People with HIV and cardiovascular disease have higher levels of the interleukin-1 receptor antagonist (IL-1Ra) and soluble regulator sIL-1R1 up to 10 years before the first myocardial infarction (MI) compared with people with HIV and no cardiovascular disease, according to a study published in The Journal of Infectious Diseases. After adjusting for traditional risk factors, IL-1Ra still successfully predicted MI within this population.
Previous research has demonstrated that people with HIV have a higher cardiovascular disease risk than the general population. This nested case control study of people with HIV (n=55) with a first MI and people with HIV with no cardiovascular disease (n=182) measured soluble markers of IL-1 activation in plasma samples from 4 different time points: 1) most recent prior to initiating antiretroviral therapy (ART); 2) after 3 months of receiving ART; 3)1 year before MI; and 4) last sample before MI. Data were extracted from the Danish National Patient Register.
The MI group had higher IL-1Ra levels at all time points and higher sIL-1R1 at time points 1, 2, and 3 compared with participants of the control group. Although sIL-1R1 levels initially decreased in controls after ART initiation, this was not observed in the MI group. An initial decrease in IL-1Ra levels was seen in both groups after ART initiation, but at time points 3 and 4 returned to baseline for controls and increased for the MI group. Levels of IL-18 were only higher for the MI group at time point 3, and no significant differences at any time point were seen between controls and cases for IL-1β, sIL-1R2, sIL-1RAcP, or IL-18 BPa. However, throughout the observation period after ART initiation, both groups demonstrated an increase in sIL-1R2 and a decrease in IL-18 and IL-18 BPa. At time points 1 and 3, IL-1Ra correlated positively with HIV RNA (r=.22, P =.006 and r=.20, P =.004, respectively).
Study investigators concluded that higher IL-1Ra levels are associated with an approximate 1.5-fold increase in MI risk, and these findings “support the rationale for targeting IL-1 activation in order to reduce cardiovascular risk during HIV infection.”
Hoel H, Ueland T, Knudsen A, et al. Soluble markers of IL-1 activation as predictors of first-time myocardial infarction in HIV-infected individuals [published online May 11, 2019]. J Infect Dis. doi:10.1093/infdis/jiz253