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Natriuretic peptide receptor-C (NPR-C) is highly expressed in adipose tissues, and regulates obesity related diseases, however the detailed mechanism remains unknown. In this research, we aimed to explore the potential role of NPR-C in cold exposure and high-fat/high-sugar (HF/HS) diet induced metabolic changes, especially in regulating white adipose tissue (WAT) mitochondrial function. Our findings showed that NPR-C expression, especially in epididymal WAT (eWAT), was reduced after cold exposure. Global Npr3 (gene encoding NPR-C protein) deficiency led to reduced body weight, increased WAT browning, thermogenesis, and enhanced expression of genes related to mitochondrial biogenesis. RNA-sequencing of eWAT showed that Npr3 deficiency enhanced expression of mitochondrial respiratory chain complex genes and promoted mitochondrial oxidative phosphorylation in response to cold exposure. In addition, Npr3 KO mice were able to resist obesity induced by HF/HS diet. Npr3 knockdown in stromal vascular fraction (SVF)-induced white adipocytes promoted the expression of proliferator-activated receptor gamma coactivator 1α (PGC1α), uncoupling protein 1 (UCP1) and mitochondrial respiratory chain complexes. Mechanistically, NPR-C inhibited cGMP and calcium signaling in an NPR-B-dependent manner but suppressed cAMP signaling in an NPR-B-independent manner. Moreover, Npr3 knockdown induced browning via AKT and p38 pathway activation, which were attenuated by Npr2 knockdown. Importantly, treatment with the NPR-C specific antagonist, AP-811, decreased WAT mass and increased PGC-1α, UCP1 and mitochondrial complex expression. These findings demonstrate that NPR-C deficiency enhances metabolic health by boosting energy expenditure in WAT, emphasizing the potential of NPR-C inhibition for treating obesity and related metabolic disorders.
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BACKGROUND: Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP)-lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP-lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients. METHODS: In a multi-center, randomized, actively controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and community health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis. RESULTS: In the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was - 13.8 ± 1.2 mmHg in the amlodipine/benazepril group and - 12.3 ± 1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of - 1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were - 1.47 (p = 0.18) in 24-h diastolic BP, - 2.86 (p = 0.13) and - 2.74 (p = 0.03) in daytime systolic and diastolic BP, and - 0.45 (p = 0.82) and - 0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04). CONCLUSIONS: The amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP-lowering effect in the daytime and a lower incidence rate of dry cough. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03682692. Registered on 18 September 2018.
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Hipertensão , Hipotensão , Humanos , Anti-Hipertensivos , Anlodipino , Hidroclorotiazida , China , TosseRESUMO
We reported findings from participants screened during the May Measurement Month 2021 in China, which aimed to raise awareness of raised blood pressure (BP), and to investigate the risk factors of BP. The study participants were adults (≥18 years), ideally in whom BP had not been measured in the previous year. Blood pressure was measured three times consecutively with 1â min intervals in the sitting position, using a validated upper-arm cuff automated BP monitor (Omron HEM-7081IT), and transmitted to a central cloud database via a smartphone app. The measurement was performed in 218 844 participants in 183 sites across 31 China provinces. The mean (standard deviation) age was 47.0 (15.7) years, and 51.8% (n = 113 466) were women. The mean systolic/diastolic BP was 120.2/77.5â mmHg. Among 57 178 (26.1%) participants with hypertension, the awareness, treatment, and control rates of hypertension were 30.4% (n = 17 354), 28.7% (n = 16 369), and 17.1% (n = 9743), respectively. After adjustment for age, sex, and use of antihypertensive medication, both systolic and diastolic BP were significantly (P ≤ 0.01) higher in current smokers (n = 22 344, +0.4/+0.7â mmHg) and with moderate (n = 4780, +1.4/+4.2â mmHg) or daily alcohol intake (n = 2427, +1.3/+2.5â mmHg). Blood pressure was lower in those reporting regular exercise (n = 32 328, -2.2/-1.4â mmHg). In addition, individuals with previous COVID-19 vaccination had lower systolic and diastolic BP (n = 88 945, -1.8/-1.5â mmHg, P ≤ 0.001). In conclusion, our study showed that long-term large-scale screening for hypertension is feasible, and there is a strong association between BP and major lifestyle factors.
