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Background: We previously found that cardioplegic arrest and cardiopulmonary bypass are associated with altered coronary arteriolar response to serotonin in patients undergoing cardiac surgery. In this study, we investigated the effects of hypertension on coronary microvascular vasomotor tone in response to serotonin and alterations in serotonin receptor protein expression in the setting of cardioplegic arrest and cardiopulmonary bypass., Methods: Coronary arterioles were dissected from harvested pre- and post-cardioplegic arrest and cardiopulmonary bypass right atrial tissue samples of patients undergoing cardiac surgery with normotension, well-controlled hypertension, and uncontrolled hypertension. Vasomotor tone was assessed by video-myography, and protein expression was measured with immunoblotting., Results: Pre-cardioplegic arrest and cardiopulmonary bypass, serotonin induced moderate relaxation responses of coronary arterioles in normotension and well-controlled hypertension patients, whereas serotonin caused moderate contractile responses in uncontrolled hypertension patients. Post-cardioplegic arrest and cardiopulmonary bypass, serotonin caused contractile responses of coronary arterioles in all 3 groups. The post-cardioplegic arrest and cardiopulmonary bypass contractile response to serotonin was significantly higher in the uncontrolled hypertension group compared with the normotension or well-controlled hypertension groups (P < .05). Pre-cardioplegic arrest and cardiopulmonary bypass, expression of the serotonin 1A receptor was significantly lower in the uncontrolled hypertension group compared with the well-controlled hypertension and normotension groups (P = .01 and P < .001). Serotonin 1B receptor expression was higher in the uncontrolled hypertension group compared with the normotension or well-controlled hypertension groups post-cardioplegic arrest and cardiopulmonary bypass (P = .03 and P = .046)., Conclusion: Uncontrolled hypertension is associated with an increased coronary contractile response of coronary microvessels to serotonin and altered serotonin receptor protein expression after cardioplegic arrest and cardiopulmonary bypass. These findings may contribute to a worse postoperative coronary spasm and worsened recovery of coronary perfusion in patients with uncontrolled hypertension after cardioplegic arrest and cardiopulmonary bypass and cardiac surgery., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although in vitro experiments have demonstrated the potential of flavonoid compounds in regulating blood pressure, there is still a lack of evidence from large population studies. We conducted a cross-sectional study using the National Health and Nutrition Examination Survey to investigate the relationship between flavonoid intake levels (natural log transformation) and hypertension events. A total of 15 752 participants aged over 20 years were included, and a weighted multivariable logistic regression analysis was performed to explore the relationship between total flavonoids, five sub types intake, and hypertension events. Smooth curve fitting was used to explore potential nonlinear relationships. Higher total flavonoids intake was associated with a lower risk of hypertension than the lowest group. The adjusted odds ratios (95% CIs) were 0.79 (0.70-0.88) for total flavonoids intake. Elevated total flavonoids intake levels were significantly and linearly associated with a lower risk of hypertension. For each unit increase in the total flavonoids intake level, the adjusted ORs for risk of hypertension decrease by 5% (OR 0.95; 95% CI, 0.92-0.98). In addition, in restricted cubic spline regression, we found that flavan-3-ols, anthocyanidins, and flavonols intake were linearly and negatively related to prevalence of hypertension. Flavones intake showed nonlinear associations with prevalence of hypertension with inflection points of -1.90. Within a certain range, a negative correlation exists between flavonoids intake and hypertension events. This finding provides insights into dietary modifications in the prevention of hypertension., (© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: Chronic kidney disease (decreased kidney function) is common in hypertensive patients. The SIRI is a novel immune biomarker. We investigated the correlation between the SIRI and kidney function in hypertensive patients., Methods: The present study analyzed data from participants who suffered from hypertension in the NHANES from 2009 to 2018. Multivariate regression analysis and subgroup analysis were used to clarify whether the SIRI was an independent risk factor for decreased kidney function. RCSs were utilized to evaluate the correlation between the SIRI and the eGFR and between the SIRI and the ACR. In addition, we modeled the mediating effect of the SIRI on the eGFR and the ACR using blood pressure as a mediating variable., Results: The highest SIRI was an independent risk factor for a decreased eGFR [odds ratio (OR) = 1.46, 95% CI (1.15, 1.86)] and an increased ACR [OR = 2.26, 95% CI (1.82, 2.82)] when the lowest quartile was used as the reference. The RCS results indicated an inverted U-shaped relationship between the SIRI and the eGFR and between the SIRI and the ACR (the inflection points were 1.86 and 3.09, respectively). The mediation effect analysis revealed that the SIRI was the main factor influencing kidney function, and diastolic blood pressure was a mediating variable. In particular, there was a fully mediating effect between the SIRI and UCr, with a mediating effect value of -0.61 (-0.90, -0.36)., Conclusions: The association between the SIRI and renal function in hypertensive patients was significant and was particularly dominated by the association between the SIRI and the ACR. This difference may be due to the mediating effect of diastolic blood pressure., (© 2024. The Author(s).)

Introduction: Cardioplegia and cardiopulmonary bypass (CP/CPB) alters coronary arteriolar response to thromboxane A2 (TXA2) in patients undergoing cardiac surgery. Comorbidities, including hypertension (HTN), can further alter coronary vasomotor tone. This study investigates the effects of HTN on coronary arteriolar response to TXA2 pre and post-CP/CPB and cardiac surgery., Materials and Methods: Coronary arterioles pre and post-CP/CPB were dissected from atrial tissue samples in patients with no HTN (NH, n = 9), well-controlled HTN (WC, n = 12), or uncontrolled HTN (UC, n = 12). In-vitro coronary microvascular reactivity was examined in the presence of TXA2 analog U46619 (10 -9 -10 -4 M). Protein expression of TXA2 receptor in the harvested right atrial tissue samples were measured by immunoblotting., Results: TXA2 analog U46619 induced dose-dependent contractile responses of coronary arterioles in all groups. Pre-CPB contractile responses to U46619 were significantly increased in microvessels in the UC group compared to the NH group (P < 0.05). The pre-CP/CPB contractile responses of coronary arterioles were significantly diminished post-CP/CPB among the three groups (P < 0.05), but there remained an increased contractile response in the microvessels of the UC group compared to the WC and NH groups (P < 0.05). There were no significant differences in U46619-induced vasomotor tone between patients in the NH and WC groups (P > 0.05). There were no differences in expression of TXA2R among groups., Conclusions: Poorly controlled HTN is associated with increased contractile response of coronary arterioles to TXA2. This alteration may contribute to worsened recovery of coronary microvascular function in patients with poorly controlled HTN after CP/CPB and cardiac surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The quantification of cardiovascular health (CVH) was updated by the American Heart Association recently by using the "Life's Essential 8" (LE8) score. We aimed to investigate the associations of baseline and longitudinal CVH status measured by the new LE8 score (except for blood pressure) with the risk of hypertension., Methods: A total of 52 990 participants with complete data on LE8 metrics and without hypertension were enrolled from the Kailuan study, Tangshan, China. The associations of incident hypertension with the overall baseline, time-updated, and time-varying CVH score (ranging 0 [lowest] to 100 [highest]), and each component of LE8, were assessed by Cox regressions., Results: During a median follow-up of 10.73 years 28 380 cases of incident hypertension were identified. The risk of hypertension attenuated with increased CVH score (P trend < 0.0001), the hazard ratios (HRs) in high CVH versus low CVH group was 0.54 (95% confidence interval [CI], 0.51-0.57) for baseline CVH, 0.47 (95% CI, 0.45-0.50) for time-updated CVH, and 0.59 (95% CI, 0.55-0.63) for time-varying CVH. The predictive value of CVH in predicting hypertension improved by using LE8 than using Life's Simple 7 metrics. Among LE8 components, body mass index score was the strongest risk factor for hypertension. Subgroup analyses showed that the benefit of a higher CVH score on hypertension was more prominent in young adults and in women (P interaction < 0.05)., Conclusions: A higher CVH score assessed by new LE8 is associated with a lower risk of subsequent hypertension, especially young adults and women.

