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BACKGROUND: Although bronchiectasis has been shown to be associated with cardiovascular disease, there is limited evidence of an association with subclinical atherosclerosis, especially carotid intima-media thickness (CIMT). METHODS: This prospective study compared CIMT among patients with and without bronchiectasis, and among bronchiectatic patients classified according to disease severity using the FACED score. The study was carried out at a major regional hospital and tertiary respiratory referral centre in Hong Kong. RESULTS: Total 155 Chinese patients with non-cystic fibrosis (CF) bronchiectasis and 512 controls were recruited. The mean CIMT was 0.58 ± 0.10 mm, 0.63 ± 0.11 mm and 0.66 ± 0.08 mm respectively among controls, patients with mild-to-moderate bronchiectasis and patients with severe bronchiectasis. There was no statistically significant difference in CIMT between patients with mild-to-moderate bronchiectasis and controls. Multivariate linear regression revealed that CIMT was significantly increased in patients with severe bronchiectasis relative to controls. The same phenomenon was observed among patients without a history of cardiovascular disease or cardiovascular risk factors. CONCLUSIONS: CIMT was significantly increased in patients with severe bronchiectasis compared with controls without bronchiectasis, but not among patients with mild-to-moderate bronchiectasis, which suggested the subclinical atherosclerosis to be more prevalent among patients with severe bronchiectasis.
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Bronquiectasia , Doenças das Artérias Carótidas , Espessura Intima-Media Carotídea , Índice de Gravidade de Doença , Humanos , Bronquiectasia/diagnóstico por imagem , Bronquiectasia/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Hong Kong/epidemiologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Estudos de Casos e Controles , Idoso , Valor Preditivo dos Testes , Adulto , Fatores de Risco , Medição de RiscoRESUMO
BACKGROUND: Elevation of systemic inflammatory markers were found to correlate with increased disease extent, reduced lung function and higher risk of future severe exacerbations in patients with bronchiectasis. Although a significant correlation of circulating hs-CRP levels with HRCT scores and resting oxygen saturation in patients with stable-state non-cystic fibrosis (CF) bronchiectasis was suggested, there is little data on the relationship between hs-CRP and the prognosis of bronchiectasis and a lack of data on the role of hs-CRP in predicting bronchiectasis exacerbation. METHODS: A prospective study was conducted on Chinese patients with non- CF bronchiectasis from 1st October to 31st December 2021. Baseline serum hs-CRP were obtained at stable-state. The follow-up period lasted for one year. Co-primary endpoints were the development of any bronchiectasis exacerbation and hospitalized bronchiectasis exacerbation. RESULTS: Totally 123 patients were included. Higher hs-CRP was associated with increased risk to develop any bronchiectasis exacerbation, adjusted odds ratio (aOR) of 2.254 (95% CI = 1.040-4.885, p = 0.039), and borderline significantly increased hospitalized bronchiectasis exacerbation with aOR of 1.985 (95% CI = 0.922-4.277, p = 0.080). CONCLUSION: Baseline serum hs-CRP level at stable-state can predict risk of bronchiectasis exacerbation, which is reflecting chronic low-grade inflammation in bronchiectasis.
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Bronquiectasia , Fibrose Cística , Humanos , Proteína C-Reativa/metabolismo , Estudos Prospectivos , Prognóstico , InflamaçãoRESUMO
BACKGROUND: Major intracerebral hemorrhage (ICH) trials have largely been unable to demonstrate therapeutic benefit in improving functional outcomes. This may be partly due to the heterogeneity of ICH outcomes based on their location, where a small strategic ICH could be debilitating, thus confounding therapeutic effects. We aimed to determine the ideal hematoma volume cutoff for different ICH locations in predicting ICH outcomes. METHODS: We retrospectively analyzed consecutive ICH patients enrolled in the University of Hong Kong prospective stroke registry from January 2011 to December 2018. Patients with premorbid modified Rankin Scale score >2 or who underwent neurosurgical intervention were excluded. ICH volume cutoff, sensitivity, and specificity in predicting respective 6-month neurological outcomes (good [modified Rankin Scale score 0-2], poor [modified Rankin Scale score 4-6], and mortality) for specific ICH locations were determined using receiver operating characteristic curves. Separate multivariate logistic regression models were also conducted for each location-specific volume cutoff to determine whether these cutoffs were independently associated with respective outcomes. RESULTS: Among 533 ICHs, the volume cutoff for good outcome according to ICH location was 40.5 mL for lobar, 32.5 mL for putamen/external capsule, 5.5 mL for internal capsule/globus pallidus, 6.5 mL for thalamus, 17 mL for cerebellum, and 3 mL for brainstem. ICH smaller than the cutoff for all supratentorial sites had higher odds of good outcomes (all P<0.05). Volumes exceeding 48 mL for lobar, 41 mL for putamen/external capsule, 6 mL for internal capsule/globus pallidus, 9.5 mL for thalamus, 22 mL for cerebellum, and 7.5 mL for brainstem were at greater risk of poor outcomes (all P<0.05). Mortality risks were significantly higher for volumes that exceeded 89.5 mL for lobar, 42 mL for putamen/external capsule, and 21 mL for internal capsule/globus pallidus (all P<0.001). All receiver operating characteristic models for location-specific cutoffs had good discriminant values (area under the curve >0.8), except in predicting good outcome for cerebellum. CONCLUSIONS: ICH outcomes differed with location-specific hematoma size. Location-specific volume cutoff should be considered in patient selection for ICH trials.
