High-Mobility Group Box-1 Is Associated With Obesity, Inflammation, and Subclinical Cardiovascular Risk Among Young Adults: A Longitudinal Cohort Study.

OBJECTIVE: We aimed to characterize circulating HMGB1 (high-mobility group box-1) levels, one of the better-characterized damage-associated molecular patterns, with respect to age, sex, and race in the general population, and investigate the longitudinal associations of HMGB1 with inflammatory markers, obesity, and preclinical markers of cardiovascular disease. Approach and Results: The analyses included 489 participants (50% Blacks, aged 24.6±3.3 years at the first visit) with up to 4 follow-up visits (1149 samples) over a maximum of 8.5 years. Systolic blood pressure, diastolic blood pressure, carotid-femoral pulse wave velocity, and carotid intima-media thickness together with plasma HMGB1, hs-CRP (high-sensitivity C-reactive protein), IFN-γ (interferon-γ), IL-6 (interleukin-6), IL-10 (interleukin-10), and TNF-α (tumor necrosis factor-α) were measured at each visit. At baseline, plasma HMGB1 concentrations were higher in Blacks compared with Whites (3.86 versus 3.20 ng/mL, P<0.001), and in females compared with males (3.75 versus 3.30 ng/mL, P=0.005). HMGB1 concentrations increased with age (P=0.007), and higher levels of obesity measures (P<0.001). Without adjustment for age, sex, race, and body mass index, HMGB1 concentrations were positively associated with hs-CRP, IL-6, TNF-α, systolic blood pressure, diastolic blood pressure, and carotid-femoral pulse wave velocity (P<0.05) but not IL-10, IFN-γ or carotid intima-media thickness. After covariate adjustments, the associations of HMGB1 with hs-CRP, and carotid-femoral pulse wave velocity remained statistically significant (P<0.05). CONCLUSIONS: This study demonstrates the age, sex, and race differences in circulating HMGB1. The increasing circulating concentrations of HMGB1 with age suggest a potential role of HMGB1 in the pathogenesis of chronic low-grade inflammation, obesity, and subclinical cardiovascular disease risk.

Ethnic and sex differences in the longitudinal association between heart rate variability and blood pressure.

PURPOSE: Elevated blood pressure is a risk factor for increased cardiovascular morbidity and mortality. Decreased vagally-mediated heart rate variability has previously been prospectively linked with increased blood pressure; however, to date, no such prospective data exist regarding this relationship among Blacks. MATERIALS AND METHODS: We examined this association in 387 normotensive young adults (mean age, 23 years, 52% female, 54% Black) who participated in two laboratory evaluations spanning approximately six years. Blood pressure was measured at both timepoints with a non-invasive oscillometric device and heart rate variability was assessed via bio-impedance. RESULTS: In the total sample, heart rate variability significantly predicted systolic (p = .022) and diastolic (p < .001) blood pressure increases six years into the future. However, this pattern varied as a function of ethnicity and sex with the effect of heart rate variability on Time 2 systolic blood pressure only significant among White males (p = .007). Heart rate variability was also predictive of Time 2 diastolic blood pressure in White males (p = .038) as well as among both White (p = .032) and Black (p = .015) females, but was not related to blood pressure among Black males. CONCLUSION: We report for the first time significant ethnic and sex differences in the prospective relationship between heart rate variability and blood pressure change. These findings may give clues as to the underlying mechanisms that are involved in the well-known health disparities in blood pressure and hypertension-related cardiovascular diseases.

Sirt1 during childhood is associated with microvascular function later in life.

