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1.
BMJ Glob Health ; 5(11)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33148540

RESUMO

OBJECTIVES: We aimed to examine the relationship between access to medicine for cardiovascular disease (CVD) and major adverse cardiovascular events (MACEs) among people at high risk of CVD in high-income countries (HICs), upper and lower middle-income countries (UMICs, LMICs) and low-income countries (LICs) participating in the Prospective Urban Rural Epidemiology (PURE) study. METHODS: We defined high CVD risk as the presence of any of the following: hypertension, coronary artery disease, stroke, smoker, diabetes or age >55 years. Availability and affordability of blood pressure lowering drugs, antiplatelets and statins were obtained from pharmacies. Participants were categorised: group 1-all three drug types were available and affordable, group 2-all three drugs were available but not affordable and group 3-all three drugs were not available. We used multivariable Cox proportional hazard models with nested clustering at country and community levels, adjusting for comorbidities, sociodemographic and economic factors. RESULTS: Of 163 466 participants, there were 93 200 with high CVD risk from 21 countries (mean age 54.7, 49% female). Of these, 44.9% were from group 1, 29.4% from group 2 and 25.7% from group 3. Compared with participants from group 1, the risk of MACEs was higher among participants in group 2 (HR 1.19, 95% CI 1.07 to 1.31), and among participants from group 3 (HR 1.25, 95% CI 1.08 to 1.50). CONCLUSION: Lower availability and affordability of essential CVD medicines were associated with higher risk of MACEs and mortality. Improving access to CVD medicines should be a key part of the strategy to lower CVD globally.

2.
Am J Hypertens ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33197265

RESUMO

BACKGROUND: Although low sodium intake (<2g/day) and high potassium intake (>3·5g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke and its subtypes. METHODS: We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls (8,761 matched pairs for conditional analysis) from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes. RESULTS: The mean estimated 24-hour sodium and potassium urinary excretion was 3·29g/day and 1·57g/day, with 0·01% of participants having both low sodium (<2·0g/day) and high potassium excretion (>3·5g/day). There was a moderate positive correlation between sodium and potassium excretion (r=0·4435, P<0.001) and between sodium excretion and blood pressure (P<0.001). Compared with an estimated urinary sodium excretion of 2·8-3·5g/day (second quartile, reference), higher (>4·26g/day) (OR 1.81;95%CI,1.65-2.00) and lower (<2·8g/day) sodium excretion (OR 1.39;95%CI,1.26-1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4·26g/day) was significantly greater (P<0.001) for intracerebral haemorrhage (ICH) (OR 2.38;95%CI,1.93-2.92) than for ischemic stroke (OR 1.67;95%CI,1.50-1.87), and greater for large vessel and small vessel ischemic stroke than for cardioembolic ischemic stroke. Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P=0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1·58g/day) and moderate sodium intake (2.8-3.5 g/day) was associated with the lowest risk of stroke. CONCLUSION: The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for intracerebral haemorrhage than ischemic stroke. Our data suggest that moderate sodium intake - rather than low sodium intake - combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.

3.
Eur Heart J ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33197271

RESUMO

OBJECTIVE : Recent European Guidelines for Diabetes, Prediabetes and Cardiovascular Diseases introduced a shift in managing patients with type 2 diabetes at high risk for or established cardiovascular (CV) disease by recommending GLP-1 receptor agonists and SGLT-2 inhibitors as initial glucose-lowering therapy. This is questioned since outcome trials of these drug classes had metformin as background therapy. In this post hoc analysis, the effect of dulaglutide on CV events was investigated according to the baseline metformin therapy by means of a subgroup analysis of the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial. RESEARCH DESIGN AND METHODS : Patients in REWIND (n = 9901; women: 46.3%; mean age: 66.2 years) had type 2 diabetes and either a previous CV event (31%) or high CV risk (69%). They were randomized (1:1) to sc. dulaglutide (1.5 mg/weekly) or placebo in addition to standard of care. The primary outcome was the first of a composite of nonfatal myocardial infarction, nonfatal stroke, and death from cardiovascular or unknown causes. Key secondary outcomes included a microvascular composite endpoint, all-cause death, and heart failure. The effect of dulaglutide in patients with and without baseline metformin was evaluated by a Cox regression hazard model with baseline metformin, dulaglutide assignment, and their interaction as independent variables. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by a Cox regression model with adjustments for factors differing at baseline between people with vs. without metformin, identified using the backward selection. RESULTS : Compared to patients with metformin at baseline (n = 8037; 81%), those without metformin (n = 1864; 19%) were older and slightly less obese and had higher proportions of women, prior CV events, heart failure, and renal disease. The primary outcome occurred in 976 (12%) participants with baseline metformin and in 281 (15%) without. There was no significant difference in the effect of dulaglutide on the primary outcome in patients with vs. without metformin at baseline [HR 0.92 (CI 0.81-1.05) vs. 0.78 (CI 0.61-0.99); interaction P = 0.18]. Findings for key secondary outcomes were similar in patients with and without baseline metformin. CONCLUSION : This analysis suggests that the cardioprotective effect of dulaglutide is unaffected by the baseline use of metformin therapy.

