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OBJECTIVES: To compared the effect of early antihypertensive treatment started within 24-48 h of stroke onset versus delaying treatment until day eight on reducing dependency or death. DESIGN: Multicentre, randomised, open label trial. SETTING: 106 hospitals in China between 13 June 2018 and 10 July 2022. PARTICIPANTS: 4810 patients (≥40 years) were enrolled with acute ischaemic stroke within 24-48 h of symptom onset and elevated systolic blood pressure between 140 mm Hg and <220 mm Hg. INTERVENTIONS: Patients were randomly assigned to receive antihypertensive treatment immediately after randomisation (aimed at reducing systolic blood pressure by 10%-20% within the first 24 h and a mean blood pressure <140/90 mm Hg within seven days) or to discontinue antihypertensive medications for seven days if they were taking them, and then receive treatment on day 8 (aimed at achieving mean blood pressure <140/90 mm Hg). MAIN OUTCOME MEASURES: The primary outcome was the combination of functional dependency or death (modified Rankin scale score ≥3) at 90 days. Intention to treat analyses were conducted. RESULTS: 2413 patients were assigned to the early treatment group and 2397 were assigned to the delayed treatment group. Mean systolic blood pressure was reduced by 9.7% (from 162.9 mm Hg to 146.4 mm Hg) in the early treatment group and by 4.9% (from 162.8 mm Hg to 154.3 mm Hg) in the delayed treatment group within 24 h after randomisation (P for group difference <0.001). Mean systolic blood pressure was 139.1 mm Hg in the early treatment group and 150.9 mm Hg in the delayed treatment group on day seven (P for group difference <0.001). Additionally, 54.6% of patients in the early treatment group and 22.4% in the delayed treatment group had blood pressure of less than 140/90 mm Hg (P<0.001 for group difference) on day seven. At day 90, 289 trial participants (12.0%) in the early treatment group, compared with 250 (10.5%) in the delayed treatment group, had died or experienced a dependency (odds ratio 1.18 (95% confidence interval 0.98 to 1.41), P=0.08). No significant differences in recurrent stroke or adverse events were reported between the two groups. CONCLUSIONS: Among patients with mild-to-moderate acute ischaemic stroke and systolic blood pressure between 140 mm Hg and <220 mm Hg who did not receive intravenous thrombolytic treatment, early antihypertensive treatment did not reduce the odds of dependency or death at 90 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03479554.
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Isquemia Encefálica , Hipertensión , Hipotensión , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Antihipertensivos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Resultado del Tratamiento , Presión SanguíneaRESUMEN
BACKGROUND: Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention on cardiovascular disease has not been established. We aimed to test the effectiveness of such an intervention compared with usual care on risk of cardiovascular disease and all-cause death among individuals with hypertension. METHODS: In this open-label, blinded-endpoint, cluster-randomised trial, we recruited individuals aged at least 40 years with an untreated systolic blood pressure of at least 140 mm Hg or a diastolic blood pressure of at least 90 mm Hg (≥130 mm Hg and ≥80 mm Hg for those at high risk for cardiovascular disease or if currently taking antihypertensive medication). We randomly assigned (1:1) 326 villages to a non-physician community health-care provider-led intervention or usual care, stratified by provinces, counties, and townships. In the intervention group, trained non-physician community health-care providers initiated and titrated antihypertensive medications according to a simple stepped-care protocol to achieve a systolic blood pressure goal of less than 130 mm Hg and diastolic blood pressure goal of less than 80 mm Hg with supervision from primary care physicians. They also delivered discounted or free antihypertensive medications and health coaching for patients. The primary effectiveness outcome was a composite outcome of myocardial infarction, stroke, heart failure requiring hospitalisation, and cardiovascular disease death during the 36-month follow-up in the study participants. Safety was assessed every 6 months. This trial is registered with ClinicalTrials.gov, NCT03527719. FINDINGS: Between May 8 and Nov 28, 2018, we enrolled 163 villages per group with 33 995 participants. Over 36 months, the net group difference in systolic blood pressure reduction was -23·1 mm Hg (95% CI -24·4 to -21·9; p<0·0001) and in diastolic blood pressure reduction, it was -9·9 mm Hg (-10·6 to -9·3; p<0·0001). Fewer patients in the intervention group than the usual care group had a primary outcome (1·62% vs 2·40% per year; hazard ratio [HR] 0·67, 95% CI 0·61-0·73; p<0·0001). Secondary outcomes were also reduced in the intervention group: myocardial infarction (HR 0·77, 95% CI 0·60-0·98; p=0·037), stroke (0·66, 0·60-0·73; p<0·0001), heart failure (0·58, 0·42-0·81; p=0·0016), cardiovascular disease death (0·70, 0·58-0·83; p<0·0001), and all-cause death (0·85, 0·76-0·95; p=0·0037). The risk reduction of the primary outcome was consistent across subgroups of age, sex, education, antihypertensive medication use, and baseline cardiovascular disease risk. Hypotension was higher in the intervention than in the usual care group (1·75% vs 0·89%; p<0·0001). INTERPRETATION: The non-physician community health-care provider-led intensive blood pressure intervention is effective in reducing cardiovascular disease and death. FUNDING: The Ministry of Science and Technology of China and the Science and Technology Program of Liaoning Province, China.
