P. T. Chan

Life expectancy, standardized mortality ratios, and causes of death in six rheumatic diseases in Hong Kong, China.

OBJECTIVE To examine the life expectancy, standardized mortality ratios (SMRs), and causes of death in 6 groups of patients from Hong Kong with different rheumatic diseases. METHODS Patients with a diagnosis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic vasculitis (SV), or systemic sclerosis (SSc) registered in 37 public hospitals between 1999 and 2008 were identified in the hospital registry. SMRs were calculated by comparing the mortality rate in patients with each disease with that in the general population. Life expectancy was calculated by abridged life-table analysis, and the causes of death were compared. RESULTS In 2008, data on 8,367 RA, 5,243 SLE, 2,154 AS, 1,636 SV, 778 PsA, and 449 SSc patients were available in our registry. The age- and sex-adjusted SMRs were highest for SLE (5.25 [95% confidence interval 4.79-5.70]), SSc (3.94 [95% confidence interval 3.20-4.68]), and SV (2.64 [95% confidence interval 2.36-2.93]). In female patients, the loss in life expectancy was greatest for SSc (34.1 years), SV (19.3 years), and SLE (19.7 years). In male patients, the loss in life expectancy was highest for SV (28.3 years), SLE (27 years), and SSc (16 years). There were 2,486 deaths during the study period (1999-2008), and the principal causes were infections (28%), cardiovascular complications (18%), cancer (16%), and disease activity (7%). Infection was the leading cause of death in SLE, RA, AS, and PsA, whereas deaths from disease-related activity and cardiovascular complications were most frequent in SSc. Cancer was the most common cause of death in SV. CONCLUSION Our findings indicate that patients with SLE, RA, AS, PsA, SV, and SSc have increased mortality rates and reduced life expectancy. SLE has the highest adjusted SMR, and female SSc patients have the greatest loss in life expectancy. Infection is the leading cause of death, followed by cardiovascular complications and malignancies.

Prevalence of atherosclerotic risk factors and the metabolic syndrome in patients with chronic inflammatory arthritis

To evaluate the prevalence of the metabolic syndrome in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA).

Anti–müllerian hormone and ovarian reserve in systemic lupus erythematosus

OBJECTIVE To study the level of anti-müllerian hormone (AMH) and its relationship to age and previous exposure to cyclophosphamide (CYC) in patients with systemic lupus erythematosus (SLE). METHODS Consecutive female patients ages 18-52 years who had menses at least once during the preceding 12 months and fulfilled ≥4 American College of Rheumatology criteria for SLE were recruited. AMH was determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum AMH levels were compared in patients with and without previous use of immunosuppressive agents. The relationship of the AMH level to the patients age and CYC exposure was studied by linear regression and receiver operating characteristic (ROC) curve analysis. RESULTS A total of 216 patients were studied (mean±SD age 35.1±10.1 years, mean±SD SLE duration 7.6±5.9 years). The mean±SD AMH level was significantly lower in patients previously exposed to CYC therapy than in those who had not been exposed after adjustment for age (1.58±2.92 versus 1.73±2.11 ng/ml; P=0.04). The median time interval between the AMH assay and the last dose of CYC administered was 6.7 years (interquartile range 3.4-8.5). AMH levels in users versus nonusers of other immunosuppressive agents, including mycophenolate mofetil, azathioprine, and the calcineurin inhibitors, were not statistically different. Linear regression revealed increasing age (beta -0.32, P=0.02) and each 5 gm of CYC exposure (beta -0.28, P=0.047) were independently associated with a lower AMH level. In patients ages 30 years and younger, a cumulative CYC dose cutoff of 5.9 gm yielded a sensitivity of 0.75 and a specificity of 0.80 for the prediction of undetectable AMH level on ROC curve analysis. CONCLUSION AMH is a sensitive marker for ovarian damage due to previous CYC exposure in women with SLE.