Background: Anlotinib plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC) achieves good efficacy, but there is still room for improvement. This clinical study examined the effectiveness of anlotinib plus etoposide for maintenance therapy in ES-SCLC., Methods: The current single-arm, prospective phase II study was performed at Jiangsu Cancer Hospital (March 2019 to March 2022). After successful primary etoposide-based therapy, anlotinib was administered at 12 mg/day on days 1 to 14 of 21-day cycles until disease progression or consent withdrawal. All patients also received etoposide at 50 mg/day on days 1 to 14 of 21-day cycles for a maximum of six cycles. Progression-free survival (PFS) constituted the primary study endpoint. Secondary endpoints were overall survival (OS), objective remission rate (ORR), disease control rate (DCR), and safety. In addition, adverse events (AEs) were assessed., Results: Twenty-eight patients were treated. Median PFS and OS were 8.02 (95%CI 5.36-10.67) and 11.04 (95%CI 10.37-11.68) months, respectively. Totally 9 and 18 participants showed a partial response and stable disease, respectively; ORR and DCR were 32.14% and 96.43%, respectively. The commonest all-grade AEs were fatigue (n = 11, 39.28%), hypertension (n = 11, 39.28%), loss of appetite (n = 9, 32.14%), oral mucositis (n = 7, 25.00%) and proteinuria (n = 6, 21.40%). Grade 3-4 AEs included fatigue (n = 4, 14.28%), hypertension (n = 2, 7.14%), hand and foot syndrome (n = 2, 7.14%), oral mucositis (n = 1, 3.57%), hemoptysis (n = 1, 3.57%), proteinuria (n = 1, 3.57%), gingival bleeding (n = 1, 3.57%), and serum creatinine elevation (n = 1, 3.57%)., Conclusion: Maintenance anlotinib plus etoposide achieves promising PFS and OS in clinical ES-SCLC., Registration Number: ChiCTR1800019421., (© 2023. The Author(s).)

Objectives: The aim of this study was to assess the changes in salt intake and concomitant changes in blood pressure (BP) and cardiovascular disease (CVD) mortality in England from 2003 to 2018., Methods: National surveys and death registration data were used for the analysis of salt intake as measured by 24-h urinary sodium excretion (449-1069 participants per year), BP (2651-6738 participants per year) and CVD mortality., Results: A decline in salt intake from 9.38 (SD 4.64) to 7.58 (3.41) g/d was observed between 2003 and 2014 ( P  < 0.01), followed by an increase to 8.39 (4.13) g/d in 2018 ( P  < 0.01). Similar trends in BP and CVD mortality were also observed between 2003 and 2018. SBP/DBP decreased from 125.3 (15.92)/74.48 (11.33) mmHg to 122.57 (14.92)/73.33 (10.75) mmHg between 2003 and 2014 ( P  < 0.01), followed by a plateau up to 2018 [122.04 (14.64)/73.84 (10.54) mmHg, P  > 0.05]. Likewise, a fall in stroke and ischaemic heart disease mortality rates was observed between 2003 and 2014, from 12.24 and 43.44 cases per 100 000, to 8.19 and 27.23 cases per 100 000 ( P  < 0.01), respectively, followed by a plateau afterwards ( P  > 0.05)., Conclusion: The UK salt reduction programme was initially successful in reducing population salt intake by 19% (from 9.38 g/d in 2003 to 7.58 g/d in 2014). However, in recent years, the programme stalled and thus led to an interruption in the decline of salt intake. BP and CVD mortality reduction was also interrupted when salt reduction stalled. The changes in salt intake may have played an important role in the concomitant changes in BP and CVD mortality. Urgent action is needed to reinvigorate the UK's once world-leading salt reduction programme., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: It has been reported that there are sex differences in plaque composition and hemodynamically significant stenosis. This study aimed to explore the impact of sex on cardiovascular risk factors for specific plaque compositions and hemodynamically significant stenosis., Methods: Data regarding demographics and cardiovascular risk factors were collected. Hemodynamically significant stenosis was identified by a computed tomography-derived fractional flow reserve of ≤ 0.8. Associations among cardiovascular risk factors, plaque composition, and hemodynamically significant stenosis were assessed using a multivariate binary logistic regression analysis across sexes. The discriminating capacity of diverse plaque components for hemodynamically significant stenosis was assessed by area under the receiver-operating characteristics curve with 95% confidence intervals., Results: A total of 1164 patients (489 men and 675 women) were included. For men, hyperlipidemia and cigarette smoking were risk factors for each plaque component (all P < 0.05), and diabetes mellitus also predicted fibrotic components (P < 0.05). For women, risk factors for each plaque component were hypertension and diabetes mellitus (all P < 0.01). Nonetheless, hyperlipidemia (P < 0.05) was a specific risk factor for non-calcified components. Calcified components combined with fibrotic components showed superior discrimination of hemodynamically significant stenosis in men and calcified components alone in women (all P < 0.01). Hypertension (P < 0.01) was a risk factor for hemodynamically significant stenosis in women. In contrast, diabetes, hyperlipidemia, and cigarette smoking were risk factors for hemodynamically significant stenosis in men (all P < 0.05)., Conclusions: In men, hemodynamically significant stenosis was predicted by a combination of calcified and fibrotic components with multiple risk factors. In women, hemodynamically significant stenosis was predicted by calcified components caused by a single risk factor. It might be a key point to improve prognosis by more precise risk management between men and women, which needs to be proved by further prospective trials., (© 2023. BioMed Central Ltd., part of Springer Nature.)

With the increasing prevalence of diabetes mellitus (DM) and diabetic nephropathy (DN), effective treatment is particularly important for the recovery of patients. However, the currently approved drugs are usually tailored to clinical symptoms and no mechanism-targeted drugs are available. In this study, the combination of metabolomics and network pharmacology was applied to provide reasonable medication combination regimens to meet the different clinical needs for the targeted treatment of DM and DN. An NMR-based metabolomic strategy was applied to identify the potential urinary biomarkers of DM or/and DN, while network pharmacology was used to identify the therapy targets of DM and DN by intersecting the targets of diseases and currently approved drugs. According to the enriched signaling pathways using the potential biomarkers and the therapy targets, the specific medication combinations were recommended for the specific clinical demands in terms of hypoglycemic, hypertensive, and/or lipid-lowering. For DM, 17 potential urinary biomarkers and 12 disease-related signaling pathways were identified, and 34 combined medication regimens related to hypoglycemia, hypoglycemia, and hypertension, and hypoglycemia, hypertension, and lipid-lowering were administered. For DN, 22 potential urinary biomarkers and 12 disease-related signaling pathways were identified, and 21 combined medication regimens related to hypoglycemia, hypoglycemia, and hypertension were proposed. Molecular docking was used to verify the binding ability, docking sites, and structure of the drug molecules to target proteins. Moreover, an integrated biological information network of the drug-target-metabolite-signaling pathways was constructed to provide insights into the underlined mechanism of DM and DN as well as clinical combination therapy.

The use of low-sodium salt substitute (LSSS) has the potential to reduce sodium and increase potassium intake. LSSS has been available in the Chinese market for years. However, its real-world use and impact on sodium/potassium intake is unclear. Baseline data of 4000 adult individuals who participated in three similarly designed randomized controlled trials were pooled together for this analysis. Self-reported awareness and use of LSSS were collected using a standardized questionnaire, and the participants' 24-h urinary sodium and potassium excretion was used to estimate their dietary intake. Mixed-effects models were developed to assess the relationship between LSSS and 24-h urinary sodium and potassium excretion. 32.0% of the participants reported awareness of LSSS and 11.7% reported its current use. After adjusting for location, sex, age, and education, compared with the group of participants unaware of LSSS, participants who were aware of but not using LSSS and those who were using LSSS had a lower 24-h urinary sodium excretion by -356.1 (95% CI: -503.9, -205.9) mg/d and -490.6 (95% CI: -679.2, -293.7) mg/d, respectively ( p < 0.001). No significant difference was found for 24-h urinary potassium excretion or sodium-to-potassium ratio among the three groups ( p > 0.05). In conclusion, the findings of low usage of LSSS and the reduced urinary sodium excretion associated with the awareness and use of LSSS provide further support for the prometon of LSSS as a key salt reduction strategy in China.

Objectives: We conducted this study to assess the application effect of the family doctor contract service mode of 'basic package+personalised package' in the management of hypertension patients., Design: Observational study., Setting: The study was conducted at a community health centre in Southwest China. Data were collected from 1 January 2018 to 31 December 2020., Participants: From 1 January 2018 to 31 December 2020, hypertensive patients (age ≥65 years) who participated in the contract services of family doctors at a community health service centre in Chengdu, Southwest China, were selected as the study subjects., Main Outcome Measures: The primary outcomes included mean blood pressure (systolic, diastolic) and the rate of blood pressure control, secondary outcomes included the level of cardiovascular disease risk and self-management ability. Assessments of baseline and 6 months after signing up were conducted on all outcomes. The major statistical analysis methods included two independent sample t-tests, paired t-tests, Pearson's χ 2 test, McNemar's test, two independent sample Mann-Whitney U tests and paired sample marginal homogeneity tests., Results: Of the 10 970 patients screened for eligibility, 968 (8.8%) were separated into an observation group (receiving 'basic package+personalised package (hypertension)' service) (n=403) and a control group (receiving 'basic package' service) (n=565) according to the type of service package they received. In comparison to the control group, the observation group had lower mean systolic blood pressure (p=0.023), higher blood pressure control rate (p<0.001), lower cardiovascular disease risk level (p<0.001) and higher self-management ability level (p<0.001) at 6 months after signing up. The mean diastolic blood pressure of the two groups was not significantly different (p=0.735)., Conclusions: The family doctor contract service model of 'basic package+personalised package (hypertension)' has a good application effect in the management of elderly hypertension, which can improve the average blood pressure, the rate of blood pressure control, the level of cardiovascular disease risk and self-management ability of the elderly with hypertension., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To explore the relationship between Dietary Approaches to Stop Hypertension (DASH) diet and serum uric acid (SUA) levels among the Chinese adult population, and verify the mediating effect of BMI between DASH diet and SUA levels. A total of 1125 adults were investigated using a self-administered food frequency questionnaire. SUA levels were determined by uricase colorimetry. The total DASH score ranged from 9 to 72. The relationship between the DASH diet and SUA levels was examined by multiple adjusted regression analysis. Method of Bootstrap was used to test the mediation effect of BMI in the correlation of the DASH diet and SUA levels. After multivariable adjustment, there was a significant linear relationship between the DASH diet and SUA (P < 0.001). Compared with the lowest group, SUA of participants in group of highest DASH diet score decreased by 34.907 (95% CI - 52.227, - 17.588; P trend < 0.001) μmol/L. The association between the DASH diet scores and SUA levels was partly mediated by BMI (- 0.26, Bootstrap 95% CI - 0.49, - 0.07), with 10.53% of the total effect being mediated. Adopting the DASH diet might be helpful in reducing SUA level, and the effect might be partly mediated by BMI., (© 2023. The Author(s).)

