Holly John

Hypertension in rheumatoid arthritis

RA associates with an increased burden of cardiovascular disease, which is at least partially attributed to classical risk factors such as hypertension (HT) and dyslipidaemia. HT is highly prevalent, and seems to be under-diagnosed and under-treated among patients with RA. In this review, we discuss the mechanisms that may lead to increased blood pressure in such patients, paying particular attention to commonly used drugs for the treatment of RA. We also suggest screening strategies and management algorithms for HT, specific to the RA population, although it is clear that these need to be formally assessed in prospective randomized controlled trials designed specifically for the purpose, which, unfortunately, are currently lacking.

Methotrexate therapy associates with reduced prevalence of the metabolic syndrome in rheumatoid arthritis patients over the age of 60- more than just an anti-inflammatory effect? A cross sectional study

IntroductionThe metabolic syndrome (MetS) may contribute to the excess cardiovascular burden observed in rheumatoid arthritis (RA). The prevalence and associations of the MetS in RA remain uncertain: systemic inflammation and anti-rheumatic therapy may contribute. Methotrexate (MTX) use has recently been linked to a reduced presence of MetS, via an assumed generic anti-inflammatory mechanism. We aimed to: assess the prevalence of the MetS in RA; identify factors that associate with its presence; and assess their interaction with the potential influence of MTX.MethodsMetS prevalence was assessed cross-sectionally in 400 RA patients, using five MetS definitions (National Cholesterol Education Programme 2004 and 2001, International Diabetes Federation, World Health Organisation and European Group for Study of Insulin Resistance). Logistic regression was used to identify independent predictors of the MetS. Further analysis established the nature of the association between MTX and the MetS.ResultsMetS prevalence rates varied from 12.1% to 45.3% in RA according to the definition used. Older age and higher HAQ scores associated with the presence of the MetS. MTX use, but not other disease modifying anti-rheumatic drugs (DMARDs) or glucocorticoids, associated with significantly reduced chance of having the MetS in RA (OR = 0.517, CI 0.33–0.81, P = 0.004).ConclusionsThe prevalence of the MetS in RA varies according to the definition used. MTX therapy, unlike other DMARDs or glucocorticoids, independently associates with a reduced propensity to MetS, suggesting a drug-specific mechanism, and makes MTX a good first-line DMARD in RA patients at high risk of developing the MetS, particularly those aged over 60 years.

Vascular Function and Inflammation in Rheumatoid Arthritis: the Role of Physical Activity

Inflammation disturbs biochemical pathways involved in homeostasis of the endothelium. Research has established clear links between inflammatory mediators, particularly C-reactive protein and tumour necrosis factor alpha, endothelial dysfunction, and atherosclerosis. Endothelial dysfunction and atherosclerosis may be subclinical at early stages, and thus the ability to detect them with non-invasive techniques is crucially important, particularly in populations at increased risk for cardiovascular disease, such as those with rheumatoid arthritis. This may allow the identification of interventions that may reverse these processes early on. One of the best non-pharmacological interventions that may achieve this is physical activity. This review explores the associations between inflammation, endothelial dysfunction, and atherosclerosis and discusses the role of exercise in blocking specific pathways in the inflammation, endothelial dysfunction - atherosclerosis network.

Cardiovascular co-morbidity in early rheumatoid arthritis

Rheumatoid arthritis (RA) is associated with increased morbidity and mortality due to cardiovascular disease (CVD), mostly accelerated atherosclerotic CVD, and there is evidence that this occurs early in the inflammatory disease process. Both traditional and novel CVD risk factors as well as the effects of the RA disease process and its treatment interact and contribute to the development of CVD in RA. In this review we discuss the evidence for co-morbid CVD complicating early RA. This includes examining studies of mortality outcome and CVD events in cohorts of early RA patients as well as studies using surrogate markers for atherosclerotic CVD in RA. The evidence for shared risk factors for RA and CVD is presented. Screening and modification of CVD risk factors should be an integral part of care for any patient diagnosed with RA. Novel methods to diagnose CVD in high-risk asymptomatic RA patients need to be evaluated.

