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BACKGROUND: Contemporary data describing the national trends on vascular risk factor control among stroke survivors are limited. METHODS AND RESULTS: This is a cross-sectional analysis of the National Health and Nutrition Examination Survey cycles 2009 to 2010 to 2017 to March 2020. Adults (≥18 years of age) with a self-reported diagnosis of stroke were identified. Age-adjusted trends in hypertension, diabetes, and hyperlipidemia control were examined. Sex and racial differences in vascular risk factor control were also investigated. Among 32 497 adult individuals who participated in the National Health and Nutrition Examination Survey, 1354 participants (4.2%) self-reported a prior diagnosis of stroke (55% were women). The rates of age-adjusted blood pressure control worsened when using the cutoff <140/90 mm Hg (79.1% in 2009-2010 versus 61.5% in 2017-March 2020, Ptrend<0.001) and using the cutoff <130/80 mm Hg (53.3% in 2009-2010 versus 38.6% in 2017-March 2020, Ptrend=0.006). Age-adjusted diabetes control (hemoglobin A1c <7 mg/dL) did not significantly change during the study period (88.8% in 2009-2010 versus 85.9% in 2017-March 2020, Ptrend=0.41). Achieving a total cholesterol level <200 mg/dL did not change during the study period (67.3% in 2009-2010 versus 73.3% in 2017-March 2020, Ptrend=0.16). These findings were mostly consistent in men and women and across the different racial and ethnic groups. CONCLUSIONS: In the United States, secondary prevention was suboptimal for stroke survivors, and there has not been any major significant improvement in the rates of achieving the recommended targets for vascular risk factors during the past decade. These findings highlight the need for targeted interventions to improve these modifiable risk factors.
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Diabetes Mellitus , Acidente Vascular Cerebral , Masculino , Adulto , Humanos , Feminino , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Estudos Transversais , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , SobreviventesRESUMO
BACKGROUND: It is important to consider biological sex as a variable that might influence exercise adaptation in order to optimize exercise prescription for men and women. OBJECTIVE: The aim of this study was to quantify the impact of biological sex on maximal oxygen uptake ([Formula: see text]O2max) and performance outcomes after high-intensity interval training (HIIT). METHODS: A systematic search and review was conducted by two independent reviewers up to 8 September 2022 using MEDLINE, SPORTDiscus, and Sports Medicine & Education Index in ProQuest. Trials including healthy adults were included if they presented data for or compared male and female [Formula: see text]O2max or performance outcomes in response to HIIT. Performance outcomes included measures of exercise performance and concurrently measured physiological adaptations. Where appropriate, a random-effects, pre-post meta-analysis was undertaken. Data were sub-grouped for men and women, baseline training level, mean age, intervention type, and intervention length. Heterogeneity was assessed using Chi2, Cochran's Q, and Higgins I2 and sensitivity analyses, where required. Study quality was assessed using the Newcastle-Ottawa Scale and publication bias was assessed through visual inspection of funnel plots. RESULTS: Thirty-three references from 28 trials were included in the review (n = 965; 462 women and 503 men). Meta-analyses included 19 studies for [Formula: see text]O2max, eight for peak power output from [Formula: see text]O2max testing (PPO), and five for threshold power (powerAT). Meta-analyses revealed similar increases in [Formula: see text]O2max in women (g = 0.57; 95% CI 0.44-0.69) and men (g = 0.57; 95% CI 0.42-0.72), and powerAT in women (g = 0.38; 95% CI 0.13-0.64) and men (g = 0.38; 95% CI 0.11-0.64). Raw mean differences for change in [Formula: see text]O2max were Δ 0.32 L·min-1 and 3.50 mL·kg-1·min-1 in men, versus Δ 0.20 L·min-1 and 3.34 mL·kg-1·min-1 for women. No significant sex differences were present for the primary analysis of any outcome. After sub-grouping, significant differences were present for PPO where the effect size was higher for well-trained women (g = 0.37) compared with well-trained men (g = 0.17), and for [Formula: see text]O2max where interventions with a duration of 4 weeks or less had significantly smaller effect sizes compared with those longer than 4 weeks (p < 0.001). Unweighted mean percentage change in [Formula: see text]O2max, PPO, and powerAT across studies was 11.16 ± 7.39%, 11.16 ± 5.99%, and 8.07 ± 6.55% for women, and 10.90 ± 5.75%, 8.22 ± 5.09%, and 7.09 ± 7.17% for men, respectively. Significant heterogeneity was present for both [Formula: see text]O2max and PPO (I2, range: 62.06-78.80%). Sub-grouping by baseline training status and intervention length decreased heterogeneity in most groups. A qualitative synthesis of other outcomes indicated similar improvements in fitness and performance for men and women with some evidence suggesting differences in the mechanisms of adaptation. LIMITATIONS AND RISK OF BIAS: Publication bias is unlikely to have significantly influenced results for [Formula: see text]O2max or powerAT, but the meta-analysis of PPO could have benefitted from additional study data to strengthen results. The overlap in age categories and sensitivity of the analysis limits the accuracy of the results of the sub-grouping by age. CONCLUSIONS: Findings indicated no sex-specific differences for any fitness or performance outcomes. Baseline training status and intervention length accounted for most variability in outcomes. PROSPERO registration number: CRD42021272615.
