The Family Blood Pressure Program is an ongoing, NHLBI-sponsored, multi-center program to study the genetic determinants of high blood pressure. The goal of this particular study was to study patterns of metabolic syndrome (MetS) in four ethnic groups: African Americans, Caucasians, Hispanics, and Asians.
A major part of participants in three networks GENOA, HyperGEN and SAPPHIRe were recruited mainly through hypertensive probands. MetS was defined as a categorical trait following the National Cholesterol Education Program definition (c-MetS). MetS was also characterized quantitatively through multivariate factor analyses (FA) of 10 risk variables (q-MetS). Logistic regression and frequency tables were used for studying associations among traits.
Using the NCEP definition, the Hispanic sample, which by design was enriched for type 2 diabetes (T2D), had a very high prevalence of MetS (73%). In contrast, its prevalence in Chinese was the lowest (17%). In African Americans and Hispanics, c-MetS was more prevalent in women than in men. Association of c-MetS with type 2 diabetes (T2D) was prominent in the Hispanics and African Americans, less pronounced in the Whites and Japanese, (although still significant), and weakest in the Chinese sample.
Using FA without rotation, we found that the main factor loaded obesity (OBS) and blood pressure (BP) in African Americans; OBS and insulin (INS) in Hispanics, in Japanese, and in Whites; and OBS alone in Chinese. In Hispanics, Whites, and Japanese, BP loaded as a separate factor. Lipids in combination with INS also loaded in a separate factor. Using FA with Varimax rotation, 4 independent factors were identified: "Obesity-INS," "Blood pressure," "Lipids-INS," and "Central obesity." They explained about 60% of the variance present in the original risk variables.
MetS ethnic differences were identified. Ascertaining for hypertension or T2D increased the MetS prevalence in networks compared with the one in the US general population. Obesity was the most prominent risk factor contributing to both c-MetS and q-MetS. INS contributed in two important factors (obesity and lipids). The information imbedded into c-MetS trait /q-MetS factors scores can contribute in future research of the MetS, especially its utilization in the genetic analysis.
African Americans generally have lower circulating levels of 25 hydroxyvitamin D (25(OH)D) than whites, attributed to skin pigmentation and dietary habits. Little is known about the genetic determinants of 25(OH)D levels, nor whether the degree of African ancestry associates with circulating 25(OH)D.
Using a panel of 276 ancestry informative genetic markers, we estimated African and European admixture for a sample of 758 African American and non-Hispanic white Southern Community Cohort Study participants. For African Americans, cutpoints of <85%, 85%–95%, and ≥95% defined “low”, “medium”, and “high” African ancestry. We estimated the association between African ancestry and 25(OH)D, and also explored whether vitamin D exposure (sunlight, diet) had varying effects on 25(OH)D levels dependent on ancestry level.
Mean serum 25(OH)D levels among whites and among African Americans of low, medium, and high African ancestry were 27.2, 19.5, 18.3, and 16.5ng/mL, respectively. Serum 25(OH)D was estimated to decrease by 1.0–1.1ng/mL per 10% increase in African ancestry. The effect of high vitamin D exposure from sunlight and diet was 46% lower among African Americans with high African ancestry than among those with low/medium ancestry.
We found novel evidence that the level of African ancestry may play a role in clinical vitamin D status.
This is the first study to describe how 25(OH)D levels vary in relation to genetic estimation of African ancestry. Further study is warranted to replicate these findings and uncover the potential pathways involved.
vitamin D; African Americans; health status disparities; genetics; epidemiology
We compared the odds of vitamin D deficiency in three chronic diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and type 2 diabetes (T2DM), adjusting for medications, demographics, and laboratory parameters, common to all three diseases. We also designed multivariate models to determine whether different factors are associated with vitamin D deficiency in different racial/ethnic groups.
We identified all patients with non-overlapping diagnoses of SLE, RA, and T2DM, with 25-hydroxyvitamin D (25OHD) levels measured between 2000 and 2009. Vitamin D deficiency was defined as 25OHD levels <20 ng/ml, based on previously established definitions. Race/ethnicity was analyzed as African-American non-Hispanic (African-American), Hispanic non-African-American (Hispanic), and Other based on self report.
