樊家俐
中国医学科学院阜外医院 高血压
OBJECTIVE:Mounting evidence has linked microbiome and metabolome to systemic autoimmunity and cardiovascular diseases (CVDs). Takayasu arteritis (TAK) is a rare disease that shares features of immune-related inflammatory diseases and CVDs, about which there is relatively limited information. This study was undertaken to characterize gut microbial dysbiosis and its crosstalk with phenotypes in TAK.METHODS:To address the discriminatory signatures, we performed shotgun sequencing of fecal metagenome across a discovery cohort (n = 97) and an independent validation cohort (n = 75) including TAK patients, healthy controls, and controls with Behçet's disease (BD). Interrogation of untargeted metabolomics and lipidomics profiling of plasma and fecal samples were also used to refine features mediating associations between microorganisms and TAK phenotypes.RESULTS:A combined model of bacterial species, including unclassified Escherichia, Veillonella parvula, Streptococcus parasanguinis, Dorea formicigenerans, Bifidobacterium adolescentis, Lachnospiraceae bacterium 7 1 58FAA, Escherichia coli, Streptococcus salivarius, Klebsiella pneumoniae, Bifidobacterium longum, and Lachnospiraceae Bacterium 5 1 63FAA, distinguished TAK patients from controls with areas under the curve (AUCs) of 87.8%, 85.9%, 81.1%, and 71.1% in training, test, and validation sets including healthy or BD controls, respectively. Diagnostic species were directly or indirectly (via metabolites or lipids) correlated with TAK phenotypes of vascular involvement, inflammation, discharge medication, and prognosis. External validation against publicly metagenomic studies (n = 184) on hypertension, atrial fibrillation, and healthy controls, confirmed the diagnostic accuracy of the model for TAK.CONCLUSION:This study first identifies the discriminatory gut microbes in TAK. Dysbiotic microbes are also linked to TAK phenotypes directly or indirectly via metabolic and lipid modules. Further explorations of the microbiome-metagenome interface in TAK subtype prediction and pathogenesis are suggested.
Arthritis & rheumatology (Hoboken, N.J.) 2023
Background:The STEP (Strategy of Blood Pressure Intervention in the older Hypertensive Patients) trial showed that intensive systolic blood pressure (SBP) control resulted in a lower incidence of cardiovascular events than standard treatment. This study analyzed the effects of intensive SBP lowering on cognitive function.Methods:STEP was a multicenter, randomized controlled trial of hypertensive patients aged 60-80 years. Participants were randomly assigned (1:1) to SBP goals of 110-130 mmHg (intensive treatment) or 130-150 mmHg (standard treatment). Each individual was asked to complete a cognitive function test (Mini-Mental State Examination; MMSE) at baseline and during follow-up. The primary outcome for this study was the annual change in MMSE score. Subjects with a score less than education-specific cutoff point were categorized as cognitive decline.Results:The analysis enrolled 6,501 participants (3,270 participants in the intensive-treatment and 3,231 participants in the standard-treatment groups). Median follow-up was 3.34 years. There was a minor change in MMSE score, with an annual change of -0.001 [95% confidence interval [CI] -0.020, 0.018] and 0.030 (95% CI 0.011, 0.049) in the intensive- and standard-treatment groups, respectively (p = 0.052). Cognitive decline occurred in 46/3,270 patients (1.4%) in the intensive-treatment group and 42/3,231 (1.3%) in the standard-treatment group (hazard ratio 0.005, 95% CI 0.654, 1.543, p = 0.983).Conclusions:Compared with standard treatment, intensive SBP treatment did not result in a significant change in cognitive function test score. The impact of intensive blood pressure lowering was not evident using this global cognitive function test.Trial registration:ClinicalTrials.gov. Unique identifier: NCT03015311.
