Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention versus usual care on cardiovascular disease (CRHCP): an open-label, blinded-endpoint, cluster-randomised trial.

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.

Comparative Effectiveness of Team-Based Care With and Without a Clinical Decision Support System for Diabetes Management : A Cluster Randomized Trial.

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.

A village doctor-led multifaceted intervention for blood pressure control in rural China: an open, cluster randomised trial.

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.

Comparative effectiveness of team-based care with a clinical decision support system versus team-based care alone on cardiovascular risk reduction among patients with diabetes: Rationale and design of the D4C trial.

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.

Serum Dkk-1 (Dickkopf-1) Is a Potential Biomarker in the Prediction of Clinical Outcomes Among Patients With Acute Ischemic Stroke.

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.

Increased Serum Netrin-1 Is Associated With Improved Prognosis of Ischemic Stroke.

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.

Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study.

BACKGROUND: Although exposure to cigarette smoking and air pollution is common, the current prevalence of chronic obstructive pulmonary disease (COPD) is unknown in the Chinese adult population. We conducted the China Pulmonary Health (CPH) study to assess the prevalence and risk factors of COPD in China. METHODS: The CPH study is a cross-sectional study in a nationally representative sample of adults aged 20 years or older from ten provinces, autonomous regions, and municipalities in mainland China. All participants underwent a post-bronchodilator pulmonary function test. COPD was diagnosed according to 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. FINDINGS: Between June, 2012, and May, 2015, 57 779 individuals were invited to participate, of whom 50 991 (21 446 men and 29 545 women) had reliable post-bronchodilator results and were included in the final analysis. The overall prevalence of spirometry-defined COPD was 8·6% (95% CI 7·5-9·9), accounting for 99·9 (95% CI 76·3-135·7) million people with COPD in China. Prevalence was higher in men (11·9%, 95% CI 10·2-13·8) than in women (5·4%, 4·6-6·2; p<0·0001 for sex difference) and in people aged 40 years or older (13·7%, 12·1-15·5) than in those aged 20-39 years (2·1%, 1·4-3·2; p<0·0001 for age difference). Only 12·0% (95% CI 8·1-17·4) of people with COPD reported a previous pulmonary function test. Risk factors for COPD included smoking exposure of 20 pack-years or more (odds ratio [OR] 1·95, 95% CI 1·53-2·47), exposure to annual mean particulate matter with a diameter less than 2·5 µm of 50-74 µg/m3 (1·85, 1·23-2·77) or 75 µg/m3 or higher (2·00, 1·36-2·92), underweight (body-mass index <18·5 kg/m2; 1·43, 1·03-1·97), sometimes childhood chronic cough (1·48, 1·14-1·93) or frequent cough (2·57, 2·01-3·29), and parental history of respiratory diseases (1·40, 1·23-1·60). A lower risk of COPD was associated with middle or high school education (OR 0·76, 95% CI 0·64-0·90) and college or higher education (0·47, 0·33-0·66). INTERPRETATION: Spirometry-defined COPD is highly prevalent in the Chinese adult population. Cigarette smoking, ambient air pollution, underweight, childhood chronic cough, parental history of respiratory diseases, and low education are major risk factors for COPD. Prevention and early detection of COPD using spirometry should be a public health priority in China to reduce COPD-related morbidity and mortality. FUNDING: Ministry of Health and Ministry of Science and Technology of China.

Increased Growth Differentiation Factor 15 Is Associated with Unfavorable Clinical Outcomes of Acute Ischemic Stroke.

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.

Serum Rheumatoid Factor Levels at Acute Phase of Ischemic Stroke are Associated with Poststroke Cognitive Impairment.

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%, P = .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.