We included 3,914 patients in the final analysis: 123 SLE, 100 RA, and 3,691 T2DM. Among African-Americans the frequency of vitamin D deficiency was 59% in SLE, 47% in RA, and 67% in T2DM. Among Hispanics the frequency of vitamin D deficiency was 67% in SLE, 50% in RA, and 59% in T2DM. Compared with the SLE group, the adjusted odds ratio of vitamin D deficiency was 1.1, 95% CI (0.62, 2.1) in the RA group, and 2.0, 95% CI (1.3, 3.1) in the T2DM group. In the multivariate analysis, older age, higher serum calcium and bisphosphonate therapy were associated with a lower odds of vitamin D deficiency in all three racial/ethnic groups: 1,330 African-American, 1,257 Hispanic, and 1,100 Other. T2DM, serum creatinine, and vitamin D supplementation were associated with vitamin D deficiency in some, but not all, racial/ethnic groups.
Vitamin D deficiency is highly prevalent in our patients with SLE, RA, and T2DM. While the odds of vitamin D deficiency are similar in RA and SLE patients in a multivariate analysis, T2DM patients have much higher odds of being vitamin D deficient. Different demographic and laboratory factors may be associated with vitamin D deficiency within different racial/ethnic groups. Therefore, disease-specific and race/ethnicity-specific definitions of vitamin D deficiency need to be established in future studies in order to define goals of vitamin D replacement in patients with autoimmune and non-autoimmune chronic diseases.
Vitamin D reportedly influences vascular function, which is worse in African Americans (AAs) relative to European Americans (EAs). It is not clear if ethnic differences in 25(OH)D mediate differences in vascular function. This study examined the relationships of serum 25-hydroxyvitamin D (25(OH)D) with indicators of vascular function among healthy, young AA and EA adults.
This is a cross sectional study involving 23 AAs and 22 EAs. The main outcomes were augmentation index (AIx75), central aortic pressure, pulse wave velocity (PWV), flow-mediated dilation (FMD), and seated and supine blood pressures.
Results indicated that 25(OH)D was inversely associated with AIx75, supine systolic blood pressure (SBP), central aortic SBP and central aortic diastolic blood pressure (DBP), independent of age, sex, and percent body fat (standardized β= -0.29 to -0.43, P < 0.05 for all). AAs had greater AIx75 (P = 0.04) and PWV (P = 0.07) and lower FMD (P = 0.02) compared to EA after adjusting for age and percent body fat; further adjustment for 25(OH)D reduced the ethnic differences (P = 0.44, 0.53, and 0.20, respectively).
The 25(OH)D was associated with vascular function in healthy adults, and lower 25(OH)D among AAs may contribute to their greater arterial stiffness and reduced endothelial function (Clinical trials.gov NCT01041365, NCT01041547).
Vitamin D; Hypertension; Blood pressure; African Americans; Augmentation index; Pulse wave velocity; Flow mediated dilation; Vascular function
Multiple studies have identified FTO gene variants associated with measures of adiposity in European-derived populations. The study objective was to determine whether FTO variants were associated with adiposity, including visceral and subcutaneous adipose tissue (VAT; SAT), and glucose homeostasis measures in the Insulin Resistance Atherosclerosis Family Study (IRASFS). A total of 27 SNPs in FTO intron 1, including SNPs prominent in the literature (rs9939609, rs8050136, rs1121980, rs17817449, rs1421085, and rs3751812), were genotyped in 1,424 Hispanic Americans and 604 African Americans. Multiple SNPs were associated with BMI and SAT (p-values ranging from 0.001 to 0.033), and trending or associated with waist circumference (p-values ranging from 0.008 to 0.099) in the Hispanic Americans. No association was observed with VAT, illustrating that FTO variants are associated with overall fat mass instead of specific fat depots. For the glucose homeostasis measures, variants were associated with fasting insulin but, consistent with other studies, after BMI adjustment, no evidence of association remained. The lack of association of FTO SNPs with insulin sensitivity is consistent with the lack of association with VAT, since these traits are strongly correlated. In the African Americans, only rs8050136 and rs9939609 were associated with BMI and WAIST (p-values of 0.011 and 0.034), and associated or trending towards association with SAT (p-values of 0.038 and 0.058). These results confirm that FTO variants are associated with adiposity measures, predisposing individuals to obesity by increasing overall fat mass in Hispanic Americans and to a lesser degree in African Americans.
fat mass and obesity associated (FTO) gene; single nucleotide polymorphism; genetic association; adiposity; glucose homeostasis
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.
This study evaluated the influence of somatostatin receptor type 2 (SSTR2) polymorphisms on measures of glucose homeostasis in the Insulin Resistance Atherosclerosis Family Study (IRASFS). SSTR2 is a G-protein–coupled receptor that, in response to somatostatin, mediates inhibition of insulin, glucagon, and growth hormone release and thus may affect glucose homeostasis.
