Metabolic Syndrome in Rheumatoid Arthritis
Metabolic Syndrome in Rheumatoid Arthritis
This case-control study suggested that RA is associated with increased frequency of metabolic syndrome compared to control groups, but its frequency depends on the definition used. Higher systemic inflammatory markers (ESR) and glucocorticoid use were independent predictors associated with the presence of metabolic syndrome in patients with RA.
The metabolic syndrome describes a constellation of major risk factors for cardiovascular diseases (CVDs) such as atherogenic dyslipidemia, obesity, hypertension and diabetes. These associated risk factors have been previously called syndrome X2 or the insulin resistance syndrome.
The frequency of metabolic syndrome has varied markedly between different studies, most likely because of the lack of accepted criteria for the definition of metabolic syndrome. Recently, Karvounaris et al found a frequency of metabolic syndrome (defined according to the NCEP ATP III criteria) in RA patients (40%), comparable with their control population. In South Asia, Dodani and al found that the frequency of metabolic syndrome was 13.3% and 40%, respectively, according to WHO and NCEP ATP III criteria. Another study showed that metabolic syndrome was significantly more prevalent in American patients with long-standing RA (42% – WHO and NCEP/ATPIII criteria) as well as in early RA patients (31% and 30% – WHO and NCEPIII criteria respectively) than in controls (11% and 22% – WHO and NCEP/ATPIII criteria, respectively). Allowing comparison of our results with those of other studies in RA and other conditions, In the literature, the frequency of metabolic syndrome varied considerably, even using the same criteria; for example, using the NCEP 2001, the frequency ranged from 17% in Mexican, 19% in South African, 19.9% in Dutch, 38.3% in English, to 41.5% in Swedish, 42% in American, and 44% in Greek patients with RA and 24.6% in our study. Such diversity can be explained by differences in the baseline characteristics and disease characteristics.
The factors found in this study to be associated independently with the metabolic syndrome in RA, irrespective of the definition used, included higher systemic inflammatory markers, and glucocorticoid usage. In our study, we didn't find an association between older age and metabolic syndrome contrary to others studies. The association with older age is not surprising, because in the general population, metabolic syndrome has been shown to affect primarily older subjects, as a consequence of age-related modification of some of its components. The association between higher ESR and the presence of metabolic syndrome in patients with RA in our study was also previously reported. These findings further support the role of chronic inflammation in insulin resistance development. However, ESR can be affected by a number of comorbid conditions (renal disease) as well as age. Furthermore, metabolic syndrome is an inflammatory condition, and thus ESR may be elevated to some degree by the presence of metabolic syndrome. Moreover, the cross-sectional design of our study limit the ability to describe causal relationships to the associations detected.
Another finding from this study was the association between glucocorticoids use and the presence of metabolic syndrome. This relationship may be explained by the effects of glucocorticoids on different components of the lipid profile. To the contrary, the study among Mediterranean RA patients found that metabolic syndrome in RA is independent of gender and body mass index (BMI). Current corticosteroid use does not increase the risk of metabolic syndrome while it may even reduce its prevalence. On the other hand, the risk of having moderate to severe RA is higher in patients with metabolic syndrome than in those without the syndrome. Furthermore, another study showed that the use of glucocorticoids is not associated with the presence of metabolic syndrome. Dessein and coworkers found that corticosteroid use was not associated with dyslipidemia in RA patients but was associated with insulin resistance. Therefore, the lipoprotein effects of glucocorticoids are unlikely to be the sole cause (if any) of the impact of these drugs on cardiovascular risk. Indeed, the analysis of lipid levels in the COBRA ("Combination therapy in rheumatoid arthritis") study found that combination therapy with glucocorticoids, methotrexate, and sulfasalazine was associated with a more rapid and favorable impact on the atherogenic index (total/HDL cholesterol ratio) in RA. In the literature, Glucocorticoid use is associated with adverse lipid profiles in the general population, and its long-term use is a risk factor for CVD. However, the relationship between glucocorticoid use and cardiovascular risk in patients with RA is complicated by the fact that these drugs tend to be used more often in patients with severe or intractable disease; therefore, it is difficult to determine whether the disease or the treatment increase the risk.
The limitations of the current study should be addressed. The cross-sectional design and small size of our study limit the ability to describe causal relationships to the associations detected. Furthermore; the small sample size of this study, and recruitment from a single center, which is a tertiary care center with recruitment of the most active and severe disease expose to bias selection and the risk of surestmation of the real frequency of metabolic syndrome. The international COMORA study (comorbidities in RA); in which Morocco has participated with 300 patients across 10 centers in the country (private and public structures) will be interesting, it can given the frequency of metabolic syndrome and its components and compared these data through countries. Moreover, the Moroccan ESPOIR study (Etude et Suivi des POlyarthrites rhumatoïdes et arthrites Indifférenciées Récentes), a prospective multicenter cohort study of 10 years of follow-up will provide some information on the epidemiological profile of the RA in Morocco. Further prospective studies should prove valuable in determining these causal relationships.
