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, we reported six 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; carotid artery intima-media thickness (IMT), nitroglycerin-mediated dilation (NMD), ambulatory BP, and office BP. Sedentary African American adults (53.4±6.2yrs;21F,5M) showed improved vascular health, but no change in BP. Carotid artery IMT decreased 6.4%, plasma NO levels increased 76.6%, plasma EMP levels decreased, percent FMD increased 59.6%, and FMD/NMD ratio increased 36.2% (P <0.05 for all). Six months of aerobic exercise training is sufficient to elicit improvements in vascular structure and function in African Americans, even without improvements in BP measures or NMD (i.e., smooth muscle function). To our knowledge, this is the first study to report such findings in African Americans.
Vascular health; endothelial function; flow-mediated dilation; ambulatory blood pressure monitoring; blood pressure; exercise; African Americans
African American women present an understudied population in menopause research, yet face greater post-menopausal challenges associated with mortality than their white peers. We investigated the effect of a mild-intensity aerobic exercise training program on markers of mortality risk in both pre- and post-menopausal African American women.
16 pre- and 19 post-menopausal 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 pre- and post-menopausal groups only differed in terms of age, LDL, and total cholesterol levels, with the latter two being higher in the post-menopausal 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 pre-menopausal group.
Mild-intensity aerobic exercise training was successful in improving some markers of cardiovascular disease and mortality in post-menopausal women. Higher levels of exercise intensity or perhaps additional interventions may need to be considered in this population to further decrease mortality risk.
menopause; aerobic exercise; endothelial microparticles; African American; kidney function
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.
Pre-hypertension; Nitric oxide; High-sensitivity C-reactive protein; African-Americans
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.
Blood pressure variability; endothelial function; endothelial microparticles; smooth muscle function; blood pressure; ambulatory blood pressure monitoring
Office-blood pressure (BP) measurements alone overlook a significant number of individuals with masked-hypertension (office-BP: 120/80 -139/89 mmHg & 24-hr ambulatory BP monitoring, ABPM: daytime >135/85 mmHg or nighttime >120/70 mmHg). Diminished endothelial function contributes to the pathogenesis of hypertension. To better understand the pathophysiology involved in the increased cardiovascular disease (CVD) risk associated with masked-hypertension, we estimated the occurrence, assessed the endothelial function, compared plasma levels of inflammatory markers, white blood cell count, tumor necrosis factor-α and high sensitivity C-reactive protein (hsCRP) and examined the possible relationship between endothelial function and inflammatory markers in apparently healthy prehypertensive (office-BP: 120/80-139/89 mmHg) African-Americans.
50 African-Americans who were sedentary, non-diabetic, non-smoking, devoid of CVD were recruited. Office-BP was measured according to JNC-7 guidelines to identify prehypertensives in whom ABPM was then assessed. Fasting plasma samples were assayed for inflammatory markers. Brachial artery flow-mediated dilation at rest and during reactive hyperemia was measured in a subset of prehypertensives.
Subjects in the masked-hypertension sub-group had a higher hsCRP (P=0.04) and diminished endothelial function (P=0.03) compared to the true-prehypertensive sub-group (office-BP: 120/80-139/89 mmHg & ABPM: daytime <135/85 mmHg or nighttime <120/70 mmHg). Regression analysis showed that endothelial function was inversely related to hsCRP amongst the masked-hypertensive sub-group (R2=0.160; P=0.04).
Masked-hypertension was identified in 58% of African-Americans which suggests that a masking phenomenon may exist in a sub-group of prehypertensives who also seem to have a diminished endothelial function that could be mediated by an elevated subclinical inflammation leading to the increased CVD.
Masked Hypertension; Prehypertension; Endothelial Dysfunction; Flow-mediated Dilation; high sensitivity C-Reactive protein; 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.
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.
Blood pressure variability; high sensitivity C-reactive protein; African Americans; tumor necrosis factor-alpha; white blood cells; inflammation
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.
The effects of exercise training on nocturnal blood pressure (BP) dipping status remain unclear. African Americans have the highest prevalence of non-dippers compared to other racial/ethnic populations. In this 6-month study we tested the hypothesis that long-term aerobic exercise training would increase the levels of nocturnal BP dipping in African American non-dippers.
Methods and Results
We recruited African Americans who were non-diabetic, non-smoking and free of cardiovascular (CV) and renal disease. For this analysis, only African Americans with a non-dipping profile, defined as those with absence of a nocturnal decline in systolic or diastolic BP (< 10% of daytime values) which was determined by ambulatory BP monitoring. A pre-post design was employed with baseline and final evaluation including office blood pressure measurement, 24-hour ambulatory blood pressure monitoring, fasted blood sampling, and graded exercise testing. Participants engaged in 6 months of supervised aerobic exercise training (AEXT). Following the AEXT intervention, there were significant increases in systolic BP dipping (baseline: 5.8 ± 3.9% vs. final: 9.4 ± 6.1%, p=0.0055) and pulse pressure dipping (Baseline: −3.1% ± 6.6% vs. final: 5.0% ± 12.8%, p=0.0109). Of the 18 participants with a non-dipping profile at baseline, 8 were non-classified as non-dippers after the AEXT intervention. There were no significant changes in office SBP/DBP following the AEXT intervention.
This study suggests that the non-dipping pattern of ambulatory BP can be improved by chronic AEXT in African American non-dippers and regardless of a change in 24-hr average BP. This finding may be clinically important because of the target organ implication of non-dipping nocturnal BP.
dipping status; exercise; nocturnal blood pressure; African American
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.