RESEARCH DESIGN AND METHODS
Ten single nucleotide polymorphisms (SNPs) spanning the gene were chosen using a SNP density selection algorithm and genotyped on 1,425 Hispanic-American individuals from 90 families in the IRASFS. These families comprised two samples (set 1 and set 2), which were analyzed individually and as a combined set. Single SNP tests of association were performed for four glucose homeostasis measures—insulin sensitivity (SI), acute insulin response (AIR), disposition index (DI), and fasting blood glucose (FBG)—using generalized estimating equations.
The SSTR2 locus was encompassed by a single linkage disequilibrium (LD) block (D′ = 0.91–1.00; r2 = 0.09–0.97) that contained four of the ten SNPs evaluated. Within the SSTR2-containing LD block, evidence of association was observed in each of the two sets and in a combined analysis with decreased SI(βhomozygous = −0.16; Pmeta-analysis = 0.0024–0.0030), decreased DI (βhomozygous = −0.35 to −5.16; Pmeta-analysis = 0.0075–0.027), and increased FBG (βhomozygous = 2.30; Pmeta-analysis = 0.045). SNPs outside the SSTR2-containing LD block were not associated with measures of glucose homeostasis.
We observed evidence for association of SSTR2 polymorphisms with measures of glucose homeostasis. Thus, variants in SSTR2 may influence pathways of SIto modulate glucose homeostasis.
African-Americans have a disproportionate burden of hypertension compared to Caucasians, while data on Hispanics is less well-defined. Mechanisms underlying these differences are unclear, but could be due in part to ancestral background and vascular function.
Methods and Results
660 African-Americans and 635 Hispanics from the Multi-Ethnic Study of Atherosclerosis (MESA) with complete data on genetic ancestry, pulse pressure (PP), and large and small arterial elasticity (LAE, SAE) were studied. LAE and SAE were obtained using the HDI PulseWave CR-2000 Research CardioVascular Profiling Instrument. Among African-Americans higher European ancestry was marginally associated with higher LAE (p=0.05) and lower PP (p=0.05) among African-Americans; results for LAE were attenuated after adjustment for potential mediators (p=0.30). Ancestry was not associated with SAE in African-Americans. Among Hispanics, higher Native American ancestry was associated with higher SAE (p=0.0006); higher African ancestry was marginally associated with lower SAE (p=0.07). Ancestry was not significantly associated with LAE or PP in Hispanics.
Among African-Americans, higher European ancestry may be associated with less large artery damage as measured by LAE and PP, although these associations warrant further study. Among Hispanics, ancestry is strongly associated with SAE. Future studies should consider information on genetic ancestry when studying hypertension burden in race/ethnic minorities, particularly among Hispanics.
large artery elasticity; small artery elasticity; admixture; pulse pressure
Cardiovascular disease has a progressively earlier age of onset, and disproportionately affects African Americans in the US. It has been difficult to establish the extent to which group differences are due to physiological, genetic, social, or behavioral factors. In this study, we examined the association between blood pressure and these factors among a sample of 294 children, identified as African-, European-, or Hispanic-American. We use body composition, behavioral (diet and physical activity), and survey-based measures (socio-economic status and perceived racial discrimination), as well as genetic admixture based on 142 ancestry informative markers (AIM) to examine associations with systolic and diastolic blood pressure. We find that associations differ by ethnic/racial group. Notably, among African Americans, physical activity and perceived racial discrimination, but not African genetic admixture, are associated with blood pressure, while the association between blood pressure and body fat is nearly absent. We find an association between blood pressure and an AIM near a marker identified by a recent genome-wide association study. Our findings shed light on the differences in risk factors for elevated blood pressure among ethnic/racial groups, and the importance of including social and behavioral measures to grasp the full genetic/environmental etiology of disparities in blood pressure.
blood pressure; racial/ethnic disparities; children; genetic admixture; social and behavioral risk factors
We evaluated vitamin D status in HIV+ and HIV− postmenopausal African-American (AA) and Hispanic women. Most women (74–78%) had insufficient 25-hydroxyvitamin D (25OHD) levels, regardless of HIV status. 25OHD was lower in AA women and women lacking supplement use, providing support for screening and supplementation. Among HIV+ women, 25OHD was associated with current CD4 but not type of antiretroviral therapy.
To evaluate vitamin D status and factors associated with vitamin D deficiency and insufficiency in HIV-infected (HIV+) postmenopausal minority women.
In this cross-sectional study, 89 HIV+ and 95 HIV− postmenopausal women (33% AA and 67% Hispanic) underwent assessment of 25OHD, 1,25-dihydroxyvitamin D, parathyroid hormone, markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry.