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OBJECTIVE: We investigated the accuracy of the OMRON HEM-7361T automated oscillometric blood pressure (BP) monitor in the differentiation between atrial fibrillation and sinus rhythm. METHODS: An approximately equal number of patients with persistent atrial fibrillation and individuals with sinus rhythm were recruited from outpatients and inpatients of Ruijin Hospital, Shanghai, China. BP was measured three times consecutively with a 30-s interval with the OMRON HEM-7361T automatic electronic BP monitor for atrial fibrillation detection. A hand-held single lead electrocardiogram device was used for simultaneous electrocardiogram recordings. RESULTS: The device accurately identified atrial fibrillation in 100 (99.0%) of the 101 patients, with only 1 patient incorrectly classified as non-atrial fibrillation. The device correctly identified 99 (95.2%) of the 104 participants with sinus rhythm as non-atrial fibrillation, with five participants incorrectly classified as atrial fibrillation. The device had a positive predictive value of 95.2%, negative predictive value of 99.0%, and overall accuracy of 97.1%. Among the six misclassified participants, one with atrial fibrillation had a heart rate of 65 beats/min, and four of the five participants with sinus rhythm had cardiac arrhythmias (atrial or ventricular premature beat in one participants, sinus tachycardia in one participant, and both arrhythmias in one participant). CONCLUSION: The OMRON HEM-7361T BP monitor is accurate in the differentiation between atrial fibrillation and sinus rhythm. Whether the device is sufficiently accurate in the differentiation between atrial fibrillation and other cardiac arrhythmias remains under investigation.
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Fibrilação Atrial , Humanos , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Eletrocardiografia/instrumentação , Monitores de Pressão Arterial , Arritmia Sinusal/fisiopatologia , Arritmia Sinusal/diagnóstico , Pressão Sanguínea , Adulto , Determinação da Pressão Arterial/instrumentação , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: We investigated seasonal variation in ambulatory blood pressure control in hypertensive patients on clinic blood pressure-guided antihypertensive treatment. METHODS: The study participants were hypertensive patients enrolled in an 8-week therapeutic study. Antihypertensive treatment was initiated with long-acting dihydropyridine calcium channel blockers amlodipine 5âmg/day or the gastrointestinal therapeutic system (GITS) formulation of nifedipine 30âmg/day, with the possible up-titration to amlodipine 10âmg/day or nifedipine-GITS 60âmg/day at 4âweeks of follow-up. RESULTS: The proportion of up-titration to higher dosages of antihypertensive drugs at 4âweeks of follow-up was higher in patients who commenced treatment in autumn/winter ( n â=â302) than those who commenced treatment in spring/summer ( n â=â199, 24.5 vs. 12.0%, P â<â0.001). The control rate of clinic blood pressure, however, was lower in autumn/winter than in spring/summer at 4 (56.7 vs. 70.7%, P â=â0.003) and 8âweeks of follow-up (52.5 vs. 74.9%, P â<â0.001). At 8âweeks, patients who commenced treatment in autumn/winter, compared with those who commenced treatment in spring/summer, had a significantly ( P ≤0.03) smaller daytime (mean between-season difference -3.2/-2.8âmmHg) but greater nighttime SBP/DBP reduction (3.6/1.6âmmHg). Accordingly, at 8âweeks, the prevalence of nondippers was significantly ( P â<â0.001) higher in spring/summer than in autumn/winter for both SBP (54.8 vs. 30.0%) and DBP (53.4 vs. 28.8%). CONCLUSION: Clinic blood pressure-guided antihypertensive treatment requires a higher dosage of medication in cold than warm seasons, which may have led to over- and under-treatment of nighttime blood pressure, respectively.
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Anti-Hipertensivos , Hipertensão , Humanos , Nifedipino/uso terapêutico , Nifedipino/efeitos adversos , Estações do Ano , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Anlodipino/uso terapêuticoRESUMO
INTRODUCTION: Mild cognitive impairment (MCI) is an important intervenable stage for the prevention of dementia. Hypertension is associated with impaired cognition, and when combined with MCI, it may lead to a poor prognosis. Digital computerised cognitive training (CCT) has recently become a potential instrument for improving cognition, but evidence for its efficacy remains limited. This study aims to evaluate the efficacy of a digital adaptive CCT intervention in older patients with hypertension and MCI. METHODS AND ANALYSIS: The multicentre, double-blinded, randomised, actively -controlled clinical trial will recruit 200 older (≥60 years) patients with hypertension and MCI from 11 hospitals across China. Participants will be randomly assigned in a 1:1 ratio to the intervention group (multidomain adaptative CCT) and active control group (non-adaptive cognitive training) for 12-week cognitive training for 30 min/day and 5 days/week. Those who have completed their 12-week training in the intervention group will be rerandomised into the continuation and discontinuation training groups. All participants will be followed up to 24 weeks. Neuropsychological assessments and structural and functional 7.0 T MRI will be obtained at baseline and at 12-week and 24-week follow-up. The primary outcome is the possible improvement of global cognitive function at 12 weeks, as measured by the Basic Cognitive Aptitude Tests. Secondary and exploratory endpoints include the major cognitive domain function improvement, self-efficacy, mental health, quality of life and MRI measurements of the brain. ETHICS AND DISSEMINATION: The trial has been approved by the institutional review board of Beijing Anzhen Hospital and thereafter by all other participating centres. Trial findings will be disseminated in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05704270.
