Search

Background. C-reactive protein (CRP) is an independent biomarker of systemic inflammation and a predictor of future cardiovascular disease (CVD). More than just a pure bystander, CRP directly interacts with endothelial cells to decrease endothelial nitric oxide synthase (eNOS) expression and bioactivity, decrease nitric oxide (NO) production, and increase the release of vasoconstrictors and adhesion molecules. Race is significantly associated with CRP levels and CVD risks. With aerobic exercise, the vessel wall is exposed to chronic high laminar shear stress (HiLSS) that shifts the endothelium phenotype towards an anti-inflammatory, antioxidant, antiapoptotic, and antiproliferative environment. Thus, the purpose of this study was to assess the racial differences concerning the CRP-induced effects in endothelial cells and the potential role of HiLSS in mitigating these differences. Methods. Human umbilical vein endothelial cells (HUVECs) from four African American (AA) and four Caucasian (CA) donors were cultured and incubated under the following conditions: (1) static control, (2) CRP (10 μg/mL, 24 hours), (3) CRP receptor (FcγRIIB) inhibitor followed by CRP stimulation, (4) HiLSS (20 dyne/cm2, 24 hours), and (5) HiLSS followed by CRP stimulation. Results. AA HUVECs had significantly higher FcγRIIB receptor expression under both basal and CRP incubation conditions. Blocking FcγRIIB receptor significantly attenuated the CRP-induced decrements in eNOS expression only in AA HUVECs. Finally, HiLSS significantly counteracted CRP-induced effects. Conclusion. Understanding potential racial differences in endothelial function is important to improve CVD prevention. Our results shed light on FcγRIIB receptor as a potential contributor to racial differences in endothelial function in AA.

We quantify the robustness of the semantic segmentation model U-Net, applied to single cell nuclei detection, with respect to the following factors: (1) automated vs manual training annotations, (2) quantity of training data, and (3) microscope image focus. The difficulty of obtaining sufficient volumes of accurate manually annotated training data to create an accurate Convolutional Neural Networks (CNN) model is overcome by the temporary use of fluorescent labels to automate the creation of training datasets using traditional image processing algorithms. The accuracy measurement is computed with respect to manually annotated masks which were also created to evaluate the effectiveness of using automated training set generation via the fluorescent images. The metric to compute the accuracy is the false positive/negative rate of cell nuclei detection. The goal is to maximize the true positive rate while minimizing the false positive rate. We found that automated segmentation of fluorescently labeled nuclei provides viable training data without the need for manual segmentation. A training dataset size of four large stitched images with medium cell density was enough to reach a true positive rate above 88% and a false positive rate below 20%.

Purpose: Systemic inflammation, measured by C-reactive protein (CRP), is an important risk factor for cardiovascular disease (CVD) and mortality. We investigated whether aerobic exercise training (AEXT) affects African Americans with high inflammation (HI) the same way it does African Americans with low inflammation (LI) in terms of CVD risk factors. Methods: 23 African Americans with CRP levels Results: The LI group improved aerobic fitness by 10%, body mass index by 3%, and plasma triglycerides by 20%, with no change being observed in HI group for these variables. The HI group improved fasting plasma glucose levels by 10%, with no change occurring in the LI group. Both groups improved CD62E+ EMPs by 38% and 59% for the LI and HI group, respectively. Conclusions: A standard AEXT intervention differentially affected CVD risk factors among African Americans with high and low inflammation. This may indicate that, in African Americans with high inflammation, AEXT alone may not be enough to reap the same benefits as their low-inflammation peers in terms of CVD risk modification. Ethn Dis. 2017;27(3):233-240; doi:10.18865/ed.27.3.233

