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1.  The Effect of Short Term Vitamin D Supplementation on the Inflammatory and Oxidative Mediators of Arterial Stiffness 
Health  2014;6(12):1503-1511.
Vitamin D deficiency has been implicated as a potential risk factor for cardiovascular disease. The high rate of vitamin D deficiency (<30 ng/ml) exhibited by African Americans may account for some of the excess prevalence of cardiovascular morbidity and mortality in this vulnerable US population. Vitamin D supplementation may reduce the risk of cardiovascular disease by ameliorating the onset and progression of arterial stiffness, a strong predictor of cardiovascular mortality, usually assessed by pulse wave velocity and augmentation index. Very few prospective studies have evaluated the effect of vitamin D supplementation on the inflammatory and oxidative stress mediators of arterial stiffness.
In a double blind randomized placebo controlled study we evaluated the effect of a monthly dose of 100,000IU of vitamin D3 for three months on the level of serum 25(OH)D, intact parathyroid hormone (PTH), urinary isoprostane, adipocyte cytokine expression and arterial stiffness among 130 overweight and obese (BMI > 25) African Americans with elevated blood pressure (130 - 150/85 - 100 mmHg) and low serum vitamin D level (10 - 25 ng/ml).
There was a significant increase in the serum 25(OH)D levels to a mean level of 34.5 ng/ml (SD = 7.1) with the intervention (p < 0.001). The increase in 25(OH)D levels was associated with a significant decrease in the serum level of intact PTH (p = 0.02), mean urinary isoprostane (p = 0.02) and adipocyte cytokine expression. Although the increase in the 25(OH)D levels was not associated with any significant change in the Pulse Wave Velocity (PWV) in the overall study sample, it was associated with a significant decrease in the augmentation index among the participants with the highest tertile of urinary isoprostane (p = 0.007).
We concluded that vitamin D supplementation increased serum 25(OH)D levels, decreased intact PTH level and the levels of select inflammatory and oxidative stress mediators of arterial stiffness. Longer term prospective studies are warranted to evaluate the effect of high dose vitamin D supplementation on arterial stiffness.
PMCID: PMC4260399  PMID: 25505940
Vitamin D; Overweight; Hypovitaminosis D
3.  Association between Vitamin D and Adiponectin and Its Relationship with Body Mass Index: The META-Health Study 
Background: Low vitamin D and adiponectin levels are both associated with obesity and cardiovascular disease. Previous studies have indicated that vitamin D levels are directly associated with adiponectin, and that this association varies across body mass index (BMI) categories; stronger with increasing BMI. Few studies examined this association in African-Americans (AA), known to have lower levels of vitamin D and adiponectin, and in whites.
Methods: We assessed whether serum vitamin D is associated with serum adiponectin in a biracial population-based sample. Cross-sectional analyses were performed on 426 non-diabetic participants (218 whites and 208 AA) from the META-Health Study, a random sample from the metro Atlanta. Age-adjusted correlations and multivariable linear regression were used for analyses. We investigated the effect modification of the BMI categories of lean, overweight, and obese as defined by standard cut-points (25 and 30 kg/m2).
Results: The mean (SD) age of our study sample was 50.5 (9) years. The mean (SD) levels of vitamin D were 27.4 (9.8) ng/mL in white women, 25.5 (9.3) ng/mL in white men, 16.9 (7.3) ng/mL in AA women, and 18.8 (7.3) ng/mL in AA men. The mean (SD) levels of adiponectin were 17.0 (17.1) μg/mL in white women, 9.9 (11.3) μg/mL in white men, 6.6 (4.8) μg/mL in AA women, and 9.4 (11.6) μg/mL in AA men. Among lean white women (n = 63), there was a significant direct association between vitamin D and adiponectin (β = 0.02, p = 0.04) after adjustment for age, systolic blood pressure, HDL-cholesterol, triglycerides, income, and season of blood drawing. On the contrary, in lean AA women (n = 23), there was a significant inverse association (β = −0.06, p = 0.01).
Conclusion: The association of vitamin D and adiponectin is dependent on race, gender, and BMI category. Among lean white women, there was a significant direct association, whereas in lean AA women the association was inverse. No association was present among obese individuals.
PMCID: PMC4196512  PMID: 25353014
vitamin D; adiponectin; obesity; minorities; African-Americans; obesity
4.  A Genetic Risk Variant for Myocardial Infarction on Chromosome 6p24 Is Associated With Impaired Central Hemodynamic Indexes 
American journal of hypertension  2012;25(7):797-803.
Genome-wide association studies (GWAS) have identified novel variants associated with myocardial infarction (MI) in Caucasians. We hypothesized that those variants whose mechanism of risk is currently unknown, confer risk via pathways mediating arterial wave reflections which is an increasingly recognized risk factor for cardiovascular disease.