Frontiers in neurology 2023
BACKGROUND:In the STEP trial (Strategy of Blood Pressure Intervention in older Hypertensive Patients), the risk of cardiovascular events is significantly lower in patients who received intensive systolic blood psressure (BP) treatment than in those who received standard treatment. This study compared the lifetime health benefits and medical costs of intensive BP treatment with those of standard BP treatment.METHODS:A microsimulation model included 10 000 hypothetical samples of Chinese adults aged 60 to 80 years old with baseline systolic BP higher than 140 mm Hg. Primary outcome was the incremental cost-effectiveness ratio from a payer's perspective. Secondary outcome was cardiovascular events, including acute coronary syndrome, stroke, acute decompensated heart failure, atrial fibrillation, and death from cardiovascular causes.RESULTS:The model simulated that cardiovascular events occurred in 36.88% of the patients in the intensive treatment group, as compared to 41.28% of the patients in the standard treatment group over the lifetime horizon. The mean number of quality-adjusted life-years would be 0.16 higher in patients who received intensive treatment than in those who received standard treatment and would cost Chinese yuan 12 614 (International dollars 3018) more per quality-adjusted life-year gained. Most simulation results indicated that intensive treatment would be cost-effective (82%-95% below the willingness-to-pay threshold of Chinese yuan 72 000 [1× the gross domestic product per capita in China in 2020]). Sensitivity analyses showed that these conclusions were robust.CONCLUSIONS:In this study, intensive BP treatment prevented cardiovascular events among older patients with hypertension in China and was cost-effective in most scenarios.REGISTRATION:URL: https://www.CLINICALTRIALS:gov; Unique identifier: NCT03015311.
Hypertension (Dallas, Tex. : 1979) 2022
OBJECTIVE:The present study aimed to evaluate the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) aiding in diagnosing and evaluating disease activity in Takayasu arteritis (TA) patients with atypical clinical manifestations.METHODS:A retrospective study of 22 TA patients was conducted. All the participants were classified into two groups. Group one including 12 patients, who did not fulfill American College of Rheumatology (ACR) criteria, were diagnosed by modified Ishikawa criteria. Group two involving ten patients, who did not satisfy the modified Ishikawa criteria or ACR criteria, were clinically diagnosed as TA after panel discussion by a combination of clinical data, excluding other diagnoses. PET/CT results were analyzed using quantitative and qualitative metrics. Disease activity was evaluated using the US National Institutes of Health (NIH) criteria.RESULTS:In group one, nine patients in active stage and two patients in inactive stage had active FDG uptake. One patient in inactive stage had inactive PET/CT results. In group two, five patients in active stage had active FDG uptake and five patients in inactive stage had inactive FDG uptake with SUVmax values of several vascular lesions slightly lower than livermean in each person. The sensitivity of PET/CT scans for evaluating disease activity was 100.0%, specificity was 75.0%, positive predictive value was 87.5%, and negative predictive value was 100.0% compared to NIH criteria.CONCLUSIONS:PET/CT plays a unique role in diagnosing these TA with atypical manifestation and assisting in evaluating disease activity. Key Points • Diagnosis of these TA patients with atypical manifestations may be difficult. • PET/CT plays a unique role in diagnosing these TA patients and assisting in evaluating disease activity.
