Methotrexate Therapy Associates With Reduced Prevalence of the Metabolic Syndrome in Rheumatoid Arth
Methotrexate Therapy Associates With Reduced Prevalence of the Metabolic Syndrome in Rheumatoid Arthritis Patients
Introduction The 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.
Methods MetS 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.
Results MetS 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).
Conclusions The 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.
Rheumatoid arthritis (RA) patients have a reduced life expectancy and higher mortality rates than the general population, with cardiovascular disease (CVD) accounting for approximately half of this. Although traditional cardiovascular risk factors such as hypertension, central obesity and insulin resistance may occur more frequently among RA patients, this does not fully account for the rates of CVD observed, and besides genetic predisposition, novel risk factors and mechanisms, including systemic inflammation per se, have also been implicated.
The metabolic syndrome (MetS) reflects a clustering of classical cardiovascular risk factors including insulin resistance, central obesity, elevated blood pressure, high triglyceride (TG) levels and low levels of high-density lipoprotein (HDL). The MetS has been identified as an independent cardiovascular risk factor, conferring risk above and beyond the sum of its individual components, although this has recently been questioned. The MetS has been shown to be highly prevalent among American patients with RA, with rates being four times those reported in the general population. In contrast, another study among Mediterranean RA patients also showed a high MetS prevalence but failed to demonstrate a significant difference from local general population controls.
To date, five definitions for the MetS have been developed: The National Cholesterol Education Programme (NCEP) 2004 and NCEP 2001, the World Health Organization (WHO), the International Diabetes Federation (IDF) and the European Group for Study of Insulin Resistance (EGIR). These share many similarities; however, they differ in some of the components, as well as their specified cut-offs and weighting. In the general population, prevalence rates of the MetS have been shown to vary dramatically according to the definition used, with the IDF classification tending to report the highest and the EGIR classification the lowest within a European study population. To date, two comparative studies have been performed in an RA population, both of which found a similar prevalence of the MetS according to the WHO and NCEP 2001 criteria.
Several of the individual components of the MetS have been shown to be influenced by demographic, anthropometric and RA-specific factors, but there has been very little work aimed at identifying factors that may be associated with the presence of MetS as a whole in patients with RA. Such associations may be key to tackling MetS and reducing CVD-related morbidity and mortality in RA. Studies have demonstrated significant reductions in CVD-related mortality in patients treated with methotrexate. This finding has been attributed to the potent anti-inflammatory properties of methotrexate. Interestingly, another study in 107 exclusively female RA patients has recently reported a negative association between methotrexate use and the MetS. This relationship was again assumed to be the result of the anti-inflammatory properties exhibited by methotrexate, but no further sub-analyses were performed to confirm or refute this.
In this study we aimed to: (1) assess the prevalence of the MetS in a large RA population according to all definitions currently used, in order to develop a bench-mark allowing comparisons between other relevant studies in the future; (2) to identify demographic, anthropometric and RA-disease specific factors that may be associated with the presence of the MetS in RA patients; (3) to establish if anti-rheumatic drug use (in particular methotrexate), is associated with the presence of the MetS, and whether this occurs in a drug-specific manner or as a result of an overall anti-inflammatory effect.
Abstract and Introduction
Abstract
Introduction The 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.
Methods MetS 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.
Results MetS 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).
Conclusions The 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.
Introduction
Rheumatoid arthritis (RA) patients have a reduced life expectancy and higher mortality rates than the general population, with cardiovascular disease (CVD) accounting for approximately half of this. Although traditional cardiovascular risk factors such as hypertension, central obesity and insulin resistance may occur more frequently among RA patients, this does not fully account for the rates of CVD observed, and besides genetic predisposition, novel risk factors and mechanisms, including systemic inflammation per se, have also been implicated.
The metabolic syndrome (MetS) reflects a clustering of classical cardiovascular risk factors including insulin resistance, central obesity, elevated blood pressure, high triglyceride (TG) levels and low levels of high-density lipoprotein (HDL). The MetS has been identified as an independent cardiovascular risk factor, conferring risk above and beyond the sum of its individual components, although this has recently been questioned. The MetS has been shown to be highly prevalent among American patients with RA, with rates being four times those reported in the general population. In contrast, another study among Mediterranean RA patients also showed a high MetS prevalence but failed to demonstrate a significant difference from local general population controls.
To date, five definitions for the MetS have been developed: The National Cholesterol Education Programme (NCEP) 2004 and NCEP 2001, the World Health Organization (WHO), the International Diabetes Federation (IDF) and the European Group for Study of Insulin Resistance (EGIR). These share many similarities; however, they differ in some of the components, as well as their specified cut-offs and weighting. In the general population, prevalence rates of the MetS have been shown to vary dramatically according to the definition used, with the IDF classification tending to report the highest and the EGIR classification the lowest within a European study population. To date, two comparative studies have been performed in an RA population, both of which found a similar prevalence of the MetS according to the WHO and NCEP 2001 criteria.
Several of the individual components of the MetS have been shown to be influenced by demographic, anthropometric and RA-specific factors, but there has been very little work aimed at identifying factors that may be associated with the presence of MetS as a whole in patients with RA. Such associations may be key to tackling MetS and reducing CVD-related morbidity and mortality in RA. Studies have demonstrated significant reductions in CVD-related mortality in patients treated with methotrexate. This finding has been attributed to the potent anti-inflammatory properties of methotrexate. Interestingly, another study in 107 exclusively female RA patients has recently reported a negative association between methotrexate use and the MetS. This relationship was again assumed to be the result of the anti-inflammatory properties exhibited by methotrexate, but no further sub-analyses were performed to confirm or refute this.
In this study we aimed to: (1) assess the prevalence of the MetS in a large RA population according to all definitions currently used, in order to develop a bench-mark allowing comparisons between other relevant studies in the future; (2) to identify demographic, anthropometric and RA-disease specific factors that may be associated with the presence of the MetS in RA patients; (3) to establish if anti-rheumatic drug use (in particular methotrexate), is associated with the presence of the MetS, and whether this occurs in a drug-specific manner or as a result of an overall anti-inflammatory effect.
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