Single-nucleotide polymorphisms (SNPs) at eight MI risk loci were genotyped and correlated with noninvasively determined pulse wave analysis (PWA)-derived central hemodynamic indexes (augmentation index (AIx); augmented pressure (AP); time to reflected wave (TrW) and central systolic blood pressure (SBP) and diastolic BP (DBP)) in two independent Caucasian populations including (i) those free of measured cardiovascular risk factors (n = 133) and (ii) a community-based population (n = 270).
Of the eight SNPs examined in the healthy group, the variants at loci 6p24 (AIx and AP both P < 0.001, TrW P = 0.02) and 21q22 (AIx P = 0.002, TrW P = 0.037) were significantly associated with PWA indexes. In the replication group, only the 6p24 variant correlated with these phenotypes (AIx P = 0.005, AP P = 0.049, TrW P = 0.013). In the pooled population (n = 403), no new associations were identified but the association with 6p24 and AIx remained significant even after Bonferroni correction and adjustment for covariates including age, mean arterial pressure, height, gender, glucose, cholesterol, body mass index (BMI), and smoking (AIx (P = 0.03)). Each copy of the risk allele C increased the AIx by 3.5%.
The GWAS discovered MI risk variant at 6p24 in the protein phosphatase 1 regulator gene (PHACTR1) is associated with adverse arterial wave reflection indexes and may mediate MI risk through this pathway.
PMCID: PMC4127881  PMID: 22513829
6p24; augmentation index; blood pressure; elasticity; genetic; genomic; GWAS; hypertension; myocardial infarction; SNP; stiffness
5.  Effect of Meditation on Endothelial Function in Black Americans with Metabolic Syndrome: A Randomized Trial 
Psychosomatic medicine  2013;75(6):591-599.
Psychological stress may play a role in metabolic syndrome. A consequence of metabolic syndrome is endothelial dysfunction, which is also influenced by psychological stress. We sought to compare the effect of consciously resting meditation (CRM), a sound (mantra)-based meditation, with a control intervention of health education (HE) on endothelial function in the setting of metabolic syndrome.
Sixty-eight black Americans with metabolic system risk factors (age 30 to 65 years) were randomized to either CRM (N=33), or to HE (N=35); interventions were matched for frequency and duration of sessions and lasted 12 months. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD%) at baseline, 6 and 12 months. Arterial elasticity, metabolic risk factors, psychosocial and behavioral variables were secondary endpoints.
Although FMD % improved in the CRM group over 12 months, this increase was not significantly higher than in the HE group (p=0.51 for the interaction between group and time). Non-endothelium dependent dilation and arterial elasticity did not change in either group. Most metabolic syndrome risk factors showed beneficial trends in the CRM group only. A risk factor score counting the number of metabolic syndrome components decreased in the CRM group but not in the control HE group (p=0.049 for the interaction between treatment group and time).
Among black Americans with metabolic syndrome risk factors, CRM, a sound-based meditation, did not improve endothelial function significantly more than a control intervention of health education. CRM resulted in favorable trends in metabolic syndrome risk factors which were examined as secondary outcomes.
PMCID: PMC3774317  PMID: 23788695
Endothelium; stress; metabolic syndrome; obesity
6.  A comprehensive cardiovascular disease lifestyle treatment controlled trial among high-risk African Americans 
The purpose of this study was to assess the effects of a comprehensive lifestyle intervention on modifiable cardiovascular risk factors among high-risk African Americans.
The study included a randomized treatment/controlled intervention trial among 136 African Americans residing in Atlanta, GA who were overweight and had elevated blood pressure. The treatment group was exposed to 3-months of a multi-component intervention and the control to an abbreviated 6-week intervention after the completion of the treatment group’s intervention. The main outcomes included mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), mean waist circumference, mean body mass index (BMI), mean number of times exercise per week, mean number of servings of fruits and vegetables per day, and mean level of daily stress. Data were collected at baseline and at 6-month follow-up. Separate linear regressions were used with an established significance level of p < 0.05.
Results revealed significant net improvement in treatment group when compared to controls in waist circumference, BMI, times weekly exercise, servings of fruit and vegetables per day (p < 0.001, 0.04, 0.02, 0.002, respectively). Diastolic blood pressure also significantly improved within the treatment group for overall hypertensives from baseline to 6-month follow-up (90.9 mmHg to 83.1 mmHg, p = 0.002).
These results show that a comprehensive lifestyle intervention can improve cardiovascular risk factor profile among high risk African Americans. Caregivers should encourage patients to participate in such programs and public health policymakers should allocate resources to community based health oriented organizations to implement comprehensive lifestyle program.
PMCID: PMC4062311  PMID: 24955290
African American; Cardiovascular Disease Risk Factors; Lifestyle Modification
7.  Social Determinants of Cardiovascular Health among Black and White Women Residing in Stroke Belt and Buckle Regions of the South 
Ethnicity & disease  2014;24(2):133-143.