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Hemorragia Cerebral , Acidente Vascular Cerebral , Humanos , Estudos Retrospectivos , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Globo Pálido , Hematoma/diagnóstico por imagem , Hematoma/cirurgiaRESUMO
BACKGROUND: Intracerebral hemorrhage (ICH) survivors are at high risk for recurrent stroke and cardiovascular events. Blood pressure (BP) control represents the most potent intervention to lower these risks, but optimal treatment targets in this patient population remain unknown. We sought to determine whether survivors of ICH achieving more intensive BP control than current guideline recommendations (systolic BP <130 mmHg and diastolic BP <80 mmHg) were at lower risk of major adverse cardiovascular and cerebrovascular events and mortality. METHODS: We analyzed data for 1828 survivors of spontaneous ICH from 2 cohort studies. Follow-up BP measurements were recorded 3 and 6 months after ICH, and every 6 months thereafter. Outcomes of interest were major adverse cardiovascular and cerebrovascular events (recurrent ICH, incident ischemic stroke, myocardial infarction), vascular mortality (defined as mortality attributed to recurrent ICH, ischemic stroke, or myocardial infarction), and all-cause mortality. RESULTS: During a median follow-up of 46.2 months, we observed 166 recurrent ICH, 68 ischemic strokes, 69 myocardial infarction, and 429 deaths. Compared with survivors of ICH with systolic BP 120 to 129 mmHg, participants who achieved systolic BP <120 mmHg displayed reduced risk of recurrent ICH (adjusted hazard ratio [AHR], 0.74 [95% CI, 0.59-0.94]) and major adverse cardiovascular and cerebrovascular events (AHR, 0.69 [95% CI, 0.53-0.92]). All-cause mortality (AHR, 0.76 [95% CI, 0.57-1.03]) and vascular mortality (AHR, 0.68 [95% CI, 0.45-1.01]) did not differ significantly. Among participants aged >75 years or with modified Rankin Scale score 4 to 5, systolic BP <120 mmHg was associated with increased all-cause mortality (AHR, 1.38 [95% CI, 1.02-1.85] and AHR, 1.36 [95% CI, 1.03-1.78], respectively), but not vascular mortality. We found no differences in outcome rates between survivors of ICH with diastolic BP <70 versus 70 to 79 mmHg. CONCLUSIONS: Targeting systolic BP <120 mmHg in select groups of survivors of ICH could result in decreased major adverse cardiovascular and cerebrovascular events risk without increasing mortality. Our findings warrant investigation in dedicated randomized controlled trials.
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AVC Isquêmico , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Pressão Sanguínea/fisiologia , Hemorragia Cerebral/epidemiologia , Infarto do Miocárdio/complicações , Estudos de Coortes , AVC Isquêmico/complicações , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND AND PURPOSE: The current coronavirus disease 2019 (COVID-19) pandemic represents a global public health crisis, disrupting emergency healthcare services. We determined whether COVID-19 has resulted in delays in stroke presentation and affected the delivery of acute stroke services in a comprehensive stroke center in Hong Kong. METHODS: We retrospectively reviewed all patients with transient ischemic attack and stroke admitted via the acute stroke pathway of Queen Mary Hospital, Hong Kong, during the first 60 days since the first diagnosed COVID-19 case in Hong Kong (COVID-19: January 23, 2020-March 24, 2020). We compared the stroke onset to hospital arrival (onset-to-door) time and timings of inpatient stroke pathways with patients admitted during the same period in 2019 (pre-COVID-19: January 23, 2019-March 24, 2019). RESULTS: Seventy-three patients in COVID-19 were compared with 89 patients in pre-COVID-19. There were no significant differences in age, sex, vascular risk factors, nor stroke severity between the 2 groups (P>0.05). The median stroke onset-to-door time was ≈1-hour longer in COVID-19 compared with pre-COVID-19 (154 versus 95 minutes, P=0.12), and the proportion of individuals with onset-to-door time within 4.5 hours was significantly lower (55% versus 72%, P=0.024). Significantly fewer cases of transient ischemic attack presented to the hospital during COVID-19 (4% versus 16%, P=0.016), despite no increase in referrals to the transient ischemic attack clinic. Inpatient stroke pathways and treatment time metrics nevertheless did not differ between the 2 groups (P>0.05 for all comparisons). CONCLUSIONS: During the early containment phase of COVID-19, we noted a prolongation in stroke onset to hospital arrival time and a significant reduction in individuals arriving at the hospital within 4.5 hours and presenting with transient ischemic attack. Public education about stroke should continue to be reinforced during the COVID-19 pandemic.
