Cardiovascular Risk in Inflammatory Arthritis

Smulders, Y.M. [Promotor]Peters, M.J.L. [Copromotor]Nurmohamed, M.T. [Copromotor]Voskuijl, A.E. [Copromotor

Cardiovascular disease prevalence in patients with inflammatory arthritis, diabetes mellitus and osteoarthritis: a cross-sectional study in primary care

<p>Abstract</p> <p>Background</p> <p>There is accumulating evidence for an increased cardiovascular burden in inflammatory arthritis, but the true magnitude of this cardiovascular burden is still debated. We sought to determine the prevalence rate of non-fatal cardiovascular disease (CVD) in inflammatory arthritis, diabetes mellitus and osteoarthritis (non-systemic inflammatory comparator) compared to controls, in primary care.</p> <p>Methods</p> <p>Data on CVD morbidity (ICPC codes K75 (myocardial infarction), K89 (transient ischemic attack), and/or K90 (stroke/cerebrovascular accident)) from patients with inflammatory arthritis (n = 1,518), diabetes mellitus (n = 11,959), osteoarthritis (n = 4,040) and controls (n = 158,439) were used from the Netherlands Information Network of General Practice (LINH), a large nationally representative primary care based cohort. Data were analyzed using multi-level logistic regression analyses and corrected for age, gender, hypercholesterolemia and hypertension.</p> <p>Results</p> <p>CVD prevalence rates were significantly higher in inflammatory arthritis, diabetes mellitus and osteoarthritis compared with controls. These results attenuated - especially in diabetes mellitus - but remained statistically significant after adjustment for age, gender, hypertension and hypercholesterolemia for inflammatory arthritis (OR = 1.5 (1.2-1.9)) and diabetes mellitus (OR = 1.3 (1.2-1.4)). The association between osteoarthritis and CVD reversed after adjustment (OR = 0.8 (0.7-1.0)).</p> <p>Conclusions</p> <p>These results confirm an increased prevalence rate of CVD in inflammatory arthritis to levels resembling diabetes mellitus. By contrast, lack of excess CVD in osteoarthritis further suggests that the systemic inflammatory load is critical to the CVD burden in inflammatory arthritis.</p

Management of cardiovascular risk in patients with rheumatoid arthritis: evidence and expert opinion.

The risk of cardiovascular morbidity and mortality is increased in rheumatoid arthritis. The classical cardiovascular risk factors, including smoking, hypertension, dyslipidaemia, insulin resistance and diabetes mellitus, obesity and physical inactivity do not appear to explain the excess cardiovascular risk in rheumatoid arthritis, although they do contribute, albeit in a different way or to a lesser extent, to rheumatoid arthritis in comparison with the general population. A very important link between rheumatoid arthritis and cardiovascular disease is inflammation as it plays a key role in all stages of atherosclerosis: from endothelial dysfunction to plaque rupture and thrombosis. It also has an influence on and accentuates some traditional cardiovascular risk factors, such as dyslipidaemia, obesity and insulin resistance. To date, the exact pathophysiologic mechanism by which this relation between cardiovascular disease and rheumatoid arthritis can be explained is not completely clear. Cardiovascular risk management in rheumatoid arthritis is mandatory. Unfortunately, the way this should be done remains a point of discussion. In this review issues regarding cardiovascular risk in rheumatoid arthritis and its management will be addressed, according to evidence presented in the latest studies and our own experience-based opinion

Confounding by Indication Probably Distorts the Relationship between Steroid Use and Cardiovascular Disease in Rheumatoid Arthritis: Results from a Prospective Cohort Study

OBJECTIVE: To evaluate the risk of cardiovascular disease in patients with rheumatoid arthritis exposed to glucocorticoids. METHODS: Retrospective analysis of exposure to glucocorticoids in a prospective cohort of 353 patients with rheumatoid arthritis followed from June 2001 up to November 2011 for incident cardiovascular disease in a hospital-based outpatient cohort in the Netherlands. Hazard ratios with 95%-confidence intervals were calculated for the association between different types of exposure to glucocorticoids and incident cardiovascular disease. Associations were adjusted for demographics, cardiovascular risk factors and disease related parameters. RESULTS: Recent and current exposure to glucocorticoids were associated with incident cardiovascular disease, as was a longer duration of exposure and cumulative exposure to glucocorticoids. Adjustment for disease activity and severity negated the association. CONCLUSION: In observational studies the finding of incident cardiovascular disease in patients with rheumatoid arthritis exposed to glucocorticoids is strongly confounded by indication due to high disease activity. The adverse cardiovascular effects of glucocorticoids might be balanced by positive effects working through inflammation control

Subclinical renal dysfunction is independently associated with cardiovascular events in rheumatoid arthritis: the CARRE Study

Background Patients with rheumatoid arthritis (RA) have double the risk of cardiovascular (CV) disease, largely independently of traditional CV risk factors. Renal dysfunction is associated with CV morbidity and mortality in the general population, but data on this association in RA are lacking. Objective To investigate the association between renal function and CV events in RA. Methods The CARRE Study is an ongoing prospective cohort study of Dutch patients with RA, which records CV events. Glomerular filtration rate (GFR) was estimated with the abbreviated Modification of Diet in Renal Disease formula. Logistic regression determined the association between estimated GFR and the occurrence of CV events. Results 353 patients were followed for 3 years, and 23 (7%) had a CV event. Patients who had an event had a significantly lower baseline GFR than those who did not (59 vs 79 ml/min, p=0.001). This association remained significant after adjustment for traditional risk factors: in this analysis, a decrease in GFR of 5 ml/min was associated with a 30% (95% CI 7% to 59%) increase in the occurrence of CV events. During follow-up, an unfavourable change in GFR was noted in patients who later had a CV event compared with those who did not. Conclusion These data confirm that, in RA, renal dysfunction is associated with a higher risk of CV disease independently of traditional CV risk factor

The effect of TNF-alpha blocking therapy on lipid levels in rheumatoid arthritis: a meta-analysis

&lt;p&gt;Objectives: Changes in the lipid profile have been described in patients with rheumatoid arthritis (RA) following therapy with tumor necrosis factor (TNF)-alpha blocking agents. However, thus far, results have been inconsistent. Therefore, we investigated changes in lipid levels after TNFalpha blocking therapy using meta-analysis of published data.&lt;/p&gt; &lt;p&gt;Methods: The literature was searched to identify studies assessing changes in total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol, triglycerides, atherogenic index (ie, TC/HDLc ratio), and apolipoprotein levels in response to TNF-alpha blocking therapy. Weighted mean levels of lipids at different time points and subsequent changes in these lipid levels between these time points were calculated with multivariate linear mixed models.&lt;/p&gt; &lt;p&gt;Results: Data were available on TC in 15 studies encompassing 766 RA patients and on HDLc in 14 studies encompassing 736 RA patients. TC increased significantly (maximum increase of 10%) and HDLc increased significantly in the first 2 to 6 weeks of therapy (maximum increase of 7%), after which it remained more or less stable. The atherogenic index did not significantly change over time. There was too limited information to evaluate changes in other lipids and apolipoproteins.&lt;/p&gt; &lt;p&gt;Conclusions: TNF-alpha blocking therapy has a modest effect on TC and HDLc levels in RA patients with no significant overall effect on the atherogenic index. Whether TNF-alpha blocking effects on qualitative lipid changes (structure and function) are more relevant to their presumed vascular benefits requires further study.&lt;/p&gt