Microvascular dysfunction often precedes other age-related macrovascular conditions and predicts future cardiovascular risk. Sirtuin 1 (Sirt1) has recently emerged as a protein that protects the vasculature and reduces the risk of cardiovascular diseases. We tested the hypothesis that lower Sirt1 during childhood is associated with a reduced microvascular function during adulthood. Thirty-four adults (34 ± 3 yr) from the Augusta Heart Study returned to participate in the present clinical observational study. Sirt1 was assessed in samples collected during both adulthood and participants' childhood (16 ± 3 yr), and data were divided based on childhood Sirt1 concentrations: <3 ng/dL (LowCS; n = 16) and ≥3 ng/dL (HighCS; n = 18). MVF was evaluated in all of the adults using laser-Doppler flowmetry coupled with three vascular reactivity tests: 1) local thermal hyperemia (LTH), 2) post-occlusive reactive hyperemia (PORH), and 3) iontophoresis of acetylcholine (ACh). The hyperemic response to LTH was significantly (P ≤ 0.044) lower in the LowCS than in the HighCS group. Similarly, the LowCS also exhibited an ameliorated (P ≤ 0.045) response to the PORH test and lower (P ≤ 0.008) vasodilation in response to iontophoresis of ACh when compared with the HighCS. Positive relationships were identified between childhood Sirt1 and all MVF reactivity tests (r≥0.367, P ≤ 0.004). Novel observations suggest that lower Sirt1 during childhood is associated with premature microvascular dysfunction in adulthood. These findings provide evidence that Sirt1 may play a critical role in microvascular function and have therapeutic potential for the prevention of age-associated vascular dysfunction in humans.NEW & NOTEWORTHY With a longitudinal cohort, novel observations from the present study demonstrate that individuals who had lower Sirt1 early in life exhibit premature microvascular dysfunction during adulthood and may be at higher risk to develop CVD. These results provide experimental evidence that Sirt1 may play an important role in microvascular function with age and represent a potential therapeutic target to prevent premature vascular dysfunction.

Angiotensin II and the Natriuretic and Blood Pressure Response to Mental Stress in African Americans.

Objective: To test the hypothesis that Angiotensin II (Ang II) is a contributing factor to the response pattern in African Americans (AAs) who retain rather than excrete sodium during mental stress. Design/Study Participants: Double-blind, randomized, cross-over trial of 87 healthy AAs aged 18 to 50 years. Interventions: The study participants received either a placebo or irbesartan, (150 mg PO), an Ang II receptor antagonist, for seven days prior to stress testing. Urinary sodium excretion (UNaV) and systolic blood pressure (SBP) were collected prior to and throughout a mental stress protocol (rest and stress period). Setting: A southeastern university. Main Outcome Measures: Ang II, SBP, and sodium retention. Results: During the placebo condition, 62 participants showed the expected increase in UNaV (excreters) while 25 participants reduced UNaV during stress (retainers). Irbesartan retainers demonstrated a reversal in the direction of their natriuretic response, now increasing UNaV in response to stress (∆ UNaV of -.094 mmol/min with placebo vs .052 mmol/min on irbesartan; P<.001). In excreters, irbesartan reduced SBP levels during both rest (-2.36 mm Hg; P=.03) and stress (-4.59;P<.0001), and an even more pronounced reduction in SBP was demonstrated by retainers on treatment during both rest (-4.29 mm Hg; P=.03) and stress (-6.12; P<.001). Conclusions: Ang II contributes to sodium retention in retainers. Furthermore, our findings indicate that suppression of Ang II has a beneficial effect on SBP during rest and stress in this population.

Adverse childhood experiences and blood pressure trajectories from childhood to young adulthood: the Georgia stress and Heart study.

BACKGROUND: The purposes of this study were to assess the long-term effect of adverse childhood experiences (ACEs) on blood pressure (BP) trajectories from childhood to young adulthood and to examine whether this relation is explained by childhood socioeconomic status (SES) or risk behaviors that are associated with ACEs. METHODS AND RESULTS: Systolic and diastolic BPs were measured up to 16 times (13 times on average) over a 23-year period in 213 African Americans and 181 European Americans 5 to 38 years of age. Retrospective data on traumatic experiences before 18 years of age were collected, including abuse, neglect, and household dysfunction. Individual growth curve modeling within a multilevel framework was used to examine the relation between exposure to ACEs and BP development. No main effect of ACEs on average BP levels was found. However, a significant interaction of ACE score with age(3) was observed (systolic BP, P=0.033; diastolic BP, P=0.017). Subjects who experienced multiple traumatic events during childhood showed a faster rise in BP levels after 30 years of age than those without ACEs. As expected, a graded association of ACEs with childhood socioeconomic status and negative health behaviors was observed (P<0.001). The ACE-systolic BP relation was not explained by these factors, whereas the ACE-diastolic BP relation was partially mediated by illicit drug use. CONCLUSION: In this novel longitudinal study, we observed that participants who were exposed to multiple ACEs displayed a greater increase in BP levels in young adulthood compared with their counterparts without ACEs.