African American; NADPH oxidase; HUVECs
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.
African Americans; Sub-maximal Exercise; Antioxidants; Nitric Oxide; Superoxide Dismutase; Total Antioxidant Capacity
Oxidative stress that is mediated through NADPH oxidase activity plays a role in the pathology of hypertension, and aerobic exercise training reduces NADPH oxidase activity. The involvement of genetic variation in the p22phox (CYBA) subunit genes in individual oxidative stress responses to aerobic exercise training has yet to be examined in Pre and Stage 1 hypertensives.
Ninety-four sedentary Pre and Stage 1 hypertensive adults underwent 6 months of aerobic exercise training at a level of 70% V̇O2max to determine whether the CYBA polymorphisms, C242T and A640G, were associated with changes in urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), urinary nitric oxide metabolites (NOx), and plasma total antioxidant capacity (TAC).
Demographic and subject characteristics were similar among genotype groups for both polymorphisms. At baseline, a significant (P = 0.03) difference among the C2424T genotype groups in 8-iso-PGF2α levels was detected, with the TT homozygotes having the lowest levels and the CC homozygotes having the highest levels. However, no differences were found at baseline between the A640G genotype groups. After 6 months of aerobic exercise training, there was a significant increase in V̇O2max (P < 0.0001) in the entire study population. In addition, there were significant increases in both urinary 8-iso-PGF2α (P = 0.002) and plasma TAC (P = 0.03) levels and a significant decrease in endogenous urinary NOx (P < 0.0001). Overall, aerobic exercise training elicited no significant differences among genotype groups in either CYBA variant for any of the oxidative stress variables.
We found that compared with CYBA polymorphisms C242T and A640G, it was aerobic exercise training that had the greatest influence on the selected biomarkers; furthermore, our results suggest that the C242T CYBA variant influences baseline levels of urinary 8-iso-PGF2α but not the aerobic exercise-induced responses.
OXIDATIVE STRESS; AEROBIC EXERCISE; CYBA GENE; NITRIC OXIDE; ISOPROSTANES
African Americans have endothelial dysfunction which likely contributes to their high prevalence of hypertension. Endothelial cell responses to stimuli could play a role in the development of endothelial dysfunction and hypertension. High physiological levels of vascular laminar shear stress can profoundly alter endothelial cell phenotype. It is not known whether there are race-dependent endothelial cell responses to laminar shear stress.
Endothelial cell; shear stress; exercise; African American; oxidative stress; inflammation
African Americans (AA) tend to have heightened systemic inflammation and endothelial dysfunction. Endothelial microparticles (EMP) are released from activated/apoptotic endothelial cells (EC) when stimulated by inflammation. The purpose of our study was to assess EMP responses to inflammatory cytokine (TNF-α) and antioxidant (superoxide dismutase, SOD) conditions in human umbilical vein ECs (HUVECs) obtained from AA and Caucasians. EMPs were measured under four conditions: control (basal), TNF-α, SOD, and TNF-α + SOD. Culture supernatant was collected for EMP analysis by flow cytometry and IL-6 assay by ELISA. IL-6 protein expression was assessed by Western blot. AA HUVECs had greater EMP levels under the TNF-α condition compared to the Caucasian HUVECs (6.8 ± 1.1 vs 4.7% ± 0.4%, P = 0.04). The EMP level increased by 89% from basal levels in the AA HUVECs under the TNF-α condition (P = 0.01) compared to an 8% increase in the Caucasian HUVECs (P = 0.70). Compared to the EMP level under the TNF-α condition, the EMP level in the AA HUVECs was lower under the SOD only condition (2.9% ± 0.3%, P = 0.005) and under the TNF-α + SOD condition (2.1% ± 0.4%, P = 0.001). Basal IL-6 concentrations were 56.1 ± 8.8 pg/mL/μg in the AA and 30.9 ± 14.9 pg/mL/μg in the Caucasian HUVECs (P = 0.17), while basal IL-6 protein expression was significantly greater (P < 0.05) in the AA HUVECs. These preliminary observational results suggest that AA HUVECs may be more susceptible to the injurious effects of the proinflammatory cytokine, TNF-α.
endothelium; inflammation; endothelial microparticles; African Americans
African American ethnicity is an independent risk factor for exaggerated oxidative stress, which is related to inflammation, hypertension, and cardiovascular disease. Recently, we reported that in vitro oxidative stress and inflammation levels differ between African American and Caucasian human umbilical vein endothelial cells (HUVECs), African American HUVECs having higher levels of both. However, it remains to be shown whether the cells would respond differently to external stimuli.
We used a cone and plate viscometer to apply laminar shear stress (LSS) as an aerobic exercise mimetic to compare the responses by race. HUVECs were exposed to static conditions (no LSS), low LSS (5 dyne/cm2), and moderate LSS (20 dyne/cm2).
It was found that African American HUVECs had higher levels of oxidative stress under static conditions, and when LSS was applied protein expression levels (NADPH oxidase NOX2, NOX4 and p47phox subunits, eNOS, SOD2, and catalase) and biomarkers (NO, SOD, and total antioxidant capacity) were modulated to similar levels between race.
African American HUVECs may be more responsive to LSS stimulus indicating that aerobic exercise prescriptions may be valuable for this population since the potential exists for large in vivo improvements in oxidative stress levels along the endothelial layer in response to increased shear flow.
shear stress; African American; NADPH oxidase; HUVECs; oxidative stress
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.
Aging; Oxidative Stress; African Americans; Fitness; BMI