A longitudinal study of blood pressure circadian rhythm from childhood to early adulthood.

Altered blood pressure (BP) circadian rhythmicity has been increasingly linked with cardiovascular risk. However, little is known about BP circadian rhythm change with age and its possible sociodemographic, anthropometric, and genetic moderators. Twenty-four-hour ambulatory BP was measured up to 16 times over a 23-year period in 339 European Americans (EAs) and 293 African Americans (AAs), with an average age of 15 years at the initial visit. BP circadian rhythms were indexed by amplitude and percent rhythm (a measure of rhythm integrity) and calculated using Fourier analysis. BP amplitude and percent rhythm increased with age and average BP (BP mesor). AAs were more likely to have lower BP amplitude and percent rhythm than their EA counterparts. BP amplitude and percent rhythm also decreased with adiposity (BMI and waist circumference). The summer season was associated with lower BP amplitude in AAs and lower percent rhythm in both AAs and EAs. Sex, height, socioeconomic status, physical activity, and family history of essential hypertension did not have an independent impact on BP amplitude or percent rhythm. The results of the present study suggest that BP circadian rhythm increases with age and BP mesor from childhood to young adulthood, decreases with adiposity, and that AAs are more likely to have lower circadian rhythm than EAs. Furthermore, we demonstrated that the summer season is associated with lower BP rhythmicity.

Nocturnal blood pressure dipping, blood pressure variability, and cognitive function in early and middle-aged adults.

Higher nighttime blood pressure (BP), less BP dipping, and higher BP variability have been linked with worse cognitive function in the elderly. The goal of this study is to explore whether this relationship already exists in early and middle adulthood. We further examined whether ethnic differences between African Americans and European Americans in BP parameters can explain ethnic differences in cognitive function. 24-h ambulatory BP monitoring and cognitive function were obtained from 390 participants (average age: 37.2 years with a range of 25-50; 54.9% African Americans; 63.6% females). We observed that higher nighttime BP, decreased dipping, and higher variability were significantly associated with lower scores on the Picture Sequence Memory Test. Significant negative associations between variability and overall composite scores were also observed. No significant associations between average 24-h or daytime BP and cognitive function were observed. Ethnic differences in nighttime diastolic pressures and dipping can explain 6.81% to 10.8% of the ethnicity difference in the score of the Picture Sequence Memory Test (ps < .05). This study suggests that the associations of nighttime BP, dipping, and variability with cognitive function already exist in young and middle-aged adults. Ethnic differences in nighttime BP and dipping can at least partially explain ethnic differences in cognitive function. The stronger association of these parameters with cognitive function than daytime or average BP in this age range raises the importance of using ambulatory BP monitoring for more precise detection of abnormal BP patterns in young adulthood.

Racial disparities in the relationship of regional socioeconomic status and colorectal cancer survival in the five regions of Georgia.

INTRODUCTION: The study's purpose was to examine 5-year colorectal cancer (CRC) survival rates between White and Black patients. We also determined whether regional socioeconomic status (SES) is associated with CRC survival between White and Black patients in the Clayton, West Central, East Central, Southeast, and Northeast Georgia public health districts. METHODS: We performed a retrospective cohort analysis using data from the 1975 to 2016 Surveillance, Epidemiology, and End Results program. The 2015 United States Department of Agriculture Economic Research Services county typology codes were used to identify region-level SES with persistent poverty, low employment, and low education. Kaplan-Meier method and Cox proportional hazard regression were performed. RESULTS: Among 10,876 CRC patients (31.1% Black patients), 5-year CRC survival rates were lower among Black patients compared to White patients (65.4% vs. 69.9%; p < 0.001). In multivariable analysis, White patients living in regions with persistent poverty had a 1.1-fold increased risk of CRC death (HR, 1.12; 95% CI, 1.00-1.25) compared to those living in non-persistent poverty regions. Among Black patients, those living in regions with low education were at a 1.2-fold increased risk of CRC death (HR, 1.19; 95% CI, 1.01-1.40) compared to those living in non-low education regions. DISCUSSION AND CONCLUSIONS: Black patients demonstrated lower CRC survival rates in Georgia compared to their White counterparts. White patients living in regions with persistent poverty, and Black patients living in regions with low education had an increased risk of CRC death. Our findings provide important evidence to all relevant stakeholders in allocating health resources aimed at CRC early detection and prevention and timely referral for CRC treatment by considering the patient's regional SES in Georgia.