To assess the associations of social determinants on cardiovascular health among White and Black residing in Stroke Belt (urban) and Stroke Buckle (rural) regions of the South.
A cross-sectional observational analysis based on a random digit-dial telephone survey of a representative sample of White and Black adults residing in urban and rural Georgia conducted from 2004–2005. Separate logistic regression analyses examined the effects of social determinants on cardiovascular health within and between White and Black women and within and between urban and rural residential location. The main outcome measure was poor cardiovascular health defined as ≥2 self-reported clinical cardiovascular disease risk factors (hypertension, diabetes, elevated cholesterol, overweight or obese). Social determinants were defined as socioeconomic status (SES), general daily stress, racial discrimination, and stress due to exposure to racial discrimination. Significance was established as a two-tailed P,.05.
A total of 674 White and Black women aged 18–90 years were included in the sample. Results showed Black women with lower SES had worse cardiovascular health than White women in both rural and urban areas (rural odds ratio [OR] 2.68; confidence interval [CI] 1.44, 4.90; P=.001; urban OR=2.92; CI=1.62, 5.23; P=.0003). White women reporting high or very high exposure to general daily stress where more likely to have worse cardiovascular health than White women reporting very little to no daily stress (OR =2.85; CI=1.49, P5.44; P5.001).
Our findings demonstrate the importance of social determinants associated with cardiovascular health. Tailored cardiovascular risk reduction intervention is needed among lower SES Black women in Stroke Belt and Buckle regions of the South, as well as stress-reduction intervention among White women in the South. (Ethn Dis. 2014;24[2]:133–143)
PMCID: PMC4051397  PMID: 24804357
Black; White; Women; Cardiovascular Risk Factor; Social Determinants; Stroke; South
8.  The Association between Depression and Leptin is Mediated by Adiposity 
Psychosomatic medicine  2012;74(5):483-488.
Depression and obesity share overlapping psychosocial and pathophysiological etiologies. Animal models suggest that impaired leptin production, or leptin resistance, may contribute to depression. The link between leptin and depression could be mediated by obesity, which is more common in depression and increases leptin production.
We administered the Beck Depression Inventory II (BDI-II) to 537 participants (mean age 51, standard deviation 9 years, 49% African American, 61% female) enrolled in the Morehouse-Emory Partnership to Eliminate Cardiovascular Health Disparities (META-Health) study. BDI-II scores of 0–13 indicated minimal to no depression, 14–19 mild depression, and 20–63 moderate to severe depression. Levels of leptin were examined as continuous, log-transformed values.
Participants with moderate to severe depression had higher levels of leptin (median 37.7, interquartile range [17.6–64.9] ng/mL) than those with mild depression (22.9 [7.0–57.9] ng/mL) or minimal to no depression (19.8 ng/mL, [7.8–39.1], p=0.003). Participants with moderate to severe depression had higher body mass index (BMI) than those with mild or minimal depression (33±8 vs. 31±9 vs. 29±7 kg/m2, p<0.001). After multivariate adjustment for age, gender, race, smoking, history of hypertension and diabetes, blood pressure, lipids, and CRP, the BDI-II score remained a significant predictor of leptin levels (β=0.093, p=0.01). Further adjustment for BMI eliminated the association between the BDI-II score and leptin (β=0.03, p=0.3). Adjusting for waist circumference in place of BMI revealed similar findings.
The association between depression and leptin appears to be mediated by increased adiposity in depressed individuals. Leptin may represent a pathway through which obese individuals may develop depression, or a common mechanism leading to both depression and obesity.
PMCID: PMC3951007  PMID: 22582314
leptin; depression; adiposity; adiponectin
9.  Association between Depression and Inflammation – Differences by Race and Sex: The META-Health Study 
Psychosomatic medicine  2011;73(6):462-468.
To test whether the association between depression and inflammation differs by race and sex. Depressive symptoms have been associated with higher levels of CRP. However few studies have examined this association in samples including a significant number of African Americans, or whether the association differs by race and gender.
Depressive symptoms and CRP were assessed in 512 African American and White participants, age 30–65 years, as part of the community-based META-Health Study. Depression was determined by responses to the Beck’s Depression Inventory-II (BDI-II). Multivariable linear regression models were used to adjust for demographic and metabolic risk factors.
African American men had higher total BDI-II scores than White men (p=0.03), while there was no difference in women. There was a significant race X gender X depression interaction in predicting CRP levels (p=0.02). White women with mild to severe depressive symptoms had higher levels of CRP compared to those with minimal to no depressive symptoms (p<0.05). There were no differences in levels of CRP by severity of depressive symptoms in White men or African Americans of either sex. Higher BDI-II scores were related to higher CRP levels in White women after adjusting for age and level of education (β=0.227, p=0.006). However the association was eliminated after further adjustment for metabolic risk factors (β=0.077, p=0.35).