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Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Hipertensión , Hipotensión , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Enfermedades Cardiovasculares/complicaciones , Presión Sanguínea , Antihipertensivos/uso terapéutico , Salud Pública , Hipertensión/tratamiento farmacológico , Hipertensión/complicaciones , Hipotensión/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Infarto del Miocardio/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológicoRESUMEN
BACKGROUND: Uncontrolled hyperglycemia, hypercholesterolemia, and hypertension are common in persons with diabetes. OBJECTIVE: To compare the effectiveness of team-based care with and without a clinical decision support system (CDSS) in controlling glycemia, lipids, and blood pressure (BP) among patients with type 2 diabetes. DESIGN: Cluster randomized trial. (ClinicalTrials.gov: NCT02835287). SETTING: 38 community health centers in Xiamen, China. PATIENTS: 11 132 persons aged 50 years or older with uncontrolled diabetes and comorbid conditions, 5475 receiving team-based care with a CDSS and 5657 receiving team-based care alone. INTERVENTION: Team-based care was delivered by primary care physicians, health coaches, and diabetes specialists in all centers. In addition, a computerized CDSS, which generated individualized treatment recommendations based on clinical guidelines, was implemented in 19 centers delivering team-based care with a CDSS. MEASUREMENTS: Coprimary outcomes were mean reductions in hemoglobin A1c (HbA1c) level, low-density lipoprotein cholesterol (LDL-C) level, and systolic BP over 18 months and the proportion of participants with all 3 risk factors controlled at 18 months. RESULTS: During the 18-month intervention, HbA1c levels, LDL-C levels, and systolic BP significantly decreased by -0.9 percentage point (95% CI, -0.9 to -0.8 percentage point), -0.49 mmol/L (CI, -0.53 to -0.45 mmol/L) (-19.0 mg/dL [CI, -20.4 to -17.5 mg/dL]), and -9.1 mm Hg (CI, -9.9 to -8.3 mm Hg), respectively, in team-based care with a CDSS and by -0.6 percentage point (CI, -0.7 to -0.5 percentage point), -0.32 mmol/L (CI, -0.35 to -0.29 mmol/L) (-12.5 mg/dL [CI, -13.6 to -11.3 mg/dL]), and -7.5 mm Hg (CI, -8.4 to -6.6 mm Hg), respectively, in team-based care alone. Net differences were -0.2 percentage point (CI, -0.3 to -0.1 percentage point) for HbA1c level, -0.17 mmol/L (CI, -0.21 to -0.12 mmol/L) (-6.5 mg/dL [CI, -8.3 to -4.6 mg/dL]) for LDL-C level, and -1.5 mm Hg (CI, -2.8 to -0.3 mm Hg) for systolic BP. The proportion of patients with controlled HbA1c, LDL-C, and systolic BP was 16.9% (CI, 15.7% to 18.2%) in team-based care with a CDSS and 13.0% (CI, 11.7% to 14.3%) in team-based care alone. LIMITATION: There was no usual care control, and clinical outcome assessors were unblinded; the analysis did not account for multiple comparisons. CONCLUSION: Compared with team-based care alone, team-based care with a CDSS significantly reduced cardiovascular risk factors in patients with diabetes, but the effect was modest. PRIMARY FUNDING SOURCE: Xiamen Municipal Health Commission.
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Sistemas de Apoyo a Decisiones Clínicas , Diabetes Mellitus Tipo 2 , Hipertensión , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , LDL-Colesterol , Resultado del Tratamiento , Hipertensión/complicaciones , Hipertensión/terapia , Presión SanguíneaRESUMEN
Importance: Low-carbohydrate diets decrease hemoglobin A1c (HbA1c) among patients with type 2 diabetes at least as much as low-fat diets. However, evidence on the effects of low-carbohydrate diets on HbA1c among individuals with HbA1c in the range of prediabetes to diabetes not treated by diabetes medications is limited. Objective: To study the effect of a behavioral intervention promoting a low-carbohydrate diet compared with usual diet on 6-month changes in HbA1c among individuals with elevated untreated HbA1c. Design, Setting, and Participants: This 6-month randomized clinical trial with 2 parallel groups was conducted from September 2018 to June 2021 at an academic medical center in New Orleans, Louisiana. Laboratory analysts were blinded to assignment. Participants were aged 40 to 70 years with untreated HbA1c of 6.0% to 6.9% (42-52 mmol/mol). Data analysis was performed from November 2021 to September 2022. Interventions: Participants were randomized to a low-carbohydrate diet intervention (target <40 net grams of carbohydrates during the first 3 months; <60 net grams for months 3 to 6) or usual diet. The low-carbohydrate diet group received dietary counseling. Main Outcomes and Measures: Six-month change in HbA1c was the primary outcome. Outcomes were measured at 0, 3, and 6 months. Results: Of 2722 prescreened participants, 962 underwent screening, and 150 were enrolled (mean [SD] age, 58.9 [7.9] years; 108 women [72%]; 88 Black participants [59%]) and randomized to either the low-carbohydrate diet intervention (75 participants) or usual diet (75 participants) group. Six-month data were collected on 142 participants (95%). Mean (SD) HbA1c was 6.16% (0.30%) at baseline. Compared with the usual diet group, the low-carbohydrate diet intervention group had significantly greater 6-month reductions in HbA1c (net difference, -0.23%; 95% CI, -0.32% to -0.14%; P < .001), fasting plasma glucose (-10.3 mg/dL; 95% CI, -15.6 to -4.9 mg/dL; P < .001), and body weight (-5.9 kg; 95% CI, -7.4 to -4.4 kg; P < .001). Conclusions and Relevance: In this randomized clinical trial, a low-carbohydrate dietary intervention led to improvements in glycemia in individuals with elevated HbA1c not taking glucose-lowering medication, but the study was unable to evaluate its effects independently of weight loss. This diet, if sustained, might be a useful dietary approach for preventing and treating type 2 diabetes, but more research is needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03675360.
