The assessment and modification of cardiovascular risk in inflammatory arthritis

McKellar, Gayle Elspeth (2012) The assessment and modification of cardiovascular risk in inflammatory arthritis. MD thesis, University of Glasgow.

Abstract

Background

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that primarily affects synovial joints and is the commonest form of inflammatory polyarthritis. RA potentially confers significant morbidity, loss of function and reduced quality of life. It is a multisystem disorder with extra-articular manifestations affecting skin, cardiovascular, respiratory and haematological systems.
There is an associated premature mortality associated with RA which is mainly attributable to cardiovascular disease (CVD). Much has been published on the associated increased CVD risk which RA confers, which includes increased incidence of myocardial infarction, congestive cardiac failure and hypertension. Active RA is associated with a higher burden of both traditional cardiovascular (CV) risk factors (cigarette smoking, dyslipidaemia and hypertension) and novel risk factors (endothelial dysfunction, arterial stiffness and insulin sensitivity) than would be expected in the general population. Furthermore, chronic inflammation may be atherogenic. Certain drug therapies may contribute to CV risk, such as steroids and anti-inflammatories. Whereas other drug therapies, such as anti-tumour necrosis factor agents, may modulate CV risk.
There have been many recent controversies regarding anti-inflammatories, both non-selective non-steroidal anti-inflammatory drugs (NSAID) and cyclooxygenase2 (COX2) inhibitors. These include gastrointestinal system side-effects, renal dysfunction and hypertension. The most publicised of these issues was the withdrawal of rofecoxib in 2004 by its manufacturers after clinical trial data emerged which showed a 3.5% incidence of myocardial infarction or ischaemic stroke in patients with no pre-existing CVD who were receiving therapy. This lead to a scrupulous review in the medical journals of the relative CV risks of both NSAID and COX2 inhibitor groups as whole; as well as sub-analysis and comparison of individual preparations. In 2006 the American Heart Association recommended that in order to minimise CV risk, any patient prescribed an anti-inflammatory should have the lowest dose administered for the shortest possible time.
Furthermore, it is clear from the literature that it is not just underlying disease processes and medication that can impact on CV risk. Dietary modification can have a large bearing on health outcomes. Large epidemiological studies from Greece and other countries of southern Europe have confirmed that adherence to a Mediterranean-type diet is associated with increased longevity and reduced CVD. A Mediterranean-type diet is typically rich in olive oil, fruit, vegetables, legumes and fish, with a low intake of red-meat. This type of diet is often complemented by a modest amount of alcohol, usually red wine, taken alongside meals. This contrasts starkly with the typical diet of the west of Scotland – ‘famed’ for its high amount of saturated fat and sugar and relatively low consumption of fruit and vegetables.
Of late, much interest has been generated regarding the potential relationship between social deprivation and effect on health in general, particularly: diet, cardiovascular disease and RA outcomes. This is of particular relevance to Glasgow which has some of the most deprived areas in Scotland. While traditional CV risk assessment calculators have focussed on traditional markers such as blood pressure and cholesterol, newer validated scores include a score of deprivation, higher areas of social deprivation are associated with higher incidence of CVD, and family history of CVD.

Aims

In this thesis my aims were to explore the effect of novel interventions on various aspects of RA, predominately to assess CV risk further and review whether certain aspects of risk could be modified.
First of all, I investigated the feasibility and effect of anti-inflammatory withdrawal in patients with well-controlled RA (that is to say, patients with mild disease activity scores). The rationale to the NSAID withdrawal study was that removal of therapy plus any required active intervention would provide equivalent symptom control to that achieved by continuing NSAID. Other prescribed RA therapies were continued. The impact of this intervention was assessed by disease activity score, pain score and functional assessments. Secondary study outcomes included the effect of drug withdrawal on blood pressure control, gastrointestinal symptoms and renal function.
Subsequently, the impact of a Mediterranean-type diet on disease activity within the Glasgow RA population was reviewed. The study was set up to assess if existing resources could be used as much as possible and replicate a Mediterranean-type diet in a real-life setting, predominately in areas of social deprivation in the east end and south side of Glasgow. Feasibility and acceptability to participants was explored. Additionally, the impact of such a dietary intervention on disease activity, CV parameters and haematological markers was assessed.
Finally, given recent evidence linking social deprivation with CV risk as well as poor RA outcomes, an analysis was undertaken using the cohort recruited to the Mediterranean-type diet. Results of CVD risk calculations according to conventional and new algorithms were compared.

