Showing papers by "Gerardo Heiss published in 2014"
TL;DR: Findings indicate a high prevalence of diabetes but considerable diversity as a function of Hispanic background and the low rates of diabetes awareness, diabetes control, and health insurance in conjunction with the negative associations between diabetes prevalence and both household income and education among Hispanics/Latinos in the U.S. have important implications for public health policies.
Abstract: OBJECTIVE We examine differences in prevalence of diabetes and rates of awareness and control among adults from diverse Hispanic/Latino backgrounds in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). RESEARCH DESIGN AND METHODS The HCHS/SOL, a prospective, multicenter, population-based study, enrolled from four U.S. metropolitan areas from 2008 to 2011 16,415 18–74-year-old people of Hispanic/Latino descent. Diabetes was defined by either fasting plasma glucose, impaired glucose tolerance 2 h after a glucose load, glycosylated hemoglobin (A1C), or documented use of hypoglycemic agents (scanned medications). RESULTS Diabetes prevalence varied from 10.2% in South Americans and 13.4% in Cubans to 17.7% in Central Americans, 18.0% in Dominicans and Puerto Ricans, and 18.3% in Mexicans ( P P P P = 0.0010) but was negatively related to education ( P = 0.0005) and household income ( P = 0.0043). Rate of diabetes awareness was 58.7%, adequate glycemic control (A1C CONCLUSIONS Present findings indicate a high prevalence of diabetes but considerable diversity as a function of Hispanic background. The low rates of diabetes awareness, diabetes control, and health insurance in conjunction with the negative associations between diabetes prevalence and both household income and education among Hispanics/Latinos in the U.S. have important implications for public health policies.
317 citations
TL;DR: In this paper, a two-stage area probability sample of households in four U.S. locales, yielding 16,319 adults (52% women) who self-identified as Cuban, Dominican, Mexican, Puerto Rican, Central American, or South American was used to quantify the prevalence of metabolic syndrome among men and women 18-74 years of age of diverse Hispanic/Latino background.
Abstract: OBJECTIVE Approximately one-third of the adult U.S. population has the metabolic syndrome. Its prevalence is the highest among Hispanic adults, but variation by Hispanic/Latino background is unknown. Our objective was to quantify the prevalence of the metabolic syndrome among men and women 18–74 years of age of diverse Hispanic/Latino background. RESEARCH DESIGN AND METHODS Two-stage area probability sample of households in four U.S. locales, yielding 16,319 adults (52% women) who self-identified as Cuban, Dominican, Mexican, Puerto Rican, Central American, or South American. The metabolic syndrome was defined according to the American Heart Association/National Heart, Lung, and Blood Institute 2009 Joint Scientific Statement. The main outcome measures were age-standardized prevalence of the metabolic syndrome per the harmonized American Heart Association/National Heart, Lung, and Blood Institute definition and its component abnormalities. RESULTS The metabolic syndrome was present in 36% of women and 34% of men. Differences in the age-standardized prevalence were seen by age, sex, and Hispanic/Latino background. The prevalence of the metabolic syndrome among those 18–44, 45–64, and 65–74 years of age was 23%, 50%, and 62%, respectively, among women; and 25%, 43%, and 55%, respectively, among men. Among women, the metabolic syndrome prevalence ranged from 27% in South Americans to 41% in Puerto Ricans. Among men, prevalences ranged from 27% in South Americans to 35% in Cubans. In those with the metabolic syndrome, abdominal obesity was present in 96% of the women compared with 73% of the men; more men (73%) than women (62%) had hyperglycemia. CONCLUSIONS The burden of cardiometabolic abnormalities is high in Hispanic/Latinos but varies by age, sex, and Hispanic/Latino background. Hispanics/Latinos are thus at increased, but modifiable, predicted lifetime risk of diabetes and its cardiovascular sequelae.
148 citations
TL;DR: In this article, the authors studied 13 541 participants (56% women, 26% black) in the Atherosclerosis Risk in Communities Study, aged 52 to 66 years and free of CVD at exams in 1987 through 1989, 1990 through 1992, 1993 through 1995, or 1996 through 1998.
