CV Risk in Rheumatic Disease

January 23, 2019

(1) Inflammatory diseases raise risk of venous thromboembolism; (2) antiphospholipid antibodies play a role in MI; (3) persistent hyperuricemia predicts mortality.

Several rheumatic diseases are associated with a higher risk of cardiovascular (CV) events and death. Three new studies highlight the CV risks: (1) venous thromboembolism (VTE) is associated with three chronic inflammatory diseases-psoriatic arthritis (PsA), psoriasis, and rheumatoid arthritis (RA); (2) IgG antiphospholipid antibodies are a commonly overlooked risk factor in myocardial infarction (MI); and (3) failure to reach optimal serum urate targets in gout increases mortality.^1-3 Scroll through the slides for the latest findings and their clinical implications.

A large, population-based study with long-term follow-up determined the risk of venous thromboembolism (VTE), defined as the combined endpoint of deep venous thrombosis (DVT) and pulmonary embolism (PE), among 12,084 patients with psoriatic arthritis (PsA), 194,288 patients with psoriasis, and 51,762 patients with rheumatoid arthritis (RA) compared with 1,225,571 matched controls.

Patients who had RA (with and without a disease-modifying antirheumatic drug [DMARD] prescription) and those with mild psoriasis had significantly elevated risks of VTE (hazard ratio, 1.35) after adjusting for traditional risk factors. Patients with severe psoriasis and PsA who had been prescribed a DMARD had an elevated, but not statistically significant, risk of VTE. Findings were similar for DVT. The age- and sex-adjusted risk of PE was elevated in patients with RA, severe psoriasis, and PsA who had been prescribed a DMARD.

Clinical Implications: “While systemic inflammation is a risk factor for VTE, the risk of VTE compared with controls is different among patients with three different inflammatory disorders: RA, PsA, and psoriasis,” stated the researchers, led by Alexis Ogdie-Beatty, MD, Assistant Professor of Medicine at the University of Pennsylvania in Philadelphia. The researchers speculate that efforts to lower inflammation may affect the risk of VTE in these patients.

In a large cohort of well-characterized patients with a first-time myocardial infarction (MI) and in age- and gender-matched population controls, standardized methods were used to determine the prevalence of antiphospholipid autoantibodies (anti-cardiolipin and/or anti-Î²₂glycoprotein-I antibodies). The study divided patients into two groups: 805 patients, age less than 75 years, who were investigated for 6 to 10 weeks after a first-time MI, and 805 age-, sex-, and area-matched controls who were MI-free.

Results showed 10.9% of patients with MI were positive for IgG anti-cardiolipin versus 0.9% of controls, and 10.4% of patients with MI were positive for anti-Î²₂glycoprotein-I antibodies versus 0.9% of controls. Many patients with MI also had high IgG titers.

IgG positivity for anti-cardiolipin and anti-Î²₂glycoprotein-I antibodies was highly correlated, and these antibodies were evaluated together as combined antiphospholipid autoantibodies IgG positivity. Using this definition, antiphospholipid autoantibodies IgG positivity remained associated with MI after adjusting for traditional cardiovascular risk factors, including smoking, hypertension, diabetes, and body-mass index.

Clinical Implications: “We are now conducting longitudinal studies which address two remaining pivotal questions: If the observed antiphospholipid autoantibodies IgG in patients with MI are persistent or transient, and if the prognosis of MI patients who are antiphospholipid autoantibodies IgG positive differs compared to other MI patients,” said co-author Elisabet Svenungsson, MD, Senior Consultant, Professor of Rheumatology at Karolinska Institutet/Karolinska University Hospital in Stockholm, Sweden. “If our results and hypotheses are confirmed, antiphospholipid autoantibodies testing may become part of routine MI care, and help identify MI patients who are at high risk for complications and who may benefit from anticoagulation treatment as protection from future vascular events.”

A prospective, follow-up cohort study included 1193 patients treated at a gout clinic from 1992 to 2017; 85% of the patients had a confirmed diagnosis of gout. All had at least one follow-up visit. Serum uric acid levels were monitored during follow-up, and mortality was confirmed from medical records, patients’ families, or local death registries.

Mean serum uric acid level at baseline was 9.1 mg/dL; 16.3% of patients maintained serum uric acid levels of 6 mg/dL or higher despite treatment. There was a total of 158 deaths, which represents a 13% overall mortality rate.

Overall crude mortality rate was 32.7 per 1000 patient-years. This was significantly higher for patients whose serum uric acid level was greater than 6 mg/dL (80.9 per 1000 person-years). After adjusting for age, sex, previous cardiovascular events, and baseline serum uric acid concentration, a serum uric acid level of 6 mg/dL or higher was associated with increased mortality risk (hazard ratio, 2.39). Failure to reach a target serum urate level of 6 mg/dL was an independent predictor of mortality in patients with gout.

Clinical Implications: “There are two current approaches for hyperuricemia in gout: treat-to-target interventions to reach therapeutic serum urate levels, or treat to flare unless severe gout develops,” said lead author Fernando Perez-Ruiz, MD, PhD, Senior Specialist, Rheumatology Division, Hospital Universitario Cruces in Baracaldo, Spain. “This new analysis shows that although a signal for developing severe gout remains, reaching serum urate therapeutic target is associated with lower mortality risk than being over target. Although we cannot exclude other variables not included in our database, such as control of comorbid conditions, our results encourage making any clinically acceptable effort to reach and maintain target serum urate levels. Keep in mind that development of severe gout is not a desirable outcome either.”

References

1. Ogdie A, McGill K, Shin DB, et al. Risk of venous thromboembolism in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a general population-based cohort study. Eur Heart J. 2018;39:3608-3614. doi: 10.1093/eurheartj/ehx145.

2. Grosso G, Sippl N, Kjellstrom B, et al. IgG antiphospholipid antibodies, a common but neglected finding in patients with myocardial infarction [abstract]. ArthritisRheumatol. 2018;70(suppl 10).

3. Perez-Ruiz F, Richette P, Stack A, et al. Failure to reach serum urate target is associated with elevated mortality in gout [abstract]. Arthritis Rheumatol. 2018;70(suppl 10).

CV Risk in Rheumatic Disease

Mark L. Fuerst