Improvements in indices of vascular health and endothelial function have been inversely associated with hypertension, a risk factor for cardiovascular disease (e.g., myocardial infarction, stroke, and heart failure), renal failure, and mortality. Aerobic exercise training (AEXT) has been positively associated with improvements in clinical health values, as well as vascular health biomarkers, and endothelial function. The purpose of this study was to evaluate whether measures of exercise adherence were related to clinical outcome measures and indices of vascular health subsequent to a 6-month AEXT intervention in a middle-to-older aged African American cohort. Following dietary stabilization, sedentary, apparently healthy, African American adults (40 – 71 y/o) underwent baseline testing including blood pressure, flow-mediated dilation (FMD) studies, fasting blood sampling, and graded exercise testing. Upon completion of a supervised 6-month AEXT intervention, participants repeated all baseline tests. Exercise adherence was measured three ways: exercise percentage, exercise volume, and exercise score. There were no significant correlations between the changes in the vascular health biomarkers of the participants and any of the adherence measures. In addition, there were no significant correlations between any of the adherence measures and the clinical values of the participants that had been significantly changed pre-post-AEXT. Participants improved their clinical and vascular health and decreased risk factors for hypertension and cardiovascular disease regardless of their level of adherence to AEXT. Future studies should continue to accurately quantify adherence in order to assess the exercise dose for improvements in vascular and clinical health.

African-American women represent an understudied population in menopause research yet face greater postmenopausal challenges associated with mortality than their white peers. We investigated the effects of a mild-intensity aerobic exercise training program on markers of mortality risk in both premenopausal and postmenopausal African-American women.Sixteen premenopausal women and 19 postmenopausal women underwent 6 months of mild-intensity aerobic exercise training. Measurements included markers of blood lipid and glucose profile, inflammation, kidney function, vascular health, and aerobic fitness before and after the exercise intervention.Before the exercise intervention, the premenopausal and postmenopausal groups only differed in age, low-density lipoprotein, and total cholesterol levels, with the latter two being higher in the postmenopausal group. Both triglycerides and markers of early-stage endothelial dysfunction (CD62E endothelial microparticles) improved in both groups with aerobic exercise training. Aerobic fitness, glomerular filtration rate, body mass index, plasma glucose levels, and markers of late-stage endothelial dysfunction (CD31/CD42b endothelial microparticles) only improved in the premenopausal group.Mild-intensity aerobic exercise training succeeds in improving some markers of cardiovascular disease and mortality in postmenopausal women. Higher levels of exercise intensity or perhaps additional interventions may need to be considered to further decrease mortality risk in this population.

As healthcare progresses toward individualized medicine, understanding how different racial groups respond to lifestyle interventions is valuable. It is established that African Americans have disproportionate levels of cardiovascular disease and impaired vascular health, and clinical practice guidelines suggest lifestyle interventions as the first line of treatment. Recently, the authors reported that 6 months of aerobic exercise improved inflammatory markers, flow-mediated dilation (FMD), and levels of circulating endothelial microparticles (EMPs) in African American adults. This study is a subgroup analysis of the aerobic exercise–induced changes in vascular health and blood pressure (BP) measures, including carotid artery intima-media thickness (IMT), nitroglycerin-mediated dilation (NMD), ambulatory BP, and office BP. Sedentary African American adults (53.4±6.2 years; 21 women and 5 men) showed improved vascular health but no change in BP. Carotid artery IMT decreased 6.4%, plasma nitric oxide levels increased 76.6%, plasma EMP levels decreased, percentage of FMD increased 59.6%, and FMD/NMD ratio increased 36.2% (P

