Clinical Infectious Diseases, August 2019
Due to complex interactions between HIV, antiretroviral therapy, and the chronic immune activation and inflammation that can be seen in people living with HIV, there is an increased risk for cardiovascular diseases including acute myocardial infarctions (heart attacks). Because traditional risk scores for predicting myocardial infarction (which are based on cholesterol, blood pressure, and smoking status) don’t take these HIV-specific drivers into account, these prediction tools can be inaccurate in people living with HIV. Thus, one of the key issues researchers face is how to identify which individuals are most likely to develop cardiovascular disease and hence might be appropriate to enroll into clinical trials aimed at investigating or reducing cardiovascular risk. NWCS 432 investigated whether biomarkers of inflammation, endothelial function, and microbial translocation (specifically lipopolysaccharide-binding protein) in people living with HIV might be able to help identify those who will go on to develop cardiovascular disease.
The study utilized samples stored in the ACTG specimen repository from a variety of studies. The investigation did not use specimens from a single trial, but innovatively identified individuals across ACTG studies who had experienced a myocardial infarction (MI) while enrolled in a study and pulled their samples. The study then used samples from control participants matched for age and sex who had no history of MI. Participants from 14 different ACTG protocols were ultimately included.
As described in the brief report published in Clinical Infectious Diseases, the study found people living with HIV who experienced an MI were more likely to be current smokers, have higher cholesterol, a family history of heart disease, or high blood pressure, which are all traditional risk factors. Interestingly, the participants with MIs also had higher lipopolysaccharide-binding protein levels, which remained positively associated with further MI events following adjustment for the more traditional cardiovascular risk factors. Lipopolysaccharide-binding protein is an acute phase protein and is associated with the development of fatty streaks in artery walls, likely by prolonging the survival of macrophages (the cells that ingest cholesterol and form the basis of these fatty plaques). Further work is needed to determine if lipopolysaccharide-binding protein can help improve the prediction of MI events or if this biomarker can be affected by anti-inflammatory medications. The possibility of a new biomarker to predict MIs in people with HIV is intriguing.
Trevillyan, J. M., Moser, C., Currier, J. S., & Sallam, T. (2020). Immune Biomarkers in the Prediction of Future Myocardial Infarctions in People With Human Immunodeficiency Virus. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 70(8), 1764–1767. doi.org/10.1093/cid/ciz765