Abstract: Background—The extent to which the relative contributions of traditional cardiovascular risk factors to incident cardiovascular disease (CVD) may have changed over time remains unclear. Methods and Results—We studied 13 541 participants (56% women, 26% black) in the Atherosclerosis Risk in Communities Study, aged 52 to 66 years and free of CVD at exams in 1987 through 1989, 1990 through 1992, 1993 through 1995, or 1996 through 1998. At each examination, we estimated the population attributable risks (PAR) of traditional risk factors (hypertension, diabetes mellitus, obesity, hypercholesterolemia, and smoking) for the 10-year incidence of CVD. Overall, the PAR of all risk factors combined appeared to decrease from the late 1980s to the late 1990s (0.58 to 0.53). The combined PAR was higher in women than men in 1987 through 1989 (0.68 versus 0.51, P<0.001) but not by the late 1990s (0.58 versus 0.48, P=0.08). The combined PAR was higher in blacks than whites in the late 1980s (0.67 versus 0.57, P=0.049), an...
119 citations
TL;DR: A better understanding of the differences in cardiac structure and function through the spectrum of heart failure stages in elderly persons generally, and between sexes and racial/ethnic groups specifically, will deepen the understanding ofThe pathophysiology driving heart failure progression in these at-risk populations and may inform novel prevention or therapeutic strategies.
Abstract: Background— Heart failure is an important public health concern, particularly among persons >65 years of age. Women and blacks are critically understudied populations that carry a sizeable portion of the heart failure burden. Limited normative and prognostic data exist on measures of cardiac structure, diastolic function, and novel measures of systolic deformation in older adults living in the community.
Methods and Results— The Atherosclerosis Risk in Communities (ARIC) study is a large, predominantly biracial, National Heart, Lung, and Blood Institute–sponsored epidemiological cohort study. Between 2011 and 2013, ≈6000 surviving participants, now in their seventh to ninth decade of life, are expected to return for a fifth study visit during which comprehensive 2-dimensional, Doppler, tissue Doppler, and speckle-tracking echocardiography will be performed uniformly in all cohort clinic visit participants. The following objectives will be addressed: (1) to characterize cardiac structural and functional abnormalities among the elderly and to determine how they differ by sex and race/ethnicity, (2) to determine the relationship between ventricular and vascular abnormalities, and (3) to prospectively examine the extent to which these noninvasive measures associate with incident heart failure.
Conclusions— We describe the design, imaging acquisition and analysis methods, and quality assurance metrics for echocardiography in visit 5 of the ARIC cohort. A better understanding of the differences in cardiac structure and function through the spectrum of heart failure stages in elderly persons generally, and between sexes and racial/ethnic groups specifically, will deepen our understanding of the pathophysiology driving heart failure progression in these at-risk populations and may inform novel prevention or therapeutic strategies.
112 citations
TL;DR: Education did not have a strong relationship with change in cognitive test performance, although the rate of decline was somewhat slower among persons with lower levels of education, and methods used to account for selective dropout only marginally changed these observed associations.
Abstract: Studies of long-term cognitive change should account for the potential effects of education on the outcome, since some studies have demonstrated an association of education with dementia risk. Evaluating cognitive change is more ideal than evaluating cognitive performance at a single time point, because it should be less susceptible to confounding. In this analysis of 14,020 persons from a US cohort study, the Atherosclerosis Risk in Communities (ARIC) Study, we measured change in performance on 3 cognitive tests over a 20-year period, from ages 48-67 years (1990-1992) through ages 70-89 years (2011-2013). Generalized estimating equations were used to evaluate the association between education and cognitive change in unweighted adjusted models, in models incorporating inverse probability of attrition weighting, and in models using cognitive scores imputed from the Telephone Interview for Cognitive Status for participants not examined in person. Education did not have a strong relationship with change in cognitive test performance, although the rate of decline was somewhat slower among persons with lower levels of education. Methods used to account for selective dropout only marginally changed these observed associations. Future studies of risk factors for cognitive impairment should focus on cognitive change, when possible, to allow for reduction of confounding by social or cultural factors.
109 citations
TL;DR: In this article, the authors examined 15 0004 middle-aged blacks and whites enrolled in the Atherosclerosis Risk in Communities (ARIC) cohort study and found that the rate of incident AF was inversely associated with low forced expiratory volume in 1 second (FEV1).
