346-OR: Hypothalamic Gliosis Is Associated with CVD Risk Factors in the Framingham Heart Study (FHS)

Introduction: Hypothalamic gliosis is linked to obesity and insulin resistance in rodent models and humans. We tested associations between a radiologic measure of hypothalamic gliosis and clinically relevant cardiovascular disease (CVD) risk factors, as well as prevalent coronary heart disease (CHD).

Methods: Using brain MRI images from FHS participants (n=867), T2 signal intensities were extracted bilaterally from the region of interest in the mediobasal hypothalamus (MBH) and reference regions in amygdala (AMY) and putamen (PUT). T2 signal ratios were created in which greater values suggest gliosis. The primary measure compared MBH to AMY (MBH/AMY); a positive control ratio (MBH/PUT) also assessed MBH whereas a negative control (PUT/AMY) did not. Outcomes were BMI, HDL-C, LDL-C, triglycerides, and the presence of hypertension (HTN; n=225), diabetes mellitus (DM; n=66), or metabolic syndrome (MetS; n=254). Prevalent CHD (n=22) was adjudicated by FHS. Linear and logistic regression models included age, sex, smoking, treatment status (e.g., lipids), and BMI (for outcomes except BMI and MetS).

Results: Mean age was 54.9±8.8 y; 54.9% were female. Greater MBH/AMY ratios were associated with higher BMI (P<0.001). MBH/AMY ratios were associated with higher triglycerides, presence of HTN, and lower HDL-C, and the latter two were independent of BMI (both P<0.05). Results were consistent for the MBH/PUT ratios (all P<0.05). Findings for DM were mixed and attenuated by adjusting for BMI. MetS was strongly associated with MBH/AMY and MBH/PUT ratios (P<0.001). PUT/AMY ratios were unrelated to any outcome. No T2 signal ratio was associated with prevalent CHD (P>0.05), and confidence intervals were wide.

Conclusion: Using a well-established study of CVD development, we found evidence linking hypothalamic gliosis to multiple CVD risk factors, independent of adiposity. Our results highlight the need to consider neurologic mechanisms in efforts to understand and improve cardiometabolic health.