Commentary: Cancer Survivorship and Subclinical Myocardial Damage.

The rate of cardiovascular disease among cancer survivors is higher than in the general population. This difference is due to traditional cardiovascular disease (CVD) risk factors and also to the cardiotoxicity of cancer treatment. In a population-based cohort study of 3,512 men and women who were free of CVD at visit 5 of a large, community-based cohort study, Florido et al. (Am J Epidemiol. 2019;188(12):2188-2195) evaluated the association of cancer survivorship with subclinical myocardial damage, as assessed by elevated high-sensitivity cardiac troponin T (hs-cTnT). Cancer survivors had significantly higher odds of elevated hs-cTnT (odds ratio = 1.26, 95% confidence interval: 1.03, 1.53). Results were similar for survivors of non-sex-related and colorectal cancers. There was no association between survivorship from breast and prostate cancers and elevated hs-cTnT. The findings of Florido et al. indicate that survivors of some cancers might be more likely to have elevated hs-cTnT than patients without prior cancer. These findings have important implications because identifying cancer survivors who have elevated CVD risk is of paramount importance in order to prevent CVD manifestations such as heart attack, congestive heart failure, or stroke. Additional research is needed to clarify the associations of elevated hs-cTnT levels among survivors of specific cancer sites, stage at diagnosis, and histologic types.

Higher cardiac vagal activity predicts lower peripheral resistance 6 years later in European but not African Americans.

African American (AA) individuals are at a greater risk for the development of cardiovascular complications, such as hypertension, compared with European Americans (EAs). Higher vagally mediated heart rate variability (HRV) is typically associated with lower blood pressure (BP) and total peripheral resistance (TPR). However, research has yet to examine the differential impact of HRV on longitudinal hemodynamic activity between AAs and EAs. We sought to rectify this in a sample of 385 normotensive youths (207 AAs, 178 EAs; mean age 23.16 ± 2.9 yr). Individuals participated in two laboratory evaluations spanning approximately 6 yr. Bioimpedance was used to assess HRV at time 1 and cardiac output at both time 1 and time 2. Mean arterial pressure (MAP) was measured at both time points via an automated BP machine. TPR was calculated as MAP divided by cardiac output. Results showed AAs to have higher BP and higher TPR at time 2 compared with EAs, independent of several important covariates. Also, higher HRV at time 1 significantly predicted both lower TPR and BP at time 2 among EAs only; these associations were attenuated and not significant in AAs. HRV did not significantly predict cardiac output at time 2 in the full sample or split by ethnicity. Our findings highlight that AAs show TPR mediated long-term increases in BP irrespective of resting HRV, providing a physiological pathway linking AAs with a greater risk for mortality and morbidity from hypertension and potentially other cardiovascular disease.NEW & NEWSWORTHY African Americans and European Americans differ in hemodynamics underlying long-term blood pressure regulation. Over 6 yr, African Americans show total peripheral resistance-mediated increases in blood pressure compared with European Americans. Higher heart rate variability predicts lower blood pressure and total peripheral resistance 6 yr later in European Americans but not African Americans.

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.

Adenosine kinase inhibition enhances microvascular dilator function and improves left ventricle diastolic dysfunction.

