Carolyn Neville

Thromboembolic risk in patients with high titre anticardiolipin and multiple antiphospholipid antibodies

Asymptomatic antiphospholipid antibody (aPL) carriers with high risk for thrombosis may benefit from preventive anticoagulation. It was our objective to test whether the risk of thrombosis increases with: 1). increasing titres of anticardiolipin antibodies (aCL) after adjustment for other cardiovascular risk factors and 2). the number of aPL detected. In a cross-sectional study, blood was collected from clinics in two teaching hospitals. The study included 208 individuals suspected of having an aPL and 208 age- and sex-matched controls having blood drawn for a complete blood count. Clinical variables included history of previous arterial (ATE) or venous (VTE) thrombotic events, traditional risk factors for cardiovascular disease, and systemic lupus erythematosus (SLE). Laboratory variables included IgG/IgM aCL, lupus anticoagulant, and IgG/IgM anti-beta2-glycoprotein I. Mean age was 46.5 years and 83% were female. Seventy-five of the 416 participants had >or= 1 aPL, and 69 had confirmed >or= 1 ATE or VTE. Family history was positive in 48% of participants, smoking in 28%, hypertension in 16%, diabetes in 6%, and SLE in 20%. A 10-unit increase in aCL IgG titre was associated with an odds ratio (OR) [95% CI] of 1.07 [1.01-1.13] for ATE and 1.06 [1.02-1.11] for VTE. The odds of a previous thrombosis increased with each additional aPL detected: 1.5 [0.93-2.3] for ATE and 1.7 [1.1-2.5] for VTE. These results indicate that increased titres of aCL and multiple aPL were associated with an increased risk of a previous thrombotic event.

Discordance between patients and their physicians in the assessment of lupus disease activity: relevance for clinical trials

Discordance between patient and physician assessment of lupus activity occurs frequently and its determinants are not known. Examples of discordance between patients and physicians in other disease models can be found in the literature. A better understanding of the discordance between patients and physicians can help us achieve a shared decision-making model of health care, improve patient satisfaction, improve patient compliance, and improve physician understanding of how lupus impacts on their patients. Understanding discordance also impacts on the design and interpretation of clinical trials.

Antiphospholipid antibodies predict imminent vascular events independently from other risk factors in a prospective cohort

Antiphospholipid antibodies (aPL) are associated with vascular events, but the magnitude of this risk, alone, or in combination with other atherogenic and thrombophilic risk factors, remains unclear. A prospective cohort of 415 persons was studied for arterial and venous events (AE and VE) over a median time of 7.4 years. aPL and coagulation abnormalities were measured upon beginning of the study and annually for the first four years. Within the cohort, a nested case-control study was conducted to investigate the role of endothelial and inflammatory markers in predicting new vascular events. Forty-five individuals had new vascular events: 18 occurred during the first year of follow-up. The proportion of event-free survivors at eight years was 90% (95%CI = 87%, 94%) for aPL-negative and 72% (60%, 85%) for aPL-positive individuals, respectively. Predictors for new AE were previous AE (HR = 5.7 [2.7, 12.0]), diabetes (5.6 [2.4, 13.2]), aPL positivity (2.6 ([1.2, 5.9]), and age (1.04 [1.01, 1.07]). New VE were predicted by previous VE (6.1 [1.9, 19.9]), anti-beta2-glycoprotein I (abeta2GPI) positivity (5.8 [1.4, 24.1]), activated protein C resistance (APCR) (4.1 [1.1, 15.1]), and gender (3.7 [1.1, 12.9]). In the nested case-control study, similar predictors were observed for AE, while abnormal APCR (OR = 5.5 [1.1, 26.6]) and elevated von Willebrand factor (vWF) (OR = 5.0 [1.2, 19.8]) best predicted VE. We demonstrate that aPL independently predict new vascular events and discriminate between individuals with and without events in the first two years of follow-up, indicating that aPL are associated with a short-term risk of developing new and recurrent vascular events.

