Objective Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular (CV) disease and are also commonly prescribed non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs). New in vitro evidence suggests that this increased CV risk may be mediated through aldosterone glucuronidation inhibition (AGI), which differs between NSAIDs (diclofenac>naproxen>indomethacin>ibuprofen). Our aim was to explore the association between ns-NSAID-related AGI and arterial dysfunction.
Methods The extent (augmentation index, AIX%) and timing (reflected wave transit time, RWT, ms) of aortic wave reflection (measured using radial applanation pulse wave analysis, PWA, SphygmoCor device) were assessed on a single occasion in 114 consecutive RA patients without overt CV disease aged 40–65 years. A higher AIX% and lower RWT indicate arterial dysfunction. Assessment included a fasting blood sample, patient questionnaire and medical record review. Multivariate analysis was used to adjust for age, sex, mean blood pressure, smoking, cumulative erythrocyte sedimentation rate (ESR-years) and Stanford disability score.
Results We identified 60 patients taking ns-NSAIDs and 25 non-users. Using a ns-NSAID with the highest AGI was associated with a higher AIX% (and lower RWT) versus treatment with a ns-NSAID with the lowest AGI (diclofenac AIX% 32.3, RWT 132.7 ms vs ibuprofen AIX% 23.8, RWT 150.9 ms): adjusted mean differences AIX% 6.5 (95% CI 1.0 to 11.9; p=0.02); RWT −14.2 ms (95% CI −22.2 to −6.3; p=0.001). Indomethacin demonstrated an intermediate level of arterial dysfunction. In relation to arterial dysfunction, both indomethacin and naproxen were more similar to diclofenac than to ibuprofen.
Conclusions ns-NSAID-related AGI is associated with arterial dysfunction in patients with RA. These findings provide a potentially novel insight into the CV toxicity of commonly used ns-NSAIDs. However, the findings are limited by the small number of patients involved and require further replication in a much larger study.
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To cite: Crilly MA, Mangoni AA. Non-steroidal anti-inflammatory drug (NSAID) related inhibition of aldosterone glucuronidation and arterial dysfunction in patients with rheumatoid arthritis: a cross-sectional clinical study. BMJ Open 2011;1:e000076. doi:10.1136/bmjopen-2011-000076
Funding The original study was supported by charitable funding from NHS Grampian Rheumatology Endowments. The funders played no role in the analysis or reporting of this study.
Competing interests None.
Ethics approval This study was approved by the Grampian Research Ethics Committee (ref: 04/S0801/67).
Contributors MAC conceived and designed the study, analysed and interpreted the data, drafted and re-drafted the article and gave final approval of the version to be published. AAM proposed the original hypothesis, interpreted the data, revised the article critically for important intellectual content, re-drafted the article and gave final approval of the version to be published.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Consent for data-sharing was not obtained from study participants at the time of recruitment, but the presented data are held in an anonymised dataset. Access to the dataset is available from the corresponding author ( ) in SPSS format for clinical academic researchers interested in undertaking a formally agreed collaborative research project(s). Although the risk of individual patient identification is low, any research involving the release of the dataset to other clinical academics would require approval by Grampian Research Ethics Committee.
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