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Glucemia , Diabetes Mellitus Tipo 2 , Humanos , Femenino , Persona de Mediana Edad , Hemoglobina Glucada/análisis , Diabetes Mellitus Tipo 2/terapia , Dieta Baja en Carbohidratos , Pérdida de PesoRESUMEN
The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI's Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well as APOB, PTPRT, and ROBO1. Functional annotation resources including the Diabetes Epigenome Atlas were compiled for each signal (chromatin states, annotation principal components, and others) to elucidate variant-to-function hypotheses. We provide a catalog of nucleotide-resolution genomic variation spanning intergenic and intronic regions creating a foundation for future sequencing-based investigations of glycemic traits.
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Diabetes Mellitus Tipo 2 , Ayuno , Diabetes Mellitus Tipo 2/genética , Glucosa , Humanos , Insulina/genética , National Heart, Lung, and Blood Institute (U.S.) , Proteínas del Tejido Nervioso/genética , Polimorfismo de Nucleótido Simple , Medicina de Precisión , Receptores Inmunológicos/genética , Estados UnidosRESUMEN
BACKGROUND: The prevalence of uncontrolled hypertension is high and increasing in low-income and middle-income countries. We tested the effectiveness of a multifaceted intervention for blood pressure control in rural China led by village doctors (community health workers on the front line of primary health care). METHODS: In this open, cluster randomised trial (China Rural Hypertension Control Project), 326 villages that had a regular village doctor and participated in the China New Rural Cooperative Medical Scheme were randomly assigned (1:1) to either village doctor-led multifaceted intervention or enhanced usual care (control), with stratification by provinces, counties, and townships. We recruited individuals aged 40 years or older with an untreated blood pressure of 140/90 mm Hg or higher (≥130/80 mm Hg among those with a history of cardiovascular disease, diabetes, or chronic kidney disease) or a treated blood pressure of 130/80 mm Hg or higher. In the intervention group, trained village doctors initiated and titrated antihypertensive medications according to a standard protocol with supervision from primary care physicians. Village doctors also conducted health coaching on home blood pressure monitoring, lifestyle changes, and medication adherence. The primary outcome (reported here) was the proportion of patients with a blood pressure of less than 130/80 mm Hg at 18 months. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03527719, and is ongoing. FINDINGS: Between May 8 and November 28, 2018, we enrolled 33 995 individuals from 163 intervention and 163 control villages. At 18 months, 8865 (57·0%) of 15 414 patients in the intervention group and 2895 (19·9%) of 14 500 patients in the control group had a blood pressure of less than 130/80 mm Hg, with a group difference of 37·0% (95% CI 34·9 to 39·1%; p<0·0001). Mean systolic blood pressure decreased by -26·3 mm Hg (95% CI -27·1 to -25·4) from baseline to 18 months in the intervention group and by -11·8 mm Hg (-12·6 to -11·0) in the control group, with a group difference of -14·5 mm Hg (95% CI -15·7 to -13·3 mm Hg; p<0·0001). Mean diastolic blood pressure decreased by -14·6 mm Hg (-15·1 to -14·2) from baseline to 18 months in the intervention group and by -7·5 mm Hg (-7·9 to -7·2) in the control group, with a group difference of -7·1 mm Hg (-7·7 to -6·5 mm Hg; p<0·0001). No treatment-related serious adverse events were reported in either group. INTERPRETATION: Compared with enhanced usual care, village doctor-led intervention resulted in statistically significant improvements in blood pressure control among rural residents in China. This feasible, effective, and sustainable implementation strategy could be scaled up in rural China and other low-income and middle-income countries for hypertension control. FUNDING: Ministry of Science and Technology of China.
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Hipertensión , Antihipertensivos/uso terapéutico , Presión Sanguínea/fisiología , Monitoreo Ambulatorio de la Presión Arterial , China/epidemiología , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Hipertensión/prevención & controlRESUMEN
The accuracy of ankle-brachial index (ABI) and toe-brachial index (TBI) in discriminating lower extremity peripheral artery disease (PAD) has not been evaluated in patients with chronic kidney disease (CKD). We measured ABI, TBI, and Doppler ultrasound in 100 predialysis patients with CKD without revascularization or amputation. Leg-specific ABI was calculated using higher systolic blood pressure (SBP) in posterior tibial or dorsalis pedis artery divided by higher brachial SBP; alternative ABI was calculated using lower SBP in posterior tibial or dorsalis pedis artery. PAD was defined as ≥50% stenosis detected by Doppler ultrasound. PAD risk classification score was calculated using cardiovascular disease risk factors. The area under the curve (AUC, 95% confidence interval [CI]) for discriminating ultrasound-diagnosed PAD was 0.78 (0.69 to 0.87) by ABI, 0.80 (0.71 to 0.89) by alternative ABI, and 0.74 (0.63 to 0.86) by TBI. Sensitivity and specificity were 25% and 97% for ABI ≤0.9, 41% and 95% for alternative ABI ≤0.9, and 45% and 93% for TBI ≤0.7, respectively. AUC (95% CI) of PAD risk classification score was 0.86 (0.78 to 0.94) with sensitivity and specificity of 95% and 60% for risk score ≥0.10, 76% and 76% for risk score ≥0.25, and 43% and 95% for risk score ≥0.55. Combining risk score with ABI, alternative ABI, and TBI increased AUC (95% CI) to 0.89 (0.82 to 0.96), 0.89 (0.80 to 0.98), and 0.87 (0.78 to 0.96), respectively. In conclusion, current ABI and TBI diagnostic criteria have high specificity but low sensitivity for classifying PAD in patients with CKD. PAD classification risk score based on cardiovascular disease risk factors improves the accuracy of PAD classification.