4.
Rev Bras Ter Intensiva ; 32(3): 354-362, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-33053024

RESUMO

OBJECTIVE: The infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads worldwide and is considered a pandemic. The most common manifestation of SARS-CoV-2 infection (coronavirus disease 2019 - COVID-19) is viral pneumonia with varying degrees of respiratory compromise and up to 40% of hospitalized patients might develop acute respiratory distress syndrome. Several clinical trials evaluated the role of corticosteroids in non-COVID-19 acute respiratory distress syndrome with conflicting results. We designed a trial to evaluate the effectiveness of early intravenous dexamethasone administration on the number of days alive and free of mechanical ventilation within 28 days after randomization in adult patients with moderate or severe acute respiratory distress syndrome due to confirmed or probable COVID-19. METHODS: This is a pragmatic, prospective, randomized, stratified, multicenter, open-label, controlled trial including 350 patients with early-onset (less than 48 hours before randomization) moderate or severe acute respiratory distress syndrome, defined by the Berlin criteria, due to COVID-19. Eligible patients will be randomly allocated to either standard treatment plus dexamethasone (Intervention Group) or standard treatment without dexamethasone (Control Group). Patients in the intervention group will receive dexamethasone 20mg intravenous once daily for 5 days, followed by dexamethasone 10mg IV once daily for additional 5 days or until intensive care unit discharge, whichever occurs first. The primary outcome is ventilator-free days within 28 days after randomization, defined as days alive and free from invasive mechanical ventilation. Secondary outcomes are all-cause mortality rates at day 28, evaluation of the clinical status at day 15 assessed with a 6-level ordinal scale, mechanical ventilation duration from randomization to day 28, Sequential Organ Failure Assessment Score evaluation at 48 hours, 72 hours and 7 days and intensive care unit -free days within 28.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Adulto , Infecções por Coronavirus/fisiopatologia , Humanos , Unidades de Terapia Intensiva , Escores de Disfunção Orgânica , Pandemias , Pneumonia Viral/fisiopatologia , Estudos Prospectivos , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/virologia , Fatores de Tempo
5.
Diabetes Care ; 43(12): 3094-3101, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33060076

RESUMO

OBJECTIVE: We aimed to compare cardiovascular (CV) events, all-cause mortality, and CV mortality rates among adults with and without diabetes in countries with differing levels of income. RESEARCH DESIGN AND METHODS: The Prospective Urban Rural Epidemiology (PURE) study enrolled 143,567 adults aged 35-70 years from 4 high-income countries (HIC), 12 middle-income countries (MIC), and 5 low-income countries (LIC). The mean follow-up was 9.0 ± 3.0 years. RESULTS: Among those with diabetes, CVD rates (LIC 10.3, MIC 9.2, HIC 8.3 per 1,000 person-years, P < 0.001), all-cause mortality (LIC 13.8, MIC 7.2, HIC 4.2 per 1,000 person-years, P < 0.001), and CV mortality (LIC 5.7, MIC 2.2, HIC 1.0 per 1,000 person-years, P < 0.001) were considerably higher in LIC compared with MIC and HIC. Within LIC, mortality was higher in those in the lowest tertile of wealth index (low 14.7%, middle 10.8%, and high 6.5%). In contrast to HIC and MIC, the increased CV mortality in those with diabetes in LIC remained unchanged even after adjustment for behavioral risk factors and treatments (hazard ratio [95% CI] 1.89 [1.58-2.27] to 1.78 [1.36-2.34]). CONCLUSIONS: CVD rates, all-cause mortality, and CV mortality were markedly higher among those with diabetes in LIC compared with MIC and HIC with mortality risk remaining unchanged even after adjustment for risk factors and treatments. There is an urgent need to improve access to care to those with diabetes in LIC to reduce the excess mortality rates, particularly among those in the poorer strata of society.

