Risk for cardiovascular disease (CVD) was found to be significantly higher among patients with rheumatoid arthritis (RA) compared with the general US population, with age being a significant predictor of the RA-CVD association, according to study results published in Annals of Epidemiology.

Researchers used aggregated data from 10 continuous cycles of the National Health and Nutrition Examination Survey (NHANES), starting with the 1999 to 2000 cycle and ending with the 2017 to 2018 cycle. Data on RA and CVD diagnoses were collected from survey responses.

Design-based logistic regression was used to estimate the odds ratio (OR) for CVD among patients with RA compared with those without RA. Models were adjusted for potential confounders and risk factors for CVD, including family history, and comorbid hypertension and diabetes. Researchers also explored effect modification by age; age strata was defined as younger than 50 years, 50 to 79 years, and 80 years and older.

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The study sample included 35,062 adults, among whom 70% were aged between 20 and 49 years; 49.7% were women; and 26.3% had at least a college degree. Comorbid hypertension was reported by 54.4% of the survey respondents.

Survey data were stratified into 3 periods: 1999 through 2006, 2007 through 2012, and 2013 through 2018. The weighted proportion of respondents with RA ranged from 4.98% to 5.19% across study periods. CVD was reported in 5.6% of the 1999 to 2006 sample, 5.84% of the 2007 to 2012 sample, and 5.78% of the 2013 to 2018 sample.

A significant association was observed between RA and CVD, though the strength of the association declined slightly over time. The odds of CVD in patients with RA compared with healthy participants was 2.32 (95% CI, 1.85-2.90) in the 1999 to 2006 period, 2.19 (95% CI, 1.69-2.84) in the 2007 to 2012 period, and 1.97 (95% CI, 1.43-2.71) in the 2013 to 2018 period. Per 100 CVD events, 11, 10, and 9 additional events were associated with RA in the 1999 to 2006, 2007 to 2012, and 2013 to 2018 periods, respectively.

A significant effect modification by age was observed on both the relative and absolute risk scales. Among adults younger than 50 years, the odds of CVD in patients with RA were 3.96 (95% CI, 2.28-6.89) in the 1999 to 2006 period, 3.96 (95% CI, 2.06-7.60) in the 2007 to 2012 period, and 5.44 (95% CI, 3.25-9.12) in the 2013 to 2018 period. In the absolute scale, CVD risk was greatest in adults with RA aged at least 80 years. However, patients younger than 50 years had the greatest CVD risk relative to comparators in the same age group. Among those younger than 50 years, the odds of CVD were 3.96 (95% CI, 2.28-6.89) in the 1999 to 2006 period, 3.96 (95% CI, 2.06-7.60) in the 2007 to 2012 period, and 5.44 (95% CI, 3.25-9.12) in the 2013 to 2018 period.

Study limitations included the unmeasured confounding that may have occurred and the use of self-report to capture certain covariates that may have led to over- or underreporting.

The researchers concluded, “Our findings showed that RA was significantly associated with CVD morbidity among adults in the US over the years….[P]revention of CVD remains an essential aspect of care for patients with RA, and all patients with RA should be treated optimally regardless of age.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 


Hossain MB, Kopec J, Atiquzzaman M, Karim ME. The association between rheumatoid arthritis and cardiovascular disease among adults in the United States during 1999-2018, and age-related effect modification in relative and absolute scales. Ann Epidemiol. Published online March 14, 2022. doi:10.1016/j.annepidem.2022.03.005