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Disfunção Cognitiva , Hipertensão , Idoso , Humanos , Cognição , Disfunção Cognitiva/psicologia , Treino Cognitivo , Hipertensão/complicações , Hipertensão/terapia , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate three features of dietary cooking oil intake, namely, the consumption, cooking style, and composition of fatty acids in relation to several cardiometabolic measurements in an elderly Chinese population. METHODS: The elderly (≥ 65 years) participants for this study were recruited from two community health centers in the urban area of Shanghai. A questionnaire was administered to collect information on dietary oil consumption (low, medium and high) and cooking styles (fry or stir-fry vs. others) and the composition of fatty acids (poly-unsaturated vs. mono-unsaturated). The cardiometabolic measurements included anthropometry, blood pressure, fasting plasma glucose and serum lipids. RESULTS: The 1186 study participants had a mean age of 70.9 ± 5.4 years. The mean dietary oil consumption was 35.0 g/d, being low (< 25 g/d), medium (25-49 g/d) and high (≥ 50 g/d) in 485,467 and 234 participants, respectively. The proportion of the fry or stir-fry cooking style and oils rich in mono-unsaturated fatty acids was 30.4% and 27.4%, respectively. Both before and after adjustment for sex, age, current smoking and alcohol intake, dietary oil consumption was significantly (P ≤ 0.02) and positively associated with the prevalence of treated hypertension and fasting plasma glucose concentration. With similar adjustments as above and additional adjustment for dietary oil consumption, the fry or stir-fry cooking style was significantly (P ≤ 0.048) and positively associated with body mass index, but inversely with systolic and diastolic blood pressure and serum low-density lipoprotein cholesterol, and the dietary intake of oils rich in mono-unsaturated fat acids was significantly (P ≤ 0.02) and positively associated with diastolic blood pressure, serum triglycerides, total cholesterol and low-density lipoprotein cholesterol, and the prevalence of hypertriglyceridemia and hypercholesterolemia. CONCLUSIONS: This study showed that both the consumption and composition of fatty acids of the dietary oils mattered with regard to several cardiometabolic measurements in an elderly Chinese population.
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We investigated blood pressure (BP) variability as assessed by beat-to-beat, reading-to-reading and day-to-day BP variability indices in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). In 786 hospitalized hypertensives (mean age, 53.2 years; 42.2% women), we performed 10-min beat-to-beat (n = 705), 24-h ambulatory (n = 779), and 7-day home BP (n = 445) measurements and the full overnight polysomnography. Mild, moderate and severe OSAHS were defined as an apnea-hypopnea index of 5-14, 15-29, and ≥ 30 events per hour, respectively. BP variability indices including variability independent of the mean (VIM), average real variability (ARV), and maximum-minimum difference (MMD), were compared across the OSAHS severity groups. In univariate analysis, beat-to-beat systolic VIM and MMD, reading-to-reading asleep systolic and diastolic ARV and MMD increased from patients without OSAHS, to patients with mild, moderate and severe OSAHS. This increasing trend for beat-to-beat systolic VIM and MMD remained statistically significant after adjustment for confounders (P ≤ 0.047). There was significant (P ≤ 0.039) interaction of the presence and severity of OSAHS with age and body mass index in relation to the beat-to-beat systolic VIM and MMD and with the presence of diabetes mellitus in relation to asleep systolic ARV. The association was stronger in younger (age < 50 years) and obese (body mass index ≥ 28 kg/m²) and diabetic patients. None of the day-to-day BP variability indices reached statistical significance (P ≥ 0.16). BP variability, in terms of beat-to-beat systolic VIM and MMD and asleep reading-to-reading asleep systolic ARV, were higher with the more severe OSAHS, especially in younger and obese and diabetic patients.