The prevalence of low 25OHD did not differ by HIV status; the majority of both HIV+ and HIV− women (74–78%) had insufficient levels (<30 ng/ml). Regardless of HIV status, 25OHD was significantly lower in AA subjects, and higher in subjects who used both calcium and multi-vitamins. In HIV+ women on antiretroviral therapy (ART), 25OHD was directly associated with current CD4 count (r= 0.32; p<0.01) independent of age, ethnicity, BMI, or history of AIDS-defining illness. No association was observed between 1,25(OH)2D and CD4 count or between serum 25OHD, 1,25(OH)2D or PTH and type of ART.
In postmenopausal minority women, vitamin D deficiency was highly prevalent and associated with AA race and lack of supplement use, as well as lower current CD4 cell count. These results provide support for screening and repletion of vitamin D in HIV+ patients.
African-American; Hispanic; HIV+ postmenopausal women; Vitamin D
Vitamin D status, as indicated by 25-hydroxyvitamin D is inversely associated with adiposity, glucose homeostasis, lipid profiles, and blood pressure along with its classic role in calcium homeostasis and bone metabolism. It is also shown to be inversely associated with metabolic syndrome and cardiovascular diseases in western populations. However, evidence from the Asian population is limited. Therefore, we aim to study the prevalence of vitamin D insufficiency (< 50 nmol/L) and the association of 25-hydroxyvitamin D with metabolic risk factors among an existing Malay cohort in Kuala Lumpur.
This is an analytical cross sectional study. A total of 380 subjects were sampled and their vitamins D status (25-hydroxyvitamin D), fasting blood glucose, full lipid profile were assessed using venous blood. Systolic and diastolic blood pressure, weight, height and waist circumference were measured following standard protocols. Socio-demographic data such as sex, age, smoking status etc were also collected. Data was analysed using t-test, chi-square test, General Linear Model and multiple logistic regression.
Females made up 58% of the sample. The mean age of respondents was 48.5 (SD 5.2) years. Females had significantly lower mean Vitamin D levels (36.2; 95% CI: 34.5, 38.0 nmol/L) compared to males (56.2; 95% CI: 53.2, 59.2 nmol/L). Approximately 41% and 87% of males and females respectively had insufficient (< 50 nmol/L) levels of 25-hydroxyvitamin D (p < 0.001). The prevalence of Metabolic Syndrome for the whole sample was 38.4 (95% CI: 33.5, 43.3)%. In the multivariate model (adjusted for age, sex, abdominal obesity, HDL-cholesterol, diastolic blood pressure), insufficient Vitamin D status was significantly associated with 1-year age increments (OR: 0.93; 95% CI: 0.88, 0.98), being female (OR: 8.68; 95% CI: 5.08, 14.83) and abdominal obesity (OR: 2.57; 95% CI: 1.51, 4.39). Respondents with insufficient vitamin D were found to have higher odds of having Metabolic Syndrome (OR: 1.73; 95% CI: 1.02, 2.92) after adjusting for age and sex.
Our results highlight the high prevalence of vitamin D insufficiency among Malay adults in Kuala Lumpur. Vitamin D insufficiency is independently associated with younger age, female sex and greater abdominal obesity. Vitamin D insufficiency is also associated with Metabolic Syndrome.
Vitamin D is implicated in a wide range of health outcomes, and although environmental predictors of vitamin D levels are known, the genetic drivers of vitamin D status remain to be clarified. African Americans are a group at particularly high risk for vitamin D insufficiency but to date have been virtually absent from studies of genetic predictors of circulating vitamin D levels. Within the Southern Community Cohort Study, we investigated the association between 94 single nucleotide polymorphisms (SNPs) in five vitamin D pathway genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1) and serum 25-hydroxyvitamin D (25(OH)D) levels among 379 African American and 379 Caucasian participants. We found statistically significant associations with three SNPs (rs2298849 and rs2282679 in the GC gene, and rs10877012 in the CYP27B1 gene), although only for African Americans. A genotype score, representing the number of risk alleles across the three SNPs, alone accounted for 4.6% of the variation in serum vitamin D among African Americans. A genotype score of 5 (vs. 1) was also associated with a 7.1 ng/mL reduction in serum 25(OH)D levels and a six-fold risk of vitamin D insufficiency (<20 ng/mL) (odds ratio 6.0, p = 0.01) among African Americans. With African ancestry determined from a panel of 276 ancestry informative SNPs, we found that high risk genotypes did not cluster among those with higher African ancestry. This study is one of the first to investigate common genetic variation in relation to vitamin D levels in African Americans, and the first to evaluate how vitamin D-associated genotypes vary in relation to African ancestry. These results suggest that further evaluation of genetic contributors to vitamin D status among African Americans may help provide insights regarding racial health disparities or enable the identification of subgroups especially in need of vitamin D-related interventions.
Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients.
We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (<15 ng/ml and ≥15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type.
Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (<15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04).
Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor.
Vitamin D is obtained from the diet and synthesized in skin exposed to sunlight. Vitamin D status, assessed by circulating 25-hydroxyvitamin D [25(OH)D], has been associated with a reduced risk of colorectal cancer in previous studies. To complement existing evidence, we conducted a case-control study nested within the Multiethnic Cohort including men and women of Japanese, Latino, African American, White, and Native Hawaiian ancestry. Using a direct competitive chemiluminescence immunoassay, 25(OH)D level was determined in plasma drawn before diagnosis from 229 cases and 434 controls matched to cases by area (Hawaii, Los Angeles), sex, ethnicity, birth year, blood draw date and time, and hours fasting. Odds ratios (OR) were estimated with conditional logistic regression. An inverse trend was observed (OR per doubling of [25(OH)D], 0.68; 95% CI, 0.51–0.92; P = 0.01), but when examined in categories, relative to the first quintile (<16.8 ng/mL), the ORs in all other quintiles were quite similarly reduced between 37% and 46%. The association was not significantly heterogeneous among the four largest ethnic groups (Pheterogeneity = 0.46). In summary, this study provides evidence of an association between vitamin D status and reduced risk of colorectal cancer in an ethnically diverse population.
Vitamin D; plasma; colorectal cancer; nested case-control
There is evidence that the utilization of antidepressant medications (ADM) may vary between different ethnic groups in the United States population.
The Multi-Ethnic Study of Atherosclerosis is a population-based prospective cohort study of 6,814 US adults from 4 different ethnic groups. After excluding baseline users of ADM, we examined the relation between baseline depression and new use of ADM for 4 different ethnicities: African-Americans (n=1,822), Asians (n=784) Caucasians (n=2,300), and Hispanics (n=1,405). Estimates of the association of ethnicity and ADM use were adjusted for age, study site, gender, Center for Epidemiologic Studies Depression Scale (CES-D), alcohol use, smoking, blood pressure, diabetes, education, and exercise. Non-random loss to follow-up was present and estimates were adjusted using inverse probability of censoring weighting (IPCW).
Of the four ethnicities, Caucasian participants had the highest rate of ADM use (12%) compared with African-American (4%), Asian (2%) and Hispanic (6%) participants. After adjustment, non-Caucasian ethnicity was associated with reduced ADM use: African-American (HR: 0.42; 95% Confidence Interval (CI):0.31– 0.58), Asian (HR: 0.14; 95%CI: 0.08–0.26) and Hispanic (HR: 0.47; 95%CI: 0.31–0.65). Applying IPCW to correct for non-random loss to follow-up among the study participants weakened but did not eliminate these associations: African-American (HR: 0.48; 95%CI: 0.30–0.57), Asian (HR: 0.23; 95% CI: 0.13–0.37) and Hispanic (HR: 0.58; 95%CI: 0.47–0.67).
Non-Caucasian ethnicity is associated with lower rates of new ADM use. After IPCW adjustment, the observed ethnicity differences in ADM use are smaller although still statistically significant.