Longitudinal Evolution of Risk of Coronary Heart Disease in Systemic Lupus Erythematosus

Objective. To produce evidence on the longitudinal evolution of risk factors for coronary heart disease (CHD) in patients with systemic lupus erythematosus (SLE). Methods. Based on data for 115 patients from the Montreal General Hospital Lupus Clinic (1971–2003) and for 4367 control subjects from the Framingham Offspring Study (1971–1994), we investigated the temporal evolution of total serum cholesterol, systolic blood pressure (SBP), body mass index (BMI), blood glucose, and estimated risk for CHD (reflecting the balance of changes in different risk factors). In analyses limited to patients with SLE, we assessed the effect of SLE duration on each risk factor, adjusting for age, calendar time, sex, baseline level of the risk factor, and medication use. Next, we assessed how the adjusted difference in the values of the risk factors between SLE and controls changes over time. Results. Among patients with SLE, longer disease duration was independently associated with higher SBP and blood glucose levels. Compared with controls, these patients appeared to have accelerated rates of increase in total cholesterol, blood glucose, and overall estimated CHD risk. The rate of increase in BMI was lower in patients with SLE than in controls. Conclusion. Elevated CHD risk in patients with SLE appears to be at least partially mediated by accelerated increases in some CHD risk factors, longitudinal trajectories of which increasingly diverge over time from those of population controls.

Antiphospholipid antibodies and thrombosis: association with acquired activated protein C resistance in venous thrombosis and with hyperhomocysteinemia in arterial thrombosis

Although antiphospholipid antibodies (aPL) are associated with thrombosis, it is not known who with aPL is at higher risk for thrombosis. It was the aim of this cross-sectional study to investigate how thrombophilic factors contribute to venous or arterial thrombosis in aPL-positive individuals. In outpatient test centres at two tertiary care hospitals, two hundred and eight (208) persons requiring aPL testing were matched by age, gender and centre to 208 persons requiring a complete blood count. Persons were classified as aPL-positive (having anticardiolipin, lupus anticoagulant and/or anti-beta(2)-glycoprotein I antibodies) or aPL-negative. Several thrombophilic factors were studied using logistic regression modelling. Results showed that the aPL-positive group had three-fold more events (37%) than the aPL-negative group (12%). In unadjusted analyses, clinically important associations were observed between factor V Leiden and venous thrombosis, hyperhomocysteinemia and arterial thrombosis, and activated protein C resistance (APCR) and venous thrombosis (OR, 95% CI = 4.00, 1.35-11.91; 4.79, 2.03-11.33; and 2.03, 1.03-3.97, respectively). After adjusting for recruitment group, persons with both APCR and aPL had a three-fold greater risk (OR, 95% CI = 3.31, 1.30-8.41) for venous thrombosis than those with neither APCR nor aPL. Similarly, after adjusting for hypertension, family history of cardiovascular disease, gender and recruitment group, persons with both hyperhomocysteinemia and aPL had a five-fold increased risk (OR, 95% CI = 4.90, 1.37-17.37) for arterial thrombosis compared to those with neither risk factor. In conclusion, APCR phenotype and hyperhomocysteinemia are associated with a higher risk of venous and arterial thrombosis, respectively, in the presence of aPL.

Ten-year Absolute Fracture Risk and Hip Bone Strength in Canadian Women with Systemic Lupus Erythematosus

Objective. Women with systemic lupus erythematosus (SLE) are at risk of osteoporosis (OP) and fractures because of SLE or its treatments. We aimed to determine in women with SLE (1) the prevalence of low bone mass (LBM) in those < 50 years of age and OP in those > 50 years of age; (2) the 10-year absolute fracture risk in those > 40 years of age using the Canadian Fracture Risk Assessment Tool (FRAX); (3) bone quality using hip structural analysis (HSA); and (4) the associations between HSA and age, SLE duration, and corticosteroid exposure. Methods. Women without prior OP fractures were eligible. Bone mineral densities at the hip, spine, and femoral neck were determined using dual-energy x-ray absorptiometry. OP was determined using World Health Organization definitions for participants aged ≥ 50 years (32.8%), and LBM was defined as Z-scores ≤ −2.0 for those aged < 50 years. For those aged ≥ 40 years (63.5%), the 10-year probabilities of a major fracture (FRAX-Major) and hip fracture (FRAX-Hip) were calculated. FRAX-Major ≥ 20% or Hip ≥ 3% was considered high risk. HSA was done in a subgroup (n = 81) of patients. Results. The study group was 271 women. Mean (SD) age was 43.8 (13.1) years and SLE duration was 11.6 (10.4) years. OP was diagnosed in 14.6% and LBM in 8.8%. FRAX-Major ≥ 20% was seen in 9 patients (5.3%), of whom 6 were taking OP medications. FRAX-Hip ≥ 3% occurred in 16 patients (9.4%), of whom 9 were taking OP medications. Buckling ratio at the left hip narrow neck was positively correlated with FRAX-Major, FRAX-Hip, SLE duration, and duration of corticosteroid use. Conclusion. LBM is prevalent in women with SLE who are < 50 years of age. FRAX may identify those at higher risk of fractures while HSA can assess bone structure noninvasively.