Serum Galectin-3 and Poor Outcomes Among Patients With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Elevated galectin-3 has been associated with atherosclerosis and poor outcomes in patients with heart failure. However, it remains unclear whether galectin-3 has any effect on the poor outcomes of ischemic stroke. The aim of the present study was to examine the association between galectin-3 with poor outcomes among patients with acute ischemic stroke. METHODS: Serum galectin-3 was measured in 3082 patients with acute ischemic stroke. The primary outcome was a combination of death or major disability (modified Rankin Scale score, ≥3) at 3 months after stroke. RESULTS: Compared with the lowest quartile of galectin-3, multivariate adjusted odds ratios (95% confidence intervals) for the highest quartile of galectin-3 were 1.55 (1.15-2.09) for composite outcome, 2.10 (0.89-4.95) for death, and 1.43 (1.05-1.93) for major disability. The addition of galectin-3 to the conventional risk factors significantly improved prediction of the combined outcome of death or major disability in patients with ischemic stroke (net reclassification index, 18.9%; P<0.001; integrated discrimination improvement, 0.4%; P=0.001). CONCLUSIONS: Higher levels of serum galectin-3 were independently associated with increased risk of death or major disability after stroke onset, suggesting that galectin-3 may have prognostic value in poor outcomes of ischemic stroke.

Serum Hepatocyte Growth Factor Is Probably Associated With 3-Month Prognosis of Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Serum hepatocyte growth factor (HGF) is positively associated with poor prognosis of heart failure and myocardial infarction, and it can also predict the risk of ischemic stroke in population. The goal of this study was to investigate the association between serum HGF and prognosis of ischemic stroke. METHODS: A total of 3027 acute ischemic stroke patients were included in this post hoc analysis of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). The primary outcome was composite outcome of death or major disability (modified Rankin Scale score ≥3) within 3 months. RESULTS: After multivariate adjustment, elevated HGF levels were associated with an increased risk of primary outcome (odds ratio, 1.50; 95% confidence interval, 1.10-2.03; Ptrend=0.015) when 2 extreme quartiles were compared. Each SD increase of log-transformed HGF was associated with 14% (95% confidence interval, 2%-27%) increased risk of primary outcome. Adding HGF quartiles to a model containing conventional risk factors improved the predictive power for primary outcome (net reclassification improvement: 17.50%, P<0.001; integrated discrimination index: 0.23%, P=0.022). The association between serum HGF and primary outcome could be modified by heparin pre-treatment (Pinteraction=0.001), and a positive linear dose-response relationship between HGF and primary outcome was observed in patients without heparin pre-treatment (Plinearity<0.001) but not in those with heparin pre-treatment. CONCLUSIONS: Serum HGF levels were higher in the more severe stroke at baseline, and elevated HGF levels were probably associated with 3-month poor prognosis independently of stroke severity among ischemic stroke patients, especially in those without heparin pre-treatment. Further studies from other samples of ischemic stroke patients are needed to validate our findings.

The association of angiogenic factors and chronic kidney disease.

BACKGROUND: There are limited data on the associations of circulating angiogenic factors with chronic kidney disease (CKD). We investigate the associations of circulating vascular endothelial growth factor (VEGF)-A, angiopoietin-1, angiopoietin-1/VEGF-A ratio, VEGF receptor 1 (VEGFR-1), VEGFR-2, and pentraxin-3 with CKD. METHODS: We recruited 201 patients with CKD and 201 community controls without CKD from the greater New Orleans area. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or presence of albuminuria. Multivariable quantile and logistic regression models were used to examine the relationship between angiogenesis-related factors and CKD adjusting for confounding factors. RESULTS: After adjusting for covariables including traditional cardiovascular disease (CVD) risk factors, C-reactive protein, and history of CVD, the medians (interquartile range) were 133.08 (90.39, 204.15) in patients with CKD vs. 114.17 (72.45, 170.32) pg/mL in controls without CKD (p = 0.002 for group difference) for VEGF-A; 3951.2 (2471.9, 6656.6) vs. 4270.5 (2763.7, 6537.2) pg/mL (p = 0.70) for angiopoietin-1; 25.87 (18.09, 47.90) vs. 36.55 (25.71, 61.10) (p = 0.0001) for angiopoietin-1/VEGF-A ratio; 147.81 (122.94, 168.79) vs. 144.16 (123.74, 168.05) ng/mL (p = 0.25) for VEGFR-1; 26.20 (22.67, 29.92) vs. 26.28 (23.10, 29.69) ng/mL (p = 0.31) for VEGFR-2; and 1.01 (0.79, 1.49)vs. 0.89 (0.58, 1.18) ng/mL (p = 0.01) for pentraxin-3, respectively. In addition, an elevated VEGF-A level and decreased angiopoietin-1/VEGF-A ratio were associated with increased odds of CKD. CONCLUSIONS: These data indicate that plasma VEGF-A and pentraxin-3 levels were increased and the angiopoietin-1/VEGF-A ratio was decreased in patients with CKD. Future prospective studies are warranted to examine whether angiogenic factors play a role in progression of CKD.