Stress and salt sensitivity in primary hypertension.

As the development of hypertension and target organ damage becomes more prevalent, it becomes exceedingly important to determine the underlying mechanisms through which this detrimental development occurs. Specifically, our studies and others have explored mechanisms through which stress elicits a salt-sensitive response in approximately 20-30 % of the population, resulting in the early development of hypertension and target organ damage. Data associated with this stress-induced cardiovascular response pattern have recently demonstrated additional effects across the body systems including factors contributing to the development of osteoporosis, obesity, autoimmune disease, and chronic inflammation. As each of these diseases become more prevalent in conjunction with hypertension, further research may discover stress and salt sensitivity to be at the "heart" of the matter for the development of many of today's most deadly conditions.

DNA methylation of the LY86 gene is associated with obesity, insulin resistance, and inflammation.

BACKGROUND: Previous genome-wide association studies (GWAS) have identified a large number of genetic variants for obesity and its related traits, representing a group of potential key genes in the etiology of obesity. Emerging evidence suggests that epigenetics may play an important role in obesity. It has not been explored whether the GWAS-identified loci contribute to obesity through epigenetics (e.g., DNA (deoxyribonucleic acid) methylation) in addition to genetics. METHOD: A multi-stage cross-sectional study was designed. We did a literature search and identified 117 genes discovered by GWAS for obesity and its related traits. Then we analyzed whether the methylation levels of these genes were also associated with obesity in two genome-wide methylation panels. We examined an initial panel of seven adolescent obese cases and seven age-matched lean controls, followed by a second panel of 48 adolescent obese cases and 48 age- and gender-matched lean controls. The validated CpG sites were further replicated in two independent replication panels of youth (46 vs. 46 and 230 cases vs. 413 controls, respectively) and a general population of youth, including 703 healthy subjects. RESULTS: One CpG site in the lymphocyte antigen 86 (LY86) gene, which showed higher methylation in the obese in both the initial (p = .009) and second genome-wide DNA methylation panel (p = .008), was further validated in both replication panels (meta p = .00016). Moreover, in the general population of youth, the methylation levels of this region were significantly correlated with adiposity indices (p ≤ .02), insulin resistance (p = .001), and inflammatory markers (p < .001). CONCLUSION: By focusing on recent GWAS findings in genome-wide methylation profiles, we identified a solid association between LY86 gene DNA methylation and obesity.

A genome-wide methylation study of severe vitamin D deficiency in African American adolescents.

OBJECTIVES: To test the hypothesis that changes in DNA methylation are involved in vitamin D deficiency-related immune cell regulation using an unbiased genome-wide approach combined with a genomic and epigenomic integrative approach. STUDY DESIGN: We performed a genome-wide methylation scan using the Illumina HumanMethylation 27 BeadChip on leukocyte DNA of 11 cases of vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] ≤ 25 nmol/L) and 11 age-matched controls ([25(OH)D] > 75 nmol/L); the subjects were African American normal-weight (body mass index <85th percentile) males aged 14-19 years. The Limma package was used to analyze each CpG site for differential methylation between cases and controls. To correct for multiple testing, the set of raw P values were converted to false discovery rates (FDRs). We also compared our findings with the recent data from Genome-Wide Association Studies of circulating 25(OH)D levels and then performed a permutation test to examine whether the "double hit" genes were randomly enriched. RESULTS: A total of 79 CpG sites achieved raw P < .001. Of the 79 CpG sites, 2 CpG sites survived multiple testing: cg16317961 (raw P = 3.5 × 10(-6), FDR = 0.078, in MAPRE2) and cg04623955 (raw P = 5.9 × 10(-6), FDR = 0.078, in DIO3). Furthermore, 3 out of the 4 genes previously identified in the 2 Genome-Wide Association Studies were also significant at the methylation level (DHCR7: cg07487535, P = .015 and cg10763288, P = .017; CYP2R1: cg25454890, P = .040; CYP24A1: cg18956481, P = .022), reflecting significant enrichment (P = .0098). CONCLUSION: Severe vitamin D deficiency is associated with methylation changes in leukocyte DNA. The genomic and epigenomic approach reinforce the crucial roles played by the DHCR7, CYP2R1, and CYP24A1 genes in vitamin D metabolism.

