Non-steroidal anti-inflammatory drug (NSAID) related inhibition of aldosterone glucuronidation and arterial dysfunction in patients with rheumatoid arthritis

a cross-sectional clinical study

Michael A Crilly, Arduino Aleksander Mangoni

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective
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
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
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
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.
Original languageEnglish
Article numbere000076
JournalBMJ Open
Volume1
Issue number1
Early online date20 May 2011
DOIs
Publication statusPublished - 2011

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Aldosterone
Rheumatoid Arthritis
Anti-Inflammatory Agents
Cross-Sectional Studies
Diclofenac
Ibuprofen
Pharmaceutical Preparations
Indomethacin
Naproxen
Cardiovascular Diseases
Pulse Wave Analysis
Blood Sedimentation
Non-Steroidal Anti-Inflammatory Agents
Inhibition (Psychology)
Clinical Studies
Medical Records
Fasting
Multivariate Analysis
Smoking
Blood Pressure

Cite this

@article{71960f71f66b4be8ae73802d118d6253,
title = "Non-steroidal anti-inflammatory drug (NSAID) related inhibition of aldosterone glucuronidation and arterial dysfunction in patients with rheumatoid arthritis: a cross-sectional clinical study",
abstract = "Objective 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 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 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 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.",
author = "Crilly, {Michael A} and Mangoni, {Arduino Aleksander}",
year = "2011",
doi = "10.1136/bmjopen-2011-000076",
language = "English",
volume = "1",
journal = "BMJ Open",
issn = "2044-6055",
publisher = "BMJ Publishing Group",
number = "1",

}

TY - JOUR

T1 - Non-steroidal anti-inflammatory drug (NSAID) related inhibition of aldosterone glucuronidation and arterial dysfunction in patients with rheumatoid arthritis

T2 - a cross-sectional clinical study

AU - Crilly, Michael A

AU - Mangoni, Arduino Aleksander

PY - 2011

Y1 - 2011

N2 - Objective 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 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 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 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.

AB - Objective 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 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 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 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.

U2 - 10.1136/bmjopen-2011-000076

DO - 10.1136/bmjopen-2011-000076

M3 - Article

VL - 1

JO - BMJ Open

JF - BMJ Open

SN - 2044-6055

IS - 1

M1 - e000076

ER -