Abstract: Background—Reduced low forced expiratory volume in 1 second (FEV1) is reportedly associated with an increased risk of atrial fibrillation (AF). Extant reports do not provide separate estimates for never smokers or for blacks, who incongruously have lower AF incidence than whites. Methods and Results—We examined 15 004 middle-aged blacks and whites enrolled in the Atherosclerosis Risk in Communities (ARIC) cohort study. Standardized spirometry data were collected at the baseline examination. Incident AF was identified from the first among the following: International Classification of Diseases codes for AF on hospital discharge records or death certificates or 12-lead ECGs performed during 3 triennial follow-up visits. Over an average follow-up of 17.5 years, a total of 1691 participants (11%) developed new-onset AF. The rate of incident AF was inversely associated with FEV1 in each of the 4 race and sex groups. After multivariable adjustment for traditional cardiovascular disease risk factors and height, ...
95 citations
TL;DR: Weighted estimators that reflect unequal selection probabilities and differential nonresponse rates are developed, and variance estimators are derived that properly account for the sampling design and the potential relatedness of participants in different sampling units.
Abstract: The cohort design allows investigators to explore the genetic basis of a variety of diseases and traits in a single study while avoiding major weaknesses of the case-control design. Most cohort studies employ multistage cluster sampling with unequal probabilities to conveniently select participants with desired characteristics, and participants from different clusters might be genetically related. Analysis that ignores the complex sampling design can yield biased estimation of the genetic association and inflation of the type I error. Herein, we develop weighted estimators that reflect unequal selection probabilities and differential nonresponse rates, and we derive variance estimators that properly account for the sampling design and the potential relatedness of participants in different sampling units. We compare, both analytically and numerically, the performance of the proposed weighted estimators with unweighted estimators that disregard the sampling design. We demonstrate the usefulness of the proposed methods through analysis of MetaboChip data in the Hispanic Community Health Study/Study of Latinos, which is the largest health study of the Hispanic/Latino population in the United States aimed at identifying risk factors for various diseases and determining the role of genes and environment in the occurrence of diseases. We provide guidelines on the use of weighted and unweighted estimators, as well as the relevant software.
69 citations
Vanderbilt University1, Heidelberg University2, University of North Carolina at Chapel Hill3, University of Washington4, Rutgers University5, National Institutes of Health6, University of Wisconsin-Madison7, National University of Singapore8, Singapore National Eye Center9, Pennsylvania State University10
TL;DR: While most associations did not generalize in the non-European populations, variants within lipid-related genes were found to be associated with AMD, highlighting the need for larger well-powered studies in non- European populations.
Abstract: Purpose.
Substantial progress has been made in identifying susceptibility variants for AMD in European populations; however, few studies have been conducted to understand the role these variants play in AMD risk in diverse populations. The present study aims to examine AMD risk across diverse populations in known and suspected AMD complement factor and lipid-related loci.
56 citations
TL;DR: The findings suggest that the HCV epidemic among US Hispanics/Latinos is heterogeneous and differs significantly by Hispanic/Latino background in HCHS/SOL.
Abstract: Prevalence of hepatitis C virus (HCV) antibody has been reported in Mexican Americans, but its prevalence in other US Hispanic/Latino groups is unknown. We studied 2 populations of US Hispanic/Latino adults; 3210 from the National Health and Nutrition Examination Survey (NHANES) 2007–2010 and 11 964 from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Age-standardized prevalence of HCV antibody was similar in NHANES 2007–2010 (1.5%) and HCHS/SOL (2.0%) but differed significantly by Hispanic/Latino background in HCHS/SOL (eg, 11.6% in Puerto Rican men vs 0.4% in South American men). These findings suggest that the HCV epidemic among US Hispanics/Latinos is heterogeneous.
50 citations
Fred Hutchinson Cancer Research Center1, Boston University2, University of Southern California3, Wake Forest University4, University of Washington5, University of Minnesota6, University of North Carolina at Chapel Hill7, National Institutes of Health8, University of Mississippi9, Cedars-Sinai Medical Center10, University of Michigan11, Roswell Park Cancer Institute12, City of Hope National Medical Center13, University of Texas Health Science Center at San Antonio14, University of Pennsylvania15, Vanderbilt University16, Stanford University17, Harvard University18, University of Hawaii at Manoa19, Case Western Reserve University20, Johns Hopkins University21, Group Health Cooperative22, University of Pittsburgh23
TL;DR: There is evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA, and associations of 14 loci are directionally consistent with previous reports.
Abstract: Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA.
49 citations
TL;DR: An increased risk of ischemic stroke in blacks with sickle cell trait is observed, and further investigation of the incidence and pathophysiology of stroke in patients with SCT is warranted.