Prevalence and risk factors of low bone mineral density in Chinese patients with systemic sclerosis: a case–control study

OBJECTIVE To study the prevalence and risk factors of low BMD in patients with SSc. METHODS Consecutive patients with SSc and an equal number of age- and gender-matched healthy subjects were screened for BMD, fat and lean mass by DXA scan. BMD, body composition and osteoporosis risk factors were compared between patients and controls. Associated factors for low BMD in SSc patients were studied by linear regression. RESULTS A total of 84 patients with SSc were studied [89% women; age 49.4 (11.3) years; 21% diffuse subtype; disease duration 7.8 (6.4) years]. Except for significantly lower BMI (P = 0.001), fat mass (P = 0.02) and lean body mass (P = 0.006) observed in SSc patients, the prevalence of other osteoporosis risk factors was similar to controls. Fourteen (17%) and five (6%) SSc patients had low BMD expected for age (z-score <-2.0) at the lumbar spine and hip, respectively. BMD of the lumbar spine, hip, femoral neck and whole body was significantly lower in SSc patients than controls, adjusted for age, sex, menopause and BMI (P < 0.05 in all; effect size 0.44-0.54). Linear regression revealed increasing age, menopause and low BMI were independently associated with low BMD at the spine or hip in SSc patients. However, BMD did not correlate with the severity of involvement of the skin and other systems. CONCLUSION BMD of the spine and hip is significantly lower in patients with SSc than in healthy subjects, which is independent of age, sex, menopause, low BMI and altered body composition.

Prevalence of the antiphospholipid syndrome and its effect on survival in 679 Chinese patients with systemic lupus erythematosus: a cohort study.

AbstractIn this work we evaluate the prevalence of the antiphospholipid syndrome (APS) and its impact on survival in Chinese patients with systemic lupus erythematosus (SLE). We studied a prospective cohort of southern Chinese patients who fulfilled ≥4 American College of Rheumatology criteria for SLE. The cumulative rate of survival over time was calculated by the Kaplan-Meier method. APS was defined by the 2006 updated consensus criteria. We evaluated the prevalence and manifestations of APS, and compared the survival of patients with and without APS. We followed 679 patients with SLE (92% women; age of onset, 32.5 ± 14 yr) for 9.7 ± 7.3 years. Sixty-eight (10%) patients died and 33 (4.9%) patients were lost to follow-up. Forty-four (6.5%) patients met the criteria for APS, manifested by the following: ischemic stroke (55%), deep venous thrombosis (32%), obstetric morbidity (14%), cardiovascular events (9%), and peripheral vascular disease (9%). Nine (9/44 [20%]) APS patients died, which was more frequent than the non-APS patients (59/635 [9%]; p = 0.02). The cumulative mortality of patients with APS was 4.6% at 5 years, 7.8% at 10 years, and 22.2% at 15 years, which was not significantly higher than that of non-APS patients (5.4% at 5 years, 9.2% at 10 years, and 11.3% at 15 years; p = 0.14). However, if we considered only patients with APS caused by arterial thrombosis, the presence of APS was significantly associated with mortality (hazard ratio, 2.29; 95% confidence interval, 1.13–4.64; p = 0.02). We conclude that the presence of APS increases the mortality risk of Chinese patients with SLE, which is mainly contributed by arterial thrombotic events.Clinical significance: 1) APS is infrequent in southern Chinese patients with SLE compared to white patients. 2) Arterial thrombosis is a more common manifestation of APS than venous thrombosis in Chinese SLE patients. 3) APS related to arterial thrombosis is associated with increased mortality in Chinese patients with SLE.

THU0299 Factors Associated with Long-Term Renal Function Deterioration in Lupus Nephritis Treated Initially with Combined Prednisolone and Mycophenolate Mofetil (MMF) or Tacrolimus (TAC)