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Pressão Sanguínea , Polissonografia , Apneia Obstrutiva do Sono , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Pressão Sanguínea/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/complicações , Adulto , Idoso , Hipertensão/fisiopatologia , Monitorização Ambulatorial da Pressão ArterialRESUMO
We investigated the clinical characteristics of primary aldosteronism (PA) screened from patients with hypertension in China. The participants were hypertensive patients who were suspected of PA and registered in the China Primary Aldosteronism Prospective Study. Plasma aldosterone-to-renin ratio (ARR) was used as the screening test. In patients screened positive for PA, that is, an ARR exceeding the thresholds and plasma aldosterone concentration (PAC) > 100 pg/mL, a confirmatory test was performed for diagnosis. Patients with PA underwent a CT scan and adrenal venous sampling for subtyping. Of the 1497 screened patients, 754 (50.4%) had an ARR exceeding the diagnostic threshold and 637 (84.5% of those eligible) were registered. These registered hypertensive patients with suspected PA had a mean (standard deviation) age of 52.6 ± 12.1 years, and included 442 (58.6%) women. In multiple stepwise logistic regression, the significant odds ratios for the presence of diagnosed (n = 490) versus suspected and non-diagnosed PA (n = 147) were 4.54 (95% CI: 2.78-7.39) for a history of hypokalemia, 0.79 (95% CI: 0.64-0.98) for a 0.9 mmol/l higher serum total cholesterol, and 2.25 (95% CI: 1.63-3.10) for a doubling of PAC in the supine or standing/sitting position. In multiple stepwise logistic regression, the significant odds ratios for the presence of unilateral (n = 135) versus bilateral PA (n = 53) were 3.04 (95% CI: 1.90-4.87) for a 0.4 mmol/l lower minimum serum potassium concentration and 1.86 (95% CI: 1.20-2.86) for a 0.3 mmol/l higher serum high-density lipoprotein cholesterol. PA might be a biochemical continuum in the adrenal hypersecretion of aldosterone as well as hypokalemia.
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We investigated fasting hypertriglyceridemia as predictors of all-cause, cardiovascular, and non-cardiovascular mortality in an elderly male Chinese population, while accounting for various conventional cardiovascular risk factors. Our participants were elderly men recruited from residents living in a suburban town of Shanghai (≥60 years of age, n = 1583). Hypertriglyceridemia was defined as a fasting serum triglycerides concentration ≥1.70 mmol/L. Subgroup analyses were performed according to current smoking (yes vs. no), alcohol intake (yes vs. no), and the presence and absence of hypertension and hyperglycemia. During a median of 7.9 years follow-up, all-cause, cardiovascular, and non-cardiovascular deaths occurred in 279, 112, and 167 participants, respectively. After adjustment for confounding factors, fasting hypertriglyceridemia was not significantly (p ≥ .33) associated with the risk of all-cause, cardiovascular, and non-cardiovascular mortality. However, there was significant (p = .03) interaction between hypertriglyceridemia and the presence and absence of hypertension in relation to all-cause mortality. In normotensive, but not hypertensive individuals, hypertriglyceridemia was significantly associated with a higher risk of all-cause mortality (hazard ratio 1.57, 95% confidence interval 1.06-2.31). In further non-parametric analyses in normotensive individuals, the age-standardized rate for all-cause mortality increased from 18.9 in quartile 1 to 20.0, to 24.7, and to 39.9 per 1000 person-years in quartiles 2, 3, and 4 of serum triglycerides concentration, respectively (ptrend = .0004). Similar results were observed for cardiovascular mortality. Our study in elderly male Chinese showed that fasting hypertriglyceridemia was associated with a higher risk of all-cause and cardiovascular mortality in patients with normotension but not those with hypertension.
