Sharon Van Doornum

Prevalence of coronary heart disease and cardiovascular risk factors in a national cross-sectional cohort study of systemic sclerosis

Objectives To determine the prevalence of coronary heart disease (CHD) and cardiovascular risk factors in a well-characterised cohort of systemic sclerosis (SSc) patients, and to compare this with the general population. Methods A cross-sectional study of the prevalence of CHD and cardiovascular risk factors in participants in the Australian Scleroderma Cohort Study was performed. Controls were drawn from the 2007–8 National Health Survey (NHS) and the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). OR and 95% CI were calculated to determine the prevalence of CHD and cardiovascular risk factors in SSc patients compared with controls. Results Data were available for 850 SSc patients (86% female), 15 787 NHS participants (53% female) and 8802 AusDiab participants (56% female). Adjusted for age and gender, the OR of CHD in SSc patients was 1.9 (95% CI 1.4 to 2.4) compared with controls from AusDiab and 2.0 (95% CI 1.5 to 2.5) compared with controls from the NHS. The OR of CHD increased to 3.2 (95% CI 2.3 to 4.5) for SSc patients compared with controls from AusDiab after further adjustment for cardiovascular risk factors. Hypercholesterolaemia, diabetes mellitus and obesity were significantly less prevalent in the SSc cohort than in AusDiab. Within the SSc cohort, the presence of pulmonary arterial hypertension was associated with CHD. Conclusions This is the first report of an increased prevalence of CHD in SSc patients. Further studies are required to determine the relative contribution of scleroderma-specific factors such as microvascular disease to the development of CHD.

Cardiovascular disease in systemic sclerosis - an emerging association?

Microvascular disease is a prominent feature of systemic sclerosis (SSc) and leads to Raynauds phenomenon, pulmonary arterial hypertension, and scleroderma renal crisis. The presence of macrovascular disease is less well established, and, in particular, it is not known whether the prevalence of coronary heart disease in SSc is increased. Furthermore, in terms of cardiac involvement in SSc, there remains conjecture about the relative contributions of atherosclerotic macrovascular disease and myocardial microvascular disease. In this review, we summarize the literature describing cardiovascular disease in SSc, discuss the pathophysiological mechanisms common to SSc and atherosclerosis, and review the surrogate markers of cardiovascular disease which have been examined in SSc. Proposed mediators of the vasculopathy of SSc which have also been implicated in atherosclerosis include endothelial dysfunction, a reduced number of circulating endothelial progenitor cells, and an increased number of microparticles. Excess cardiovascular risk in SSc is suggested by increased arterial stiffness and carotid intima thickening and reduced flow-mediated dilatation. Cohort studies of adequate size are required to resolve whether this translates into an increased incidence of cardiovascular events in patients with SSc.

Rheumatoid arthritis patients receive less frequent acute reperfusion and secondary prevention therapy after myocardial infarction compared with the general population

IntroductionThe 30-day case-fatality rate after acute myocardial infarction (MI) for rheumatoid arthritis (RA) patients is twice that of the general population. This study compared the frequency and timeliness of early reperfusion therapy and treatment with secondary prevention medications after acute MI in RA patients and controls.MethodsWe performed a structured medical chart review of RA patients and matched controls who had been admitted with acute MI to one of three hospitals in Victoria, Australia, between 1995 and 2005. The administration and timing of acute reperfusion therapy and in-hospital treatment with secondary prevention medications were compared between the two groups. Acute reperfusion was defined as thrombolysis or percutaneous coronary intervention (PCI) within 12 hours of the first symptom of MI.ResultsThe medical charts of 90 RA patients and 90 matched controls were reviewed. The RA patients were significantly less likely to receive acute reperfusion compared with the controls (16% versus 37%: odds ratio (OR), 0.27; 95% confidence interval (CI), 0.10 to 0.64)), and this difference persisted after adjusting for type of MI, clinical setting of MI, and prior MI (OR, 0.2; 95% CI, 0.05 to 0.6). The RA patients also received less-frequent in-hospital treatment with beta blockers (71% versus 83%; OR, 0.42; 95% CI, 0.18 to 0.96) and lipid-lowering agents (40% versus 70%; OR, 0.21; 95% CI, 0.09 to 0.46).ConclusionsRA patients who experience acute MI receive acute reperfusion and secondary prevention medications less frequently than do controls. This may contribute to higher case-fatality rates after MI in RA patients.