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Aptidão Cardiorrespiratória , Treinamento Intervalado de Alta Intensidade , Adulto , Feminino , Humanos , Masculino , Treinamento Intervalado de Alta Intensidade/métodos , Consumo de Oxigênio/fisiologiaRESUMO
Background: Randomized clinical trials (RCTs) evaluating the role of intravenous (IV) iron administration in patients with heart failure (HF) and iron deficiency (ID) have yielded inconsistent results. Methods: Electronic search of MEDLINE, EMBASE and OVID databases was performed until November 2022 for RCTs that evaluated the role of IV iron administration in patients with HF and ID. The main study outcomes were the composite of HF hospitalization or cardiovascular mortality, and individual outcome of HF hospitalization. Summary estimates were evaluated using random effects model. Results: The final analysis included 12 RCTs with 3,492 patients (1,831 patients in the IV iron group and 1,661 patients in the control group). The mean follow-up was 8.3 months. IV iron was associated with a lower incidence in the composite of HF hospitalization or cardiovascular mortality (31.9% vs. 45.3%; relative risk [RR] 0.72; 95% confidence interval [CI] 0.59-0.88) and individual outcome of HF hospitalization (28.4% vs. 42.2; RR 0.69; 95% CI 0.57-0.85). There was no significant difference between both groups in cardiovascular mortality (RR 0.88; 95% CI 0.75-1.04) and all-cause mortality (RR 0.95; 95% CI 0.83-1.09). IV iron was associated with lower New York Heart Association class and higher left ventricular ejection fraction (LVEF). Meta-regression analyses showed no effect modification for the main outcomes based on age, hemoglobin level, ferritin level or LVEF. Conclusion: Among patients with HF and ID, IV iron administration was associated with reduction in the composite of HF hospitalization or cardiovascular mortality and driven by a reduction in HF hospitalization.
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Randomized controlled trials (RCTs) examining the outcomes of "polypill" therapy in cardiovascular disease prevention have yielded mixed results. We performed an electronic search through January 2023 for RCTs that examined the use of polypills for cardiovascular disease primary or secondary prevention. The primary outcome was the incidence of major adverse cardiac and cerebrovascular events (MACCEs). The final analysis included 11 RCTs with 25,389 patients; 12,791 patients were in the polypill arm, and 12,598 patients were in the control arm. The follow-up period ranged from 1 to 5.6 years. Polypill therapy was associated with a lower risk of MACCE (5.8% vs 7.7%; risk ratio [RR] 0.78, 95% confidence interval [CI] 0.67 to 0.91). The reduction of MACCE risk was consistent in both primary and secondary prevention. Polypill therapy was associated with a lower incidence of cardiovascular mortality (2.1% vs 3%; RR 0.69, 95% CI 0.55 to 0.87), myocardial infarction (2.3% vs 3.2%; RR 0.72, 95% CI 0.61 to 0.84) and stroke (0.9% vs 1.6%; RR 0.62, 95% CI 0.42 to 0.90). Polypill therapy was associated with a higher degree of adherence. There was no difference between both groups in the incidence of serious adverse events (16.1% vs 15.9%; RR 1.12, 95% CI 0.93 to 1.36). In conclusion, we found that a polypill strategy was associated with a lower incidence of cardiac events and higher adherence, without an increased incidence of adverse events. This benefit was consistent for both primary and secondary prevention.
