Improved Incidence of Cardiovascular Disease in Patients With Incident Rheumatoid Arthritis in the 2000s: A Population-based Cohort Study

Abstract

Objective To assess trends in incidence of cardiovascular disease (CVD) and mortality following incident CVD events in patients with rheumatoid arthritis (RA) onset in 1980- 2009 versus non-RA subjects. Methods We studied Olmsted County, Minnesota residents with incident RA (age ≥ 18 years, 1987 ACR criteria met in 1980-2009) and non-RA subjects from the same source population with similar age, sex and calendar year of index. All subjects were followed until death, migration, or 12/31/2016. Incident CVD events included myocardial infarction and stroke. Patients with CVD before RA incidence/index date were excluded. Cox models were used to compare incident CVD events by decade, adjusting for age, sex and CVD risk factors. Results The study included 905 patients with RA and 904 non-RA subjects. Cumulative incidence of any CVD event was lower in patients with incident RA in 2000s versus 1980s. Hazard Ratio [HR] for any incident CVD 2000s versus 1980s: 0.53; 95% confidence interval (CI): 0.31-0.93. The strength of association attenuated after adjustment for anti-rheumatic medication use: HR 0.64, 95%CI 0.34-1.22. Patients with RA in 2000s had no excess in CVD over non-RA subjects (HR: 0.71, 95%CI:0.42-1.19). Risk of death after a CVD event was somewhat lower in patients with RA after 1980s: HR: 0.54, 95%CI:0.33-0.90 in 1990s and HR: 0.68, 95%CI:0.33-1.41 in 2000s versus 1980s. Conclusion Incidence of major CVD events in RA has declined in recent decades. The gap in CVD occurrence between RA patients and the general population is closing. Mortality after CVD events in RA may be improving.

Is the Gap in Incidence of Cardiovascular Events in Rheumatoid Arthritis Really Closing?

“…Given the small total number of mortality events (83 RA, 57 non-RA), this finding could again reflect insufficient power to detect a difference. This report by Myasoedova, et al 8 adds to the growing data suggesting that CV event rates-AMIs in particular-are declining in successive incident RA cohorts, but leaves open questions about whether the gaps in CV event rates and CV mortality rates between RA and non-RA are truly declining. Other reports of CV event rates in RA vs non-RA comparators that include time periods after 2000 are scarce.…”

“…What could be the explanation for the discrepancy in results between the Myasoedova study 8 showing closing of the CV gap in recent decades, compared to the Yazdani 9 and Holmqvist 7 studies, which did not? All were population-based studies with matched comparators, but the Holmqvist 7 and Yazdani 9 studies had much larger sample sizes that yielded significantly higher numbers of CV events than Myasoedova, et al 8 Thus, the lack of a statistically significant difference in CV event rates between the RA and non-RA groups in the 2000s vs the 1980s in the Myasoedova study 8 may have been due to inadequate power. A strength of the Myasoedova study was that all AMIs were adjudicated by a cardiologist, whereas the other 2 studies utilized International Classification of Diseases codes for AMI diagnosis, although the latter 2 studies reported excellent positive predictive values for this methodology.…”

“…8 In contrast, Holmqvist, et al 7 did not report on these confounders, and Yazdani, et al's 9 presentation of them was arguably less robust than Myasoedova, et al 8 However, despite Myasoedova, et al's rich data resource, RA disease activity measures were apparently not systematically gathered; they were also not available in the administrative dataset examined in the Yazdani study. 8,9 In contrast, Holmqvist, et al had robust measures of RA disease activity, enabling the authors to investigate and report on the significant contribution of disease activity to the risk of subsequent AMI in the RA group. 7 In summary, while data are consistent and encouraging in identifying a substantial decrease in AMI rates in newly diagnosed patients with RA over consecutive decades, it is still unclear whether the gap in AMI rates between RA and the general population has truly narrowed or not.…”

“…A strength of the Myasoedova study was that all AMIs were adjudicated by a cardiologist, whereas the other 2 studies utilized International Classification of Diseases codes for AMI diagnosis, although the latter 2 studies reported excellent positive predictive values for this methodology. 7,8,9 Another particular strength of the Myasoedova study was the availability of robust medical records that yielded detailed information on conventional CV risk factors and allowed for statistical adjustment for these potential confounders in the RA vs non-RA event comparisons. 8 In contrast, Holmqvist, et al 7 did not report on these confounders, and Yazdani, et al's 9 presentation of them was arguably less robust than Myasoedova, et al 8 However, despite Myasoedova, et al's rich data resource, RA disease activity measures were apparently not systematically gathered; they were also not available in the administrative dataset examined in the Yazdani study.…”

“…7,8,9 Another particular strength of the Myasoedova study was the availability of robust medical records that yielded detailed information on conventional CV risk factors and allowed for statistical adjustment for these potential confounders in the RA vs non-RA event comparisons. 8 In contrast, Holmqvist, et al 7 did not report on these confounders, and Yazdani, et al's 9 presentation of them was arguably less robust than Myasoedova, et al 8 However, despite Myasoedova, et al's rich data resource, RA disease activity measures were apparently not systematically gathered; they were also not available in the administrative dataset examined in the Yazdani study. 8,9 In contrast, Holmqvist, et al had robust measures of RA disease activity, enabling the authors to investigate and report on the significant contribution of disease activity to the risk of subsequent AMI in the RA group.…”