence of the benefits of levoamlodipine maleate for antihypertensive treatment using a head-to-head comparison in the real-world. This study aims to examine the effectiveness of levoamlodipine maleate used to treat outpatients with primary hypertension compared with amlodipine besylate in a real-world setting. METHODS: This was a pragmatic comparative effectiveness study carried out at 110 centers across China in outpatients with primary hypertension treated with levoamlodipine maleate or amlodipine besylate, with 24 months of follow-up. The primary outcomes used for evaluating the effectiveness were composite major cardiovascular and cerebrovascular events (MACCE), adverse reactions, and cost-effectiveness. RESULTS: Among the included 10,031 patients, there were 482 MACCE, 223 (4.4%) in the levoamlodipine maleate group (n = 5018) and 259 (5.2%) in the amlodipine besylate group (n = 5013) (adjusted hazard ratio = 0.90, 95%CI: 0.75-1.08, P = 0.252). The levoamlodipine maleate group had lower overall incidences of any adverse reactions (6.0% vs. 8.4%, P < 0.001), lower extremity edema (1.1% vs. 3.0%, P < 0.001) and headache (0.7% vs. 1.1%, P = 0.045). There was a nearly 100% chance of the levoamlodipine maleate being cost-effective at a willingness to pay threshold of 150,000 Yuan per quality-adjusted life years (QALYs) gained, resulting in more QALYs (incremental QALYs: 0.00392) and cost savings (saving 2725 Yuan or 28.8% reduction in overall costs) per patient. CONCLUSION: In conclusion, levoamlodipine maleate could reduce cost by 29% with a similar MACCE incidence rate and lower occurrence of adverse reactions (especially edema and headache) compared with amlodipine besylate. TRIAL REGISTRATION: Clinicaltrials.gov NCT01844570 registered at May 1, 2013.

Refractory hypertension secondary to renal artery stenosis with a honeycomb-like structure.

BACKGROUND: A honeycomb-like structure (HLS) is a rare abnormality characterized by a braid-like appearance. Angiograph and intravascular examination, including coherence tomography and intravascular ultrasound (IVUS), can further confirm the multiple intraluminal channels or honeycomb structure, which can also be described as looking like 'swiss cheese', a 'spider web' or a 'lotus root'. Previous studies have mostly reported this abnormality in coronary arteries, with a few cases in renal arteries. More information about the characteristics and development of HLS is needed. CASE PRESENTATION: A 69-year-old Han man with resistant hypertension received abdominal enhanced computerised tomography and was revealed to have left renal artery stenosis with the possibility of left renal infarction. Renal artery angiography confirmed a 95% stenosis located in the proximal segment of the left renal artery, and the middle segment was blurred with multi-channel-like blood flow. Further IVUS was performed and identified multiple channels surrounded by fibrous tissue. It was a rare case of HLS in the renal artery secondary to the thrombus, with organisation and recanalisation. Balloon dilatation and stent implantation at the proximal segment of the left renal artery were performed successfully. Blood pressure was well controlled after the procedure. CONCLUSIONS: The IVUS findings are helpful for forming interventional therapeutic strategies for HLS lesions in the renal artery.

Inhibiting (pro)renin receptor-mediated p38 MAPK signaling decreases hypoxia/reoxygenation-induced apoptosis in H9c2 cells.