Age, sex and race distribution of accelerometer-derived sleep variability in US school-aged children and adults.

Sleep variability (e.g. intra-individual variabilities in sleep duration or sleep timing, social jetlag, and catch-up sleep) is an important factor impacting health and mortality. However, limited information is available on the distribution of these sleep parameters across the human life span. We aimed to provide distribution of sleep variability related parameters across lifespan by sex and race in a national representative sample from the U.S. population. The study included 9981 participants 6 years and older from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, who had 4-7 days of valid 24-h accelerometer recording with at least one day obtained during weekend (Friday or Saturday night). Of the study participants, 43% showed ≥ 60 min sleep duration standard deviation (SD), 51% experienced ≥ 60 min catch-up sleep, 20% showed ≥ 60 min sleep midpoint SD, and 43% experienced ≥ 60 min social jetlag. American youth and young adults averaged greater sleep variability compared to other age groups. Non-Hispanic Blacks showed greater sleep variability in all parameters compared to other racial groups. There was a main effect of sex on sleep midpoint SD and social jetlag with males averaging slightly more than females. Our study provides important observations on sleep variability parameters of residents of the United States by using objectively measured sleep patterns and will provide unique insights for personalized advice on sleep hygiene.

Sleep Variability, Sleep Irregularity, and Nighttime Blood Pressure Dipping.

BACKGROUND: Circadian rhythm regulates many important biological functions in humans. The goal of this study is to explore the impact of day-to-day deviations in the sleep-wake cycle on nighttime blood pressure (BP) dipping and further examine whether the ethnic difference in day-to-day deviations in sleep patterns can explain the ethnic difference in nighttime BP dipping. METHODS: Twenty-four-hour ambulatory BP monitoring and 7-day accelerometer data were obtained from 365 adult participants (age range, 18.7-50.1 years; 52.6% Black participants and 47.3% European Americans; 64.1% females). Systolic BP dipping level was used to represent nighttime BP dipping. The SD of sleep duration was calculated as the index of sleep variability, and the SD of sleep midpoint was calculated as the index of sleep irregularity. RESULTS: A 1-hour increase in the SD of sleep midpoint was associated with a 1.16% decrease in nighttime BP dipping (P<0.001). A 1-hour increase in the SD of sleep duration was associated with a 1.39% decrease in nighttime BP dipping (P=0.017). The ethnic difference in the SD of sleep midpoint can explain 29.2% of the ethnicity difference in BP dipping (P=0.008). CONCLUSIONS: Sleep variability and sleep irregularity are associated with blunted BP dipping in the general population. In addition, data from the present investigation also demonstrate that the ethnic difference in sleep irregularity could partly explain the ethnic difference in BP dipping, an important finding that may help reduce the health disparity between Black participants and European Americans.

Day-to-day deviations in sleep parameters and biological aging: Findings from the NHANES 2011-2014.

OBJECTIVES: The majority of the previous research has focused on the impact of average sleep parameters on longevity. In this study, we aimed to investigate the associations of day-to-day deviations in sleep parameters with biological ages among 6052 adults participating in the 2011-2014 waves of the US National Health and Nutrition Examination Survey. METHODS: Sleep parameters, including sleep duration, efficiency, midpoint, and day-to-day deviations in sleep parameters, including standard deviation of sleep duration (sleep variability), standard deviation of sleep midpoint (sleep irregularity), catch-up sleep, and social jetlag, were obtained from 4 to 7 days of 24-h accelerometer recording. We used physiological data to compute measurements of biological aging according to 3 published algorithms: PhenoAge, Klemera-Doubal method Biological Age, and homeostatic dysregulation. RESULTS: After adjustment of multiple covariates, we observed that all parameters of day-to-day deviations in sleep were significantly associated with biological aging with larger sleep variability, larger sleep irregularity, more catch-up sleep, and more social jetlag linked with more advanced biological aging. The significant associations of sleep irregularity, catch-up sleep, and social jetlag with biological aging indices remained even after adjustment for sleep duration, efficiency, and midpoint. CONCLUSION: In this study, we found that day-to-day deviations in sleep parameters are independently associated with biological aging in US general population. Since day-to-day deviation in sleep is a modifiable behavioral factor, our finding suggests that intervention aiming at increasing regularity in sleep patterns may be a novel approach for extending a healthy life span.