Retinal vascular calibre is altered in patients with rheumatoid arthritis: a biomarker of disease activity and cardiovascular risk?

OBJECTIVES Alterations in retinal vascular calibre, particularly wider venular calibre, have been independently associated with elevated markers of inflammation and cardiovascular risk in the general population. We hypothesized that retinal vascular calibre would be altered in patients with RA, who are known to have both elevated cardiovascular risk and chronic, systemic inflammation. METHODS Retinal vascular calibre was measured from digital retinal photographs using computerized methods in 51 RA patients and 51 age- and gender-matched controls. Retinal vascular calibre was compared between RA and control patients with adjustment for relevant variables including cardiovascular risk factors and companion vessel calibre. The relationship between retinal venular calibre and inflammation was assessed by comparing controls and RA patients with high and lower disease activity. RESULTS Retinal venular calibre [mean (s.d.)] was significantly wider in RA patients than in controls [235.9 (24.6) vs. 211.6 (21.0) µm, P < 0.001]. After adjustment for all relevant variables, mean venular calibre remained 20.3 µm (95% CI 10.4, 30.3) wider in RA patients compared with controls. Retinal venular calibre [mean (s.d.)] also increased with increasing levels of systemic inflammation: 211.6 (21.0) µm in controls, 232.3 (22.4) µm in RA patients with moderate or lower disease activity and 255.5 (28.3) µm in RA patients with high disease activity (P for trend < 0.0001). CONCLUSIONS This study demonstrates that RA patients have dilated retinal venular calibre, reflecting systemic inflammation and possibly increased cardiovascular risk. Longitudinal studies correlating retinal vascular calibre with subsequent cardiovascular events will clarify the clinical utility of this test in patients with RA.

Safety of anti-rheumatic drugs for rheumatoid arthritis in pregnancy and lactation.

Women with rheumatoid arthritis (RA) are often of childbearing age and therefore questions regarding reproductive health and the use of medications, including disease‐modifying anti‐rheumatic drugs (DMARDs) may arise during the clinical consultation. Each patient requires individual assessment in order to effectively manage the disease while minimizing any treatment‐associated risks to the fetus. Although good‐quality controlled trials are lacking, there is an increasing volume of evidence surrounding the use of immunosuppressive therapies in pregnancy and lactation. This review summarizes the currently available information which can be of benefit to clinicians guiding patients and their families through the risks and benefits of continuing RA therapy during pregnancy and lactation. Further studies and ongoing surveillance of drug safety in pregnancy are required to resolve the uncertainties that remain regarding synthetic and biologic DMARDs.

Establishing cross-discipline consensus on contraception pregnancy and breast feeding-related educational messages and clinical practices to support women with rheumatoid arthritis: an Australian Delphi study.

Objective Recognising the need for a best-practice and consistent approach in providing care to women with rheumatoid arthritis (RA) in relation to (1) general health, (2) contraception, (3) conception and pregnancy, (4) breast feeding and (5) early parenting, we sought to achieve cross-discipline, clinical consensus on key messages and clinical practice behaviours in these 5 areas. Design 3-round eDelphi study. In round 1, panellists provided free-text responses to open-ended questions about care for women with RA across the 5 areas. Subsequently, panellists refined and scored the synthesised responses, presented as metathemes, themes and detailed elements. Where ≥5% of panellists did not support a theme in a given round, it was removed. Setting Panel of practicing Australian rheumatologists (n=22), obstetricians/obstetric medicine physicians (n=9) and pharmacists (n=5). Results 34 (94.4%) panellists participated in all 3 rounds. The panel supported 18 themes across the 5 areas (support/strongly support: 88.2–100%) underpinned by 5 metathemes. Metathemes focused on coordination in information delivery, the mode and timing of information delivery, evidence underpinning information, engagement of the right health professionals at the right time and a non-judgemental approach to infant feeding. Themes included practices for primary prevention of chronic disease and their sequelae, the importance of contraception and planning pregnancy and breast feeding, close monitoring of medications, supporting mental well-being, managing disease activity and providing practical support for early parenting. Conclusions A cross-disciplinary clinical panel highly supported key information and clinical practices in the care for women with RA across the continuum of contraception to early parenting within a whole-person, chronic disease management approach.