Abstract: Background and Purpose—Numerous case reports describe stroke in individuals with sickle cell trait (SCT) in the absence of traditional risk factors for cerebrovascular disease. To date, no prospective epidemiological studies have investigated this association. Methods—A population-based sample of blacks (n=3497; mean age=54 years; female=62%) was followed from 1987 to 2011 in the Atherosclerosis Risk in Communities (ARIC) study, contributing a total of 65 371 person-years. Hazard ratios and incidence rate differences for ischemic stroke were estimated, contrasting SCT to homozygous hemoglobin A. Models were adjusted for age, sex, smoking, diabetes mellitus, hypertension, total cholesterol, atrial fibrillation, and coronary heart disease. Results—SCT was identified in 223 (6.4%) participants. During a median follow-up of 22 years, 401 subjects experienced incident stroke (89% ischemic). Incident ischemic stroke was more frequent among those with SCT (13%) than those with homozygous hemoglobin A (10%). SCT ...
TL;DR: In this paper, the relationship between ankle brachial index (ABI) and risk for heart failure (HF) was investigated. But the ABI is a simple, non-invasive measure associated with atherosclerotic cardiovascular disease and death; however, the relationship among ABI and risk of heart failure is less well characterized.
Abstract: Objectives The aim of this study was to describe the relationship between ankle brachial index (ABI) and the risk for heart failure (HF). Background The ABI is a simple, noninvasive measure associated with atherosclerotic cardiovascular disease and death; however, the relationship between ABI and risk for HF is less well characterized. Methods Between 1987 and 1989 in the ARIC (Atherosclerosis Risk In Communities) study, an oscillometric device was used to measure blood pressure in a single upper and randomly chosen lower extremity to determine the ABI. Incident HF events were defined by the first hospitalization with an International Classification of Diseases, Ninth Revision, code of 428.x through 2008. The risk for HF was assessed across the ABI range using restricted cubic splines and Cox proportional hazards models. Results ABI was available in 13,150 participants free from prevalent HF. Over a mean 17.7 years of follow-up, 1,809 incident HF events occurred. After adjustment for traditional HF risk factors, prevalent coronary heart disease, subclinical carotid atherosclerosis, and interim myocardial infarction, compared with an ABI of 1.01 to 1.40, participants with ABIs ≤0.90 were at increased risk for HF (hazard ratio: 1.40; 95% confidence interval: 1.12 to 1.74), as were participants with ABIs of 0.91 to 1.00 (hazard ratio: 1.36; 95% confidence interval: 1.17 to 1.59). Conclusions In a middle-age community cohort, an ABI ≤1.00 was significantly associated with an increased risk for HF, independent of traditional HF risk factors, prevalent coronary heart disease, carotid atherosclerosis, and interim myocardial infarction. Low ABI may reflect not only overt atherosclerosis but also pathologic processes in the development of HF beyond epicardial atherosclerotic disease and myocardial infarction alone. A low ABI, as a simple, noninvasive measure, may be a risk marker for HF.
Cancer Prevention Institute of California1, Fred Hutchinson Cancer Research Center2, Vanderbilt University3, Mayo Clinic4, German Cancer Research Center5, University of North Carolina at Chapel Hill6, University of Hawaii at Manoa7, University of Utah8, Harvard University9, National Institutes of Health10, University of Southern California11, Translational Genomics Research Institute12, Northwestern University13, University of Melbourne14, Stanford University15, American Cancer Society16, Massey University17, Kaiser Permanente18, University of Pittsburgh19, New York University20, University of Nantes21, University of Ottawa22, Ontario Institute for Cancer Research23, University of Toronto24, University of Washington25
TL;DR: This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding coloreCTal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q 24.
Abstract: Objective Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. Design We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10 −4 was used to determine statistical significance of the associations. Results Two correlated SNPs—rs10090154 and rs4242382—in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10 −5 ), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. Conclusions This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.
University of Southern California1, Fred Hutchinson Cancer Research Center2, University of Edinburgh3, University of Hawaii at Manoa4, Dartmouth College5, National Institutes of Health6, Vanderbilt University7, Rutgers University8, Wayne State University9, University of Texas MD Anderson Cancer Center10, University of Liverpool11, University of Göttingen12, German Cancer Research Center13, International Agency for Research on Cancer14, University of Cambridge15, American Cancer Society16, University of North Carolina at Chapel Hill17, Harvard University18, University of Toronto19, Cancer Prevention Institute of California20
TL;DR: A novel pleiotropic association between the breast cancer LSP1 risk region marked by variant rs3817198 and lung cancer risk is demonstrated.