Cardiovascular risk factors and not disease activity, severity or therapy associate with renal dysfunction in patients with rheumatoid arthritis

Objectives The present study aimed to evaluate the prevalence and associations of renal dysfunction in patients with rheumatoid arthritis (RA). It specifically addressed the hypotheses that renal dysfunction in these patients may associate with the presence of insulin resistance, dyslipidaemia, uric acid levels and/or current levels of systemic inflammation. Methods Renal function was assessed by estimated glomerular filtration rate (GFR) using the modification of diet in renal disease equation in 400 consecutive RA patients for this cross-sectional, single-centre study. Risk factors for renal dysfunction were recorded/measured in all participants. Correlations between GFR and other variables were analysed by Pearson or Spearman test as appropriate. Linear regression was used to test the independence of the associations between GFR and other variables. Results In this RA patient cohort, 67.75% of patients had a reduced GFR of less than 90 ml/minute per 1.73 m2 and 12.75% had a GFR of less than 60 ml/minute per 1.73 m2. Multivariable analysis revealed significant associations between GFR and age (β = −0.370, p<0.001), female sex (β = −0.181, p=0.002), total cholesterol (β = −0.112, p=0.022), serum uric acid (SUA) (β = −0.425, p<0.001) and the presence of extra-articular disease, apart from sicca and/or nodules (β = −0.084, p=0.040). Conclusions Renal dysfunction in RA is quite common and associates with classic cardiovascular risk factors such as advanced age and dyslipidaemia, levels of SUA and the presence of extra-articular disease. Renal dysfunction was not related to other RA-related factors including disease activity and duration, disability and past or present use of nephrotoxic medications.

Rheumatoid arthritis: is it a coronary heart disease equivalent?

Purpose of review This review examines current evidence to address the question whether rheumatoid arthritis (RA) is a coronary heart disease equivalent, similar to type 2 diabetes mellitus (DM2). Recent findings Cross-sectional and longitudinal epidemiological studies show a two-fold higher risk of cardiovascular disease (CVD) in patients with RA, and the magnitude of this increased risk is comparable to the risk associated with DM2. However, the mechanisms responsible for this appear to be different in the two conditions, with RA-related CVD being attributed to ‘high-grade’ systemic inflammation as well as classical CVD risk factors. Several classical risk factors are affected by RA or its medications, and there are some paradoxical associations between obesity or lipid abnormalities and CVD death in RA. Summary Management of RA-related CVD is likely to require both aggressive control of inflammation and systematic screening and management of classical CVD risk factors. It remains unknown whether primary prevention strategies applied successfully in DM2 would be equally easy to implement and demonstrate similar benefits in people with RA.

Target organ damage in patients with rheumatoid arthritis: The role of blood pressure and heart rate

BACKGROUND Rheumatoid arthritis (RA) is characterised by increased cardiovascular morbidity and mortality. Even though hypertension (HT) is highly prevalent in RA, the extent of target organ damage (TOD) caused by it remains unknown. Inflammation and sympathetic overdrive may also associate with TOD. We investigated the prevalence and associations of TOD in RA. METHODS In this cross-sectional, observational study, 251 RA patients with no overt cardiovascular or renal disease had extensive clinical and laboratory evaluations, including a 12-lead electrocardiogram and urine albumin:creatinine ratio. Pulse pressure (PP) was used as a proxy of arterial stiffness and heart rate (HR) of autonomic activity. TOD was defined as described in the European guidelines for the management of arterial hypertension. Binary logistic regression analysis was used to evaluate the independence of the variables that associated with the presence of TOD. RESULTS TOD prevalence was 23.5% (59/251). Of the 59 patients with TOD, 45.8% had suboptimally controlled HT, whereas 32.3% had undiagnosed HT. In univariable analysis, TOD was significantly associated with higher age (64.2+/-11.7 years vs. 58.0+/-12.4 years, p=0.001), HT prevalence (89.8% vs. 60.4%, p<0.001), systolic blood pressure (SBP) (150.3+/-18.8mmHg vs. 139.7+/-20.7mmHg, p=0.001), PP (70.6+/-16.6mmHg vs. 60.3+/-17.3mmHg, p<0.001), HR (77.1+/-15.4bpm vs. 72.2+/-12.2bpm, p<0.001), serum uric acid (320.6+/-88.8mumol/l vs. 285.0+/-74.9mumol/l, p=0.03) and type 2 diabetes mellitus prevalence (13.6% vs. 4.7%, p=0.019). Binary logistic regression analysis revealed that only hypertension indices and HR associated independently with TOD. CONCLUSIONS TOD is highly prevalent in patients with RA and associates independently with hypertension, arterial stiffness and heart rate. Further prospective studies are needed to confirm these findings and examine the role of beta-blockers in this particular population.

