Insomnia and Mechanistic Pathways to Atherosclerotic CVD in HIV
Creators: name: Polanka, Brittanny
Publisher: name: Purdue University Graduate School
Year: 2020
Subjects: Psychopharmacology
Psychophysiology
Clinical psychology

description: <b>Study 1:</b><b>Background:</b> Insomnia may be a risk factor for cardiovascular disease in HIV (HIV-CVD); however, mechanisms have yet to be elucidated. <b>Methods:</b> We examined cross-sectional associations of insomnia symptoms with biological mechanisms of HIV-CVD (immune activation, systemic inflammation, and coagulation) among 1,542 people living with HIV from the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Past-month insomnia symptoms were assessed by the item, “Difficulty falling or staying asleep?,” with the following response options: “I do not have this symptom” or “I have this symptom and…” “it doesn’t bother me,” “it bothers me a little,” “it bothers me,” “it bothers me a lot.” Circulating levels of the monocyte activation marker soluble CD14 (sCD14), inflammatory marker interleukin-6 (IL-6), and coagulation marker D-dimer were determined from blood specimens. Demographic- and fully-adjusted (CVD risk factors, potential confounders, HIV-related factors) regression models were constructed, with log-transformed biomarker variables as the outcomes. We present the exponentiated regression coefficient (exp[b]) and its 95% confidence interval (<i>CI</i>). <b>Results:</b> For sCD14 and D-dimer, we observed no significant associations. For IL-6, veterans in the “bothers a lot” group had 15% higher IL-6 than veterans in the “I do not have this symptom” group in the demographic-adjusted model (exp[b]=1.15, 95%<i>CI</i>=1.02-1.29, <i>p</i>=.03). This association was nonsignificant in the fully-adjusted model (exp[b]=1.07, 95%<i>CI</i>=0.95-1.19, <i>p</i>=.25). <b>Conclusion:</b> We observed little evidence of relationships between insomnia symptoms and markers of biological mechanisms of HIV-CVD. Other mechanisms may be responsible for the insomnia-CVD relationship in HIV; however, future studies with comprehensive assessments of insomnia symptoms are warranted.<b>Study 2:</b><b>Background:</b> While insomnia has been identified as a potential risk factor for cardiovascular disease in HIV (HIV-CVD), research on the underlying pathophysiological mechanisms is scarce. <b>Methods:</b> We examined associations between 0-to-12-week changes in sleep disturbance and the concurrent 0-to-12-week changes and the subsequent 12-to-24-week changes in markers of systemic inflammation, coagulation, and endothelial dysfunction among people living with HIV (<i>n</i> = 33-38) enrolled in a depression clinical trial. Sleep disturbance was measured using the Pittsburgh Sleep Quality Index. Inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP) and coagulation marker D-dimer were determined from blood specimens; endothelial dysfunction marker brachial flow-mediated dilation (FMD) was determined by ultrasound. 0-to-12-week variables were calculated as 12-week visit minus baseline, and 12-to-24-week variables were calculated as 24-week minus 12-week. We constructed multivariate linear regression models for each outcome adjusting for age, sex, race/ethnicity, Framingham risk score, and baseline depressive symptoms. <b>Results:</b> We did not observe statistically significant associations between 0-to-12-week changes in sleep disturbance and 0-to-12-week or 12-to-24-week changes in IL-6, CRP, D-dimer, or FMD. However, we did observe potentially meaningful associations, likely undetected due to low power. For 0-to-12-weeks, every 1-standard deviation (<i>SD</i>) increase, or worsening, in the sleep disturbance change score was associated with a 0.41 pg/mL and 80 ng/mL decease in IL-6 and D-dimer, respectively. For 12-to-24-weeks, every 1-<i>SD</i> increase in sleep disturbance change score was associated with a 0.63 mg/L, 111 ng/mL, and 0.82% increase in CRP, D-dimer, and FMD, respectively. <b>Conclusion:</b> We observed potentially meaningful, though not statistically significant, associations between changes in sleep disturbance and changes in biological mechanisms underlying HIV-CVD over time. Some associations were in the expected direction, but others were not. Additional studies are needed that utilize larger samples and validated, comprehensive assessments of insomnia.