Background: Best practice standards for measuring analyte levels in saliva recommend that all biospecimens be tested in replicate with mean concentrations used in statistical analyses. This approach prioritizes minimizing laboratory-based measurement error but, in the process, expends considerable resources. We explore the possibility that, due to advances in salivary assay precision, the contribution of laboratory-based measurement error in salivary analyte data is very small relative to more important and meaningful variability in analyte levels across biological replicates (i.e., between different specimens). To evaluate this possibility, we examine the utility of the repeatability intra-class correlation (rICC) as an additional index of salivary analyte data precision. Using randomly selected subsamples (Ns=200 and 60) of salivary analyte data collected as part of a larger epidemiologic study, we compute the rICCs for seven commonly assayed salivary measures in biobehavioral research – cortisol, alpha-amylase, c-reactive protein, interlekin-6, uric acid, secretory immunoglobulin A, and testosterone. We assess the sensitivity of rICC estimates to assay type and the unique distributions of the underlying analyte data. We also use simulations to examine the bias, precision, and coverage probability of rICC estimates calculated for small to large sample sizes. For each analyte, the rICCs revealed that less than 5% of variation in analyte levels was attributable to laboratory-based measurement error. rICC estimates were similar across all analytes despite differences in analyte levels, average intra-assay coefficients of variation, and in the distributional properties of the data. Guidelines for calculating rICC are provided to enable investigators and laboratory staff to apply this metric and more accurately quantify, and communicate, the magnitude of laboratory-based measurement error in their data. By helping investigators scale measurement error relative to more scientifically meaningful variability between biological replicates, the application of the rICC has the potential to influence research strategies and tactics such that resources (e.g., finances, effort, number/volume of biospecimens) are allocated more efficiently and effectively.
Reactivity of Salivary Uric Acid in Response To Social Evaluative Stress in African Americans.
Background: High uric acid (UA) is associated with hypertension and cardiovascular disease (CVD), both of which occur disproportionately among African Americans. High UA also predicts greater blood pressure reactivity responses to acute social stress. However, whether UA itself shows reactivity in response to stress is unknown. We evaluated salivary uric acid (sUA) and blood pressure reactivity in response to acute social stress. Healthy African Americans (N = 103; 32% male; M age = 31.36 years), completed the Trier Social Stress Test. sUA and blood pressure measurements were taken before, during and after the stressor task. sUA showed significant reactivity and recovery, especially among older African Americans. Total sUA activation was also associated with systolic and diastolic blood pressure total activation. Findings illuminate that acute stress may be a way in which UA is implicated in hypertension and CVD, suggesting a critical need to explore UA reactivity as a novel parameter of the acute stress response.
Salivary uric acid: Associations with resting and reactive blood pressure response to social evaluative stress in healthy African Americans.
High levels of uric acid are associated with greater risk of stress-related cardiovascular illnesses that occur disproportionately among African Americans. Whether hyperuricemia affects biological response to acute stress remains largely unknown, suggesting a need to clarify this potential connection. The current study examined how salivary uric acid (sUA) is associated with resting and reactive blood pressure – two robust predictors of hypertension and related cardiovascular disease and disparity. Healthy African Americans (N = 107; 32% male; M age = 31.74 years), completed the Trier Social Stress Test to induce social-evaluative stress. Systolic and diastolic blood pressure readings were recorded before, during, and after the task to assess resting and reactive change in blood pressure. Participants also provided a saliva sample at baseline that was assayed for sUA. At rest, and controlling for age, sUA was modestly associated with higher systolic (r = .201, p = .044), but not diastolic (r = .100, p = .319) blood pressure. In response to the stressor task, and once again controlling for age, sUA was also associated with higher total activation of both systolic (r = .219, p = .025) and diastolic blood pressure (r = .198, p < .044). A subsequent moderation analysis showed that associations between sUA and BP measures were significant for females, but not for males. Findings suggest that uric acid may be implicated in hypertension and cardiovascular health disparities through associations with elevated blood pressure responses to acute social stress, and that low levels of uric acid might be protective, particularly for females.
The validity, stability, and utility of measuring uric acid in saliva.
Background: Uric acid (UA) is associated with cardiovascular and metabolic disorders, as well as a wide range of other health conditions and behaviors. A non-invasive measure of UA would be particularly useful in biobehavioral health and clinical research. We examined the validity and stability of salivary UA as a noninvasive measure of serum UA.
Methods: To interrogate the validity of salivary UA as a marker of systemic UA, we measured UA levels in blood and saliva samples collected on a single occasion from healthy adults (n=99; age 18-36 years, 54% male). We examined the serum-saliva correlation for UA and associations between salivary UA and inflammatory markers in serum and saliva, and with self-reported oral health indices. We also tested whether associations of UA with adiponectin and C-reactive protein, circulating markers of cardiovascular health, are evident in saliva. Using longitudinal data from young adults (n=182; age 18-31 years; 46% male) we examined salivary UA stability. Correlations and latent state-trait modeling examined the stability of salivary UA levels; the percent of variance in salivary UA estimates attributable to trait and state-components; and associations of the salivary UA trait component with body mass index (BMI) and sex.
Results: We found a strong positive association between salivary and serum UA. Neither the direction nor the magnitude of this association was related to total protein in saliva, blood leakage into oral fluid, proinflammatory cytokines, or biobehavioral indices of poor oral health. Results also revealed robust inverse associations between UA and adiponectin in both serum and saliva. Salivary UA levels were also highly correlated within and between assessment points 3 hours as well as 2 months apart. Advanced statistical modeling showed the majority (62-66%) of the variance in salivary UA could be attributed to a latent trait component suggesting relative stability in salivary UA levels. Furthermore, BMI and sex were associated with the stable trait-like component of salivary UA.
Conclusions: The findings demonstrate strong measurement validity and stability when UA is measured in saliva, and provide evidence supporting salivary UA as a robust indicator of systemic UA activity. These finding suggest that salivary UA could serve as a biomarker for a wide range of potential conditions and disease states.
The hippocampal response to psychosocial stress varies with salivary uric acid level.
Uric acid is a naturally occurring, endogenous compound that impacts mental health. In particular, uric acid levels are associated with emotion-related psychopathology (e.g., anxiety and depression). Therefore, understanding uric acid’s impact on the brain would provide valuable new knowledge regarding neural mechanisms that mediate the relationship between uric acid and mental health. Brain regions including the prefrontal cortex, amygdala, and hippocampus underlie stress reactivity and emotion regulation. Thus, uric acid may impact emotion by modifying the function of these brain regions. The present study used functional magnetic resonance imaging (fMRI) during a psychosocial stress task to investigate the relationship between baseline uric acid levels (in saliva) and brain function. Results demonstrate that activity within the bilateral hippocampal complex varied with uric acid concentrations. Specifically, activity within the hippocampus and surrounding cortex increased as a function of uric acid level. The current findings suggest that uric acid levels modulate stress-related hippocampal activity. Given that the hippocampus has been implicated in emotion regulation during psychosocial stress, the present findings offer a potential mechanism by which uric acid impacts mental health.