A randomized controlled trial of a cognitive behavioural patient education intervention vs a traditional information leaflet to address the cardiovascular aspects of rheumatoid disease

OBJECTIVES Cardiovascular disease (CVD) is responsible for 50% of the excess mortality for patients with RA. This study aimed to evaluate a novel 8-week cognitive behavioural patient education intervention designed to effect behavioural change with regard to modifiable CVD risk factors in people with RA. METHODS This was a non-blinded randomized controlled trial with a delayed intervention arm. Participants were randomly assigned to receive the cognitive behavioural education intervention or a control information leaflet at a ratio of 1:1. The primary outcome measure was patients knowledge of CVD in RA; secondary measures were psychological measures relating to effecting behaviour change, actual behaviour changes and clinical risk factors. Data were collected at baseline, 2 and 6 months. RESULTS A total of 110 participants consented (52 in the intervention group and 58 in the control group) to participate in the study. At 6 months, those in the intervention group had significantly higher knowledge scores (P < 0.001); improved behavioural intentions to increase exercise (P < 0.001), eat a low-fat diet (P = 0.01) and lose weight (P = 0.06); and lower mean diastolic blood pressure by 3.7 mmHg, whereas the control groups mean diastolic blood pressure increased by 0.8 mmHg. There was no difference between the groups on actual behaviours. CONCLUSIONS Patient education has a significant role to play in CVD risk factor modification for patients with RA, and the detailed development of this programme probably contributed to its successful results. It is disappointing that behaviours, as we measured them, did not change. The challenge, as always, is how to translate behavioural intentions into action. Larger studies, powered specifically to look at behavioural changes, are required. Trial registration. National Institute for Health Research, UKCRN 4566.

Uric acid is a strong independent predictor of renal dysfunction in patients with rheumatoid arthritis

IntroductionRecent evidence suggests that uric acid (UA), regardless of crystal deposition, may play a direct pathogenic role in renal disease. We have shown that UA is an independent predictor of hypertension and cardiovascular disease (CVD), and that CVD risk factors associate with renal dysfunction, in patients with rheumatoid arthritis (RA). In this study we investigated whether UA associates with renal dysfunction in patients with RA and whether such an association is independent or mediated through other comorbidities or risk factors for renal impairment.MethodsRenal function was assessed in 350 consecutive RA patients by estimated glomerular filtration rate (GFR) using the six-variable Modification of Diet in Renal Disease equation. Risk factors for renal dysfunction were recorded or measured in all participants. Linear regression was used to test the independence of the association between GFR and UA.ResultsUnivariable analysis revealed significant associations between GFR and age, systolic blood pressure, total cholesterol, triglycerides, RA duration and UA. UA had the most powerful association with renal dysfunction (r = -0.45, P < 0.001). A basic model was created, incorporating all of the above parameters along with body mass index and gender. UA ranked as the first correlate of GFR (P < 0.001) followed by age. Adjustments for the use of medications (diuretics, low-dose aspirin, cyclooxygenase II inhibitors and nonsteroidal anti-inflammatory drugs) and further adjustment for markers of inflammation and insulin resistance did not change the results.ConclusionsUA is a strong correlate of renal dysfunction in RA patients. Further studies are needed to address the exact causes and clinical implications of this new finding. RA patients with elevated UA may require screening for renal dysfunction and appropriate management.

Translating patient education theory into practice: Developing material to address the cardiovascular education needs of people with rheumatoid arthritis

Objective This paper describes the rationale and design of a theory-informed patient education programme addressing cardiovascular disease for people with rheumatoid arthritis (RA) to illustrate how theory can explicitly be translated into practice. Methods A steering group of rheumatologists and psychologists was convened to design the programme. The Common Sense Model, the Theory of Planned Behaviour and the Stages of Change Model were used to underpin the topics and activities in the programme. User involvement was sought. The programme was formatted into a manual and the reading age of the materials was calculated. Results A small group 8-week programme was designed. The structure of the patient education programme, including topics, underlying psychological theory as well as behaviour change techniques, is described. Conclusion This patient education programme addresses a currently unmet educational need for patients with RA and uses theory to design, not just evaluate, the programme. This will allow both enhanced interpretation of the results when the programme is implemented and replication by other units if successful. Practice implications The actual design and detail of education programmes merit wider dissemination to facilitate progress in the process of development and application.