Characterization of Resting-State Functional Connectivity Changes in Hypertension by a Modified Difference Degree Test.

Introduction: Hypertension affects over a billion people worldwide, and the application of neuroimaging may elucidate changes brought about by the disease. We have applied a graph theory approach to examine the organizational differences in resting-state functional magnetic resonance imaging (rs-fMRI) data between hypertensive and normotensive participants. To detect these groupwise differences, we performed statistical testing using a modified difference degree test (DDT). Methods: Structural and rs-fMRI data were collected from a cohort of 52 total (29 hypertensive and 23 normotensive) participants. Functional connectivity maps were obtained by partial correlation analysis of participant rs-fMRI data. We modified the DDT null generation algorithm and validated the change through different simulation schemes and then applied this modified DDT to our experimental data. Results: Through a comparative analysis, the modified DDT showed higher true positivity rates (TPR) when compared with the base DDT while also maintaining false positivity rates below the nominal value of 5% in nearly all analytically thresholded trials. Applying the modified DDT to our rs-fMRI data showed differential organization in the hypertension group in the regions throughout the brain including the default mode network. These experimental findings agree with previous studies. Conclusions: While our findings agree with previous studies, the experimental results presented require more investigation to prove their link to hypertension. Meanwhile, our modification to the DDT results in higher accuracy and an increased ability to discern groupwise differences in rs-fMRI data. We expect this to be useful in studying groupwise organizational differences in future studies.

Age, sex and race distribution of accelerometer-derived sleep variability in US school-aged children and adults.

Background: Sleep variability (e.g. intra-individual variabilities in sleep duration or sleep timing, social jetlag, and catch-up sleep) is an important factor impacting health and mortality. However, limited information is available on the distribution of these sleep parameters across the human life span. We aimed to provide distribution of sleep variability related parameters across lifespan by sex and race in a national representative sample from the U.S. population. Methods: The study included 9,799 participants 6 years and older from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, who had at least 3 days of valid sleep parameters with at least one day obtained during weekend (Friday or Saturday night). These were calculated from 7-day 24-h accelerometer recordings. Results: Of the study participants, 43% showed ≥ 60 minutes sleep duration standard deviation (SD), 51% experienced ≥ 60 minutes catch-up sleep, 20% showed ≥ 60 minutes midpoint of sleep SD, and 43% experienced ≥ 60 minutes social jetlag. American youth and young adults averaged greater sleep variability compared to other age groups. Non-Hispanic Blacks showed greater sleep variability in all parameters compared to other racial groups. There was a main effect of sex on sleep midpoint SD and social jetlag with males averaging slightly more than females. Conclusion: Our study provides important observations on sleep irregularity parameters of residents of the United States by using objectively measured sleep patterns and will provide unique insights for personalized advice on sleep hygiene.

Blunted Rest-Activity Circadian Rhythm Is Associated With Increased Rate of Biological Aging: An Analysis of NHANES 2011-2014.

Impaired rest-activity circadian rhythm has been associated with increased risk for morbidity and mortality. Animals with mutations in clock genes display accelerated aging and shortened life span. Whether impaired rest-activity circadian rhythm is also associated with processes of aging in humans has not been explored. We analyzed accelerometry and physiological data from 7 539 adults participating in the 2011-2014 waves of the U.S. National Health and Nutrition Examination Surveys. We used accelerometry data to compute rest-activity rhythm measurements. We used physiological data to compute measurements of biological aging according to 3 published algorithms: Klemera-Doubal method (KDM) Biological Age, PhenoAge, and homeostatic dysregulation (HD). In the models adjusting multiple covariates, participants with higher relative amplitude (RA) and interdaily stability (IS) and lower intradaily variability (IV) exhibited less advanced biological aging indexed by KDM and PhenoAge (effect sizes for 1-quantile increase in these rest-activity measurements ranged from 0.54 to 0.57 "years" for RA, 0.24 to 0.28 "years" for IS, and 0.24 to 0.35 "years" for IV, ps < .001). Similar finding was observed for biological aging indexed by HD, but the significance was limited to RA with 1-quantile increase in RA associated with 0.09 log units decrease in HD (p < .001). The results indicate that blunted rest-activity circadian rhythm is associated with accelerated aging in the general population, suggesting that interventions aiming at enhancing circadian rhythm may be a novel approach for the extension of a healthy life span.