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Betacoronavirus , Infecções por Coronavirus , Ataque Isquêmico Transitório/epidemiologia , Pandemias , Pneumonia Viral , Acidente Vascular Cerebral/epidemiologia , Tempo para o Tratamento/estatística & dados numéricos , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Atenção à Saúde/estatística & dados numéricos , Serviços Médicos de Emergência , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hong Kong/epidemiologia , Hospitais Especializados/estatística & dados numéricos , Hospitais Urbanos/estatística & dados numéricos , Humanos , Ataque Isquêmico Transitório/terapia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/terapia , Trombectomia/estatística & dados numéricos , Terapia Trombolítica/estatística & dados numéricos , Ativador de Plasminogênio Tecidual/uso terapêuticoRESUMO
BACKGROUND: Recent studies in Caucasians with transient ischaemic attack or ischaemic stroke have demonstrated significant age-specific associations between cerebral small vessel disease (SVD) burden on magnetic resonance imaging and renal impairment. We aimed to validate these findings in a large cohort of Chinese with ischaemic stroke. METHODS: In 959 Chinese with ischaemic stroke who received a brain magnetic resonance imaging at the University of Hong Kong, we determined the age-specific associations of renal impairment (glomerular filtration rate < 60 mL/min/1.73 m2) with neuroimaging markers of SVD as well as with the SVD score. RESULTS: Although renal impairment was associated with the SVD score in univariate analysis in all patients (odds ratio 1.61, 95% confidence interval 1.24-2.09, P < .0001), these associations were attenuated after adjusting for age and sex (Pâ¯=â¯.38). Similar findings were noted in patients with ischaemic stroke due to SVD and non-SVD subtypes. However, in 222 of 959 patients aged <60, renal impairment was independently associated with an increasing microbleed (adjusted odds ratio 6.82, 2.26-20.59), subcortical (4.97, 1.62-15.24) periventricular white matter hyperintensity (3.96, 1.08-14.51) and global SVD burden (3.41, 1.16-10.04; all P < .05) even after adjusting for age, sex, and vascular risk factors. Nevertheless, there were no associations between renal impairment and individual neuroimaging markers of SVD nor with the SVD score in patients aged ≥60 after adjusting for age and sex (all P > .05). CONCLUSIONS: In Chinese with ischaemic stroke, renal impairment was independently associated with microbleed, white matter hyperintensity and global SVD burden in individuals aged <60, but not in those aged ≥60, suggesting that there may be shared susceptibilities to premature systemic disease.
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Isquemia Encefálica/etnologia , Doenças de Pequenos Vasos Cerebrais/etnologia , Taxa de Filtração Glomerular , Nefropatias/etnologia , Rim/fisiopatologia , Acidente Vascular Cerebral/etnologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Estudos Transversais , Imagem de Difusão por Ressonância Magnética , Feminino , Hong Kong/epidemiologia , Humanos , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologiaRESUMO
BACKGROUND: Recent intensive low-density lipoprotein cholesterol (LDL-C) lowering trials, including FOURIER, ODYSSEY OUTCOMES, and Treat Stroke to Target (TST) trials, have mostly refuted the concern surrounding statin use, LDL-C lowering, and intracerebral hemorrhage (ICH) risk. However, the results from these trials may not be fully applied to ICH survivors, as the populations studied were mainly patients without prior ICH, in whom the inherent ICH risk is more than 10 times lower than that of ICH survivors. Although available literature on statin use after ICH has demonstrated no excess risk of recurrent ICH, other potential factors that may modify ICH risk, especially hypertension control and ICH etiology, have not generally been considered. Notably, data on LDL-C levels following ICH are lacking. AIMS: We aim to investigate the association between LDL-C levels and statin use with ICH risk among ICH survivors, and to determine whether the risk differed with patients' characteristics, especially ICH etiology. METHODS: Follow-up data of consecutive spontaneous ICH survivors enrolled in the University of Hong Kong prospective stroke registry from 2011 to 2019 were retrospectively analyzed. ICH etiology was classified as cerebral amyloid angiopathy (CAA) using the modified Boston criteria or hypertensive arteriopathy, while the mean follow-up LDL-C value was categorized as <1.8 or ⩾1.8 mmol/L. The primary endpoint was recurrent ICH. The association of LDL-C level and statin use with recurrent ICH was determined using multivariable Cox regression. Pre-specified subgroup analyses were performed, including based on ICH etiology and statin prescription. Follow-up blood pressure was included in all the regression models. RESULTS: In 502 ICH survivors (mean age = 64.2 ± 13.5 years, mean follow-up LDL-C = 2.2 ± 0.6 mmol/L, 28% with LDL-C <1.8 mmol/L), 44 had ICH recurrence during a mean follow-up of 5.9 ± 2.8 years. Statin use after ICH was not associated with recurrent ICH (adjusted hazard ratio (AHR) = 1.07, 95% confidence interval (CI) = 0.57-2.00). The risk of ICH recurrence was increased for follow-up LDL-C <1.8 mmol/L (AHR = 1.99, 95% CI = 1.06-3.73). This association was predominantly observed in ICH attributable to CAA (AHR = 2.52, 95% CI = 1.06-5.99) and non-statin users (AHR = 2.91, 95% CI = 1.08-7.86). CONCLUSION: The association between post-ICH LDL-C <1.8 mmol/L and recurrent ICH was predominantly observed in CAA patients and those with intrinsically low LDL-C (non-statin users). While statins can be safely prescribed in ICH survivors, LDL-C targets should be individualized and caution must be exercised in CAA patients.
