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.

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.

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.

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.

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.

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.

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.

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.

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.

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 receptor blocker attenuates stress pressor response in young adult African Americans.

African Americans (AAs) are susceptible to hypertension (HTN) and its associated organ damage leading to adverse cardiovascular (CV) outcomes. Psychological stress is proposed to contribute to the development of HTN; however, the potential role of the renin-angiotensin system (RAS) in stress-related HTN in AAs is largely unknown. In this study, we tested the hypothesis that activation of RAS is a potential contributing factor for altered CV responses to stress, and suppression of angiotensin II (Ang II) activity will improve hemodynamic responses to a prolonged mental stressor in healthy young AAs. Utilizing a double-blind, randomized, crossover study design, 132 normotensive AAs (25 ± 7 years) were treated with either a placebo (PLC) or 150 mg/d irbesartan (an Ang II type 1 receptor blocker; ARB) for 1 week. On the final day of each treatment, hemodynamic measures and urinary sodium excretion (UNaV) were collected before, during and after a 45 minute-mental stress. The magnitude of stress-induced increase in blood pressure with ARB was blunted and delayed compared to PLC. Systolic blood pressure at the end of recovery on ARB was significantly lower compared to either PLC (110 ± 13 vs 117 ± 12 mm Hg respectively; P < 0.001) or the prestress level on ARB (P = 0.02). ARB treatment reduced overall vasoconstriction and improved poststress UNaV. ARB attenuated blood pressure responses to mental stress and improved the poststress BP recovery process which were partly linked to reduced overall vasoconstriction and improved stress-induced UNaV in young adult AAs prior to the development of disease conditions. These results suggest that treatment approaches that inhibit RAS action could have significant relevance to potentially lower susceptibility to stress responses and eventually the premature development of HTN in AAs.

Ethnic Differences in Nighttime Melatonin and Nighttime Blood Pressure: A Study in European Americans and African Americans.

BACKGROUND: Ethnic differences in nighttime blood pressure (BP) have long been documented with African Americans (AAs) having higher BP than European Americans (EAs). At present, lower nighttime melatonin, a key regulator of circadian rhythms, has been associated with higher nighttime BP levels in EAs. This study sought to test the hypothesis that AAs have lower nighttime melatonin secretion compared with EAs. We also determined if this ethnic difference in melatonin could partially explain the ethnic difference in nighttime BP. METHODS: A total of 150 young adults (71 AA; 46% females; mean age: 27.7 years) enrolled in the Georgia Stress and Heart study provided an overnight urine sample for the measurement of 6-sulfatoxymelatonin, a major metabolite of melatonin. Urine melatonin excretion (UME) was calculated as the ratio between 6-sulfatoxymelatonin concentration and creatinine concentration. Twenty-four-hour ambulatory BP was assessed and nighttime systolic BP (SBP) was used as a major index of BP regulation. RESULTS: After adjustment of age, sex, body mass index, and smoking, AAs had significantly lower UME (P = 0.002) and higher nighttime SBP than EAs (P = 0.036). Lower UME was significantly associated with higher nighttime SBP and this relationship did not depend on ethnicity. The ethnicity difference in nighttime SBP was significantly attenuated after adding UME into the model (P = 0.163). CONCLUSION: This study is the first to document the ethnic difference in nighttime melatonin excretion, demonstrating that AAs have lower melatonin secretion compared with EAs. Furthermore, the ethnic difference in nighttime melatonin can partially account for the established ethnic difference in nighttime SBP.

Sodium Reduction, Metabolomic Profiling, and Cardiovascular Disease Risk in Untreated Black Hypertensives.

Dietary sodium restriction has multiple beneficial effects on cardiovascular health. The underlying mechanisms are not fully understood, and the roles of metabolomics have been rarely studied. We aimed to test the hypothesis that the reduction in dietary sodium intake would induce changes in metabolomic profiling among black hypertensives, and the changes would be associated with reduced blood pressure (BP) and improved skin capillary density. A total of 64 untreated black hypertensives were included from a randomized, double-blind, placebo-controlled cross-over trial of sodium reduction. The participants were given either 9 slow sodium tablets (10 mmol sodium per tablet) or placebo tablets daily for 6 weeks, they then crossed over to receive the other tablets for another 6 weeks, while on reduced sodium diet aiming at achieving daily sodium intake around 2.0 g. Untargeted metabolomic profiling was performed in paired serum samples, which were collected at the end of each period, so were BP and capillary density. Mixed-effects models were used. There were 34 metabolites identified with raw P's<0.05. Among those, 2 metabolites including ß-hydroxyisovalerate and methionine sulfone were significantly increased with sodium reduction (false discovery rate =0.006 and 0.099, respectively). Increased ß-hydroxyisovalerate was associated with reduced office systolic BP and ambulatory daytime systolic BP, whereas increased methionine sulfone was associated with reduced 24-hour diastolic BP, ambulatory nighttime diastolic BP, and increased skin capillary density. Our results suggest that dietary sodium reduction increases the circulating levels of ß-hydroxyisovalerate and methionine sulfone. Further studies are warranted. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00152074.

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.

Sodium Reduction, miRNA Profiling and CVD Risk in Untreated Hypertensives: a Randomized, Double-Blind, Placebo-Controlled Trial.