Blunted rest-activity circadian rhythm increases the risk of all-cause, cardiovascular disease and cancer mortality in US adults.

To examine whether rest-activity circadian rhythm parameters can predict all-cause, cardiovascular disease and cancer mortality in a general adult population of the US. We further compared the mortality predictive performance of these parameters with that of traditional risk factors. This study included 7,252 adults from US National Health and Nutrition Examination Surveys (NHANES) 2011-2014, who had wrist accelerometer data obtained at baseline and follow-up status linked to the National Death Index records (2011-2019). During a median of 81 months (interquartile range, 69-94 months) of follow-up, 674 (9.3%) deaths occurred. There were inverse associations between relative amplitude (RA) and all-cause mortality, cardiovascular disease and cancer mortality with increased quartiles RA associated with lower mortality risk (all P < 0.05). The Hazard Ratios ranged from 0.61 to 0.79. Furthermore, RA outperformed all the tested traditional predictors of all-cause mortality with the exception of age. This study suggests that participants with blunted rest-activity circadian rhythms had a higher risk of all-cause, cardiovascular disease and cancer mortality. Future studies will be needed to test whether interventions that regulate rest-activity circadian activity rhythms will improve health outcomes.

Neuropsychiatric sequelae of long COVID-19: Pilot results from the COVID-19 neurological and molecular prospective cohort study in Georgia, USA.

Background: As the coronavirus disease 2019 (COVID-19) pandemic continues, there has been a growing interest in the chronic sequelae of COVID-19. Neuropsychiatric symptoms are observed in the acute phase of infection, but there is a need for accurate characterization of how these symptoms evolve over time. Additionally, African American populations have been disproportionately affected by the COVID-19 pandemic. The COVID-19 Neurological and Molecular Prospective Cohort Study in Georgia (CONGA) was established to investigate the severity and chronicity of these neurologic findings over the five-year period following infection. Methods: The CONGA study aims to recruit COVID-19 positive adult patients in Georgia, United States from both the inpatient and outpatient setting, with 50% being African American. This paper reports our preliminary results from the baseline visits of the first 200 patients recruited who were on average 125 days since having a positive COVID-19 test. The demographics, self-reported symptoms, comorbidities, and quantitative measures of depression, anxiety, smell, taste, and cognition were analyzed. Cognitive measures were compared to demographically matched controls. Blood and mononuclear cells were drawn and stored for future analysis. Results: Fatigue was the most reported symptom in the study cohort (68.5%). Thirty percent of participants demonstrated hyposmia and 30% of participants demonstrated hypogeusia. Self-reported neurologic dysfunction did not correlate with dysfunction on quantitative neurologic testing. Additionally, self-reported symptoms and comorbidities were associated with depression and anxiety. The study cohort performed worse on cognitive measures compared to demographically matched controls, and African American patients scored lower compared to non-Hispanic White patients on all quantitative cognitive testing. Conclusion: Our results support the growing evidence that there are chronic neuropsychiatric symptoms following COVID-19 infection. Our results suggest that self-reported neurologic symptoms do not appear to correlate with associated quantitative dysfunction, emphasizing the importance of quantitative measurements in the complete assessment of deficits. Self-reported symptoms are associated with depression and anxiety. COVID-19 infection appears to be associated with worse performance on cognitive measures, though the disparity in score between African American patients and non-Hispanic White patients is likely largely due to psychosocial, physical health, and socioeconomic factors.

Epidemiology of accelerometer-based sleep parameters in US school-aged children and adults: NHANES 2011-2014.