A comparison of damage accrual across different calendar periods in systemic lupus erythematosus patients

Therapeutic approaches in systemic lupus erythematosus (SLE) have evolved over the last few decades, but their impact on prevention of organ damage is unknown. The objective of this study was to compare new cumulative damage in SLE patients across different calendar periods. Patients from a large SLE cohort were divided into two subcohorts; the first diagnosed and followed between 1978 and 1988 (cohort #1, n = 100) and the second between 1989 and 1999 (cohort #2, n = 51). Initial Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) scores, and changes in scores over the observation intervals, were compared for the two groups. Logistic regression estimated adjusted odds ratios (OR) comparing damage accrual between the two cohorts. Medication exposures were noted. Baseline characteristics were similar between the two groups. At first assessment, the adjusted OR for a SLICC/ACR DI score ≥1 was 1.79 (95% CI 0.82, 3.88) for cohort #1 versus cohort #2. At the end of the observation interval, the adjusted OR for a SLICC/ACR DI score ≥1 was 1.22 (0.58, 2.55) for cohort #1 versus cohort #2. The adjusted OR for accruing damage over the observation interval in cohort #1 versus cohort #2 was 0.94 (0.39, 2.44). Increased medication exposure was evident for cohort #2 compared to cohort #1. Despite increased therapeutic measures used for patients in more recent periods, our data do not establish a clear difference in damage accrual. This emphasizes the need for strategies to effectively treat lupus-specific manifestations, while minimizing side effects and comorbidities.

Improving transition readiness and quality of life (QOL) with a pediatric lupus health passport

Methods We adapted the pHLP from an adult LHP developed by the Canadian Network for Improved Outcomes in SLE (CaNIOS), by modifying the content and design to tailor to the needs of teens; and we then assessed acceptability through pilot testing and structured interviews. Patients with cSLE age 14-21 years recruited from three North American centers were instructed on the use of the pLHP. Transition readiness was assessed by a modified version of the California Healthy and Ready to Work Transition Health Care Guide, self-efficacy by a modified version of the Children’s Arthritis Self-Efficacy Scale, medication adherence by the MASRI, and SLE knowledge by a tool developed by the investigators. Baseline data is presented here.

Yoga in Systemic Lupus Erythematosus: Results of a Pragmatic Trial

Objective : To evaluate the feasibility and potential benefits of initiating a yoga program adapted for persons with systemic lupus erythematosus (SLE). Methods : We conducted a pragmatic trial of standard treatment (control group) or standard treatment plus yoga classes (intervention group) in persons with SLE. The intervention consisted of 16 yoga classes over an eight-week period. Evaluation of feasibility and benefits included measurements of compliance and results of post-intervention surveys and focus group discussions following completion of the yoga intervention. Results : The average age was 38.6±12.6, 96% were female, the mean SLE disease duration was 9.8±7.9 years, and mean SLE Disease Activity Index (SLEDAI-2K) score was 4.0±4.0. There were no significant differences between baseline characteristics between the groups. In the yoga intervention group, class attendance averaged 63% (range 39-87%); home practice averaged 1.2±1.3 hours/week. Results of post intervention surveys and focus group discussions indicated that all participants who had received the yoga intervention experienced improvement in physical and psychological well-being, including improvement in stress and pain management, improved sleep quality and decreased fatigue. Participants expressed satisfaction with the yoga program and recommended longer and more frequent classes. All yoga participants voiced interest in continuing the adapted program but were hesitant to try programs not tailored for chronic diseases like SLE. Conclusions : Our adapted yoga program was well tolerated and positive effects were experienced. The results suggest that an adapted yoga program provides persons with SLE with an opportunity to experience yoga and its accompanying benefits.