Jiuliang Zhao

Chinese SLE Treatment and Research group (CSTAR) registry: II. Prevalence and risk factors of pulmonary arterial hypertension in Chinese patients with systemic lupus erythematosus.

Objectives To estimate the prevalence of pulmonary arterial hypertension (PAH) and risk factors for PAH in patients registered in the Chinese SLE Treatment and Research group (CSTAR) database, the first online registry of Chinese patients with systemic lupus erythematosus (SLE). Methods A prospective cross-sectional study of patients with SLE was conducted using the CSTAR registry. Resting transthoracic echocardiography was used to estimate pulmonary artery pressure (PAP); PAH was defined as systolic PAP (PASP) ≥40 mmHg. Patients with interstitial lung disease, valvular disease or cardiomyopathy were excluded because of disease influence on PAP. We explored potential risk factors for PAH including patient characteristics, organ involvement, laboratory findings and SLE disease activity. Results Of 1934 patients with SLE, 74 had PASP with 54.2 ± 17.1 (40,106) mmHg and were diagnosed with probable PAH. The incidences of lupus nephritis, pleuritis, pericarditis, hypocomplementemia, anti-SSA, and anti-ribonucleoprotein (RNP) were significantly higher in patients with PAH than in those without (p<0.05). SLE disease activity was significantly higher in patients with PAH than in unaffected patients (p<0.05). Multivariate analysis indicated that pericarditis (odds ratio (OR) = 4.248), pleuritis (OR = 3.061) and anti-RNP (OR = 2.559) were independent risk factors for PAH in patients with SLE (p<0.05). Conclusions The possible prevalence of PAH was 3.8% in Chinese patients with SLE in the CSTAR registry. The significant association of pericarditis, pleuritis and anti-RNP positivity with PAH suggests that higher disease activity and vasculopathy may both contribute to the development of PAH in SLE, which need be treated aggressively to improve prognosis.

Long-Term Survival and Death Causes of Systemic Lupus Erythematosus in China: A Systemic Review of Observational Studies

AbstractSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with an increased risk of death compared to general population. Although previous studies showed improvement in survival of SLE, the long-term prognosis has not been elaborated in China.This study aims to integrate the observational studies estimating current long-term survival of Chinese SLE patients and analyze the death-cause situation of SLE in China.The study is a systemic review of English and non-English articles using MEDLINE, EMBASE, CNKI, WANFANG, and SINOMED databases. Additional studies were found by consultation with clinical experts, browse of references in selected papers, and search of related textbooks. Our major search terms were SLE, follow-up, prognosis, survival, mortality, and China.We included cohort studies for survival analysis, and both cohort studies and case series for death-cause analysis in China.The extraction of the articles were done by 2 authors independently using predesigned charts, including characteristics of study, clinical data, analyzing data, and study quality indicators.All pooled analyses were conducted both for random-effects model and fixed-effects model. Funnel plots and Egger regression tests were applied to check potential publication bias. Heterogeneity was tested by sensitivity analysis. We identified 5 studies for survival analysis comprising 4469 Chinese patients with SLE (380 observed deaths). Thirty-six studies were suitable for death-cause analysis with 2179 observed deaths (derived from more than 20,000 Chinese patients with SLE). The overall pooled survival rates for SLE in China were 94% for 5-year survival rate and 89% for 10-year survival rate after disease onset from the year 1995 to 2013, which were similar with previous publications in Asia-Pacific area. The proportions of different causes of death showed infection (33.2%), renal involvement (18.7%), lupus encephalopathy (13.8%), and cardiovascular disease (11.5%) as the top 4 causes.The overall survival rates for Chinese patients with SLE resembled previous publications in Asia-Pacific area. But the death causes of SLE in China were of some differences indicating relatively higher proportion of infection and lupus encephalopathy and lower cardiovascular disease. Ethnicity and more aggressive treatment might have contributed to the difference in death composition.

Baseline Characteristics and Risk Factors of Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus Patients