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Índice Tobillo Braquial , Enfermedad Arterial Periférica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Ultrasonografía Doppler , Anciano , Anciano de 80 o más Años , Presión Sanguínea , Arteria Braquial/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/complicaciones , Insuficiencia Renal Crónica/complicaciones , Medición de Riesgo , Sensibilidad y Especificidad , Arterias Tibiales/fisiopatología , Dedos del Pie/irrigación sanguíneaRESUMEN
BACKGROUND: Diabetes has become a major public health challenge worldwide, especially in low- and middle-income countries (LMICs). Uncontrolled hyperglycemia, hypertension, and dyslipidemia major risk factors for all-cause mortality and cardiovascular disease (CVD) are common in patients with diabetes in China. We propose to compare the effectiveness of team-based care plus a clinical decision support system (CDSS) with team-based care alone on glycemic, blood pressure (BP), and lipid control, and clinical CVD reduction among patients with type-2 diabetes and at high risk for CVD. METHODS: The Diabetes Complication Control in Community Clinics (D4C) study is a cluster-randomized trial conducted among 38 community health centers in Xiamen City, China. Nineteen clinics have been randomly assigned to team-based care plus CDSS and 19 to team-based care alone. Team-based care includes primary care providers, health coaches, and diabetes specialists working collaboratively with patients to achieve shared treatment goals for CVD risk factor reduction. The CDSS integrates guideline-based treatment algorithms for glycemic, BP, and lipid control, along with a patient's medical history and insurance policy, to recommend treatment and follow-up plans. In phase 1, the co-primary outcomes are mean reduction in glycated hemoglobin (HbA1c), systolic BP (SBP), and low-density lipoprotein (LDL)-cholesterol over 18 months, and the proportion of patients with controlled HbA1c, SBP, and LDL-cholesterol at 18 months' between the 2 comparison groups. In phase 2, the primary outcome is the difference in major CVD incidence (non-fatal stroke, non-fatal myocardial infarction, hospitalized heart failure, and CVD mortality) between the 2 comparison groups. Mean reduction in HbA1c, SBP, and LDL-cholesterol levels will be simultaneously modeled for a single overall treatment effect. CONCLUSION: The D4C trial will generate evidence on whether a CDSS will further reduce the CVD burden among patients with diabetes beyond team-based care at community clinics. If proven effective, this implementation strategy could be scaled up within primary care settings in China and other LMICs to reduce CVD incidence and mortality among patients with diabetes.
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Enfermedades Cardiovasculares/prevención & control , Sistemas de Apoyo a Decisiones Clínicas , Diabetes Mellitus Tipo 2/complicaciones , Factores de Riesgo de Enfermedad Cardiaca , Grupo de Atención al Paciente/organización & administración , Conducta de Reducción del Riesgo , Presión Sanguínea , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , China , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Femenino , Hemoglobina Glucada , Insuficiencia Cardíaca/prevención & control , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/prevención & control , Accidente Cerebrovascular/prevención & controlRESUMEN
[Figure: see text].
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Presión Sanguínea/fisiología , Resistencia a Medicamentos , Hipertensión/fisiopatología , Medición de Riesgo/estadística & datos numéricos , Adulto , Presión Sanguínea/efectos de los fármacos , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/etiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Modelos Teóricos , Estudios Prospectivos , Medición de Riesgo/métodos , Factores de Riesgo , Sodio/orina , Sodio en la Dieta/administración & dosificación , Sodio en la Dieta/efectos adversosRESUMEN
BACKGROUND AND OBJECTIVES: Endothelial dysfunction is common among patients with CKD. We tested the efficacy and safety of combination treatment with sodium nitrite and isoquercetin on biomarkers of endothelial dysfunction in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This randomized, double-blind, placebo-controlled phase 2 pilot trial enrolled 70 patients with predialysis CKD. Thirty-five were randomly assigned to combination treatment with sodium nitrite (40 mg twice daily) and isoquercetin (225 mg once daily) for 12 weeks, and 35 were randomly assigned to placebo. The primary outcome was mean change in flow-mediated vasodilation over the 12-week intervention. Secondary and safety outcomes included biomarkers of endothelial dysfunction, inflammation, and oxidative stress as well as kidney function, methemoglobin, and adverse events. Intention-to-treat analysis was conducted. RESULTS: Baseline characteristics, including age, sex, race, cigarette smoking, history of hypertension and diabetes, use of renin-angiotensin system blockers, BP, fasting glucose, lipid profile, kidney function, urine albumin-creatinine ratio, and endothelial biomarkers, were comparable between groups. Over the 12-week intervention, flow-mediated vasodilation increased 1.1% (95% confidence interval, -0.1 to 2.3) in the treatment group and 0.3% (95% confidence interval, -0.9 to 1.5) in the placebo group, and net change was 0.8% (95% confidence interval, -0.9 to 2.5). In addition, changes in biomarkers of endothelial dysfunction (vascular adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, vWf, endostatin, and asymmetric dimethylarginine), inflammation (TNF-α, IL-6, C-reactive protein, IL-1 receptor antagonist, and monocyte chemoattractant protein-1), and oxidative stress (oxidized LDL and nitrotyrosines) were not significantly different between the two groups. Furthermore, changes in eGFR, urine albumin-creatinine ratio, methemoglobin, and adverse events were not significantly different between groups. CONCLUSIONS: This randomized phase 2 pilot trial suggests that combination treatment with sodium nitrite and isoquercetin did not significantly improve flow-mediated vasodilation or other endothelial function biomarkers but also did not increase adverse events compared with placebo among patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Nitrite, Isoquercetin, and Endothelial Dysfunction (NICE), NCT02552888.
