IL-1 Activation as Predictor of Myocardial Infarction in Patients With HIV

Scientist looking at blood specimen
Scientist looking at blood specimen
People with HIV and cardiovascular disease have higher levels of the interleukin-1 receptor antagonist and soluble regulator sIL-1R1 up to 10 years before the first myocardial infarction.

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).

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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.”

Reference

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