Estimating prevalence of chronic obstructive pulmonary disease in the Southern Cone of Latin America: how different spirometric criteria may affect disease burden and health policies.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. The study aimed to determine and compare the prevalence of COPD in the general population aged 45-74 years old according to fixed ratio and lower limit of normal (LLN) thresholds in four cities in the Southern Cone of Latin America. METHODS: The Pulmonary Risk in South America (PRISA) study used a 4-stage stratified sampling method to select 5814 participants from 4 cities in the Southern Cone of Latin America (Bariloche and Marcos Paz, Argentina; Temuco, Chile; and Pando-Barros Blancos, Uruguay). Data on demographic information, medical history, risk factors, pre-bronchodilator and post-bronchodilator spirometry were obtained using a standard protocol. According to GOLD, COPD was defined as a post-bronchodilator ratio of forced expiratory volume in one second (FEV1) over forced vital capacity (FVC) less than 70%. The LLN threshold was defined as the lower fifth percentile for predicted FEV1/FVC, and was evaluated as an alternative COPD definition. RESULTS: Overall COPD prevalence was 9.3% (95% CI 8.4, 10.2%), and men had a higher prevalence [11.8% (95% CI 10.3, 13.3%)] than women [7.3% (95% CI 6.2, 8.3%)] with the fixed ratio. Overall COPD prevalence using LLN was 4.7% (95% CI 4.1, 5.3%), higher in men: 5.8% (95% CI 4.7, 6.8%) than women: 3.9% (95% CI 3.1, 4.7%). COPD prevalence was significantly higher among those who were older, had

Effect of a Community Health Worker-Led Multicomponent Intervention on Blood Pressure Control in Low-Income Patients in Argentina: A Randomized Clinical Trial.

Importance: Despite extensive knowledge of hypertension treatment, the prevalence of uncontrolled hypertension is high and increasing in low- and middle-income countries. Objective: To test whether a community health worker-led multicomponent intervention would improve blood pressure (BP) control among low-income patients with hypertension. Design, Setting, and Participants: A cluster randomized trial was conducted in 18 centers for primary health care within a national public system providing free medications and health care to uninsured patients in Argentina. A total of 1432 low-income adult patients with uncontrolled hypertension were recruited between June 2013 and April 2015 and followed up to October 2016. Interventions: Nine centers (743 patients) were randomized to the multicomponent intervention, which included a community health worker-led home intervention (health coaching, home BP monitoring, and BP audit and feedback), a physician intervention, and a text-messaging intervention over 18 months. Nine centers (689 patients) were randomized to usual care. Main Outcomes and Measures: The coprimary outcomes were the differences in systolic and diastolic BP changes from baseline to the end of follow-up of patients with hypertension. Secondary outcomes included the proportion of patients with controlled hypertension (BP <140/90 mm Hg). Three BP measurements were obtained at each of 2 baseline and 2 termination visits using a standard protocol, the means of which were used for analyses. Results: Of 1432 participants (mean age, 55.8 years [SD, 13.3]; 772 women [53.0%]), 1357 (94.8%) completed the trial. Baseline mean systolic BP was 151.7 mm Hg for the intervention group and 149.8 mm Hg for the usual care group; the mean diastolic BP was 92.2 mm Hg for the intervention group and 90.1 mm Hg for the usual care group. Systolic BP reduction from baseline to month 18 was 19.3 mm Hg (95% CI, 17.9-20.8 mm Hg) for the intervention group and 12.7 mm Hg (95% CI, 11.3-14.2 mm Hg) for the usual care group; the difference in the reduction was 6.6 mm Hg (95% CI, 4.6-8.6; P < .001). Diastolic BP decreased by 12.2 mm Hg (95% CI, 11.2-13.2 mm Hg) in the intervention group and 6.9 mm Hg (95% CI, 5.9-7.8 mm Hg) in the control group; the difference in the reduction was 5.4 mm Hg (95% CI, 4.0-6.8 mm Hg; P < .001). The proportion of patients with controlled hypertension increased from 17.0% at baseline to 72.9% at 18 months in the intervention group and from 17.6% to 52.2% in the usual care group; the difference in the increase was 20.6% (95% CI, 15.4%-25.9%; P < .001). No adverse events were reported. Conclusions and Relevance: Low-income patients in Argentina with uncontrolled hypertension who participated in a community health worker-led multicomponent intervention experienced a greater decrease in systolic and diastolic BP than did patients who received usual care over 18 months. Further research is needed to assess generalizability and cost-effectiveness of this intervention and to understand which components may have contributed most to the outcome. Trial Registration: clinicaltrials.gov Identifier: NCT01834131.