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Endotelio/efectos de los fármacos , Quercetina/análogos & derivados , Insuficiencia Renal Crónica/tratamiento farmacológico , Nitrito de Sodio/farmacología , Vasodilatación/efectos de los fármacos , Anciano , Amina Oxidasa (conteniendo Cobre)/sangre , Antioxidantes/farmacología , Arginina/análogos & derivados , Arginina/sangre , Biomarcadores/sangre , Moléculas de Adhesión Celular/sangre , Quimioterapia Combinada , Selectina E/sangre , Endostatinas/sangre , Endotelio/fisiopatología , Femenino , Tasa de Filtración Glomerular , Humanos , Inflamación/sangre , Molécula 1 de Adhesión Intercelular/sangre , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Estrés Oxidativo/efectos de los fármacos , Proyectos Piloto , Quercetina/efectos adversos , Quercetina/farmacología , Insuficiencia Renal Crónica/fisiopatología , Nitrito de Sodio/efectos adversos , Factor de von Willebrand/metabolismoRESUMEN
Stroke is the leading cause of death and long-term disability worldwide, and cognitive impairment and dementia are major complications of ischemic stroke. Cystatin C (CysC) has been found to be a neuroprotective factor in animal studies. However, the relationship between CysC levels and cognitive dysfunction in previous studies has revealed different results. This prospective observational study investigated the correlation between serum CysC levels and post-stroke cognitive dysfunction at 3 months. Data from 638 patients were obtained from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE) at 3 months after stroke. According to the MMSE score, 308 patients (52.9%) had post-stroke cognitive dysfunction. After adjusting for potential confounding factors, the odds ratio (95% CI) of post-stroke cognitive dysfunction for the highest quartile of serum CysC levels was 0.54 (0.30-0.98), compared with the lowest quartile. The correlation between serum CysC and cognitive dysfunction was modified by renal function status. We observed a negative linear dose-response correlation between CysC and cognitive dysfunction in patients with normal renal function (Plinearity = 0.044), but not in those with abnormal renal function. Elevated serum CysC levels were correlated with a low risk of 3-month cognitive dysfunction in patients with acute ischemic stroke, especially in those with normal renal function. The current results suggest that CysC is a protective factor for post-stroke cognitive dysfunction, and could be used to treat post-stroke cognitive dysfunction. The CATIS study was approved by the Institutional Review Boards at Soochow University from China (approval No. 2012-02) on December 30, 2012, and was registered at ClinicalTrials.gov (identifier No. NCT01840072) on April 25, 2013.
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INTRODUCTION: Lifestyle modification, such as healthy diet habits, regular physical activity, and maintaining a normal body weight, must be prescribed to all hypertensive individuals. This study aims to test whether a multicomponent intervention is effective in improving lifestyle and body weight among low-income families. STUDY DESIGN: Cluster randomized trial conducted between June 2013 and October 2016. SETTING/PARTICIPANTS: A total of 1,954 uninsured adult patients were recruited in the study within 18 public primary healthcare centers of Argentina. INTERVENTION: Components targeting the healthcare system, providers, and family groups were delivered by community health workers; tailored text messages were sent for 18 months. MAIN OUTCOME MEASURES: Changes in the proportion of behavioral risk factors and body weight from baseline to end of follow-up. Data were analyzed in 2017. RESULTS: Low fruit and vegetable consumption (fewer than 5 servings per day) decreased from 96.4% at baseline to 92.6% at 18 months in the intervention group, whereas in the control group it increased from 97.0% to 99.9% (p=0.0110). The proportion of low physical activity (<600 MET-minutes/week) decreased from 54.3% at baseline to 46.2% at 18 months in the intervention group and kept constant around 52% (p=0.0232) in the control group. The intervention had no effect on alcohol intake (p=0.7807), smoking (p=0.7607), addition of salt while cooking or at the table (p=0.7273), or body weight (p=0.4000). CONCLUSIONS: The multicomponent intervention was effective for increasing fruit and vegetable intake and physical activity with no effect on alcohol consumption, smoking, addition of salt, or body weight among low-income families in Argentina. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT01834131.
