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OBJECTIVE - Natriuretic peptides (NPs) are hormones with cardioprotective effects. NP levels vary by race; however, the pathophysiological consequences of lower NP levels are not well understood. We aimed to quantify the association between NPs and endothelial function as measured by flow-mediated dilation (FMD) and the contribution of NP levels to racial differences in endothelial function.
METHODS - In this cross-sectional study of 2938 Multi-Ethnic Study of Atherosclerosis participants (34% Caucasian, 20% African-American, 20% Asian-American and 26% Hispanic) without cardiovascular disease at baseline, multivariable linear regression models were used to examine the association between serum N-terminal pro-B-type NP (NT-proBNP) and natural log-transformed FMD. We also tested whether NT-proBNP mediated the relationship between race and FMD using the product of coefficients method.
RESULTS - Among African-American and Chinese-American individuals, lower NT-proBNP levels were associated with lower FMD, β=0.06 (95% CI: 0.03 to 0.09; p<0.001) and β=0.06 (95% CI: 0.02 to 0.09; p=0.002), respectively. Non-significant associations between NT-proBNP and FMD were found in Hispanic and Caucasian individuals. In multivariable models, endothelial function differed by race, with African-American individuals having the lowest FMD compared with Caucasians, p<0.001. Racial differences in FMD among African-Americans and Chinese-Americans were mediated in part by NT-proBNP levels (African-Americans, mediation effect: -0.03(95% CI: -0.05 to -0.01); Chinese-Americans, mediation effect: -0.03(95% CI: -0.05 to -0.01)).
CONCLUSIONS - Lower NP levels are associated with worse endothelial function among African-Americans and Chinese-Americans. A relative NP deficiency in some racial/ethnic groups may contribute to differences in vascular function.
© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

OBJECTIVE - South Asians have a higher prevalence of type 2 diabetes compared with other race/ethnic groups. Body composition is associated with the risk for type 2 diabetes. Differences in body composition between South Asians and other race/ethnic groups are one hypothesized mechanism to explain the disproportionate prevalence of type 2 diabetes in this population.
RESEARCH DESIGN AND METHODS - This study used data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and the Multi-Ethnic Study of Atherosclerosis (MESA) cohorts to determine whether body composition mediated the elevated prevalence of impaired fasting glucose and type 2 diabetes in South Asians. Participants ( = 2,615) with complete body composition data were included. Ordinal logistic regression models were calculated to determine the odds for glycemic impairment in South Asians compared with the MESA cohort.
RESULTS - In multivariate models, South Asians had a significantly higher prevalence of glycemic impairment and type 2 diabetes compared with all four race/ethnic groups included in the MESA ( < 0.001 for all). In unadjusted and multivariate adjusted models, South Asians had higher odds for impaired fasting glucose and type 2 diabetes compared with all other race/ethnic groups ( < 0.001 for all). The addition of body composition measures did not significantly mitigate this relationship.
CONCLUSIONS - We did not identify strong evidence that accounting for body composition explains differences in the risk for type 2 diabetes. Future prospective studies of the MESA and MASALA cohorts are needed to understand how adipose tissue impacts the risk for type 2 diabetes and how to best assess this risk.
© 2019 by the American Diabetes Association.

Few studies have investigated the association between ectopic fat from different depots and cardiovascular risk scores and their components in the same population, and none have investigated these relations in South Asians. In a cross-sectional analysis of 796 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study who had measurements of visceral, subcutaneous, pericardial, hepatic, and intermuscular fat from abdominal and cardiac computed tomography scans, we used linear regression to determine the associations of 1 standard deviation difference in each ectopic fat depot with pooled cohort risk score and its components. Pericardial and visceral fat were more strongly associated with the pooled cohort risk score (3.1%, 95% confidence interval [CI] 2.5 to 3.7, and 2.7%, 95% CI 2.1 to 3.3, respectively) and components than intermuscular fat (2.3%, 95% CI 1.7 to 3.0); subcutaneous fat was inversely associated with the pooled cohort risk score (-2.6%, 95% CI -3.2 to 1.9) and hepatic fat attenuation was not linearly associated with the pooled cohort risk score when mutually adjusted (-0.3%, 95% CI -0.9 to 0.4). Associations for risk factor components differed by fat depot. In conclusion, subcutaneous and hepatic fat may have different functions than fat stored in other depots in South Asians. Determining whether these relations are heterogeneous by race may help elucidate the mechanisms underlying CVD disparities.
Copyright © 2017 Elsevier Inc. All rights reserved.

