Greater N-Acetylaspartate to Creatine Ratio within Left Anterior Insula Predicts Sympathetic Imbalance in Postmenopausal Women Living with Hypertension and/or HIV

Abstract

Context: Brain metabolite ratios derived from magnetic resonance spectroscopy (MRS) has been used to document changes in neuronal viability, glial activation and inflammation associated with Human Immunodeficiency Virus (HIV) infection and cardiovascular disease. Aims: To determine whether brain metabolite ratios in the left anterioar insula predicts cardio-autonomic regulation indexed by the ratio of low- to high-frequency heart rate varaibility (LF:HF) after accounting for post-menopausal age, HIV and hypertensive (HTN) status. Design: Thirty women, (n=14 HIV+ and n=16 HTN+) with an average age of 54.5 (SD=6.4) years and no history of neurological disease were recruited for the study. Methods: After conventional MR imaging, single-voxel 1H-MRS (TR = 1500 msec; TE = 35 msec) was performed by using a PROBE-SV system implemented on a 3T GE Discovery MR750 scanner. Shift-selective imaging pulses for water suppression were acquired from a voxel placed in the midline of the left anterior insula with an average voxel size of 15×15×15 mm. Heart rate variability was estimated over a 7 minutes resting state scan using an MR-compatible photoplethysmogram. Statistics: A stepwise regression analysis controlling for (1) age, disease status (HIV+ and HTN+) was modelled separately for the ratio of N-acetylaspartate (NAA), Myo-inostol (mI), and Choline (Ch) to Creatine (Cr) ratios to predict LF:HF. Results: Higher ratios of NAA/Cr were associated with lower LF:HF (β= -.393, t(29)= -2.26, p= .033). Ratios of mI:Cr and Cho:Cr did not predict LF:HF. Conclusions: Decreased neuronal viability in the left anterior insula, indexed by lower NAA/Cr metabolite ratios explain a significant proportion of the variance in the skew towards sympathetic overarusal in postmenopausal women at risk for cerebrovacular disease.