Background: High salt intake is a major cause of hypertension and cardiovascular diseases. The out-of-home sectors have been identified as one of the contributors of high salt intake in the population. The National Salt Reduction Policy of Malaysia was initiated in 2015; however, out-of-home sectors are yet to be emphasized and perception by policy-makers and the food industries towards salt reduction are yet unknown. This study aimed to determine the perceptions, barriers and enablers towards salt reduction in the out-of-home sector in Malaysia, as well as among policy-makers and the food industries., Methods: This is a qualitative study via semi-structured in-depth interviews (IDI) and focus group discussions (FGD) involving several stakeholders consisting of policy-makers from five ministries, five nongovernment organizations (NGOs) and food science/food technology researchers from five regions (West, North, East, and South Peninsular and East Malaysia/Borneo), as well as the food industries. The IDI and FGD sessions were recorded, transcribed verbatim and analysed thematically using Nvivo software version 12., Results: All participants agreed that salt intake in Malaysia is high and leads to hypertension and cardiovascular diseases. Lack of awareness, poor eating culture and behaviour and frequent eating out were among the causes of high salt intake. Awareness campaigns and education, sodium content labelling and product reformulation were strategies that have been implemented by the government; whilst for the food industries, some of them have tried to reduce salt and labelled the sodium content on their food products. However, there were several barriers including perceived poor consumer acceptance, lack of knowledge and resources, and challenges in reformulation, as well as unavailability of guidelines and salt targets. Hence, several enablers have been suggested, which include prioritizing the salt reduction strategy, creating more awareness, collaboration and engagement, research and technology particularly for reformulation and shelf-life stability, incentives and salt tax., Conclusions: Salt reduction efforts of the out-of-home sector in Malaysia could be achieved through several measures or enablers that can overcome the barriers currently faced by stakeholders, especially policy-makers, food industries and the consumers themselves. This study will benefit the policy-makers to improve the salt reduction policy of out-of-home sectors and highlight the concerns among the food industries on the policy., (© 2023. The Author(s).)

Background: Although hypertension requiring medication (HTNm) is a well-known cardiovascular comorbidity, its association with postoperative outcomes is understudied. This study aimed to evaluate whether preoperative HTNm is independently associated with specific complications after pancreaticoduodenectomy., Study Design: Adults undergoing elective pancreaticoduodenectomy were included from the 2014-2019 NSQIP-targeted pancreatectomy dataset. Multivariable regression models compared outcomes between patients with and without HTNm. Endpoints included significant complications, any complication, unplanned readmissions, length of stay (LOS), clinically relevant postoperative pancreatic fistula (CR-POPF), and cardiovascular and renal complications. A subgroup analysis excluded patients with diabetes, heart failure, chronic obstructive pulmonary disease, estimated glomerular filtration rate from serum creatinine (eGFRCr) < 60 ml/min per 1.73 m 2 , bleeding disorder, or steroid use., Results: Among 14,806 patients, 52% had HTNm. HTNm was more common among older male patients with obesity, diabetes, congestive heart failure, chronic obstructive pulmonary disease, functional dependency, hard pancreatic glands, and cancer. After adjusting for demographics, preoperative comorbidities, and laboratory values, HTNm was independently associated with higher odds of significant complications (aOR 1.12, p = 0.020), any complication (aOR 1.11, p = 0.030), cardiovascular (aOR 1.78, p = 0.002) and renal (aOR 1.60, p = 0.020) complications, and unplanned readmissions (aOR 1.14, p = 0.040). In a subgroup analysis of patients without major preoperative comorbidity, HTNm remained associated with higher odds of significant complications (aOR 1.14, p = 0.030) and cardiovascular complications (aOR 1.76, p = 0.033)., Conclusions: HTNm is independently associated with cardiovascular and renal complications after pancreaticoduodenectomy and may need to be considered in preoperative risk stratification. Future studies are necessary to explore associations among underlying hypertension, specific antihypertensive medications, and postoperative outcomes to investigate potential risk mitigation strategies., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

We determined whether a town-level comprehensive intervention program could lower the salt intake of a population. The parallel, cluster randomized controlled trial was carried out between October 2018 and January 2020 in 48 towns from 12 counties across 6 provinces in China. All participants were asked to complete the 24 h urine collections, anthropometric measurements and questionnaires at the baseline and one-year post-intervention survey. A total of 2693 participants aged 18 to 75 years were recruited at the baseline. A total of 1347 individuals in 24 towns were allocated to the intervention group and the others were allocated to the control group. Valid information from 2335 respondents was collected in the follow-up survey. The 24-h urinary sodium excretion was 189.7 mmol/24 h for the intervention group and 196.1 mmol/24 h for the control group at baseline. At a one-year follow-up, the mean effect of salt intake did not show a significant change (p = 0.31) in the intervention group compared to the control group. However, the mean result of potassium excretion in the intervention group increased by 2.18 mmol/24 h (85.03 mg/24 h) (p = 0.004) and systolic blood pressure decreased by 2.95 mmHg (p < 0.001). The salt-related knowledge and attitude toward salt reduction improved significantly in the intervention group (p < 0.05). A longer period of intervention and follow-up assessment might be needed to evaluate the long-term effectiveness of the program on salt reduction.

Salt intake in China is very high, which increases the risk of hypertension and cardiovascular disease. This study aimed to assess the levels of salt-related knowledge, attitudes, and behaviors (KABs) and the factors that influence them and to explore the relationship between the scores of salt-related KAB and 24-h urinary sodium excretion. In 2018, we collected data from 5453 individuals aged 18-75 years from six provinces in China. A face-to-face survey was carried out, focusing on the KAB related to salt reduction. All participants were asked to collect one 24-h urine sample. Of the 5453 participants, 5352 completed urine collection. The mean score for overall KAB was 31.27 (SD = 9.18), which was composed of three elements: knowledge 4.80 (SD = 5.14), attitude 9.33 (SD = 3.93), and behavior 17.14 (SD = 4.43). The average 24-h urinary sodium excretion was 187.70 (SD = 77.48) mmol, which was equivalent to a urinary sodium excretion of 4.32 (SD = 1.78) g/d. We found that salt-related knowledge, attitude, behavior, and overall KAB scores were all inversely associated with 24-h urinary sodium excretion. For every one-point increase in the KAB score, the 24-h urinary sodium excretion decreased by 0.851 mmol (95% CI: -1.095, -0.602). We also found that location (rural/urban), sex, age, and education are associated with salt-related KAB scores. These results suggest that large-scale health education is needed to reduce salt intake in the Chinese population. In particular, efforts should be focused on reaching those who live in rural areas with low educational levels and older people.

Background: Previous studies suggested blood pressure variability (BPV) might help reveal interactions between blood pressure fluctuation and white matter lesions, and the impact of elevated BPV on white matter hyperintensity (WMH) or cerebral arterial dilation is unclear., Methods: This retrospective observational study involved 2634 stroke-free individuals (68.6±11.1 years, 50.3% female), who underwent magnetic resonance imaging and magnetic resonance angiography scans, from a single center in Shanghai, China. Measurements for variability of blood pressure were made based on 7 days blood pressure recordings. WMHs were quantified from T2-FLAIR images and further classified as periventricular WMH or deep WMH. M1 segment of middle cerebral artery dilation was assessed from magnetic resonance angiography images. General linear model was used to examine the associations., Results: Both increased systolic and diastolic BPV were associated with increased WMH volume (systolic: β =0.02 [95% CI, 0.004-0.03], P =0.01; diastolic: β =0.05 [95% CI, 0.03-0.08], P <0.001). Only periventricular WMH was associated with BPV (systolic: β =0.02 [95% CI, 0.005-0.04], P =0.01; diastolic: β =0.06 [95% CI, 0.04-0.09], P <0.001). MCA dilation was found in 125 individuals (4.75%). Systolic BPV was associated with MCA dilation only in the hypertensive individuals ( β =0.11 [95% CI, 0.06-0.17], P <0.001). Increased WMH volume was found associated with dilated MCA ( β =0.17 [95% CI, 0.11-0.23], P <0.001)., Conclusions: Increased BPV might be one of the pathophysiological phenomena involving in the small vessel disease independent of hypertension. Increased BPV might independently contribute to intracranial arterial dilation. Management of BPV might be a target to preserve cerebrovascular wellness.

