马文君
中国医学科学院阜外医院
OBJECTIVE:The aim of this study is to evaluate performance of aldosterone-to-renin ratio (ARR) before washout of antihypertensive drugs as a screening test for primary aldosteronism (PA).METHODS:This retrospective analysis included consecutive patients suspected of having secondary hypertension during a period from January 2017 to May 2022 at authors' institute. For inclusion in the final analysis, ARR must be available prior to as well as after discontinuation of antihypertensives. Patients with ARR ≥2.4(ng/dL)/(μIU/mL) after washout proceeded to confirmatory tests. Diagnosis of PA was established based on positive result of the confirmatory test. Diagnostic accuracy of ARR prior to the washout in predicting PA are shown as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).RESULTS:The analysis included a total of 1306 patients [median age of 50.2 (41.0-59.0) years, 64.0% male]. Confirmatory tests showed PA in 215(16.5%) patients and essential hypertension (EH) in the remaining 1091(83.5%) patients. In comparison to the second screening test, the first screening test (before washout of antihypertensives) yielded lower plasma aldosterone and higher renin, and consequently lower ARR in both the PA and EH groups. At a cutoff of 0.7(ng/dL)/(μIU/ml), ARR before washout had 96.3% sensitivity, 61.2% specificity, 0.33 PPV and 0.99 NPV. At a lower cutoff of 0.5(ng/dL)/(μIU/ml), the sensitivity, specificity, PPV and NPV are 97.7%, 52.0%, 0.29 and 0.99.CONCLUSIONS:ARR prior to washout of antihypertensives is a sensitive screening test for PA. Washout of antihypertensives could be omitted and further investigation for PA is not warranted if ARR was ≤ 0.7(ng/dL)/(μIU/ml) before washout.
The Journal of clinical endocrinology and metabolism 2024
Objective:To examine the consistency of plasma aldosterone concentration at 1 and 2 h in the captopril challenge test (CCT) and to explore the possibility of replacing 2-h aldosterone concentration with 1-h aldosterone concentration for diagnosis of primary aldosteronism (PA).Methods:This retrospective analysis included a total of 204 hypertensive patients suspected of having PA. Subjects received oral captopril challenge at 50 mg (25 mg if the systolic blood pressure was <120 mmHg), and plasma aldosterone concentration and direct renin concentration were measured at 1 and 2 h afterward (chemiluminescence immunoassay Liaison® DiaSorin, Italy). Sensitivity and specificity were used to reflect the diagnostic performance of 1-h aldosterone concentration using 2-h aldosterone concentration (11 ng/dl as the cutoff) as the reference. A receiver operating characteristic curve analysis was also conducted.Results:Among the 204 included patients [median age of 57.0 (48.0-61.0) years, 54.4% men], a diagnosis of PA was established in 94 patients. Aldosterone concentration in the patients with essential hypertension was 8.40 (interquartile range 7.05-11.00) ng/dl at 1 h and 7.65 (5.98-9.30) ng/dl at 2 h (P < 0.001). In patients with PA, aldosterone concentration was 16.80 (12.58-20.50) ng/dl at 1 h and 15.55 (12.60-20.85) ng/dl at 2 h (P > 0.999). At a cutoff of 11 ng/dl, the sensitivity and specificity of using 1-h aldosterone concentration to diagnose PA were 87.2% and 78.2%, respectively. A higher cutoff of 12.5 ng/ml increased specificity to 90.0% but decreased sensitivity to 75.5%. A lower cutoff of 9.3 ng/ml increased sensitivity to 97.9% but decreased specificity to 65.4%.Conclusions:When diagnosing PA with CCT, 1-h aldosterone concentration could not be used to replace 2-h aldosterone concentration.
Frontiers in endocrinology 2023
BACKGROUND:Mid-aortic syndrome (MAS), characterized by segmental stricture of the distal thoracic and abdominal aorta, is a heterogeneous clinical syndrome with multiple etiologies.METHODS:We retrospectively analyzed 143 consecutive patients (99 females and 44 males, mean age 40.93 ± 15.31 years) with MAS seen from January 1, 2010 to January 1, 2019.RESULTS:Takayasu arteritis (76.9%, 110/143) and atherosclerosis (19.6%, 28/143) were the most-common causes. There were also one patient with Behçet's disease and one with congenital MAS in the cohort. Hypertension was the most-common manifestation. Constitutional symptoms were mainly seen in Takayasu arteritis, and neurological, gastrointestinal and vascular symptoms were common in both Takayasu arteritis and atherosclerosis. The infrarenal segment was the most-commonly involved in atherosclerosis (89.3%, 25/28), whereas lesions were more distributed in Takayasu arteritis. The mean length of involved segments was longer (43.45 ± 23.64 mm vs. 30.68 ± 12.66 mm; P = 0.018) and the degree of stenosis was lower (80.20 ± 13.36% vs. 87.50 ± 13.95%, P = 0.004) in Takayasu arteritis than atherosclerosis. The most-common concurrently involved branch was the renal artery, followed by the celiac trunk and mesenteric arteries, in both Takayasu arteritis (51.8%, 32.7% and 27.3%, respectively) and atherosclerosis (53.6%, 25.0% and 17.9%, respectively). Concurrent artery involvement and coexisting lesions were absent in MAS caused by congenial coarctation of the abdominal aorta and Behçet's disease.CONCLUSIONS:Takayasu arteritis and atherosclerosis were the most-common causes of MAS among these adults. Imaging tests provided evidence of involved segments and luminal and mural changes, aiding conclusive diagnoses and etiological differentiation of MAS.