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Doenças Cardiovasculares , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Infarto do Miocárdio/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Prevenção SecundáriaRESUMO
Background Well-conducted meta-analyses are considered to be at the top of the evidence-based hierarchy pyramid, with an expansion of these publications within the cardiovascular research arena. There are limited data evaluating the trends and quality of such publications. The objective of this study was to evaluate the methodological rigor and temporal trends of cardiovascular medicine-related meta-analyses published in the highest impact journals. Methods and Results Using the Medline database, we retrieved cardiovascular medicine-related systematic reviews and meta-analyses published in The New England Journal of Medicine, The Lancet, Journal of the American Medical Association, The British Medical Journal, Annals of Internal Medicine, Circulation, European Heart Journal, and Journal of American College of Cardiology between January 1, 2012 and December 31, 2018. Among 6406 original investigations published during the study period, meta-analyses represented 422 (6.6%) articles, with an annual decline in the proportion of published meta-analyses (8.7% in 2012 versus 4.6% in 2018, Ptrend=0.002). A substantial number of studies failed to incorporate elements of Preferred Reporting Items for Systematic Reviews and Meta-Analyses or Meta-Analysis of Observational Studies in Epidemiology guidelines (51.9%) and only a minority of studies (10.4%) were registered in PROSPERO (International Prospective Register of Systematic Reviews). Fewer manuscripts failed to incorporate the Preferred Reporting Items for Systematic Reviews and Meta-Analyses or Meta-Analysis of Observational Studies in Epidemiology elements over time (60.2% in 2012 versus 40.0% in 2018, Ptrend<0.001) whereas the number of meta-analyses registered at PROSPERO has increased (2.4% in 2013 versus 17.5% in 2018, Ptrend<0.001). Conclusions The proportion of cardiovascular medicine-related meta-analyses published in the highest impact journals has declined over time. Although there is an increasing trend in compliance with quality-based guidelines, the overall compliance remains low.
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Cardiologia , Metanálise como Assunto , Publicações Periódicas como Assunto , Revisões Sistemáticas como Assunto , Bibliometria , Humanos , Publicações Periódicas como Assunto/normasRESUMO
Background Critical limb ischemia (CLI) represents the most severe form of peripheral artery disease and is associated with significant mortality and morbidity. Contemporary data comparing the sex differences in trends, revascularization strategies, and in-hospital outcomes among patients with CLI are scarce. Methods and Results Using the National Inpatient Sample database years 2002 to 2015, we identified hospitalizations for CLI. Temporal trends for hospitalizations for CLI were evaluated. The differences in demographics, revascularization, and in-hospital outcomes between both sexes were compared. Among 2 400 778 CLI hospitalizations, 43.6% were women. Women were older and had a higher prevalence of obesity, hypertension, heart failure, and prior stroke. Women were also less likely to receive any revascularization (34.7% versus 35.4%, P<0.001), but the trends of revascularization have been increasing among both sexes. Revascularization was associated with lower in-hospital mortality among women (adjusted odds ratio [OR], 0.76; 95% CI, 0.71-0.81) and men (adjusted OR, 0.69; 95% CI, 0.65-0.73). On multivariable analysis adjusting for patient- and hospital-related characteristics as well as revascularization, women had a higher incidence of in-hospital mortality, postoperative hemorrhage, need for blood transfusion, postoperative infection, ischemic stroke, and discharge to facilities compared with men. Conclusions In this nationwide contemporary analysis of CLI hospitalizations, women were older and less likely to undergo revascularization. Women had a higher incidence of in-hospital mortality and bleeding complications compared with men. Sex-specific studies and interventions are needed to minimize these gaps among this high-risk population.