6.
Rev Bras Ter Intensiva ; 32(3): 337-347, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32965395

RESUMO

INTRODUCTION: Pro-inflammatory markers play a significant role in the disease severity of patients with COVID-19. Thus, anti-inflammatory therapies are attractive agents for potentially combating the uncontrolled inflammatory cascade in these patients. We designed a trial testing tocilizumab versus standard of care intending to improve the outcomes by inhibiting interleukin-6, an important inflammatory mediator in COVID-19. METHODS AND ANALYSIS: This open-label multicentre randomized controlled trial will compare clinical outcomes of tocilizumab plus standard of care versus standard of care alone in patients with moderate to severe COVID-19. Two of the following four criteria are required for protocol enrolment: D-dimer > 1,000ng/mL; C reactive protein > 5mg/dL, ferritin > 300mg/dL, and lactate dehydrogenase > upper limit of normal. The primary objective will be to compare the clinical status on day 15, as measured by a 7-point ordinal scale applied in COVID-19 trials worldwide. The primary endpoint will be assessed by an ordinal logistic regression assuming proportional odds ratios adjusted for stratification variables (age and sex). ETHICS AND DISSEMINATION: The TOCIBRAS protocol was approved by local and central (national) ethical committees in Brazil following current national and international guidelines/directives. Each participating center had the study protocol approved by their institutional review boards before initiating protocol enrolment. The data derived from this trial will be published regardless of the results. If proven active, this strategy could alleviate the consequences of the inflammatory response in COVID-19 patients and improve their clinical outcomes.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anticorpos Monoclonais Humanizados/farmacologia , Brasil , Infecções por Coronavirus/fisiopatologia , Humanos , Interleucina-6/antagonistas & inibidores , Pandemias , Pneumonia Viral/fisiopatologia , Índice de Gravidade de Doença
7.
JAMA ; 324(13): 1307-1316, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32876695

RESUMO

Importance: Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients. Objective: To determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19-associated ARDS. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted in 41 intensive care units (ICUs) in Brazil. Patients with COVID-19 and moderate to severe ARDS, according to the Berlin definition, were enrolled from April 17 to June 23, 2020. Final follow-up was completed on July 21, 2020. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients. Interventions: Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n =151) or standard care alone (n = 148). Main Outcomes and Measures: The primary outcome was ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Secondary outcomes were all-cause mortality at 28 days, clinical status of patients at day 15 using a 6-point ordinal scale (ranging from 1, not hospitalized to 6, death), ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, and Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) at 48 hours, 72 hours, and 7 days. Results: A total of 299 patients (mean [SD] age, 61 [14] years; 37% women) were enrolled and all completed follow-up. Patients randomized to the dexamethasone group had a mean 6.6 ventilator-free days (95% CI, 5.0-8.2) during the first 28 days vs 4.0 ventilator-free days (95% CI, 2.9-5.4) in the standard care group (difference, 2.26; 95% CI, 0.2-4.38; P = .04). At 7 days, patients in the dexamethasone group had a mean SOFA score of 6.1 (95% CI, 5.5-6.7) vs 7.5 (95% CI, 6.9-8.1) in the standard care group (difference, -1.16; 95% CI, -1.94 to -0.38; P = .004). There was no significant difference in the prespecified secondary outcomes of all-cause mortality at 28 days, ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, or the 6-point ordinal scale at 15 days. Thirty-three patients (21.9%) in the dexamethasone group vs 43 (29.1%) in the standard care group experienced secondary infections, 47 (31.1%) vs 42 (28.3%) needed insulin for glucose control, and 5 (3.3%) vs 9 (6.1%) experienced other serious adverse events. Conclusions and Relevance: Among patients with COVID-19 and moderate or severe ARDS, use of intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04327401.