The (pro)renin receptor is a new molecular member of the renin-angiotensin system and participates in regulating many physiological and pathological processes. However, the role of (pro)renin receptor-mediated signaling pathways in myocardial ischemic/reperfusion injury remains unclear. In this study, we hypothesized that p38 mitogen-activated protein kinase (MAPK) signaling pathway activation by the (pro)renin receptor had effects on myocardial apoptosis induced by ischemia/reperfusion. This analysis was performed using a hypoxia/reoxygenation model in H9c2 cells to mimic ischemia/reperfusion injury. The H9c2 rat cardiomyocyte cell line was subjected to 2 h of hypoxia followed by 6 h of reoxygenation. The (pro)renin receptor, caspase 3, and phosphorylated p38 MAPK protein expression levels were analyzed by Western blot. After 2 h of hypoxia followed by 6 h of reoxygenation, apoptosis increased in H9c2 cells; the (pro)renin receptor, caspase 3, and phosphorylated p38 MAPK protein expressions were upregulated. siRNA silencing of the (pro)renin receptor significantly decreased p38 MAPK phosphorylation. siRNA silencing of the (pro)renin receptor and treatment with the p38MAPK inhibitor SB203580 significantly decreased the hypoxia/reoxygenation-induced apoptosis and caspase 3 protein expression in H9c2 cells. Furthermore, we found that the role of the (pro)renin receptor was independent of angiotensin II (Ang II). Thus, we concluded that (pro)renin receptor activation could trigger hypoxia/reoxygenation-induced apoptosis in H9c2 cells, partially through the p38 MAPK/caspase 3 signaling pathway, independent of Ang II. Therefore, this study may provide new therapeutic targets for myocardial ischemic/reperfusion injury prevention, and further in vivo studies are needed.

Use of Dual-Source Computed Tomography to Evaluate Renal Cortical Perfusion in Patients With Essential Hypertension Without Diabetes: Preliminary Results.

OBJECTIVES: To assess renal cortical perfusion parameter changes using computed tomography (CT) renal perfusion examination in patients with essential hypertension (EH), especially those with EH-related target organ damage (TOD), and to correlate renal perfusion parameters with clinical and laboratory data. METHODS: Consecutive patients with EH (without exclusion criteria) and healthy controls underwent 128-slice dual-source CT perfusion imaging. Quantitative perfusion analysis of renal cortex parameters [blood flow (BF), blood volume, time to peak, and mean transit time] was performed. RESULTS: Ninety-one participants (60 patients with EH, 31 healthy controls) underwent renal perfusion CT imaging, and 84 participants (92.3%) were eligible for perfusion analysis. The BF values were lower in patients with EH than that in controls. Blood flow was correlated with age (P < 0.01), duration of hypertension (P < 0.01), estimated glomerular filtration rate (eGFR; P < 0.01), pulse pressure (P < 0.05), and body mass index (BMI; P < 0.05). Duration of hypertension, eGFR, and BMI were independently associated with BF. No parameter differed between control subjects and those with EH but not. Blood flow was lower in patients with TOD than in control subjects (P < 0.01), but no other parameter differed. Blood flow was lower (P < 0.01) and mean transit time and time to peak were higher (P < 0.05) in the TOD than that in the non-TOD group. CONCLUSIONS: Essential hypertension, especially EH-related TOD, alters renal cortical perfusion parameters, especially BF. Four-dimensional spiral CT renal perfusion examination showed that duration of hypertension, eGFR, and BMI were independently associated with decreased BF.

Identification of genes related to the early stage of Angiotensin II-induced acute renal injury by microarray and integrated gene network analysis.

BACKGROUND/AIMS: Angiotensin II (Ang II) mediated signaling plays a key role in the development of chronic kidney damage that contributes to renal fibrosis. However, the gene expression changes regulated by Ang II in the early stage of acute renal injury remain unclear. METHODS: C57BL/6 wild-type (WT) mice were injected with Ang II (1500 ng/kg/min) for 1, 3 and 7 days. A time series analysis of microarrays was performed to evaluate Ang II-induced differentially gene expression in the kidneys. The data of gene expression in the kidney was further dissected by ANOVA analysis, gene expression profiles, gene network construction and quantitative real-time RT-PCR. Ang II-induced renal inflammation and fibrosis in mice were confirmed by pathological examination. RESULTS: Our microarray data showed that a total of 1,511 differentially expressed genes were identified in the kidneys at 1, 3 and 7 days after Ang II infusion. These genes function in multiple biological processes, including response to stimuli, immune response, cell adhesion, metabolic process, kidney development, regulation of blood pressure, and ion transport, which may play critical roles in the pathobiology of Ang II-induced acute renal injury at the early stage. Furthermore, among these genes, 20 genes were further selected for final investigation. The dynamic gene network analysis demonstrated that fatty acid binding protein 1 (Fabp1) localized in the core of the network. CONCLUSIONS: Our data suggests that genes involved in lipid metabolic process, especially Fabp1, may play a central role in the development of Ang II-induced acute renal injury at the early stage.