Inverse probability of censoring weighting; ethnicity; antidepressants; drug utilization; Multi-Ethnic Study of Atherosclerosis; non-random loss to follow-up
Background. The NCEP metabolic syndrome (MetS) is a combination of dichotomized interrelated risk factors from predominantly Caucasian populations. We propose a continuous MetS score based on principal component analysis (PCA) of the same risk factors in a multiethnic cohort and compare prediction of incident CVD events with NCEP MetS definition. Additionally, we replicated these analyses in the Health, Aging, and Body composition (Health ABC) study cohort. Methods and Results. We performed PCA of the MetS elements (waist circumference, HDL, TG, fasting blood glucose, SBP, and DBP) in 2610 Caucasian Americans, 801 Chinese Americans, 1875 African Americans, and 1494 Hispanic Americans in the multiethnic study of atherosclerosis (MESA) cohort. We selected the first principal component as a continuous MetS score (MetS-PC). Cox proportional hazards models were used to examine the association between MetS-PC and 5.5 years of CVD events (n = 377) adjusting for age, gender, race, smoking and LDL-C, overall and by ethnicity. To facilitate comparison of MetS-PC with the binary NCEP definition, a MetS-PC cut point was chosen to yield the same 37% prevalence of MetS as the NCEP definition (37%) in the MESA cohort. Hazard ratio (HR) for CVD events were estimated using the NCEP and Mets-PC-derived binary definitions. In Cox proportional models, the HR (95% CI) for CVD events for 1-SD (standard deviation) of MetS-PC was 1.71 (1.54–1.90) (P < 0.0001) overall after adjusting for potential confounders, and for each ethnicity, HRs were: Caucasian, 1.64 (1.39–1.94), Chinese, 1.39 (1.06–1.83), African, 1.67 (1.37–2.02), and Hispanic, 2.10 (1.66-2.65). Finally, when binary definitions were compared, HR for CVD events was 2.34 (1.91–2.87) for MetS-PC versus 1.79 (1.46–2.20) for NCEP MetS. In the Health ABC cohort, in a fully adjusted model, MetS-PC per 1-SD (Health ABC) remained associated with CVD events (HR = 1.21, 95%CI 1.12–1.32) overall, and for each ethnicity, Caucasian (HR = 1.24, 95%CI 1.12–1.39) and African Americans (HR = 1.16, 95%CI 1.01–1.32). Finally, when using a binary definition of MetS-PC (cut point 0.505) designed to match the NCEP definition in terms of prevalence in the Health ABC cohort (35%), the fully adjusted HR for CVD events was 1.39, 95%CI 1.17–1.64 compared with 1.46, 95%CI 1.23–1.72 using the NCEP definition. Conclusion. MetS-PC is a continuous measure of metabolic syndrome and was a better predictor of CVD events overall and in individual ethnicities. Additionally, a binary MetS-PC definition was better than the NCEP MetS definition in predicting incident CVD events in the MESA cohort, but this superiority was not evident in the Health ABC cohort.
The genome-wide association study by Herbert and colleagues identified the INSIG2 single nucleotide polymorphism (SNP) rs7566605 as contributing to increased BMI in ethnically distinct cohorts. The present study sought to further clarify by testing whether SNPs of INSIG2 influenced quantitative adiposity or glucose homeostasis traits in Hispanics of the Insulin Resistance Atherosclerosis Family Study (IRASFS). Using a tagging SNP approach, rs7566605 and 31 additional SNPs were genotyped in 1425 IRASFS Hispanics. SNPs were tested for association with six adiposity measures: BMI, waist circumference (WAIST), waist to hip ratio (WHR), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and VAT to SAT ratio (VSR). SNPs were also tested for association with fasting glucose (GFAST), fasting insulin (FINS), and three measures obtained from the frequently sampled intravenous glucose tolerance test: insulin sensitivity (SI), acute insulin response (AIR), and disposition index (DI). Most prominent association was observed with direct CT-measured adiposity phenotypes, including VAT, SAT, and VSR (P-values range from 0.007 to 0.044 for rs17586756, rs17047718, rs17047731, rs9308762, rs12623648, and rs11673900). Multiple SNP associations were observed with all glucose homeostasis traits (P-values range from 0.001 to 0.031 for rs17047718, rs17047731, rs2161829, rs10490625, rs889904, and rs12623648). Using BMI as a covariate in evaluation of glucose homeostasis traits slightly reduced their association. However, association with adiposity and glucose homeostasis phenotypes is not significant following multiple comparisons adjustment. Trending association after multiple comparisons adjustment remains suggestive of a role for genetic variation of INSIG2 in obesity, but these results require validation.
Insulin-induced gene 2; single nucleotide polymorphism; genetic association; adiposity; glucose homeostasis
Disparities in hypertension between African Americans and non-Hispanic whites have been well-documented, yet an explanation for this persistent disparity remains elusive. Since African Americans and non-Hispanic white Americans tend to live in very different social environments, it is not known whether race disparities in hypertension would persist if non-Hispanic whites and African Americans were exposed to similar social environments. We compared data from the Exploring Health Disparities in Integrated Communities-SWB (EHDIC-SWB) Study with the National Health and Nutrition Examination Survey (NHANES) 1999–2004 to determine if race disparities in hypertension in the USA were attenuated in EHDIC-SWB, which is based in a raciallyintegrated community without race differences in income. Hypertension was defined as systolic Blood Pressure (BP)>= 140 millimeters of mercury (mmHg) and/or diastolic BP >= 90 mm Hg or respondent’s report of taking antihypertensive medications. Of the 1408 study participants, 835 (59.3%) were African American, 628 (44.6%) were men, and the mean age was 40.6 years. After adjustment for potential confounders, various analytic models from EHDIC-SWB and NHANES 1999–2004 data, we found the race odds ratio was between 29.0% and 34% smaller in the EHDIC-SWB sample. We conclude that social and environmental exposures explained a substantial proportion of the race difference in hypertension.