Coronary microvascular disease (CMD), which affects the arterioles and capillary endothelium that regulate myocardial perfusion, is an increasingly recognized source of morbidity and mortality, particularly in the setting of metabolic syndrome. The coronary endothelium plays a pivotal role in maintaining homeostasis, though factors such as diabetes, hypertension, hyperlipidemia, and obesity can contribute to endothelial injury and consequently arteriolar vasomotor dysfunction. These disturbances in the coronary microvasculature clinically manifest as diminished coronary flow reserve, which is a known independent risk factor for cardiac death, even in the absence of macrovascular atherosclerotic disease. Therefore, a growing body of literature has examined the molecular mechanisms by which coronary microvascular injury occurs at the level of the endothelium and the consequences on arteriolar vasomotor responses. This review will begin with an overview of normal coronary microvascular physiology, modalities of measuring coronary microvascular function, and clinical implications of CMD. These introductory topics will be followed by a discussion of recent advances in the understanding of the mechanisms by which inflammation, oxidative stress, insulin resistance, hyperlipidemia, hypertension, shear stress, endothelial cell senescence, and tissue ischemia dysregulate coronary endothelial homeostasis and arteriolar vasomotor function.

Introduction: There is an urgent need to reduce the burden of non-communicable diseases (NCDs), particularly in low-and middle-income countries, where the greatest burden lies. Yet, there is little research concerning the specific issues involved in scaling up NCD interventions targeting low-resource settings. We propose to examine this gap in up to 27 collaborative projects, which were funded by the Global Alliance for Chronic Diseases (GACD) 2019 Scale Up Call, reflecting a total funding investment of approximately US$50 million. These projects represent diverse countries, contexts and adopt varied approaches and study designs to scale-up complex, evidence-based interventions to improve hypertension and diabetes outcomes. A systematic inquiry of these projects will provide necessary scientific insights into the enablers and challenges in the scale up of complex NCD interventions., Methods and Analysis: We will apply systems thinking (a holistic approach to analyse the inter-relationship between constituent parts of scaleup interventions and the context in which the interventions are implemented) and adopt a longitudinal mixed-methods study design to explore the planning and early implementation phases of scale up projects. Data will be gathered at three time periods, namely, at planning (T P ), initiation of implementation (T 0 ) and 1-year postinitiation (T 1 ). We will extract project-related data from secondary documents at T P and conduct multistakeholder qualitative interviews to gather data at T 0 and T 1. We will undertake descriptive statistical analysis of T P data and analyse T 0 and T 1 data using inductive thematic coding. The data extraction tool and interview guides were developed based on a literature review of scale-up frameworks., Ethics and Dissemination: The current protocol was approved by the Monash University Human Research Ethics Committee (HREC number 23482). Informed consent will be obtained from all participants. The study findings will be disseminated through peer-reviewed publications and more broadly through the GACD network., Competing Interests: Competing interests: JvO reports Horizon2020 grants (643 692 and 825432) outside the submitted work. AGT declares funding from the National Health & Medical Research Council (NHMRC, Australia: GNT1042600, GNT1122455, GNT1171966, GNT1143155, GNT1182017), Stroke Foundation Australia (SG1807), and Heart Foundation Australia (VG102282) outside the submitted work. ML-P declares support from Fogarty International Centre, National Institutes of Health [R21TW009982], under the Global Alliance for Chronic Diseases (GACD) Diabetes ProgramProgramme. MEE reports grant funding from the Argentinian Ministry of Health (MoH) under the GACD program. AS declares funding from the Japan Agency for Medical Research & Development, as part of the GACD, outside the submitted work. FJH is partially funded by the National Institute for Health Research (NIHR) and the Medical Research Council (MRC), and is a member of the Action on Salt, and World Action on Salt, Sugar and Health (WASSH). AB declares grants from the MoH Argentina, National Institutes of Health, and World Diabetes Foundation, outside the submitted work. AP declares grant and fellowship support from the NHMRC outside the submitted work, Member of the Board of Directors, The George Institute India, and past Member of the Board of Directors, Heart Health Research Center, Beijing, PRC. RJ declares grant, outside the submitted work, from WHO Geneva, WHO South-East Asia Region (SEARO), Elrha Research for Health in Humanitarian Crises (R2HC), (Wellcome Trust, UK AID and NHS), DBT/ Wellcome Trust India Alliance and Gates Foundation. In the past 3 years, MDH has received research funding from American Heart Association, Verily, and AstraZeneca for research unrelated to this manuscript and has patents pending for heart failure polypills. The George Institute for Global Health has a patent, license, and has received investment funding with intent to commercialize fixed-dose combination therapy through its social enterprise business, George Medicines. None of the others authors has any conflict of interest to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Apparent treatment-resistant hypertension (aTRH) is the most commonly used term to report resistant hypertension (RH) and is considered as a common problem in dialysis population. However, few reports have focused on peritoneal dialysis (PD) hypertensive patients. The authors conducted a multi-center cross-sectional study involving 1789 PD patients from nine centers in Guangdong, China. The prevalence of aTRH was estimated by home blood pressure (BP) monitoring. Evaluating drug adherence through Eight-item Morisky Medication Adherence Scale (MMAS-8) and pill counting was performed to assess RH in one PD center. Related factors of aTRH were analyzed using logistic regression analysis. The prevalence of aTRH in PD patients was estimated at 42.2% (755 out of 1789 hypertensive patients) based on home BP. Of those, 91.4% patients were classified as uncontrolled RH, 2.0% as controlled RH, and 6.6% as refractory hypertension. The prevalence of RH was 40.6% and 41.9% among those with medium/high adherence based on the MMAS-8 scores and the pill counting rate, respectively. PD patients who were younger, with higher body mass index, with lower serum albumin and poorer dialysis adequacy were significantly associated with higher aTRH incident. In conclusion, the present study demonstrates a high prevalence of aTRH in PD population, which occurs in about two in five treated hypertensive patients. Nutritional status and dialysis adequacy might tightly associate with aTRH., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

This study aimed to investigate the cross-sectional association between serum sodium and blood pressure at baseline and, more importantly, investigate the prospective association between serum sodium and the risk of incident hypertension. We used data from 1 638 workers aged 18 to 71 years who participated in 2015-2016 survey of the Furukawa Nutrition and Health Study. During a maximum follow-up of 3 years, 229 participants developed hypertension. Multivariable linear regression models were used to evaluate the cross-sectional association. The Cox proportional hazards model was used to calculate the hazard ratio and 95% confidence interval of incident hypertension across quartiles of serum sodium (137-140, 141-142, 143, and 144-147 mmol/L). In the cross-sectional analysis, we did not observe a significant association between serum sodium and blood pressure at baseline. In the prospective analysis, the multivariable-adjusted hazard ratios (95% confidence intervals) for incident hypertension were 1.03 (0.71-1.51), 1.35 (0.87-2.08), and 1.46 (0.97-2.20) for the upper three quartiles of the serum sodium levels compared with the lowest quartile (P for trend=0.02). When serum sodium was treated as a continuous variable, the multivariable-adjusted hazard ratio for hypertension was 1.10 (1.03-1.18). The association was slightly attenuated after additionally adjusting for baseline blood pressure, with a hazard ratio of 1.08 (1.00-1.16) for a 1 mmol/L increase in serum sodium. In conclusion, an elevated serum sodium level was associated with an increased risk of developing hypertension, suggesting that serum sodium could be a potential risk factor for hypertension., (© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Health literacy has been recognized as a significant social determinant of health, defined as the ability to access, understand, appraise, and apply health-related information across healthcare, disease prevention, and health promotion. This systematic review aims to understand the relationship between health literacy, blood pressure, and dietary salt intake. A web-based search of PubMed, Web of Science, CINAHL, ProQuest, Scopus, Cochrane Library, and Prospero was performed using specified search/MESH terms and keywords. Two reviewers independently performed the data extraction and analysis, cross-checked, reviewed, and resolved any discrepancies by the third reviewer. Twenty out of twenty-two studies met the inclusion criteria and were rated as good quality papers and used in the final analysis. Higher health literacy had shown to have better blood pressure or hypertension knowledge. However, the relationship between health literacy with dietary salt intake has shown mixed and inconsistent findings. Studies looking into the main four domains of health literacy are still limited. More research exploring the links between health literacy, blood pressure, and dietary salt intake in the community is warranted. Using appropriate and consistent health literacy tools to evaluate the effectiveness of salt reduction as health promotion programs is required.