Sodium reduction decreases blood pressure (BP) and cardiovascular mortality. However, the underlying molecular mechanisms are not well understood. We tested the hypothesis that reduction of sodium intake would change miRNA expression in hypertensive patients, and those changes would be associated with improved cardiovascular phenotypes. A whole genome RNA sequencing was performed in paired serum samples collected at the end of usual sodium intake and reduced sodium intake periods from 10 (age 56.8 ± 8.9) untreated black male hypertensives, selected from a randomized crossover trial of sodium reduction as the discovery cohort. Validation was carried out by the PCR Serum/Plasma Focus panel profiling in paired samples in all 64 (50% males, age 50.2 ± 9.5) untreated black hypertensives from the same trial. Fifteen respondent miRNAs were identified in the discovery stage. miR-143-3p was replicated. Sodium reduction up-regulated miR-143-3p. The increase in miR-143-3p was associated with the reduction of BP and arterial stiffness and the increase in skin capillary density. In conclusion, dietary sodium reduction alters circulating miRNA expressions, and those miRNA changes are associated with reduced BP and improved arterial compliance in untreated black hypertensives, suggesting that miRNA regulation may be one of the underlying mechanisms that dietary sodium regulates cardiovascular health.

Relation of urinary endothelin-1 to stress-induced pressure natriuresis in healthy adolescents.

We hypothesize that delayed natriuresis during mental stress increases the risk of hypertension and other diseases. Our preclinical studies demonstrate an important role for renal endothelin-1 (ET-1) in regulating sodium excretion. Thus, we predict ET-1 may be linked to the delayed stress response in at-risk individuals. We hypothesize that reduced renal ET-1 accounts for derangements in sodium handling under stress, a link never explored in a large human cohort. We determined urinary ET-1 excretion in three observational studies of changes in sodium excretion during mental stress, in which 776 healthy youth (15-19 years) enrolled in a 5-hour protocol (2 hours of rest before and after 1 hour of mental stress). In all studies, 60-minute urine samples were obtained throughout the protocol. Subjects were grouped as retainers (reduced sodium excretion during stress relative to baseline) or excreters (increased sodium excretion during stress relative to baseline). In excreters, ET-1 excretion was significantly increased from baseline to stress (+0.02 pg/min; P < .001). In contrast, ET-1 excretion was significantly higher (P = .028) in retainers than excreters at baseline but significantly reduced in retainers under stress (-0.02 pg/min; P < .001). ET-1 excretion declined further in retainers during recovery but returned to prestress levels in excreters. Albumin excretion and albumin-to-creatinine ratio were significantly higher in retainers (P = .022, P < .001, respectively). Thus, loss of ET-1-dependent natriuresis may account for sodium retention during stress and may predispose retainers to renal diseases such as hypertension and kidney disease.

Blood Pressure Trajectories From Childhood to Young Adulthood Associated With Cardiovascular Risk: Results From the 23-Year Longitudinal Georgia Stress and Heart Study.

The purpose of this study is to identify subgroups of individuals with similar trajectories in blood pressure (BP) from childhood to young adulthood and to determine the relationship of BP trajectories with carotid intima-media thickness (IMT) and left ventricular mass index (LVMI). BP was measured ≤16 times during a 23-year period in 683 participants from childhood to young adulthood. IMT and LVMI were measured in 551 participants and 546 participants, respectively. Using latent class models, 3 trajectory groups in BP from childhood to young adulthood were identified, including high-increasing, moderate-increasing, and low-increasing groups. We found that trajectory of systolic BP was a significant predictor of both IMT and LVMI with increased rate of growth in systolic BP associated with higher levels of IMT and LVMI (Pfor trend <0.001). Similar to the BP trajectory groups from childhood to young adulthood, 3 trajectory groups in BP during childhood (≤18 years) were identified, and participants in the high-increasing group had thicker IMT (P<0.001) and increased LVMI (P=0.043) in comparison with those in the low-increasing group. Results were similar for mid-BP trajectories but not for diastolic BP trajectories. Our results suggested that different BP trajectories exist from childhood to young adulthood, and the trajectories were independently associated with IMT and LVMI. We, for the first time, reported the association between systolic BP trajectories derived from childhood with subclinical cardiovascular risk in young adulthood, indicating that monitoring trajectories of BP from childhood may help identify a high cardiovascular risk population in early life.

Outcomes following routine antithrombin III replacement during neonatal extracorporeal membrane oxygenation.

BACKGROUND: We sought to examine the effect of routine antithrombin III (AT3) infusion on hemorrhagic and thrombotic complications, blood product utilization, and circuit lifespan in neonatal extracorporeal membrane oxygenation (ECMO). METHODS: We performed a retrospective cohort study of 162 infants placed on ECMO for hypoxic respiratory failure. Infants requiring ECMO for primary cardiac support were excluded. Demographic data, time on ECMO, blood product usage, coagulation profile, and complications were compared between 90 control patients and 72 patients treated with AT3. RESULTS: Infants receiving AT3 during ECMO had less thrombotic and similar bleeding complications as compared to infants receiving standard anticoagulation therapy. Total blood product infusion during ECMO was decreased (54.7±20.1 vs. 67.4±34.9mL/kg per day, p=0.001) in infants receiving AT3 during ECMO. Tighter control of activated clotting time and higher serum heparin anti-Xa levels were observed in the AT3 cohort during the first days of ECMO support. 1st ECMO circuit lifespan did not differ between groups. CONCLUSIONS: Routine administration of AT3 in neonates receiving ECMO therapy was associated with tighter control of anticoagulation and a reduction in thrombotic events without increasing unwanted bleeding. However, circuit lifespan was unaffected. LEVEL OF EVIDENCE: Level III.

Correction: Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation: Cross-Sectional and Interventional Findings.

[This corrects the article DOI: 10.1371/journal.pone.0152849.].