AbstractPeking Union Medical College Hospital (PUMCH) has started a single-center right heart catheterization (RHC)-based pulmonary arterial hypertension (PAH) study in systemic lupus erythematosus (SLE) since 2006. The baseline characteristics of these patients were described and the risk factor for PAH in lupus was identified.The demographic, clinical, laboratory, and treatment characteristics of SLE patients with PAH when they were registered were collected as the baseline data. A case-control study was conducted by taking the admitted SLE-non-PAH patients adjusted for age and gender in a 4:1 ratio during the same period as the controls. The associated variables were examined by binary multivariate logistic regression analysis to identify possible risk factors. A total of 111 RHC-confirmed SLE-PAH patients were enrolled, with the onset age of 34.6 ± 8.6 years old and the average SLE duration of 5 years. RHC revealed mPAP as 46.4 ± 11.4 mm Hg, CI as 2.7 ± 0.8 L/min × m2, and PVR as 10.5 ± 4.8 WU. 46% of patients were WHO Fc I–II. All patients were treated with immunosuppressive agents and 65% patients had PAH-targeted therapy. The case-control study had confirmed 2 independent risk factors previously published: pericardial effusion (OR = 21.290, P < 0.001) and anti-RNP antibody (OR = 12.399, P < 0.001). Meanwhile, 6 independent variables were discovered: baseline SLE duration (OR = 1.118, P = 0.007), interstitial lung disease (OR = 17.027, P < 0.001=, without acute rash (OR = 3.258, P = 0.019), anti-SSA antibody (OR = 4.836, P = 0.004), SLEDAI⩽9 (OR = 26.426, P < 0.001), ESR⩽20 mm/h (OR = 12.068, P < 0.001), and uric acid > 357 &mgr;mol/L (OR = 9.666, P < 0.001) to be associated with PAH in SLE patients.The PUMCH study has shown that SLE patients complicated with PAH are usually earlier diagnosed and have less disease severity than patients without PAH. The immunosuppressive therapy rate and the PAH target therapy rate were high, which is consistent with reports from Western countries. This study has confirmed that pericardial effusion and positive anti-RNP antibody are risk factors for SLE-associated PAH. Long SLE disease duration, the presence of interstitial lung disease, without acute skin rash, positive anti-SSA antibody, low SLEDAI and ESR, and high uric acid levels are also associated with PAH in SLE patients.

Clinical characteristics and survival of pulmonary arterial hypertension associated with three major connective tissue diseases: A cohort study in China

OBJECTIVE Pulmonary arterial hypertension (PAH) is a major cause of death in connective tissue disease patients. This study investigated the clinical characteristics and survival of CTD-PAH in Chinese patients. METHODS This cohort study enrolled 190 consecutive PAH patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), or primary Sjögrens syndrome (pSS) who visited our referral center between May 2006 and December 2014. Baseline demographics, clinical features, laboratory results, and hemodynamic assessments were analyzed. Cox proportional hazards regression analysis was used to identify independent factors associated with increased risk of mortality. RESULTS The PAH patients were more likely to have SLE (58.4%) as the underlying CTD than SSc (26.3%) or pSS (15.3%). Mean age was 37.8±10.4years, and patients with SLE were youngest at the time of PAH diagnosis. The most prevalent autoantibody was anti-U1RNP antibody (55.8%). The three groups did not differ significantly regarding World Health Organization functional class or hemodynamic results. The overall 1-, 3-, and 5-year survival rates were 87.1%, 79.1%, and 62.9%, respectively. The 3-year survival rate of 81.3% for those with SLE-PAH was significantly better than that for patients with SSc-PAH (63.6%, P<0.05). Independent predictors of mortality were 6-minute walk distance (6MWD) ≤380m (HR 3.222, 95% CI 1.485-6.987, P=0.003) and underlying CTD (HR 1.684; 95CI% 1.082-2.622, P=0.021). CONCLUSION Independent predictors of mortality for CTD-PAH were 6MWD <380m and SSc as the underlying CTD. Increased awareness of pSS-PAH is needed because of its worse prognosis compared to SLE-PAH.

Cause of death in Chinese Takayasu arteritis patients.