Results

Thirty patients with RA and a 44-joint disease activity score of ≤2.8 were recruited to a 12-week anti-inflammatory withdrawal study. All completed the study period without requiring re-introduction of anti-inflammatories and all continued on their previously prescribed RA therapy. Eleven patients required a steroid injection at either the 6 or 12-week study visit and only 1 required escalation of disease modifying therapy. There was no significant deterioration in disease activity score or components at the 12-week assessment. A significant improvement in blood pressure was recorded with a maximal median reduction of 7 millimetres of mercury (p=0.037).
Seventy-five patients with RA were recruited to the intervention arm of the Mediterranean-type dietary study and attended weekly cookery classes over a 6 week period. Fifty-five patients with RA were recruited to the control arm and received basic printed information only. All routine medication was continued and patients assessed at baseline, 3 and 6 months. Significant benefits were seen in the intervention group with regards to features of RA activity: reduced duration of early morning stiffness at 6 months (p=0.041), patient global health assessment score at 6 months (p=0.002) and pain score at 3 and 6 months (p= 0.011 and 0.049 respectively). Then intervention group demonstrated a benefit in systolic blood pressure. There was a significant increase in fruit, vegetable and legume consumption as assessed by food frequency questionnaire.
The substantial amount of baseline demographic and CV data collected from the Mediterranean-type diet study allowed a comprehensive assessment of the influence of social deprivation on CV risk scores in a cohort of female patients with RA living in the Glasgow area to be undertaken. Three different CV risk calculators were used: Joint British Societies Coronary Risk Prediction, Framingham and the newer, Scottish, ASSIGN score which incorporates social deprivation. ASSIGN was more likely to classify an individual with a >20% 10-year CVD risk (23% of total cohort) than Framingham or JBSCRP. By using ASSIGN, an additional 16 individuals were identified as having a >20% 10-year CV risk than would have been identified by using traditional JBSCRP alone.

Conclusions

The anti-inflammatory withdrawal intervention was limited by an open-label design and small participant numbers (n=30). However, it was well tolerated and did not result in the need for significant medical intervention, nor loss of disease control. A significant improvement in systolic blood pressure was noted over the study follow-up. To my knowledge this is the first supportive evidence to guide the limitation of anti-inflammatory use in patients with stable RA and should inform further work in this area.
The Mediterranean-type diet intervention demonstrated that a 6-week intervention can prove instrumental in increasing intake of healthy foods at a relatively low cost. This dietary intervention was well received, on reviewing feedback, and resulted in beneficial effects on RA disease features as well as on blood pressure. This could be an area of future disease modification which is cost-effective and easy to implement as well as being popular with patients.
Using the ASSIGN score allowed the identification of a greater number of study participants with a high 10-year CVD risk score. This is in addition to the increased CV risk which RA confers. Increased use of this score would allow the targeting of a greater number of patients to target interventions and minimise future CVD.

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Keywords: Inflammatory arthritis, rheumatoid arthritis, cardiovascular risk, anti-inflammatory drugs, Mediterranean-type diet, cardiovascular risk assessment, blood pressure
• Subjects: R Medicine > R Medicine (General); R Medicine > RC Internal medicine
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Supervisor's Name: McInnes, Prof. Iain B.
• Date of Award: 2012
• Depositing User: Dr Gayle E McKellar
• Unique ID: glathesis:2012-3681
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 15 Nov 2012
• Last Modified: 10 Dec 2012 14:09
• URI: https://theses.gla.ac.uk/id/eprint/3681