Background: The oscillometric blood pressure (BP) measurement technique estimates BPs from analyzing the envelop of oscillometric cuff pressure waveform. The oscillometric waveform envelope shape is associated with physiological changes and influences BP measurement accuracy. The aim of this study was to comprehensively quantify BP- and age-related changes of oscillometric waveform envelope characteristics., Method: Manual systolic and diastolic BPs were measured from 472 patients (219 female, 253 male), and the cuff pressure were digitally recorded during linear cuff deflation that was used to derive oscillometric waveform envelopes. All patients were divided into different categories according to their BP level and age. The envelope width in high-pressure region (above mean arterial pressure, MAP) and low-pressure region (below MAP) were compared between different BP and age categories to qualify their changes with increased BP and aging., Results: The envelop widths increased significantly with increased BPs (P < 0.001 between optimal, normotensive and hypertensive groups) and aging (P < 0.001 for >50 years old group in comparison with younger groups). The envelope widths in high-pressure region were significantly larger than in low-pressure region in normal and hypertensive categories (all P < 0.05) and elderly patients aged over 60 years (all P < 0.001), and the envelope width ratios between them increased with increased BP and aging., Conclusion: This study has concluded an asymmetrical oscillometric waveform envelope in normotensive and hypertensive categories, as well as in elderly group (aged over 60 years), and their asymmetrical features were significantly more obvious with increased BP and aging., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Sodium and potassium appear to interact with each other in their effects on blood pressure with potassium supplementation having a greater blood pressure lowering-effect when sodium intake is high. Whether the effect of sodium reduction on blood pressure varies according to potassium intake levels is unclear. We carried out a systematic review and meta-analysis to examine the impact of baseline potassium intake on blood pressure response to sodium reduction in randomized trials in adult populations, with sodium and potassium intake estimated from 24-h urine samples. We included 68 studies involving 5708 participants and conducted univariable and multivariable meta-regression. The median intake of baseline potassium was 67.7 mmol (Interquartile range: 54.6-76.4 mmol), and the mean reduction in sodium intake was 128 mmol (95% CI: 107-148). Multivariable meta-regression that included baseline 24-h urinary potassium excretion, age, ethnicity, baseline blood pressure, change in 24-h urinary sodium excretion, as well as the interaction between baseline 24-h urinary potassium excretion and change in 24-h urinary sodium excretion did not identify a significant association of baseline potassium intake levels with the blood pressure reduction achieved with a 50 mmol lowering of sodium intake (p > 0.05 for both systolic and diastolic blood pressure). A higher starting level of blood pressure was consistently associated with a greater blood pressure reduction from reduced sodium consumption. However, the nonsignificant findings may subject to the limitations of the data available. Additional studies with more varied potassium intake levels would allow a more confident exclusion of an interaction., (© 2021. Crown.)

Introduction: This study aimed to examine the medication prescriptions for hypertension in a class 1 and grade A hospital in Shanxi province to provide references for clinical rational drug use., Methods: An inpatient medical record inquiry system was used to evaluate the use of antihypertensives in a hypertensive population (age ≥ 18 years old) who received a prescription for one or more antihypertensives between January 2017 and December 2019. The hypertensive population was categorized into grades (1, 2, and 3), age groups, and different comorbidities to analyze the medication prescriptions. Drug analysis included angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor antagonist (ARB), calcium channel blocker (CCB), diuretics, and beta-receptor blockers (B-RB). SPSS16.0 was used for statistical analysis, including one-way analysis of variance (ANOVA,) chi-squared test, and multifactor logistic regression analysis., Results: The overall control rate of blood pressure was 60.79%. The control rates of single, double, triple, and quadruple antihypertensives were 70.08%, 59.97%, 56.27%, and 45.23%, respectively. There were more cases of grade 3 than grades 1 and 2. The 18-65 years group was larger than the 66-79 years and ≥ 80 years groups. With the increase in grade, the prescription rate of the single drug decreased and the prescription rate of the combination drug increased, but this phenomenon was not obvious in different age groups. The most common drug prescribed for monotherapy was CCB; CCB combined with B-RB had the highest drug use in the double group by age or grade. Statistically significant differences were detected in the type of comorbidities between different age groups (P < 0.001), while only some differences were observed between different grades. Also, statistically significant differences were observed in the drugs prescribed for patients with hypertension with different comorbidities (P < 0.001). Factors influencing the efficiency of antihypertensives included sex, age, diabetes, heart failure, and usage of CCB and B-RB. The prescription rate of ARB combined with B-RB was relatively higher in grade 2 cases. B-RB was the primary drug for patients with diabetes, significantly increasing the blood glucose level., Conclusions: The medication prescription of this hospital was in line with the requirements of China's hypertension prevention and treatment guidelines. The pathophysiology of patients with hypertension in different age groups, increased use of combination drugs, and rational drug requirement should be considered when prescribing drugs., (© 2021. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Research reports on associations of urinary sodium excretion with central hemodynamic parameters and vascular changes are quite limited in general or non-hypertensive population. The purpose of the current study was to explore such associations in Chinese general Tibetans living at high altitude. This cross-sectional study was conducted in Luhuo County, Ganzi Tibetan Autonomous Prefecture with average elevation of 3800 meters from December 2018 to January 2019. A total of 294 Tibetans were included in the current study. Twenty-four hour urinary sodium excretion was estimated by second fasting spot urine in the morning using Kawasaki formula. Central hemodynamic parameters, including central systolic blood pressure (CSBP), central diastolic blood pressure (CDBP), central pulse pressure (CPP), central mean arterial pressure (CMAP), augmentation pressure (AP), and augmentation index standardized for heart rate of 75 (AIx 75 ), were evaluated using the SphygmoCor system. Vascular structures and functions were assessed by carotid intima media thickness (CIMT) test and brachial ankle pulse wave velocity (baPWV), respectively. Estimated mean 24h urinary sodium excretion of Tibetans in Luhuo County was 5.26±1.61 g. After adjustment, estimated 24h urinary sodium was positively associated with CSBP (β = 1.15, p = .008) and CPP (β = 0.87, p = .013). Line graph of means across urinary sodium quartiles showed that associations of 24 h urinary sodium excretion with AIx 75 and baPWV presented approximate "J" shape after controlling for confounders. Estimated 24 h sodium excretion was independently and positively associated with CSBP and CPP. Moreover, association between urinary sodium excretion and arterial elasticity, as evaluated by baPWV and AIx 75 , presented "J" shape. Further studies are needed to verify J-shaped association and "safe" zone of sodium intake., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

There is a causal relationship between dietary salt intake and blood pressure. A reduction in salt intake from the current world average of ∼10 g/day to the WHO recommended level of <5 g/day, lowers blood pressure and reduces the risk of cardiovascular disease and all-cause mortality. However, a few cohort studies have claimed that there is a J-shaped relationship between salt intake and cardiovascular risk, i.e. both high and low salt intakes are associated with an increased risk. These cohort studies have several methodological problems, including reverse causality, and inaccurate and biased estimation of salt intake, e.g. from a single spot urine sample with formulas. Recent studies have shown that the formulas used to estimate salt intake from spot urine cause a spurious J-curve. Research with inappropriate methodology should not be used to refute the robust evidence on the enormous benefits of population-wide reduction in salt intake. Several countries, e.g. Finland, the UK, have successfully reduced salt intake, which has resulted in falls in population blood pressure and deaths from stroke and ischaemic heart disease. Every country should develop and implement a coherent, workable strategy to reduce salt intake. Even a modest reduction in salt intake across the whole population will lead to a major improvement in public health, along with huge cost-savings to the healthcare service., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: High sodium intake was an established risk factor for stroke and cardiovascular diseases. The objective of this study was to investigate factors associated with high sodium intake based on 24-h urinary sodium excretion from the MyCoSS study., Methods: The cross-sectional survey was conducted among adults aged 18 years and above in Malaysia. A multi-stage stratified sampling was used to represent nationally. Twenty-four-hour urine was collected from a total of 900 respondents. Indirect ion-selective electrode (ISE) method was used to measure sodium intake. Descriptive and logistic regression analysis was applied to determine factors associated with high sodium intake based on 24-h urinary sodium excretion., Results: A total of 798 respondents (76% response rate) completed the 24-h urine collection process. Logistic regression revealed that high sodium intake associated with obese [aOR 2.611 (95% CI 1.519, 4.488)], male [aOR 2.436 (95% CI 1.473, 4.030)], having a waist circumference of > 90cm for adult males [aOR 2.260 ( 95% CI 1.020, 5.009) and >80cm for adult females [aOR 1.210 (95% CI 0.556, 2.631)], being a young adult [aOR 1.977 (95% CI 1.094, 3.574)], and living in urban areas [aOR 1.701 (95% CI 1.094, 2.645)]., Conclusion: Adults who are obese, have a large waist circumference, of male gender, living in urban areas, and belonging to the young adult age group were found to have higher sodium intake than other demographic groups. Hence, reduction of salt consumption among these high-risk groups should be emphasised to reduce the risk of cardiovascular diseases.