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Hemorragia Cerebral , LDL-Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases , Recidiva , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , LDL-Colesterol/sangue , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sistema de Registros , Idoso de 80 Anos ou mais , Hong Kong/epidemiologiaRESUMO
Background: Although renal dysfunction is associated with adverse clinical outcomes in patients with atrial fibrillation (AF) following stroke, the impact of renal function variability is unclear. Aim: This study aimed to assess the association between renal function variability and various adverse clinical outcomes in patients with transient ischemic attack (TIA)/ischemic stroke and atrial fibrillation (AF). Methods: We conducted a population-based study and retrospectively identified patients hospitalized with a diagnosis of TIA/ischemic stroke and AF during 2016-2020 using the Clinical Data Analysis and Reporting System of Hong Kong. Serial serum creatinine tested upon the onset of TIA/ischemic stroke and during their subsequent follow-up was collected. Renal function variability was calculated using the coefficient of variation of the estimated glomerular filtration rate (eGFR). Clinical endpoints that occurred during the study period were captured and included ischemic stroke/systemic embolism, intracerebral hemorrhage (ICH), total bleeding, major adverse cardiovascular events (MACE), cardiovascular, non-cardiovascular, and all-cause mortality. Competing risk regression and Cox proportional hazard regression models were used to assess the associations of renal function variability with the outcomes of interest. Results: A total of 3,809 patients (mean age 80 ± 10 years, 43% men) who satisfied the inclusion and exclusion criteria were followed up for a mean of 2.5 ± 1.5 years (9,523 patient-years). The mean eGFR was 66 ± 22 mL/min/1.73 m2 at baseline, and the median number of renal function tests per patient during the follow-up period was 20 (interquartile range 11-35). After accounting for potential confounders, a greater eGFR variability was associated with increased risks of recurrent ischemic stroke/systemic embolism [fully adjusted subdistribution hazard ratio 1.11, 95% confidence interval (CI) 1.03-1.20], ICH (1.17, 1.01-1.36), total bleeding (1.13, 1.06-1.21), MACE (1.22, 1.15-1.30), cardiovascular (1.49, 1.32-1.69), non-cardiovascular (1.43, 1.35-1.52), and all-cause mortality (fully adjusted hazard ratio 1.44, 1.39-1.50). Conclusion: Visit-to-visit renal function variability is independently associated with adverse clinical outcomes in TIA/ischemic stroke patients with AF. Further large-scale studies are needed to validate our results.
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Although Coronavirus disease 2019 (COVID-19) vaccinations are generally recommended for persons with epilepsy (PwE), a significant vaccination gap remains due to patient concerns over the risk of post-vaccination seizure aggravation (PVSA). In this single-centre, retrospective cohort study, we aimed to determine the early (7-day) and delayed (30-day) risk of PVSA, and to identify clinical predictors of PVSA among PwE. Adult epilepsy patients aged ≥18 years without a history of COVID-19 infection were recruited from a specialty epilepsy clinic in early 2022. Demographic, epilepsy characteristics, and vaccination data were extracted from a centralized electronic patient record. Seizure frequency before and after vaccination, vaccination-related adverse effects, and reasons for or against vaccination were obtained by a structured questionnaire. A total of 786 PwEs were included, of which 27.0% were drug-resistant. At the time of recruitment, 74.6% had at least 1 dose of the COVID-19 vaccine. Subjects with higher seizure frequency (p < 0.0005), on more anti-seizure medications (p = 0.004), or had drug-resistant epilepsy (p = 0.001) were less likely to be vaccinated. No significant increase in seizure frequency was observed in the early (7 days) and delayed phases (30 days) after vaccination in our cohort. On the contrary, there was an overall significant reduction in seizure frequency 30 days after vaccination (1.31 vs. 1.89, t = 3.436; p = 0.001). This difference was seen in both types of vaccine (BNT162b2 and CoronaVac) and drug-resistant epilepsy, but just missed significance for the second dose (1.13 vs. 1.87, t = 1.921; p = 0.055). Only 5.3% had PVSA after either dose of vaccine. Higher pre-vaccination seizure frequency of ≥1 per week (OR 3.01, 95% CI 1.05-8.62; p = 0.04) and drug-resistant status (OR 3.32, 95% CI 1.45-249 7.61; p = 0.005) were predictive of PVSA. Meanwhile, seizure freedom for 3 months before vaccination was independently associated with a lower risk of PVSA (OR 0.11, 95% CI 0.04-0.28; p < 0.0005). This may guide epilepsy treatment strategies to achieve better seizure control for at least 3 months prior to vaccination. As COVID-19 shifts to an endemic phase, this study provides important data demonstrating the overall safety of COVID-19 vaccinations among PwE. Identification of high-risk patients with subsequent individualized approaches in treatment and monitoring strategies may alleviate vaccination hesitancy among PwE.