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OBJECTIVES: Blood pressure (BP) variability (BPV) can be assessed using office (OBP), home (HBP), or ambulatory BP (ABP) measurements. This analysis investigated the association and agreement between OBP, HBP, and ABP measurements for BPV assessment at baseline and 10âweeks after initiating antihypertensive drug therapy. METHODS: Untreated hypertensive patients with elevated BPV were randomized to receive an angiotensin-converting enzyme inhibitor (ramipril) or a calcium channel blocker (nifedipine GITS) in a 10-week, open-label, blinded-end point study. BPV was assessed using standard deviation (SD) and coefficient of variation (CV) (reading-to-reading analyses). RESULTS: Data from 146 participants from three research centers (Athens/Greece; Milan/Italy; Shanghai/China) were analyzed [mean age 53â±â10 (SD) years, male individuals 60%, baseline systolic OBP, HBP, and 24âh ABP 144â±â9, 138â±â10, and 143â±â10âmmHg, respectively]. Post-treatment minus pre-treatment systolic CV difference was: OBP: 0.3%, P â=â0.28; HBP: -0.2%, P â=â0.20; 24âh ABP: 1.1%, P â<â0.001. Home and ambulatory (not office) BPV indices presented weak-to-moderate correlation, both before and during treatment (range of coefficients 0.04-0.33). The correlation coefficient between systolic HBP and awake ABP CV was 0.21 and 0.28 before and during treatment, respectively ( P â<â0.05/<â0.001, respectively). Home and ambulatory (not office) BPV indices presented slight-to-fair agreement (range 64-73%) in detecting participants with high systolic BPV (top quartile of respective distributions) both before and during treatment (kappa range 0.04-0.27). CONCLUSION: These data showed a weak-to-moderate association between out-of-office (but not office) BPV indices both before and during BP-lowering treatment, with reasonable agreement in detecting individuals with high BPV. Out-of-office BP measurements provide more similar and consistent BPV information than office measurements.
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Anti-Hipertensivos , Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Hipertensão , Humanos , Masculino , Pessoa de Meia-Idade , Anti-Hipertensivos/uso terapêutico , Feminino , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Monitorização Ambulatorial da Pressão Arterial/métodos , Adulto , Ramipril/uso terapêutico , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Nifedipino/uso terapêuticoRESUMO
Hypertension and atrial fibrillation are closely related. However, hypertension is already prevalent in young adults, but atrial fibrillation usually occurs in the elderly. In the present analysis, we investigated incident atrial fibrillation in relation to new-onset hypertension in an elderly Chinese population. Our study participants were elderly (≥65 years) hypertensive residents, recruited from community health centers in the urban Shanghai (n = 4161). Previous and new-onset hypertension were defined as the use of antihypertensive medication or elevated systolic/diastolic blood pressure (≥140/90 mmHg), respectively, at entry and during follow-up on ≥ 2 consecutive clinic visits. Atrial fibrillation was detected by a 30-s single-lead electrocardiography (ECG, AliveCor® Heart Monitor) and further evaluated with a regular 12-lead ECG. During a median of 2.1 years follow-up, the incidence rate of atrial fibrillation was 7.60 per 1000 person-years in all study participants; it was significantly higher in patients with new-onset hypertension (n = 368) than those with previous hypertension (n = 3793, 15.76 vs. 6.77 per 1000 person-years, P = 0.02). After adjustment for confounding factors, the hazard ratio for the incidence of atrial fibrillation was 2.21 (95% confidence interval 1.15-4.23, P = 0.02) in patients with new-onset hypertension versus those with previous hypertension. The association was even stronger in those aged ≥ 75 years (hazard ratio 2.70, 95% confidence interval 1.11-6.56, P = 0.03). In patients with previous hypertension, curvilinear association (P for non-linear trend = 0.04) was observed between duration of hypertension and the risk of incident atrial fibrillation, with a higher risk in short- and long-term than mid-term duration of hypertension. Our study showed a significant association between new-onset hypertension and the incidence of atrial fibrillation in elderly Chinese. In an elderly Chinese population with previous and new-onset hypertension, we found that the new-onset hypertension during follow-up, compared with previous hypertension, was associated with a significantly higher risk of incident atrial fibrillation. In patients with previous hypertension, curvilinear association was observed between duration of hypertension and the risk of incident atrial fibrillation, with a higher risk in short- and long-term than mid-term duration of hypertension.
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Fibrilação Atrial , Hipertensão , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Hipertensão/epidemiologia , Hipertensão/complicações , Masculino , Feminino , Idoso , Incidência , China/epidemiologia , Idoso de 80 Anos ou mais , Fatores de Risco , EletrocardiografiaRESUMO
BACKGROUND: In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals. METHODS: This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90âmmHg) were randomized to perindopril 5âmg/indapamide 1.25 mg/amlodipine 5âmg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4âmg/indapamide 1.25 mg plus amlodipine 5âmg (Per/Ind + Aml) for 6âmonths. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2âmonths. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90âmmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM). RESULTS: A total of 532 patients were randomized: Per/Ind/Aml ( n â=â262) and Per/Ind + Aml ( n â=â269). Overall, the mean (±SD) age was 55.7â±â8.8âyears, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2âmmHg. Systolic BP decreased in both groups at 2âmonths from baseline: -14.99â±â14.46âmmHg Per/Ind/Aml versus -14.49â±â12.87âmmHg Per/Ind +Aml. A predefined noninferiority margin of 4âmmHg was observed ( P â<â0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24âh. Both treatments were well tolerated. CONCLUSIONS: Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24âh in a single pill, with comparable safety.
