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Interim effects of salt substitution on urinary electrolytes and blood pressure in the China Salt Substitute and Stroke Study (SSaSS).
Huang, L, Tian, M, Yu, J, Li, Q, Liu, Y, Yin, X, Wu, JH, Marklund, M, Wu, Y, Li, N, et al
American heart journal. 2020;:136-145
Abstract
The Salt Substitute and Stroke Study is an ongoing 5-year large-scale cluster randomized trial investigating the effects of potassium-enriched salt substitute compared to usual salt on the risk of stroke. The study involves 600 villages and 20,996 individuals in rural China. Intermediate risk markers were measured in a random subsample of villages every 12 months over 3 years to track progress against key assumptions underlying study design. Measures of 24-hour urinary sodium, 24-hour urinary potassium, blood pressure and participants' use of salt substitute were recorded, with differences between intervention and control groups estimated using generalized linear mixed models. The primary outcome of annual event rate in the two groups combined was determined by dividing confirmed fatal and non-fatal strokes by total follow-up time in the first 2 years. The mean differences (95% CI) were -0.32 g (-0.68 to 0.05) for 24-hour urinary sodium, +0.77 g (+0.60 to +0.93) for 24-hour urinary potassium, -2.65 mmHg (-4.32 to -0.97) for systolic blood pressure and +0.30 mmHg (-0.72 to +1.32) for diastolic blood pressure. Use of salt substitute was reported by 97.5% in the intervention group versus 4.2% in the control group (P<.0001). The overall estimated annual event rate for fatal and non-fatal stroke was 3.2%. The systolic blood pressure difference and the annual stroke rate were both in line with the statistical assumptions underlying study design. The trial should be well placed to address the primary hypothesis at completion of follow-up.
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Efficacy of low-dose nicardipine for emergent treatment of severe postpartum hypertension in maternal intensive care units: An observational study.
Qi, H, Qin, J, Ren, L, Li, L, Lan, L, Yan, Y, Gan, S, Zhang, Y
Pregnancy hypertension. 2020;:43-49
Abstract
OBJECTIVES To investigate the efficacy of low-dose intravenous nicardipine for emergent management of severe postpartum hypertension in maternal intensive care units (ICUs). STUDY DESIGN The initial dosage of nicardipine was dependent upon patient systolic blood pressure (SBP). Patients with an SBP of 160-179 mmHg received an initial dosage of 2 mg/h, and 4 mg/h was administered to patients where SBP exceeded 180 mmHg. MAIN OUTCOME MEASURES The efficacy of nicardipine was evaluated by measuring the time interval for achieving the target blood pressure, and its safety was determined by the incidence of severe adverse maternal effects. RESULTS A total number of 101 patients were admitted to the ICU for severe postpartum hypertension and treated with nicardipine. For patients with an SBP of 160-179 mmHg (n = 28), the interval was 14.04 ± 11.00 min (mean ± SD) for achieving the target blood pressure, and the frequency for adjusting the nicardipine dosage was 1.46 ± 1.17. For patients with an SBP ≥ 180 mmHg (n = 73), the interval was 30.75 ± 16.15 min, and the frequency was 1.62 ± 1.38. Three patients with an SBP ≥ 240 mmHg and/or a diastolic blood pressure (DBP) ≥ 130 mmHg failed to achieve the target blood pressure within 60 min. No severe adverse effects occurred in this study. CONCLUSIONS Our findings showed that low-dose nicardipine could be used to lower elevated blood pressure safely and rapidly in patients admitted to the ICU for severe postpartum hypertension.
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Pediatric Liddle Syndrome Caused by a Novel SCNN1G Variant in a Chinese Family and Characterized by Early-Onset Hypertension.