Background: High blood pressure or hypertension has become one of the main health problems, worldwide. A number of studies have proven that an increased intake of salt was related to an increased prevalence of cardiovascular diseases. Of late, its relationship with high salt intake has received a lot of attention. Studies in Malaysia have shown both rising hypertension over time as well as high salt consumption. Actions to reduce salt intake are essential to reduce hypertension and its disease burden. As such, we carried out a study to determine associations between knowledge, attitude and behaviour towards salt intake and hypertension among the Malaysian population., Methods: Data obtained from the Malaysian Community Salt Survey (MyCoSS) was used partially for this study. The survey used a cross-sectional two-stage sampling design to select a nationally representative sample of Malaysian adults aged 18 years and above living in non-institutional living quarters (LQ). Face-to-face interviews were done by trained research assistants (RA) to obtain information on sociodemography, medical report, as well as knowledge, attitude and behaviour of the respondents towards salt intake and blood pressure., Results: Majority of the respondents have been diagnosed with hypertension (61.4%) as well as knowledge of the effects of high salt intake on blood pressure (58.8%). More than half of the respondents (53.3%) said they controlled their salt intake on a regular basis. Those who knew that a high salt diet could contribute to a serious health problem (OR=0.23) as well as those who controlled their salt intake (OR=0.44) were significantly less likely to have hypertension., Conclusion: Awareness of the effects of sodium on human health, as well as the behaviour of controlling salt intake, is essential towards lowering the prevalence of hypertension among Malaysians.

Background: Hypertension is one of the most common risk factors for cardiovascular disease and leading cause of mortality globally. The aims of this study were to assess the prevalence of hypertension and its associated risk factors among Malaysian population using data from the Malaysian Community Salt Study (MyCoSS)., Methods: This study was a cross-sectional study using multi-stage stratified sampling method. Data collection was carried out via face-to-face interview at the respondent's home from October 2017 until March 2018. A total of 1047 respondents aged 18 years and above completed the questionnaires and blood pressure measurement. A person who reported diagnosis of hypertension by a physician and had systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg on three readings was categorised as hypertensive. Risk factors of hypertension were analysed using multiple logistic regression., Results: The prevalence of hypertension in the present study was 49.39% (95% CI 44.27-54.51). There was no statistically significant difference in gender. Age, household income, BMI, and diabetes were significantly associated with hypertension. Hypertension found had inverse association with the level of education. Age was the strongest predictor of hypertension (35-44 years old; OR=2.39, 95% CI=1.39-4.09, 45-54 years old; OR=5.50, 95% CI=3.23-9.38, 55-64 years old OR=13.56, 95% CI=7.77-23.64 and 65 years old and above; OR=25.28, 95% CI=13.33-48.66). Those who had higher BMI more likely to be hypertensive as compared to respondents with normal weight (overweight, OR=1.84; 95% CI=1.18-2.86; obese, OR=4.29% CI=2.56-7.29)., Conclusion: The findings showed that hypertension is prevalent among adults in Malaysia. Those with older age, higher BMI, and diabetes are more likely to have hypertension. Efforts regarding lifestyle modification and education could be important in hypertension management and prevention.

Background: Atrial fibrillation (AF) is the most common serious cardiac rhythm disturbances and is responsible for substantial morbidity and mortality in general population. Hypertension is the most prevalent and potentially modifiable risk factor for AF. This study is aimed at evaluating the effect of angiotensin receptor blocker (ARB) or calcium channel blocker (CCB) on AF recurrence among patients with hypertension and AF., Methods: The PubMed, EMBASE, Medline, and Cochrane Collaboration of Controlled Clinical Trials registry databases were searched from their inception to September 2020., Results: A total of 7 randomized controlled trials (RCTs) enrolling 1495 patients were included in our study. This finding showed that ARB had a statistically significant superiority in preventing AF recurrence (OR: 0.43, 95% CI: 0.30-0.72, P = 0.0006) and persistent AF (OR: 0.41, 95% CI: 0.24-0.71, P = 0.001) compared to CCB. Subgroup analysis showed that there was a significant difference in telmisartan subgroup (OR: 0.54, 95% CI: 0.23-1.29, P = 0.17) and nontelmisartan subgroup (OR: 0.42, 95% CI: 0.23-0.77, P = 0.005). Subgroup analysis indicated that nifedipine subgroup did not show a statistically significant difference on AF recurrence between ARB and CCB (OR: 0.88, 95% CI: 0.46-1.68, P = 0.69), but amlodipine subgroup showed that ARB had a significant superiority in prevention of AF recurrence (OR: 0.39, 95% CI: 0.27-0.56, P < 0.0001) compared with CCB., Conclusions: This study suggests that ARB is superior to CCB for preventing the AF recurrence and persistent AF among patients with hypertension and AF., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2021 Haotian Ma et al.)

[Figure: see text].

Fluoride exposure may cause changes in blood pressure, but this conclusion is controversial. Therefore, this meta-analysis aims to investigate the potential relationship between fluoride exposure and blood pressure or hypertension. PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), WANFANG MED ONLINE, and Chinese Scientific Journals Full-Text Databases (VIP) were searched; in addition, two related studies were added manually. In total, 7 observational studies were identified, the pooled odds ratios (ORs) for hypertension between high and reference fluoride exposure groups were calculated, and the pooled standardized weighted mean difference (SMD) of systolic blood pressure (SBP) and diastolic blood pressure (DBP) was estimated using an inverse-variance weighted random-effects model; next, sensitivity analysis and subgroup analysis were used to assess potential sources of heterogeneity; furthermore, publication bias was assessed using the Begg and Egger test. In brief, there were no statistical differences between exposure groups and control groups in terms of blood pressure or hypertension when all included studies considered. However, subgroup analysis indicated that blood pressure will rise with the increase of fluoride exposure concentrations in endemic fluorosis areas. The corresponding pooled SMD estimates were 0.31 (95% CI 0.11, 0.51) and 0.27 (95% CI 0.11, 0.43) for SBP and DBP. Funnel plots suggested no asymmetry. Our findings support the possibility of a positive correlation between fluoride exposure and blood pressure in endemic fluorosis areas. Additional evidence is needed to assess the dose-response relationship between fluoride exposure and blood pressure.

Dysfunction of late endothelial progenitor cells (EPCs) has been suggested to be associated with hypertension. β 2 -Adrenergic receptor (β 2 AR) is a novel and key target for EPC homing. Here, we proposed that attenuated β 2 AR signaling contributes to EPCs dysfunction, whereas enhanced β 2 AR signaling restores EPCs' functions in hypertension. EPCs derived from hypertensive patients exhibited reduced cell number, impaired in vitro migratory and adhesion abilities, and impaired re-endothelialization after transplantation in nude mice with carotid artery injury. β 2 AR expression of EPCs from hypertensive patients was markedly downregulated, whereas the phosphorylation of the p38 mitogen-activated protein kinase (p38-MAPK) was elevated. The cleaved caspase-3 levels were elevated in EPCs. The overexpression of β 2 AR in EPCs from hypertensive patients inhibited p38-MAPK signaling, whereas it enhanced in vitro EPC proliferation, migration, and adhesion and in vivo re-endothelialization. The β 2 AR-mediated effects were attenuated by treating the EPCs with a neutralizing monoclonal antibody against β 2 AR, which could be partially antagonized by the p38-MAPK inhibitor SB203580. Moreover, shear stress stimulation, a classic nonpharmacological intervention, increased the phosphorylation levels of β 2 AR and enhanced the in vitro and in vivo functions of EPCs from hypertensive patients. Collectively, the current investigation demonstrated that impaired β 2 AR/p38-MAPK/caspase-3 signaling at least partially reduced the re-endothelialization capacity of EPCs from hypertensive patients. Restoration of β 2 AR expression and shear stress treatment could improve their endothelial repair capacity by regulating the p38-MAPK/caspase-3 signaling pathway. The clinical significance of β 2 AR in endothelium repair still requires further investigation. NEW & NOTEWORTHY Impaired β 2 -adrenergic receptor (β 2 AR) expression with an elevation of p38-MAPK/caspase-3 signaling at least partially contributes to the decline of re-endothelialization capacity of late endothelial progenitor cells (EPCs) from hypertensive patients. β 2 AR gene transfer and shear stress treatment improve the late EPC-mediated enhancement of the re-endothelialization capacity in hypertensive patients through activating β 2 AR/p38-MAPK/caspase-3 signaling. The present study is the first to reveal the potential molecular mechanism of the impaired endothelium-reparative capacity of late EPCs in hypertension after vascular injury and strongly suggests that β 2 AR is a novel and crucial therapeutic target for increasing EPC-mediated re-endothelialization capacity in hypertension.