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Anlodipino , Anti-Hipertensivos , Hipertensão , Indapamida , Perindopril , Humanos , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Indapamida/administração & dosagem , Indapamida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Método Duplo-Cego , Perindopril/administração & dosagem , Perindopril/uso terapêutico , Feminino , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Idoso , Resultado do Tratamento , Pressão Sanguínea/efeitos dos fármacos , China , Adulto , Combinação de Medicamentos , Quimioterapia Combinada , População do Leste AsiáticoRESUMO
Background: Masked hypertension is associated with target organ damage (TOD) and adverse health outcomes, but whether antihypertensive treatment improves TOD in patients with masked hypertension is unproven. Methods: In this multicentre, randomised, double-blind, placebo-controlled trial at 15 Chinese hospitals, untreated outpatients aged 30-70 years with an office blood pressure (BP) of <140/<90 mm Hg and 24-h, daytime or nighttime ambulatory BP of ≥130/≥80, ≥135/≥85, or ≥120/≥70 mm Hg were enrolled. Patients had ≥1 sign of TOD: electrocardiographic left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s, or urinary albumin-to-creatinine ratio (ACR) ≥3.5 mg/mmol in women and ≥2.5 mg/mmol in men. Exclusion criteria included secondary hypertension, diabetic nephropathy, serum creatinine ≥176.8 µmol/L, and cardiovascular disease within 6 months of screening. After stratification for centre, sex and the presence of nighttime hypertension, eligible patients were randomly assigned (1:1) to receive antihypertensive treatment or placebo. Patients and investigators were masked to group assignment. Active treatment consisted of allisartan starting at 80 mg/day, to be increased to 160 mg/day at month 2, and to be combined with amlodipine 2.5 mg/day at month 4, if the ambulatory BP remained uncontrolled. Matching placebos were used likewise in the control group. The primary endpoint was the improvement of TOD, defined as normalisation of baPWV, ACR or LVH or a ≥20% reduction in baPWV or ACR over the 48-week follow-up. The intention-to-treat analysis included all randomised patients, the per-protocol analysis patients who fully adhered to the protocol, and the safety analysis all patients who received at least one dose of the study medication. This study is registered with ClinicalTrials.gov, NCT02893358. Findings: Between February 14, 2017, and October 31, 2020, 320 patients (43.1% women; mean age ± SD 53.7 ± 9.7 years) were enrolled. Baseline office and 24-h BP averaged 130 ± 6.0/81 ± 5.9 mm Hg and 136 ± 8.6/84 ± 6.1 mm Hg, and the prevalence of elevated baPWV, ACR and LVH were 97.5%, 12.5%, and 7.8%, respectively. The 24-h BP decreased on average (±SE) by 10.1 ± 0.9/6.4 ± 0.5 mm Hg in 153 patients on active treatment and by 1.3 ± 0.9/1.0 ± 0.5 mm Hg in 167 patients on placebo. Improvement of TOD occurred in 79 patients randomised to active treatment and in 49 patients on placebo: 51.6% (95% CI 43.7%, 59.5%) versus 29.3% (22.1, 36.5%; p < 0.0001). Per-protocol and subgroup analyses were confirmatory. Adverse events were generally mild and occurred in 38 (25.3%) and 43 (26.4%) patients randomised to active treatment and placebo, respectively (p = 0.83). Interpretation: Our results suggest that antihypertensive treatment improves TOD in patients with masked hypertension, highlighting the need of treatment. However, the long-term benefit in preventing cardiovascular complications still needs to be established. Funding: Salubris China.