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Isquemia Crônica Crítica de Membro , Mortalidade Hospitalar , Isquemia Crônica Crítica de Membro/mortalidade , Isquemia Crônica Crítica de Membro/terapia , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar/tendências , Humanos , Masculino , Distribuição por Sexo , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the trend and outcomes of acute pulmonary embolism (PE) during pregnancy and puerperium using a large national database. PATIENTS AND METHODS: The National Inpatient Sample was queried to identify pregnancy-related hospitalizations in the United States from January 1, 2007, through September 30, 2015. Temporal trends in the rates of acute PE and in-hospital mortality rates were extracted. RESULTS: Among 37,524,314 hospitalizations, 6,333 patients (0.02%) had acute PE. The prevalence of comorbidities and risk factors such as hypertension, obesity, and smoking increased, but rates of acute PE did not change significantly (18.01 in 2007 vs 19.36 in 2015, per 100,000 hospitalizations, Ptrends=.21). Advanced therapies were used in a small number of women (systemic thrombolysis: 2.4%, surgical pulmonary embolectomy: 0.5%, and inferior vena cava filter in 8.3%). Rates of in-hospital mortality were almost 200-fold higher among those who had acute PE (29.3 vs 0.13, per 1000 pregnancy-related, P<.001). The rate of in-hospital mortality did not change among women with acute PE (2.6% in 2007 vs 2.5% in 2015, Ptrends=.74). CONCLUSION: In this contemporary analysis of pregnancy-related hospitalizations, acute PE was uncommon, but rates have not decreased over the past decade. Acute PE during pregnancy and puerperium was associated with high maternal mortality, and the rates of in-hospital mortality have not improved. Future studies to improve prevention and management of acute PE during pregnancy and puerperium are warranted.
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Hospitalização/estatística & dados numéricos , Complicações Cardiovasculares na Gravidez/epidemiologia , Embolia Pulmonar/epidemiologia , Doença Aguda , Adulto , Feminino , Mortalidade Hospitalar/tendências , Humanos , Incidência , Período Pós-Parto , Gravidez , Complicações Cardiovasculares na Gravidez/terapia , Embolia Pulmonar/terapia , Estudos Retrospectivos , Fatores de Risco , Terapia Trombolítica/métodos , Estados Unidos/epidemiologia , Filtros de Veia Cava , Adulto JovemAssuntos
COVID-19/epidemiologia , Exercício Físico , Jejum , Islamismo , Adulto , Doença Crônica , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pandemias , SARS-CoV-2RESUMO
The novel pandemic called coronavirus disease 2019 (COVID-19), as a global public health emergency, seems to be having a major impact on physical activity (PA) behaviors. Older adults are at high risk of death from the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Health authorities around the world have been implementing preventive health measures, including quarantine and self-isolation, to mitigate the COVID-19 outbreak. This period is characterized by the cessation of outdoor exercising. During this period of lockdown, PA has been one of the rare reasons for going out in some countries. To avoid the harmful effects of periods of exercise cessation, PA could be prescribed to older adults, which is of great importance for breaking their sedentary lifestyle and improving their immunity. The present review discusses the potential impacts of the COVID-19 pandemic on sedentary behavior and physical inactivity in older adults. The importance of performing PA to reduce the harmful effects of the COVID-19 pandemic is discussed, and useful recommendations on home-based exercise for the older adults to maintain their level of independence, physical and mental health as well as their well-being are provided.
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COVID-19/epidemiologia , Comportamentos Relacionados com a Saúde , Estilo de Vida Saudável , Saúde Mental/estatística & dados numéricos , Comportamento Sedentário , Idoso , COVID-19/psicologia , Exercício Físico/psicologia , Feminino , Humanos , Masculino , Isolamento Social/psicologiaRESUMO
Background The currently used atherosclerotic cardiovascular disease risk calculator relies on several measured variables and does not incorporate some well-established risk factors such as family history of premature myocardial infarction and other nontraditional risk factors. Our study aimed to develop and validate a simple risk score to predict 10-year risk of incident cardiovascular events using patient-reported information. Methods and Results Using data from the Atherosclerosis Risk in Communities cohort, we identified adults with no previous history of cardiovascular disease and randomly divided the cohort into "development" (70%) and "validation" (30%) subgroups. Adjusted Cox regression modeling was used to develop a prediction model. The predictive performance of the new risk score was compared with the score derived from the atherosclerotic cardiovascular disease risk calculator. A total of 9285 individuals met the inclusion criteria. During follow-up (median 8.93 years), a total of 694 (7.47%) incident cardiovascular events occurred. The following 6 factors were included: male sex, age, current smoking, diabetes mellitus, hypertension, and family history of premature myocardial infarction. The C-statistic was 0.72 in the validation cohort with good calibration. The area under the curve for the simple risk score was comparable to the atherosclerotic cardiovascular disease risk score. Conclusions The novel simple risk score is an easy-to-use tool to predict cardiovascular events in adults from self-reported information without need for laboratory or physical examination data. This risk score included 6-items and had comparable predictive performance to the guideline recommended atherosclerotic cardiovascular disease risk score but relies solely on self-reported information.