Abstract: Background Genome-wide association studies have identified hundreds of genetic variants associated with specific cancers. A few of these risk regions have been associated with more than one cancer site; however, a systematic evaluation of the associations between risk variants for other cancers and lung cancer risk has yet to be performed. Methods We included 18 023 patients with lung cancer and 60 543 control subjects from two consortia, Population Architecture using Genomics and Epidemiology (PAGE) and Transdisciplinary Research in Cancer of the Lung (TRICL). We examined 165 single-nucleotide polymorphisms (SNPs) that were previously associated with at least one of 16 non–lung cancer sites. Study-specific logistic regression results underwent meta-analysis, and associations were also examined by race/ethnicity, histological cell type, sex, and smoking status. A Bonferroni-corrected P value of 2.5 × 10–5 was used to assign statistical significance. Results The breast cancer SNP LSP1 rs3817198 was associated with an increased risk of lung cancer (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.05 to 1.14; P = 2.8 × 10–6). This association was strongest for women with adenocarcinoma (P = 1.2 × 10–4) and not statistically significant in men (P = .14) with this cell type (Phet by sex = .10). Two glioma risk variants, TERT rs2853676 and CDKN2BAS1 rs4977756, which are located in regions previously associated with lung cancer, were associated with increased risk of adenocarcinoma (OR = 1.16; 95% CI = 1.10 to 1.22; P = 1.1 × 10–8) and squamous cell carcinoma (OR = 1.13; CI = 1.07 to 1.19; P = 2.5 × 10–5), respectively. Conclusions Our findings demonstrate a novel pleiotropic association between the breast cancer LSP1 risk region marked by variant rs3817198 and lung cancer risk.
TL;DR: Redistribution of ill-defined UCD would improve the accuracy and comparability of mortality statistics used to allocate public health resources and monitor mortality trends.
Abstract: Heart failure is sometimes incorrectly listed as the underlying cause of death (UCD) on death certificates, thus compromising the accuracy and comparability of mortality statistics. Statistical redistribution of the UCD has been used to examine the effect of misclassification of the UCD attributed to heart failure, but sex- and race-specific redistribution of deaths on coronary heart disease (CHD) mortality in the United States has not been examined. We used coarsened exact matching to infer the UCD of vital records with heart failure as the UCD from 1999 to 2010 for decedents 55 years old and older from states encompassing regions under surveillance by the Atherosclerosis Risk in Communities (ARIC) Study (Maryland, Minnesota, Mississippi, and North Carolina). Records with heart failure as the UCD were matched on decedent characteristics (five-year age groups, sex, race, education, year of death, and state) to records with heart failure listed among the multiple causes of death. Each heart failure death was then redistributed to plausible UCDs proportional to the frequency among matched records. After redistribution the proportion of deaths increased for CHD, chronic obstructive pulmonary disease, diabetes, hypertensive heart disease, and cardiomyopathy, P < 0.001. The percent increase in CHD mortality after redistribution was the highest in Mississippi (12%) and lowest in Maryland (1.6%), with variations by year, race, and sex. Redistribution proportions for CHD were similar to CHD death classification by a panel of expert reviewers in the ARIC study. Redistribution of ill-defined UCD would improve the accuracy and comparability of mortality statistics used to allocate public health resources and monitor mortality trends.
TL;DR: Some of the HCHS/SOL findings concerning cardiometabolic and other CVD risk factors are reviewed and relate them to the need for increased access to health care and attention to lifestyle variables including nutrition.
University of Southern California1, University of Hawaii2, Fred Hutchinson Cancer Research Center3, Vanderbilt University4, University of North Carolina at Chapel Hill5, Rutgers University6, National Institutes of Health7, Wayne State University8, Northwestern University9, University of Tennessee Health Science Center10, Case Western Reserve University11, Cancer Prevention Institute of California12
TL;DR: This study has identified rs578776 and rs11249433 as risk variants for IMPC and these findings may help to identify genetic regions associated with IMPC.
Abstract: Background: Multiple primary cancers account for approximately 16% of all incident cancers in the United States. Although genome-wide association studies (GWAS) have identified many common genetic variants associated with various cancer sites, no study has examined the association of these genetic variants with risk of multiple primary cancers (MPC).