Assuntos
Anti-Inflamatórios/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Dexametasona/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Respiração Artificial/estatística & dados numéricos , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Administração Intravenosa , Idoso , Anti-Inflamatórios/efeitos adversos , Betacoronavirus , Brasil , Infecções Relacionadas a Cateter/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Dexametasona/efeitos adversos , Término Precoce de Ensaios Clínicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório do Adulto/etiologia
8.
Stroke ; 51(10): 2901-2909, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32951537

RESUMO

BACKGROUND AND PURPOSE: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. METHODS: Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. RESULTS: At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38-0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37-1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27-1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. CONCLUSIONS: Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.


Assuntos
Aspirina/uso terapêutico , Infarto Encefálico/prevenção & controle , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Idoso , Infarto Encefálico/complicações , Infarto Encefálico/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Quimioterapia Combinada , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Resultado do Tratamento
9.
Lancet ; 396(10256): 959-967, 2020 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-32896292

RESUMO

BACKGROUND: The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19. METHODS: We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278. FINDINGS: 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94-1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups. INTERPRETATION: In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19. FUNDING: COALITION COVID-19 Brazil and EMS.


Assuntos
Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso , Antivirais/efeitos adversos , Azitromicina/efeitos adversos , Betacoronavirus , Brasil/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Quimioterapia Combinada , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Terapia Respiratória , Padrão de Cuidado , Resultado do Tratamento
10.
JAMA Cardiol ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32997098

RESUMO

Importance: Patients with symptomatic lower extremity peripheral artery disease (LE-PAD) experience an increased risk of major vascular events. There is limited information on what clinical features of symptomatic LE-PAD prognosticate major vascular events and whether patients at high risk have a greater absolute benefit from low-dose rivaroxaban and aspirin. Objective: To quantify the risk of major vascular events and investigate the response to treatment with low-dose rivaroxaban and aspirin among patients with symptomatic LE-PAD based on clinical presentation and comorbidities. Design, Setting, and Participants: This is a subanalysis of a previously reported subgroup of patients with symptomatic LE-PAD who were enrolled in a large, double-blind, placebo-controlled randomized clinical trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies [COMPASS]) in 602 centers in 33 countries from March 2013 to January 2020. Data analysis was completed from May 2016 to June 2020. Interventions: A combination of low-dose rivaroxaban and aspirin compared with aspirin alone. Main Outcomes and Measures: Thirty-month incidence risk of myocardial infarction, stroke and cardiovascular death (MACE), major adverse limb events (MALE) including major vascular amputation, and bleeding. Results: The COMPASS trial enrolled 4129 patients with symptomatic LE-PAD (mean [SD] age, 66.8 [8.8] years; 2932 men [71.0%]). The 30-month Kaplan-Meier incidence risk of MACE or MALE, including major amputation, was 22.6% in those with prior amputation (this outcome was observed in 54 patients), 17.6% (n = 15) in those with Fontaine III or IV symptoms, and 11.8% (n = 142) in those with previous peripheral artery revascularization, classifying these features as high-risk limb presentations. The 30-month incidence risk of MACE or MALE, including major amputation, was 14.1% (n = 118) in those with kidney dysfunction, 13.5% (n = 67) in those with heart failure, 13.4% (n = 199) in those with diabetes, and 12.8% (n = 222) in those with polyvascular disease, classifying these features as high-risk comorbidities. Among patients with either high-risk limb presentations or high-risk comorbidities, treatment with rivaroxaban and aspirin compared with aspirin alone was associated with an estimated 4.2% (95% CI, 1.9%-6.2%) absolute risk reduction for MACE or MALE, including major amputation, at 30 months. Although the estimated absolute risk increase of major bleeding was higher with rivaroxaban and aspirin in combination than aspirin alone (2.0% [95% CI, 0.5%-3.9%]) for patients with either high-risk limb presentation or high-risk comorbidity, the estimated absolute risk increase of fatal or critical organ bleeding was low in this high-risk group (0.4% [95% CI, 0.2%-1.8%]), such that the net clinical benefit was estimated to be 3.2% (95% CI, 0.6%-5.3%). Conclusions and Relevance: Patients with LE-PAD with high-risk limb presentations or high-risk comorbidities had a high incidence of major vascular events. For these patients, treatment with rivaroxaban and aspirin in combination compared with aspirin alone led to a large absolute reduction in vascular risk.