Noninvasive assessment of left atrial phasic function in patients with hypertension and diabetes using two-dimensional speckle tracking and volumetric parameters.

OBJECTIVE: To evaluate the left atrial phasic function of hypertensive patients with or without coexisting diabetes using two-dimensional speckle tracking echocardiography (2DSTE)-based strain and strain rate imaging and volumetric parameters. METHODS: The study included an isolated hypertension group (HT group) comprising 99 patients, a hypertension and diabetes group (HT + DM group) comprising 65 patients, and 26 age-matched healthy controls. The 2DSTE-based strain and strain rate images were studied, and the following parameters were measured: peak left atrial longitudinal strain (LAS-S ), early diastolic (LAS-E ) and late diastolic (LAS-A ) atrial longitudinal strains, and systolic (LASR-S ), early diastolic (LASR-E ) and late diastolic (LASR-A ) strain rates. RESULTS: The LAS-S and LASR-S were lower in the HT group and the HT + DM group compared with the control group (P < 0.001). The LAS-E and LASR-E were lower in the HT group (14.9 ± 5.5% and -1.1 ± 0.4/sec, respectively) than in the control group (22.1 ± 8.3% and -1.7 ± 0.6/sec, respectively) (P < 0.001), and they were further depressed in the HT + DM group (12.3 ± 6.3% and -1.0 ± 0.4/sec, respectively) (P < 0.05). There were no significant differences in LAS-A or LASR-A among the 3 groups (P > 0.05). Multivariate regression analysis revealed that HT and DM were independently related to LAS-E and LASR-E . CONCLUSIONS: Hypertension can lead to abnormal left atrial reservoir and conduit functions, and coexisting diabetes can further impair conduit function. 2DSTE-derived strain and strain rate imaging are sensitive methods for evaluating left atrial phasic function.

Ginsenoside RH4 inhibits Ang II-induced myocardial remodeling by interfering with NFIL3.

Ventricular remodeling refers to the structural and functional changes of the heart under various stimuli or disease influences and may also be accompanied by myocardial fibrosis, where an excessive amount of fibrous tissue appears in the myocardial tissue, affecting the heart's normal contraction and relaxation. Hypertension is posing the potential risk of causing myocardial injury and remodeling. The significance of the renin-angiotensin-aldosterone system (RAAS) in myocardial remodeling cannot be overlooked. Drug targeting of RAAS can effectively lower blood pressure and reduce left ventricular mass. Studies have shown that ginsenoside Rh4 can inhibit oxidative stress and inflammatory responses. In this study, a myocardial remodeling model was established using angiotensin (Ang) II, and the inhibitory effect of RH4 on myocardial hypertrophy and remodeling induced by Ang II was investigated using pathological staining and quantitative polymerase chain reaction (qPCR). Immunofluorescence and qPCR demonstrated that Rh4 causes myocardial hypertrophy and the generation of reactive oxygen species (ROS) in vitro. The Rh4 target was identified using transcriptomics. The findings indicated that RH4 could inhibit myocardial hypertrophy, inflammatory fibrosis, and oxidative stress induced by Ang II, suggesting potential cardiovascular protection effects. In vitro experiments have shown that Rh4 inhibits myocardial hypertrophy. Transcriptomics revealed that nuclear factor interleukin-3 (NFIL3) is a downstream regulator of Rh4. By constructing AAV9-NFIL3 and injecting it into mice, it was found that NFIL3 overexpression interfered with anti-Ang II-induced myocardial remodeling of Rh4. These results indicate that Rh4 demonstrates potential therapeutic effects on myocardial hypertrophy and fibrosis.

Evaluation of adrenal vein anatomy by adrenal venous sampling in patients with primary aldosteronism in Chinese.