Aldosterone contributes to elevated left ventricular mass in black boys.

BACKGROUND: Left ventricular hypertrophy (LVH) poses a great risk of cardiovascular morbidity and mortality in adults and may pose a serious risk in children. Adult studies have shown that renin-angiotensin-aldosterone system (RAAS) levels directly correlate with left ventricular mass index (LVMI). The purpose of this study is to explore race- and sex-related effects of the RAAS on LVMI in adolescents. METHODS: Data were collected from a sample of 89 blacks (44 girls, 45 boys) and 102 whites (40 girls, 62 boys) aged 15-19. Data collected included sex, age, body mass index (BMI), LVMI, baseline blood pressure, and levels of aldosterone and angiotensin II. RESULTS: In black males, increased aldosterone levels correlated with decreased sodium excretion (r= -0.336, p=0.024), increased blood pressure (r=0.358, p=0.016), and increased LVMI (r=0.342, p=0.022). In black females, increased aldosterone levels correlated with increased baseline blood pressure (r=0.356, p=0.018). In white males, increased aldosterone correlated with decreased sodium excretion (r= -0.391, p=0.002). In white females, aldosterone levels correlated with increased baseline blood pressure (r=0.323, p=0.042) and decreased sodium excretion (r= -0.342, p=0.031). CONCLUSIONS: The results suggest the following model in black males: increased aldosterone leads to increased sodium retention, causing a volume-mediated increase in blood pressure; increased blood pressure results in increased left ventricular mass, and eventually LVH.

Stress reduces diastolic function in youth.

OBJECTIVE: Research regarding the influence of mental stress (MS) on heart function focused primarily on heart contractility. We hypothesized that MS results in attenuated diastolic function (DF) as early as in adolescence and this effect may differ by race and sex. METHODS: 161 normotensive adolescents (81 blacks and 80 females) performed resting (control) and MS (experimental) conditions on separate visits. Visits lasted for 3 hours (1-hour rest, video game challenge and recovery for experimental visit. Mitral inflow early (E) to late (A) filling velocities (E/A) ratio; mitral valve annular early velocity (E') and E/E' ratio were recorded every 30 minutes to evaluate DF. RESULTS: BP and HR increased during experimental visit (all p values < .01). E/A ratio progressively increased during control visit (mean [SE], from 1.93 ± 0.42 to 2.01 ± 0.47) but decreased during the stress phase of experimental visit (from 1.91 ± 0.44 to 1.87 ± 0.50, p interaction < .001). In white males, E' increased from rest to stress phase (from 10.3 ± 2.55 to 10.7 ± 2.28 cm/s), whereas E' decreased in white females (from 11.0 ± 2.62 to 10.6 ± 2.53 cm/s), black males (from 10.5 ± 2.31 to 9.9 ± 2.19 cm/s), and black females (from 10.6 ± 2.22 to 10.3 ± 1.86 cm/s, p interaction < .04). During stress, higher A was associated with higher E/E' ratio. CONCLUSIONS: Recurrent episodes of mental stress may increase the risk of poor DF, and these adverse effects may be stronger in females and black males.

Ethnic differences and heritability of blood pressure circadian rhythm in African and European American youth and young adults.