11.
Diabetes Care ; 43(11): 2643-2650, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32873587

RESUMO

OBJECTIVE: Previous prospective studies on the association of white rice intake with incident diabetes have shown contradictory results but were conducted in single countries and predominantly in Asia. We report on the association of white rice with risk of diabetes in the multinational Prospective Urban Rural Epidemiology (PURE) study. RESEARCH DESIGN AND METHODS: Data on 132,373 individuals aged 35-70 years from 21 countries were analyzed. White rice consumption (cooked) was categorized as <150, ≥150 to <300, ≥300 to <450, and ≥450 g/day, based on one cup of cooked rice = 150 g. The primary outcome was incident diabetes. Hazard ratios (HRs) were calculated using a multivariable Cox frailty model. RESULTS: During a mean follow-up period of 9.5 years, 6,129 individuals without baseline diabetes developed incident diabetes. In the overall cohort, higher intake of white rice (≥450 g/day compared with <150 g/day) was associated with increased risk of diabetes (HR 1.20; 95% CI 1.02-1.40; P for trend = 0.003). However, the highest risk was seen in South Asia (HR 1.61; 95% CI 1.13-2.30; P for trend = 0.02), followed by other regions of the world (which included South East Asia, Middle East, South America, North America, Europe, and Africa) (HR 1.41; 95% CI 1.08-1.86; P for trend = 0.01), while in China there was no significant association (HR 1.04; 95% CI 0.77-1.40; P for trend = 0.38). CONCLUSIONS: Higher consumption of white rice is associated with an increased risk of incident diabetes with the strongest association being observed in South Asia, while in other regions, a modest, nonsignificant association was seen.

12.
Eur. j. prev. cardiol ; 27(3): 1-12, Ago. 2020. gráfico, tabela
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1050001

RESUMO

Abstract Aims: Secondary prevention in patients with coronary artery disease and peripheral artery disease involves antithrombotic therapy and optimal control of cardiovascular risk factors. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) study, adding low-dose rivaroxaban on top of aspirin lowered cardiovascular events, but there is limited data about risk factor control in secondary prevention. We studied the association between risk factor status and outcomes, and the impact of risk factor status on the treatment effect of rivaroxaban, in a large contemporary population of patients with coronary artery disease or peripheral artery disease. Methods and results: We reported ischemic events (cardiovascular death, stroke, or myocardial infarction) in participants from the randomized, double-blind COMPASS study by individual risk factor (blood pressure, smoking status, cholesterol level, presence of diabetes, body mass index, and level of physical activity), and by number of risk factors. We compared rates and hazard ratios of patients treated with rivaroxaban plus aspirin vs aspirin alone within each risk factor category and tested for interaction between risk factor status and antithrombotic regimen. Complete baseline risk factor status was available in 27,117 (99%) patients. Status and number of risk factors were both associated with increased risk of ischemic events. Rates of ischemic events (hazard ratio 2.2; 95% confidence interval 1.8­2.6) and cardiovascular death (hazard ratio 2.0; 1.5­2.7) were more than twofold higher in patients with 4­6 compared with 0­1 risk factors (p<0.0001 for both). Rivaroxaban reduced event rates independently of the number of risk factors (p interaction 0.93), with the largest absolute benefit in patients with the highest number of risk factors. Conclusion: More favorable risk factor status and low-dose rivaroxaban were independently associated with lower risk of cardiovascular events. (AU)


Assuntos
Doença da Artéria Coronariana , Prevenção Secundária
13.
Cardiovasc Res ; 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32777820