Antiphosphatidylserine Antibodies and Clinical Outcomes in Patients With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Antiphosphatidylserine antibodies (aPS) have been associated with the risk of ischemic stroke. However, it remains unclear whether aPS will influence clinical outcomes in patients with acute ischemic stroke. METHODS: A total of 3013 patients with acute ischemic stroke recruited from 26 hospitals across China from August 2009 to May 2013 were included in the study The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke. Secondary outcomes included death, major disability, recurrent stroke, and vascular events. RESULTS: Composite outcome of death and major disability rates were 29.1% versus 23.9% in aPS-positive and aPS-negative groups. Compared with aPS-negative, adjusted odds ratios or hazard ratios (95% confidence interval) associated with aPS-positive were 1.35 (1.07-1.71), 1.63 (0.99-2.69), and 1.25 (0.98-1.59) for composite outcome of death or major disability, death, and major disability, respectively. For 1 interquartile range increase of aPS, the adjusted odds ratios or hazard ratios were 1.10 (1.01-1.20), 1.19 (1.05-1.35), and 1.05 (0.96-1.14), respectively. Adding aPS status to a model containing conventional risk factors improved risk prediction for composite outcome of death or major disability (net reclassification improvement index=11.3%, P=0.006; integrated discrimination improvement=0.2%, P=0.04). There was no significant association between aPS and risks of recurrent stroke and vascular events. CONCLUSIONS: We found that positive aPS increased risks of death or major disability at 3 months after an acute ischemic stroke, suggesting that aPS might be a prognostic marker for ischemic stroke.

Early Blood Pressure Reduction in Acute Ischemic Stroke with Various Severities: A Subgroup Analysis of the CATIS Trial.

BACKGROUND: Clinical trials have generally showed a neutral effect of blood pressure (BP) reduction on clinical outcomes among acute ischemic stroke patients. We conducted a prespecified subgroup analysis to assess whether disease severity modifies the effect of early antihypertensive treatment on death and disability among patients with acute ischemic stroke. METHODS: In the China Antihypertensive Trial in Acute Ischemic Stroke, 4,071 patients with acute ischemic stroke and elevated BP were randomly assigned to receive antihypertensive treatment or to discontinue all hypertension medications within 48 h of symptom onset. The primary outcome was a combination of death and major disability at 14 days or hospital discharge. In this subgroup analysis, participants were categorized into 3 groups according to their baseline NIH Stroke Scale (NIHSS) scores (0-4, 5-15, or ≥16). RESULTS: At 24 h after randomization, mean systolic BP differences (95% CIs) were -8.5 (-10.0 to -7.1), -9.8 (-11.4 to -8.3), and -9.1 (-14.4 to -3.8) mm Hg between the treatment and control groups (all p values <0.001) for patients with a baseline NIHSS score of 0-4, 5-15, and ≥16, respectively. At day 7 after randomization, the corresponding mean systolic BP differences were -9.3 (-10.5 to -8.2), -9.1 (-10.3 to -7.8), and -10.1 (-15.1 to -5.1) mm Hg between the treatment and control groups (all p values <0.001). The primary outcome was not significantly different between the treatment and control groups at day 14 or hospital discharge among all NIHSS subgroups (p value for homogeneity = 0.66). ORs (95% CI) associated with treatment were 1.14 (0.87-1.49, p = 0.33), 1.04 (0.86-1.25, p = 0.70), and 0.67 (0.18-2.44, p = 0.54) for patients with a baseline NIHSS score of 0-4, 5-15, and ≥16, respectively. The composite outcome of death and major disability at 3-month follow-up did not differ between the 2 comparison groups for all NIHSS subgroups. In addition, vascular events and recurrent stroke were not significantly different between the 2 comparison groups at the 3-month follow-up visit among all NIHSS subgroups except that there was a suggestive risk reduction for recurrent stroke among those with an NIHSS score of 5-15 (OR 0.45, 95% CI 0.20-0.99, p = 0.05). CONCLUSION: Early BP reduction with antihypertensive medications did not reduce or increase the risk of death, major disabilities, recurrent instances of stroke, and vascular events in acute ischemic stroke patients with a variety of disease severities.