AbstractTo analyze the causes of death and the related risk factors for in-patients with Takayasu arteritis (TAK) admitted to a referral center of China during 1983 to 2014.The medical charts of 12 deceased TAK patients (10 women, 2 men) were reviewed by two senior rheumatologists. The demographic data, clinical manifestations, angiographic presentations, and the direct causes of death were analyzed retrospectively. Medical records of 40 TAK patients (32 women, 8 men) were selected as controls by age and sex matching method from 81 patients who were sampled isometrically from 810 successively admitted TAK in-patients of the same center during the same period. In addition to the comparison of clinical manifestations between the two groups, binary logistic regression was conducted to explore the related risk factors of mortality of TAK.Twelve patients died at the median age of 33.5 (ranging from 13 to 68 years old). The median survival time was 102.5(ranging from 6 to 567) months. The direct causes of death were heart failure in 5 (5/12, 41.7%), hemorrhage in 2 (2/12, 16.7%), pulmonary infection in 2 (2/12, 16.7%), sudden death in 1 (1/12, 8.3%), postoperative complication in 1 (1/12, 8.3%), and end-stage malignancy in 1 (1/12, 8.3%). Ischemia (4/12, 33.3%) and hemorrhage (4/12, 33.3%) were the two most common presentations in deceased patients. Eight patients had received surgical procedures related to TAK changes. Among them, 2 patients died after surgical procedure, the other 6 patients died later of non-operation-related causes. Compared with the control group (n = 40), patients in the deceased group had longer disease duration (P = 0.017), higher proportion of active disease (P = 0.020), secondary hypertension (P = 0.004), and congestive heart failure (P = 0.017). A model of binary logistic regression had revealed that secondary hypertension (odds ratio [OR] = 9.333, 95% confidence interval [CI]: 1.721 – 50.614, P = 0.010), congestive heart failure (OR = 5.667, 95% CI: 1.248 – 25.734, P = 0.025), and longer disease duration (OR = 1.007, 95% CI: 1.001 – 0.735, P = 0.027) were risk factors for TAK mortality. Active disease (OR = 0.167, 95% CI: 0.038 – 50.614, P = 0.018) was negatively associated with death of TAK.Heart failure is the leading cause of death in TAK patients, followed by ischemia and pulmonary infection. Early deaths occur postoperatively but become rare later after the procedure. Well-control of hypertension, and prevention of congestive heart failure may improve the long-term prognosis.

Chinese SLE treatment and research group registry: III. association of autoantibodies with clinical manifestations in Chinese patients with systemic lupus erythematosus.

We investigated the characteristics of Chinese SLE patients by analyzing the association between specific autoantibodies and clinical manifestations of 2104 SLE patients from registry data of CSTAR cohort. Significant (P < 0.05) associations were found between anti-Sm antibody, anti-rRNP antibody, and malar rash; between anti-RNP antibody, anti-SSA antibody, and pulmonary arterial hypertension (PAH); between anti-SSB antibody and hematologic involvement; and between anti-dsDNA antibody and nephropathy. APL antibody was associated with hematologic involvement, interstitial lung disease, and a lower prevalence of oral ulcerations (P < 0.05). Associations were also found between anti-dsDNA antibody and a lower prevalence of photosensitivity, and between anti-SSA antibody and a lower prevalence of nephropathy (P < 0.05). Most of these findings were consistent with other studies in the literature but this study is the first report on the association between anti-SSA and a lower prevalence of nephropathy. The correlations of specific autoantibodies and clinical manifestations could provide clues for physicians to predict organ damages in SLE patients. We suggest that a thorough screening of autoantibodies should be carried out when the diagnosis of SLE is established, and repeated echocardiography annually in SLE patients with anti-RNP or anti-SSA antibody should be performed.

Evaluation of the diagnostic potential of antibodies to beta2-glycoprotein 1 domain 1 in Chinese patients with antiphospholipid syndrome.

In this study, we evaluated the clinical performance of anti-β2-glycoprotein 1 domain 1 antibodies (aβ2GP1-D1) in the diagnosis of antiphospholipid syndrome (APS). Sera from 229 subjects were tested, including 35 patients with primary APS, 51 patients with APS associated to other diseases, 30 patients with non-APS thrombosis, 32 patients with non-APS pregnancy-related morbidity, 42 patients with systemic lupus erythematosus, and 39 healthy controls (HC). Serum IgG aβ2GP1-D1, IgG/IgM anti-cardiolipin (aCL) and IgG/IgM aβ2GP1 were measured by a chemiluminescence assay. The levels of IgG aβ2GP1-D1 were significantly increased in patients with APS, compared with disease controls and HCs (p < 0.001). Significant correlation was identified between IgG aβ2GP1-D1 and IgG aβ2GP1 (p < 0.0001), indicating IgG aβ2GP1-D1 were the predominant domain-specific antibodies in IgG aβ2GP1 family. Importantly, aβ2GP1-D1, but not aβ2GP1 non-D1, was significantly correlated with thrombotic events. Interestingly, no significant correlation between IgG aβ2GP1-D1 and obstetric complications was observed. Additionally, significantly higher levels of IgG aβ2GP1-D1 were found in patients with triple aPL positivity, compared with patients with double and single aPL positivity. Our findings suggest a potential role of IgG aβ2GP1-D1 in identifying APS patients with high risk of thrombosis, shedding insight on the introduction of IgG aβ2GP1-D1 in China.

Survival and prognostic factors of systemic lupus erythematosus-associated pulmonary arterial hypertension: A PRISMA-compliant systematic review and meta-analysis.

