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1.  Genetic ancestry and lower extremity peripheral artery disease in the Multi-Ethnic Study of Atherosclerosis 
Using self-report of race/ethnicity, African Americans consistently have a higher prevalence of peripheral artery disease (PAD) compared to other ethnic groups. We aimed to determine the associations between estimated genetic admixture and PAD among African and Hispanic Americans. We studied the association between genetic ancestry and PAD among 1417 African and Hispanic American participants in the Multi-Ethnic Study of Atherosclerosis who were genotyped for ancestry informative markers (AIMs). PAD was defined as an ankle–brachial index (ABI) < 0.90. The overall prevalence of PAD among the 712 self-identified African American subjects was 15.2% and 4.6% among the 705 self-identified Hispanic Americans. A one standard deviation increment in European ancestry was associated with non-significant reductions in the odds for PAD among African (OR: 0.96 [95% CI: 0.78–1.18]) and Hispanic Americans (0.84 [0.58–1.23]), while the same increment in Native American ancestry was significantly associated with a lower odds of PAD in Hispanic Americans (0.56 [0.36–0.96]). Adjustment for demographic variables, field center, cardiovascular disease (CVD) risk factors and inflammatory markers strengthened the odds for European ancestry among African (0.85 [0.66–1.10]) and Hispanic Americans (0.68 [0.41–1.11]). The magnitude of the association for Native American ancestry among Hispanic Americans did not materially change (0.56 [0.29–1.09]). In conclusion, a higher percent Native American ancestry in Hispanics is associated with a lower odds of PAD while in both Hispanics and African Americans, greater European ancestry does not appear to be associated with lower odds for PAD.
PMCID: PMC4077267  PMID: 20926494
epidemiology; genetics; peripheral artery disease
2.  Combined Hyperlipidemia in relation to Race/Ethnicity, Obesity, and Insulin Resistance in the Multi-Ethnic Study of Atherosclerosis (MESA) 
We have asked whether the prevalence of combined hyperlipidemia (CHL) differs by race/ethnicity, obesity, and insulin resistance in a contemporary, multi-ethnic, US cohort.
Methods & Results
We determined the prevalence and adjusted odds of CHL in a cohort of 5,923 men and women free of clinically-recognized cardiovascular disease and diabetes, according to race/ethnicity (White, Chinese, African-American, and Hispanic), obesity, and insulin resistance. Untreated lipid values were imputed for those on lipid lowering therapy. CHL was defined using age and gender-specific ≥75th percentile cut points for LDL-C and triglycerides obtained from a predominantly Caucasian North American population study. Compared to Whites, adjusted odds ratios (OR) for CHL were 0.48 in African Americans (95% confidence interval (CI): 0.30, 0.75), 1.33 in Hispanics (95% CI 0.93, 1.91), and 1.06 in Asians (95% CI 0.62, 1.82). Within the entire population, the adjusted odds of CHL was over 2-fold higher in overweight and obese participants compared with normal weight and more than 4-fold higher in quartiles 2 through 4 of insulin resistance, compared with quartile 1.
African-Americans had lower odds for CHL than Whites despite higher BMI and abdominal adiposity. Hispanics had a non-significantly higher trend and Asians had no significantly different odds than Whites. Modest increases in weight and insulin resistance were associated with significantly higher odds of CHL in a multi-ethnic US population. Further research is needed to determine the most efficacious diet, exercise and drug management to decrease the risk of CHL and CHD among racial/ethnic groups in the United States.
PMCID: PMC2677914  PMID: 19154954
3.  Supplement use contributes to meeting recommended dietary intakes for calcium, magnesium and vitamin C in four ethnicities of middle-aged and older Americans: The Multi-Ethnic Study of Atherosclerosis 
Low intake of nutrients is associated with poor health outcomes. Therefore, we examined the contribution of dietary supplementation to meeting recommended dietary intakes of calcium, magnesium, potassium and vitamin C in participants of the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort of Caucasian, African-American, Hispanic and Chinese participants ages 45-84 years. We also assessed the prevalence of intakes above Tolerable Upper Intake Levels (ULs).
At the baseline exam in 2000-01, 2,938 men and 3,299 women completed food-frequency questionnaires and provided information about dietary supplementation. We used relative risk regression to estimate the probability of meeting RDAs or AIs in supplement-users vs. non-users and Fisher's exact tests to compare the proportion of those exceeding ULs between the two groups. RDAs, AIs, and ULs were defined by the National Academy of Sciences Food and Nutrition Board's Dietary Reference Intakes (DRIs).
After adjustment for age and education, the relative risk (RR) of meeting RDAs or AIs in supplement-users vs. nonusers ranged from 1.9 (1.6, 2.3) in Caucasian men to 5.7 (4.1, 8.0) in African American women for calcium, from 2.5 (1.9, 3.3) in Hispanic men to 5.2 (2.4, 11.2) in Chinese men for magnesium, and from 1.4 (1.3, 1.5) in African American women to 2.0 (1.7, 2.2) in Chinese men for vitamin C. The RRs for meeting RDAs for calcium differed significantly by ethnicity (p<0.021) and gender (p<0.001), by ethnicity for magnesium (p=0.001). The RR for each gender/ethnicity strata was close to 1 and did not reach statistical significance at alpha=0.05 for potassium. For calcium, 15% of high-dose supplement-users exceeded the UL compared with only 2.1% of nonusers. For vitamin C, the percentages were 6.6% and 0%, and for magnesium, 35.3% and 0% (p<0.001 for all).
Although supplement use is associated with meeting DRI guidelines for calcium, vitamin C and magnesium, many adults are not meeting the DRI guidelines even with the help of dietary supplements, and the effect of supplementation can vary according to ethnicity and gender. However, supplementation was not significantly associated with meeting DRIs for potassium. Also, high-dose supplement use is associated with intakes above ULs for calcium, magnesium and vitamin C.