BACKGROUND: The aim of this study was to investigate whether blood pressure (BP) circadian rhythm in African Americans differed from that in European Americans. We further examined the genetic and/or environmental sources of variances of the BP circadian rhythm parameters and the extent to which they depend on ethnicity or sex. METHOD: Quantification of BP circadian rhythm was obtained using Fourier transformation from the ambulatory BP monitoring data of 760 individuals (mean age, 17.2 ±â€Š3.3; 322 twin pairs and 116 singletons; 351 African Americans). RESULTS: BP circadian rhythm showed a clear difference by ethnic group with African Americans having a lower amplitude (P = 1.5e-08), a lower percentage rhythm (P = 2.8e-11), a higher MESOR (P = 2.5e-05) and being more likely not to display circadian rhythm (P = 0.002) or not in phase (P = 0.003). Familial aggregation was identified for amplitude, percentage rhythm and acrophase with genetic factors and common environmental factors together accounting for 23 to 33% of the total variance of these BP circadian rhythm parameters. Unique environmental factors were the largest contributor explaining up to 67--77% of the total variance of these parameters. No sex or ethnicity difference in the variance components of BP circadian rhythm was observed. CONCLUSION: This study suggests that ethnic differences in BP circadian rhythm already exist in youth with African Americans having a dampened circadian rhythm and better BP circadian rhythm may be achieved by changes in environmental factors.

α-Adrenergic receptor blockade attenuates pressor response during mental stress in young black adults.

Black individuals exhibit increased blood pressure (BP) responses to sympathetic stimulation that are associated with an increased risk of hypertension (HTN). We tested the hypothesis that α1 -adrenergic blockade inhibits the increased BP response during and after 45-min stress in young normotensive Black adults, which may be mediated, in part, by dampened vasoconstriction and decreased renal sodium retention. Utilizing a double-masked randomized, crossover study design, 51 normotensive Black adults (31 ± 8 yr) were treated with either a placebo or 1 mg/day of prazosin for 1 week. On the final day of each treatment, hemodynamic measures and urinary sodium excretion (UNaV) were collected before (Rest), during (Stress) and after (Recovery) 45 min of mental stress induced via a competitive video game task. During the Stress period, diastolic BP and total peripheral resistance (TPR) were significantly lower with prazosin compared to placebo (p < .05 for both). Similarly, we observed lower systolic BP, diastolic BP, and TPR during the Recovery period with prazosin versus placebo (p < .05 for both). There was no effect of prazosin on stress-associated UNaV. The change in systolic BP from Rest to Recovery was positively associated with the change in TPR with both treatments (p < .05 for both). In summary, prazosin treatment dampened BP reactivity to 45-min mental stress and lowered post-stress BP over the recovery period, which was linked to reduce TPR in young normotensive Black adults. These results suggest that α1 -adrenergic receptor activity may contribute to BP responses and delayed BP recovery to prolonged mental stress through increased vasoconstriction in Black adults.

Rapid decline of resting heart rate trajectories from childhood to young adulthood is paradoxically associated with increased cardiac mass.

BACKGROUND: Little is known about the varied resting heart rate (RHR) trajectory patterns from childhood to young adulthood and their clinical significance. We aim to identify RHR trajectories from childhood to young adulthood, and to determine their relationship with left ventricular mass (LVM) index. METHODS: RHR was measured up to 15 times over a 21-year period in 759 participants from childhood to young adulthood. LVM was measured using echocardiography and was normalised to body surface area to obtain LVM index in 546 participants. RESULTS: Using latent class models, three trajectory groups in RHR from childhood to young adulthood were identified, including high-decreasing group (HDG), moderate-decreasing group (MDG), and low-decreasing group (LDG). We found that trajectory of RHR was a significant predictor of LVM index with faster decrease of RHR associated with higher levels of total peripheral resistance (P for trend <0.001) and LVM index (P for trend <0.001). Compared to the LDG, individuals in the HDG showed higher LVM index (ß = 6.08, p < 0.001). In addition, the interactions between race and RHR trajectories for LVM index was significant (p < 0.05). CONCLUSION: Our findings show an association between RHR trajectories from childhood to young adulthood with cardiac mass, suggesting that monitoring RHR may help identify subpopulation at high cardiovascular risk.

Effects of Race, Cardiac Mass, and Cardiac Load on Myocardial Function Trajectories from Childhood to Young Adulthood: The Augusta Heart Study.