BACKGROUND AND AIMS - Most familial hypercholesterolemia (FH) patients remain undertreated, and it is unclear what role health disparities may play for FH patients in the US. We sought to describe sex and racial/ethnic disparities in a national registry of US FH patients.
METHODS - We analyzed data from 3167 adults enrolled in the CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia (CASCADE-FH) registry. Logistic regression was used to evaluate for disparities in LDL-C goals and statin use, with adjustments for covariates including age, cardiovascular risk factors, and statin intolerance.
RESULTS - In adjusted analyses, women were less likely than men to achieve treated LDL-C of <100 mg/dL (OR 0.68, 95% CI, 0.57-0.82) or ≥50% reduction from pretreatment LDL-C (OR 0.79, 95% CI, 0.65-0.96). Women were less likely than men to receive statin therapy (OR, 0.60, 95% CI, 0.50-0.73) and less likely to receive a high-intensity statin (OR, 0.60, 95% CI, 0.49-0.72). LDL-C goal achievement also varied by race/ethnicity: compared with whites, Asians and blacks were less likely to achieve LDL-C levels <100 mg/dL (Asians, OR, 0.47, 95% CI, 0.24-0.94; blacks, OR, 0.49, 95% CI, 0.32-0.74) or ≥50% reduction from pretreatment LDL-C (Asians, OR 0.56, 95% CI, 0.32-0.98; blacks, OR 0.62, 95% CI, 0.43-0.90).
CONCLUSIONS - In a contemporary US population of FH patients, we identified differences in LDL-C goal attainment and statin usage after stratifying the population by either sex or race/ethnicity. Our findings suggest that health disparities contribute to the undertreatment of US FH patients. Increased efforts are warranted to raise awareness of these disparities.
Copyright © 2017 Elsevier B.V. All rights reserved.

BACKGROUND - The role of estrogen metabolism in determining breast cancer risk and differences in breast cancer rates between high-incidence and low-incidence nations is poorly understood.
METHODS - We measured urinary concentrations of estradiol and estrone (parent estrogens) and 13 estrogen metabolites formed by irreversible hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring in a nested case-control study of 399 postmenopausal invasive breast cancer case participants and 399 matched control participants from the population-based Shanghai Women's Health Study cohort. Odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by quartiles of metabolic pathway groups, pathway ratios, and individual estrogens/estrogen metabolites were estimated by multivariable conditional logistic regression. Urinary estrogen/estrogen metabolite measures were compared with those of postmenopausal non-hormone-using Asian Americans, a population with three-fold higher breast cancer incidence rates. All statistical tests were two-sided.
RESULTS - Urinary concentrations of parent estrogens were strongly associated with breast cancer risk (ORQ4vsQ1 = 1.94, 95% CI = 1.21 to 3.12, Ptrend = .01). Of the pathway ratios, the 2-pathway:total estrogens/estrogen metabolites and 2-pathway:parent estrogens were inversely associated with risk (ORQ4vsQ1 = 0.57, 95% CI = 0.35 to 0.91, Ptrend = .03, and ORQ4vsQ1 = 0.61, 95% CI = 0.37 to 0.99, Ptrend = .04, respectively). After adjusting for parent estrogens, these associations remained clearly inverse but lost statistical significance (ORQ4vsQ1 = 0.65, 95% CI = 0.39 to 1.06, Ptrend = .12 and ORQ4vsQ1 = 0.76, 95% CI = 0.44 to 1.32, Ptrend = .28). The urinary concentration of all estrogens/estrogen metabolites combined in Asian American women was triple that in Shanghai women.
CONCLUSIONS - Lower urinary parent estrogen concentrations and more extensive 2-hydroxylation were each associated with reduced postmenopausal breast cancer risk in a low-risk nation. Markedly higher total estrogen/estrogen metabolite concentrations in postmenopausal United States women (Asian Americans) than in Shanghai women may partly explain higher breast cancer rates in the United States.
Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the United States.