PMCID: PMC2684701  PMID: 19248857
Dietary supplements; micronutrient intake; race; ethnicity; gender
4.  Menthol cigarettes and smoking cessation among racial/ethnic groups in the United States 
Addiction (Abingdon, England)  2010;105(0 1):84-94.
To examine the association between smoking mentholated cigarettes and smoking cessation, separately for different racial/ethnic groups.
Secondary data analysis of the 2003 and 2006–07 Tobacco Use Supplements to the Current Population Survey.
United States.
African American, Asian American/Pacific Islander, Hispanic/Latino, Native American, non-Hispanic white adults.
Examined relations between the use of mentholated cigarettes and measures of smoking cessation.
Among African Americans (ORadj = 1.62, 95% CI: 1.35–1.95) and Hispanics/Latinos (ORadj = 1.21, 95% CI: 1.00–1.47), those who currently smoked mentholated cigarettes were more likely be seriously considering quitting in the next six months than were non-menthol smokers, after adjusting for sociodemographic factors. African Americans (ORadj = 1.87, 95% CI: 1.60– 2.19) and Hispanics/Latinos (ORadj = 1.34, 95% CI: 1.11–1.62) who smoked mentholated cigarettes were also significantly more likely to have a positive estimation of successfully quitting in the next six months compared to non-menthol smokers. These associations were not found among Asian Americans/Pacific Islanders, Native Americans/Alaska Natives and Non-Hispanic Whites. Among former smokers, across racial/ethnic groups, those who smoked mentholated cigarettes (vs. non-menthols) were significantly less likely to have successfully quit for at least six months: African Americans (ORadj = 0.23, 95% CI: 0.17–0.31), Asian Americans/Pacific Islanders (ORadj = 0.22, 95% CI: 0.11–0.45), Hispanics/Latinos (ORadj = 0.48, 95% CI: 0.34–0.69) and Non-Hispanic Whites (ORadj = 0.28, 95% CI: 0.25–0.33).
Across race/ethnic groups, those who used to regularly smoke mentholated cigarettes were less likely to have experienced long-term quitting success. Cessation programs should consider the type of cigarette typically smoked by participants, particularly menthols.
PMCID: PMC4214376  PMID: 21059139
Cessation; race/ethnicity
5.  Outcomes in Ethnic Minority Renal Transplant Recipients Receiving Everolimus versus Mycophenolate: Comparative Risk Assessment Results From a Pooled Analysis 
Transplantation  2013;96(12):1073-1081.
Everolimus (EVR) has demonstrated good efficacy after renal transplantation. Racial disparities in clinical outcomes after de novo renal transplantation are well documented; whether the efficacy of EVR varies based on recipient ethnicity is unknown. We conducted a comparative risk assessment of EVR by ethnicity.
Data on 2004 renal transplant recipients from three EVR studies were pooled to identify the impact of ethnicity on efficacy outcomes across EVR dosing groups and control groups. Ethnic groups compared were African Americans, non-U.S. blacks, Asians, Hispanics, and Caucasians. EVR groups received either 1.5 or 3 mg per day, with either standard-dose cyclosporine or reduced-dose cyclosporine. Control groups received mycophenolic acid (MPA) with standard-dose cyclosporine. Composite efficacy failure endpoint was graft loss, death, biopsy-proven acute rejection, or lost to follow-up. Adjusted odds ratios were calculated using a logistic regression model.
The proportion of renal transplant recipients who met the composite endpoint was African Americans (46%), non-U.S. black (35%), Caucasian (31%), Hispanic (28%), and Asian (25%). The odds of meeting the composite endpoint were significantly (P=0.0001) greater for African Americans versus Caucasians but did not differ among the other ethnic groups (ethnic groups were only compared with Caucasians). EVR and MPA were associated with similar efficacy among each of the ethnic groups.
In this pooled data analysis in more than 2000 renal transplant recipients, EVR versus MPA resulted in similar composite endpoint incidence events across ethnicities. Consistent with previously published data, African Americans had poorer clinical outcomes. EVR is efficacious regardless of ethnicity.
PMCID: PMC3888463  PMID: 24345868
Everolimus; Mycophenolate; African American; Renal transplantation
6.  Fasting Glucose GWAS Candidate Region Analysis across Ethnic Groups in the Multi-Ethnic Study of Atherosclerosis (MESA) 
Genetic epidemiology  2012;36(4):384-391.
Genetic variants associated with fasting glucose in European ancestry populations are increasingly well understood. However, the nature of the associations between these SNPs and fasting glucose in other racial and ethnic groups is unclear. We sought to examine regions previously identified to be associated with fasting glucose in Caucasian GWAS across multiple ethnicities in the Multi-Ethnic Study of Atherosclerosis (MESA). Non-diabetic MESA participants with fasting glucose measured at the baseline exam and with GWAS genotyping were included; 2349 Caucasians, 664 individuals of Chinese descent, 1366 African Americans, and 1171 Hispanics. Genotype data was generated from the Affymetrix 6.0 array and imputation in IMPUTE. Fasting glucose was regressed on SNP dosage data in each ethnic group adjusting for age, gender, MESA study center, and ethnic-specific principal components. SNPs from the three gene regions with the strongest associations to fasting glucose in previous Caucasian GWAS (MTNR1B / GCK / G6PC2) were examined in depth. There was limited power to replicate associations in other ethnic groups due to smaller allele frequencies and limited sample size; SNP associations may also have differed across ethnic groups due to differing LD patterns with causal variants. rs10830963 in MTNR1B and rs4607517 in GCK demonstrated consistent magnitude and direction of association with fasting glucose across ethnic groups, although the associations were often not nominally significant. In conclusion, certain SNPs in MTNR1B and GCK demonstrate consistent effects across four racial and ethnic groups, narrowing the putative region for these causal variants.
PMCID: PMC3507617  PMID: 22508271
GWAS; fasting glucose; SNP
7.  Preventing relapse in recurrent depression using mindfulness-based cognitive therapy, antidepressant medication or the combination: trial design and protocol of the MOMENT study 
BMC Psychiatry  2012;12:125.
