Decreased levels of platelet-derived soluble glycoprotein VI detected prior to the first diagnosis of coronary artery disease in HIV-positive individuals

ABSTRACT

HIV-positive patients are at increased risk for coronary artery disease (CAD); changes in platelet activation may play a role. This study was performed to determine if levels of soluble glycoprotein VI (sGPVI), a platelet-specific marker of activation, were different in HIV-positive patients compared with HIV-negative controls and further if levels were predictive of CAD in HIV. Twenty-four HIV-positive individuals (HIV cases) with CAD were compared with 46 age- and sex-matched HIV-positive controls without CAD and 41 HIV-negative controls (healthy controls). Platelet activation (represented by sGPVI level) was compared 12 months and 1 month prior to CAD diagnosis. sGPVI was quantified by ELISA. sGPVI levels were higher in HIV-positive subjects (combined) than healthy controls (122.5 ng/mL [interquartile ranges (IQR) 90.3–160.5] versus 84.7 ng/mL [IQR 48.6–119.5], p <0.001). Twelve months before the event, there was no difference in sGPVI between HIV cases and HIV controls (113.4 ng/mL [IQR 85.6–141.65] versus 128.0 ng/mL [IQR 96.6–179.4], p = 0.369). One month prior to the event, sGPVI was significantly lower in HIV cases compared with HIV controls (109.0 ng/mL [IQR 79.4–123.4] versus 133.9 ng/mL [IQR 112.7–171.9], p = 0.010). These results remained significant following adjustment for possible confounders. This work demonstrates that HIV infection is associated with higher sGPVI levels. A fall in sGPVI immediately prior to first coronary artery event may reflect a loss of negative-feedback mechanism and be an important pathological step in the development of symptomatic CAD, but further work is needed to confirm these findings and determine their clinical impact.

Keyword:

• HIV
• Cardiovascular disease
• soluble glycoprotein VI
• Thrombosis

Acknowledgments

The authors would like to acknowledge the use of the Victorian HIV services Database. We gratefully acknowledge the contribution of the Victorian Operational Infrastructure Support Program received by the Burnet Institute and the Victorian HIV Blood and Tissue Storage Bank (VHBTSB) for provision of the relevant stored plasma specimens. This work was supported in part by the National Health and Medical Research Council of Australia and the National Heart Foundation. JMT was supported by an Australian Postgraduate Award. AM is supported by the Postdoctoral Programme of the German Academic Exchange Service (DAAD) and an Occupational Trainee Scholarship of the Burnet Institute.

Declarations of interest

Jennifer Hoy’s institution has received reimbursement for her participation in Advisory Boards for Gilead Science, Merck Sharp& Dohme, ViiV Healthcare and Abbvie. There are no other conflicts of interest to be declared.