Accurate cannulation of the adrenal vein is challenging during adrenal venous sampling (AVS) because of the variations in adrenal vein anatomy. This study aimed to investigate the adrenal venous morphology in Chinese and improve the success rate of AVS. A total of 221 participants with primary aldosteronism (PA) who underwent AVS were enrolled. Compare the morphology among subgroups divided according to sex, body mass index (BMI), and with or without adenoma. The success rate of right, left, and bilateral AVS was 98.60%, 97.20%, and 96.85%, respectively. The triangular pattern was the most common (39.37%) on the right side, while the glandlike pattern (70.14%) on the left. The proportion of adrenal venous morphology varies among patients with different sexecs (χ2 = 21.335, P < .001), BMI (χ2 = 10.642 P = .031), and with or without adenoma (χ2 = 10.637, P = .031) on the right side, and the male, obese and adenoma group showed a higher proportion of glandlike pattern than triangular pattern. If only dependent on computed tomography, 9.05% of patients incorrectly diagnose the dominant side, 14.48% of patients would have inappropriate surgery meanwhile 25.34% of patients would miss the surgical opportunity. In conclusion, the most common types of right and left adrenal venous morphology were triangular pattern and glandlike pattern, respectively. Sex, BMI, and the presence of adenoma affected right adrenal venous morphology. Adequate knowledge of the adrenal venous morphology is critical for improving the success rate of AVS and making an appropriate treatment for PA.

Comparison of saline infusion test and captopril challenge test in the diagnosis of Chinese with primary aldosteronism in different age groups.

Background: To explore the diagnostic accuracy and the optimal cutoff value between the saline infusion test (SIT) and captopril challenge test (CCT) [including the value and suppression of plasma aldosterone concentration (PAC)] for primary aldosteronism (PA) diagnosing. Methods: A total of 318 patients with hypertension were consecutively enrolled, including 126 patients with PA and 192 patients with essential hypertension (EH), in this observational study. The characteristics of patients and laboratory examinations were collected and compared. The comparison between SIT and CCT was carried by drawing the receiver operator characteristic curve (ROC) and calculating the area under the curve (AUC) to explore the diagnostic accuracy and the optimal cutoff value. Results: The average age was 51.59 ± 10.43 in the PA group and 45.72 ± 12.44 in the EH group (p<0.05). The optimal cutoff value was 10.7 ng/dL for post-CCT PAC, 6.8 ng/dL for post-SIT PAC, and 26.9% for suppression of post-CCT PAC. The diagnostic value of post-CCT PAC was the highest with 0.831 for the AUC and 0.552 for the Youden index. The optimal cutoff value for patients who were <50 years old was 11.5 ng/dL for post-CCT PAC and 8.4 ng/dL for post-SIT PAC. The suppression of post-CCT PAC turned to 18.2% for those of age 50 or older. Conclusion: Compared with SIT, CCT had a higher diagnostic value when post-CCT PAC was used as the diagnostic criterion in Chinese people, while the selection of diagnostic thresholds depended on patient age.

Poly-(ADP-ribose) polymerases inhibition by olaparib attenuates activities of the NLRP3 inflammasome and of NF-κB in THP-1 monocytes.

Poly-(ADP-ribose) polymerases (PARPs) are a protein family that make ADP-ribose modifications on target genes and proteins. PARP family members contribute to the pathogenesis of chronic inflammatory diseases, including atherosclerosis, in which monocytes/macrophages play important roles. PARP inhibition is protective against atherosclerosis. However, the mechanisms by which PARP inhibition exerts this beneficial effect are not well understood. Here we show that in THP-1 monocytes, inhibition of PARP by olaparib attenuated oxidized low-density lipoprotein (oxLDL)-induced protein expressions of nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing-3 (NLRP3) inflammasome components: NLRP3, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and caspase-1. Consistent with this effect, olaparib decreased oxLDL-enhanced interleukin (IL)-1ß and IL-18 protein expression. Olaparib also decreased the oxLDL-mediated increase in mitochondrial reactive oxygen species. Similar to the effects of the NLRP3 inhibitor, MCC950, olaparib attenuated oxLDL-induced adhesion of monocytes to cultured human umbilical vein endothelial cells and reduced foam cell formation. Furthermore, olaparib attenuated the oxLDL-mediated activation of nuclear factor (NF)-κB through the oxLDL-mediated increase in IκBα phosphorylation and assembly of NF-κB subunits, demonstrated by co-immunoprecipitation of IκBα with RelA/p50 and RelB/p52 subunits. Moreover, PARP inhibition decreased oxLDL-mediated protein expression of a NF-κB target gene, VCAM1, encoding vascular cell adhesion molecule-1. This finding indicates an important role for NF-κB activity in PARP-mediated activation of the NLRP3 inflammasome. Thus, PARP inhibition by olaparib attenuates NF-κB and NLRP3 inflammasome activities, lessening monocyte cell adhesion and macrophage foam cell formation. These inhibitory effects of olaparib on NLRP3 activity potentially protect against atherosclerosis.