Fan, P, Pan, XC, Zhang, D, Yang, KQ, Zhang, Y, Tian, T, Luo, F, Ma, WJ, Liu, YX, Wang, LP, et al
American journal of hypertension. 2020;(7):670-675
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Abstract
BACKGROUND Liddle syndrome (LS), an autosomal dominant disorder, is a common monogenic hypertension in pediatrics. In this study, we reported a novel SCNN1G variant in a Chinese family with pediatric LS, and conduct a systematic review of epithelial sodium channel (ENaC)-gene-positive LS cases to conclude the clinical genetic features of LS in childhood. METHODS Next-generation sequencing and in silico analysis were performed in the proband to discover candidate variants. Sanger sequencing was used to identify the predicted likely pathogenic variant. LS patients in this family were treated with amiloride. The Medline database was searched to summarize clinical features of pediatric LS cases whose age at genetic diagnosis was not more than 18 years. RESULTS Genetic analysis identified a novel SCNN1G missense variant (c.1874C>T, p.Pro625Leu) in the proband with LS in childhood. In silico analysis revealed this heterozygous variant was highly conserved and deleterious. A total of 38 publications described pediatric LS associated with 25 pathogenic variants in SCNN1B and SCNN1G in 54 children. Despite the phenotypic heterogeneity, early-onset hypertension is the most common feature. All LS patients in this family or the reviewed cases showed significantly improvements in hypertension and hypokalemia after treatment with ENaC inhibitors. CONCLUSIONS This study identified a novel SCNN1G missense variant in a patient with pediatric LS, expanding the genetic spectrum of SCNN1G and demonstrating the PY motif of γ-ENaC as a potential mutant region. Early identification and specific management of LS in children and adolescents are important to prevent the development of hypertensive end-organ disease.
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Degree of Blood Pressure Control and Incident Diabetes Mellitus in Chinese Adults With Hypertension.
Zhang, Y, Nie, J, Zhang, Y, Li, J, Liang, M, Wang, G, Tian, J, Liu, C, Wang, B, Cui, Y, et al
Journal of the American Heart Association. 2020;(16):e017015
Abstract
Background The association between blood pressure (BP) control and incident diabetes mellitus remains unknown. We aim to investigate the association between degree of time-averaged on-treatment systolic blood pressure (SBP) control and incident diabetes mellitus in hypertensive adults. Methods and Results A total of 14 978 adults with hypertension without diabetes mellitus at baseline were included from the CSPPT (China Stroke Primary Prevention Trial). Participants were randomized double-masked to daily enalapril 10 mg and folic acid 0.8 mg or enalapril 10 mg alone. BP measurements were taken every 3 months after randomization. The primary outcome was incident diabetes mellitus, defined as physician-diagnosed diabetes mellitus, or use of glucose-lowering drugs during follow-up, or fasting glucose ≥126 mg/dL at the exit visit. Over a median of 4.5 years, a significantly higher risk of incident diabetes mellitus was found in participants with time-averaged on-treatment SBP 130 to <140 mm Hg (10.3% versus 7.4%; odds ratio [OR], 1.37; 95% CI, 1.15‒1.64), compared with those with SBP 120 to <130 mm Hg. Moreover, the risk of incident diabetes mellitus increased by 24% (OR, 1.24; 95% CI, 1.00‒1.53) and the incidence of regression to normal fasting glucose (<100 mg/dL) decreased by 29% (OR, 0.71; 95% CI, 0.57‒0.89) in participants with intermediate BP control (SBP/diastolic blood pressure, 130 to <140 and/or 80 to <90 mm Hg), compared with those with a tight BP control of <130/<80 mm Hg. Similar results were found when the time-averaged BP were calculated using the BP measurements during the first 6- or 24-month treatment period, or in the analysis using propensity scores. Conclusions In this non-diabetic, hypertensive population, SBP control in the range of 120 to <130 mm Hg, compared with the 130 to <140 mm Hg, was associated with a lower risk of incident diabetes mellitus.
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Self-management and blood pressure control in China: a community-based multicentre cross-sectional study.