PURPOSE - Subclinical coronary artery calcification is an established predictor of cardiovascular events. While a history of kidney stones has been linked to subclinical carotid atherosclerosis, to our knowledge no study has examined its relationship with coronary artery calcification. We studied the association between kidney stone history and prevalent coronary artery calcification in MESA (Multi-Ethnic Study of Atherosclerosis).
MATERIALS AND METHODS - MESA is a multisite cohort study of participants 45 to 84 years old without known cardiovascular disease at baseline from 2000 to 2002. Computerized tomography was done in 3,282 participants at followup in 2010 to 2012 to determine coronary artery calcification and kidney stone history was assessed by self-report. Coronary artery calcification scores were categorized as none-0, mild-1 to 99, moderate-100 to 399 or severe-400 or greater. Cross-sectional analysis was performed adjusting for demographic and dietary factors related to kidney stones.
RESULTS - The prevalence of kidney stone disease history was approximately 9%, mean ± SD participant age was 69.5 ± 9.3 years, 39% of participants were Caucasian, 47% were men and 69% had detectable coronary artery calcification (score greater than 0). No difference in the score was seen between single stone formers and nonstone formers. Recurrent kidney stone formation was associated with moderate or severe calcification on multivariable logistic regression vs none or mild calcification (OR 1.80, 95% CI 1.22-2.67). When coronary artery calcification scores were separated into none, mild, moderate and severe calcification, recurrent stone formation was associated with a higher score category on multivariable ordinal logistic regression (OR 1.44 per category, 95% CI 1.04-2.01).
CONCLUSIONS - Recurrent kidney stone formation is associated with subclinical coronary atherosclerosis. This association appeared stronger with coronary artery calcification severity than with coronary artery calcification presence.
Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

BACKGROUND - Circulating trans fatty acids (TFAs), which cannot be synthesized by humans, are linked to adverse health outcomes. Although TFAs are obtained from diet, little is known about subsequent influences (e.g., relating to incorporation, metabolism, or intercompetition with other fatty acids) that could alter circulating concentrations and possibly modulate or mediate impacts on health.
OBJECTIVE - The objective was to elucidate novel biologic pathways that may influence circulating TFAs by evaluating associations between common genetic variation and TFA biomarkers.
DESIGN - We performed meta-analyses using 7 cohorts of European-ancestry participants (n = 8013) having measured genome-wide variation in single-nucleotide polymorphisms (SNPs) and circulating TFA biomarkers (erythrocyte or plasma phospholipids), including trans-16:1n-7, total trans-18:1, trans/cis-18:2, cis/trans-18:2, and trans/trans-18:2. We further evaluated SNPs with genome-wide significant associations among African Americans (n = 1082), Chinese Americans (n = 669), and Hispanic Americans (n = 657) from 2 of these cohorts.
RESULTS - Among European-ancestry participants, 31 SNPs in or near the fatty acid desaturase (FADS) 1 and 2 cluster were associated with cis/trans-18:2; a top hit was rs174548 (β = 0.0035, P = 4.90 × 10(-15)), an SNP previously associated with circulating n-3 and n-6 polyunsaturated fatty acid concentrations. No significant association was identified for other TFAs. rs174548 in FADS1/2 was also associated with cis/trans-18:2 in Hispanic Americans (β = 0.0053, P = 1.05 × 10(-6)) and Chinese Americans (β = 0.0028, P = 0.002) but not African Americans (β = 0.0009, P = 0.34); however, in African Americans, fine mapping identified a top hit in FADS2 associated with cis/trans-18:2 (rs174579: β = 0.0118, P = 4.05 × 10(-5)). The association between rs174548 and cis/trans-18:2 remained significant after further adjustment for individual circulating n-3 and n-6 fatty acids, except arachidonic acid. After adjustment for arachidonic acid concentrations, the association between rs174548 and cis/trans-18:2 was nearly eliminated in European-ancestry participants (β-coefficient reduced by 86%), with similar reductions in Hispanic Americans and Chinese Americans.
CONCLUSIONS - Our findings provide novel evidence for genetic regulation of cis/trans-18:2 by the FADS1/2 cluster and suggest that this regulation may be influenced/mediated by concentrations of arachidonic acid, an n-6 polyunsaturated fat.
© 2015 American Society for Nutrition.

