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Dr. Jayatilleke: Research provides credible evidence for an increase in dementia in RA patients with CVD

Dr. Jayatilleke scans the journals, so you don’t have to!

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Arundathi Jayatilleke, MD

Rheumatoid arthritis (RA) is well-known to be associated with an increased risk of cardiovascular events, especially in the setting of active disease or inflammation. Several recent RA studies delve more deeply into risk factors and mitigating factors associated with development of comorbidities. Baker et al investigated incidence of diabetes mellitus (DM) in the Veterans Affairs RA Registry. In this large study of nearly 1900 patients, DM was associated with RA disease activity after accounting for age, BMI, RA therapy, and glucocorticoid use; methotrexate use was associated with lower incidence of DM. IL-1 a and IL-6 levels were independently associated with DM, suggesting that systemic inflammation plays a role in development of DM. This study highlights yet another condition that seems to be impacted by the increased systemic inflammation found in RA; however, its use of the predominantly male VA registry limits its generalizability.


Li et al looked at risk of thromboembolic disease in patients with RA within the first 5 years of diagnosis compared to those without RA. Using a population database in British Columbia, Canada, 39,142 RA patients were matched to 78,078 non-RA patients and those with prior venous thromboembolism (VTE) were excluded. Incidence rates of VTE, pulmonary embolism (PE), and deep venous thrombosis (DVT) were higher among the RA cohort than the non-RA cohort; this observation held true after adjusting for age, sex, glucocorticoid, and contraceptive use. It would be interesting to know if the increased risk holds true after control of inflammation (i.e. in patients with established RA in low vs. high disease activity states). In the absence of information about BMI and tobacco use, more studies are necessary to provide further support for this finding.

As noted above, RA is associated with cardiovascular disease (CVD), along with risk of death from cardiovascular complications. Because CVD is itself a risk factor for dementia, Sattui et al examined the potential for systemic inflammation and CVD to increase risk of developing dementia in RA patients. Using CMS claims data from 2006 to 2014, they studied 56,000 RA patients age 65 or older and looked at risk of dementia according to CVD status (no CVD or risk factors, CVD risk factors without disease, and CVD). Incidence rates for dementia were higher among RA patients with CVD risk factors than those without, and highest among RA patients with CVD. This effect was age-dependent, with a more significant risk among RA patients age 65-74, perhaps because of a general increase in dementia in older adults. As RA disease activity was not obtainable in this study, the effects of systemic inflammation are difficult to attribute. In addition, there may be some misclassification of data regarding coding of dementia subtypes (i.e. vascular and Alzheimer dementia). However, as there are limited studies in this area, this study provides credible evidence for an increase in dementia in RA patients with CVD, which should be further investigated.

Finally, hydroxychloroquine (HCQ) has come under increased scrutiny in the past year in terms of its potential use outside of treatment of lupus and RA as well as potential side effects. Cardiac toxicity related to HCQ is thought to be rare; Sorour et al looked at the association between chronic HCQ use in patients with RA and the development of heart failure (HF) using a retrospective study comparing patients who developed HF after RA diagnosis to those who did not develop HF. HCQ use was similar in both groups and a higher cumulative HCQ dose was not associated with increased risk of HF. As it is small and retrospective, larger prospective studies would be helpful, but this remains reassuring as to the safety of HCQ in RA patients.

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