Although depressive symptoms are associated with inflammation, the association varies by race and gender.
PMCID: PMC3951048  PMID: 21715300
depression; inflammation; race/ethnicity; gender
10.  Associations of adiponectin with individual European ancestry in African Americans: the Jackson Heart Study 
Background: Compared with European Americans, African Americans (AAs) exhibit lower levels of the cardio-metabolically protective adiponectin even after accounting for adiposity measures. Because few studies have examined in AA the association between adiponectin and genetic admixture, a dense panel of ancestry informative markers (AIMs) was used to estimate the individual proportions of European ancestry (PEA) for the AAs enrolled in a large community-based cohort, the Jackson Heart Study (JHS). We tested the hypothesis that plasma adiponectin and PEA are directly associated and assessed the interaction with a series of cardio-metabolic risk factors.
Methods: Plasma specimens from 1439 JHS participants were analyzed by ELISA for adiponectin levels. Using pseudo-ancestral population genotype data from the HapMap Consortium, PEA was estimated with a panel of up to 1447 genome-wide preselected AIMs by a maximum likelihood approach. Interaction assessment, stepwise linear and cubic multivariable-adjusted regression models were used to analyze the cross-sectional association between adiponectin and PEA.
Results: Among the study participants (62% women; mean age 48 ± 12 years), the median (interquartile range) of PEA was 15.8 (9.3)%. Body mass index (BMI) (p = 0.04) and insulin resistance (p = 0.0001) modified the association between adiponectin and PEA. Adiponectin was directly and linearly associated with PEA (β = 0.62 ± 0.28, p = 0.03) among non-obese (n = 673) and insulin sensitive participants (n = 1141; β = 0.74 ± 0.23, p = 0.001), but not among those obese or with insulin resistance. No threshold point effect was detected for non-obese participants.
Conclusions: In a large AA population, the individual proportion of European ancestry was linearly and directly associated with plasma adiponectin among non-obese and non insulin-resistant participants, pointing to the interaction of genetic and metabolic factors influencing adiponectin levels.
PMCID: PMC3918651  PMID: 24575123
cohort study; adiponectin; individual European ancestry; minorities; African Americans; obesity; insulin resistance
12.  SUV39H1 orchestrates temporal dynamics of centromeric methylation essential for faithful chromosome segregation in mitosis 
Histone methylation performs multiple functions such as DNA replication, transcription regulation, heterochromatin formation, and chromatin condensation. How this methylation gradient is orchestrated in the centromere during chromosome segregation is not known. Here we examine the temporal dynamics of protein methylation in the centromere by SUV39H1 methyltransferase, a key mitotic regulator, using fluorescence resonance energy transfer-based sensors in living HeLa cells and immunofluorescence of native SUV39H1 substrates. A quantitative analysis of methylation dynamics, using centromere-targeted sensors, reveals a temporal change during chromosome segregation. These dynamics result in an accurate chromosome congression to and alignment at the equator as an inhibition of methylation dynamics using SUV39H1 inhibitor perturbs chromosome congression in living HeLa cells. Surprisingly, this inhibition of methylation results in a brief increase in Aurora B kinase activity and an enrichment of microtubule depolymerase MCAK in the centromere with a concomitant kinetochore–microtubule destabilization and a reduced tension across the sister kinetochores with ultimate chromosome misalignments. We reason that SUV39H1 generates a gradient of methylation marks at the kinetochore that provides spatiotemporal information essential for accurate chromosome segregation in mitosis.
PMCID: PMC3464394  PMID: 22831836
mitosis; SUV39H1; methylation; MARC; syntelin
13.  Historically Black Medical Schools: Addressing the Minority Health Professional Pipeline and the Public Mission of Care For Vulnerable Populations 
Substantial changes in not only access to care, cost, and quality of care, but also health professions education are needed to ensure effective national healthcare reform. Since the actionable determinants of health such as personal beliefs and behaviors, socioeconomic factors, and the environment disproportionately affect the poor (and often racial/ethnic minorities), many have suggested that focusing efforts on this population will both directly and indirectly improve the overall health of the nation. Key to the success of such strategies are the ongoing efforts by historically black medical schools (HBMSs) as well as other minority serving medical and health professional schools, who produce a disproportionate percentage of the high-quality and diverse health professionals that are dedicated to maintaining the health of an increasingly diverse nation. Despite their public mission, HBMSs receive limited public support threatening their ability to not only meet the increasing minority health workforce needs but to even sustain their existing contributions. Substantial changes in health education policy and funding are needed to ensure HBMSs as well as other minority-serving medical and health professional schools can continue to produce the diverse, high-quality health professional workforce necessary to maintain the health of an increasingly diverse nation. We explore several model initiatives including focused partnerships with legislative and business leaders that are urgently needed to ensure the ability of HBMSs to maintain their legacy of providing compassionate, quality care to the communities in greatest need.