African Americans (AA) have the highest prevalence of hypertension (HTN) in the world which may emanate from their predisposition to heightened endothelial inflammation. Long-term exposure of the endothelium to proinflammatory cytokines leads to increased oxidative stress, inflammation, and endothelial dysfunction which support an environment favoring HTN. It is thought that the balance between pro- and anti-inflammation plays a crucial role as a determinant of endothelial homeostasis and health. Positive associations between proinflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) with HTN have been reported. Elevated circulating levels of the anti-inflammatory cytokine, interleukin-10 (IL-10) have been associated with improved endothelial function. In addition, aerobic exercise training (AEXT) has been associated with favorable endothelial adaptations. PURPOSE: To evaluate the effect of a 6-month AEXT intervention on the inflammatory biomarkers CRP, IL-6, and IL-10 in African Americans. A secondary purpose was to determine whether there are relationships between the changes in CRP, IL-6, and IL-10 subsequent to the 6-month AEXT intervention. METHODS: A Pre-Post design was employed following the completion of screening, dietary stabilization, and antihypertensive medication tapering. Subjects were sedentary, putatively healthy, 45-71 y/o AA men and women. Baseline evaluation included fasting blood sampling and graded exercise testing (GXT). Participants engaged in 6-months of AEXT. At the conclusion of the AEXT intervention, baseline tests were repeated. Concentrations of CRP, IL-6, and IL-10 were determined using an ELISA. RESULTS: There was a significant decrease in CRP (n=37; p=0.01) and a significant decrease in IL-6 (n=32; p=0.04) following AEXT. IL-10 was increased following the AEXT intervention, however it was not statistically significant (n=26; p=0.08). There were no significant relationships between the changes in the inflammatory biomarkers measured. CONCLUSION: Based on the favorable adaptations in the inflammatory biomarkers CRP and IL-6, AEXT may be a viable, nonpharmacologic method to reduce the risk for HTN in AA by improving inflammation status and endothelial function.

Background: Vascular cell adhesion molecule-1 (VCAM-1) mediates the adhesion of monocytes to vascular endothelium, which play a role in the development of endothelial dysfunction and atherosclerosis. Flow-mediation dilation (FMD) is an endothelium-dependent response, which is mediated by nitric oxide and closely related to endothelial function. The purpose of the study was to test whether levels of VCAM-1 were associated the endothelial-dependent (FMD) in normotensive African Americans. Normotensives were studied in order to eliminate the influence of hypertension. Methods and Results: Blood was collected in 22 subjects aged 41-62 yrs with normal blood pressure (125.0 ± 9.1 mmHg) after 12 hr fast. Plasma was obtained by centrifugation within 15 min after collection in 4 degree. A commercially available solid phase sandwich enzyme linked immuno-sorbent assay kit was used to detect VCAM-1 levels in plasma. FMD was measured after 5-min cuff occlusion using Doppler ultrasound. The maximum FMD diameters were calculated. In the entire study population, levels of VCAM-1 (556.92 ± 154.20 ng/mL) were negatively correlated with the true peak FMD (FMD: 7.81 ± 2.22 %, r=-0.484, P=0.023). Conclusion: Levels of VCAM-1 were associated with endothelial responsiveness in healthy African Americans with normal blood pressure. These results suggest that the level of VCAM-1 may be a predictive of endothelial dysfunction in the unique healthy populations.

African Americans have the highest prevalence of hypertension in the world which may emanate from their predisposition to heightened endothelial inflammation. The purpose of this study was to determine the effects of a 6-month aerobic exercise training (AEXT) intervention on the inflammatory biomarkers interleukin-10 (IL-10), interleukin-6 (IL-6), and endothelial microparticle (EMP) CD62E+ and endothelial function assessed by flow-mediated dilation (FMD) in African Americans. A secondary purpose was to evaluate whether changes in IL-10, IL-6, or CD62E+ EMPs predicted the change in FMD following the 6-month AEXT intervention. A pre-post design was employed with baseline evaluation including office blood pressure, FMD, fasting blood sampling, and graded exercise testing. Participants engaged in 6 months of AEXT. Following the AEXT intervention, all baseline tests were repeated. FMD significantly increased, CD62E+ EMPs and IL-6 significantly decreased, and IL-10 increased but not significantly following AEXT. Changes in inflammatory biomarkers did not significantly predict the change in FMD. The change inVO2 maxsignificantly predicted the change in IL-10. Based on these results, AEXT may be a viable, nonpharmacological method to improve inflammation status and endothelial function and thereby contribute to risk reduction for cardiovascular disease in African Americans.