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BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; p = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH.
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Doenças de Pequenos Vasos Cerebrais , Ataque Isquêmico Transitório , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Masculino , Prognóstico , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/diagnóstico por imagem , Estudos Prospectivos , Hemorragias Intracranianas , Acidente Vascular Cerebral/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Hemorragia CerebralRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) patients are at increased risk of developing cardiovascular events. Unfortunately traditional risk assessment scores, including the Framingham Risk Score (FRS), have only modest accuracy in cardiovascular risk prediction in these patients. METHODS: We sought to determine the prognostic values of different non-invasive markers of atherosclerosis, including brachial artery endothelial function, carotid artery atheroma burden, ankle-brachial index, arterial stiffness and computed tomography coronary artery calcium score (CACS) in 151 T2DM Chinese patients that were identified low-intermediate risk from the FRS recalibrated for Chinese (<20% risk in 10 years). Patients were prospectively followed-up and presence of atherosclerotic events documented for a mean duration of 61 ± 16 months. RESULTS: A total of 17 atherosclerotic events in 16 patients (11%) occurred during the follow-up period. The mean FRS of the study population was 5.0 ± 4.6% and area under curve (AUC) from receiver operating characteristic curve analysis for prediction of atherosclerotic events was 0.59 ± 0.07 (P = 0.21). Among different vascular assessments, CACS > 40 had the best prognostic value (AUC 0.81 ± 0.06, P < 0.01) and offered significantly better accuracy in prediction compared with FRS (P = 0.038 for AUC comparisons). Combination of FRS with CACS or other surrogate vascular markers did not further improve the prognostic values over CACS alone. Multivariate Cox regression analysis identified CACS > 40 as an independent predictor of atherosclerotic events in T2DM patients (Hazards Ratio 27.11, 95% Confidence Interval 3.36-218.81, P = 0.002). CONCLUSIONS: In T2DM patients identified as low-intermediate risk by the FRS, a raised CACS > 40 was an independent predictor for atherosclerotic events.
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Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/epidemiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/epidemiologia , Idoso , Índice Tornozelo-Braço , Área Sob a Curva , Aterosclerose/fisiopatologia , Artéria Braquial/fisiopatologia , Artérias Carótidas/patologia , Espessura Intima-Media Carotídea , Distribuição de Qui-Quadrado , Comorbidade , Angiografia Coronária/métodos , Angiopatias Diabéticas/fisiopatologia , Intervalo Livre de Doença , Endotélio Vascular/fisiopatologia , Feminino , Seguimentos , Hong Kong/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Placa Aterosclerótica , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Onda de Pulso , Medição de Risco , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Calcificação Vascular/diagnóstico , Calcificação Vascular/epidemiologia , Rigidez VascularRESUMO
Background: Uncontrolled blood pressure (BP) in intracerebral hemorrhage (ICH) survivors is common and associated with adverse clinical outcomes. We investigated whether characteristics of the ICH itself were associated with uncontrolled BP at follow-up. Methods: Subjects were consecutive patients aged ⩾18 years with primary ICH enrolled in the prospective longitudinal ICH study at Massachusetts General Hospital between 1994 and 2015. We assessed the prevalence of uncontrolled BP (mean BP ⩾140/90 mmHg) 6 months after index event. We used multivariable logistic regression models to assess the effect of hematoma location, volume, and event year on uncontrolled BP. Results: Among 1492 survivors, ICH was lobar in 624 (42%), deep in 749 (50%), cerebellar in 119 (8%). Lobar ICH location was associated with increased risk for uncontrolled BP after 6 months (OR 1.35; 95% CI [1.08-1.69]). On average, lobar ICH survivors were treated with fewer antihypertensive drugs compared to the rest of the cohort: 2.1 ± 1.1 vs 2.5 ± 1.2 (p < 0.001) at baseline and 1.8 ± 1.2 vs. 2.4 ± 1.2 (p < 0.001) after 6 months follow-up. After adjustment for the number of antihypertensive drugs prescribed, the association of lobar ICH location with risk of uncontrolled BP was eliminated. Conclusions: ICH survivors with lobar hemorrhage were more likely to have uncontrolled BP after 6 months follow-up. This appears to be a result of being prescribed fewer antihypertensive medications. Future treatment strategies should focus on aggressive BP control after ICH independent of hemorrhage location.