PMCID: PMC3739050  PMID: 19806842
historically black colleges and universities; minority; health disparities
14.  Differences in Systemic Oxidative Stress Based on Race and the Metabolic Syndrome: The Morehouse and Emory Team up to Eliminate Health Disparities (META-Health) Study 
Classification schema such as metabolic syndrome may underestimate cardiovascular disease (CVD) risk in African Americans, despite a higher burden of CVD in African Americans. Oxidative stress results from an imbalance of prooxidants and antioxidants and leads to endothelial dysfunction that promotes vascular inflammation and atherosclerosis. Aminothiol markers of oxidative stress are associated with CVD risk factors and metabolic syndrome; however, little is known about racial differences in levels of oxidative stress. We sought to investigate whether oxidative stress would be higher in African Americans compared to whites independently of traditional risk factor burden.
We assessed oxidative stress in a biracial, community-based cohort. In 620 subjects (59% female, 52% African American) in the Morehouse and Emory Team up to Eliminate Health Disparities (META-Health) study, we measured plasma levels of glutathione, an intracellular antioxidant, and its redox potential as a ratio of reduced and oxidized glutathione (Eh glutathione).
African Americans had lower glutathione levels (P<0.001) compared to whites. There was a trend toward more oxidized Eh glutathione (P=0.07) in African Americans; however, this did not reach statistical significance. After adjustment for demographics and CVD risk factors, African-American race remained a significant correlate of lower glutathione levels (P<0.001) and a more oxidized Eh glutathione (P=0.04). After further adjustment for high-sensitivity C-reactive protein (hsCRP), glutathione remained significantly lower in African Americans (P=0.001). African Americans with or without metabolic syndrome had lower glutathione levels compared to whites with or without metabolic syndrome, respectively (both P≤0.001), and African Americans without metabolic syndrome had a more oxidized Eh glutathione compared to whites without metabolic syndrome (P=0.003).
African Americans have higher levels of oxidative stress than whites, even after adjustment for differences in CVD risk factors and inflammation. Racial differences in oxidative stress may play a key role in understanding observed racial disparities in CVD.
PMCID: PMC3449394  PMID: 22385338
15.  Associations of Adiponectin and Leptin with Incident Coronary Heart Disease and Ischemic Stroke in African Americans: The Jackson Heart Study 
Background: Because the predictive significance of previously reported racial differences in leptin and adiponectin levels remains unclear, we assessed the prospective association of these adipokines with the risk of cardiovascular disease (CVD) events in African Americans, a population with a high prevalence of cardiometabolic risk factors.
Methods: Serum specimens from 4,571 Jackson Heart Study participants without prevalent CVD at baseline examination (2000–2004) were analyzed for adiponectin and leptin levels. Cox proportional hazard regression models were used to estimate the associations of the two adipokines with incident coronary heart disease (CHD) and incident ischemic stroke.
Results: During 6.2 years average of follow-up, 98 incident CHD and 87 incident ischemic stroke events were documented. Among study participants (64% women; mean age 54 ± 13 years), the mean (standard deviation, SD) was 6.04 (4.32) μg/mL in women and 4.03 (3.14) μg/mL in men for adiponectin and 37.35 (23.90) ng/mL in women and 11.03 (10.05) ng/mL in men for leptin. After multivariable adjustment that included age, body mass index, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, insulin resistance by homeostasis model assessment for insulin resistance, systolic blood pressure, hypertension medication, smoking, and physical activity, adiponectin was directly associated in women with incident stroke, HR = 1.41 (1.04–1.91) per one SD increase (p = 0.03), but not in men (p = 0.42). It was not associated with incident CHD in women or men. Leptin was not associated with incident CHD or incident stroke.
Conclusion: In the largest community-based African American cohort, adiponectin was associated among women with a higher risk of incident stroke. Whether adiponectin harbors harmful properties, or it is produced in response to vascular inflammation to counter the atherosclerotic process, or the putative “adiponectin resistance” phenomenon acts, should be further assessed.
PMCID: PMC3854845  PMID: 24350185
cohort study; adiponectin; leptin; cardiovascular events; stroke; minorities; African Americans
16.  Gender differences in the association of visceral and subcutaneous adiposity with adiponectin in African Americans: the Jackson Heart Study 
Adiponectin, paradoxically reduced in obesity and with lower levels in African Americans (AA), modulates several cardiometabolic risk factors. Because abdominal visceral adipose tissue (VAT), known to be reduced in AA, and subcutaneous adipose tissue (SAT) compartments may confer differential metabolic risk profiles, we investigated the associations of VAT and SAT with serum adiponectin, separately by gender, with the hypothesis that VAT is more strongly inversely associated with adiponectin than SAT.
Participants from the Jackson Heart Study, an ongoing cohort of AA (n = 2,799; 64% women; mean age, 55 ± 11 years) underwent computer tomography assessment of SAT and VAT volumes, and had stored serum specimens analyzed for adiponectin levels. These levels were examined by gender in relation to increments of VAT and SAT.