Objectives To study the risk factors for renal function decline in patients with lupus nephritis treated initially with combined steroid and MMF or Tac. Methods Data were extracted from a randomized controlled trial of the efficacy of MMF vs Tac for induction treatment of lupus nephritis. All patients recruited were treated with high-dose prednisolone (0.6mg/kg/day for 6-8 weeks and tapered) with either MMF (2-3g/day) or Tac (0.1-0.06mg/kg/day) for 6 months. Patients with good clinical response were shifted to azathioprine (AZA) (2mg/kg/day) and continued on low dose prednisolone (<10mg/day) for maintenance. Rescue therapies were given to patients who did not have response to treatment at the discretion of the attending physicians. Factors associated with renal function decline at 5 years were studied by Cox regression analyses. Results 150 patients (92% women) with biopsy confirmed active lupus nephritis were studied (ISN/RPS class III 17%; IVG 31%; IVS 12%; III/IV+V 21%; pure V 20%). The mean age was 35.5±12.8 years and SLE duration was 50.2±62 months at the time of renal biopsy. 102 (68%) patients had first time glomerulonephritis while the others had relapsed disease. The mean histological activity and chronicity score was 8.2±3.4 and 2.6±1.6, respectively. 59(39%) patients were hypertensive, 62(41%) had active urinary casts and 112(75%) had microscopic hematuria at presentation. The mean creatinine clearance (CrCl) was 79.0±30.8 ml/min and 67% patients had CrCl less than 90ml/min. At 6 months, 61% patients achieved good clinical response, 25% had partial response but 15% patients had no response (NR) (urine P/Cr improvement <50% or >3.0 or deterioration in CrCl (>20%) ± persistently active urinary sediments and lupus serology). Rescue regimens for NR patients included: oral or intravenous pulse cyclophosphamide (68%), Tac or MMF (14%) and MMF + Tac combination (18%). 128(85%) patients received AZA (83.1±23mg/day) for maintenance therapy. After a mean follow-up of 56±28 months, 27(18%) patients had loss of CrCl by >=30% and 17 (11%) patients developed stage 4/5 chronic kidney disease (CKD) (CrCl <30ml/min). The cumulative risk of loss of CrCl by >=30% or stage 4/5 CKD was 3% at 12 months, 7.7% at 24 months, 8.4% at 36 months, 13.6% at 48 months and 17.3% at 60 months. Cox regression revealed histological activity score (HR 0.78[0.65-0.94]; p=0.007), chronicity score (1.46[1.06-2.01]; p=0.02), non-response at 6 months (HR 3.87[1.34-11.2]; p=0.01), class V histology (HR 0.35[0.16-0.74]; p=0.006) and number of renal flares (HR 1.59[1.01-2.49; p=0.04] were independent risk factors for CrCl loss by 30% of stage 4/5 CKD, after adjustment for age, sex, SLE duration, first-time renal disease, proteinuria and CrCl at presentation and the treatment arm during induction phase (MMF or Tac). Conclusions Combined prednisolone with MMF or Tac is equally effective for the initial treatment of active lupus nephritis. No response at 6 months, proliferative types of lupus nephritis, lower activity but higher chronicity score on renal biopsy and the number of renal flares are predictive of renal function decline at 5 years. Disclosure of Interest None Declared

FRI0252 Severity of skin, tendon and joint damage in chinese patients with systemic sclerosis (SSC) is associated with higher disability and poorer health-related quality of life: A case-control study

