Risk Factors Identified for Venous Thromboembolism and Atherosclerotic Cardiovascular Disease in Rheumatoid Arthritis

Thromboembol in blood vessel
Thromboembol in blood vessel. Clot formation, 3D illustration
Researchers compared the risk factors for unprovoked venous thromboembolism and atherosclerotic cardiovascular disease in patients with rheumatoid arthritis.

In patients with rheumatoid arthritis (RA), unprovoked venous thromboembolism (VTE) may be a spectrum of pan-cardiovascular syndrome and a risk factor for atherosclerotic cardiovascular disease (ASCVD), according to study results published in RMD Open.

Researchers sought to compare risk factors for unprovoked VTE and ASCVD in patients with RA and to evaluate subsequent ASCVD risk following an unprovoked VTE.

A cohort study was conducted using FORWARD, The National Databank for Rheumatic Diseases, a longitudinal observational registry in the US. Participants were enrolled from US rheumatologists and were followed up by self-reported semi-annual questionnaires. Between January 1998 and December 2018, participants with RA in the FORWARD registry without prior CVD (VTE or ASCVD) at baseline and any active cancer during follow-up were included in the current study.

Study outcomes included incident ASCVD as a composite endpoint of the first confirmed fatal or nonfatal myocardial infarction (MI), stroke, or related death; and incident unprovoked VTE as a composite endpoint of the first confirmed deep vein thrombosis (DVT) and/or pulmonary embolism (PE) or related death. For the secondary objective, the study outcome was incident ASCVD.

All possible VTE and ASCVD events were identified from study questionnaires, physician reports, and hospitalization/procedural/death records. If hospital/death records were not available, the patient, physician, or the family was contacted via a structured, protocolized interview that was intended to address the reported condition. Incident unprovoked VTE included DVT and PE not associated with cancer, recent surgery, hospitalization, pregnancy, or fracture; ASCVD included MI or stroke.

During follow-up, the first of any of these CVD events was evaluated. Further, the risk for ASCVD and VTE was investigated separately against patients who did not experience any of these outcomes. For those who experienced both events at different times, the patient could contribute only to the first outcome that occurred.

Over a median period of 4 years (range, 1.5-7 years) of follow-up in a total of 31,366 patients with RA, the researchers identified 539 unprovoked VTE events and 1648 ASCVD events. Adjusted models demonstrated that increased VTE and ASCVD risk was associated with the male sex, older age, presence of comorbidities, worse disability, prior fracture, higher disease activity, and glucocorticoid use.

Traditional CVD risk factors were common among both ASCVD and VTE, but ASCVD risk was increased only with obesity (VTE hazard ratio [HR], 1.46; 95% CI, 1.13-1.87 and ASCVD HR, 0.58; 95% CI, 0.58; 95% CI, 0.50-0.68). Following an unprovoked VTE, risk for ASVD doubled (HR, 2.05; 95% CI, 1.43-2.95).

Study limitations included the fact that event rates were lower than those from previous studies assessing VTE and ASCVD in patients with RA; the inability to assess VTE risk with Janus kinase inhibitors due to the small number of patients receiving these medications; and the possibility of survivor bias with a disease duration of more than 15 years.

Researchers concluded, “Our results may help stratify the VTE and ASCVD risk and encourage physicians to integrate well-known CVD risk reduction strategies into the prevention of VTE and subsequent ASCVD.”


Ozen G, Pedro S, Schumacher R, Simon T, Michaud K. Risk factors for venous thromboembolism and atherosclerotic cardiovascular disease: do they differ in patients with rheumatoid arthritis? RMD Open. 2021;7(2):e001618. doi:10.1136/rmdopen-2021-001618