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Pulse pressure amplification (PPA) is the brachial-to-aortic pulse pressure ratio and decreases with age and cardiovascular risk factors. This individual-participant meta-analysis of population studies aimed to define an outcome-driven threshold for PPA. Incidence rates and standardized multivariable-adjusted hazard ratios (HRs) of cardiovascular and coronary endpoints associated with PPA, as assessed by the SphygmoCor software, were evaluated in the International Database of Central Arterial Properties for Risk Stratification (n = 5608). Model refinement was assessed by the integrated discrimination (IDI) and net reclassification (NRI) improvement. Age ranged from 30 to 96 years (median 53.6). Over 4.1 years (median), 255 and 109 participants experienced a cardiovascular or coronary endpoint. In a randomly defined discovery subset of 3945 individuals, the rounded risk-carrying PPA thresholds converged at 1.3. The HRs for cardiovascular and coronary endpoints contrasting PPA < 1.3 vs ≥1.3 were 1.54 (95% confidence interval [CI]: 1.00-2.36) and 2.45 (CI: 1.20-5.01), respectively. Models were well calibrated, findings were replicated in the remaining 1663 individuals analyzed as test dataset, and NRI was significant for both endpoints. The HRs associating cardiovascular and coronary endpoints per PPA threshold in individuals <60 vs ≥60 years were 3.86 vs 1.19 and 6.21 vs 1.77, respectively. The proportion of high-risk women (PPA < 1.3) was higher at younger age (<60 vs ≥60 years: 67.7% vs 61.5%; P < 0.001). In conclusion, over and beyond common risk factors, a brachial-to-central PP ratio of <1.3 is a forerunner of cardiovascular coronary complications and is an underestimated risk factor in women aged 30-60 years. Our study supports pulse wave analysis for risk stratification.
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[RESUMEN]. La Comisión Lancet de Hipertensión determinó que una medida clave para responder a la carga mundial que representa la hipertensión arterial era mejorar la calidad de las mediciones de la presión arterial, mediante la utilización de dispositivos cuya exactitud haya sido validada. En la actualidad existen 3000 dispositivos comercializados, pero muchos no tienen datos publicados sobre pruebas de exactitud conformes a las normas científicas establecidas. La falta de regulación o su ineficiencia, que permiten la autorización de dispositivos para uso comercial sin una validación oficial, posibilitan este problema. Además, han surgido tecnologías nuevas de medición de la presión arterial (por ejemplo, los sensores sin brazalete) sobre las cuales no existe unanimidad en la comunidad científica con respecto a las normas de exactitud de la medición. En conjunto, estos aspectos contribuyen a la disponibilidad generalizada de tensiómetros de consultorio o domiciliarios que ofrecen una exactitud limitada o incierta, que llevan a diagnósticos, manejo y farmacoterapia inapropiados de la hipertensión a escala mundial. Los problemas más importantes relacionados con la exactitud de los dispositivos de medición de la presión arterial se pueden resolver mediante el requisito regulatorio de una validación independiente obligatoria de los dispositivos, en consonancia con la norma ISO universalmente aceptada. Esta es una recomendación básica y constituye una necesidad internacional acuciante. Otras recomendaciones clave son la elaboración de normas de validación específicas para las tecnologías nuevas de medición de la presión arterial y la publicación en línea de listas de los dispositivos nuevos exactos que están a la disposición de los usuarios y los profesionales de salud. Las recomendaciones están en consonancia con las políticas de la Organización Mundial de la Salud sobre los dispositivos médicos y la atención universal de la salud. El cumplimiento de las recomendaciones aumentará la disponibilidad mundial de dispositivos de medición de la presión arterial que sean exactos y tendrá como efecto un mejor diagnóstico y tratamiento, reduciendo así la carga mundial de la hipertensión.
[ABSTRACT]. The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3 000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organization for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP.
[RESUMO]. A Comissão Lancet sobre Hipertensão Arterial identificou que uma iniciativa central para enfrentar a carga mundial da hipertensão arterial seria a melhoria na qualidade da mensuração da pressão arterial pelo uso aparelhos de pressão arterial validados quanto à acurácia. Atualmente, existem mais de 3 000 aparelhos de pressão arterial disponíveis comercialmente; entretanto, muitos não têm dados publicados sobre testes de acurácia realizados de acordo com padrões científicos estabelecidos. Este problema resulta de regulamentação fraca ou inexistente, o que permite a aprovação para uso comercial de dispositivos sem validação formal. Além disso, surgiram novas tecnologias de mensuração da pressão arterial (por exemplo, sensores sem algemas) sem consenso científico quanto aos padrões de acurácia. No conjunto, essas questões contribuem para a oferta generalizada de dispositivos de pressão arterial clínica e domiciliar com acurácia limitada ou incerta, levando a diagnóstico, gerenciamento e tratamento inadequados da hipertensão em escala global. Os problemas mais significativos relacionados com a acurácia dos dispositivos de pressão arterial podem ser resolvidos por regulamentação que imponha a obrigatoriedade de validação independente dos aparelhos de pressão arterial, de acordo com a norma universalmente aceita pela Organização Internacional de Normalização. Esta é uma recomendação fundamental para a qual existe uma necessidade internacional urgente. Outras recomendações essenciais incluem o desenvolvimento de padrões de validação especificamente para novas tecnologias de mensuração da pressão arterial e listas on-line de aparelhos com acurácia adequada que sejam acessíveis aos consumidores e profissionais de saúde. As recomendações estão alinhadas com as políticas da Organização Mundial da Saúde (OMS) sobre dispositivos médicos e atenção universal à saúde. A adesão às recomendações aumentaria a oferta global de dispositivos de pressão arterial com acurácia adequada e resultaria em melhor diagnóstico e tratamento da hipertensão arterial, diminuindo assim a carga mundial dessa doença.