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Doenças Cardiovasculares/epidemiologia , Medição de Risco/métodos , Autorrelato , Idoso , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Doenças Cardiovasculares/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
IN BRIEF Patient awareness of prediabetes and an increased diabetes risk is crucial to diabetes prevention. This article reports on a study investigating perceptions of diabetes risk among U.S. adults with prediabetes and the role of physician communication about risks in influencing patient perceptions. This study demonstrates that few patients with undiagnosed prediabetes are even told that they are at high risk for diabetes. This study provides further evidence that diabetes prevention requires improved patient-centered care, which likely begins with the delivery of adequate information to patients.
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OBJECTIVES: The authors sought to investigate the incidence, predictors, and causes of 30-day nonelective readmissions after endovascular thrombectomy (EVT). BACKGROUND: Randomized trials have demonstrated that EVT improves outcomes in patients with acute ischemic stroke. METHODS: The Nationwide Readmissions Database, years 2013 and 2014, was used to identify hospitalizations for a primary diagnosis of acute ischemic stroke during which patients underwent EVT, with or without intravenous thrombolysis. The incidence and reasons of 30-day readmissions were investigated. A hierarchical Cox regression model was used to identify independent predictors of 30-day nonelective readmissions. A propensity score-matched analysis was performed to compare the risk of 30-day nonelective readmissions in those who underwent EVT versus thrombolysis alone. RESULTS: Among 2,055,365 weighted hospitalizations with acute ischemic stroke and survival to discharge, 10,795 (0.5%) underwent EVT. The 30-day readmission rate was 12.4% within a median of 9 days (interquartile range: 4 to 18 days). Diabetes mellitus, coagulopathy, Medicare or Medicaid insurance, and gastrostomy during the index hospitalization were independent predictors of 30-day readmission, but coadministration of thrombolytics with EVT was not an independent predictor. The most common reasons for readmission were infections (17.2%), cardiac causes (17.0%), and recurrent stroke or transient ischemic attack (14.8%). Compared with thrombolysis alone, the hazard of 30-day readmissions was similar (hazard ratio: 0.98; 95% confidence interval: 0.91 to 1.05; p = 0.55). CONCLUSIONS: In patients hospitalized with acute ischemic stroke who underwent EVT, 30-day nonelective readmissions were common, occurring in approximately 1 in 8 patients, but were similar to those of patients treated with thrombolysis alone. Risk of readmission was associated with certain patient demographics, comorbidities, and complications, but not thrombolysis coadministration. Infections, cardiac causes, and recurrent stroke or transient ischemic attack are the most common reasons for readmission after EVT, emphasizing the need for comprehensive multidisciplinary treatment in the transition to outpatient care.
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Isquemia Encefálica/terapia , Procedimentos Endovasculares/efeitos adversos , Readmissão do Paciente , Acidente Vascular Cerebral/terapia , Trombectomia/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/terapia , Bases de Dados Factuais , Procedimentos Endovasculares/métodos , Feminino , Cardiopatias/epidemiologia , Cardiopatias/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Trombectomia/métodos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
The aim of this study was to determine the long-term prognostic value of the Duke Activity Status Index-estimated metabolic equivalents (METs) values among women with suspected ischemic heart disease. At a median of 9.6â¯years, the incidence of death was 23.4% in those with METs <4.8 versus 8.2% in METs >9.9, Pâ¯<â¯.01. In conclusion, use of the simple, patient-reported Duke Activity Status Index could help identify higher-risk women with suspected ischemic heart disease for targeted risk management.