RESUMO

AIMS: To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine anti-thrombotic use and clinical outcomes. METHODS AND RESULTS: Baseline ECGs were collected in 153,152 middle-aged participants (ages 35 to 70 years) to document AF in two community-based studies, spanning 20 countries. Medication use and clinical outcome data (mean follow up of 7.4 years) were available in one cohort. Cross sectional analyses were performed to document the prevalence of AF and medication use, and associations between AF and clinical events were examined prospectively. Mean age of participants was 52.1 years, and 57.7% were female. Age and sex-standardized prevalence of AF varied 12-fold between regions; with the highest in North America, Europe, China and Southeast Asia (270-360 cases per 100,000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100,000 persons)(p < 0.001). Compared with low-income countries (LICs), AF prevalence was 7-fold higher in middle-income countries (MICs) and 11-fold higher in high-income countries (HICs)(p < 0.001). Differences in AF prevalence remained significant after adjusting for traditional AF risk factors. In LICs/MICs, 24% of participants with AF and a CHADS2 score ≥1 received anti-thrombotic therapy, compared with 85% in HICs. AF was associated with an increased risk of stroke (hazard ratio [HR: 2.29; 95% confidence interval [CI] 1.49-3.52) and death (HR: 2.97; 95% CI 2.25-3.93); with similar rates in different country income levels. CONCLUSIONS: Large variations in AF prevalence occur in different regions and country income settings, but this is only partially explained by traditional AF risk factors. Anti-thrombotic therapy is infrequently used in poorer countries despite the high risk of stroke associated with AF. TRANSLATIONAL PERSPECTIVE: We examined atrial fibrillation (AF) prevalence in 153,152 middle-aged participants spanning 20 countries. Age and sex-standardized prevalence of AF varied by as much as 12-fold between regions; highest in North America, Europe, China and Southeast Asia (270-360 cases per 100,000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100,000 persons)(p < 0.001); and by as much as 11-fold between groups of countries at different income levels (p < 0.001). Global variations were poorly explained by traditional AF risk factors. Future studies are needed to understand the predominant determinants driving the variation in AF burden across different regions of the world.

14.
N Engl J Med ; 383(21): 2041-2052, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32706953

RESUMO

BACKGROUND: Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. METHODS: We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. RESULTS: A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. CONCLUSIONS: Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).

15.
Europace ; 22(6): 870-877, June., 2020. tab., ilus.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1123436

RESUMO

ABSTRACT: Aims Data on patient characteristics, prevalence, and outcomes of atrial fibrillation (AF) patients without traditional risk factors, often labelled 'lone AF', are sparse. METHODS AND RESULTS: The RE-LY AF registry included 15 400 individuals who presented to emergency departments with AF in 47 countries. This analysis focused on patients without traditional risk factors, including age ≥60 years, hypertension, coronary artery disease, heart failure, left ventricular hypertrophy, congenital heart disease, pulmonary disease, valve heart disease, hyperthyroidism, and prior cardiac surgery. Patients without traditional risk factors were compared with age- and region-matched controls with traditional risk factors (1:3 fashion). In 796 (5%) patients, no traditional risk factors were present. However, 98% (779/796) had less-established or borderline risk factors, including borderline hypertension (130-140/80-90 mmHg; 47%), chronic kidney disease (eGFR < 60 mL/min; 57%), obesity (body mass index > 30; 19%), diabetes (5%), excessive alcohol intake (>14 units/week; 4%), and smoking (25%). Compared with patients with traditional risk factors (n = 2388), patients without traditional risk factors were more often men (74% vs. 59%, P < 0.001) had paroxysmal AF (55% vs. 37%, P < 0.001) and less AF persistence after 1 year (21% vs. 49%, P < 0.001). Furthermore, 1-year stroke occurrence rate (0.6% vs. 2.0%, P = 0.013) and heart failure hospitalizations (0.9% vs. 12.5%, P < 0.001) were lower. However, risk of AF-related re-hospitalization was similar (18% vs. 21%, P = 0.09). CONCLUSION: Almost all patients without traditionally defined AF risk factors have less-established or borderline risk factors. These patients have a favourable 1-year prognosis, but risk of AF-related re-hospitalization remains high. Greater emphasis should be placed on recognition and management of less-established or borderline risk factors.


Assuntos
Fibrilação Atrial , Transtorno da Personalidade Borderline , Fatores de Risco
16.
Lancet Planet Health ; 4(6): e235-e245, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32559440