OBJECTIVE: Inhibition of adenosine kinase (ADK), via augmenting endogenous adenosine levels exerts cardiovascular protection. We tested the hypothesis that ADK inhibition improves microvascular dilator and left ventricle (LV) contractile function under metabolic or hemodynamic stress. METHODS AND RESULTS: In Obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid rats, treatment with the selective ADK inhibitor, ABT-702 (1.5 mg/kg, intraperitoneal injections for 8-week) restored acetylcholine-, sodium nitroprusside-, and adenosine-induced dilations in isolated coronary arterioles, an effect that was accompanied by normalized end-diastolic pressure (in mm Hg, Lean: 3.4 ± 0.6, Obese: 17.6 ± 4.2, Obese + ABT: 6.6 ± 1.4) and LV relaxation constant, Tau (in ms, Lean: 6.9 ± 1.5, Obese: 13.9 ± 1.7, Obese + ABT: 6.0 ± 1.1). Mice with vascular endothelium selective ADK deletion (ADKVEC KO) exhibited an enhanced dilation to acetylcholine in isolated gracilis muscle (lgEC50 WT: -8.2 ± 0.1, ADKVEC KO: -8.8 ± 0.1, P < .05) and mesenteric arterioles (lgEC50 WT: -7.4 ± 0.2, ADKVEC KO: -8.1 ± 1.2, P < .05) when compared to wild-type (WT) mice, whereas relaxation of the femoral artery and aorta (lgEC50 WT: -7.03 ± 0.6, ADKVEC KO: -7.05 ± 0.8) was similar in the two groups. Wild-type mice progressively developed LV systolic and diastolic dysfunction when they underwent transverse aortic constriction surgery, whereas ADKVEC -KO mice displayed a lesser degree in decline of LV function. CONCLUSIONS: Our results indicate that ADK inhibition selectively enhances microvascular vasodilator function, whereby it improves LV perfusion and LV contractile function under metabolic and hemodynamic stress.

Exercise effects on arterial stiffness and heart health in children with excess weight: The SMART RCT.

INTRODUCTION: Childhood obesity and inactivity are associated with cardiovascular risk. Evidence is limited for exercise effects on arterial health in children. METHODS: One hundred and seventy-five inactive children with overweight or obesity (8-11 years, ≥85th percentile BMI, 61% female, 87% Black, 73% with obesity) were randomized to an 8-month daily after-school aerobic exercise program (40 min/day, n = 90) or a sedentary control condition (n = 85). Carotid-femoral pulse wave velocity (PWV, primary outcome, arterial stiffness), fitness, adiposity, blood pressure (BP), glucose, insulin resistance, lipids, and C-reactive protein were measured at baseline and posttest (8 months). Adiposity, fitness, and BP were measured again at follow-up, 8-12 months later. Intent-to-treat analyses were conducted using mixed models. RESULTS: The study had 89% retention, with attendance of 59% in exercise and 64% in the control condition, and vigorous exercise participation (average heart rate 161 ± 7 beats/min). Compared with controls, the exercise group had twice the improvement in fitness (VÈ®2 peak, 2.7 (95% CI 1.8, 3.6) vs. 1.3 (0.4, 2.3) mL/kg/min) and adiposity (-1.8 (-2.4, -1.1) vs. -0.8 (-1.5, -0.1)%), each p = 0.04, and a large improvement in HDL-cholesterol (0.13 (0.075, 0.186) vs. -0.028 (-0.083, 0.023) mmol/L, p < 0.0001). There was no group × time effect on other outcomes at 8 months, or on any outcomes at follow-up. The change in PWV at 8 months correlated with changes in insulin and insulin resistance (both r = 0.32), diastolic BP (r = 0.24), BMI (r = 0.22), and adiposity (r = 0.18). CONCLUSIONS: Eight months of aerobic exercise training improved fitness, adiposity, and HDL-cholesterol levels, but did not reduce arterial stiffness in children with excess weight. PWV improved as a function of insulin resistance, BP, BMI, and adiposity. Weight loss may be required to improve arterial stiffness. Exercise benefits waned after discontinuing the program.

Ethnic Differences in Resting Total Peripheral Resistance: A Systematic Review and Meta-Analysis.

