MicroRNA biomarkers associated with type 1 myocardial infarction in HIV positive individuals

OBJECTIVE: Individuals with HIV suffer a higher burden of cardiovascular diseases. Traditional cardiovascular risk scores consistently underestimate cardiovascular risk in this population. Subsets of microRNAs (miRNAs) are differentially expressed among individuals with cardiovascular disease and individuals infected with HIV. However, no study has clarified whether specific miRNAs may be biomarkers for cardiovascular disease in individuals with HIV. DESIGN/METHODS: We compared the miRNA expression profiles of 34 HIV-positive individuals who had experienced clinically adjudicated type I myocardial infarctions (MI) with the profiles of 76 HIV-positive controls matched by traditional cardiovascular risk factors and HIV-specific measures. Using the elastic net algorithm, we selected miRNAs most strongly associated with incident MI and then used conditional Cox proportional hazards regression and cross-validation to evaluate miRNAs and their association with incident MI. We evaluated whether miRNA markers would improve risk classification relative to the Framingham Risk Score. RESULTS: Higher miR-125a-5p and miR-139-5p expression levels were each associated with increased risk of developing MI after adjustment for Framingham Risk Score and HIV-related factors (hazard ratio 2.43, P = 0.018; hazard ratio 2.13, P = 0.048, respectively). Compared with the Framingham Risk Score alone, adding expression levels of miR-125a-5p or miR-139-5p resulted in an integrated discrimination improvement of 10.1 or 5.8%, respectively. CONCLUSION: MiR-125a-5p and miR-139-5p, transcripts known to be differentially expressed in HIV-positive individuals, may serve as unique biomarkers predictive of cardiovascular disease in these patients and may help clarify processes because of HIV infection that contribute to cardiovascular disorders in this population.