RESUMO

BACKGROUND: Most studies of long-term exposure to outdoor fine particulate matter (PM2·5) and cardiovascular disease are from high-income countries with relatively low PM2·5 concentrations. It is unclear whether risks are similar in low-income and middle-income countries (LMICs) and how outdoor PM2·5 contributes to the global burden of cardiovascular disease. In our analysis of the Prospective Urban and Rural Epidemiology (PURE) study, we aimed to investigate the association between long-term exposure to PM2·5 concentrations and cardiovascular disease in a large cohort of adults from 21 high-income, middle-income, and low-income countries. METHODS: In this multinational, prospective cohort study, we studied 157 436 adults aged 35-70 years who were enrolled in the PURE study in countries with ambient PM2·5 estimates, for whom follow-up data were available. Cox proportional hazard frailty models were used to estimate the associations between long-term mean community outdoor PM2·5 concentrations and cardiovascular disease events (fatal and non-fatal), cardiovascular disease mortality, and other non-accidental mortality. FINDINGS: Between Jan 1, 2003, and July 14, 2018, 157 436 adults from 747 communities in 21 high-income, middle-income, and low-income countries were enrolled and followed up, of whom 140 020 participants resided in LMICs. During a median follow-up period of 9·3 years (IQR 7·8-10·8; corresponding to 1·4 million person-years), we documented 9996 non-accidental deaths, of which 3219 were attributed to cardiovascular disease. 9152 (5·8%) of 157 436 participants had cardiovascular disease events (fatal and non-fatal incident cardiovascular disease), including 4083 myocardial infarctions and 4139 strokes. Mean 3-year PM2·5 at cohort baseline was 47·5 µg/m3 (range 6-140). In models adjusted for individual, household, and geographical factors, a 10 µg/m3 increase in PM2·5 was associated with increased risk for cardiovascular disease events (hazard ratio 1·05 [95% CI 1·03-1·07]), myocardial infarction (1·03 [1·00-1·05]), stroke (1·07 [1·04-1·10]), and cardiovascular disease mortality (1·03 [1·00-1·05]). Results were similar for LMICs and communities with high PM2·5 concentrations (>35 µg/m3). The population attributable fraction for PM2·5 in the PURE cohort was 13·9% (95% CI 8·8-18·6) for cardiovascular disease events, 8·4% (0·0-15·4) for myocardial infarction, 19·6% (13·0-25·8) for stroke, and 8·3% (0·0-15·2) for cardiovascular disease mortality. We identified no consistent associations between PM2·5 and risk for non-cardiovascular disease deaths. INTERPRETATION: Long-term outdoor PM2·5 concentrations were associated with increased risks of cardiovascular disease in adults aged 35-70 years. Air pollution is an important global risk factor for cardiovascular disease and a need exists to reduce air pollution concentrations, especially in LMICs, where air pollution levels are highest. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

17.
JAMA Psychiatry ; 77(10): 1052-1063, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32520341

RESUMO

Importance: Depression is associated with incidence of and premature death from cardiovascular disease (CVD) and cancer in high-income countries, but it is not known whether this is true in low- and middle-income countries and in urban areas, where most people with depression now live. Objective: To identify any associations between depressive symptoms and incident CVD and all-cause mortality in countries at different levels of economic development and in urban and rural areas. Design, Setting, and Participants: This multicenter, population-based cohort study was conducted between January 2005 and June 2019 (median follow-up, 9.3 years) and included 370 urban and 314 rural communities from 21 economically diverse countries on 5 continents. Eligible participants aged 35 to 70 years were enrolled. Analysis began February 2018 and ended September 2019. Exposures: Four or more self-reported depressive symptoms from the Short-Form Composite International Diagnostic Interview. Main Outcomes and Measures: Incident CVD, all-cause mortality, and a combined measure of either incident CVD or all-cause mortality. Results: Of 145 862 participants, 61 235 (58%) were male and the mean (SD) age was 50.05 (9.7) years. Of those, 15 983 (11%) reported 4 or more depressive symptoms at baseline. Depression was associated with incident CVD (hazard ratio [HR], 1.14; 95% CI, 1.05-1.24), all-cause mortality (HR, 1.17; 95% CI, 1.11-1.25), the combined CVD/mortality outcome (HR, 1.18; 95% CI, 1.11-1.24), myocardial infarction (HR, 1.23; 95% CI, 1.10-1.37), and noncardiovascular death (HR, 1.21; 95% CI, 1.13-1.31) in multivariable models. The risk of the combined outcome increased progressively with number of symptoms, being highest in those with 7 symptoms (HR, 1.24; 95% CI, 1.12-1.37) and lowest with 1 symptom (HR, 1.05; 95% CI, 0.92 -1.19; P for trend < .001). The associations between having 4 or more depressive symptoms and the combined outcome were similar in 7 different geographical regions and in countries at all economic levels but were stronger in urban (HR, 1.23; 95% CI, 1.13-1.34) compared with rural (HR, 1.10; 95% CI, 1.02-1.19) communities (P for interaction = .001) and in men (HR, 1.27; 95% CI, 1.13-1.38) compared with women (HR, 1.14; 95% CI, 1.06-1.23; P for interaction < .001). Conclusions and Relevance: In this large, population-based cohort study, adults with depressive symptoms were associated with having increased risk of incident CVD and mortality in economically diverse settings, especially in urban areas. Improving understanding and awareness of these physical health risks should be prioritized as part of a comprehensive strategy to reduce the burden of noncommunicable diseases worldwide.