OBJECTIVE: Decades of research suggest that there may be important ethnic differences in the hemodynamic mechanisms that co-determine arterial blood pressure, the primary diagnostic index of hypertension. In general, studies have observed that, compared with European Americans (EAs), African Americans (AAs) exhibit higher total peripheral resistance (TPR), an important summative index of peripheral vascular constriction. In contrast, EAs have been reliably shown to exhibit greater cardiac output (CO), which is directly linked to left ventricle and overall cardiac blood flow. We have previously proposed that elevated basal TPR, in particular, represents one component of the cardiovascular conundrum, characterized, paradoxically, by elevated resting heart rate variability among AAs relative to EAs. The present meta-analysis and systematic review of the literature sought to extend this previous work by establishing the magnitude of the empirically implied ethnic differences in resting TPR and CO. METHODS: A search of the literature yielded 140 abstracts on differences in TPR between AAs and EAs; 40 were included. Sample sizes, means, and standard deviations for baseline TPR with samples that included EAs and AAs were collected, and Hedges g was computed. RESULTS: Findings indicated that AAs had higher baseline TPR than did EAs (Hedges g = 0.307, SE = 0.043, confidence interval= 0.224 to 0.391, p < .001). In addition, EAs had higher resting CO than did AAs (Hedges g = -0.214, SE = 0.056, confidence interval = -0.324 to -0.104, p < .001). CONCLUSIONS: We discuss the present findings in the context of the role of elevated TPR in the deleterious effects of high blood pressure specifically for AAs.

Ethnic differences in resting heart rate variability: a systematic review and meta-analysis.

BACKGROUND: Ethnic disparities in cardiovascular morbidity and mortality are widely documented in the literature. Recently, research has shown that decreased parasympathetic cardiac modulation is associated with the established and emerging risk factors for cardiovascular disease (CVD) and stroke. In consideration of the disproportionate CVD risk and disease profile of African Americans (AAs), it is plausible that decreased cardiac parasympathetic functioning may partially explain these disparities. In the present systematic review and meta-analysis, we assess the available evidence for a reliable ethnic difference in tonic vagally mediated heart rate variability (HRV), an indicator of parasympathetic cardiac modulation. METHODS: A systematic literature search was conducted yielding studies comparing tonic HRV in AAs and European Americans. Adjusted standardized effect sizes (Hedges g) were calculated using a mixed-effects model, with restricted maximum likelihood estimation for 17 studies containing appropriate measures of vagally mediated HRV. RESULTS: Meta-analysis results suggest that AAs have greater HRV than do European Americans (Hedges g = 0.93, 95% confidence interval = 0.25-1.62), even after consideration of several covariates including health status, medication use, and subgroup stratification by sex and age. CONCLUSIONS: These findings suggest that decreased vagally mediated HRV is not likely to account for the persistent health disparities experienced by AAs with respect to CVD risk and burden. These disparities underscore the need for continued research addressing socioethnic cardiovascular differences and the biobehavioral mechanisms involved.

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.

Racial differences in baroreflex function: Implications for the cardiovascular conundrum.

Study objective: African Americans (AAs) show early signs of vascular dysfunction paired with elevated blood pressure (BP) and total peripheral resistance (TPR), which is thought to underlie their increased rates of cardiovascular health complications relative to European Americans (EAs). AAs paradoxically have higher cardiac vagal tone, indexed by heart rate variability (HRV), which is cardio-protective. This paradox has been termed the Cardiovascular Conundrum. The physiological mechanism underlying this phenomenon is not well understood. We examined race differences in baroreflex function, which might be an important mechanism underlying the Cardiovascular Conundrum. Design: Participants completed a 5-minute baseline period where resting cardiac metrics were assessed. Setting: Laboratory. Participants: 130 college-aged individuals (54 women, 57 AAs). Main outcome measures: Baroreflex function was indexed as baroreflex sensitivity (BRS; the magnitude of changes in cardiovascular activity in accordance with BP changes) and effectiveness (BEI; the ratio of BP changes that elicit changes in cardiovascular activity) in the cardiac, vascular, and myocardial limbs. Results and conclusions: Results showed AAs to have higher HRV and cardiac BRS in comparison to EAs, suggesting the baroreflex is more sensitive to correcting the heart period for changes in BP among AAs compared to EAs. However, AAs showed lower vascular BEI relative to EAs, suggesting less effective control of TPR. In sum, lower BEI in the vascular branch might be an important mechanism underlying the Cardiovascular Conundrum (i.e., higher HRV and BP) and by extension, health disparities in cardiovascular diseases between AAs and EAs.