OBJECTIVE This study aims to evaluate the survival of patients with systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH) by a systematic review and meta-analysis. METHODS Studies were searched from MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trial and Scopus databases, and were selected according to the inclusion and exclusion criteria. Two independent reviewers extracted data from selected studies. Quality assessments were also performed using the Newcastle-Ottawa Scale. All pooled analyses were conducted both for random-effects model and fixed-effects model. Subgroup analysis and sensitivity analysis were conducted to investigate the origins of heterogeneity. Publication bias was evaluated using Beggs funnel plots and Eggers test. RESULTS Six studies encompassing 323 patients with SLE-associated PAH were included in the meta-analysis. The pooled 1-, 3- and 5-year survival rates were 88% (95% CI, 0.80-0.93), 81% (95% CI, 0.67-0.90) and 68% (95% CI, 0.52-0.80), respectively. No significant publication bias was shown. WHO Functional class (Fc) III/IV was found to be an independent prognostic factor of mortality. Higher mean pulmonary arterial pressure (mPAP), higher pulmonary vascular resistance (PVR), lower six minutes walking distance (6MWD), higher brain natriuretic peptide (BNP) and higher N-terminal proBNP (NT-proBNP) level were also related to poor survival. CONCLUSION The long-term survival of patients with SLE-associated PAH is poor, which is worth paying greater clinical and academic attention. This study suggested that early diagnosis and management are recommended in patients with SLE-associated PAH for a better outcome of survival.

Protein-Losing Enteropathy in Systemic Lupus Erythematosus: 12 Years Experience from a Chinese Academic Center

Objective Protein-losing enteropathy (PLE) is a complication in some systemic lupus erythematosus (SLE) patients that is often misdiagnosed. With this study, we provide insight into clinical characteristics, laboratory characteristics, diagnostic tests, risk factors, treatment, and prognosis of the disease. Methods A retrospective, case-control study was performed in 44 patients with SLE-related PLE (PLE group) and 88 patients with active SLE (control group) admitted to our care from January 2000−January 2012. Risk factors for SLE-related PLE were examined, and we analyzed the accuracy of single and combined laboratory characteristics in discriminating SLE-related PLE from active SLE. Serum albumin and C3 levels were measured as outcome during and after treatment with corticosteroids and immunosuppressive agents. Results The PLE group had lower mean serum albumin and 24-hour urine protein levels, higher mean total plasma cholesterol levels, and greater frequencies of anti-SSA and SSB seropositivity compared with the control group. Anti-SSA seropositivity, hypoalbuminemia, and hypercholesterolemia were independent risk factors for SLE-related PLE. The simultaneous presence of serum albumin (<22 g/l) and 24-hour urine protein (<0.8 g/24 h) had high specificity, positive predictive value, negative predictive value, and positive likelihood ratio, a low negative likelihood ratio and no significant reduction in sensitivity. High dosage of glucocorticosteroid combined with cyclophosphomide were mostly prescribed for SLE-related PLE. Conclusion SLE-related PLE should be considered when an SLE patient presents with generalized edema, anti-SSA antibody seropositivity, hypercholesterolemia, severe hypoalbuminemia, and low 24-hour urine protein levels. Aggressive treatment for lupus might improve prognosis.

The clinical characteristics of Chinese Takayasu’s arteritis patients: a retrospective study of 411 patients over 24 years

BackgroundWe aimed to investigate the clinical characteristics of 411 Chinese Takayasu’s arteritis (TAK) patients using a retrospective analysis.MethodsWe retrospectively reviewed 810 medical charts of patients with a diagnosis of TAK who were admitted to Peking Union Medical College Hospital from 1990 to 2014. 411 patients with a complete dataset were finally included in the analysis. The demographic data, clinical features, angiographic patterns, and TAK-related surgical procedures were collected and analyzed.ResultsThe median age at disease onset was 23 (18, 30) years old, with a median disease duration of 21 (6, 60) months; 325 (79.1%) were female. The angiographic involvement pattern was type I in 91 (22.1%) patients, type IIa in 16 (3.9%) patients, type IIb in 16 (3.9%) patients, type III in 12 (2.9%) patients, type IV in 26 (6.3%) patients, and type V in 250 (60.8%) patients. Subclavian arteries (79.8%) were the most commonly involved, followed by carotid arteries (79.1%). The occurrence rate (4.1%) of aortic aneurysm in this study was low; 119 operations and interventions were performed. The most common cause of death in this study was heart failure.ConclusionSubclavian arteries, carotid arteries, and type V were the most frequently involved arteries and angiography pattern in this Chinese TAK study. The difference in angiographic features may lead to differences in clinical manifestations. Surgical operation and interventions should be performed at different stages of the disease course.