Glucocorticoid-induced bone loss is associated with abnormal intravertebral areal bone mineral density distribution.

Individuals with glucocorticoid-induced osteoporosis experience vertebral fractures at an increased rate and at higher vertebral areal bone mineral density (aBMD) than individuals with primary osteoporosis. Standard posteroanterior- (PA-) projection dual energy X-ray absorptiometry (DXA) lacks the diagnostic sensitivity required for reliable estimation of vertebral fracture risk in individuals. Assessment of subregional vertebral aBMD using lateral-projection DXA may improve the predictive value of DXA parameters for fracture. One hundred and four individuals were recruited and grouped for this study: primary osteoporosis with no history of vertebral fracture (n = 43), glucocorticoid-induced bone loss (n = 13), and healthy controls (n = 48). Standard PA-projection and supine-lateral scans were performed, and lateral scans were analysed according to an established protocol to measure aBMD within 6 subregions. Main effects for subregion and group were assessed and observed, by ANCOVA. Ratios were calculated between subregions and compared between groups, to overcome the potentially confounding influence of variability in subregional geometry. Significantly lower values were observed in the glucocorticoid group for the ratios of (i) anterior subregion: whole vertebral body and (ii) posterior: whole vertebral body when compared to the primary osteoporosis and control groups (P < 0.05). Lower anterior subregional aBMD in individuals on glucocorticoid therapy may help to explain the increased vertebral fracture risk in this patient group.

Suppression of inflammatory disease activity in rheumatoid arthritis is associated with improvements in retinal microvascular health

OBJECTIVE To investigate the effect of suppressing inflammation on retinal microvascular health in patients with RA. METHODS Two groups of patients with RA were recruited and studied concurrently. Group A included patients with moderate to high disease activity [28-joint DAS with CRP (DAS28-CRP) >3.2] requiring treatment escalation, while group B had stable low disease activity (DAS28-CRP ≤3.2) not requiring treatment escalation. Retinal photography was performed at baseline and weeks 6 and 24 in group A and at baseline and week 12 in group B. RESULTS Group A included 26 patients with a mean age of 50.7 years (s.d. 3.5) and a mean disease duration of 7.1 years (s.d. 8.0). Disease activity significantly improved during follow-up and was accompanied by a significant reduction in retinal venular calibre at week 6 [mean difference (MD) -7.9 μm (95% CI -13.3, -2.5)] and at week 24 [MD -6.8 μm (95% CI -12.2, -1.4)]. No significant change in retinal arteriolar calibre was identified at week 6 [MD -0.6 μm (95% CI -4.5, 3.28)] or week 24 [MD 0.7 μm (95% CI -3.1, 4.5)]. Group B included 27 patients with a mean age of 54.6 years (s.d. 1.8) and a mean disease duration of 14.5 years (s.d. 10.9). Disease activity and therapy remained unchanged during follow-up and no significant changes in retinal venular [MD 1.81 μm (95% CI -2.32, 5.95)] or arteriolar [MD 0.54 μm (95% CI -2.77, 3.86)] calibre were observed. CONCLUSION We demonstrated that suppression of inflammation in RA is associated with a reduction of retinal venular calibre, suggesting that therapies targeting inflammation could improve vascular health in RA.

Closing the pregnancy-related information gap for women with rheumatoid arthritis