Interactive influences of ethnicity, endothelin-1 gene, and everyday discrimination upon nocturnal ambulatory blood pressure.

BACKGROUND: Everyday discrimination scale scores are associated with increased ambulatory blood pressure (BP) and reduced nocturnal dipping, and the endothelin-1 (ET-1)/Lys198Asn polymorphism is associated with increased resting BP and exaggerated BP reactivity among African Americans compared to European Americans. Combined influences of these factors on BP control are unknown. PURPOSE: This study tested the hypothesis of a three-way interaction between ethnicity, ET-1 carrier status, and everyday discrimination upon ambulatory BP and nocturnal dipping. METHODS: Baseline laboratory anthropometrics and the everyday discrimination scale were completed by 352 (175 African American) young adult normotensives, followed by 24-h ambulatory BP monitoring. RESULTS: For nocturnal dipping, multiple regression models controlling for age, sex, ethnicity, and body mass index revealed significant three-way ET-1 × everyday discrimination × ethnicity interactions. Specifically, among African American ET-1 T-allele carriers, increases in everyday discrimination led to reduced nocturnal dipping. CONCLUSIONS: African Americans that carry the ET-1/Lys198Asn T-allele and report higher everyday discrimination scores may be at particular risk for reduced nocturnal dipping.

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.

Mice with endothelial cell-selective adhesion molecule deficiency develop coronary microvascular rarefaction and left ventricle diastolic dysfunction.

Endothelial cell-selective adhesion molecule (ESAM) regulates inflammatory cell adhesion and transmigration and promotes angiogenesis. Here, we examined the role of ESAM in cardiac vascularization, inflammatory cell infiltration, and left ventricle (LV) diastolic function under basal and hemodynamic stress conditions. We employed mice with homozygous genetic deletion of ESAM (ESAM-/- ) and also performed uninephrectomy and aldosterone infusion (UNX-Aldo) to induce volume and pressure overload. Using echocardiography, we found that ESAM-/- mice display no change in systolic function. However, they develop LV diastolic dysfunction, as indicated by a significantly reduced E/A ratio (E = early, A = late mitral inflow peak velocities), increased E/e' ratio, isovolumic relaxation time (IVRT), and E wave deceleration time. An unbiased automated tracing and 3D reconstruction of coronary vasculature revealed that ESAM-/- mice had reduced coronary vascular density. Arteries of ESAM-/- mice exhibited impaired endothelial sprouting and in cultured endothelial cells siRNA-mediated ESAM knockdown reduced tube formation. Changes in ESAM-/- mice were accompanied by elevated myocardial inflammatory cytokine and myeloperoxidase-positive neutrophil levels. Furthermore, UNX-Aldo procedure in wild type mice induced LV diastolic dysfunction, which was accompanied by significantly increased serum ESAM levels. When compared to wild types, ESAM-/- mice with UNX-Aldo displayed worsening of LV diastolic function, as indicated by increased IVRT and pulmonary edema. Thus, we propose that ESAM plays a mechanistic role in proper myocardial vascularization and the maintenance of LV diastolic function under basal and hemodynamic stress conditions.

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.

Impact of transcendental meditation on left ventricular mass in african american adolescents.