The American journal of the medical sciences 2023
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:Hypertension is currently the leading modifiable cause of global morbidity and mortality, leading to substantial health and financial burdens. Although multiple studies of management models and innovative therapeutic strategies for hypertension have been conducted, there are still gaps in the field, with a poor control rate reflecting a lack of novel, effective, clinically translated medication or intervention options. Recent animal and human studies repeatedly confirmed a link between the microbiota and hypertension. Of note is our previous study establishing a cause-and-effect relationship between the gut microbiota and blood pressure elevation. A hypothesis of gut microbiota intervention for treating hypertension is thus postulated, and fecal microbiota transplantation (FMT) from healthy donors was performed.METHODS:A multicenter, randomized, placebo-controlled, blinded clinical trial will be performed in 120 grade 1 hypertensive patients for 3 months. All recruited patients will be randomly assigned in a 1:1 ratio to take oral FMT capsules or placebo capsules on day 1, day 7, and day 14 and will be followed up on day 30, day 60, and day 90. The primary outcome is the change in office systolic blood pressure from baseline to day 30. The main secondary outcomes are BP indicators, including changes in systolic and diastolic blood pressure from office and 24-h ambulatory blood pressure monitoring; assessments of ankle-branchial index and pulse wave velocity; profiling of fecal microbial composition and function; profiling of fecal and serum metabolome; changes in levels of blood glucose, blood lipids, and body mass index; and assessment of adverse events as a measure of safety.DISCUSSION:Expanding upon our previous research on the role of the gut microbiota in the pathogenesis of hypertension, this study serves as a clinical translation advancement and explores the potential of fecal microbiota transplantation for treating hypertension. The underlying mechanisms, particularly the roles of specific microorganisms or their postbiotics in blood pressure amelioration, will also be investigated via multiple approaches, such as metagenomic sequencing and metabolomic profiling.TRIAL REGISTRATION:ClinicalTrials.gov NCT04406129 . Registered on May 28, 2020.
Trials 2022
BACKGROUND:Eighteen-hydroxycortisol (18-OHF) is a potential biomarker for differential diagnosis of the two major primary aldosteronism subtypes, aldosterone-producing adenoma, and idiopathic hyperaldosteronism.METHODS:Urine samples were processed, and the 18-OHF in urine samples were successfully quantified by in-house established dilute-and-shoot liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Separation was accomplished on a Sigma Ascentis Express C18 column with a gradient mixture of phase (A) 0.2% formic acid in water and phase (B) 0.2% formic acid in methanol at a flow rate of 0.4 ml/min. Mass spectrometric detection was performed in positive electrospray ionization mode via a mass spectrometer.RESULTS:The linearity of urinary 18-OHF ranged from 4.28 to 8.77 × 103 nmol/L, with a lower limit of quantification at 4.28 nmol/L. The intra- and inter-precision were both below 3%. The range of analytical recovery was 97.8%-109.2%. The validated dilute-and-shoot LC-MS/MS method was compared with the SPE LC-MS/MS method modified from the one reported in 2013. The results by Passing-Bablok regression analysis and Bland-Altman plotting demonstrated a good agreement between the two methods. The presented method was then applied to establish sex-specific reference intervals from 62 males and 62 females, respectively. The calculated 2.5%-97.5% reference intervals for 24-h urinary 18-OHF were 113-703 nmol/day for males and 71.2-450 nmol/day for females.CONCLUSION:The presented dilute-and-shoot LC-MS/MS method for 18-OHF quantification showed a good performance in the clinical application. Furthermore, the sex-specific reference intervals for 24-h urinary 18-OHF were first established and quite important for its application in primary aldosteronism subtyping.