Background: The objective was a large-scale analysis of the relation between hypertension, memory problems, and brain function., Methods: The study design was to measure the association between a history of hypertension, and the functional connectivity between 94 brain regions, and prospective and numeric memory, in 19,507 participants from the UK Biobank, with cross-validation in 1,002 participants in the Human Connectome Project, and 13,441 individuals in the second release of the UK Biobank. A history of hypertension was measured by whether individuals were admitted to hospital for the treatment of hypertension, with the control group admissions for other reasons., Findings: A history of hypertension was associated with reduced functional connectivity of the hippocampus, and with reduced prospective memory score (FDR correction p<0.01). The reduced functional connectivity mediated the association between the hypertension history and the prospective memory score. A graded linear relation between both the hippocampal functional connectivity and memory impairment, was found across a wide range of blood pressure (r=-0.04). In 502,537 participants from the UK Biobank, a history of hypertension was associated with impaired prospective memory (p = 9.1 × 10 -41 , Cohen's d=-0.08) and numeric memory (p = 4.7 × 10 -24 , Cohen's d=-0.10). The association between hypertension, functional connectivity, and impaired memory was cross-validated with 1,002 participants from the Human Connectome Project; and for functional connectivity in 13,441 individuals in the second release of the UK Biobank imaging dataset., Interpretation: The reduced functional connectivity of the hippocampus, and the memory impairments, both related to hypertension across a wide range of blood pressure, are important for clinical practice., Competing Interests: Declaration of interests The authors report no disclosures and competing interests relevant to the manuscript., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

High-sodium diet may modulate the gut microbiome. Given the circulating short-chain fatty acids (SCFAs) are microbial in origin, we tested the hypothesis that the modest sodium reduction would alter circulating SCFA concentrations among untreated hypertensives, and the changes would be associated with reduced blood pressure and improved cardiovascular phenotypes. A total of 145 participants (42% blacks, 19% Asian, and 34% females) were included from a randomized, double-blind, placebo-controlled cross-over trial of sodium reduction with slow sodium or placebo tablets, each for 6 weeks. Targeted circulating SCFA profiling was performed in paired serum samples, which were collected at the end of each period, so as all outcome measures. Sodium reduction increased all 8 SCFAs, among which the increases in 2-methylbutyrate, butyrate, hexanoate, isobutyrate, and valerate were statistically significant ( P s<0.05). Also, increased SCFAs were associated with decreased blood pressure and improved arterial compliance. There were significant sex differences of SCFAs in response to sodium reduction ( P s<0.05). When stratified by sex, the increases in butyrate, hexanoate, isobutyrate, isovalerate, and valerate were significant in females only ( P s<0.05), not in males ( P s>0.05). In females, changes in isobutyrate, isovalerate, and 2-methylbutyrate were inversely associated with reduced blood pressures ( P s<0.05). Increased valerate was associated with decreased carotid-femoral pulse wave velocity ( P =0.040). Our results show that dietary sodium reduction increases circulating SCFAs, supporting that dietary sodium may influence the gut microbiome in humans. There is a sex difference in SCFA response to sodium reduction. Moreover, increased SCFAs are associated with decreased blood pressures and improved arterial compliance. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00152074.

Objective: The objective of the study was to investigate the association between mitochondrial DNA (mtDNA) mutations and essential hypertension (EH)., Methods: One Han Chinese pedigree with maternally inherited EH was recruited in the current study. The matrilineal relatives from this family underwent clinical, genetic, and molecular analysis. Moreover, the mtDNA gene mutations were screened by PCR and direct Sanger sequence. Evolutionary conservation was performed and the secondary structure of mt-tRNA Ser(UCN) with and without the 7471delC was evaluated by the RNA Fold Webserver program. Moreover, the pathogenicity scoring system was used to assess the 7471delC., Results: This Chinese pedigree exhibited a relative high penetrance and expressivity of EH. Of 13 matrilineal relatives, 5 of them suffered from high blood pressure (BP). Genetic analysis of the complete mtDNA genes showed the presence of a novel tRNA Ser(UCN) 7471delC, together with a set of polymorphisms belonging to the human mitochondrial haplogroup G2a1. In fact, the 7471delC occurred within the T-stem and extra arm of tRNA Ser(UCN) , which was very conserved from bacteria to human mitochondria. Interestingly, the 7472insC which was located at the same position had been regarded as a pathogenic mutation associated with non-syndromic hearing loss. In addition, bioinformatics analysis revealed that the 7471delC affected the secondary structure of tRNA Ser(UCN) . The pathogenicity scoring system showed that the 7471delC may be "possibly pathogenic" associated with EH., Conclusion: We believed that the 7471delC may impair the mitochondrial functional and played an active role in the pathogenesis of EH in this pedigree. The 7471delC may be a novel risk factor for maternally transmitted EH.

There is strong evidence for a causal relationship between salt intake and blood pressure. Randomized trials demonstrate that salt reduction lowers blood pressure in both individuals who are hypertensive and those who are normotensive, additively to antihypertensive treatments. Methodologically robust studies with accurate salt intake assessment have shown that a lower salt intake is associated with a reduced risk of cardiovascular disease, all-cause mortality, and other conditions, such as kidney disease, stomach cancer, and osteoporosis. Multiple complex and interconnected physiological mechanisms are implicated, including fluid homeostasis, hormonal and inflammatory mechanisms, as well as more novel pathways such as the immune response and the gut microbiome. High salt intake is a top dietary risk factor. Salt reduction programs are cost-effective and should be implemented or accelerated in all countries. This review provides an update on the evidence relating salt to health, with a particular focus on blood pressure and cardiovascular disease, as well as the potential mechanisms., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: In a randomised controlled trial, we investigated the blood pressure (BP) lowering effect of continuous positive airway pressure (CPAP) in patients with moderate-severe obstructive sleep apnoea syndrome (OSAS, an apnoea-hypopnoea index, AHI of 15 or higher) and nocturnal hypertension (night-time systolic/diastolic BP ≥120/70 mmHg). Methods: Sixty patients were randomly assigned to CPAP or sham CPAP, while maintaining their antihypertensive treatment. Ambulatory BP monitoring was performed at baseline (first run-in visit) and the end of follow-up. Clinic and home BP were measured at baseline and each of the monthly follow-up visits. Results: Of the 60 patients, 47 completed the 3-month study. CPAP ( n  = 26), compared with sham CPAP ( n  = 21), slightly and non-significantly reduced 24-h systolic/diastolic BP by -2.8/-2.5 mmHg ( p  ≥ 0.27), with a slightly greater between-group difference in the daytime (-4.0/-2.8 mmHg, p  ≥ 0.29) than night-time (-0.2/-1.5 mmHg, p  ≥ 0.50). The CPAP treatment did not significantly influence clinic or home BP during follow-up ( p  ≥ 0.27). Nonetheless, simple and partial correlation analyses showed that the ambulatory BP lowering effect was dependent on the daytime pulse rate at baseline ( r  ≥ 0.47, p  ≤ 0.01). In patients with a daytime pulse rate greater than 85 beats/min, the mean changes in daytime systolic BP were significantly greater in the CPAP ( n  = 10) than sham CPAP group ( n  = 11), with a between-group mean difference of -10.1 mmHg ( p  = 0.048). Conclusions: The CPAP treatment did not show significant ambulatory BP lowering effect in patients with moderate-severe OSAS and nocturnal hypertension. However, it may be effective in lowering daytime BP in patients with a faster pulse rate.

Introduction: Salt intake in China (≈12 g/day) is more than twice the upper limit recommended by the WHO (5 g/day). To reduce salt intake, Action on Salt China (ASC) was launched in 2017. As one of four randomised controlled trials (RCTs) in the ASC programme, a comprehensive intervention study was designed to test whether all the components of the interventions adopted by other RCTs are acceptable, scalable and effective when provided to a region in the real world., Methods and Analysis: Using a cluster RCT design, 2688 participants were selected from 48 towns (clusters) in 12 counties in 6 provinces and assigned to the intervention group or the control group. Randomisation was performed after the baseline survey was completed. Information on salt-related knowledge, attitude and practice (KAP), blood pressure and 24-hour urinary sodium were collected. The intervention includes government engagement, health education and other intervention components targeting restaurants, home cooks and primary school students and their families that have been used in other RCTs. The control group will not receive the intervention. The project will be followed up for 2 years, with the intervention being carried out for the first year only. The primary outcome is salt intake measured by 24-hour urinary sodium excretion after 1 year. The secondary outcomes are the long-lasting effectiveness on salt intake and blood pressure measured by the same method, as well as salt-related KAP and blood pressure at the 1-year and 2-year follow-ups. Process evaluation and health economics analysis will be conducted as well., Ethics and Dissemination: The study was reviewed and approved by the Institutional Review Board of the National Center for Chronic and Noncommunicable Disease Control and Prevention, the Chinese Center for Disease Control and Prevention, and Queen Mary Research Ethics Committee. Results will be disseminated through presentations, publications and social media., Trial Registration Number: ChiCTR1800018119., Competing Interests: Competing interests: FJH is a member of the Consensus Action on Salt & Health (CASH) group, a non-profit charitable organisation, and its international branch World Action on Salt & Health (WASH) and does not receive any financial support from CASH or WASH. GAM is the Chairman of Blood Pressure UK (BPUK), Chairman of CASH and Chairman of WASH and does not receive any financial support from any of these organisations. BPUK, CASH and WASH are non-profit charitable organisations. All other authors have no competing interests to declare., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