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Background Survivors of intracranial hemorrhage (ICH) are at increased risk for major adverse cardiovascular and cerebrovascular events (MACCE), in the form of recurrent stroke and myocardial Infarction. We investigated whether long-term blood pressure (BP) variability represents a risk factor for MACCE after ICH, independent of average BP. Methods and Results We analyzed data from prospective ICH cohort studies at Massachusetts General Hospital and the University of Hong Kong. We captured long-term (ie, visit-to-visit) BP variability, quantified as individual participants' variation coefficient. We explored determinants of systolic and diastolic BP variability and generated survival analyses models to explore their association with MACCE. Among 1828 survivors of ICH followed for a median of 46.2 months we identified 166 with recurrent ICH, 68 with ischemic strokes, and 69 with myocardial infarction. Black (coefficient +3.8, SE 1.3) and Asian (coefficient +2.2, SE 0.4) participants displayed higher BP variability. Long-term systolic BP variability was independently associated with recurrent ICH (subhazard ratio [SHR], 1.82; 95% CI, 1.19-2.79), ischemic stroke (SHR, 1.62; 95% CI, 1.06-2.47), and myocardial infarction (SHR, 1.54; 95% CI, 1.05-2.24). Average BP during follow-up did not modify the association between long-term systolic BP variability and MACCE. Conclusions Long-term BP variability is a potent risk factor for recurrent hemorrhage, ischemic stroke, and myocardial infarction after ICH, even among survivors with well-controlled hypertension. Our findings support the hypothesis that combined control of average BP and its variability after ICH is required to minimize incidence of MACCE.
Assuntos
Hipertensão , AVC Isquêmico , Infarto do Miocárdio , Acidente Vascular Cerebral , Pressão Sanguínea/fisiologia , Hemorragia Cerebral/etiologia , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/epidemiologia , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologiaRESUMO
Background Recent trials have shown that low-density lipoprotein cholesterol (LDL-C) <1.80 mmol/L (<70 mg/dL) is associated with a reduced risk of major adverse cardiovascular events in White patients with ischemic stroke with atherosclerosis. However, it remains uncertain whether the findings can be generalized to Asian patients, or that similar LDL-C targets should be adopted in patients with stroke without significant atherosclerosis. Methods and Results We performed a prospective cohort study and recruited consecutive Chinese patients with ischemic stroke with magnetic resonance angiography of the intra- and cervicocranial arteries performed at the University of Hong Kong between 2008 and 2014. Serial postevent LDL-C measurements were obtained. Risk of major adverse cardiovascular events in patients with mean postevent LDL-C <1.80 versus ≥1.80 mmol/L, stratified by presence or absence of significant (≥50%) large-artery disease (LAD) and by ischemic stroke subtypes, were compared. Nine hundred four patients (mean age, 69±12 years; 60% men) were followed up for a mean 6.5±2.4 years (mean, 9±5 LDL-C readings per patient). Regardless of LAD status, patients with a mean postevent LDL-C <1.80 mmol/L were associated with a lower risk of major adverse cardiovascular events (with significant LAD: multivariable-adjusted subdistribution hazard ratio, 0.65; 95% CI, 0.42-0.99; without significant LAD: subdistribution hazard ratio, 0.53; 95% CI, 0.32-0.88) (both P<0.05). Similar findings were noted in patients with ischemic stroke attributable to large-artery atherosclerosis (subdistribution hazard ratio, 0.48; 95% CI, 0.28-0.84) and in patients with other ischemic stroke subtypes (subdistribution hazard ratio, 0.64; 95% CI, 0.43-0.95) (both P<0.05). Conclusions A mean LDL-C <1.80 mmol/L was associated with a lower risk of major adverse cardiovascular events in Chinese patients with ischemic stroke with and without significant LAD. Further randomized trials to determine the optimal LDL-C cutoff in stroke patients without significant atherosclerosis are warranted.
Assuntos
Aterosclerose/sangue , LDL-Colesterol/sangue , Dislipidemias/sangue , AVC Isquêmico/sangue , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Aterosclerose/diagnóstico por imagem , Aterosclerose/etnologia , Biomarcadores/sangue , Angiografia Cerebral , Dislipidemias/diagnóstico , Dislipidemias/etnologia , Feminino , Hong Kong/epidemiologia , Humanos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/etnologia , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
Background Survivors of intracerebral hemorrhage (ICH) are at high risk for recurrent stroke, which is associated with blood pressure control. Because most recurrent stroke events occur within 12 to 18 months of the index ICH, rapid blood pressure control is likely to be crucial. We investigated the frequency and prognostic impact of uncontrolled short-term hypertension after ICH. Methods and Results We analyzed data from Massachusetts General Hospital (n=1305) and the University of Hong Kong (n=523). We classified hypertension as controlled, undertreated, or treatment resistant at 3 months after ICH and determined the following: (1) the risk factors for uncontrolled hypertension and (2) whether hypertension control at 3 months is associated with stroke recurrence and mortality. We followed 1828 survivors of ICH for a median of 46.2 months. Only 9 of 234 (4%) recurrent strokes occurred before 3 months after ICH. At 3 months, 713 participants (39%) had controlled hypertension, 755 (41%) had undertreated hypertension, and 360 (20%) had treatment-resistant hypertension. Black, Hispanic, and Asian race/ethnicity and higher blood pressure at time of ICH increased the risk of uncontrolled hypertension at 3 months (all P<0.05). Uncontrolled hypertension at 3 months was associated with recurrent stroke and mortality during long-term follow-up (all P<0.05). Conclusions Among survivors of ICH, >60% had uncontrolled hypertension at 3 months, with undertreatment accounting for the majority of cases. The 3-month blood pressure measurements were associated with higher recurrent stroke risk and mortality. Black, Hispanic, and Asian survivors of ICH and those presenting with severe acute hypertensive response were at highest risk for uncontrolled hypertension.