Journal of clinical laboratory analysis 2022
OBJECTIVE:Evidence-based studies on endovascular approaches for childhood Takayasu arteritis (TAK) are limited. Our objective was to present the largest current real-world scenario for patients with childhood TAK undergoing interventions and their postinterventional outcomes.METHODS:Data were collected for patients with childhood TAK admitted from 2002 to 2017. Complication/reintervention-free survival was projected by Kaplan-Meier methods. Associated factors for intervention and predictors for postinterventional complications/reinterventions were assessed via regression models.RESULTS:Among 101 patients enrolled, 69 (68.3%) underwent 121 interventions (angioplasty 95, stenting 26) during a 3.1-year follow-up. Compared with the nonintervention group, the intervention group independently associated with a male population (odds ratio [OR] 0.27, P = 0.035) and type IV disease (OR 17.92, P = 0.001). Male sex also marginally indicated a risk for reintervention (hazard ratio [HR] 3.22, P = 0.05). Baseline retinopathy, delay in diagnosis, and descending thoracic aorta involvement were associated with stent insertion (P < 0.05). Hypertension secondary to renal artery stenosis (RAS; 59.4%) or mid-aorta stenosis (MAS; 14.5%), heart failure (21.7%), and claudication (21.7%) were leading clinical hints for interventions. The technical success rate was 96.7%. During a median 2.88-year of follow-up after intervention, 36 lesions occurred with complications in 28 patients, and 22 lesions in 17 patients, particularly on the renal artery or mid-aorta. The 5-year complication-free and reintervention-free survivals were 50.7% and 65.8%, respectively. Peri-interventional dual antiplatelet therapy (DAPT; HR 0.31), concurrent surgery (HR 26.5), and technical failure (HR 3.65) were independent predictors for complications (P < 0.05). Male sex (HR 2.52), retinopathy secondary to hypertension (HR 3.41), and pulmonary artery hypertension (PAH; HR 3.64) were baseline indicators for complications (P < 0.05).CONCLUSION:Over two-thirds of patients with childhood TAK require interventions, and the 5-year complication-free survival is 50.7%. Male sex, retinopathy, and PAH at baseline indicate the possibility of unfavorable outcomes. Interventions on MAS or RAS in childhood TAK raise specific concerns. DAPT peri-intervention appears to protect patients with childhood TAK from postinterventional complications.
Arthritis care & research 2021
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:Mid-aortic syndrome (MAS) may induce changes in cardiac structure among patients with Takayasu arteritis (TA).METHODS:Consecutive adult patients with TA (January 1, 2011 to January 1, 2018) were enrolled and their data was retrospectively analyzed.RESULTS:Patients were divided into MAS group (100/457 patients, 21.8%) and non-MAS group (357, 78.1%). The left ventricular mass index (LVMI) was higher in the MAS group than the non-MAS (113.78±26.82 versus 100.74±23.66 g/m2, respectively; P<0.001). The MAS group showed higher prevalence than the non-MAS group of mild-to-severe mitral regurgitation (9.0% and 3.9%, respectively; P=0.040) and aortic regurgitation (26% and 14.8%, respectively; P=0.003). No difference was found in the rates of heart failure (27.0% and 19.9% for MAS and non-MAS, respectively; P=0.126). The MAS group also showed lower estimated glomerular filtration rates than the non-MAS group (89.93±18.89 versus 96.16±21.60 mL/min/1.73 m2, respectively; P=0.009) and higher prevalence of renal artery stenosis (57% versus 43.7%; P=0.018). MAS was independently related to greater LVMI in both unadjusted model [β=12.60; 95% confidence interval (CI): 7.09-18.11; P<0.001] and the model adjusted for multiple indices (β=9.91; 95% CI: 4.57-15.25; P<0.001) in multivariate linear analysis. The LVMI significantly decreased from 111.49±25.65 to 100.36±22.91 g/m2 (P<0.001) among 55 patients who underwent successful revascularization treatment for MAS, while no significant difference (P=0.635) was observed among patients treated with medicine alone.CONCLUSIONS:TA-induced MAS is a potential independent risk factor for increased LVMI, and revascularization therapy for MAS is effective in reversing structural changes in the heart.
Annals of translational medicine 2021
BACKGROUND:Chronic heart failure (CHF) is a serious complication and a major cause of mortality in patients with Takayasu arteritis (TA). We aimed to explore the clinical features and long-term outcomes in TA patients with CHF.METHODS AND RESULTS:Adult TA patients admitted to our hospital between January 2009 to April 2018 were classified as HF and non-HF group. The adverse events were defined as a composite of all-cause mortality and hospitalization for HF. The outcome of the HF-group was further analyzed. A total of 61 HF patients and 102 non-HF patients were identified. In the HF group, the median age at assessment was 41.9 years, and female was predominant (82.0%). The multivariable logistic regression model revealed that pulmonary hypertension, aortic regurgitation, mitral regurgitation, level albumin, and uric acid were independently associated with CHF. After a median follow-up of 1347 days, 25 adverse events occurred in HF patients, and the 5-year event-free rate was 54.7%. The Cox model showed that coronary artery involvement, aortic regurgitation, without interventional treatment were related to adverse events.CONCLUSIONS:The 5-year event-free rate was not satisfying. Aggressive intervention may decreased the likelihood of adverse events in patients with CHF.
International journal of cardiology 2021