Depression is a common psychiatric disorder characterized by a high rate of relapse and recurrence. The most commonly used strategy to prevent relapse/recurrence is maintenance treatment with antidepressant medication (mADM). Recently, it has been shown that Mindfulness-Based Cognitive Therapy (MBCT) is at least as effective as mADM in reducing the relapse/recurrence risk. However, it is not yet known whether combination treatment of MBCT and mADM is more effective than either of these treatments alone. Given the fact that most patients have a preference for either mADM or for MBCT, the aim of the present study is to answer the following questions. First, what is the effectiveness of MBCT in addition to mADM? Second, how large is the risk of relapse/recurrence in patients withdrawing from mADM after participating in MBCT, compared to those who continue to use mADM after MBCT?
Two parallel-group, multi-center randomized controlled trials are conducted. Adult patients with a history of depression (3 or more episodes), currently either in full or partial remission and currently treated with mADM (6 months or longer) are recruited. In the first trial, we compare mADM on its own with mADM plus MBCT. In the second trial, we compare MBCT on its own, including tapering of mADM, with mADM plus MBCT. Follow-up assessments are administered at 3-month intervals for 15 months. Primary outcome is relapse/recurrence. Secondary outcomes are time to, duration and severity of relapse/recurrence, quality of life, personality, several process variables, and incremental cost-effectiveness ratio.
Taking into account patient preferences, this study will provide information about a) the clinical and cost-effectiveness of mADM only compared with mADM plus MBCT, in patients with a preference for mADM, and b) the clinical and cost-effectiveness of withdrawing from mADM after MBCT, compared with mADM plus MBCT, in patients with a preference for MBCT.
Trial registration NCT00928980
PMCID: PMC3469366  PMID: 22925198
Mindfulness-based cognitive therapy; Antidepressant medication; Depression; Relapse prevention; Randomized controlled trial
8.  Multi-Ethnic Differences in Responses to Laboratory Pain Stimuli among Children 
A growing body of literature suggests ethnic differences in experimental pain. However, these studies largely focus on adults and the comparison between Caucasians and African-Americans. The primary aim of this study is to determine ethnic differences in laboratory induced pain in a multi-ethnic child sample.
Participants were 214 healthy children (mean age = 12.7, SD= 3.0 yrs). Ninety-eight Caucasian, 58 Hispanic, 34 African-American, and 24 Asian children were exposed to four trials of pressure and radiant heat pain stimuli. Pain responses were assessed with self-report measures (i.e., pain intensity and unpleasantness) and behavioral observation (i.e., pain tolerance).
Asians demonstrated more pain sensitivity than Caucasians, who evidenced more pain sensitivity than African-Americans and Hispanics. The results hold even after controlling for age, sex, SES, and experimenter’s ethnicity. Asians also showed higher anticipatory anxiety compared with other ethnic groups. Anticipatory anxiety accounted for some ethnic differences in pain between Asians, Hispanics, and African Americans.
By examining response to laboratory pain stimuli in children representing multiple ethnicities, an understudied sample, the study reveals unique findings compared to the existing literature. These findings have implications for clinicians who manage acute pain in children from diverse ethnic backgrounds. Future investigations should examine mechanisms that account for ethnic differences in pain during various developmental stages.
PMCID: PMC3742024  PMID: 23668844
ethnicity; laboratory pain; children; health disparity; anticipatory anxiety
9.  NAFLD prevalence differs among hispanic subgroups: The multi-ethnic study of atherosclerosis 
AIM: To compare prevalence rates of non-alcoholic fatty liver disease (NAFLD) between Hispanics of Mexican origin and Hispanics of Dominican and Puerto Rican origin.
METHODS: We evaluated prevalence rates of NAFLD between the two largest sub-populations of Hispanics in the United States; Hispanics of Mexican origin and Hispanics of Caribbean origin (Dominican and Puerto Rican), in the multi-ethnic study of atherosclerosis (MESA) cohort. MESA is a large, population based, multi-center cohort study comprised of 6814 healthy Caucasian, African-American, Hispanic, and Asian men and women aged 45-84. We utilized the baseline serum, anthropometric and radiographic measurements obtained between 2000 and 2002. NAFLD was measured via computed tomography scan and was defined as liver/spleen attenuation ratio < 1.
RESULTS: There were 788 Hispanic participants included in the study after exclusions. The prevalence of NAFLD was 29% (n = 225). Hispanics of Mexican origin had a significantly higher prevalence of NAFLD (33%), compared to Hispanics of Dominican origin (16%), (P < 0.01) and Hispanics of Puerto Rican origin (18%), (P < 0.01). After controlling for age, sex, BMI, waist circumference, hypertension, serum HDL, triglyceride and CRP level and insulin resistance, Hispanics of Mexican origin remained significantly more likely to have NAFLD than those of Dominican and Puerto Rican origin.
CONCLUSION: United States Hispanics of Mexican origin have a significantly higher prevalence of NAFLD when compared to United States Hispanics of Dominican or Puerto Rican origin after controlling for known risk factors. Care should be taken when performing risk assessment in Hispanic populations not to make assumptions of homogeneity.
PMCID: PMC4009531  PMID: 24803810
Non-alcoholic fatty liver disease; Prevalence; Hispanic subpopulations
10.  Genetic Ancestry, Self-Reported Race and Ethnicity in African Americans and European Americans in the PCaP Cohort 
PLoS ONE  2012;7(3):e30950.
Family history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP.
Individual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states.
Mean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered “no” to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA.
Mean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP.
PMCID: PMC3313995  PMID: 22479307
11.  Is neighborhood racial/ethnic composition associated with depressive symptoms? The multi-ethnic study of atherosclerosis 
Social science & medicine (1982)  2010;71(3):541-550.
