Background/Purpose: Chronic inflammation is linked to increased risk of cardiovascular disease (CVD) in RA that may manifest as venous thromboembolism (VTE) or atherosclerotic CVD (ASCVD). VTE is a potentially fatal condition that has been an increasing concern due to recent associations with the use of JAK inhibitors. However, our knowledge is limited about what factors determine VTE development in patients with RA, and if these risk factors are different than the ones for atherosclerotic CVD (ASCVD). We performed a cohort study aiming to assess risk factors favoring VTE over ASCVD in patients with RA.

Methods: RA patients participating in FORWARD, The National Databank for Rheumatic Diseases, from 1998 through 2018 were assessed for incident nonfatal or fatal unprovoked VTE (deep venous thrombosis and pulmonary emboli not associated with active cancer, recent surgery, hospitalization, fracture, pregnancy) and ASCVD (myocardial infarction and stroke) validated from hospital/death records. Patients with prior VTE/ASCVD and active cancer were excluded. Event rates were calculated, and the risk factors for VTE and ASCVD were determined separately using Cox proportional hazards compared to patients who had no history of VTE and ASCVD.  

Results: Of 31,366 RA patients, we identified 539 first unprovoked VTE and 1,648  first ASCVD events during median (IQR) 4 (1.5-7) years of follow-up. The crude incidence rates per 1,000 patient-years (95% CI) were 0.34 (0.31-0.37) for VTE and 1.57 (1.51-1.63) for ASCVD. Baseline characteristics of patients by the CVD type are presented in Table 1. Patients with VTE were significantly more obese than patients with ASCVD but not different in terms of the history of prior cancer, fracture and traditional CV risk factors (diabetes [DM], hypertension [HT], and smoking). The multivariable models showed that older age, being male, having more comorbidities, history of fracture, worse HAQ scores, moderate/high disease activity and glucocorticoid use were associated with both increased VTE and ASCVD risks (Table 2). However, age and gender were stronger risk factors for ASCVD than for VTE and history of prior fracture and glucocorticoid use were stronger risk factors for VTE than for ASCVD.  Traditional CV risk factors, DM and HT increased only ASCVD risk. Obesity had opposite effects on VTE and ASCVD risks: increased VTE risk (HR [95% CI], 1.46 [1.13-1.87]) and decreased ASCVD risk (HR [95% CI], 0.58 [0.50-0.68]) while underweight (HR [95% CI], 1.51 [1.13-2.02]) increased ASCVD risk. Hydroxycholoroquine use was found to be associated with a lower risk of VTE and ASCVD (Table 2).

Conclusion: With different risk magnitudes, VTE and ASCVD share common risk factors representing RA disease severity including disability, high disease activity and glucocorticoid use. The main difference in risk factors for these CV events is the traditional CV risk factors; DM and HT increase ASCVD risk and obesity increases VTE risk with a paradoxical effect on ASCVD. Being obese and having a prior fracture may be promoting immobilization and hence VTE. These risk factors can be helpful in individual risk assessment, particularly in the availability of JAK inhibitors that may increase VTE risk.

Table 1 for VTE vs. ASCVD

Table 2 for VTE vs. ASCVD

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/first-cardiovascular-event-in-rheumatoid-arthritis-do-patients-with-venous-thromboembolism-have-a-different-risk-profile-than-patients-with-atherosclerotic-cardiovascular-disease/