Compared to women, men had significantly lower mean levels of adiponectin (3.9 ± 3.0 μg/mL vs. 6.0 ± 4.4 μg/mL; p < 0.01) and mean volume of SAT (1,721 ± 803 cm3 vs. 2,668 ± 968 cm3; p < 0.01) but significantly higher mean volume of VAT (884 ± 416 cm3 vs. 801 ± 363 cm3; p < 0.01). Among women, a one standard deviation increment in VAT was inversely associated with adiponectin (β = − 0.13; p < 0.0001) after controlling for age, systolic blood pressure, fasting plasma glucose, high-density lipoprotein cholesterol, triglycerides, education, pack-years of smoking and daily intake of alcohol. The statistically significant inverse association of VAT and adiponectin persisted after additionally adjusting for SAT, body mass index (BMI) and waist circumference (WC), suggesting that VAT provides significant information above and beyond BMI and WC. Among men, after the same multivariable adjustment, there was a direct association of SAT and adiponectin (β = 0.18; p = 0.002) that persisted when controlling for BMI and WC, supporting a beneficial effect of SAT. Insulin resistance mediated the association of SAT with adiponectin in women.
In African Americans, abdominal visceral adipose tissue had an inverse association with serum adiponectin concentrations only among women. Abdominal subcutaneous adipose tissue appeared as a protective fat depot in men.
PMCID: PMC3586352  PMID: 23433085
17.  Differences in Weight Perception Among Blacks and Whites 
Journal of Women's Health  2011;20(12):1805-1811.
The prevalence of obesity is higher in blacks than whites, especially in black women, and is known to be associated with major cardiovascular disease risk factors, which are also more prevalent in blacks than whites. Weight perception may contribute to these differences if blacks are more likely to underestimate their weight. We explored race and gender differences in underestimation of weight using body mass index (BMI) and waist circumference (WC), after adjusting for other cardiovascular risk factors.
Methods and Results
We studied 219 white and 240 black women and men as part of the META-Health Study. Perceived weight was assessed over the phone and categorized into three categories: underweight or normal weight, overweight, or obesity. Height, weight, and WC were measured at a subsequent visit, and BMI was calculated. Logistic regression was used to compare the likelihood of underestimating actual weight category by race, before and after adjusting for sociodemographic, lifestyle factors, and medical history. In multivariate analysis, the odds of underestimating BMI category was greater than threefold in blacks compared with whites (OR 3.1, 95% CI 1.9–4.8) and was larger for black women than for black men (p<0.01 for interaction). When abdominal adiposity was taken into account by utilizing WC as a measure of weight, the observed difference in weight underestimation remained.
Our data reveal a significant misperception of weight among blacks, particularly black women, who have the highest burden of obesity. A multifaceted approach with efficient identification of social, cultural, and environmental factors that give rise to obesity tolerance in blacks will provide potential targets for intervention, which may ameliorate weight misperception and the prevalence of excess weight in the black population.
PMCID: PMC3236990  PMID: 21988528
18.  Association of Adiponectin with Left Ventricular Mass in African Americans: The Jackson Heart Study 
Circulation. Heart failure  2011;4(6):747-753.
African Americans (AA) have a higher prevalence of left ventricular hypertrophy than whites. Several population-based studies have reported an inverse association between adiponectin and left ventricular mass (LVM). However, the relationship between adiponectin levels and LVM has yet to be defined in AA. The Jackson Heart Study (JHS) cohort provides an opportunity to test the hypothesis that the inverse association between adiponectin and LVM may be modified by risk factors common among AA.
Methods and Results
The study population included 2,649 AA JHS participants; mean age, 51 ± 12 years, 63% women, 51% obese, 54% with hypertension and 16% with diabetes. Multiple linear and spline regression was used to assess the association adjusting for demographic, clinical and behavioral covariates. Among all the participants, there was a statistically significant but modest inverse association between adiponectin and left ventricular mass index (LVMI). Hypertension and insulin resistance emerged as statistically significant effect modifiers of this relationship. The inverse association present among the normotensive participants was explained by obesity measures such as the body mass index. Among participants with both hypertension and insulin resistance there was a significant direct association between adiponectin and LVMI after multivariable adjustment (β = 1.55, p = 0.04; per one standard deviation increments in the adiponectin log-value).
The association between serum adiponectin and LVM among AA in the JHS cohort was dependent on hypertension and insulin resistance status. Normotensive AA exhibited an inverse adiponectin – LVM association, whereas participants with hypertension and insulin resistance had a direct association.
PMCID: PMC3218236  PMID: 21840935
adiponectin; biomarkers; epidemiology; left ventricular mass; obesity
19.  Glomerular Expression of Kidney Injury Molecule-1 and Podocytopenia in Diabetic Glomerulopathy 
American Journal of Nephrology  2011;34(3):268-280.
