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Journal of human hypertension  2013;27(11):671-677.
The purpose of this study was to investigate the association of visit-to-visit and 24-h 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 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. Significantly lower CD31+CD42− endothelial microparticles were found in participants with high visit-to-visit SBP variability or high 24-h 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+ endothelial microparticles; 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, BMI, 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 cardiovascular disease, in part, through influences on vascular health.
PMCID: PMC3745784  PMID: 23615389
Blood pressure variability; endothelial function; endothelial microparticles; smooth muscle function; blood pressure; ambulatory blood pressure monitoring
2.  Clinical Risk Factors Demonstrate an Age-dependent Relationship with Oxidative Stress Biomarkers in African Americans 
Ethnicity & disease  2010;20(4):403-408.
To examine the interaction of oxidative stress biomarkers with age, and also factors that influence oxidative stress such as body mass index (BMI) and fitness in a population of individuals with established higher risk of cardiovascular disease, African Americans.
Blood samples were obtained from healthy college-age and middle-age to older African Americans. Participants underwent a graded exercise test. Superoxide dismutase (SOD) activity, total antioxidant capacity and thiobarbituric acid reactive substances (TBARS) levels were measured.
TBARS levels were significantly (P=.001) lower in young participants relative to middle-age to older participants. SOD activity was significantly (P=.001) lower in middle-age to older participants with low fitness relative to participants with normal fitness, and lower (P=.04) in middle-age to older participants that were overweight relative to normal weight participants.
In a healthy middle-age to older population of African Americans, BMI and fitness are crucial for maintaining a healthy endothelium.
PMCID: PMC3103990  PMID: 21305829
Aging; Oxidative Stress; African Americans; Fitness; BMI
3.  Endothelial Activation Microparticles and Inflammation Status Improve with Exercise Training in African Americans 
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 in VO2 max significantly 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.
PMCID: PMC3652180  PMID: 23691280
4.  Racial differences in oxidative stress and inflammation: in vitro and in vivo 
African American race is an independent risk factor for enhanced oxidative stress and inflammation. We sought to examine whether oxidative stress and inflammatory markers that are typically measured in human also differ by race in cell culture. We compared levels between African American and Caucasian young adults and then separately in human umbilical vein endothelial cells (HUVECs) from both races. We found heightened oxidative stress and inflammation in the African Americans both in vitro and in vivo. African American HUVECs showed higher nitric oxide (NO) levels (10.8±0.4 vs 8.8±0.7umol/L/mg, P=0.03), IL-6 levels (61.7±4.2 vs 23.9±9.0pg/mg, P=0.02), and lower superoxide dismutase activity (15.6±3.3 vs. 25.4±2.8U/mg, P=0.04), and also higher protein expression (p<0.05) of NADPH oxidase subunit p47phox, isoforms NOX2 and NOX4, endothelial nitric oxide synthase, inducible NOS, as well as IL-6. African American adults had higher plasma protein carbonyls (1.1±0.1 vs 0.8±0.1nmol/mg, P=0.01) and antioxidant capacity (2.3±0.2 vs 1.1±0.3mM, P=0.01). This preliminary translational data demonstrates a racial difference in HUVECs much like that in humans, but should be interpreted with caution given its preliminary nature. It is known that racial differences exist in how humans respond to development and progression of disease, therefore these data suggest that ethnicity of cell model may be important to consider with in vitro clinical research.
PMCID: PMC3077905  PMID: 21348953
African American; NADPH oxidase; HUVECs
5.  Prehypertensive African-American Women Have Preserved Nitric Oxide and Renal Function but High Cardiovascular Risk 
Kidney & Blood Pressure Research  2010;33(4):282-290.
African-Americans, in particular women, exhibit disproportionate levels of hypertension, inflammation, and oxidative stress compared to other ethnic groups. The relationship between prehypertension, renal function, inflammation, and oxidative stress was examined.