Effect of Accessory Renal Arteries on Essential Hypertension and Related Mechanisms.

BACKGROUND: This case-control study aimed to determine whether there were differences between patients with essential hypertension with accessory renal arteries (ARAs) and those without ARAs. METHODS AND RESULTS: The enrolled patients with essential hypertension were divided into the ARA group (n=200) and control group without ARAs (n=238). After propensity matching, 394 patients (197 in each of the 2 groups), were included. The 24-hour BP (4.33/2.43 mm Hg) and daytime BP (4.48/2.61 mm Hg) of patients in the ARA group were significantly higher than those of the control group (P<0.05). The flow-mediated dilation was lower in the ARA group (5.98±2.70 versus 5.18±2.66; P<0.05). In correlation analysis, the horizontal plasma aldosterone concentration had the highest correlation with 24-hour, daytime, and nighttime systolic BP (r=0.263, 0.247, and 0.243, respectively; P<0.05) and diastolic BP (r=0.325, 0.298, and 0.317, respectively; P<0.05). As for multivariate regression analysis, plasma aldosterone concentration was a significant risk factor for elevated 24-hour, daytime, and nighttime systolic BP (ß=0.249 [95% CI, 0.150-0.349], 0.228 [95% CI, 0.128-0.329], and 0.282 [95% CI, 0.187-0.377], respectively; P<0.05) and elevated diastolic BP (ß=0.289 [95% CI, 0.192-0.385], 0.256 [95% CI, 0.158-0.353], and 0.335 [95% CI, 0.243-0.427], respectively; P<0.05). Direct renin concentration was also a risk factor for 24-hour and daytime BPs, whereas heart rate was a risk factor correlated with 24-hour, daytime, and nighttime diastolic BP (all P<0.05). For the mixed-effects model for repeated measures, the results were similar to results of the multivariate regression analysis (all P<0.05). CONCLUSIONS: ARAs could contribute a higher BP of patients with essential hypertension and might promote the development of essential hypertension. The mechanism might be related to overactivation of the renin-angiotensin-aldosterone system and sympathetic nervous system.

Efficacy and safety of a single-pill versus free combination of perindopril/indapamide/amlodipine: a multicenter, randomized, double-blind study in Chinese patients with hypertension.

BACKGROUND: In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals. METHODS: This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90 mmHg) were randomized to perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4 mg/indapamide 1.25 mg plus amlodipine 5 mg (Per/Ind + Aml) for 6 months. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2 months. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90 mmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM). RESULTS: A total of 532 patients were randomized: Per/Ind/Aml ( n  = 262) and Per/Ind + Aml ( n  = 269). Overall, the mean (±SD) age was 55.7 ±â€Š8.8 years, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2 mmHg. Systolic BP decreased in both groups at 2 months from baseline: -14.99 ±â€Š14.46 mmHg Per/Ind/Aml versus -14.49 ±â€Š12.87 mmHg Per/Ind +Aml. A predefined noninferiority margin of 4 mmHg was observed ( P  < 0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24 h. Both treatments were well tolerated. CONCLUSIONS: Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24 h in a single pill, with comparable safety.

Management of nocturnal hypertension: An expert consensus document from Chinese Hypertension League.