A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010.

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease, and premature death. Here we estimated the global prevalence and absolute burden of CKD in 2010 by pooling data from population-based studies. We searched MEDLINE (January 1990 to December 2014), International Society of Nephrology Global Outreach Program-funded projects, and bibliographies of retrieved articles and selected 33 studies reporting gender- and age-specific prevalence of CKD in representative population samples. The age-standardized global prevalence of CKD stages 1-5 in adults aged 20 and older was 10.4% in men (95% confidence interval 9.3-11.9%) and 11.8% in women (11.2-12.6%). This consisted of 8.6% in men (7.3-9.8%) and 9.6% in women (7.7-11.1%) in high-income countries, and 10.6% in men (9.4-13.1%) and 12.5% in women (11.8-14.0%) in low- and middle-income countries. The total number of adults with CKD was 225.7 million (205.7-257.4 million) men and 271.8 million (258.0-293.7 million) women. This consisted of 48.3 million (42.3-53.3 million) men and 61.7 million (50.4-69.9 million) women in high-income countries, and 177.4 million (159.2-215.9 million) men and 210.1 million (200.8-231.7 million) women in low- and middle-income countries. Thus, CKD is an important global-health challenge, especially in low- and middle-income countries. National and international efforts for prevention, detection, and treatment of CKD are needed to reduce its morbidity and mortality worldwide.

Association of C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 with chronic kidney disease.

BACKGROUND: We studied the association of inflammatory biomarkers including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) with chronic kidney disease (CKD). METHODS: We conducted a case-control study among 201 CKD patients and 201 community-based controls in the greater New Orleans area. CKD was defined as estimated-glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) or albuminuria ≥30 mg/24-h. Serum CRP, TNF-α, and IL-6 were measured using standard methods. Multivariable regression models were used to examine associations between the inflammatory biomarkers and CKD adjusting for important CKD risk factors, history of cardiovascular disease, and use of antihypertensive, antidiabetic, and lipid-lowering agents and aspirin. RESULTS: The multivariable-adjusted medians (interquartile-range) were 2.91 (1.47, 5.24) mg/L in patients with CKD vs. 1.91 (0.99, 3.79) mg/L in controls without CKD (p = 0.39 for group difference) for CRP; 1.86 (1.51, 2.63) pg/mL vs. 1.26 (1.01, 1.98) pg/mL (p < 0.0001) for TNF-α; and 2.53 (1.49, 4.42) pg/mL vs. 1.39 (0.95, 2.15) pg/mL (p = 0.04) for IL-6, respectively. Compared to the lowest tertile, the highest tertile of TNF-α (OR 7.1, 95% CI 3.2 to 15.5) and IL-6 (OR 2.5, 95% CI 1.1 to 5.5) were significantly associated with higher odds of CKD in multivariable-adjusted models. Additionally, higher TNF-α and IL-6 were independently and significantly associated with lower eGFR and higher albuminuria. CONCLUSIONS: Our data suggest that TNF-α and IL-6, but not CRP, are associated with the prevalence and severity of CKD, independent from established CKD risk factors, history of cardiovascular disease, and use of antihypertensive, antidiabetic, and lipid-lowering agents and aspirin.

Effects of low-carbohydrate and low-fat diets: a randomized trial.

