C-Reactive Protein as an Independent Cardiovascular Risk Predictor in HIV+ Patients: A Focused Review of Published Studies

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Patients infected with the human immunodeficiency virus (HIV+) are living longer and at heightened risk for developing cardiovascular events (CVEs). Commonly used prediction tools appear to misrepresent their CVE risk to varying degrees and in varying directions. Inclusion of markers of cellular infection, chronic immune activation and/or systemic inflammation into risk models might provide better predictive accuracy. Observational studies assessing the relationship of high-sensitivity C-reactive protein (hs-CRP) to CVE in HIV+ patients have reported inconsistent findings. This review of published studies attempted to determine if the available evidence supports its potential use in new models for stable, treated HIV+ patients. We searched the PubMed database using keywords and combinations of "HIV" AND "cardiovascular risk" AND "CRP". Papers presenting original analyses, associating hs-CRP concentration as an independent variable to hard cardiovascular outcomes (myocardial infarction and cardiovascular death), or to hard CVE as part of a composite endpoint, were included. Five observational studies met inclusion/exclusion criteria for review. Three papers identified an association between elevated hs-CRP and CVE, while two others failed to find any significant association. All reports were heterogeneous in terms of independent variables, controls, and designs. The larger and more rigorous studies, employing higher rates of confounder controls and more objective endpoints in their composites, showed positive associations. Though not conclusive, the preponderance of the evidence at this time supports CRP as a potentially valuable factor to be studied in prospective cardiovascular risk prediction investigations in HIV+ patients.