Uncontrolled HIV and inflammation is associated with intracranial saccular aneurysm presence

Abstract

Objective: To study biomarkers of inflammation in cerebrovascular disease, exploring modifiable and non-modifiable biochemical and clinical risk factors associated with the presence of intracranial saccular aneurysms (ISAs) in an HIV-positive cohort.

Design: A cross-sectional community-based study was used to study blood biomarkers of inflammation as predictors of cerebrovascular disease, specifically the presence of ISAs in persons with HIV. Potential biochemical and clinical predictors of ISA presence were identified.

Methods: Time of flight magnetic resonance angiography and magnetic resonance imaging data identified the presence of ISAs in an HIV-positive cohort. Quantitative assays for neuroinflammatory biomarkers were performed on plasma blood samples. Lasso regression models were used to identify neuroinflammatory biomarkers and clinical risk factors associated with ISAs.

Results: Eight of 72 participants had radiographically identified ISAs. ISAs were more common in non-Hispanic black participants (18.5% vs. 0% presence in nonblack patients). Participants with well controlled HIV (defined as CD4+ count >200 cells/ml and undetectable viral load at time of magnetic resonance imaging) had lower odds of ISAs (odds ratio: 0.19, 95% confidence interval 0.05-0.79) independent of age, sex, ethnicity and vascular risk factors. Macrophage inflammatory protein-1 p, an HIV- suppressive factor detected in participant blood samples, was inversely associated with aneurysm presence.

Conclusion: Well controlled HIV is associated with fewer ISAs. The identification of non-modifiable and modifiable risk factors contributing to ISA formation may provide valuable insight to impact clinical practice and inform the pathophysiology underlying ISA formation.

Figure 1:. Significant Variables Predicting Intracranial Saccular Aneurysm Presence Across Models

The above lasso regression models (original model, hypertension model, smoking model, CD4nadir model, unsuppressed viral load model, and CD4nadir x unsuppressed viral load model) identified the same three variables of black race, well-controlled HIV (defined as CD4 count >200 with suppressed viral load at time of MRI), and MIP-1β as significant explanatory variables to the presence of intracranial saccular aneurysms. These three variables are more robust potential predictors of ISA presence given their consistent significance across models, The original model included age, male sex, black race, well-controlled HIV, vascular risk factor composite score, drug use, CRP level and each cytokine as potential predictors of ISA presence. The hypertension model and smoking model included hypertension and smoking as a predictor variable in lieu of the vascular risk factor composite score, respectively. The CD4nadir model and unsuppressed viral load model included the variable CD4nadir less than 200 and an unsuppressed viral load in addition to the original model variables, respectively. The CD4nadir x unsuppressed viral load model includes the predictor variables from the original model in addition to unsuppressed viral load, CD4nadir less than 200 and the combination of unsuppressed viral load with a CD4 nadir less than 200.