The racial/ethnic composition of a neighborhood may be related to residents’ depressive symptoms through differential levels of neighborhood social support and/or stressors. We used the Multi-Ethnic Study of Atherosclerosis to investigate cross-sectional associations of neighborhood racial/ethnic composition with the Center for Epidemiologic Studies-Depression (CES-D) scale in adults aged 45–84. The key exposure was a census-derived measure of the percentage of residents of the same racial/ethnic background in each participant’s census tract. Two-level multilevel models were used to estimate associations of neighborhood racial/ethnic composition with CES-D scores after controlling for age, income, marital status, education and nativity. We found that living in a neighborhood with a higher percentage of residents of the same race/ethnicity was associated with increased CES-D scores in African American men (p < 0.05), and decreased CES-D scores in Hispanic men and women and Chinese women, although these differences were not statistically significant. Models were further adjusted for neighborhood-level covariates (social cohesion, safety, problems, aesthetic quality and socioeconomic factors) derived from survey responses and census data. Adjusting for other neighborhood characteristics strengthened protective associations amongst Hispanics, but did not change the significant associations in African American men. These results demonstrate heterogeneity in the associations of race/ethnic composition with mental health and the need for further exploration of which aspects of neighborhood environments may contribute to these associations.
PMCID: PMC2922985  PMID: 20541303
Neighborhoods; Depressive symptoms; Mental health; Race/ethnicity; Ethnic density effect; USA
12.  Methods for Estimation of Disparities in Medication Use in an Observational Cohort Study: Results from the Multi-Ethnic Study of Atherosclerosis 
Evaluating disparities in health care is an important aspect of understanding differences in disease risk. The purpose of this study is to describe methodology for estimating such disparities, with application to a large multi-ethnic cohort study.
The Multi-Ethnic Study of Atherosclerosis (MESA) includes 6814 participants aged 45–84 years free of cardiovascular disease. Prevalence ratio (PR) regression was used to model baseline lipid lowering medication (LLM) or anti-hypertensive medication use at baseline as a function of gender, race, risk factors and estimated pre-treatment biomarker values.
Hispanics and African-Americans had lower prevalence of medication use than non-Hispanic whites, even at the same risk factor profile. This became non-significant after adjustment for socio-economic status. Although gender did not influence the prevalence of LLM use (PR=1.09, 95% CI 0.95 to 1.25), there were differences in the association of diabetes and HDL with LLM use by gender. Men were significantly less likely to be on anti-hypertensive medications than women (PR=0.86, 95% CI 0.80 to 0.92, p<0.001) and this was not explained by risk factors or socioeconomic status. Lack of health insurance strongly influenced medication use, controlling for risk factors and other markers of socio-economic status.
Disparities exist in the treatment of cholesterol and hypertension. Hispanics and African Americans had less use of LLM, men had less use of anti-hypertensives. Risk factors have differential associations with medication use depending on gender. Methods described in this paper can provide improved disparity estimation in observational cohort studies.
PMCID: PMC3652567  PMID: 23382107
disparities; medication; statistical methods; statins; anti-hypertensives
13.  Differences in the Incidence of Congestive Heart Failure by Ethnicity 
Archives of internal medicine  2008;168(19):2138-2145.
The relationship between incident congestive heart failure (CHF) and ethnicity as well as racial/ethnic differences in the mechanisms leading to CHF have not been demonstrated in a multiracial, population-based study. Our objective was to evaluate the relationship between race/ethnicity and incident CHF.
The Multi-Ethnic Study of Atherosclerosis (MESA) is a cohort study of 6814 participants of 4 ethnicities: white (38.5%), African American (27.8%), Hispanic (21.9%), and Chinese American (11.8%). Participants with a history of cardiovascular disease at baseline were excluded. Cox proportional hazards models were used for data analysis.
During a median follow-up of 4.0 years, 79 participants developed CHF (incidence rate: 3.1 per 1000 person-years). African Americans had the highest incidence rate of CHF, followed by Hispanic, white, and Chinese American participants (incidence rates: 4.6, 3.5, 2.4, and 1.0 per 1000 person-years, respectively). Although risk of developing CHF was higher among African American compared with white participants (hazard ratio, 1.8; 95% confidence interval, 1.1-3.1), adding hypertension and/or diabetes mellitus to models including ethnicity eliminated statistical ethnic differences in incident CHF. Moreover, African Americans had the highest proportion of incident CHF not preceded by clinical myocardial infarction (75%) compared with other ethnic groups (P = .06).
The higher risk of incident CHF among African Americans was related to differences in the prevalence of hypertension and diabetes mellitus as well as socioeconomic status. The mechanisms of CHF also differed by ethnicity; interim myocardial infarction had the least influence among African Americans, and left ventricular mass increase had the greatest effect among Hispanic and white participants.
PMCID: PMC3038918  PMID: 18955644
14.  Ethnic Identity Predicts Experimental Pain Sensitivity In African Americans and Hispanics 
Pain  2007;129(1-2):177-184.
The aim of this study was to examine experimental pain sensitivity in three ethnic groups, African Americans, Hispanic Americans and non-Hispanic whites, and to determine whether ethnic identity is differentially associated with pain sensitivity across ethnic groups. Participants included sixty-three African American, sixty-one Hispanic and eighty-two non-Hispanic white participants who were assessed using three experimental pain measures: thermal, cold-pressor and ischemic. Participants’ ethnic identity was assessed using the Multi-group Ethnic Identity Measure (MEIM). Ethnic group differences in pain responses were observed, with African American and Hispanic subjects showing lower cold and heat pain tolerances than non-Hispanic whites. In addition, pain range (i.e. tolerance – threshold) was computed for heat, cold and ischemic pain, and the two minority groups again had lower values compared to non-Hispanic whites. Ethnic identity was associated with pain range only for African American and Hispanic groups. Statistically controlling for ethnic identity rendered some of the group differences in pain range non-significant. These findings indicate that ethnic identity is associated with pain sensitivity in ethnic minority groups, and may partially mediate group differences in pain perception. The results of the present investigation provide evidence of ethnic group differences in responses to experimental pain across multiple noxious stimuli, with both minority groups exhibiting greater sensitivity to laboratory evoked pain compared to non-Hispanic whites.