Qu, Z, Parry, M, Liu, F, Wen, X, Li, J, Zhang, Y, Wang, D, Li, X
BMJ open. 2019;(3):e025819
Abstract
OBJECTIVES This study explored the relationship between self-management and blood pressure (BP) control in China. DESIGN A cross-sectional study. SETTING Eight community health centres from four cities in the Northeast (Shenyang), Northwest (Xi'an), Southwest (Chengdu) and South (Changsha) of China. PARTICIPANTS A total of 873 adults with hypertension, including 360 men and 513 women. Hypertension was defined as systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg. OUTCOME MEASUREMENTS BP control was the primary outcome variable. This was categorised as good control if individuals with hypertension reduced their BP to <140/90 mm Hg, otherwise, it was categorised as poor control. Secondary outcomes included self-management, defined as: (1) context or condition-specific factors or physical/social environments (eg, age, sex, marital status, education, personal income and health insurance) and (2) process or knowledge/beliefs, self-regulation skills/abilities and social facilitation (eg, treatment, diet, exercise and risk factor management). Data were analysed using logistic regression models using SPSS V.20. RESULTS A total of 67.1% (n=586) participants had poor BP control. Limited outpatient care benefits in mainly rural residents (OR 2.26, 95% CI 1.06 to 4.81) and longer disease duration (OR 1.03, 95% CI 1.01 to 1.04) were associated with poor BP control. Self-management practices reduced the odds of having poor BP control (OR 0.98, 95% CI 0.97 to 0.99). CONCLUSIONS The individual and family self-management theory can serve as an effective theory for understanding the key contexts, processes and outcomes essential for BP control in China. Future research should evaluate the effect of a self-management intervention (eg, self-monitoring, medication adherence, regular and routine doctor visits, and social supports) for BP control in China using a multisite cluster randomised controlled trial. Sex and gender difference, cost and patient-reported outcomes should also be examined.
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Effects of salt substitute on home blood pressure differs according to age and degree of blood pressure in hypertensive patients and their families.
Hu, J, Zhao, L, Thompson, B, Zhang, Y, Wu, Y
Clinical and experimental hypertension (New York, N.Y. : 1993). 2018;(7):664-672
Abstract
BACKGROUND It is known that home blood pressure (HBP) is a more reliable assessment of hypertension treatments than clinical blood pressure (BP). Despite this, HBP response to a salt substitute has only been evaluated by one study which, did not look at the salt substitute's effect on family members and did not analyze by age, gender, or BP degree. The aim of this current study was to assess the effects of a low-sodium and high-potassium salt substitute on HBP among hypertensive patients and their family members. METHODS A total of 220 households (including 220 hypertensive patients and 380 their families) were randomly assigned to the regular salt or salt substitute groups. HBP was measured at the beginning, 3rd, 6th, and 12th months. Among the patients (n = 220), only home systolic blood pressure (HSBP) was significantly reduced, by an adjusted baseline BP of 4.2 mm Hg (95% CI: 1.3-7.0 mm Hg), in the salt substitute group compared with those in the regular salt group at each visit (all P < 0.05). There were no detectable differences between groups for home diastolic blood pressure (HDBP) at any visit. Among the family members, HSBP and HDBP were not significantly different between the groups. Furthermore, Individuals ≥60 years old, hypertensive patients with stage-2 hypertension, family members with hypertension, and women experienced greater HSBP reduction. CONCLUSIONS Older subjects, those with higher blood pressure, and women experienced greater home blood pressure reduction from the salt substitute compared to regular salt.
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Impact of achieved blood pressure on renal function decline and first stroke in hypertensive patients with chronic kidney disease.