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Peso Corporal , Ejercicio Físico , Estilo de Vida Saludable , Hipertensión/terapia , Adulto , Anciano , Argentina , Presión Sanguínea , Agentes Comunitarios de Salud , Femenino , Humanos , Masculino , Persona de Mediana Edad , PobrezaRESUMEN
Importance: Clinical trials have generally shown a neutral effect of early blood pressure (BP) decreases on clinical outcomes after acute ischemic stroke. Whether the effect of early antihypertensive therapy differs for patients with ischemic stroke with or without prior hypertension is unclear. Objective: To investigate the association between immediate antihypertensive treatment and patient outcomes according to the presence or absence of hypertension before stroke onset. Design, Setting, and Participants: This study was a prespecified subgroup analysis of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS), a multicenter, single-blind, blinded end-points randomized clinical trial of 4071 patients with acute ischemic stroke and elevated systolic BP. Patients were recruited from August 2009 to May 2013, and this statistical analysis was performed using the intention-to-treat population from January to October 2018. Interventions: Participants were randomly assigned to receive antihypertensive treatment (aimed at decreasing systolic BP by 10%-25% within the first 24 hours after randomization, achieving systolic BP <140 mm Hg and diastolic BP <90 mm Hg within 7 days, and maintaining this level during hospitalization) or to the control arm (discontinued all antihypertensive medications). Main Outcomes and Measures: Primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3; range 0-6, with higher values indicating greater disability) at 14 days or hospital discharge. Results: In total, 2038 patients were randomized to receive antihypertensive treatment, and 2033 patients were randomized to the control group. The mean (SD) age was 62.0 (10.9) years, and 2604 participants (64.0%) were men. At day 14 or hospital discharge, the primary outcome was not different between the treatment and control groups among patients with or without prior hypertension (P = .97 for homogeneity): odds ratios (ORs) associated with treatment were 1.00 (95% CI, 0.87-1.16) for patients with prior hypertension and 1.00 (95% CI, 0.75-1.32) for patients without. Early antihypertensive treatment was associated with different rates of 3-month recurrent stroke (patients with hypertension: OR, 0.44; 95% CI, 0.25-0.77 vs without hypertension: OR, 3.43; 95% CI, 0.94-12.55; P = .005 for homogeneity) and vascular events (patients with hypertension: OR, 0.66; 95% CI, 0.43-1.02 vs those without hypertension: OR, 1.91; 95% CI, 0.75-4.83; P = .04 for homogeneity) by hypertension history. Conclusions and Relevance: Among patients with acute ischemic stroke, early antihypertensive treatment was not associated with different death and major disability outcomes by hypertension history. However, early antihypertension therapy was associated with a decreased rate of recurrent stroke among patients with a history of hypertension and may inform future studies in the optimal approach to hypertension management in the setting of acute ischemic stroke. Trial Registration: ClinicalTrials.gov identifier: NCT01840072.
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Antihipertensivos/administración & dosificación , Hipertensión/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Factores de Tiempo , Anciano , Presión Sanguínea/efectos de los fármacos , Femenino , Humanos , Hipertensión/complicaciones , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Método Simple Ciego , Accidente Cerebrovascular/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Antiphospholipid activity was reported to be increased in depressive patients, while the impact of antiphospholipid antibodies (aPLs) on post-stroke depression (PSD) is unclear. We aimed to investigate the associations of aPLs, including antiphosphatidylserine (aPS) and anticardiolipin (aCL) antibodies with depression after acute ischemic stroke. METHODS: aPS and aCL were measured in 497 ischemic stroke patients recruited from 7 of 26 participating hospitals of China Antihypertensive Trial in Acute Ischemic Stroke. 24-item Hamilton Depression Rating Scale was used to evaluate PSD status at 3 months after stroke. RESULTS: Compared with aPS-negative or aCL-negative, the adjusted odds ratios (ORs) [95% confidence intervals (CIs)] associated with aPS-positive or aCL-positive were 1.77 (1.07-2.92) or 2.06 (1.11-3.80) for risk of PSD. On continuous analyses, per 1-SD increment of aPS and aCL were associated with 29% (OR 1.29, 95% CI 1.06-1.58) and 30% (OR 1.30, 95% CI 1.06-1.60) increased risks for PSD, respectively. Adding aPLs to conventional risk factors models significantly improved risk reclassification for PSD (net reclassification improvement index = 21.87%, Pâ¯=â¯0.016 for aPS; net reclassification improvement index = 32.24%, Pâ¯=â¯0.0004 for aCL). LIMITATIONS: aPLs levels were tested only at baseline without serial measurements, and we were unable to detect the association between aPLs changes and PSD. CONCLUSIONS: Higher aPS and aCL levels in the acute phase of ischemic stroke were associated with increased risk of 3-month PSD, suggesting that aPLs may play an important role in post-stroke depression prediction.