The purpose of this study was to investigate the association of visit-to-visit and 24-h blood pressure (BP) variability with markers of endothelial injury and vascular function. We recruited 72 African Americans who were non-diabetic, non-smoking and free of cardiovascular (CV) and renal disease. Office BP was measured at three visits and 24-h ambulatory BP monitoring was conducted to measure visit-to-visit and 24-h BP variability, respectively. The 5-min time-course of brachial artery flow-mediated dilation and nitroglycerin-mediated dilation were assessed as measures of endothelial and smooth muscle function. Fasted blood samples were analyzed for circulating endothelial microparticles (EMPs). Significantly lower CD31+CD42- EMPs were found in participants with high visit-to-visit systolic blood pressure (SBP) variability or high 24-h diastolic blood pressure (DBP) variability. Participants with high visit-to-visit DBP variability had significantly lower flow-mediated dilation and higher nitroglycerin-mediated dilation at multiple time-points. When analyzed as continuous variables, 24-h mean arterial pressure variability was inversely associated with CD62+ EMPs; visit-to-visit DBP variability was inversely associated with flow-mediated dilation normalized by smooth muscle function and was positively associated with nitroglycerin-mediated dilation; and 24-h DBP variability was positively associated with nitroglycerin-mediated dilation. All associations were independent of age, gender, body mass index and mean BP. In conclusion, in this cohort of African Americans visit-to-visit and 24-h BP variability were associated with measures of endothelial injury, endothelial function and smooth muscle function. These results suggest that BP variability may influence the pathogenesis of CV disease, in part, through influences on vascular health.

One of the precursors to hypertension (HTN) is systemic inflammation which can lead to vascular dysfunction and eventually HTN. Aerobic exercise training (AEXT) is known to be an important intervention tool in the prevention and treatment of HTN, inflammation and vascular dysfunction. However, no study has yet determined the effect of AEXT on inflammation in normotensive versus non-normotensive participants. Purpose: To assess whether there are differential changes in the inflammatory marker C-reactive protein (CRP) in normotensive versus non-normotensive participants in response to AEXT. METHODS: 27 participants ages 41-71 were assessed. To be considered for inclusion participants had to be free of any cardiovascular disease, non-smoking and sedentary. After inclusion participants underwent blood draws, blood pressure (BP) measurements and aerobic exercise testing. Aerobic fitness was by measuring VO2max. Participants then underwent AEXT (3 days/week, 65% of VO2max, 40 minutes/day) for 6 months. Whole blood was sent to Quest Diagnostics for the measurement of serum levels of CRP. Results: CRP levels were not significantly different between normotensive (avg. BP=113/74 mmHg, N=13) and non-normotensive (avg. BP=131/82 mmHg, N=14) participants before (2.86 ± 0.82 vs. 3.65 ± 0.90 mg/L) or after (3.28 ± 1.00 vs. 2.75 ± 0.73 mg/L) AEXT. However, non-normotensive participants significantly (p≤0.016) lowered their CRP levels (3.65 ± 0.90 vs. 2.75 ± 0.73 mg/L), whereas the normotensive group did not. Neither group lowered their BP levels. Conclusion: AEXT is a proven tool for the treatment and prevention of HTN and systemic inflammation. Although AEXT did not lower BP in our setting, results suggest that AEXT may be an important tool in lowering systemic inflammation in non-normotensives who are at greater risk for cardiovascular disease.