18.
Am Heart J ; 225: 69-77, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32474206

RESUMO

BACKGROUND: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need. METHODS: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD. CONCLUSION: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Embolia/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Cardiopatia Reumática/tratamento farmacológico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Vitamina K/antagonistas & inibidores , Adulto , Idoso , Fibrilação Atrial/complicações , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Cardiopatia Reumática/complicações , Rivaroxabana/efeitos adversos
19.
Environ. pollut ; 262(114197): 1-41, Jul, 2020. gráfico, tabela, ilustração
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1103363

RESUMO

Exposure to air pollution has been linked to elevated blood pressure (BP) and hypertension, but most research has focused on short-term (hours, days, or months) exposures at relatively low concentrations. We examined the associations between long-term (3-year average) concentrations of outdoor PM2.5 and household air pollution (HAP) from cooking with solid fuels with BP and hypertension in the Prospective Urban and Rural Epidemiology (PURE) study. Outdoor PM2.5 exposures were estimated at year of enrollment for 137,809 adults aged 35­70 years from 640 urban and rural communities in 21 countries using satellite and ground-based methods. Primary use of solid fuel for cooking was used as an indicator of HAP exposure, with analyses restricted to rural participants (n = 43,313) in 27 study centers in 10 countries. BP was measured following a standardized procedure and associations with air pollution examined with mixed-effect regression models, after adjustment for a comprehensive set of potential confounding factors. Baseline outdoor PM2.5 exposure ranged from 3 to 97 µg/m3 across study communities and was associated with an increased odds ratio (OR) of 1.04 (95% CI: 1.01, 1.07) for hypertension, per 10 µg/m3 increase in concentration. This association demonstrated non-linearity and was strongest for the fourth (PM2.5 > 62 µg/m3) compared to the first (PM2.5 < 14 µg/m3) quartiles (OR = 1.36, 95% CI: 1.10, 1.69). Similar non-linear patterns were observed for systolic BP (ß = 2.15 mmHg, 95% CI: −0.59, 4.89) and diastolic BP (ß = 1.35, 95% CI: −0.20, 2.89), while there was no overall increase in ORs across the full exposure distribution. Individuals who used solid fuels for cooking had lower BP measures compared to clean fuel users (e.g. 34% of solid fuels users compared to 42% of clean fuel users had hypertension), and even in fully adjusted models had slightly decreased odds of hypertension (OR = 0.93; 95% CI: 0.88, 0.99) and reductions in systolic (−0.51 mmHg; 95% CI: −0.99, −0.03) and diastolic (−0.46 mmHg; 95% CI: −0.75, −0.18) BP. In this large international multi-center study, chronic exposures to outdoor PM2.5 was associated with increased BP and hypertension while there were small inverse associations with HAP.


Assuntos
Poluição do Ar/efeitos adversos , Pressão Arterial , Epidemiologia
20.
Europace ; 22(5): 1-13, May., 2020. tabela, ilustração
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1100489

RESUMO

The field of observational studies or "real world studies" is in rapid development with many new techniques introduced and increased understanding of traditional methods. For this reason, the current paper provides an overview of current methods with focus on new techniques. Some highlights can be emphasized: We provide an overview of sources of data for observational studies. There is an overview of sources of bias and confounding. Next There is an overview of causal inference techniques that are increasingly used. The most commonly used techniques for statistical modelling are reviewed with focus on the important distinction of risk versus prediction. The final section provides examples of common problems with reporting observational data.


Assuntos
Arritmias Cardíacas/epidemiologia , Fibrilação Atrial/epidemiologia , Estudo Observacional
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