Background. An early sign of ventricular remodeling is increased left ventricular mass (LVM) which over time may lead to left ventricular hypertrophy, the strongest predictor of cardiovascular morbidity and mortality, other than advancing age. Methods. 62 (30 TM; 32 CTL) African American adolescents (age 16.2 ± 1.3 years) with high normal systolic BP were randomly assigned to either 4-month Transcendental Meditation (TM) or health education control groups. The echocardiographic-derived measure of LVM index (LVMI = LVM/ht(2.7)) was measured before and after the 4-month TM study and at 4-month followup. 2D-guided M-mode echocardiography using a Hewlett Packard 5500 echosonograph was used to determine LVMI. Results. The TM group exhibited a greater decrease in LVMI at 4-month followup compared to the CTL group (-2.6 versus +0.3 gm/ht(2.7), P < 0.04). The TM group exhibited a lesser increase in BMI at 4-month follow-up compared to the CTL group (0.2 ± 1.6 versus 1.1 ± 1.4, P < 0.03). Conclusion. These findings indicate that among a group of prehypertensive African American adolescents, 4 months of TM compared to heath education resulted in a significant decrease in LVMI, and these changes were maintained at 4-month follow-up.

Aortic pressure-only wave separation analysis in adolescents: accuracy and associations with left ventricular mass index.

Early-life exposure to high blood pressure (BP) is associated with cardiovascular target organ damage but not all BP-related risk is attributable to systolic and diastolic BP alone. In adolescence, aortic wave separation (WS) parameters are associated with increased left ventricular mass index (LVMI) but this approach is limited by the requirement for aortic flow measurements. Several methods for estimating the aortic flow waveform from pressure waveforms have emerged, but their accuracy and associations with LVMI have never been tested in adolescents, which was the aim of our study. Carotid pressure waveforms were acquired by tonometry from 58 adolescents (age 16 ± 1.5 years, 59% female). Measured (aortic) flow and LVMI were acquired via 2D echocardiography. Three pressure-only approximations of aortic flow were synthesized, including triangular, excess, and individualized-physiologic flow. A 4th aortic flow (average flow) was approximated from the average of all 58 measured flow waveforms. Forward (Pf) and backward (Pb) pressure and reflection magnitude (Rm) were derived from WS analysis. The individualized-physiologic flow produced the best approximations of Pf (mean difference ± SD, -0.15 ± 2.38 mmHg), Pb (0.14 ± 0.25 mmHg), and Rm (0.01 ± 0.02 mmHg). Pf derived using measured, individualized-physiologic, and average flow, was similarly associated with LVMI adjusting for age, brachial systolic BP, cardiac output, and BMI (P ≤ 0.03 all). Pb derived using all flow waveforms was associated with LVMI and all associations yielded similar effect estimates. Of the estimated flow waveforms, individualized-physiologic flow yielded the best approximation of WS parameters and may provide important physiological and clinical insight among adolescents.

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.

Impaired vasodilation in pregnant African Americans: Preliminary evidence of potential antecedents and consequences.

Significant health disparities exist between African Americans (AA) and European Americans (EA) in hypertension and hypertension-related disorders. Evidence suggests that this is due to impaired vasodilation in AAs. Pregnancy is a potent systemic vasodilatory state. However, differences in vasodilation between AAs and EAs have not been investigated in pregnancy. We sought to examine the effects of pregnancy on vasodilation in AA and EA women and how this might be related to discrimination and low birth weight in their offspring. Hemodynamics [blood pressure (MAP), cardiac output (CO), total peripheral resistance (TPR)] and heart rate variability (HF-HRV) were examined at baseline in 40 pregnant AAs (n = 20) and EAs (n = 20) and matched nonpregnant women (n = 40). The Experiences of Discrimination scale and birth weight were also measured in the offspring of the pregnant participants. Whereas pregnancy was associated with decreased MAP independent of race, AAs showed impaired vasodilation independent of pregnancy status as indicated by greater TPR despite greater HF-HRV. In AAs, but not EAs, reports of fewer incidences of discrimination were associated with greater TPR. Finally, the HF-HRV of EA mothers was inversely related to the birth weight of their offspring but was uncorrelated in AAs. We report novel evidence of impaired vasodilation to an endogenous vasodilatory stimulus in AAs. Higher TPR was related to discrimination in AAs and higher HF-HRV was related to low birth weight in EAs. These findings have implications for understanding the intergenerational transmission of impaired vasodilation in AAs.

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.