Background: Chronic inflammation and elevated levels of C reactive protein (CRP) can lead to reduced bioavailability of endothelium relaxing factors such as Nitric Oxide (NO) and increased production of vasoconstrictive pro-inflammatory agents such as endothelin-1 (ET1). African Americans (AA) have impaired vasodilatory capabilities evident through reduced NO bioavailability. The purpose of this study was to investigate the potential differential racial effect of CRP on ET1 and NO. METHODS: AA and Caucasian (C) Human Umbilical Vein Endothelial Cells (HUVECs) were cultured and treated with 0, 25, 50, and 100μg/mL CRP. The secretion of ET1 and NO in HUVEC culture medium supernatant was assessed by ELISA and a modified Griess assay, respectively. Results: At baseline (0μg/mL CRP) there were no significant differences between AA and C in ET1 (457.5 ± 44.8 vs 420.6 ± 34.8 pg/mL) or NO (8.0 ± 1.4 vs 7.4 ± 1.2 μmol/L). Differences (p≤.05) were found at 50μg/mL CRP between ET1 and NO between C and AA HUVECs (ET1: 566.7 ± 17.7 vs 595.8 ± 73.6 pg/mL) (NO: 0 ± 0 vs 1.1 ± 1.0 μmol/L). There was a significant increase in ET1 in the AA HUVECs from 0μg/mL (457.5 ± 44.8 pg/mL) to 25μg/mL CRP (546.8 ± 39.8 pg/mL) while NO decreased significantly in AA HUVECs from 0μg/mL (8.0 ± 1.4 μmol/L) to 25μg/mL (0.5 ± 0.2 μmol/L), 50μg/mL (1.1 ± 1.0 μmol/L), and 100μg/mL CRP (0.1 ± 0.1 μmol/L). C HUVECs showed significant changes in ET1 between 0μg/mL (420.6 ± 34.8 pg/mL) and 50μg/mL CRP (566.7 ± 17.7 pg/mL) and in NO from 0μg/mL CRP (7.4 ± 1.2 μmol/L) to 25μg/mL (0.8 ± 0.5 μmol/L), 50μg/mL (0 ± 0 μmol/L), and 100μg/mL (0.9 ± 0.6 μmol/L). Without the influence of race, significant increases in ET1 production occurred from 0μg/mL CRP (439.0 ± 39.8 pg/mL) to 25μg/mL (512.0 ± 38.9 pg/mL) (p ≤ 0.001) and 50μg/mL CRP (581.2 ± 45.6 pg/mL) and significant decreases in NO (p ≤ 0.001) from 0μg/mL CRP (7.7 ± 1.3 μmol/L) to 25μg/mL CRP (0.6 ± 0.4 μmol/L), 50μg/mL CRP (0.5 ± 0.5 μmol/L), and 100 μg/mL CRP (0.5 ± 0.3 μmol/L). Conclusions: Our data show that differential CRP induced ET1 and NO production does not appear to contribute to the difference in hypertension prevalence between AA and C. Further investigation is needed to determine the cause of the racial differences in Hypertension between African Americans and Caucasians.

Background: African Americans tend to have greater carotid intima-media thickness (IMT), and are 60% more likely to have a stroke than Caucasians. Data on the effects of lifestyle intervention on carotid IMT in African Americans does not exist. The aim of our study was to assess the efficacy of 6 months of diet and exercise intervention on carotid IMT in sedentary African American adults. Methods: Nineteen African American subjects (15F/4M, 52 ± 6yrs) who were sedentary, non smoking, non diabetic, free of cardiovascular disease, not on antihypertensive or cholesterol medications underwent 6 weeks of dietary counseling under the supervision of a registered dietician and were required to follow an AHA low fat, low salt diet for the duration of the study. Compliance was assessed by a diet log (3 days/week). Subjects completed 6 months of supervised aerobic exercise training (3 days/week, 40 minutes/session at 65% of their estimated VO 2max ). Common carotid artery IMT was assessed using high resolution ultrasonography. Results: At baseline, IMT significantly correlated with age (r = 0.58, P = 0.003) and total cholesterol (r = 0.41, P = 0.04). At 6 months, there were significant changes in basal metabolic index (ΔBMI, -0.83 kg/m 2 , P = 0.01); Δtriglycerides (-13.7 mg/dL, P = 0.03) and Δfasting glucose (-7.2 mg/dL, P = 0.01). On repeated measures ANCOVA, the mean IMT were statistically significantly different (F (1, 15) = 7.999, P = 0.013) between before vs. after training (Mean ± SD; 0.617 ± 0.092mm vs. 0.572 ± 0.068mm), after adjusting for changed variables (ΔBMI, Δtotal cholesterol and Δmean arterial pressure) as covariates. Conclusion: Our preliminary study showed that 6 months of diet and exercise intervention reduced carotid IMT by ∼7.3% and improved the cardio-metabolic profile in sedentary African Americans. Reduction in IMT from early and effective lifestyle modification strategies may help to improve cerebrovascular health and prevent stroke in this at-risk stroke population.

