Background
The prevalence of obesity, and subsequent metabolic syndrome (MetS), is increasing in persons living with HIV (PLWH) on antiretroviral therapy (ART), with nearly 1 in 4 meeting MetS criteria. African females with HIV are at particular risk of developing obesity complicated by MetS. Obesity increases the risk of cardiovascular and cerebrovascular disease. There is limited data on the association of obesity and MetS in PLWH with biomarkers of cerebrovascular function such as cerebral blood flow (CBF), arterial transit time (ATT), cerebrovascular reactivity (CVR) and microcirculation as measured by intravoxel incoherent motion (IVIM) metrics (diffusion, D; pseudo-diffusion, D*; and perfusion fraction, f).
Methods
We conducted a cross-sectional study of PLWH at a primary care clinic in Cape Town, South Africa, suppressed on ART and newly diagnosed with MetS using the Harmonized criteria. Our primary outcome was to assess CVR, derived from resting state functional magnetic resonance imaging, CBF, ATT and water exchange rate Kw assessed via diffusion-prepared multi-delay arterial spin labelling. Brain volumetrics were assessed via T1 weighted imaging, processed with FreeSurfer. Using linear regression, we correlated our imaging findings with a composite MetS severity z-score and body fat composition quantified using dual-energy X-ray absorptiometry (DEXA).
Results
We enrolled 27 female participants aged 45.2±10 years with a body mass index (BMI) of 41.9±7.8 kg/m2. We found no association between CVR, ATT, Kw, CBF or brain volume in gray and white matter and the MetS z-score based on BMI or waistline. ATT in both gray and white matter was significantly increased with higher body mass indices. Both gray and white matter ATT increased with higher waist circumference, body fat mass, body fat percentage and visceral adipose tissue mass, with body fat percentage most striking (β=16.4, p = 0.012 and β=16.3, p = 0.009, respectively). D* in gray matter was associated with MetS severity z-score based on BMI and waistline (r=0.57, p = 0.005 and r=0.42, p = 0.047, respectively) and body fat mass (r=0.47, p=0.026 in white matter, r=0.44, p=0.035 in gray matter).
Conclusions
ATT is an index of vascular resistance that increases in the presence of cerebrovascular disease. We found that in obese African females with HIV and MetS suppressed on ART, ATT increases in proportion to body fat percentage. This finding is also reflected in alterations of the microcirculation, as measured by the IVIM metric D*.