PMCID: PMC1925263  PMID: 17296267
15.  Racial and Ethnic Differences in Albuminuria in Individuals With Estimated GFR Greater Than 60 mL/min/1.73 m2: Results From the Kidney Early Evaluation Program (KEEP) 
Albuminuria is an important marker for chronic kidney disease and progression to end-stage renal disease in the general population; understanding racial and ethnic differences can help inform efforts to reduce health disparities. We sought to estimate independent associations of race/ethnicity with albuminuria to determine whether observed differences were attributable to known kidney disease risk factors.
This cross-sectional study included 64,161 Kidney Early Evaluation Program (KEEP) participants, 2000–2008, with estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2, not on regular dialysis, and without previous kidney transplant. Albuminuria (urine albumin-creatinine ratio [ACR] ≥ 30 mg/g) was examined by self-reported race and ethnicity. Covariates were age, sex, educational level, body mass index, diabetes status or glucose level, hypertension status or blood pressure measurement, smoking status, health insurance status, and geographic region.
Albuminuria prevalence was 8% (n = 2303) in whites, 11% (n = 2310) in African Americans, 9% (n = 730) in Hispanics, 10% (n = 381) in Asians, and 15% (n = 344) in American Indians/Alaska Natives. Compared with whites, odds of albuminuria were higher for all groups after multivariate adjustment. Odds were highest for American Indians/Alaska Natives (adjusted odds ratio 1.93, 95% confidence interval 1.70–2.20), then Asians (1.42, 1.26–1.61), African Americans (1.38, 1.29–1.47), and Hispanics (1.19, 1.08–1.31).
In the KEEP study population, albuminuria prevalence was higher among African Americans, Hispanics, Asians, and American Indians/Alaska Natives than among non-Hispanic whites, suggesting a need for screening for early detection of kidney damage, especially among people at increased risk, in the community primary care setting.
PMCID: PMC3507474  PMID: 20172444
16.  Genetic variants associated with VLDL, LDL and HDL particle size differ with race/ethnicity 
Human genetics  2012;132(4):405-413.
Specific constellations of lipoprotein particle features, reflected as differences in mean lipoprotein particle diameters, are associated with risk of insulin resistance (IR) and cardiovascular disease (CVD). The associations of lipid profiles with disease risk differ by race/ethnicity, the reason for this is not clear. We aimed to examine whether there were additional genetic differences between racial / ethnic groups on lipoprotein profile.
Methods and results
Genotypes were assessed using the Affymetrix 6.0 array in 817 related Caucasian participants of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). Association analysis was conducted on fasting mean particle diameters using linear models, adjusted for age, sex and study center as fixed effects, and pedigree as a random effect. Replication of associations reaching P<1.97 * 10−05 (the level at which we achieved at least 80% power to replicate SNP-phenotype associations) was conducted in the Caucasian population of the Multi-Ethnic Study of Atherosclerosis (MESA; N=2430). Variants which replicated across both Caucasian populations were subsequently tested for association in the African-American (N=1594), Chinese (N=758) and Hispanic (N=1422) populations of MESA. Variants in the APOB gene region were significantly associated with mean VLDL diameter in GOLDN, and in the Caucasian and Hispanic populations of MESA, while variation in the hepatic lipase (LIPC) gene was associated with mean HDL diameter in both Caucasians populations only.
Our findings suggest the genetic underpinnings of mean lipoprotein diameter differ by race/ethnicity. As lipoprotein diameters are modifiable, this may lead new strategies to modify lipoprotein profiles during the reduction of IR that are sensitive to race / ethnicity.
PMCID: PMC3600091  PMID: 23263444
Lipoprotein size; race / ethnicity; ApoB; Hepatic Lipase; NMR
17.  Population Structure of Hispanics in the United States: The Multi-Ethnic Study of Atherosclerosis 
PLoS Genetics  2012;8(4):e1002640.
Using ∼60,000 SNPs selected for minimal linkage disequilibrium, we perform population structure analysis of 1,374 unrelated Hispanic individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with self-identification corresponding to Central America (n = 93), Cuba (n = 50), the Dominican Republic (n = 203), Mexico (n = 708), Puerto Rico (n = 192), and South America (n = 111). By projection of principal components (PCs) of ancestry to samples from the HapMap phase III and the Human Genome Diversity Panel (HGDP), we show the first two PCs quantify the Caucasian, African, and Native American origins, while the third and fourth PCs bring out an axis that aligns with known South-to-North geographic location of HGDP Native American samples and further separates MESA Mexican versus Central/South American samples along the same axis. Using k-means clustering computed from the first four PCs, we define four subgroups of the MESA Hispanic cohort that show close agreement with self-identification, labeling the clusters as primarily Dominican/Cuban, Mexican, Central/South American, and Puerto Rican. To demonstrate our recommendations for genetic analysis in the MESA Hispanic cohort, we present pooled and stratified association analysis of triglycerides for selected SNPs in the LPL and TRIB1 gene regions, previously reported in GWAS of triglycerides in Caucasians but as yet unconfirmed in Hispanic populations. We report statistically significant evidence for genetic association in both genes, and we further demonstrate the importance of considering population substructure and genetic heterogeneity in genetic association studies performed in the United States Hispanic population.
Author Summary
Using genotype data from about 60,000 distinct genetic markers, we examined population structure in 1,374 unrelated Hispanic individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with self-identification corresponding to Central America (n = 93), Cuba (n = 50), the Dominican Republic (n = 203), Mexico (n = 708), Puerto Rico (n = 192), and South America (n = 111). By comparing genetic ancestry of MESA Hispanic participants to reference samples representing worldwide diversity, we show major differences in ancestry of MESA Hispanics reflecting their Caucasian, African, and Native American origins, with finer differences corresponding to North-South geographic origins that separate MESA Mexican versus Central/South American samples. Based on our analysis, we define four subgroups of the MESA Hispanic cohort that show close agreement with the following self-identified regions of origin: Dominican/Cuban, Mexican, Central/South American, and Puerto Rican. We examine association of triglycerides with selected genetic markers, and we further demonstrate the importance of considering differences in genetic ancestry (or factors associated with genetic ancestry) when performing genetic studies of the United States Hispanic population.