We aimed to provide objectively measured sleep parameters across lifespan by sex and race in a national representative sample of US population. The study included 11,279 participants 6 years and older from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, who had at least 3 days of valid sleep parameters calculated from 7-day 24-h accelerometer recording. Sleep duration showed a U-shaped association with age and reached the minimum at age 40 and started to increase again around age 50. The clock time for sleep onset (CTSO) delayed with age and reached the maximum at about age 20. CTSO then advanced until age 50, leveled off until age 70, then advanced again after age 70. Sleep efficiency showed an overall decreasing trend across the lifespan but stabilized from age 30 to about age 60. US young adults in age 20 s are the ones who slept at the latest around midnight, while the middle aged US residents between 40 and 50 years old slept the least. Females generally present longer sleep duration than males, while more likely to have later sleep onset, particularly at older ages. Non-Hispanic Blacks showed worse sleep characteristics, i.e. sleep later, sleep shorter, and sleep less efficiently, compared to other racial groups. In conclusion, this study provides valuable insights on the characteristics of sleep habits of residents of the United States by using objectively measurements of sleep parameters and will help guide personalized advice on sleep hygiene.

Blunted rest-activity rhythm is associated with increased white blood-cell-based inflammatory markers in adults: an analysis from NHANES 2011-2014.

Circadian rhythm disruption is associated with immune system disturbance and has been observed in many health problems where chronic-inflammation acts as a major contributor. We aim to examine whether rest-activity circadian rhythm is associated with chronic inflammation using white blood-cell-based inflammatory indices including white blood cell (WBC) count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII). We analyzed the data from 8089 adults (age≥20) with at least 4 days of validated accelerometer recordings and a valid WBC count from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Non-parametric rest-activity circadian rhythm parameters were derived from the accelerometer recordings. In the models adjusting multiple covariates, a one-quantile increase in relative amplitude (i.e. more robust circadian rhythm) was associated with 1 × 108 cells/L decrease in WBC number (95% CI: 5 × 107 to 1.5 × 108, P < .001), 7 × 107 cells/L decrease in neutrophils (95% CI: 3 × 107 to 1.1 × 108, P = .003) and 15.2 × 109 /L decrease in SII (95% CI: 6 × 109 /L to 20 × 109/L, P = .019). Consistent results were also observed for the association of M10 value and L5 value with these inflammatory indices. Our results indicated that blunted rest-activity circadian rhythm is associated with increased white blood-cell-based inflammatory indices in adults, suggesting interventions aiming at enhancing circadian rhythm by lifestyle programs may be a novel approach to improve the general health.

Rest-activity circadian rhythm and impaired glucose tolerance in adults: an analysis of NHANES 2011-2014.

INTRODUCTION: Circadian rhythm disturbance occurs in type 2 diabetes, yet it is unknown whether it also exists in the prediagnostic phase of the disease. Thus, we examined the association of rest-activity circadian rhythm with 2-hour glucose levels and the risk of impaired glucose tolerance (IGT) in a nationally representative sample of adults without diabetes using a cross-sectional design. RESEARCH DESIGN AND METHODS: We analyzed data from 2760 adults without diabetes (age ≥20) with at least 4 days of validated accelerometer recordings and a valid oral glucose tolerance test from the National Health and Nutrition Examination Survey 2011-2014. Non-parametric rest-activity circadian rhythm parameters were derived from the accelerometer recordings. RESULTS: In the models adjusting for multiple covariates, a one-quantile increase in relative amplitude (ie, increased circadian rhythmicity) was associated with 2.66 mg/dL decrease in 2-hour glucose level (95% CI -3.94 to -1.38, p<0.001) and a decreased odds of IGT (OR 0.75, 95% CI 0.63 to 0.89, p=0.002). A one-quantile increase in intradaily variability (ie, increased rhythm fragmentation) was associated with 3.01 mg/dL increase in 2-hour glucose level (95% CI 1.52 to 4.49, p=0.001) and an increased odds of IGT (OR 1.37, 95% CI 1.19 to 1.58, p<0.001). CONCLUSIONS: Circadian disruption is significantly associated with impaired glucose homeostasis in a general population of adults without diabetes. The association of circadian rhythm abnormalities with indicators of the pre-diabetic state suggests that circadian dysfunction may contribute to early disease pathogenesis.

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.

Diurnal Cortisol Slope and Nighttime Blood Pressure: A Study in European Americans and African Americans.