Studies have shown that kidney injury molecule-1 (KIM-1) is upregulated in damaged renal proximal tubules. In this study, we examined KIM-1 expression in glomerular epithelial cells in diabetic glomerulopathy.
Renal histology, immunostaining and Western blot for protein level, and real-time PCR for mRNA expression of KIM-1 and podocyte markers were evaluated in untreated or losartan-treated Zucker lean (Fa/+) and Zucker diabetic fatty (Fa/Fa) rats.
The diabetic rats showed an increased glomerular expression of KIM-1. KIM-1 staining was localized primarily in the hyperplastic parietal epithelium of Bowman's capsule in the early stages of diabetes with subsequent increase in KIM-1-positive cells in the glomerular tuft in the more advanced stages. The increase in glomerular KIM-1 was associated with a decrease in podocytes in Fa/Fa rats. Antiproteinuric treatment with losartan attenuated podocytopenia and decreased renal expression of KIM-1 in treated diabetic rats. In an in vitro study, albumin overload increased KIM-1 protein in the primary cultures of rat glomerular epithelial cells.
These results show that glomerular KIM-1 expression was increased, in proportion to the extent of proteinuria and podocytopenia in the diabetic animals, supporting that KIM-1 could be used as a potential biomarker for glomerular injury in proteinuric kidney disease.
PMCID: PMC3169370  PMID: 21822010
Albuminuria; Kidney injury molecule-1; Parietal epithelial cells; Podocytes; Glomerulopathy
20.  Vitamin D and Cardiovascular Disease: Potential Role in Health Disparities 
Cardiovascular disease (CVD), which includes coronary artery disease and stroke, is the leading cause of mortality in the nation. Excess CVD morbidity and premature mortality in the African American community is one of the most striking examples of racial/ethnic disparities in health outcomes. African Americans also suffer from increased rates of hypovitaminosis D, which has emerged as an independent risk factor for all-cause and cardiovascular mortality. This overview examines the potential role of hypovitaminosis D as a contributor to racial and ethnic disparities in cardiovascular disease (CVD). We review the epidemiology of vitamin D and CVD in African Americans and the emerging biological roles of vitamin D in key CVD signaling pathways that may contribute to the epidemiological findings and provide the foundation for future therapeutic strategies for reducing health disparities.
PMCID: PMC3417128  PMID: 22102304
VDR; CVD; PAI; Wrch-1; Rho; Fst
21.  Elevated Circulating Angiogenic Progenitors and White Blood Cells Are Associated with Hypoxia-Inducible Angiogenic Growth Factors in Children with Sickle Cell Disease 
Anemia  2012;2012:156598.
We studied the number and function of angiogenic progenitor cells and growth factors in children aged 5–18 years without acute illness, 43 with Hemoglobin SS and 68 with normal hemoglobin. Hemoglobin SS subjects had at least twice as many mononuclear cell colonies and more circulating progenitor cell than Control subjects. Plasma concentrations of erythropoietin, angiopoietin-2, and stromal-derived growth factor (SDF)-1α were significantly higher in children with Hemoglobin SS compared to Control subjects. In a multivariate analysis model, SDF-1α concentration was found to be associated with both CPC number and total white blood cell count in the Hemoglobin SS group, suggesting that SDF-1α produced by ischemic tissues plays a role in mobilizing these cells in children with Hemoglobin SS. Despite having a higher number of angiogenic progenitor cells, children with Hemoglobin SS had slower migration of cultured mononuclear cells.
PMCID: PMC3366209  PMID: 22675614
22.  Interaction of sleep quality and psychosocial stress on obesity in African Americans: the Cardiovascular Health Epidemiology Study (CHES) 
BMC Public Health  2010;10:581.
Compared with whites, sleep disturbance and sleep deprivation appear more prevalent in African Americans (AA). Long-term sleep deprivation may increase the risk of obesity through multiple metabolic and endocrine alterations. Previous studies have reported contradictory results on the association between habitual sleep duration and obesity. Accordingly, we aimed to assess whether sleep quality and duration are inversely associated with body mass index (BMI) and obesity and test whether these associations are modified by psychosocial stress, known to influence sleep quality.
A sample of 1,515 AA residents of metropolitan Atlanta, aged 30-65 years, was recruited by a random-digit-dialing method in 2007-08. The outcome obesity was defined by BMI (kg/m2) continuously and categorically (BMI ≥ 30 versus BMI < 30). Global sleep quality (GSQ) score was computed as the sum of response values for the seven components of the Pittsburgh Sleep Quality Index (PSQI) scale. GSQ score was defined as a continuous variable (range 0-21) and as tertiles. The general perceived stress (GPS), derived from the validated Cohen scale, was categorized into tertiles to test the interaction. Chi-square tests, correlation coefficients and weighted multiple linear and logistic regression were used to assess the associations of GSQ, GPS and obesity.