Twenty-eight African-American women (53.5 ± 1.1 years) followed an AHA diet and then underwent 24-hour ambulatory BP (ABP) monitoring. Urinary albumin (uAlb), serum and urinary creatinine, glomerular filtration rate (GFR), 24-hour urinary Na+ excretion, plasma superoxide dismutase, total antioxidant capacity (TAC), urinary (uNOx) and plasma (pNOx) nitric oxide levels, and high-sensitivity C-reactive protein (hsCRP) were measured.
When the group was divided by average 24-hour ABP into optimal and nonoptimal groups, a significant difference existed between the groups for uNOx (p = 0.001; nonoptimal: 933.5 ± 140.4, optimal: 425.0 ± 52.6 μmol/gCr), and for hsCRP (p = 0.018, nonoptimal: 3.9 ± 0.7, optimal: 1.9 ± 0.6 mg/l). Significant inverse relationships existed between hsCRP and uNOx and between uAlb and pNOx in the non-optimal group, between GFR and pNOx in the entire group, and positive association existed between TAC and uNOx in the optimal group.
These results suggest that in African-American women as BP levels rise toward hypertension, the NO/NOS balance may be associated with renal function, and may have implications for CV risk based on their hsCRP levels.
PMCID: PMC3214938  PMID: 20628261
Pre-hypertension; Nitric oxide; High-sensitivity C-reactive protein; African-Americans
High blood pressure (BP) levels in African Americans elicit vascular inflammation resulting in vascular remodeling. BP variability (BPV) correlates with target organ damage. We aimed to investigate the relationship between inflammatory markers and BPV in African Americans.
36 African Americans underwent 24-hr ambulatory BP monitoring (ABPM). BPV was calculated using the average real variability (ARV) index. Fasting blood samples were assayed for high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α) and white blood cell (WBC) count.
Significant association between hs-CRP and 24-hr systolic variability (r = 0.50; p = 0.012) and awake systolic variability (r = 0.45; p =0.02) was identified after adjusting for age, BMI and 24-hr mean BP. ABPM variables were compared between the hs-CRP tertile groups. In Post-hoc analysis, there was a significant difference in 24-hr and awake periods for both systolic and diastolic variability among the groups. TNF-α and WBC count showed no associations with ABPM variables.
hs-CRP is associated with systolic variability and higher levels of hs-CRP are related with greater BPV. Higher inflammatory status influences wider fluctuations in systolic BP which in turn could facilitate early progression to target organ damage independent of absolute BP levelsin African Americans.
PMCID: PMC2945908  PMID: 20885987
Blood pressure variability; high sensitivity C-reactive protein; African Americans; tumor necrosis factor-alpha; white blood cells; inflammation
7.  Racial Differences in the Time-Course Oxidative Stress Responses to Acute Exercise 
African Americans have disproportionate levels of cardiovascular disease and oxidative stress. The purpose of our study was to examine racial differences between African American and Caucasian adults in time-course oxidative stress responses to a treadmill test. After a 12-hr fast, 18 participants (9 of each ethnic group; 21 ± 0.4 yrs) completed a submaximal treadmill test and underwent serial blood draws: Pre, Post (within 2 min), 30, 60, and 120 min after exercise. At each time-point, superoxide dismutase (SOD, U/mL), total antioxidant capacity (TAC, mM), protein carbonyls (PC, nmol/mg), and thiobarbituric acid-reactive substance (TBARs, μmol/L) were measured. We found no difference between groups for blood pressure, BMI, or exercise capacity (as measured by volume of oxygen consumed, VO2 max). African Americans had significantly (p < 0.05) higher SOD (Pre: 5.45 ± 0.4 vs. 3.69 ± 0.69; 60 min: 8.99 ± 0.7 vs. 4.23 ± 0.6; 120 min: 9.69 ± 1.6 vs. 3.52 ± 0.7), TAC (Pre: 2.31 ± 0.25 vs. 1.16 ± 0.3; Post: 2.39 ± 0.2 vs. 1.34 ± 0.2; 30 min: 2.29 ± 0.2 vs. 1.09 ± 0.2), and PC (Pre: 1.09 ± 0.1 vs. 0.82 ± 0.1; Post: 1.14 ± 0.1 vs. 0.81 ± 0.1; 30 min: 1.13 ± 0.1 vs. 0.85 ± 0.1; 60 min: 1.06 ± 0.1 vs. 0.81 ± 0.05), but not TBARs. Between groups, only SOD exhibited a different time-course response: levels for African Americans rose steadily throughout the 120 min, while levels for Caucasians peaked at 30 min and by 120 min had returned to pre-exercise levels. Race had a greater effect on oxidative stress responses than submaximal exercise did. African Americans had significantly higher TAC, SOD, and PC levels compared to Caucasians.
