ACS Risk Increased in New-Onset RA Despite Improved Disease Control

Individuals with new-onset rheumatoid arthritis (RA) are at increased risk for acute coronary syndrome (ACS), according to a nationwide population-based cohort study conducted in Sweden by researchers at the Karolinska Institutet in Stockholm.¹

Patients with rheumatoid arthritis are at higher risk than the general population for cardiovascular disease (CVD), the main underlying factor cause of morbidity and mortality in these patients.^2,3 The incidence of ACS was also found to be   higher among in patients with newly diagnosed RA than the general population.⁴ In the current study, the researchers sought to determine whether  advances in the management of new-onset RA had contributed to a reduction in the risk of ACS and other cardiovascular comorbidities. 

A total of 15,744 patients with new-onset RA between 1994 and 2017 were identified in the Swedish Rheumatology Quality Register, which includes medical data on individuals age ≥16 who fulfill the 1987 American College of Rheumatology criteria for RA. Each patient with RA was paired with up to 5 general-population comparator subjects (n=70,899) from the Swedish Population Register, a medical registry of the entire Swedish population. Of the study population, 69% were women and the average age was 57. Newly diagnosed RA was defined as a diagnosis within 12 months of patient-reported symptom onset. Subjects with a history of ACS at study outset were excluded.

ACS developed in 772 subjects in the RA cohort over the course of 103,835 person-years of follow-up and 2418 comparators over 466,930 person-years of follow-up. Incidence of ACS was higher in men, increased with age, and markedly decreased over the 17 years of follow-up. A 40% decline in ACS incidence in the general Swedish population was seen; however, a 40% higher risk of ACS (hazard ratio [HR] 1.41; 95% CI, 1.29-1.54) was seen in subjects with newly diagnosed RA. The increase was restricted to subjects with a Disease Activity Score 28-joint count (DAS28) >3.2 at diagnosis and subjects who were positive for rheumatoid factor. Death rates in the RA cohort and the general-population comparator group were similar (10.7% vs 10.4%).

“The most important message based on the findings from our study is that, even though we have been aware of the fact that patients with RA are at increased risk for ischemic heart disease for quite some time, we haven’t managed to remove the excess risk in newly diagnosed patients,” the study’s lead investigator Marie Holmqvist, MD, of the department of medicine at Karolinska Institute, told Rheumatology Advisor.

“These patients are still at increased risk compared with the general population, and it may be that we need to address ischemic heart disease risk factors that are already present at RA diagnosis. Are we doing what we can with respect to blood pressure, lipids, and so on?” she asked.  She and her co-investigators also questioned whether some treatment strategies are contributing to the risk of ACS. They noted, for example, that COX inhibitors and oral glucocorticoids, known to negatively impact cardiovascular health, might be used more frequently in the first months of active RA disease than during periods of well-controlled disease activity.

“On the upside, even though we see that the relative risk of ischemic heart disease in patients with RA — compared with the general population — is still increased, the absolute risk has decreased,” Dr Holmqvist commented. She recommended that clinicians speak with their patients about steps to take, including dietary and lifestyle modifications, to lower risk. 

Summary and Clinical Applicability

The relative risk of ischemic heart disease in patients with newly diagnosed RA remains high. As CVD is common in RA and is a primary contributor to morbidity and mortality in this population, strategies should be considered to reduce CVD risk upon diagnosis of RA.

Limitations and Disclosures

Given the thoroughness of data capture in the Swedish medical system and data pointing to a decline in ACS in a number of Western countries, the investigators contend that their findings reflect a largely accurate picture of CVD and RA epidemiology. They stated that risk of miscalculation is low in light of a previous study that had a positive predictive value of 95%.⁵

References

1. Holmqvist M, Ljung L, Askling J. Acute coronary syndrome in new-onset rheumatoid arthritis: a population-based nationwide cohort study of time trends in risks and excess risks [published online July 14, 2017]. Ann Rheum Dis.  doi:10.1136/annrheumdis-2016-211066
2. Solomon DH, Goodson NJ, Katz JN, et al. Patterns of cardiovascular risk in rheumatoid arthritis. Ann Rheum Dis. 2006;65(12):1608-1612.
3. Meune C, Touzé E, Trinquart L, Allanore Y. Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford). 2009;48(10):1309-1313.
4. Holmqvist ME, Wedrén S, Jacobsson LT, et al. Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 2006. J Intern Med. 2010;268(6):578-585.
5. Ljung L, Simard JF, Jacobsson L, et al. Treatment with tumor necrosis factor inhibitors and the risk of acute coronary syndromes in early rheumatoid arthritis. Arthritis Rheum. 2012;64(1):42-52.