The mean (standard deviation) age was 47.5 (17.0) years, and 1,096 (72%) were women. GSQ score categorized into tertiles was associated with BMI. Among women, after multivariable adjustment that included age, gender, physical activity, smoking status, education, total family income, financial stress and history of hypertension, hypercholesterolemia, diabetes and myocardial infarction, obesity was associated with sleep quality as assessed by GSQ continuous score, [odds ratio, OR (95% C.I.): 1.08 (1.03 - 1.12)], and with a worse sleep disturbance subcomponent score [OR (95% C.I.): 1.48 (1.16 - 1.89)]. Among all participants, stress modified the association between obesity and sleep quality; there was an increased likelihood of obesity in the medium stress category, OR (95% C.I.): 1.09 (1.02 - 1.17).
Sleep quality was associated with obesity in women. The association of sleep quality with obesity was modified by perceived stress. Our results indicate the need for simultaneous assessment of sleep and stress.
PMCID: PMC2955012  PMID: 20920190
23.  Predictive Value of Reactive Hyperemia for Cardiovascular Events in Patients With Peripheral Arterial Disease Undergoing Vascular Surgery 
Reactive hyperemia is the compensatory increase in blood flow that occurs after a period of tissue ischemia, and this response is blunted in patients with cardiovascular risk factors. The predictive value of reactive hyperemia for cardiovascular events in patients with atherosclerosis and the relative importance of reactive hyperemia compared with other measures of vascular function have not been previously studied.
Methods and Results
We prospectively measured reactive hyperemia and brachial artery flow-mediated dilation by ultrasound in 267 patients with peripheral arterial disease referred for vascular surgery (age 66±11 years, 26% female). Median follow-up was 309 days (range 1 to 730 days). Fifty patients (19%) had an event, including cardiac death (15), myocardial infarction (18), unstable angina (8), congestive heart failure (6), and nonhemorrhagic stroke (3). Patients with an event were older and had lower hyperemic flow velocity (75±39 versus 95±50 cm/s, P=0.009). Patients with an event also had lower flow-mediated dilation (4.5±3.0 versus 6.9±4.6%, P<0.001), and when these 2 measures of vascular function were included in the same Cox proportional hazards model, lower hyperemic flow (OR 2.7, 95% CI 1.2 to 5.9, P=0.018) and lower flow-mediated dilation (OR 4.2, 95% CI: 1.8 to 9.8, P=0.001) both predicted cardiovascular events while adjusting for other risk factors.
Thus, lower reactive hyperemia is associated with increased cardiovascular risk in patients with peripheral arterial disease. Furthermore, flow-mediated dilation and reactive hyperemia incrementally relate to cardiovascular risk, although impaired flow-mediated dilation was the stronger predictor in this population. These findings further support the clinical relevance of vascular function measured in the microvasculature and conduit arteries in the upper extremity.
PMCID: PMC2596307  PMID: 17717291
endothelium; cardiovascular risk; surrogate markers; reactive hyperemia; flow-mediated dilation
25.  Geography and genography: prediction of continental origin using randomly selected single nucleotide polymorphisms 
BMC Genomics  2007;8:68.
Recent studies have shown that when individuals are grouped on the basis of genetic similarity, group membership corresponds closely to continental origin. There has been considerable debate about the implications of these findings in the context of larger debates about race and the extent of genetic variation between groups. Some have argued that clustering according to continental origin demonstrates the existence of significant genetic differences between groups and that these differences may have important implications for differences in health and disease. Others argue that clustering according to continental origin requires the use of large amounts of genetic data or specifically chosen markers and is indicative only of very subtle genetic differences that are unlikely to have biomedical significance.
We used small numbers of randomly selected single nucleotide polymorphisms (SNPs) from the International HapMap Project to train naïve Bayes classifiers for prediction of ancestral continent of origin. Predictive accuracy was tested on two independent data sets. Genetically similar groups should be difficult to distinguish, especially if only a small number of genetic markers are used. The genetic differences between continentally defined groups are sufficiently large that one can accurately predict ancestral continent of origin using only a minute, randomly selected fraction of the genetic variation present in the human genome. Genotype data from only 50 random SNPs was sufficient to predict ancestral continent of origin in our primary test data set with an average accuracy of 95%. Genetic variations informative about ancestry were common and widely distributed throughout the genome.
Accurate characterization of ancestry is possible using small numbers of randomly selected SNPs. The results presented here show how investigators conducting genetic association studies can use small numbers of arbitrarily chosen SNPs to identify stratification in study subjects and avoid false positive genotype-phenotype associations. Our findings also demonstrate the extent of variation between continentally defined groups and argue strongly against the contention that genetic differences between groups are too small to have biomedical significance.
PMCID: PMC1828730  PMID: 17349058

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