PMCID: PMC3118095  PMID: 21691463
African Americans; Sub-maximal Exercise; Antioxidants; Nitric Oxide; Superoxide Dismutase; Total Antioxidant Capacity
8.  Increased Nitric Oxide and Attenuated Diastolic Blood Pressure Variability in African Americans with Mildly Impaired Renal Function 
We investigated the relationship between renal function, blood pressure variability (BPV), and nitric oxide (NO) in a group of African Americans with normal or mildly impaired renal function. 24-hour ambulatory blood pressure monitoring was performed, NO measured, and glomerular filtration rate (GFR) calculated in 38 African Americans. Participants were categorized as having normal (GFR > 90 mL/min per 1.73 m2) or mildly impaired (GFR 60–89 mL/min per 1.73 m2) renal function. Diastolic BPV was significantly lower in the mildly impaired renal function group. Regression analyses revealed a significant positive association between GFR and diastolic BPV for the entire study group. Plasma NO levels were significantly higher in the mildly impaired renal function group and negatively correlated with diastolic BPV. In conclusion, diastolic BPV was reduced in African Americans with mildly impaired renal function, which may be the result of increased NO production. These results conflict with previous findings in diseased and nonblack populations and could provide rationale for studying BPV early in the disease state when BP-buffering mechanisms are still preserved.
PMCID: PMC3025367  PMID: 21274440
9.  The relationship of oxidative stress and cholesterol with dipping status before and after aerobic exercise training 
Blood pressure  2009;18(4):171-179.
The purpose of this study was to examine the effects of aerobic exercise training (AEXT) on dipping status in pre-hypertensive and stage-1 hypertensive individuals. A secondary purpose was to evaluate whether AEXT alters oxidative stress and endothelial biomarkers correlated to dipping status.
Twenty-three subjects underwent 24-h ambulatory blood pressure monitoring at baseline and after 6 months of AEXT. AEXT consisted of training at 70% VO2max 3 days/week for 6 months. Total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein (LDL)-cholesterol, oxidized LDL (ox-LDL), triglycerides, urinary and plasma nitric oxide end-products, superoxide dismutase and 8-iso-PGF2α were measured before and after AEXT. Statistically, ANOVA and linear regression were used.
Before and after AEXT, there were no significant differences between dippers and non-dippers in any of the biomarkers except for total cholesterol following AEXT. In a sub-analysis following AEXT, 14 subjects retained their original dipping status, five subjects changed from dippers to non-dippers and four subjects changed from non-dippers to dippers. Significant differences existed between these groups in changes in total and LDL-cholesterol, ox-LDL, 8-iso-PGF2α and % Dip.
Changes in cholesterol levels but not oxidative stress or endothelial biomarkers were related to changes in BP variables following AEXT in dippers and non-dippers.
PMCID: PMC2922419  PMID: 19544106
Aerobic exercise; ambulatory blood pressure monitoring; dipper; non-dipper; hypertension; oxidative stress

Results 1-9 (9)