Clinical rheumatology 2021
BACKGROUND:Childhood Takayasu's arteritis (c-TA) is scarcely reported but is characterized by devastating morbidity and mortality. This study aims to investigate the clinical course of c-TA and prognostic factors associated with rehospitalization and events including vascular complications, flares, and death.METHODS:An ambispective study of 101 c-TA patients satisfying the American College of Rheumatology (ACR) criteria and/or the European League against Rheumatism (EULAR)/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS) criteria was conducted from January 2002 to December 2017. Data on demographic, clinical, laboratory, imaging, and therapeutic features were collected. Event-free survival, complication-free survival, flare-free survival, rehospitalization-free survival, and associated prognostic factors were assessed by Kaplan-Meier survival curve and propensity score analysis.RESULTS:The median age at c-TA onset was 14 (interquartile range (IQR) 12-16) years and 76.2% were female. Hypertension (70.3%), blood pressure discrepancy (55.4%), bruits (51.5%), and pulse deficits (37.6%) were core presentations. Major vascular involvement included the renal artery (62.4%), abdominal aorta (42.6%), subclavian artery (43.6%), and carotid artery (42.6%). Glucocorticoids (78.2%), antihypertensive drugs (72.3%), antiplatelet agents (72.3%), and revascularization (57.4%) were made up the majority administered. At a median 2.4 (IQR 0.7-6.1) years of follow-up, events, rehospitalization, vascular complications, flares and death were observed in 44.6%, 37.6%, 44.6%, 26.7%, and 3%, respectively. The 5-year event-free survival, rehospitalization-free survival, vascular complication-free survival, and flare-free survival were 42.8%, 55.8%, 45.9%, and 62.3%, respectively. Body mass index (BMI) (hazard ratio (HR) = 0.49, 95% confidence interval (CI) 0.30-0.81, p = 0.005), stroke (HR = 7.37, 95% CI 2.35-23.1, p = 0.001), and revascularization (HR = 0.51, 95% CI 0.27-0.94, p = 0.032) were independent prognostic predictors of events. Predictors for rehospitalization include age at admission (HR = 0.81, 95% CI 0.69-0.94, p = 0.006), renal artery involvement (HR = 0.49, 95% CI 0.25-0.96, p = 0.037), and elevated C-reactive protein (CRP; HR = 2.50, 95% CI 1.24-5.00, p = 0.01). BMI level (p = 0.024) and renal artery involvement (p = 0.015) were also associated with vascular complications, while revascularization (p = 0.002) independently correlated with re-flares.CONCLUSIONS:This large ambispective study of c-TA revealed an early 3% mortality at the first year and around 50% morbidity within 5 years after diagnosis. Hypertension, renal artery involvement, and revascularization based on anti-inflammation, antihypertension, and antiplatelet medications dominated c-TA with indications for optimistic prognosis. Patients with initial lower BMI level, a younger age at admission, stroke, and elevated CRP have a high risk of poor outcomes, requiring close c-TA monitoring and more aggressive management.TRIAL REGISTRATION:NCT03199183 , unique protocol ID: 2016-ZX43. June 26, 2017.
Arthritis research & therapy 2019
BACKGROUND:To investigate the clinical features, management, and outcomes of childhood Takayasu arteritis (c-TA) initially presenting with hypertension.METHODS:This study retrospectively reviewed medical charts of 96 inpatient c-TA cases from January 2002 to December 2016, with 5 additional patients being prospectively recruited from January 2017 to December 2017. Data were compared between c-TA groups initially presenting with and without hypertension. Blood pressure (BP) control, event-free survival, and associated risk factors were assessed by logistic regression, Kaplan-Meier survival curve, and COX regression models.RESULTS:The hypertensive cohort (N = 71, 28.2% males) as compared with non-hypertensive cohort had significantly fewer active diseases; fewer episodes of claudication, syncope, blurred vision, and myocardial ischemia; and fewer systemic symptoms (P < 0.05). The hypertensive group presented with more localized abdominal lesions (OR = 14.4, P = 0.001) and limited supradiaphragmatic arterial involvement. Renovascular disease (P = 0.001) and revascularization (P = 0.006) were associated with hypertension. At the median 3-year follow-up, 53% of hypertensive patients achieved BP control and 39% experienced events including vascular complications, flares, or death. The 1-, 3-, 5-, and 10-year event-free survival were 78.7% (95% CI: 65.7%-87.2%), 63.0% (95% CI: 48.1%-74.7%), 48.9% (95% CI: 32.0%-63.8%), and 31.6% (95% CI: 13.8%-51.2%), higher than in non-hypertensive group (P = 0.014). Heart failure, stroke, and body mass index <18.5 kg/m2 were prognostic factors for events. Intervention and baseline systolic BP were independent factors for BP control (P < 0.05).CONCLUSIONS:Majority of c-TA has hypertension, presenting with a more quiescent disease without typical systemic and/or ischemia symptoms, more localized abdominal lesions, higher proportion of revascularizations and better event-free survival. Three-year BP control is more than 50%. Intervention particularly on renal artery is beneficial for BP control and decreased events.CLINICAL TRIAL REGISTRATION:Trial Number: NCT03199183.
American journal of hypertension 2019
Following publication of the original article [1], the authors reported an error.
Arthritis research & therapy 2019