Background The overall goal of this longitudinal study was to determine if the Black population has decreased myocardial function, which has the potential to lead to the early development of congestive heart failure, compared with the White population. Methods and Results A total of 673 subjects were evaluated over a period of 30 years including similar percentages of Black and White participants. Left ventricular systolic function was probed using the midwall fractional shortening (MFS). A longitudinal analysis of the MFS using a mixed effect growth curve model was performed. Black participants had greater body mass index, higher blood pressure readings, and greater left ventricular mass compared with White participants (all P<0.01). Black participants had a 0.54% decrease of MFS compared with White participants. As age increased by 1 year, MFS increased by 0.05%. As left ventricular mass increased by 1 g, MFS decreased by 0.01%. As circumferential end systolic stress increased by 1 unit, MFS decreased by 0.04%. The MFS trajectories for race differed from early age to young adulthood. Conclusions Changes in myocardial function mirror the race-dependent variations in blood pressure, afterload, and cardiac mass, suggesting that myocardial function depression occurs early in childhood in populations at high cardiovascular risk such as Black participants.

Obesity related methylation changes in DNA of peripheral blood leukocytes.

BACKGROUND: Despite evidence linking obesity to impaired immune function, little is known about the specific mechanisms. Because of emerging evidence that immune responses are epigenetically regulated, we hypothesized that DNA methylation changes are involved in obesity induced immune dysfunction and aimed to identify these changes. METHOD: We conducted a genome wide methylation analysis on seven obese cases and seven lean controls aged 14 to 18 years from extreme ends of the obesity distribution and performed further validation of six CpG sites from six genes in 46 obese cases and 46 lean controls aged 14 to 30 years. RESULTS: In comparison with the lean controls, we observed one CpG site in the UBASH3A gene showing higher methylation levels and one CpG site in the TRIM3 gene showing lower methylation levels in the obese cases in both the genome wide step (P = 5 × 10(-6) and P = 2 × 10(-5) for the UBASH3A and the TRIM3 gene respectively) and the validation step (P = 0.008 and P = 0.001 for the UBASH3A and the TRIM3 gene respectively). CONCLUSIONS: Our results provide evidence that obesity is associated with methylation changes in blood leukocyte DNA. Further studies are warranted to determine the causal direction of this relationship as well as whether such methylation changes can lead to immune dysfunction.

Association between serum 25-hydroxyvitamin D and the effects of Angiotensin II receptor blocker on renal function among African Americans: A post hoc analysis of a randomized placebo-controlled trial.

We tested the hypothesis that vitamin D status may modify the effect of Angiotensin II receptor blocker (ARB) on renal function among African Americans. Sixty-four participants were included in this ancillary study from a randomized, double-blind, placebo-controlled, crossover trial among normotensive African Americans to test the effect of ARB on stress response of blood pressure and renal sodium handling. The participants were randomly assigned to receive either ARB or placebo for one week, washed out for one week and then cross-overed to receive the other intervention for one week. On the final day of each intervention, the participant underwent a mental stress test. Baseline serum 25-hydroxyvitamin D [25(OH)D] level was measured in this ancillary study. Sixty-four participants were included, aged 26.5 ± 10.2 years and 47% were female. Among the participants with the serum 25(OH)D concentrations in the low tertile, ARB treatment was associated with 2.58 mg/dL higher blood urea nitrogen (BUN) (P < .001) and was not associated with serum creatinine (SCr) or estimated glomerular filtration rate (eGFR) (Ps > .05). Among the participants in the high 25(OH)D tertile, ARB was associated with 1.59 mg/dL lower BUN (P < .001), 0.08 mg/dL lower SCr (P = .001), and 8.59 mL/min/1.73 m2 higher eGFR (P = .001). The interactions between vitamin D and ARB on renal function were more significant during stress and recovery than at rest. The effects of ARB treatment on renal function are modified by the vitamin D status among African Americans. ARB may improve renal function only among the ones with optimal vitamin D status.

Modest Sodium Reduction Increases Circulating Short-Chain Fatty Acids in Untreated Hypertensives: A Randomized, Double-Blind, Placebo-Controlled Trial.