Racial disparities; hypertension; residential segregation; confounding race and socioeconomic status (SES); Integrated community; USA
The SOCS3 gene product participates in the feedback inhibition of a range of cytokine signals. Most notably, SOCS3 inhibits the functioning of leptin and downstream steps in insulin signaling after being expressed by terminal transcription factors, such as STAT3 and c-fos. The SOCS3 gene is located in the chromosome region 17q24–17q25, previously linked to body mass index (BMI), visceral adipose tissue (VAT), and waist circumference (WAIST) in Hispanic families in the Insulin Resistance Atherosclerosis Family Study (IRASFS). A high density map of 1536 single nucleotide polymorphisms (SNPs) was constructed to cover a portion of the 17q linkage interval in DNA samples from 1425 Hispanic subjects from 90 extended families in IRASFS. Analysis of this dense SNP map data revealed evidence of association of rs9914220 (located 10 kb 5’ of the SOCS3 gene) with BMI, VAT, and WAIST (P-value ranging from 0 003 to 0.017). Using a tagging SNP approach, rs9914220 and 22 additional SOCS3 SNPs were genotyped for genetic association analysis with measures of adiposity and glucose homeostasis. The adiposity phenotypes utilized in association analyses included BMI, WAIST, waist to hip ratio (WHR), subcutaneous adipose tissue (SAT), VAT, and visceral to subcutaneous ratio (VSR). Linkage disequilibrium (LD) calculations revealed three haplotype blocks near SOCS3. Haplotype Block 1 (5’ of SOCS3) contained SNPs consistently associated with BMI, WAIST, WHR, and VAT (P-values ranging from 2.00x10−4 to .036). Haplotype Block 3 contained single-SNPs that were associated with most adiposity traits except for VSR (P-values ranging from 0.002 to 0.047). When trait associated SNPs were included in linkage analyses as covariates, a reduction of VAT LOD score from 1.26 to .76 above the SOCS3 locus (110 cM) was observed. Multi-SNP haplotype testing using the quantitative pedigree disequilibrium test (QPDT) was broadly consistent with the single-SNP associations. In conclusion, these results support a role for SOCS3 genetic variants in human obesity.
Suppressor of Cytokine Signalling 3; Genetic Association; Single Nucleotide Polymorphisms; Obesity/Glucose Homeostasis Traits
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.
hypertension; race/ethnicity; epidemiology; incidence
LITTLE IS KNOWN ABOUT BLOOD PRESSURE LEVELS and the extent of high blood pressure in Hispanic children and adolescents, especially in groups other than Mexican Americans. The authors of this study investigated the levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the extent of high blood pressure among Mexican-American, Cuban-American, and mainland Puerto Rican children and adolescents who participated in the Hispanic Health and Nutrition Examination Survey (HHANES). Very few children and adolescents in these three Hispanic groups had high normal or high blood pressure. Puerto Rican children had significantly lower DBP than Mexican-American (2.4 mmHg) and Cuban-American (1.8 mmHg) children. Their SBP was also lower (1.7 mmHg) than that of Cuban-American children. These findings should be interpreted cautiously, however, since a significant observer effect was also found in this study. Correlates of blood pressure in children in all three Hispanic groups were consistent with those found in studies of other ethnic groups. Age, body mass index, and pulse rate were significant predictors of both SBP and DBP (P less than 0.05). Gender was an important predictor of SBP but not DBP. Socioeconomic and cultural factors were not significant predictors of blood pressure in these Hispanic groups.
The purpose of current study was to investigate associations of serum 25-hydroxyvitamin D (OHVD) levels with markers for metabolic syndrome in elderly Koreans. We conducted a panel study on 301 individuals over 60 yr old in Seoul, Korea, and repeatedly measured serum OHVD, glucose, insulin, and lipid levels. Mixed effect model and generalized estimating equations were used to investigate relationships between serum OHVD levels with marker levels for metabolic syndrome and each of its categories. Of all subjects, 76.6% were vitamin D deficient (< 50 nM) and 16.9% were insufficient (< 75 nM). Inverse association was demonstrated between serum OHVD levels and insulin (P = 0.004), triglyceride (P = 0.023) and blood pressure (systolic blood pressure: P = 0.002; diastolic blood pressure: P < 0.001). Vitamin D deficiency was found to increase risk of 'hypertriglyceridemia' category of metabolic syndrome (odds ratio: 1.73, 95% confidence interval: 1.13-2.66). In conclusion, we found from our repeated measure analysis that decreasing serum OHVD levels are associated with increasing insulin resistance, increasing serum triglyceride levels and increasing blood pressure in elderly Koreans, and confirmed on the risk of 'hypertriglyceridemia' in vitamin D deficient subjects.