Assuntos
Saúde Global , Tecnologia Biomédica , Padrões de Referência , Equipamentos para Diagnóstico , Saúde Global , Tecnologia Biomédica , Padrões de Referência , Equipamentos para Diagnóstico , Saúde Global , Tecnologia Biomédica , Padrões de Referência , Equipamentos para DiagnósticoRESUMO
Objetivos. El boletín de notas de México correspondiente al 2018 evalúa las oportunidades a disposición de la población infantil y joven mexicana para que puedan desarrollar niveles adecuados de actividad física y sueño, y disminuyan el sedentarismo.Métodos. El boletín es un sistema de vigilancia que recopila los datos obtenidos en las encuestas nacionales, censos, documentos gubernamentales, sitios web, literatura gris y estudios publicados con respecto al análisis de 16 indicadores en 4 categorías: comportamientos diarios, estado físico, entornos y fuentes influyentes, y estrategias e inversión. Los datos fueron cotejados con los puntos de referencia establecidos. A cada indicador se le asignó una calificación entre 1 y 10 (< 6 significa reprobado) o fue marcado como "incompleto" si los datos eran nulos o insuficientes. Resultados. Las calificaciones obtenidas para los comportamientos diarios fueron: actividad física en general: 4; participación en actividades deportivas organizadas: 5; juego activo: 3; modalidades de transporte activas: 5; sueño: 7; y sedentarismo: 3. El estado físico obtuvo un 7. Las calificaciones para los entornos y fuentes influyentes fueron: familiares y pares: "incompleto"; escuela: 3; comunidad y entorno: 4. Para las estrategias e inversión: estrategias gubernamentales: 6; entidades no gubernamentales: 2.Conclusiones. Las bajas calificaciones obtenidas en 11 de los 16 indicadores demuestran que las escuelas, las familias, las comunidades y el gobierno tienen que aunar esfuerzos para mejorar las oportunidades que tiene la población infantil y joven en México para desarrollar niveles de actividad física satisfactorios.(AU)
ABSTRACT The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3 000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organization for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP.(AU)
RESUMO A Comissão Lancet sobre Hipertensão Arterial identificou que uma iniciativa central para enfrentar a carga mundial da hipertensão arterial seria a melhoria na qualidade da mensuração da pressão arterial pelo uso aparelhos de pressão arterial validados quanto à acurácia. Atualmente, existem mais de 3 000 aparelhos de pressão arterial disponíveis comercialmente; entretanto, muitos não têm dados publicados sobre testes de acurácia realizados de acordo com padrões científicos estabelecidos. Este problema resulta de regulamentação fraca ou inexistente, o que permite a aprovação para uso comercial de dispositivos sem validação formal. Além disso, surgiram novas tecnologias de mensuração da pressão arterial (por exemplo, sensores sem algemas) sem consenso científico quanto aos padrões de acurácia. No conjunto, essas questões contribuem para a oferta generalizada de dispositivos de pressão arterial clínica e domiciliar com acurácia limitada ou incerta, levando a diagnóstico, gerenciamento e tratamento inadequados da hipertensão em escala global. Os problemas mais significativos relacionados com a acurácia dos dispositivos de pressão arterial podem ser resolvidos por regulamentação que imponha a obrigatoriedade de validação independente dos aparelhos de pressão arterial, de acordo com a norma universalmente aceita pela Organização Internacional de Normalização. Esta é uma recomendação fundamental para a qual existe uma necessidade internacional urgente. Outras recomendações essenciais incluem o desenvolvimento de padrões de validação especificamente para novas tecnologias de mensuração da pressão arterial e listas on-line de aparelhos com acurácia adequada que sejam acessíveis aos consumidores e profissionais de saúde. As recomendações estão alinhadas com as políticas da Organização Mundial da Saúde (OMS) sobre dispositivos médicos e atenção universal à saúde. A adesão às recomendações aumentaria a oferta global de dispositivos de pressão arterial com acurácia adequada e resultaria em melhor diagnóstico e tratamento da hipertensão arterial, diminuindo assim a carga mundial dessa doença.(AU)