PMCID: PMC3325201  PMID: 22511882
18.  Racial/Ethnic Differences in the Association of Triglycerides with Other Metabolic Syndrome Components: The Multi-Ethnic Study of Atherosclerosis 
The aim of this study was to examine whether there are ethnic differences in the association of triglycerides (TG) with waist circumference (WC), blood pressure, high-density lipoprotein cholesterol (HDL-C), fasting glucose, and insulin resistance and to examine the disparities in the prevalence of the metabolic syndrome components between African Americans and non-Hispanic whites who do not have hypertriglyceridemia.
This study used the baseline data from the Multi-Ethnic Study of Atherosclerosis (MESA) study. The analysis included non-Hispanic whites (N = 2,427) and African Americans (N = 1,519) aged 45–84 years free of clinically evident cardiovascular disease and diabetes at baseline. The revised National Cholesterol Education Program (NCEP) criteria were used to define the metabolic syndrome and its components.
African Americans had lower prevalence of elevated TG as compared with non-Hispanic whites. The association of TG with other components of the metabolic syndrome appeared to be similar between African Americans and non-Hispanic whites except for one. There was significant association of TG with WC among white women but not among African American women after adjusting for demographic and other variables (P for interaction of TG with ethnicity <0.001). In participants with TG < 150 mg/dL, African American women had higher prevalence rates than white women of abdominal obesity, elevated blood pressure, low HDL-C, elevated fasting glucose and homeostasis model assessment of insulin resistance (HOMA-IR). In men, the prevalence rates of high blood pressure, elevated fasting glucose, and HOMA-IR were significantly higher in African Americans than in whites.
The study findings suggest that further evaluation is warranted regarding the cutoffs for elevated TG and its clustering effect with other cardiometabolic risk factors on predicting risk for diabetes and cardiovascular disease (CVD) in African Americans.
PMCID: PMC3125569  PMID: 20958206
19.  Comorbid disease and the effect of race and ethnicity on in-hospital mortality from aspiration pneumonia. 
BACKGROUND: Racial and ethnic disparities in mortality have been demonstrated in several diseases. African Americans are hospitalized at a significantly higher rate than whites for aspiration pneumonia; however, no studies have investigated racial and ethnic disparities in mortality in this population. OBJECTIVE: To assess the independent effect of race and ethnicity on in-hospital mortality among aspiration pneumonia discharges while comprehensively controlling for comorbid diseases, and to assess whether the prevalence and effects of comorbid illness differed across racial and ethnic categories. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 41,581 patients admitted to California hospitals for aspiration pneumonia from 1996 through 1998, using principal and secondary diagnoses present on admission. MEASUREMENT: The primary outcome measure was in-hospital mortality. RESULTS: The adjusted odds of in-hospital death for African-American compared with white discharges [odds ratio (OR)=1.01; 95% confidence interval (CI), 0.91-1.11] was not significantly different. The odds of death for Asian compared with white discharges was significantly lower (OR=0.83; 95% CI, 0.75-0.91). Hispanics had a significantly lower odds of death (OR=0.90; 95% CI, 0.82-0.988) compared to non-Hispanics. Comorbid diseases were more prevalent among African Americans and Asians than whites, and among Hispanics compared to non-Hispanics. Differences in effects of comorbid disease on mortality risk by race and ethnicity were not statistically significant. CONCLUSION: Asians have a lower risk of death, and the risk of death for African Americans is not significantly different from whites in this analysis of aspiration pneumonia discharges. Hispanics have a lower risk of death than non-Hispanics. While there are differences in prevalence of comorbid disease by racial and ethnic category, the effects of comorbid disease on mortality risk do not differ meaningfully by race or ethnicity.
PMCID: PMC2568617  PMID: 15586650
20.  Ethnic Differences in Hypertension Incidence among Middle-Aged and Older U. S. Adults: The Multi-Ethnic Study of Atherosclerosis 
Hypertension  2011;57(6):1101-1107.
The prevalence of hypertension is higher among African-Americans than whites. However, inconsistent findings have been reported on the incidence of hypertension among middle-aged and older African-Americans and whites and limited data are available on the incidence of hypertension among Hispanics and Asians in the US. Therefore, this study investigated the age-specific incidence of hypertension by ethnicity for 3,146 participants from the Multi-Ethnic Study of Atherosclerosis. Participants, age 45–84 years at baseline, were followed for a median of 4.8 years for incident hypertension, defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or the initiation of antihypertensive medications. The crude incidence rate of hypertension, per 1,000 person-years, was 56.8 for whites, 84.9 for African-Americans, 65.7 for Hispanics, and 52.2 for Chinese. After adjustment for age, gender, and study site, the incidence rate ratio (IRR) for hypertension was increased for African-Americans age 45–54 (IRR=2.05, 95% CI=1.47, 2.85), 55–64 (IRR=1.63, 95% CI=1.20, 2.23), and 65–74 years (IRR=1.67, 95% CI=1.21, 2.30) compared with whites, but not for those 75–84 years of age (IRR=0.97, 95% CI=0.56, 1.66). Additional adjustment for health characteristics attenuated these associations. Hispanic participants also had a higher incidence of hypertension compared with whites; however, hypertension incidence did not differ for Chinese and white participants. In summary, hypertension incidence was higher for African-Americans compared with whites between 45 and 74 years of age but not after age 75 years. Public health prevention programs tailored to middle-age and older adults are needed to eliminate ethnic disparities in incident hypertension.
PMCID: PMC3106342  PMID: 21502561
hypertension; race/ethnicity; epidemiology; incidence
21.  Socioeconomic status and prostate cancer incidence and mortality rates among the diverse population of California 
Cancer Causes & Control   2009;20(8):1431-1440.