Li, Y, Liang, M, Jiang, C, Wang, G, Li, J, Zhang, Y, Fan, F, Sun, N, Cui, Y, He, M, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2018;(3):409-417
Abstract
BACKGROUND The effect of achieved blood pressure (BP) on first stroke and renal function decline among hypertensive patients with mild to moderate chronic kidney disease (CKD) is still uncertain. METHODS In total, 3230 hypertensive patients with estimated glomerular filtration rate 30-60 mL/min/1.73 m2 and/or proteinuria were included in the present analyses. Eligible participants were randomly assigned to a daily treatment of a combined enalapril 10 mg and folic acid 0.8 mg tablet or an enalapril 10 mg tablet alone. Participants were followed up every 3 months. The study outcomes included first stroke and the progression of CKD. RESULTS The median antihypertensive treatment duration was 4.7 years. Compared with participants with a time-averaged on-treatment systolic blood pressure (SBP) of 135 to ≤140 mmHg, the incidence of total first stroke [1.7% versus 3.3%; hazard ratio (HR), 0.51; 95% confidence interval (CI): 0.26-0.99] and ischemic stroke (1.3% versus 2.8%; HR, 0.46; 95% CI: 0.22-0.98) decreased significantly in those with a time-averaged SBP of ≤135 mmHg. Furthermore, a time-averaged diastolic blood pressure (DBP) of ≤80 mmHg, compared with a time-averaged DBP level of 80 to ≤90 mmHg, was significantly related to a decreased risk of hemorrhagic stroke (0.2% versus 0.9%; HR, 0.18; 95% CI: 0.04-0.80). However, compared with participants with a time-averaged SBP of 135 to ≤140 mmHg, a lower but non-significant trend of CKD progression was found in those with a time-averaged SBP of ≤130 mmHg. CONCLUSIONS A BP treatment level of ≤135/80 mmHg, compared with a BP treatment level of 135-140/80-90 mmHg, could lead to a decreased risk of first stroke in hypertensive patients with mild-to-moderate CKD.
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Longitudinal association between fasting blood glucose concentrations and first stroke in hypertensive adults in China: effect of folic acid intervention.
Xu, RB, Kong, X, Xu, BP, Song, Y, Ji, M, Zhao, M, Huang, X, Li, P, Cheng, X, Chen, F, et al
The American journal of clinical nutrition. 2017;(3):564-570
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Background: Diabetes is a known risk factor for stroke, but data on its prospective association with first stroke are limited. Folic acid supplementation has been shown to protect against first stroke, but its role in preventing first stroke in diabetes is unknown.Objectives: This post hoc analysis of the China Stroke Primary Prevention Trial tested the hypotheses that the fasting blood glucose (FBG) concentration is positively associated with first stroke risk and that folic acid treatment can reduce stroke risk associated with elevated fasting glucose concentrations.Design: This analysis included 20,327 hypertensive adults without a history of stroke or myocardial infarction, who were randomly assigned to a double-blind daily treatment with 10 mg enalapril and 0.8 mg folic acid (n = 10,160) or 10 mg enalapril alone (n = 10,167). Kaplan-Meier survival analysis and Cox proportionate hazard models were used to test the hypotheses with adjustment for pertinent covariables.Results: During a median treatment duration of 4.5 y, 616 participants developed a first stroke (497 ischemic strokes). A high FBG concentration (≥7.0 mmol/L) or diabetes, compared with a low FBG concentration (<5.0 mmol/L), was associated with an increased risk of first stroke (6.0% compared with 2.6%, respectively; HR: 1.9; 95% CI: 1.3, 2.8; P < 0.001). Folic acid treatment reduced the risk of stroke across a wide range of FBG concentrations ≥5.0 mmol/L, but risk reduction was greatest in subjects with FBG concentrations ≥7.0 mmol/L or with diabetes (HR: 0.66; 95% CI: 0.46, 0.97; P < 0.05). There was a significant interactive effect of FBG and folic acid treatment on first stroke (P = 0.01).Conclusions: In Chinese hypertensive adults, an FBG concentration ≥7.0 mmol/L or diabetes is associated with an increased risk of first stroke; this increased risk is reduced by 34% with folic acid treatment. These findings warrant additional investigation. This trial was registered at clinicaltrials.gov as NCT00794885.
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Effect of levothyroxine on the progression of carotid intima-media thickness in subclinical hypothyroidism patients: a meta-analysis.
