In patients with rheumatoid arthritis (RA), strategies to prevent cardiovascular events, such as treating hypertension, encouraging patients to stop smoking, and reinforcing statin therapy, may be especially important, regardless of whether they have a history of coronary artery disease because their risk for adverse cardiovascular outcomes is significantly greater than for patients who have neither RA nor coronary artery disease (CAD), a large population-based study from Denmark suggests.

“Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalized treatment strategies,” wrote Brian B. Løgstrup, MD, PhD, DMSc, of Aarhus (Denmark) University Hospital, and his colleagues.

The study, published in Annals of the Rheumatic Diseases, analyzed 125,331 patients with and without CAD in the Western Denmark Heart Registry who had coronary angiography from 2003 through 2016. The cohort included 671 RA patients with no confirmed CAD and 1,061 RA patients who had CAD.

The study makes a significant contribution to the literature in reporting on the additive risk of RA and CAD, said Christie M. Bartels, MD, associate professor in the division of rheumatology at the University of Wisconsin, Madison. “Even among patients with both conditions [RA and CVD], they were less likely to get statin therapy,” she said, noting that the 82.6% of study patients with both CAD and RA were on statins vs. 86.5% of those with CAD alone, while the former had significantly higher rates of hypertension – 64.3% vs. 58.8%. “We’re doing a less effective job on secondary prevention,” she said. The anti-inflammatory properties of statins can also have an additive benefit in RA, she noted.

Dr. Christie M. Bartels, a rheumatologist at the University of Wisconsin, Madison

Dr. Christie M. Bartels

“This study shows that the rheumatologist can play a role in reinforcing the importance of primary and secondary cardiovascular disease prevention – meaning hypertension control, counseling patients to stop smoking and following up on statin therapy in RA,” Dr. Bartels added.

The study presents two novel findings, Dr. Løgstrup and colleagues noted:

  • That RA confers a statistically significant, “but numerically marginally,” heightened risk of cardiovascular events other than stroke.
  • Among patients with CAD, RA confers an increased risk of cardiac and all-cause death as well as MI and major adverse cardiovascular events (MACE).

“These finding indicate that RA may have a potential impact for precipitating cardiovascular events beyond CAD and, even more importantly, that RA seems to exacerbate the clinical risk of cardiovascular events in the presence of CAD,” Dr. Løgstrup and colleagues wrote.

The study found that patients with neither RA nor CAD had the lowest 10-year rates of MI (2.7%), ischemic stroke (2.9%), all-cause death (21.6%), cardiac death (2.3%), and MACE (7.3%).

By comparison, those with RA but no CAD had 10-year rates of 3.8% for MI, 5.5% for stroke, 35.6% for all-cause death, 3% for cardiac death, and 11.5% for MACE. Rates for those outcomes for people with CAD but no RA were 9.9% for MI, 4.6% for stroke, 33.3% for all-cause death, 7% for cardiac death, and 19.1% for MACE.

For patients with both RA and CAD, 10-year rates were 12.2% for MI, 4.4% for stroke, 49% for all-cause death, 10.9% for cardiac death, and 24.3% for MACE.

The researchers also performed a risk adjustment analysis based on potential confounding variables across the different groups, such as age, gender, comorbidities including diabetes and hypertension, active smoking status, and anticoagulant, antiplatelet, and statin therapy. The adjusted analysis revealed that patients with RA alone had a 63% greater risk of MI, 68% greater risk for stroke, 42% greater risk for all-cause death, 25% greater risk for cardiac death, and 60% greater risk for MACE than did people who had neither RA nor CAD.

For people with both RA and CAD, the adjusted risks were significantly higher when compared to people with neither: more than four times greater for MI and MACE, 55% greater for stroke, almost double for all-cause death, and 3.7 times greater for cardiac death. People with CAD but no RA also had higher adjusted risk rates compared to people with neither, but had variable rates when compared to people with RA but no CAD, and significantly lower adjusted rates compared to people with both.

The nature of CAD was also a factor, Dr. Løgstrup and colleagues noted. “We found more non-obstructive CAD but no increased incidence of one-vessel, two-vessel, and three-vessel disease in patients with RA than in patients without RA,” they wrote. That’s in line with other published studies (Semin Arthritis Rheum. 2010;40[3]:215–21 and J Rheumatol. 2007;34[5]:937–42), but counter to a study that found increased plaque burden and higher rates of multivessel disease among people with RA (Ann Rheum Dis. 2014;73:1797–804). Differences in methodology, vessel disease definitions, and study population may explain these deviations.

The study authors did not declare any outside source of funding or any competing interests.

Dr. Bartels disclosed receiving institutional grant funding through Pfizer.

SOURCE: Løgstrup BB et al. Ann Rheum Dis. 2020 May 29. doi: 10.1136/annrheumdis-2020-217154.