The racial/ethnic disparities in prostate cancer rates are well documented, with the highest incidence and mortality rates observed among African-Americans followed by non-Hispanic Whites, Hispanics, and Asian/Pacific Islanders. Whether socioeconomic status (SES) can account for these differences in risk has been investigated in previous studies, but with conflicting results. Furthermore, previous studies have focused primarily on the differences between African-Americans and non-Hispanic Whites, and little is known for Hispanics and Asian/Pacific Islanders.
To further investigate the relationship between SES and prostate cancer among African-Americans, non-Hispanic Whites, Hispanics, and Asian/Pacific Islanders, we conducted a large population-based cross-sectional study of 98,484 incident prostate cancer cases and 8,997 prostate cancer deaths from California.
Data were abstracted from the California Cancer Registry, a population-based surveillance, epidemiology, and end results (SEER) registry. Each prostate cancer case and death was assigned a multidimensional neighborhood-SES index using the 2000 US Census data. SES quintile-specific prostate cancer incidence and mortality rates and rate ratios were estimated using SEER*Stat for each race/ethnicity categorized into 10-year age groups.
For prostate cancer incidence, we observed higher levels of SES to be significantly associated with increased risk of disease [SES Q1 vs. Q5: relative risk (RR) = 1.28; 95% confidence interval (CI): 1.25–1.30]. Among younger men (45–64 years), African-Americans had the highest incidence rates followed by non-Hispanic Whites, Hispanics, and Asian/Pacific Islanders for all SES levels. Yet, among older men (75–84 years) Hispanics, following African-Americans, displayed the second highest incidence rates of prostate cancer. For prostate cancer deaths, higher levels of SES were associated with lower mortality rates of prostate cancer deaths (SES Q1 vs. Q5: RR = 0.88; 95% CI: 0.92–0.94). African-Americans had a twofold to fivefold increased risk of prostate cancer deaths in comparison to non-Hispanic Whites across all levels of SES.
Our findings suggest that SES alone cannot account for the greater burden of prostate cancer among African-American men. In addition, incidence and mortality rates of prostate cancer display different age and racial/ethnic patterns across gradients of SES.
Electronic supplementary material
The online version of this article (doi:10.1007/s10552-009-9369-0) contains supplementary material, which is available to authorized users.
PMCID: PMC2746891  PMID: 19526319
Prostate cancer; Socioeconomic status; Disparities; Incidence rates; Mortality rates
22.  Candidate Genetic Variants in the Fibrinogen, Methylenetetrahydrofolate Reductase and Intercellular Adhesion Molecule-1 Genes and Plasma levels of Fibrinogen, Homocysteine, and Intercellular Adhesion Molecule-1 Among Various Race/ethnic Groups: Data from the Women’s Genome Health Study 
American heart journal  2009;157(4):777-83.e1.
Examine the relationship between specific polymorphisms in the fibrinogen, homocysteine and intercellular adhesion molecule-1 genes and their respective inflammatory biomarker concentrations at baseline in women from different race/ethnic groups.
Although inflammation is a core element of atherogenesis and plasma levels of fibrinogen, homocysteine and intercellular adhesion molecule-1 (ICAM-1) differ by race/ethnicity, little is known about the role of genetic polymorphisms in the fibrinogen (FGB), methylenetetrahydrofolate reductase (MTHFR), and intercellular adhesion molecule-1 (ICAM-1) genes in determining plasma levels of these biomarkers.
We genotyped specific polymorphisms in FGB (-455G>A/rs1800790), MTHFR (677C>T/rs1801133) and ICAM-1 (Lys56Met/rs5491 and Gly241Arg/rs1799969) at baseline, and evaluated their relationship with respective inflammatory biomarker levels in 25, 565 white, 476 African-American (black), 277 Hispanic and 370 Asian women participating in the Women’s Genome Health Study.
Overall, the minor allele frequencies for –455G>A were similar among white, Hispanic and Asian women (17.2 to 21.9%) but significantly lower in black women (6.6%, p< 0.001). The minor allele was associated with elevated fibrinogen levels only in whites and Asians. After adjustment for age, body mass index, smoking, postmenopausal status, diabetes, hormone replacement therapy use, hypertension and education, black women had the highest fibrinogen levels compared to other race/ethnic groups. The minor allele frequency of the MTHFR 677C>T polymorphism was lowest in blacks (blacks 12.1%, whites 33.1%, Hispanics 39.0%, Asians 24.0%) and the T allele was only significantly associated with homocysteine levels in white women. Among whites, Hispanics and Asians, the Lys56Met polymorphism was rare compared to the frequency in blacks (p <0.001). Neither the Lys56Met nor Gly241Arg polymorphisms were common in Asians. Nonetheless, both polymorphisms were generally associated with lower ICAM-1 levels; the lowest levels were observed in black women.
We found significant associations between certain candidate genetic polymorphisms and baseline plasma levels of fibrinogen, homocysteine and intercellular adhesion molecule-1 in women from various race/ethnic groups. The present investigation is hypothesis generating and suggests genetic determination of differential concentrations of these atherosclerosis-related inflammatory biomarkers differ among various race/ethnic groups.
PMCID: PMC2737822  PMID: 19332210
fibrinogen; ICAM-1; homocysteine; genetic polymorphisms; race/ethnicity
23.  Race/ethnic differences in bone mineral densities in older men 
Osteoporosis International  2010;21(12):2115-2123.
BMD was compared across race/ethnic groups. There were substantial race/ethnic differences in BMD even within African or Asian origin. Additional adjustment for body size greatly attenuated or reversed the differences between US Caucasian men vs Asian men. It illustrates the role of body size on the difference between these groups.
There is insufficient epidemiologic information about men’s bone mineral density (BMD) levels across race/ethnic groups and geographic locations.