High-sodium diet may modulate the gut microbiome. Given the circulating short-chain fatty acids (SCFAs) are microbial in origin, we tested the hypothesis that the modest sodium reduction would alter circulating SCFA concentrations among untreated hypertensives, and the changes would be associated with reduced blood pressure and improved cardiovascular phenotypes. A total of 145 participants (42% blacks, 19% Asian, and 34% females) were included from a randomized, double-blind, placebo-controlled cross-over trial of sodium reduction with slow sodium or placebo tablets, each for 6 weeks. Targeted circulating SCFA profiling was performed in paired serum samples, which were collected at the end of each period, so as all outcome measures. Sodium reduction increased all 8 SCFAs, among which the increases in 2-methylbutyrate, butyrate, hexanoate, isobutyrate, and valerate were statistically significant (Ps<0.05). Also, increased SCFAs were associated with decreased blood pressure and improved arterial compliance. There were significant sex differences of SCFAs in response to sodium reduction (Ps<0.05). When stratified by sex, the increases in butyrate, hexanoate, isobutyrate, isovalerate, and valerate were significant in females only (Ps<0.05), not in males (Ps>0.05). In females, changes in isobutyrate, isovalerate, and 2-methylbutyrate were inversely associated with reduced blood pressures (Ps<0.05). Increased valerate was associated with decreased carotid-femoral pulse wave velocity (P=0.040). Our results show that dietary sodium reduction increases circulating SCFAs, supporting that dietary sodium may influence the gut microbiome in humans. There is a sex difference in SCFA response to sodium reduction. Moreover, increased SCFAs are associated with decreased blood pressures and improved arterial compliance. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00152074.

Serum 25-Hydroxyvitamin D Concentrations Are Associated with Mental Health and Psychosocial Stress in Young Adults.

: We aimed to test the hypothesis that serum 25-hydroxyvitamin D3 (25(OH)D) concentration is associated with mental health and life stress measures in young adults and investigate gender and racial disparities in these associations. This study comprised 327 black and white participants. Depression, trait anxiety, perceived stress, and hostility were measured by the following validated instruments: Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS), and Cook-Medley Hostility Scale (CMHS). Linear regression was used to estimate correlations between serum 25(OH)D concentration and mental health measurements in the total population and in subgroups stratified by gender and race. In this sample (28.2 ± 3.1 years, 52% female, 53% black), serum 25(OH)D concentration was negatively related to BDI, STAI, PSS, total CMHS score, and the majority of CMHS subscale scores (p-values < 0.05). Stratified by gender, most of these associations remained significant only in women (p-values < 0.05). Stratified by race, higher 25(OH)D concentrations in white participants were significantly related to lower BDI, STAI, PSS, and CMHS-cynicism subscales (p-values < 0.05); 25(OH)D concentrations in the black participants were only inversely associated with CMHS and most CMHS subscales (p-values < 0.05) but not with BDI, STAI, and PSS. We present novel findings of consistent inverse relationships between serum 25(OH)D concentration and various measures of mental health and life stress. Long-term interventional studies are warranted in order to investigate the roles of vitamin D supplementation in the prevention and mitigation of depression, anxiety, and psychological stress in young adults.

Urinary prostasin: a possible biomarker for renal pressure natriuresis in black adolescents.

Prostasin is a membrane-bound/secretive serine protease interacting with aldosterone and the epithelial sodium channel in the kidney. We and others have previously proposed the concept of stress-induced pressure natriuresis (SIPN) where increased urinary sodium excretion (UNaV) is coupled with elevated blood pressure (BP) in response to behavioral stress in normotensive adolescents. This study thus aimed to test the relationship between prostasin and pressure natriuresis using the SIPN model. A cohort of 102 normotensive black adolescents (mean age: 17.0 +/- 1.2 y; 56% females) were placed on a controlled sodium (4000 +/- 200 mg/d) and potassium (2600 +/- 200 mg/d) diet for three days before testing. The SIPN protocol consisted of a 1-h baseline period, a 1-h stress period (competitive video game), and a 1-h recovery period. During the stress period, BP elevation was coupled with an increase in UNaV. Urinary prostasin concentration had more than a 2-fold reduction from baseline (38.4 +/- 32.7 ng/mL) to stress (17.2 +/- 16.0 ng/mL), and further declined during recovery (12.1 +/- 16.2 ng/mL) (p < 0.001). Urinary prostasin was inversely correlated with UNaV during stress (r = -0.43, p = 0.0001), even after being normalized by urinary creatinine. Our data suggest that urinary prostasin could be a novel biomarker and/or mechanism for renal pressure natriuresis in normotensive black adolescents.