乌鸦传媒

AMSTERDAM -- Siblings of patients with rheumatoid arthritis (RA) are at increased risk of acute coronary syndromes (ACS), according to a Swedish study presented here, suggesting that there is shared susceptibility between these two conditions.

Compared with the general population, the hazard ratio for ACS among RA patients was 1.44 (95% CI 1.25-1.66), while among the RA patients' siblings, the hazard ratio was 1.23 (95% CI 1.09-1.40), reported Johan Askling, MD, of the Karolinska Institute in Stockholm in a press briefing at the , sponsored by the European League Against Rheumatism.

Studies have shown that patients with RA are at increased risk of cardiovascular disease and mortality, and the excess risks seem to be related to disease activity and duration.

"What is somewhat disturbing, and our reason for doing this study, is that we would expect over time and with more effective RA treatments the excess risk for cardiovascular diseases in RA would decline. However, that the excess risk for RA patients compared with the general population remains," he said.

"So maybe the whole risk isn't due to RA itself, but perhaps RA and ACS share susceptibility or risk factors," he said.

Previous studies have compared cardiovascular risks in RA patients with the general population, but if shared factors were driving both RA and cardiovascular disease, the optimal setting to study that would involve monozygotic twins. However, because of the small numbers of twins with RA, Askling's group chose to study full siblings of RA patients, who share certain genetic and environmental factors although they are not identical.

They took advantage of the various Swedish registers to identified a cohort of patients with early RA diagnosed from 1996 to 2015 (n=7,663) and their full siblings (n=10,962), linking patients with five general population comparators matched by age and sex (n=35,825) and their full siblings (n=48,162). For the comparative analysis, individuals with a history of ACS were excluded.

Across those four groups, incidence rates of ACS ranged from 2.2% to 3.4%.

The researchers also stratified the analysis according to rheumatoid factor seropositivity, and found that the sibling effect was very nearly exclusive to the seropositive subset.

The finding that siblings of patients with RA are at increased risk for ACS does suggest the possibility of common pathways, but the extent to which this shared susceptibility reflects genetic factors -- nature -- or shared environment factors -- nurture -- remains to be further studied. "We are looking into that currently," Askling said.

The study also suggests that not all cardiovascular risk in patients with RA can be eliminated by targeting inflammation. "The most we can do is bring down the patient's risk to their sibling risk and then focus on other factors such as lifestyle," he said. And lifestyle interventions tend to be inexpensive, nontoxic, and can be helpful for a number of other diseases, he added.

The press briefing moderator, Robert Landewé, MD, of the University of Amsterdam, described the study as "ingenious," and noted that it could only be done in a country such as Sweden with its complete and interlinked disease registers.

He also suggested that the persisting risks are likely to relate to both genes and lifestyle, and Askling agreed.

"We can never escape our genes," Askling said. "We could speculate that, if you have adverse lifestyle characteristics and bad genes and you add inflammation on top of that, you unleash hell. So removing inflammation will help but it's unlikely to take the risk down to zero," he stated.