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Tolerância ao Exercício/fisiologia , Previsões , Isquemia Miocárdica/mortalidade , Medição de Risco , Saúde da Mulher , Idoso , Angiografia Coronária , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatologia , National Heart, Lung, and Blood Institute (U.S.) , Prognóstico , Fatores de Risco , Taxa de Sobrevida/tendências , Síndrome , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Peripheral arterial disease (PAD) carries a significant morbidity and mortality. Women are more commonly affected with this condition and are mostly asymptomatic, and undertreated. The objective of the study was to develop and validate a simple risk score to identify women with PAD. HYPOTHESIS: Identifying those at early stage of the disease could help reduce the risk of complications. METHODS: Using data from the National Health and Nutrition Examination Survey 1999-2004, we identified women who had data on ankle brachial index. The cohort was divided into development (70%) and validation (30%) groups. Using variables that are self-reported or measured without laboratory data, we developed a multivariable logistic regression to predict PAD, which was evaluated in the validation cohort. RESULTS: A total of 150.6 million women were included. A diagnosis of PAD was reported in 13.7%. Age, body mass index, hypertension, diabetes mellitus, smoking, non-oral contraceptive pill usage, and parity were all independently associated with PAD. The C-statistics was 0.74, with good calibration. The model showed good stability in the validation cohort (C-statistics 0.73). CONCLUSION: This parsimonious risk model is a valid tool for risk prediction of PAD in women, and could be easily applied in routine clinical practice.
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Inquéritos Nutricionais , Doença Arterial Periférica/epidemiologia , Medição de Risco/métodos , Saúde da Mulher , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice Tornozelo-Braço , Índice de Massa Corporal , Estudos Transversais , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Morbidade/tendências , Doença Arterial Periférica/diagnóstico , Prevalência , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: To perform an updated meta-analysis to evaluate the long-term cardiovascular and cerebrovascular outcomes among migraineurs. SETTING: A meta-analysis of cohort studies performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: The MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials databases were searched for relevant articles. PARTICIPANTS: A total of 16 cohort studies (18 study records) with 394 942 migraineurs and 757 465 non-migraineurs were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: Major adverse cardiovascular and cerebrovascular events (MACCE), stroke (ie, ischaemic, haemorrhagic or non-specified), myocardial infarction (MI) and all-cause mortality. The outcomes were reported at the longest available follow-up. DATA ANALYSIS: Summary-adjusted hazard ratios (HR) were calculated by random-effects Der-Simonian and Liard model. The risk of bias was assessed by the Newcastle-Ottawa Scale. RESULTS: Migraine was associated with a higher risk of MACCE (adjusted HR 1.42, 95% confidence interval [CI] 1.26 to 1.60, P<0.001, I2=40%) driven by a higher risk of stroke (adjusted HR 1.41, 95% CI 1.25 to 1.61, P<0.001, I2=72%) and MI (adjusted HR 1.23, 95% CI 1.03 to 1.43, P=0.006, I2=59%). There was no difference in the risk of all-cause mortality (adjusted HR 0.93, 95% CI 0.78 to 1.10, P=0.38, I2=91%), with a considerable degree of statistical heterogeneity between the studies. The presence of aura was an effect modifier for stroke (adjusted HR aura 1.56, 95% CI 1.30 to 1.87 vs adjusted HR no aura 1.11, 95% CI 0.94 to 1.31, P interaction=0.01) and all-cause mortality (adjusted HR aura 1.20, 95% CI 1.12 to 1.30 vs adjusted HR no aura 0.96, 95% CI 0.86 to 1.07, Pinteraction<0.001). CONCLUSION: Migraine headache was associated with an increased long-term risk of cardiovascular and cerebrovascular events. This effect was due to an increased risk of stroke (both ischaemic and haemorrhagic) and MI. There was a moderate to severe degree of heterogeneity for the outcomes, which was partly explained by the presence of aura. PROSPERO REGISTRATION NUMBER: CRD42016052460.