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Anticuerpos Antifosfolípidos/sangre , Isquemia Encefálica/inmunología , Isquemia Encefálica/psicología , Depresión/inmunología , Accidente Cerebrovascular/inmunología , Accidente Cerebrovascular/psicología , Enfermedad Aguda , Adulto , Isquemia Encefálica/sangre , China , Ensayos Clínicos como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Accidente Cerebrovascular/sangreRESUMEN
BACKGROUND AND AIMS: We aimed to evaluate the ability of multiple novel biomarkers representing several pathophysiological pathways to improve risk prediction of post-stroke cognitive impairment. METHODS: We conducted a prospective multicenter study in 638 ischemic stroke patients with elevated blood pressure based on a random subsample from China Antihypertensive Trial in Acute Ischemic Stroke and measured 12 circulating biomarkers in these participants. Cognitive impairment was assessed at 3 months after stroke with definitions of Mini-Mental State Examination (MMSE) score <27 or Montreal Cognitive Assessment (MoCA) score <25. RESULTS: According to MMSE score, 1 SD increase of rheumatoid factor (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.02-1.46), matrix metalloproteinase-9 (OR 1.47, 95% CI 1.22-1.77) and total homocysteine (OR 1.22, 95% CI 1.01-1.49) after log transformation was significantly associated with the risk of post-stroke cognitive impairment. The ORs associated with their simultaneously high levels were 4.89 (95% CI, 2.31-10.35; ptrend<0.001) and 3.09 (95% CI, 1.60-5.98; ptrend<0.001) for cognitive impairment and the severity of cognitive impairment, respectively. Adding these 3 biomarkers to conventional model significantly improved the risk prediction of cognitive impairment (C statistic 0.729 vs. 0.688, pâ¯=â¯0.004; net reclassification improvementâ¯=â¯33.67%, pâ¯<â¯0.001; integrated discrimination indexâ¯=â¯4.61%; pâ¯<â¯0.001). Similar significant findings were observed when cognitive impairment was defined by MoCA score. CONCLUSIONS: Combination of rheumatoid factor, matrix metalloproteinase-9 and total homocysteine can improve the risk prediction of cognitive impairment among ischemic stroke patients with elevated blood pressure. Further studies are warranted to validate our findings and explore their roles as potential therapeutic targets.
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Presión Sanguínea/fisiología , Isquemia Encefálica/complicaciones , Cognición/fisiología , Disfunción Cognitiva/etiología , Homocisteína/sangre , Metaloproteinasa 9 de la Matriz/sangre , Factor Reumatoide/sangre , Biomarcadores/sangre , Isquemia Encefálica/sangre , Isquemia Encefálica/fisiopatología , China/epidemiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Proyectos Piloto , Valor Predictivo de las Pruebas , Estudios Prospectivos , Método Simple Ciego , Factores de TiempoRESUMEN
Background and Purpose- Previous experimental studies suggested that serum netrin-1 was associated with the progression of ischemic stroke. Knowledge about netrin-1 among ischemic stroke patients may provide new ideas for the prognostic assessment of ischemic stroke. The aim of this study was to investigate the association between serum netrin-1 and prognosis of ischemic stroke. Methods- Serum netrin-1 levels at baseline were measured for 3346 ischemic stroke patients from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke), and all patients were followed up at 3 months after stroke onset. The primary outcome was a combination of death and major disability (modified Rankin Scale score of ≥3) within 3 months after stroke onset. Results- Up to 3 months after stroke onset, 845 patients (25.25%) experienced death or major disability. After adjustment for baseline National Institutes of Health Stroke Scale score and other potential confounders, elevated serum netrin-1 was associated with a decreased risk of primary outcome (odds ratio, 0.65; 95% CI, 0.47-0.88; Ptrend=0.002) when 2 extreme quartiles were compared. Each SD increase of log-transformed netrin-1 was associated with 17% (95% CI, 7%-26%) decreased risk of primary outcome. Multivariable-adjusted spline regression models showed a negative linear dose-response relationship between serum netrin-1 and the risk of primary outcome ( Plinearity=0.003). Adding netrin-1 quartile to a model containing conventional risk factors improved risk prediction for primary outcome (net reclassification improvement index =14.74%; P=0.002; integrated discrimination improvement =0.40%; P=0.005). Conclusions- Elevated serum netrin-1 levels were associated with improved prognosis at 3 months after ischemic stroke, suggesting that serum netrin-1 may be a potential prognostic biomarker for ischemic stroke. Further studies from other samples of ischemic stroke patients are needed to replicate our findings and to clarify the potential mechanisms. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01840072.
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Isquemia Encefálica/sangre , Netrina-1/sangre , Accidente Cerebrovascular/sangre , Anciano , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: The effect of serum rheumatoid factor (RF) on poststroke cognitive impairment remains unknown. We aimed to investigate the association of serum RF in the acute phase with cognitive impairment at 3 months after ischemic stroke onset. METHODS: Our study was based on a random sample from the China Antihypertensive Trial in Acute Ischemic Stroke, a total of 582 patients from 7 of 26 participating sites of the trial with serum RF levels were included in this analysis. Cognitive impairment was defined as Mini-Mental State Examination less than 27 or Montreal Cognitive Assessment less than 25. RESULTS: According to Mini-Mental State Examination score, the multivariate-adjusted odds ratio and 95% confidence interval of cognitive impairment for the highest tertile of serum RF was 1.79 (1.08-2.99) compared with the lowest tertile. Each standard deviation increase of log-transformed RF was associated with 33% (95% confidence interval: 7%-66%) increased risk of cognitive impairment, and a linear association between serum RF and risk of poststroke cognitive impairment was observed (P for linearity < .01). Adding log-transformed RF to a model containing conventional risk factors improved the predictive power for poststroke cognitive impairment (net reclassification improvement: 26.21%, P < .01; integrated discrimination index: 1.24%, Pâ¯=â¯.02). Similar significant findings were observed when cognitive function was defined by Montreal Cognitive Assessment score. CONCLUSIONS: Elevated serum RF levels in the acute phase were independently associated with 3-month cognitive impairment among ischemic stroke patients. Further studies are needed to replicate our findings and to clarify the potential mechanisms.