Objectives To study the disability and health-related quality of life (HRQoL) in Chinese patients with SSc, and its relationship with the extent of skin involvement and organ damage. Methods Consecutive patients who fulfilled the ACR preliminary classification criteria for SSc and an equal number of age and gender matched healthy controls were recruited for a cross-sectional study on HRQoL and disability. HRQoL was assessed by the validated Chinese version of the 36-item Medical Outcome Short Form (SF-36) questionnaire, whereas disability was assessed by the Chinese version of Health Assessment Questionnaire (HAQ). In patients with SSc, the extent of skin involvement was assessed by the modified Rodnan Skin score (mRSS) and organ damage of SSc was assessed by the systemic sclerosis severity index proposed by Medsger. The SF36 and HAQ score was compared between SSc patients and controls. Linear regression models were established to study the correlation among HAQ, SF36 score, Medsger severity index and clinical characteristics in patients with SSc. Results 77 patients with SSc (87% women; mean age 50±12 years; disease duration 7.8±6.6 years) and 77 matched controls were studied. Fourteen (18%) patients had diffuse type of SSc (dcSSc) whereas the remaining had limited type of SSc (lcSSc). The median mRSS was 8 (IQR4-14; range0-37) points. The median severity index was 3 (IQR1-6; range0-18) points. The frequency of organ damage as assessed by the Medsger SSc severity index (≥1 point) was, in descending order: skin (96.1%), peripheral vascular damage (50.6%), joint/tendon contracture (33.8%), pulmonary system (33.8%), gastrointestinal tract (7.8%), renal system (7.8%), weight loss (5.2%), cardiovascular system (5.2%) and myopathy (2.6%). Compared to the healthy controls, the subscores of all the eight domains of the SF36, namely physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health, physical component sub-score, mental component subscore, and total SF36 score were significantly lower in SSc patients than controls (p<0.01 in all). The HAQ score was also significantly higher in patients with SSc compared to controls (p<0.01). In patients with SSc, linear regression analyses revealed that the HAQ score correlated positively and significantly with the mRSS score (Beta 0.483; p<0.01). The total SF36 score correlated inversely and significantly with the mRSS score (Beta-0.322;p=0.01), after adjustment for age, sex and duration of SSc. Regarding the individual organ systems of the Medsger severity index, the HAQ score correlated positively with skin damage (Beta0.412;p<0.01), peripheral vascular damage (Beta0.288;p=0.018), joint and tendon contracture (Beta0.377;p=0.001), myopathy (Beta0.294;p=0.011) and weight loss (beta0.314;p=0.005); whereas the total SF36 score correlated inversely and significantly with skin damage (Beta-0.353;p=0.003), joint and tendon contracture (Beta-0.291;p=0.015). Conclusions Chinese patients with SSc have poorer HRQoL and greater disability than healthy controls. The quality of life of SSc patients is adversely affected by the extent of skin involvement and contracture of the joints and tendons. More skin and peripheral vascular damage, joint/tendon contracture and myopathy is associated with greater disability. Disclosure of Interest None Declared

THU0242 Incidence and risk factors for low bone mineral density in patients with systemic sclerosis (SSC): A case-control study

Objectives To study the bone mineral density (BMD) and body composition (BC) in Chinese patients with systemic sclerosis (SSc), and the risk factors for low BMD. Methods Consecutive patients who fulfilled the ACR criteria for SSc were screened for BMD and BC (fat and lean mass) by dual energy X-ray absorptiometry (DXA) scan (Hologic, Belford USA). Exclusion criteria were: (1) Age <18 years; (2) Informed consent could not be obtained. An equal number of age and gender matched healthy controls were also recruited for the same measurements. The extent of skin involvement was assessed by the modified Rodnan skin score (mRSS) and organ damage was evaluated by the Medsger SSc severity index. Risk factors for low BMD were studied by linear regression analyses. Results 77 patients with SSc and 77 controls were studied (91% women). The mean age of SSc patients was 42.7±14 years and the mean disease duration was 7.8±6.6 years. Sixteen (21%) patients had diffuse SSc while the others had limited SSc. Only 5 (6%) patients were receiving bisphosphonates. According to the WHO criteria, 9 (12%) patients with SSc had osteoporosis (T score ≤-2.5) at the hip and 26 (34%) patients had osteoporosis at the lumbar spine. The incidence of osteoporosis at the hip and lumbar spine was significantly higher than that in normal controls (hip 1%; p=0.008, lumbar spine 14%; p=0.004). Osteopenia of the hip and spine (T score between -1 and -2.5), occurred in 58% and 36%, respectively, of the SSc patients. Four (5%) patients had personal history of fractures, all of which were non-vertebral fractures. The body weight (BW) of patients with SSc was significantly lower than controls (52.5±9.9 vs 56.4±8.3kg; p<0.001). After adjustment for age, body mass index (BMI) and other osteoporosis risk factors, BMD of the total hip (0.786±0.138 vs 0.857±0.118g/m2; p=0.01) and femoral neck (0.674±0.123 vs 0.734±0.117g/m2; p<0.001) were significantly lower in patients with SSc than controls. The BMD of the lumbar spine (L2-4) was also significantly lower in SSc patients (0.894±0.155 vs 0.972±0.148g/m2; p=0.001). On the other hand, the total bone mineral content (BMC) (1.76±0.34 vs 1.92±0.30g; p=0.002) and lean body mass (32.9±5.3 vs 35.1±5.6kg; p=0.01) were significantly lower in patients with SSc than controls. The median mRSS score and total Medsger severity index of the SSc patients was 8 (IQR 4-13) and 3 (IQR 1-6), respectively. Logistic regression analysis revealed a significant correlation between mRSS score and BMD of the total hip (OR 1.12[1.004-1.24] per point; p=0.04) but not with the lumbar spine (OR 1.10[0.996-1.210] per point; p=0.06) after adjustment for age, sex and BMI. The total Medsger severity score correlated positively but insignificantly with osteoporosis of the lumbar spine (OR 1.01[0.87-1.17]; p=0.90) or the hip (OR 1.15[0.98-1.35]; p=0.09). Increasing age was the other independent and adverse factor related to both osteoporosis of the hip and spine (p<0.01 in both). Conclusions Patients with SSc have significantly lower BMD at lumbar spine, hip and femoral neck, as well as lean body mass than age and gender matched healthy controls. Osteoporosis of the hip correlates significantly with the extent of skin involvement but not with organ damage. Disclosure of Interest None Declared