OBJECTIVES: African Americans (AAs) have higher nighttime blood pressure (BP) than European Americans (EAs). Stress has been suggested to play a role in this difference, but the mechanism is not well-understood. Flatter diurnal cortisol slope (DCS) is a well-known biological marker of stress. The objectives of this study were to: 1) examine ethnic differences in DCS; 2) evaluate the association between DCS and nighttime BP; and 3) determine the extent to which ethnic differences in nighttime BP can be explained by ethnic differences in DCS. METHODS: A total of 510 participants (age range: 14-35 years; 49.6% AAs, 54.5% females) provided four salivary cortisol samples at bedtime, wakeup, 30-minutes post-wakeup, and 60-minutes post-wakeup. Additionally, participants wore an ambulatory BP monitor for 24 hours. DCS was calculated as the average of the three morning samples minus the bedtime measurement. RESULTS: After adjustment for age, sex, BMI, and smoking, AAs had blunted DCS (P=.018) and higher nighttime systolic BP (SBP) and diastolic BP (DBP) (Ps<.001) compared with EAs. The DCS was inversely related to nighttime SBP and this relationship did not depend on ethnicity. The ethnic difference of nighttime SBP was significantly attenuated upon addition of DCS to the model. Mediation test showed that 9.5% of ethnic difference in nighttime SBP could be explained by DCS (P=.039). CONCLUSION: This study confirms ethnic differences in DCS and nighttime BP and further demonstrates that the ethnic differences in DCS can, at least partially, explain the ethnic differences found in nighttime BP.

Decreased heritability and emergence of novel genetic effects on pulse wave velocity from youth to young adulthood.

Increased arterial stiffness measured by pulse wave velocity (PWV) is an important parameter in the assessment of cardiovascular risk. Our previous longitudinal study has demonstrated that carotid-distal PWV showed reasonable stability throughout youth and young adulthood. This stability might be driven by genetic factors that are expressed consistently over time. We aimed to illustrate the relative contributions of genetic and environmental factors to the stability of carotid-distal PWV from youth to young adulthood. We also examined potential ethnic differences. For this purpose, carotid-distal PWV was measured twice in 497 European American (EA) and African American (AA) twins, with an average interval time of 3 years. Twin modelling on PWV showed that heritability decreased over time (62-35%), with the nonshared environmental influences becoming larger. There was no correlation between the nonshared environmental factors on PWV measured at visit 1 and visit 2, with the phenotypic tracking correlation (r = 0.32) completely explained by shared genetic factors over time. Novel genetic influences were identified accounting for a significant part of the variance (19%) at the second measurement occasion. There was no evidence for ethnic differences. In summary, novel genetic effects appear during development into young adulthood and account for a considerable part of the variation in PWV. Environmental influences become larger with age for PWV.

Genetic and Environmental Influences on Blood Pressure and Body Mass Index in the National Academy of Sciences-National Research Council World War II Veteran Twin Registry.

Blood pressure (BP) and obesity phenotypes may covary due to shared genetic or environmental factors or both. Furthermore, it is possible that the heritability of BP differs according to obesity status-a form of G×E interaction. This hypothesis has never been tested in White twins. The present study included 15 924 White male twin pairs aged between 15 and 33 years from the National Academy of Sciences-National Research Council World War II Veteran Twin Registry. Systolic and diastolic BPs, as well as height and weight, were measured at the induction physical examination. Body mass index (BMI) was used as the index of general obesity. Quantitative genetic modeling was performed using Mx software. Univariate analysis showed that narrow sense heritabilities (95% CI) for systolic BP, diastolic BP, height, and BMI were 0.401 (0.381-0.420), 0.297 (0.280-0.320), 0.866 (0.836-0.897), and 0.639 (0.614-0.664), respectively. Positive phenotypic correlations of BMI with systolic BP (r=0.13) and diastolic BP (r=0.08) were largely due to genetic factors (70% and 86%, respectively). The gene-BMI interaction analysis did not show any support for a modifying effect of BMI on genetic and environmental influences of systolic BP and diastolic BP. Our results suggest that correlations between BP and BMI are mainly explained by common genes influencing both. Higher BMI levels have no influence on the penetrance of genetic vulnerability to elevated BP. These conclusions may prove valuable for gene-finding studies.

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.