BACKGROUND: Low-carbohydrate diets are popular for weight loss, but their cardiovascular effects have not been well-studied, particularly in diverse populations. OBJECTIVE: To examine the effects of a low-carbohydrate diet compared with a low-fat diet on body weight and cardiovascular risk factors. DESIGN: A randomized, parallel-group trial. (ClinicalTrials.gov: NCT00609271). SETTING: A large academic medical center. PARTICIPANTS: 148 men and women without clinical cardiovascular disease and diabetes. INTERVENTION: A low-carbohydrate (<40 g/d) or low-fat (<30% of daily energy intake from total fat [<7% saturated fat]) diet. Both groups received dietary counseling at regular intervals throughout the trial. MEASUREMENTS: Data on weight, cardiovascular risk factors, and dietary composition were collected at 0, 3, 6, and 12 months. RESULTS: Sixty participants (82%) in the low-fat group and 59 (79%) in the low-carbohydrate group completed the intervention. At 12 months, participants on the low-carbohydrate diet had greater decreases in weight (mean difference in change, -3.5 kg [95% CI, -5.6 to -1.4 kg]; P = 0.002), fat mass (mean difference in change, -1.5% [CI, -2.6% to -0.4%]; P = 0.011), ratio of total-high-density lipoprotein (HDL) cholesterol (mean difference in change, -0.44 [CI, -0.71 to -0.16]; P = 0.002), and triglyceride level (mean difference in change, -0.16 mmol/L [-14.1 mg/dL] [CI, -0.31 to -0.01 mmol/L {-27.4 to -0.8 mg/dL}]; P = 0.038) and greater increases in HDL cholesterol level (mean difference in change, 0.18 mmol/L [7.0 mg/dL] [CI, 0.08 to 0.28 mmol/L {3.0 to 11.0 mg/dL}]; P < 0.001) than those on the low-fat diet. LIMITATION: Lack of clinical cardiovascular disease end points. CONCLUSION: The low-carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low-fat diet. Restricting carbohydrate may be an option for persons seeking to lose weight and reduce cardiovascular risk factors. PRIMARY FUNDING SOURCE: National Institutes of Health.

Effects of immediate blood pressure reduction on death and major disability in patients with acute ischemic stroke: the CATIS randomized clinical trial.

IMPORTANCE: Although the benefit of reducing blood pressure for primary and secondary prevention of stroke has been established, the effect of antihypertensive treatment in patients with acute ischemic stroke is uncertain. OBJECTIVE: To evaluate whether immediate blood pressure reduction in patients with acute ischemic stroke would reduce death and major disability at 14 days or hospital discharge. DESIGN, SETTING, AND PARTICIPANTS: The China Antihypertensive Trial in Acute Ischemic Stroke, a single-blind, blinded end-points randomized clinical trial, conducted among 4071 patients with nonthrombolysed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were recruited from 26 hospitals across China between August 2009 and May 2013. INTERVENTIONS: Patients (n = 2038) were randomly assigned to receive antihypertensive treatment (aimed at lowering systolic blood pressure by 10% to 25% within the first 24 hours after randomization, achieving blood pressure less than 140/90 mm Hg within 7 days, and maintaining this level during hospitalization) or to discontinue all antihypertensive medications (control) during hospitalization (n = 2033). MAIN OUTCOMES AND MEASURES: Primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 14 days or hospital discharge. RESULTS: Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg (-12.7%) within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg (-7.2%) in the control group within 24 hours after randomization (difference, -5.5% [95% CI, -4.9 to -6.1%]; absolute difference, -9.1 mm Hg [95% CI, -10.2 to -8.1]; P < .001). Mean systolic blood pressure was 137.3 mm Hg in the antihypertensive treatment group and 146.5 mm Hg in the control group at day 7 after randomization (difference, -9.3 mm Hg [95% CI, -10.1 to -8.4]; P < .001). The primary outcome did not differ between treatment groups (683 events [antihypertensive treatment] vs 681 events [control]; odds ratio, 1.00 [95% CI, 0.88 to 1.14]; P = .98) at 14 days or hospital discharge. The secondary composite outcome of death and major disability at 3-month posttreatment follow-up did not differ between treatment groups (500 events [antihypertensive treatment] vs 502 events [control]; odds ratio, 0.99 [95% CI, 0.86 to 1.15]; P = .93). CONCLUSION AND RELEVANCE: Among patients with acute ischemic stroke, blood pressure reduction with antihypertensive medications, compared with the absence of hypertensive medication, did not reduce the likelihood of death and major disability at 14 days or hospital discharge. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01840072.