CONTEXT - Aldosterone and PTH are implicated in the pathogenesis of cardiovascular and skeletal diseases. An expanding body of evidence supports a bidirectional and positive physiologic relationship between aldosterone and PTH. Large population-based studies confirming this relationship, and whether it may be targeted as a potential method to mitigate the clinical consequences associated with excess aldosterone and PTH, are needed.
OBJECTIVE - We hypothesized that higher aldosterone levels would associate with higher PTH, and that the use of renin-angiotensin-aldosterone system (RAAS) inhibitors would predict lower PTH in a large, multi-ethnic, community-based cohort.
DESIGN, SETTING, PARTICIPANTS - We conducted cross-sectional analyses of participants in the Multi-Ethnic Study of Atherosclerosis without apparent primary hyperparathyroidism or chronic kidney disease (n = 5668). We evaluated associations of RAAS inhibitor use with PTH concentration among 1888 treated hypertensive participants. We also tested associations of serum aldosterone concentration with PTH concentration among 1547 participants with these measurements.
OUTCOME - Serum PTH concentration.
RESULTS - Higher aldosterone associated with higher PTH (β = 0.19 pg/ml per 1 ng/dl of aldosterone, P < .0001), and this finding was most pronounced among those with a primary hyperaldosteronism-like phenotype. There was a stepwise increment in PTH when comparing untreated normotensives, hypertensives using RAAS inhibitors, untreated hypertensives, and treated hypertensives using non-RAAS inhibitors (40.8, 45.0, 46.2, 47.1 pg/ml, respectively). The use of any RAAS inhibitor independently associated with lower PTH (β = -2.327 pg/ml per use of RAAS inhibitor, P = .006), when compared with the use of any non-RAAS inhibitor medication.
CONCLUSIONS - Higher serum aldosterone concentration is associated with higher serum PTH concentration, and the use of RAAS inhibitors is associated with lower PTH concentration. These results extend prior evidence from observational and intervention studies suggesting a potentially important and modifiable relationship between the RAAS and PTH in humans.

OBJECTIVES - To examine racial differences in the distribution of histological subtypes of renal cell carcinoma (RCC) and associations with established RCC risk factors by subtype.
MATERIALS AND METHODS - Tumours from 1532 consecutive patients with RCC who underwent nephrectomy at Vanderbilt University Medical Center (1998-2012) were classified as clear-cell, papillary, chromophobe and other subtypes. In pairwise comparisons, we used multivariate logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between race, sex, age, end-stage renal disease (ESRD) and body mass index at diagnosis according to histological subtype.
RESULTS - The RCC subtype distribution was significantly different in black people from that in white people (P < 0.001), with a substantially higher proportion of patients with papillary RCC among black people than white people (35.7 vs 13.8%). In multivariate analyses, compared with clear-cell RCC, people with papillary RCC were significantly more likely to be black (OR 4.15; 95% CI 2.64-6.52) and less likely to be female (OR 0.60; 95% CI 0.43-0.83). People with chromophobe RCC were significantly more likely to be female (OR 2.32; 95% CI 1.44-3.74). Both people with papillary RCC (OR 6.26; 95% CI 2.75-14.24) and those with chromophobe RCC (OR 7.07; 95% CI 2.13-23.46) were strongly and significantly more likely to have ESRD, compared with those with clear-cell RCC.
CONCLUSION - We observed marked racial differences in the proportional subtype distribution of RCCs diagnosed at a large tertiary care academic centre. To our knowledge, no previous study has examined racial differences in the distribution of RCC histologies while adjusting for ESRD, which was the factor most strongly associated with papillary and chromophobe RCC compared with clear-cell RCC.
© 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.