Cardiac Changes Start Early in Rheumatoid Arthritis – MedPage Today

Arthritis Can Be Cured With Proven Natural Remedies

Cardiac Changes Start Early In Rheumatoid Arthritis - MedPage Today A cardiac MRI vertical axis view showing the 4 chambers - Cardiac Changes Start Early In Rheumatoid Arthritis - MedPage Today

Vascular abnormalities were already present at the time of diagnosis in rheumatoid arthritis in patients with no known cardiovascular disease, but improved over time with current treatment strategies, investigators reported.

Compared with healthy controls, patients with early RA showed 50% lower aortic distensibility, with a geometric mean of 3.0×10-3 mm Hg-1 vs 4.4×10-3 mm Hg-1, for an unadjusted geometric mean ratio of 1.5 (95% CI 1.2-1.8, P<0.01), according to Maya H. Buch, MBChB, PhD, of the University of Manchester in England, and colleagues.

After the patients received 1 year of treatment with methotrexate alone or in combination with etanercept (Enbrel), aortic distensibility improved by 20%, with a geometric mean ratio vs baseline of 1.2 (95% CI 1.1-1.3, P<0.01), the researchers reported in their study online in Annals of the Rheumatic Diseases.

The improvement in aortic distensibility of 20% at year 1 represents expected reductions of 12% for composite events and 13% for non-fatal cardiac events, an earlier study suggested.

Patients with RA are at elevated risk of premature cardiovascular disease, associated with both conventional risk factors and inflammation. In addition, recent studies have identified shared immune pathways and mediators between RA and cardiovascular disease, suggesting that immunomodulating therapies for RA might help alter the pathogenesis of cardiovascular disease in these patients and lower the risk of subsequent events.

To investigate this, Buch and colleagues analyzed data from the VEDERA trial, which evaluated patients with early RA treated with methotrexate, using a treat-to-target strategy, or etanercept plus methotrexate.

A subset of 81 patients in the trial underwent cardiovascular magnetic resonance imaging, a sensitive technique for assessing cardiac anatomic and functional characteristics, as did 30 matched controls. The primary endpoint of aortic distensibility was chosen because of its ability to reliably predict cardiovascular outcomes independent of conventional risk models, the team noted.

Two-thirds of the patients were women, and median age was 51. The majority of patients were seropositive, and baseline disease activity score was 5.3. Only 7% had hypertension, 2% had high cholesterol, and 5% had a family history of ischemic heart disease at baseline, while none had diabetes. A total of 55% were current or former smokers, and the median pack-years of smoking was 0.1. None had a history of cardiovascular symptoms or disease.

The significant difference between cases and controls in aortic distensibility persisted after adjustment for age, sex, blood pressure, and history of smoking, with a geometric mean ratio of 1.5 (95% CI 1.3-1.7, P<0.01).

Differences also were seen between cases and controls on other endpoints. Left ventricular mass was 20% less in the early RA patients than controls (78.2 vs 92.9 g, P<0.01) and myocardial extracellular volume, suggesting diffuse myocardial fibrosis, was 10% higher (27.2% vs 24.9%, P<0.01).

At 1 year, there were modest but significant increases in left ventricular mass, with a geometric mean ratio compared with baseline of 1 (95% CI 1-1.1, P=0.01), but no differences in other secondary outcomes such as left ventricular ejection fraction or left ventricular longitudinal strain.

After year 1, patients who had been randomized to receive etanercept plus methotrexate stopped the tumor necrosis factor inhibitor, and follow-up continued through year 2.

There were no differences at year 1 between patients receiving methotrexate alone or in combination with etanercept in aortic distensibility, left ventricular mass, or other secondary outcomes, or between patients considered responders or nonresponders.

At 2 years, the geometric mean ratio for aortic distensibility had improved by 10% from baseline (1.1, 95% CI 1-1.4, P=0.05), and the increase in left ventricular mass also remained significant, with a ratio of 1.1 (95% CI 1-1.2, P=0.02).

Cardiovascular risks increase very early in RA patients, the researchers emphasized. "The presence of abnormal vascular stiffness (adjusted for known risks including blood pressure) at the earliest stage of diagnosis of RA highlights the increased risk in this population."

Moreover, myocardial extracellular volume has been recognized as a prognostic factor for adverse outcomes. "Our observation that extracellular volume is already increased on diagnosis of early RA suggests a period of latent myocardial involvement before clinical presentation of RA," the investigators wrote.

A limitation of the study, they said, was its reliance on surrogate markers for the estimation of cardiovascular risk.

Disclosures

The study was supported by the National Institute for Health Research, and the parent study of VEDERA was supported by Pfizer.

The authors reported financial relationships with Pfizer, AbbVie, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Roche, EMD Serono, Sandoz, Sanofi, and UCB.

Primary Source

Annals of the Rheumatic Diseases

Source Reference: Plein S, et al "Cardiovascular effects of biological versus conventional synthetic disease-modifying antirheumatic drug therapy in treatment-naive, early rheumatoid arthritis" Ann Rheum Dis 2020; DOI: 10.1136/annrheumdis-2020-217653.