Discussion
This case-control study suggested that RA is associated with increased frequency of metabolic syndrome compared to control groups, but its frequency depends on the definition used. Higher systemic inflammatory markers (ESR) and glucocorticoid use were independent predictors associated with the presence of metabolic syndrome in patients with RA.
The metabolic syndrome describes a constellation of major risk factors for cardiovascular diseases (CVDs) such as atherogenic dyslipidemia, obesity, hypertension and diabetes. These associated risk factors have been previously called syndrome X2 or the insulin resistance syndrome.
The frequency of metabolic syndrome has varied markedly between different studies, most likely because of the lack of accepted criteria for the definition of metabolic syndrome. Recently, Karvounaris et al found a frequency of metabolic syndrome (defined according to the NCEP ATP III criteria) in RA patients (40%), comparable with their control population. In South Asia, Dodani and al found that the frequency of metabolic syndrome was 13.3% and 40%, respectively, according to WHO and NCEP ATP III criteria. Another study showed that metabolic syndrome was significantly more prevalent in American patients with long-standing RA (42% – WHO and NCEP/ATPIII criteria) as well as in early RA patients (31% and 30% – WHO and NCEPIII criteria respectively) than in controls (11% and 22% – WHO and NCEP/ATPIII criteria, respectively). Allowing comparison of our results with those of other studies in RA and other conditions, In the literature, the frequency of metabolic syndrome varied considerably, even using the same criteria; for example, using the NCEP 2001, the frequency ranged from 17% in Mexican, 19% in South African, 19.9% in Dutch, 38.3% in English, to 41.5% in Swedish, 42% in American, and 44% in Greek patients with RA and 24.6% in our study. Such diversity can be explained by differences in the baseline characteristics and disease characteristics.
The factors found in this study to be associated independently with the metabolic syndrome in RA, irrespective of the definition used, included higher systemic inflammatory markers, and glucocorticoid usage. In our study, we didn't find an association between older age and metabolic syndrome contrary to others studies. The association with older age is not surprising, because in the general population, metabolic syndrome has been shown to affect primarily older subjects, as a consequence of age-related modification of some of its components. The association between higher ESR and the presence of metabolic syndrome in patients with RA in our study was also previously reported. These findings further support the role of chronic inflammation in insulin resistance development. However, ESR can be affected by a number of comorbid conditions (renal disease) as well as age. Furthermore, metabolic syndrome is an inflammatory condition, and thus ESR may be elevated to some degree by the presence of metabolic syndrome. Moreover, the cross-sectional design of our study limit the ability to describe causal relationships to the associations detected.
Another finding from this study was the association between glucocorticoids use and the presence of metabolic syndrome. This relationship may be explained by the effects of glucocorticoids on different components of the lipid profile. To the contrary, the study among Mediterranean RA patients found that metabolic syndrome in RA is independent of gender and body mass index (BMI). Current corticosteroid use does not increase the risk of metabolic syndrome while it may even reduce its prevalence. On the other hand, the risk of having moderate to severe RA is higher in patients with metabolic syndrome than in those without the syndrome. Furthermore, another study showed that the use of glucocorticoids is not associated with the presence of metabolic syndrome. Dessein and coworkers found that corticosteroid use was not associated with dyslipidemia in RA patients but was associated with insulin resistance. Therefore, the lipoprotein effects of glucocorticoids are unlikely to be the sole cause (if any) of the impact of these drugs on cardiovascular risk. Indeed, the analysis of lipid levels in the COBRA ("Combination therapy in rheumatoid arthritis") study found that combination therapy with glucocorticoids, methotrexate, and sulfasalazine was associated with a more rapid and favorable impact on the atherogenic index (total/HDL cholesterol ratio) in RA. In the literature, Glucocorticoid use is associated with adverse lipid profiles in the general population, and its long-term use is a risk factor for CVD. However, the relationship between glucocorticoid use and cardiovascular risk in patients with RA is complicated by the fact that these drugs tend to be used more often in patients with severe or intractable disease; therefore, it is difficult to determine whether the disease or the treatment increase the risk.
The limitations of the current study should be addressed. The cross-sectional design and small size of our study limit the ability to describe causal relationships to the associations detected. Furthermore; the small sample size of this study, and recruitment from a single center, which is a tertiary care center with recruitment of the most active and severe disease expose to bias selection and the risk of surestmation of the real frequency of metabolic syndrome. The international COMORA study (comorbidities in RA); in which Morocco has participated with 300 patients across 10 centers in the country (private and public structures) will be interesting, it can given the frequency of metabolic syndrome and its components and compared these data through countries. Moreover, the Moroccan ESPOIR study (Etude et Suivi des POlyarthrites rhumatoïdes et arthrites Indifférenciées Récentes), a prospective multicenter cohort study of 10 years of follow-up will provide some information on the epidemiological profile of the RA in Morocco. Further prospective studies should prove valuable in determining these causal relationships.
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