Elevated Markers of Vascular Remodeling and Arterial Stiffness Are Associated With Neurocognitive Function in Older HIV+ Adults on Suppressive Antiretroviral Therapy.
BACKGROUND
HIV is associated with elevated markers of vascular remodeling that may contribute to arterial fibrosis and stiffening and changes in pulse pressure (PP). These changes may, in turn, deleteriously affect autoregulation of cerebral blood flow and neurocognitive function.


METHODS
To evaluate these mechanisms, we studied markers of vascular remodeling, PP, and neurocognitive function among older (≥50 years of age) HIV-infected (HIV+, n = 72) and HIV-seronegative (HIV-, n = 36) adults. Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well-validated comprehensive battery. Three plasma biomarkers of vascular remodeling (ie, angiopoietin 2, Tie-2, and vascular endothelial growth factor, VEGF) were collected.


RESULTS
HIV+ and HIV- participants had similar levels of plasma angiopoietin 2 (P = 0.48), Tie-2 (P = 0.27), VEGF (P = 0.18), and PP (P = 0.98). In a multivariable regression model, HIV interacted with Tie-2 (β = 0.41, P < 0.01) and VEGF (β = -0.43, P = 0.01) on neurocognitive function, such that lower Tie-2 and higher VEGF values were associated with worse neurocognitive function for HIV+ participants. Greater Tie-2 values were associated with increased PP (r = 0.31, P < 0.01). In turn, PP demonstrated a quadratic association with neurocognitive function (β = -0.33, P = 0.01), such that lower and higher, relative to mean sample, PP values were associated with worse neurocognitive function.


CONCLUSIONS
These findings indicate that vascular remodeling and altered cerebral blood flow autoregulation contribute to neurocognitive function. Furthermore, HIV moderates the association between vascular remodeling and neurocognitive function but not the association between PP and neurocognitive function.
*Joint Doctoral Program in Clinical Psychology, SDSU/UCSD, San Diego, CA; Departments of †Psychiatry; ‡Family Medicine and Public Health; §Neurosciences; and ‖Medicine, University of California, San Diego, La Jolla, CA.
Jessica L
JL
Montoya
Jennifer
J
Iudicello
Pariya L
PL
Fazeli
Suzi
S
Hong
Michael
M
Potter
Ronald J
RJ
Ellis
Igor
I
Grant
Scott L
SL
Letendre
David J
DJ
Moore
D015526:AIDS Dementia Complex / Q000209:etiology* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042702:Angiopoietin-2 / Q000097:blood; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D042787:Receptor, TIE-2 / Q000097:blood; D000072230:Sustained Virologic Response; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D066253:Vascular Remodeling; D059289:Vascular Stiffness
C586513:ANGPT2 protein, human; D042702:Angiopoietin-2; D044966:Anti-Retroviral Agents; D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2