Purpose: Evidence has accumulated to show that BP variability (BPV) has a striking relationship with cardiovascular (CV) risk and is predictive of future CV events, independent of mean BP. Despite the mounting evidence, scant attention has been paid to the ability of treatment modalities to attenuate BPV. To the best of our knowledge, no previous study has investigated the efficacy of non-pharmacologic treatment modalities on BPV. Therefore, the purpose of our study was to investigate the effects of aerobic exercise training (AEXT) on short- and long-term BPV in non-hypertensive and hypertensive African Americans. Methods: We compared the effects of a 6 month AEXT intervention (3 days/week, 65% of VO 2max , 40 min/session) on BPV in 16 non-hypertensive subjects (BP < 140/90 mmHg) and 14 hypertensive subjects (BP ≥ 140/90 mmHg or receiving antihypertensive monotherapy). Before and after AEXT, office BP was measured at 3 separate visits according to JNC7 guidelines and 24hr ambulatory BP monitoring (ABPM) was conducted. From ABPM, the standard deviation (STD), coefficient of variation (CV), and average real variability (ARV) of BP were calculated in 3 time frames (awake, sleep, and 24hr) to evaluate short-term BPV. The STD, CV, and average successive variability (ASV) of BP across 3 office visits were calculated to evaluate visit-to-visit variability, an index of long-term BPV. Results: In the hypertensive group, there was a significant reduction in systolic BPV (SBPV) during the awake period for STD (pre: 11.3 ± 2.3 vs. post: 10.9 ± 2.5 mmHg; p < 0.03) and CV (pre: 8.5 ± 1.4 vs. post: 7.2 ± 1.2%; p < 0.02); and during the 24hr period for STD (pre: 12.6 ± 2.0 vs. post: 10.9 ± 2.5 mmHg; p < 0.04) and CV (pre: 9.6 ± 1.3 vs. post: 8.2 ± 1.5%; p < 0.03). Visit-to-visit variability in SBP for STD (pre: 7.8 ± 6.2 vs. post: 4.8 ± 4.4 mmHg), CV (pre: 6.0 ± 4.9 vs. post: 3.6 ± 3.1%), and ASV (pre: 5.2 ± 3.9 vs. post: 3.7 ± 3.0 mmHg) were also reduced post-AEXT, but did not reach statistical significance. In the non-hypertensive group, all measures of BPV were increased post-AEXT with the increase reaching statistical significance for awake diastolic BPV (DBPV) for STD (pre: 7.2 ±1.4 vs. post: 8.3 ± 1.9 mmHg; p < 0.02), CV (pre: 9.3 ±2.1 vs. post: 10.8 ± 2.2%; p < 0.02), and ARV (pre: 6.8 ±1.3 vs. post: 7.6 ± 1.6 mmHg; p < 0.04). Between group comparisons of non-hypertensive and hypertensive groups showed significant between group differences in the magnitude of change in awake SBPV (STD and CV; p < 0.007), awake DBPV (STD; p < 0.05), 24hr SBPV (STD and CV; p < 0.02), 24hr DBPV (CV; p < 0.04), and visit-to-visit variability in SBP (STD and CV; p < 0.05). Conclusion: These preliminary findings provide some evidence that AEXT may reduce BPV in hypertensive African Americans, however the increase in BPV in the non-hypertensive group brings into question the potential efficacy of AEXT in the treatment of BPV. Future investigations are needed.

Adherence levels to an aerobic exercise training intervention in African Americans have no adverse impact on favorable endothelial adaptations Dianne M. Babbitt, Amanda M. Perkins, Keith M. Diaz, Deborah L. Feairheller, Kathleen M. Sturgeon, Praveen Veerabhadrappa, Sheara T. Williamson, Jan Kretzschmar, Chenyi Ling, Hojun Lee, Heather Grimm, Michael D. Brown. Columbia University, New York, NY, United States; Missouri State University, Springfield, MO, United States; Notre Dame of Maryland University, Baltimore, MD, United States; Shippensburg University, Shippensburg, PA, United States; Temple University, Philadelphia, PA, United States; University of Illinois at Chicago, Chicago, IL, United States; University of Pennsylvania, Philadelphia, PA, United States; Ursinus College, Collegeville, PA, United States