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Isquemia Encefálica/sangre , Trastornos del Conocimiento/etiología , Cognición , Factor Reumatoide/sangre , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/etiología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Isquemia Encefálica/complicaciones , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/psicología , China , Trastornos del Conocimiento/sangre , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Femenino , Humanos , Masculino , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/psicología , Factores de Tiempo , Regulación hacia ArribaRESUMEN
BACKGROUND: Growth differentiation factor 15 (GDF-15), a stress-responsive biomarker, is known to be independently associated with mortality and cardiovascular events in different disease settings, but data on the prognostic value of GDF-15 after stroke are limited. METHODS: Baseline serum GDF-15 was measured in 3066 acute ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a composite of death and major disability within 3 months. Secondary outcomes included death, major disability, vascular events, and stroke recurrence. The associations between GDF-15 and clinical outcomes after stroke were assessed by multivariate logistic regression or Cox proportional hazards models. RESULTS: At 3 months' follow-up, 676 (22.05%), 86 (2.80%), 81 (2.64%), and 51 (1.66%) patients had experienced major disability, death, vascular events, or stroke recurrence, respectively. After adjusting for age, sex, current smoking, alcohol consumption, and baseline National Institutes of Health Stroke Scale score, the odds ratio/hazard ratio (95% CI) of 1 SD higher of base-10 log-transformed GDF-15 was 1.26 (1.15-1.39) for primary outcome, 1.13 (1.02-1.25) for major disability, 1.79 (1.48-2.16) for death, and 1.26 (1.00-1.58) for vascular events. The addition of GDF-15 to established risk factors improved risk prediction of the composite outcome of death and major disability (c-statistic, net reclassification index, and integrated discrimination improvement, all P < 0.05). CONCLUSIONS: High GDF-15 concentrations are independently associated with adverse clinical outcomes of acute ischemic stroke, suggesting that baseline serum GDF-15 could provide additional information to identify ischemic stroke patients at high risk of poor prognosis.
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Biomarcadores de Tumor/metabolismo , Isquemia Encefálica/diagnóstico , Factor 15 de Diferenciación de Crecimiento/metabolismo , Accidente Cerebrovascular/diagnóstico , Anciano , Biomarcadores de Tumor/sangre , Isquemia Encefálica/mortalidad , Femenino , Factor 15 de Diferenciación de Crecimiento/sangre , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Accidente Cerebrovascular/mortalidadRESUMEN
Objective- Serum Dkk-1 (dickkopf-1) level has been shown to be elevated in patients with ischemic stroke, but its impact on clinical outcomes of ischemic stroke remains unclear. The aim of this study is to investigate the association between serum Dkk-1 and prognosis of ischemic stroke. Approach and Results- We measured serum Dkk-1 levels in 3178 patients with ischemic stroke from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). The primary outcome was a combination of all-cause mortality and major disability (modified Rankin scale score, ≥3) at 1 year after stroke. Secondary outcomes were stroke recurrence and vascular events. After multivariate adjustment, elevated Dkk-1 levels were associated with an increased risk of primary outcome (odds ratio, 1.40; 95% CI, 1.03-1.89; Ptrend=0.015) when 2 extreme quartiles were compared. Each SD increase of log-transformed Dkk-1 was associated with 12% (95% CI, 1%-24%) increased risk of primary outcome. Multiple-adjusted spline regression model showed a linear association between serum Dkk-1 and risk of primary outcome ( P for linearity, 0.039). Subgroup analyses further confirmed these associations. The addition of serum Dkk-1 to conventional risk factors improved the predictive power for primary outcome (net reclassification improvement: 10.11%, P=0.029; integrated discrimination improvement: 0.21%, P=0.028). Conclusions- High serum Dkk-1 levels at baseline were associated with poor prognosis at 1 year after ischemic stroke, suggesting that serum Dkk-1 may be a potential prognostic biomarker for ischemic stroke. Further studies from other samples of patients with ischemic stroke are needed to replicate our findings and to clarify the potential mechanisms.
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Isquemia Encefálica/sangre , Péptidos y Proteínas de Señalización Intercelular/sangre , Accidente Cerebrovascular/sangre , Anciano , Biomarcadores/sangre , Isquemia Encefálica/complicaciones , Isquemia Encefálica/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Método Simple Ciego , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/mortalidadRESUMEN
BACKGROUND: Previous studies have reported that extreme low and high hemoglobin levels are positively associated with the risk of ischemic stroke. However, there are few reports on the relationship between hemoglobin at acute phase and clinical outcomes after ischemic stroke and the results of their association to date are inconsistent. We aimed to investigate the association between them in a large prospective cohort of ischemic stroke patients. METHODS: Baseline hemoglobin levels were measured in 3881 patients with acute ischemic stroke. The primary outcome was defined as composite outcome of major disability and death (modified Rankin Scale scoreâ¯≥â¯3) at 3â¯months after stroke onset. Secondary outcomes were separately those of major disability and death. RESULTS: Compared with the lowest quartile of hemoglobin, the multivariate adjusted odds ratios (95% confidence intervals) associated with the highest quartile were 1.38 (1.03-1.86), 1.49 (1.11-1.99), 0.79 (0.41-1.52) for primary outcome, major disability and death, respectively. Multiple-adjusted spline regression model showed linear associations of hemoglobin levels with primary outcome (P for linearity =0.037) and major disability (P for linearity =0.004). Subgroup analyses further confirmed the positive association between high hemoglobin and poor prognosis of ischemic stroke. CONCLUSIONS: Elevated hemoglobin levels in the acute phase were associated with poor prognosis at 3â¯months after ischemic stroke. Further prospective studies from other samples of ischemic stroke patients are needed to validate our findings.