Assuntos
Pressão Sanguínea/fisiologia , Hemorragia Cerebral/etiologia , Hipertensão/complicações , Idoso , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/fisiopatologia , Feminino , Seguimentos , Hong Kong/epidemiologia , Humanos , Hipertensão/fisiopatologia , Incidência , Masculino , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
The clinical diagnosis of neurodegenerative disorders based on phenotype is difficult in heterogeneous conditions with overlapping symptoms. It does not take into account the disease etiology or the highly variable clinical course even amongst patients diagnosed with the same disorder. The advent of next generation sequencing (NGS) has allowed for a system-wide, unbiased approach to identify all gene variants in the genome simultaneously. With the plethora of new genes being identified, genetic rather than phenotype-based classification of Mendelian diseases such as spinocerebellar ataxia (SCA), hereditary spastic paraplegia (HSP) and Charcot-Marie-Tooth disease (CMT) has become widely accepted. It has also become clear that gene variants play a role in common and predominantly sporadic neurodegenerative diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). The observation of pleiotropy has emerged, with mutations in the same gene giving rise to diverse phenotypes, which further increases the complexity of phenotype-genotype correlation. Possible mechanisms of pleiotropy include different downstream effects of different mutations in the same gene, presence of modifier genes, and oligogenic inheritance. Future directions include development of bioinformatics tools and establishment of more extensive public genotype/phenotype databases to better distinguish deleterious gene variants from benign polymorphisms, translation of genetic findings into pathogenic mechanisms through in-vitro and in-vivo studies, and ultimately finding disease-modifying therapies for neurodegenerative disorders.
RESUMO
Genetic variants are implicated in the development of amyotrophic lateral sclerosis (ALS), but it is unclear whether the burden of rare variants in ALS genes has an effect on survival. We performed whole genome sequencing on 8 familial ALS (FALS) patients with superoxide dismutase 1 (SOD1) mutation and whole exome sequencing on 46 sporadic ALS (SALS) patients living in Hong Kong and found that 67% had at least 1 rare variant in the exons of 40 ALS genes; 22% had 2 or more. Patients with 2 or more rare variants had lower probability of survival than patients with 0 or 1 variant (p = 0.001). After adjusting for other factors, each additional rare variant increased the risk of respiratory failure or death by 60% (p = 0.0098). The presence of the rare variant was associated with the risk of ALS (Odds ratio 1.91, 95% confidence interval 1.03-3.61, p = 0.03), and ALS patients had higher rare variant burden than controls (MB, p = 0.004). Our findings support an oligogenic basis with the burden of rare variants affecting the development and survival of ALS.
Assuntos
Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/mortalidade , Estudos de Associação Genética , Variação Genética/genética , Adulto , Idoso , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/epidemiologia , D-Aminoácido Oxidase/genética , Proteínas de Ligação a DNA/genética , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores Proteína Tirosina Quinases/genética , Receptor EphA3 , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologia , Risco , Superóxido Dismutase-1/genética , Sobrevida , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Antiplatelet resumption in patients who developed intracerebral hemorrhage (ICH) while on antiplatelet therapy (antiplatelet-related ICH) represents an important medical dilemma. We aimed to study the long-term cardiovascular outcomes of antiplatelet-related ICH survivors, and the risk of recurrent ICH with antiplatelet resumption. METHODS: This was an observational study of 109 antiplatelet-related ICH survivors. The clinical end points were recurrent ICH, ischemic vascular events, and vascular death (fatal ICH or ischemic vascular events). Predictors of recurrent ICH and vascular death were derived using a multivariable Cox regression model. RESULTS: The median duration of follow-up was 3.5 years (interquartile range, 1.6-5.8 years). Ischemic vascular events were more common than recurrent ICHs (6.8 per 100 patient-years vs. 2.6 per 100 patient-years; P = 0.028). Antiplatelet use was not associated with an elevated risk of recurrent ICH (hazard ratio [HR], 1.11, 95% confidence interval [CI], 0.27-4.62). A mean follow-up systolic blood pressure of >140 mmHg increased the risk of both recurrent ICH (HR, 4.28; 95% CI, 1.01-18.11) and vascular death (HR, 11.14; 95% CI, 2.72-45.62). Cerebral amyloid angiopathy (CAA) was an independent predictor for recurrent ICH (HR, 24.34; 95% CI, 2.80-211.47). CONCLUSIONS: Antiplatelet resumption after antiplatelet-related ICH did not appear to carry a clinically significant risk of recurrent ICH, whereas inadequate blood pressure control and CAA contributed to a more robust risk. Antiplatelet resumption should be considered, especially in survivors with adequate blood pressure control and without CAA.