In a cross-sectional design, we compared BMD in older men across seven race/ethnic groups in four countries. Femoral neck, total hip, and lumbar spine BMD were measured in men (age 65 to 78 years) from the Osteoporotic Fractures in Men (MrOS) Study (4,074 Caucasian, 208 African-American, 157 Asian, and 116 Hispanic men in USA), Tobago Bone Health Study (422 Afro-Caribbean men), MrOS Hong Kong Study (1,747 Hong Kong Chinese men), and the Namwon Study (1,079 South Korean men). BMD was corrected according to the cross-site calibration results for all scanners.
When compared with US Caucasian men, Afro-Caribbean and African-American men had, respectively, 8–20% and 6–11% higher age-adjusted mean BMD at all three bone sites. Hip BMD was similar in US Caucasian and Hispanic men, US Asian, Hong Kong Chinese, and Korean men had 3–14% lower BMD at all bone sites except femoral neck in Korean men. Additional adjustment for weight and height greatly attenuated or reversed the differences between US Caucasian men vs Asian men including US Asian, Hong Kong Chinese, and South Korean men. Among Asian groups, Korean men had higher femoral neck BMD and lower total hip BMD.
These findings show substantial race/ethnic differences in BMD even within African or Asian origin and illustrate the important role of body size on the difference between Asian men and others.
PMCID: PMC2974925  PMID: 20204598
Body size; Bone densitometry; Bone mineral density; Epidemiology; Men; Race/ethnicity
24.  Frequency of the Cholesteryl Ester Storage Disease Common LIPA E8SJM Mutation (c.894G>A) in Various Racial and Ethnic Groups 
Hepatology (Baltimore, Md.)  2013;58(3):958-965.
Cholesteryl Ester Storage Disease (CESD) and Wolman disease are autosomal recessive later-onset and severe infantile disorders, respectively, which result from the deficient activity of lysosomal acid lipase (LAL). LAL is encoded by LIPA (10q23.31) and the most common mutation associated with CESD is an exon 8 splice junction mutation (c.894G>A; E8SJM), which expresses only ~3–5% of normally spliced LAL. However, the frequency of c.894G>A is unknown in most populations. To estimate the prevalence of CESD in different populations, the frequencies of the c.894G>A mutation were determined in 10,000 LIPA alleles from healthy African-American, Asian, Caucasian, Hispanic and Ashkenazi Jewish individuals from the greater New York metropolitan area and 6,578 LIPA alleles from African-American, Caucasian, and Hispanic subjects enrolled in the Dallas Heart Study. The combined c.894G>A allele frequencies from the two cohorts ranged from 0.0005 (Asian) to 0.0017 (Caucasian and Hispanic), which translated to carrier frequencies of 1 in 1,000 to ~1 in 300, respectively. No African-American heterozygotes were detected. Additionally, by surveying the available literature, c.894G>A was estimated to account for 60% (95% CI: 51%–69%) of reported mutations among multi-ethnic CESD patients. Using this estimate, the predicted prevalence of CESD in the Caucasian and Hispanic populations is ~0.8 per 100,000 (~1 in 130,000; 95% CI: ~1 in 90,000 to 1 in 170,000).
These data indicate that CESD may be under-diagnosed in the general Caucasian and Hispanic populations, which is important since clinical trials of enzyme replacement therapy for LAL deficiency are currently being developed. Moreover, future studies on CESD prevalence in African and Asian populations may require full-gene LIPA sequencing to determine heterozygote frequencies since c.894G>A is not common in these racial groups.
PMCID: PMC3690149  PMID: 23424026
lysosomal acid lipase deficiency; allele frequency; carrier frequency; disease prevalence; splice junction mutation; genotyping
25.  Biomarkers Associated With Pulse Pressure in African-Americans and Non-Hispanic Whites 
American journal of hypertension  2011;25(2):145-151.
Pulse pressure (an indirect measure of arterial stiffness) is a robust predictor of cardiovascular events, but its pathophysiology remains poorly understood. To gain insight into the pathophysiology of arterial stiffness we conducted an exploratory investigation of the associations of 47 circulating biomarkers in etiologic pathways of arteriosclerosis with brachial artery pulse pressure.
Participants included 1,193 African-Americans and 1,145 non-Hispanic whites belonging to hypertensive sibships. Blood pressure (BP) was measured with a random-zero sphygmomanometer. Multivariable linear regression was employed to assess the associations of biomarkers with pulse pressure after adjustment for age, sex, conventional risk factors, mean arterial pressure, heart rate, and use of aspirin, statins, estrogens, and antihypertensives. Statistical significance was set at P ≤ 0.001 (Bonferroni correction for multiple testing).
Log N-terminal probrain natriuretic peptide (NT-proBNP) (African-Americans: β = 2.11 ± 0.52, non-Hispanic whites: β = 2.65 ± 0.55), log midregional proatrial natriuretic peptide (African-Americans: β = 4.83 ± 0.70, non-Hispanic whites: β = 3.70 ± 0.67), and log osteoprotegerin (African-Americans: β = 4.64 ± 1.02, non-Hispanic whites: β = 4.19 ±0.99) were independently associated with pulse pressure (P < 0.001 for all) in both ethnicities. Log C-reactive protein (CRP) (β = 1.56 ± 0.35), log midregional proadrenomedullin (MR-proADM) (β = 5.53 ± 1.19) and log matrix metalloproteinase-2 (β = 3.89 ± 1.06) were associated with greater pulse pressure in African-Americans only (P ≤ 0.001 for all), whereas higher fibrinogen was associated with pulse pressure in non-Hispanic whites only (β = 0.02 ± 0.004. P < 0.001).
Our results suggest that hemodynamic stress, vascular inflammation and calcification, and matrix remodeling may have a role in the pathogenesis and/or adverse consequences of increased pulse pressure.
PMCID: PMC3707798  PMID: 22012208
adrenomedullin; arterial stiffness; atrial natriuretic peptide; biomarkers; blood pressure; brain natriuretic peptide; fibrinogen; hypertension; matrix metalloproteinase-2; osteoprotegerin; pulse pressure

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