Although RA affects women across their lifespan, it has particular implications for women who are planning a family, given the physical and psychosocial impacts of this disease and the potential adverse effects of RA drugs. Conception (and contraception), pregnancy and breastfeeding must all be planned and managed carefully, with appropriate clinical guidance [1]. There is a clear need for accurate, evidence-based and freely accessible information to support shared decision-making between women with RA, their families and the treating health-care professionals during this key stage of life. For families living in rural and remote areas or lowand middle-income countries where access to rheumatology care is limited, this is particularly important [2]. Given the recent evidence around unmet educational needs and limited evidence for the effectiveness of educational interventions, it is clear that more needs to be done to support women with RA across the pregnancy and post-natal continuum. Several qualitative studies from Australia and The Netherlands have highlighted key pregnancy-related educational needs and concerns among this patient group. Our recent study investigated the specific educational needs of women with RA who were pregnant, planning a pregnancy or who had been pregnant in the past 5 years [3]. Participants cited a lack of accessible and relevant information (particularly around the safety and toxicity of RA medications) and expressed a strong desire for practical strategies from peers to assist them in meeting the daily challenges of caring for a young baby. Another study found that women with RA experienced considerable uncertainty about the impact of RA medications on their unborn child and the effect of ceasing medications on their disease status [4]. In a study involving men and women with inflammatory arthritis (88% had RA), Nota et al. [5] reported that younger patients worried about the effect of DMARDs on fertility and pregnancy when deciding whether to commence therapy. These perspectives and others [6] suggest that contemporary arthritis education should incorporate pregnancy-related information for people with RA during their reproductive years and include a focus on both knowledge and practical skills. Patient education that is targeted to an individual’s information needs and life stage should form a fundamental component of routine care for people with inflammatory arthritis, as emphasized by recent EULAR recommendations [7]. However, with regard to the provision of pregnancy and post-natal education in the context of RA, the evidence about effective interventions is extremely limited. We recently completed a systematic literature review to determine the effectiveness of interventions designed to improve knowledge or self-management skills concerning contraception, pregnancy and breastfeeding in people with RA [8]. Of the 68 studies eligible for inclusion in our review, only one specifically evaluated pregnancy-focused education or self-management support for people with RA [9]. That particular randomized controlled trial evaluated a motherhood choices decision aid for RA, which was developed to assist women with RA in making informed choices about having children (or having additional children). The 45-page decision aid resource is publicly available and includes information on RA, pregnancy and the post-natal period, personal narratives, decision-making tasks and links to online resources and telephone helplines in several countries. The study found that participants who were given the motherhood decision aid had a greater increase in knowledge around RA and pregnancy-related topics and a greater reduction in decisional conflict compared with a no-intervention control group; however, the study did have some methodological limitations (e.g. participant follow-up beyond the immediate post-intervention period was not undertaken, and an intention-to-treat analysis was not reported). A further eight studies identified in our systematic review described interventions containing only minor components that could be considered relevant to conception, contraception, pregnancy or breastfeeding, within broader RA educational or self-management programmes. Despite the prevalence of RA among women of childbearing age, it is clear that published models of disease education do not adequately cater to this important stage of life. In the proceedings of the 2014 ACR Reproductive Health Summit [10], Kavanaugh et al. acknowledged the need for improved interdisciplinary communication among medical specialists who care for people with inflammatory and autoimmune conditions during pregnancy, and we agree that this is an important path to pursue. Conflicting advice from health professionals regarding pregnancy issues can be frustrating and confusing for women with RA [3]. To address this issue, our research group is currently undertaking a national e-Delphi study involving experienced rheumatologists, obstetricians and clinical pharmacists. The study is designed to establish cross-discipline consensus on key messages that should be delivered to women with RA by health professionals on contraception, pregnancy,

Statin initiation and treatment non-adherence following a first acute myocardial infarction in patients with inflammatory rheumatic disease versus the general population

IntroductionTo compare statin initiation and treatment non-adherence following a first acute myocardial infarction (MI) in patients with inflammatory rheumatic disease ( IRD) and the general population.MethodsWe conducted a retrospective cohort study using a population-based linked database. Cases of first MI from July 2001 to June 2009 were identified based on International Classification of Diseases (ICD-10-AM) codes. Statin initiation and adherence was identified based on pharmaceutical claims records. Logistic regression was used to assess the odds of statin initiation by IRD status. Non-adherence was assessed as the time to first treatment gap using a Cox proportional hazards model.ResultsThere were 18,518 individuals with an index MI over the time period surviving longer than 30 days, of whom 415 (2.2%) were IRD patients. The adjusted odds of receiving a statin by IRD status was significantly lower (OR =0.69, 95% CI: 0.55 to 0.86) compared to the general population. No association between IRD status and statin non-adherence was identified (hazard ratio (HR) =1.12, 95% CI: 0.82 to 1.52).ConclusionsStatin initiation was significantly lower for people with IRD conditions compared to the general population. Once initiated on statins, the proportion of IRD patients who adhered to treatment was similar to the general population. Given the burden of cardiovascular disease and excess mortality in IRD patients, encouraging the use of evidence-based therapies is critical for ensuring the best outcomes in this high risk group.