To study the effect of formulas on the estimation of dietary sodium intake (sodium intake) and its association with mortality, we analyzed the TOHP (Trials of Hypertension Prevention) follow-up data. Sodium intake was assessed by measured 24-hour urinary sodium excretion and estimations from sodium concentration using the Kawasaki, Tanaka, and INTERSALT (International Cooperative Study on Salt, Other Factors, and Blood Pressure) formulas. We used both the average of 3 to 7 urinary measurements during the trial period and the first measurement at the beginning of each trial. Additionally, we kept sodium concentration constant to test whether the formulas were independently associated with mortality. We included 2974 individuals aged 30 to 54 years with prehypertension, not assigned to sodium intervention. During a median 24-year follow-up, 272 deaths occurred. The average measured sodium intake was 3766±1290 mg/d. All estimated values, including those with constant sodium concentration, were systematically biased with overestimation at lower levels and underestimation at higher levels. There was a significant linear association between the average measured sodium intake (ie, gold standard method) and mortality. This relationship was altered by using the estimated sodium intakes. There appeared to be a J- or U-shaped relationship for the average estimated sodium by all formulas. Despite variations in the sodium-mortality relationship among various formulas, a common pattern was that all estimated values including those with constant sodium appeared to be inversely related to mortality at lower levels of sodium intake. These results demonstrate that inaccurate estimates of sodium cannot be used in association studies, particularly as the formulas per se seem to be related to mortality independent of sodium.

Dietary sodium restriction has multiple beneficial effects on cardiovascular health. The underlying mechanisms are not fully understood, and the roles of metabolomics have been rarely studied. We aimed to test the hypothesis that the reduction in dietary sodium intake would induce changes in metabolomic profiling among black hypertensives, and the changes would be associated with reduced blood pressure (BP) and improved skin capillary density. A total of 64 untreated black hypertensives were included from a randomized, double-blind, placebo-controlled cross-over trial of sodium reduction. The participants were given either 9 slow sodium tablets (10 mmol sodium per tablet) or placebo tablets daily for 6 weeks, they then crossed over to receive the other tablets for another 6 weeks, while on reduced sodium diet aiming at achieving daily sodium intake around 2.0 g. Untargeted metabolomic profiling was performed in paired serum samples, which were collected at the end of each period, so were BP and capillary density. Mixed-effects models were used. There were 34 metabolites identified with raw P's<0.05. Among those, 2 metabolites including β-hydroxyisovalerate and methionine sulfone were significantly increased with sodium reduction (false discovery rate =0.006 and 0.099, respectively). Increased β-hydroxyisovalerate was associated with reduced office systolic BP and ambulatory daytime systolic BP, whereas increased methionine sulfone was associated with reduced 24-hour diastolic BP, ambulatory nighttime diastolic BP, and increased skin capillary density. Our results suggest that dietary sodium reduction increases the circulating levels of β-hydroxyisovalerate and methionine sulfone. Further studies are warranted. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00152074.

Dietary salt reduction in the general population lowers blood pressure and cardiovascular risk. Despite being widely recommended, there is limited evidence as to whether this is applicable to individuals with end-stage renal disease (ESRD) receiving dialysis. Therefore, we carried out a systematic review and meta-analysis of randomised controlled trials (RCTs) investigating dietary salt reduction in individuals receiving dialysis. Studies were identified through search strategies for CENTRAL, MEDLINE, and EMBASE. Two authors independently assessed studies for eligibility with the inclusion criteria as follows: participants aged 18 years and over; a reduction in salt intake of at least 1 g/day over one week; no concomitant interventions during the study. The primary outcome was change in systolic and diastolic blood pressure. 848 reports were screened, from which 12 studies were selected for the systematic review. Four were RCTs (91 participants) that met the study inclusion criteria: three were conducted in haemodialysis patients and one in peritoneal dialysis patients; three were crossover trials and one was a parallel study. Dietary salt reduction was associated with an 8.4 mmHg reduction in systolic blood pressure (95% CI 4.8-12.0, Ι 2  = 0%), and a 4.4 mmHg reduction in diastolic blood pressure (95% CI 2.2-6.6, Ι 2  = 0%). In conclusion, few studies have investigated the role of dietary salt reduction in individuals with ESRD receiving dialysis, but these results suggest the importance of this intervention for lowering blood pressure in this group.

The mechanisms underlying the adverse cardiovascular effects of increased salt intake are incompletely understood, but parallel increases in serum sodium concentration may be of importance. The aim of this retrospective cohort study was to investigate the relationship between serum sodium, hypertension and incident cardiovascular disease (CVD). Routinely collected primary care data from the Royal College of General Practitioners Research and Surveillance Centre were analysed. A total of 231,545 individuals with a measurement of serum sodium concentration at baseline were included. Exclusion criteria were: age < 40 years; abnormal serum sodium; diabetes mellitus; prior CVD event; stage 5 chronic kidney disease; and liver cirrhosis. The primary outcome was incident CVD (myocardial infarction, acute coronary syndrome, coronary revascularisation, stroke, transient ischaemic attack or new heart failure diagnosis) over 5 years. There was a 'J-shaped' relationship between serum sodium concentration and primary cardiovascular events that was independent of established risk factors, medications and other serum electrolytes. The lowest cardiovascular risk was found with a serum sodium between 141 and 143 mmol/l. Higher serum sodium was associated with increased risk in hypertensive individuals, whereas lower concentrations were associated with increased risk in all individuals. Therefore, alterations in serum sodium concentration may be a useful indicator of CVD risk. Higher serum sodium could have a direct effect on the vasculature, particularly in hypertensive individuals. Lower serum sodium may be a reflection of complex volume and neuroendocrine changes.

Background: Several cohort studies with inaccurate estimates of sodium reported a J-shaped relationship with mortality. We compared various estimated sodium intakes with that measured by the gold-standard method of multiple non-consecutive 24-h urine collections and assessed their relationship with mortality., Methods: We analysed the Trials of Hypertension Prevention follow-up data. Sodium intake was assessed in four ways: (i) average measured (gold standard): mean of three to seven 24-h urinary sodium measurements during the trial periods; (ii) average estimated: mean of three to seven estimated 24-h urinary sodium excretions from sodium concentration of 24-h urine using the Kawasaki formula; (iii) first measured: 24-h urinary sodium measured at the beginning of each trial; (iv) first estimated: 24-h urinary sodium estimated from sodium concentration of the first 24-h urine using the Kawasaki formula. We included 2974 individuals aged 30-54 years with pre-hypertension, not assigned to sodium intervention., Results: During a median follow-up of 24 years, 272 deaths occurred. The average sodium intake measured by the gold-standard method was 3769 ± 1282 mg/d. The average estimated sodium over-estimated the intake by 1297 mg/d (95% confidence interval: 1267-1326). The average estimated value was systematically biased with over-estimation at lower levels and under-estimation at higher levels. The average measured sodium showed a linear relationship with mortality. The average estimated sodium appeared to show a J-shaped relationship with mortality. The first measured and the first estimated sodium both flattened the relationship., Conclusions: Accurately measured sodium intake showed a linear relationship with mortality. Inaccurately estimated sodium changed the relationship and could explain much of the paradoxical J-shaped findings reported in some cohort studies.

Sodium reduction decreases blood pressure (BP) and cardiovascular mortality. However, the underlying molecular mechanisms are not well understood. We tested the hypothesis that reduction of sodium intake would change miRNA expression in hypertensive patients, and those changes would be associated with improved cardiovascular phenotypes. A whole genome RNA sequencing was performed in paired serum samples collected at the end of usual sodium intake and reduced sodium intake periods from 10 (age 56.8 ± 8.9) untreated black male hypertensives, selected from a randomized crossover trial of sodium reduction as the discovery cohort. Validation was carried out by the PCR Serum/Plasma Focus panel profiling in paired samples in all 64 (50% males, age 50.2 ± 9.5) untreated black hypertensives from the same trial. Fifteen respondent miRNAs were identified in the discovery stage. miR-143-3p was replicated. Sodium reduction up-regulated miR-143-3p. The increase in miR-143-3p was associated with the reduction of BP and arterial stiffness and the increase in skin capillary density. In conclusion, dietary sodium reduction alters circulating miRNA expressions, and those miRNA changes are associated with reduced BP and improved arterial compliance in untreated black hypertensives, suggesting that miRNA regulation may be one of the underlying mechanisms that dietary sodium regulates cardiovascular health.