Vitamin D; Insulin Resistance; Metabolic Syndrome; Elderly; Mixed Effect Model
African American women are at greater risk for complications related to high blood pressure. This study examined relationships between high blood pressure, pulse pressure, body mass index, family adaptability, family cohesion and social support among 146 Urban African American women. Significant relationships were found between family adaptability and systolic blood pressure (p = .03) and between adaptability and pulse pressure (p ≤ .01). Based on study results, practitioners should routinely assess family functioning, specifically family adaptability, in African American women who are at risk for high blood pressure or diagnosed with high blood pressure to minimize complications associated with hypertension.
high blood pressure; family adaptability; African American women; pulse pressure; social support
Clinical guidelines recommend blood pressure (BP) lowering and renin-angiotensin-aldosterone system inhibition to slow kidney disease progression in patients with diabetic nephropathy. This study’s purpose was to determine whether an antihypertensive regimen including a maximally dosed angiotensin-converting enzyme inhibitor could safely achieve target BP in indigent, predominantly minority patients with this disease.
We studied 81 hypertensive adults (52% Hispanic and 31% African American) with nephropathy attributed to type 1 or 2 diabetes during the run-in period of a randomized controlled trial. The subjects received lisinopril titrated to 80 mg daily and additional anti-hypertensives to target a systolic BP (SBP) lower than 130 mm Hg. Blood pressure and serum potassium level were measured weekly, and a 4-gram sodium diet was prescribed. The primary outcome variable was SBP change from screening to randomization. Success in achieving SBP goal, change in urine albumin–creatinine ratio, hyperkalemia (serum potassium ≥5.5 mmol/L) and hypotension (SBP < 100 mm Hg) were also analyzed.
The median SBP decreased from 144 to 133 mm Hg (median change, −9.6%.) Fifty-eight (71%) achieved goal SBP during run-in. The median UACR decreased from 206.8 to 112.7 mg/mmol (median change, −42.7%). The UACR reduction correlated with SBP reduction. Seventeen subjects experienced hyperkalemia responsive to dietary/medical management. Two subjects experienced hypotension responsive to medication adjustments.
A regimen using a maximally dosed angiotensin-converting enzyme inhibitor is safe and effective for achieving BP goal in high-risk, predominantly minority patients with diabetic nephropathy. Implementing this regimen necessitates close monitoring of serum potassium level.
albuminuria; angiotensin-converting enzyme inhibitor; diabetes; hypertension; nephropathy
HMG-CoA reductase (HMGCR) is an enzyme involved in cholesterol synthesis. To investigate the contribution of the HMGCR gene to lipids and lipoprotein subfraction in different ethnicities, we performed an association study in the Multi-Ethnic Study of Atherosclerosis (MESA). Totally, 2444 MESA subjects (597 African-Americans (AA), 627 Chinese-Americans (CHA), 612 European-Americans (EA), and 608 Hispanic-Americans (HA)) without statin use were included. Participants had measurements of blood pressure, anthropometry, and fasting blood samples. Subjects were genotyped for 10 single nucleotide polymorphisms (SNPs). After excluding SNPs with minor allele frequency <5%, a single block was constructed. The most frequent haplotype was H1 (41-56%) in all ethnic groups except AA (H2a, 44.9%). Lower triglyceride level was associated with the H2a haplotype in AA and H2 in HA. In HA, H4 carriers had higher levels of triglyceride and small low-density lipoprotein (s-LDL), and lower high-density lipoprotein cholesterol (HDL-c), while carriers with H7 or H8 had associations with these traits in the opposite direction. No significant association was discovered in both CHA and EA. The total variation for triglyceride that could be explained by H2 alone was 2.6% in HA and 1.4% in AA. In conclusion, HMGCR gene variation is associated with multiple lipid/lipoprotein traits, especially with triglyceride, s-LDL, and HDL-c. The impact of the genetic variance is modest and differs greatly between ethnicities.
hydroxymethylglutaryl CoA reductases; association study; cholesterol; triglyceride; low density lipoprotein size