Zhao, T, Chen, B, Zhou, Y, Wang, X, Zhang, Y, Wang, H, Shan, Z
BMJ open. 2017;(10):e016053
Abstract
BACKGROUND Subclinical hypothyroidism (SCH) has been associated with increased carotid intima-media thickness (C-IMT) in recent studies, but the effects of levothyroxine (L-T4) therapy on C-IMT in SCH patients are still controversial. AIM: To evaluate the effect of L-T4 therapy on endothelial function as determined by C-IMT in patients with SCH. METHODS BeforeJuly 2016, we searched the PubMed, Embase, Cochrane Library and Google Scholar databases, selecting published randomised controlled trials (RCTs) and self-controlled trials for the meta-analysis. RESULTS Three RCTs with 117 patients were considered appropriate for the meta-analysis. The results of the meta-analysis indicated that L-T4 significantly decreased the development of C-IMT (weighted mean difference (WMD) -0.05 mm, 95% CI -0.08 to -0.01 mm; p=0.025). We also analysed nine studies (self-controlled trials) with 247 patients and extracted the IMT of SCH patients before and after L-T4 treatment. After L-T4 therapy, the pooled estimate of the WMD of decreased C-IMT was -0.04 mm (95% CI -0.07 to -0.02 mm; p=0.05). Subgroup analysis showed that L-T4 therapy was associated with a decrease in C-IMT among patients of mixed genders (WMD -0.03 mm, 95% CI -0.06 to -0.01 mm; p=0.145). L-T4 therapy was associated with a decrease in C-IMT among female patients (WMD -0.07 mm, 95% CI -0.14 to -0.01; p=0.186). Longer treatment (>6 months) also resulted in a significant decrease in C-IMT (WMD -0.05 mm, 95% CI -0.08 to -0.02; p=0.335). CONCLUSION This meta-analysis indicates that L-T4 treatment of SCH patients can reduce C-IMT, possibly as a result of the reduction of total cholesterol, triglyceride, low density lipoprotein, systolic blood pressure, diastolic blood pressure, lipoprotein(a), and flow-mediated dilatation. Decreased C-IMT was observed in SCH patients after long-term (>6 months) L-T4 treatment. RCTs with larger samples are needed to verify these observations.
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Efficacy and Safety of Sacubitril/Valsartan (LCZ696) Compared With Olmesartan in Elderly Asian Patients (≥65 Years) With Systolic Hypertension.
Supasyndh, O, Wang, J, Hafeez, K, Zhang, Y, Zhang, J, Rakugi, H
American journal of hypertension. 2017;(12):1163-1169
Abstract
OBJECTIVE Systolic hypertension is common in elderly patients and remains a challenge to treat effectively. The efficacy and safety of sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, vs. olmesartan was evaluated in elderly Asian patients (≥65 years) with systolic hypertension. METHODS In this randomized, double-blind, 14-week study, patients initially received once-daily sacubitril/valsartan 100 mg or olmesartan 10 mg, increased to sacubitril/valsartan 200 mg or olmesartan 20 mg at week 4. At week 10, for patients with blood pressure (BP) >140/90 mm Hg, the doses were up-titrated to sacubitril/valsartan 400 mg or olmesartan 40 mg. The primary assessment was superiority of sacubitril/valsartan vs. olmesartan in reducing office mean sitting (ms) systolic BP (msSBP) from baseline at week 10. Secondary efficacy assessments included changes from baseline in ms diastolic BP (msDBP), ms pulse pressure (msPP), 24-hour mean ambulatory (ma) BP (maBP), and maPP at week 10; msBP and msPP at weeks 4 and 14. RESULTS Overall, 588 patients were randomized (mean age, 70.7 years; baseline msBP, 160.3/84.9 mm Hg; msPP, 75.4 mm Hg). At week 10, sacubitril/valsartan provided superior msSBP reductions vs. olmesartan (22.71 vs. 16.11 mm Hg, respectively; P < 0.001); similarly, reductions from baseline in other BP and PP assessments were significantly greater with sacubitril/valsartan. At week 14, despite more patients requiring up-titration in the olmesartan group, msBP and msPP reductions from baseline were significantly greater with sacubitril/valsartan. Both treatments were generally well-tolerated. CONCLUSION Sacubitril/valsartan is more effective than olmesartan in reducing BP in elderly Asian patients with systolic hypertension.