Nocturnal hypertension is highly prevalent among Chinese and Asian populations, which is mainly attributed to high salt intake and high salt sensitivity. Nocturnal hypertension increases the risk of cardiovascular and all-cause mortality, independent of daytime blood pressure (BP). However, it can usually be detected by 24-h ambulatory BP monitoring, rather than routine office or home BP measurement, thus is often underdiagnosed in clinical practice. Currently, no specific guidance is available for the management of nocturnal hypertension in China or worldwide. Experts from the Chinese Hypertension League summarized the epidemiologic and pathophysiologic characteristics and clinical phenotype of nocturnal hypertension and provided consensus recommendations on optimal management of nocturnal hypertension, with the goal of maximally reducing the cardiovascular disease risks. In this consensus document, 24-h ABPM is recommended for screening and diagnosis of nocturnal hypertension, especially in the elderly, patients with diabetes, chronic kidney diseases, obstructive sleep apnea and other conditions prone to high nocturnal BP. Lifestyle modifications including salt intake restriction, exercise, weight loss, sleep improvement, and mental stress relief are recommended. Long-acting antihypertensive medications are preferred for nocturnal and 24-h BP control. Some newly developed agents, renal denervation, and other device-based therapy on nocturnal BP reduction are evaluated.

Association of sodium intake with adverse left atrial function and left atrioventricular coupling in Chinese.

OBJECTIVES: High sodium intake is strongly associated with hypertension and obesity. This study aims to investigate the relationship between 24-h urinary sodium (a surrogate measure of sodium intake), ambulatory blood pressure parameters, left atrial function, and left atrioventricular coupling. Further, we intend to examine whether blood pressure and BMI might be mediators of the relationship between 24-h urinary sodium and subclinical cardiac function. METHODS: Our study had 398 participants, all of whom were subjected to 24-h urine collection, 24-h ambulatory blood pressure measurement, and cardiac magnetic resonance imaging. RESULTS: The average age of the participants was 55.70 ±â€Š11.30 years old. The mean urinary sodium of the participants was 172.01 ±â€Š80.24 mmol/24 h. After adjusting for age, sex, history of diabetes, smoking status, alcohol consumption, and use of diuretics, 24-h urinary sodium was correlated with multiple ambulatory blood pressure parameters, BMI, left atrial function, and the left atrioventricular coupling index (LACI) (P < 0.05). Mediation analysis showed that BMI explained 16% of the indirect effect of 24-h urinary sodium and left atrial function and 30% of the indirect effect of LACI. Independent of the mediator, 24-h urinary sodium had a significant direct effect on left atrial function and left atrioventricular coupling. CONCLUSIONS: Higher 24-h urinary sodium was associated with a greater BMI as well as poor left atrial function and left atrioventricular coupling, and the BMI mediated the relationship between 24-h urinary sodium and subclinical left cardiac function. Furthermore, and more importantly, 24-h urinary sodium may have directly affected the left atrial function and left atrioventricular coupling independent of intermediary factors.

Associations of brachial-ankle pulse wave velocity with left atrial stiffness and left atrial phasic function in inpatients with hypertension.

Hypertension induces left atrial (LA) and left ventricular (LV) dysfunction, and an increase in arterial stiffness. This study aimed to investigate the associations of brachial-ankle pulse wave velocity (baPWV) with LA stiffness and LA phasic function in hypertension. A total of 305 hypertensive inpatients enrolled and were divided into two groups based on baPWV [Group I, baPWV ≤ 1515 (cm/s), n = 153; Group II, baPWV > 1515 (cm/s), n = 152]. Two-dimensional speckle tracking echocardiography (2D-STE) based LA phasic strains (LAS-S, LAS-E, LAS-A) and LV global longitudinal strain (LVGLS) were evaluated. LA stiffness index (LASI) was defined as the ratio of E/e' to LAS-S. Multivariate linear regression modeling was used to analyze the associations of baPWV with LASI and LA phasic function in all patients as well as age-specific and sex-specific subgroups. LASI was significantly higher in Group II [0.35(0.26, 0.52)] compared with Group I [0.26(0.20, 0.36)] (P < 0.001). After adjusting cardiovascular risk factors, medication, and LV structural and functional parameters (LVEF, LVMI, E/A ratio, and LVGLS), baPWV remained significantly correlated with LASI (P < 0.05). We also evaluated the predictive value of baPWV for LASI, the area under the curve (AUC) was 0.663 (95% CI: 0.607-0.716, P < 0.001). In conclusion, BaPWV was independently associated with LA stiffness in hypertensive inpatients. BaPWV also exhibited a certain predictive value for LA stiffness in these inpatients. Measuring arterial stiffness can provide clinicians clues for early cardiac target organ damage (TOD) in addition to vascular TOD.