Assuntos
Hemorragia Cerebral/induzido quimicamente , Inibidores da Agregação Plaquetária/efeitos adversos , Idoso , Hemorragia Cerebral/mortalidade , Substituição de Medicamentos , Feminino , Humanos , Isquemia/etiologia , Isquemia/mortalidade , Masculino , Recidiva , Estudos Retrospectivos , Fatores de Risco , SobreviventesRESUMO
BACKGROUND: This study was performed to determine the clinical correlates and long-term prognostic implications of microbleed burden and location in Chinese patients with ischemic stroke. METHODS AND RESULTS: We recruited 1003 predominantly Chinese patients with ischemic stroke who received magnetic resonance imaging at the University of Hong Kong. We determined the clinical correlates of microbleeds and the long-term risks (3126 patient-years of follow-up) of recurrent ischemic stroke and intracerebral hemorrhage (ICH) by microbleed burden (0 versus 1, 2-4, and ≥5) and location, adjusting for age, sex, and vascular risk factors and stratified by antithrombotic use. Microbleeds were present in 450 of 1003 of the study population (119/450 had ≥5, 187/450 had mixed location). Having ≥5 microbleeds was independently associated with prior antiplatelet and anticoagulant use, whereas microbleeds of mixed location were independently associated with hypertension and prior anticoagulant use (all P<0.05). Microbleed burden was associated with an increased risk of ICH (microbleed burden versus no microbleeds: 1 microbleed: multivariate hazard ratio: 0.59 [95% confidence interval, 0.07-5.05]; 2-4 microbleeds: multivariate hazard ratio: 2.14 [95% confidence interval, 0.50-9.12]; ≥5 microbleeds: multivariate hazard ratio: 9.51 [95% confidence interval, 3.25-27.81]; Ptrend<0.0001), but the relationship of microbleed burden and risk of recurrent ischemic stroke was not significant (Ptrend=0.054). Similar findings were noted in the 862 of 1003 patients treated with antiplatelet agents only (ICH: Ptrend<0.0001; ischemic stroke Ptrend=0.096). Multivariate analysis revealed that, independent of vascular risk factors, antithrombotic use, and other neuroimaging markers of small vessel disease, having ≥5 microbleeds (multivariate hazard ratio: 6.08 [95% confidence interval, 1.11-33.21]; P=0.037) was identified as an independent predictor of subsequent ICH, but neither microbleed burden nor location was predictive of recurrent ischemic stroke risk. CONCLUSIONS: In Chinese patients with ischemic stroke, a high burden of cerebral microbleeds was significantly associated with an increased risk of ICH; however, neither microbleed location nor burden was associated with recurrent ischemic stroke risk.
Assuntos
Isquemia Encefálica/epidemiologia , Encéfalo/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Hemorragias Intracranianas/epidemiologia , Imageamento por Ressonância Magnética/métodos , Microcirculação/fisiologia , Idoso , Encéfalo/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico , Feminino , Seguimentos , Humanos , Incidência , Hemorragias Intracranianas/complicações , Hemorragias Intracranianas/diagnóstico , Masculino , Prognóstico , Estudos Prospectivos , Recidiva , República da Coreia/epidemiologia , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
OBJECTIVES: To investigate the effect of erythropoiesis-stimulating agents (ESAs) on hemoglobin (Hb) level, fatigue and hospitalization rate in renal palliative care (PC) patients. METHOD: A retrospective cohort study was done between April 2011 and January 2013 in renal palliative care clinic of clustered hospitals in Hong Kong. The study participants included end-stage renal patients (CrCl < 15 ml/h) decided not for dialysis (ESA 39 patients; control 31 patients). From healthcare databases, we retrieved the patient demographics, laboratory results, reasons and time of hospitalizations during the study period. Fatigue was measured by Edmonton Symptom Assessment Scale. RESULTS: Most were elderly patients and about half of patients had underlying diabetes mellitus. Baseline mean Hb levels were similar (7.57 ± 0.97 g/dL for ESA vs 7.77 ± 0.72 g/dL for control). Mean Hb was raised significantly after 3 and 6 months of ESA injections (9.42 and 9.40 g/dL respectively, P < 0.05). Fatigue was reduced significantly at 3 and 6 months after treatment (P = 0.006 and P = 0.017 respectively). All-cause hospitalization was reduced significantly and there was a trend toward reduction in red blood cell transfusion requirement in the ESA group (P = 0.084). CONCLUSION: This study demonstrated that use of ESAs in renal PC was effective and might help in reducing fatigue and hospitalizations rate.