THU0303 Hypovitaminosis D and the Metabolic Syndrome in Patients with Systemic Lupus Erythematosus (SLE)

Background Low vitamin D level has been linked to cardiovascular diseases and mortality in the general population. Hypovitaminosis D is associated with certain traditional vascular risk factors in patients with SLE. Objectives To study the relationship between the metabolic syndrome (MetS) and serum 25-hydroxyvitamin D level in patients with SLE Methods Consecutive patients who fulfilled >=4 ACRcriteria for SLEin a two-month period were recruited from our out-patient lupus clinics. Blood was taken in the morning for the assay of 25-hydroxyvitamin D3 (enzyme immunoassay; Immunodiagnostic Systems Inc, Fountain Hills, AZ, USA) and high sensitivity C-reactive protein (hsCRP) (solid phase chemilluminescence immunometric assay; Siemens Healthcare Diagnostics, Deerfield, Il., USA). Clinical assessments (waist circumference, fasting glucose and lipid level, blood pressure) were made for each patient who was stratified for the MetS according to the 2009 International joint consensus criteria, using the Asian criteria for abdominal obesity(ref 1). The relationship between 25-hydroxyvitamin D level and the MetS was studied by linear regression, with adjustment for other confounding covariates. Results 257 SLE patients (94% women) were studied. All were ethnic Chinese. The mean age was 39.6±13.1 years and SLE duration was 8.3±6.9 years. Vitamin D insufficiency (25-hydroxyvitamin D3 <30ng/mL), deficiency (25-hydroxyvitamin D3 <15ng/mL, and severe deficiency (level<10ng/mL) was present in 95%, 25% and 3.5% of patients, respectively. The prevalence of the MetS was 8.3%, 11% and 22.2% in patients with vitamin D insufficiency, deficiency and severe deficiency, respectively. None of the patients with 25-hydroxyvitamin D3 levels >30ng/mL fulfilled the criteria for the MetS. Linear regression analysis revealed that levels of 25(OH)vitamin D3 were independently associated with age (Beta 0.19; p=0.002), the presence of the MetS (Beta -0.14; p=0.049) and hsCRP level (Beta -0.14; p=0.04) after adjustment for gender, SLE duration, duration of sunshine in the month of venepuncture, SLE damage scores (SDI), smoking ³3 years, renal insufficiency (estimated CrCl < 50ml/min), photosensitivity and ever use of glucocorticoids. Conclusions Vitamin D deficiency is prevalent in patients with SLE. Hypovitaminosis D is independently associated with the MetS and hsCRP, suggesting that it is a novel risk factor for vascular thrombosis in patients with SLE. References Alberti KG et al. Circulation 2009;120:1640–5. Disclosure of Interest None Declared