Impacts of obesity on global subclinical left cardiac function represented by CMR-derived myocardial strain, TyG index may be a predictor.

Obesity is a recognized risk factor for heart failure. People with similar weights may have different metabolic health. Notably, insulin resistance is a hallmark of obesity and a feature of heart failure. We aimed to evaluate the effects of obesity and metabolic health status on subclinical left cardiac function. We also investigated whether insulin resistance (TyG index) plays a role in BMI-linked subclinical left cardiac dysfunction. The study involved 403 volunteers. Hierarchical multiple regression models were used to assess associations between obesity, metabolic health, and overall subclinical left cardiac function. Mediating analysis was used to explore the role of the TyG index in the association between BMI and left cardiac function. Finally, ROC analysis was performed to explore the predictive value of the TyG index in subclinical left cardiac dysfunction. The correlation analysis showed that metabolic unhealth increased the risk of subclinical left ventricular (LV) dysfunction; obesity was associated with an increased risk of global left cardiac dysfunction regardless of metabolic health status. The TyG index mediated 25% of the associations between BMI and Left atrial (LA) functional parameters. ROC analysis exhibited that the TyG index can be used as a predictor of LA dysfunction (AUC = 0.63), and the optimal cut-off point for the TyG index is 9.33. Even a "non-obese metabolically unhealthy" is a detrimental state of early LV function; obesity remains a major risk factor for global subclinical left cardiac dysfunction. Using the TyG index could allow early identification of individuals at high risk of subclinical left cardiac dysfunction.Registration number: ChiCTR2200057991; Date of registration: 2022-03-25. URL: http://www.chictr.org.cn/showproj.aspx?proj=162316 .

Moderating effect of mindfulness on the relationship between anxiety and somatization symptoms in middle-aged and elderly female patients with hypertension.

To explore the moderating effect of mindfulness on the relationship between anxiety and somatization symptoms in middle-aged and elderly female patients with hypertension and provide a foundation for the development of more effective mindfulness intervention strategies. A total of 109 middle-aged and elderly female patients with hypertension participated in this cross-sectional study from April to July 2022 and provided valid responses to the Five Facet Mindfulness Questionnaire (FFMQ), the Hospital Anxiety and Depression Scale (HADS), and the Somatization Symptom Self-rating Scale (SSS). The moderating effect of mindfulness was determined using multiple linear regression. The participants' average scores were as follows: mindfulness: 123.86 ± 10.49; anxiety: 7.41 ± 3.62; and somatization symptoms: 41.2 ± 9.44. The anxiety (P = .000) and somatization symptoms (P = .001) of participants with high mindfulness were significantly reduced. Anxiety was positively correlated with somatization symptoms (r = 0.606, P = .000), while mindfulness was negatively correlated with both anxiety (r = -0.468, P = .000) and somatization symptoms (r = -0.439, P = .000). Moreover, mindfulness had a significant moderating effect on the relationship between anxiety and somatization symptoms (n = 109) (B = -0.166, t = -2.125, P = .036). The effect of mindfulness on anxiety and somatization symptoms was more significant in participants with low mindfulness levels (n = 56) (B = 0.144, t = 2.805, P = .008) than in participants with high mindfulness levels (n = 53) (B = -0.037, t = -0.864, P = .393). The moderating effect analysis based on regression analysis showed that mindfulness had a significant moderating effect on anxiety and somatization symptoms, especially in participants with low mindfulness levels.