Methods: As part of the National Human Genome Research Institute (NHGRI) Population Architecture using Genomics and Epidemiology (PAGE) study, we used data from the Multiethnic Cohort (MEC) and Women's Health Initiative (WHI). Incident MPC (IMPC) cases ( n = 1,385) were defined as participants diagnosed with more than one incident cancer after cohort entry. Participants diagnosed with only one incident cancer after cohort entry with follow-up equal to or longer than IMPC cases served as controls (single-index cancer controls; n = 9,626). Fixed-effects meta-analyses of unconditional logistic regression analyses were used to evaluate the associations between 188 cancer risk variants and IMPC risk. To account for multiple comparisons, we used the false-positive report probability (FPRP) to determine statistical significance.
Results: A nicotine dependence–associated and lung cancer variant, CHRNA3 rs578776 [OR, 1.16; 95% confidence interval (CI), 1.05–1.26; P = 0.004], and two breast cancer variants, EMBP1 rs11249433 and TOX3 rs3803662 (OR, 1.16; 95% CI, 1.04–1.28; P = 0.005 and OR, 1.13; 95% CI, 1.03–1.23; P = 0.006), were significantly associated with risk of IMPC. The associations for rs578776 and rs11249433 remained ( P < 0.05) after removing subjects who had lung or breast cancers, respectively ( P ≤ 0.046). These associations did not show significant heterogeneity by smoking status ( P heterogeneity ≥ 0.53).
Conclusions: Our study has identified rs578776 and rs11249433 as risk variants for IMPC.
Impact: These findings may help to identify genetic regions associated with IMPC risk. Cancer Epidemiol Biomarkers Prev; 23(11); 2568–78. ©2014 AACR .
University of North Carolina at Chapel Hill1, Emory University2, University of Washington3, Wake Forest University4, Rutgers University5, National Institutes of Health6, Johns Hopkins University7, Texas Biomedical Research Institute8, Memorial Hospital of South Bend9, Fred Hutchinson Cancer Research Center10, George Washington University11, University of Tennessee Health Science Center12, Erasmus University Rotterdam13, Northwestern University14, Harvard University15, University of Texas Health Science Center at Houston16
TL;DR: The findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans.
Abstract: Background
Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in African Americans.
Methods and Results
Up to 8,201 African Americans (including 546 first CHD events) were genotyped using the MetaboChip array in the Atherosclerosis Risk in Communities (ARIC) study and Women's Health Initiative (WHI). We tested associations using Cox proportional hazard models in sex- and study-stratified analyses and combined results using meta-analysis. Among 44 validated CHD loci available in the array, we replicated and fine-mapped the SORT1 locus, and showed same direction of effects as reported in studies of individuals of European ancestry for SNPs in 22 additional published loci. We also identified a SNP achieving array wide significance (MYC: rs2070583, allele frequency 0.02, P = 8.1×10−8), but the association did not replicate in an additional 8,059 African Americans (577 events) from the WHI, HealthABC and GeneSTAR studies, and in a meta-analysis of 5 cohort studies of European ancestry (24,024 individuals including 1,570 cases of MI and 2,406 cases of CHD) from the CHARGE Consortium.
Conclusions
Our findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans.
TL;DR: In this article, the short-term repeatability of P wave indices (P axis, maximum P area and duration, P dispersion and P terminal force in V1) and PR interval from 12-lead electrocardiograms was examined.
TL;DR: No evidence is found to suggest an association between SCH and ischemic stroke among healthy postmenopausal women in the Women's Health Initiative Observational Study.
Abstract: Background: Subclinical hypothyroidism (SCH) is postulated to increase stroke risk via atherogenic changes associated with abnormal thyroid function. However, the direct relationship of SCH with subsequent stroke is poorly studied. Methods: In this nested case–cohort study, we prospectively evaluated the association between any SCH and severity of SCH in relation to incident ischemic stroke risk among postmenopausal women in the Women's Health Initiative Observational Study. Trained Women's Health Initiative staff, masked to thyroid status, adjudicated stroke cases. We assessed thyroid function using baseline blood specimens. Women with normal free thyroxine levels and thyrotropin (TSH) levels ≥4.69 mU/L were considered to have SCH. Primary analysis included 639 ischemic stroke cases and 2927 randomly selected subcohort members with an average of seven years of follow-up. Results: The multivariable adjusted hazard ratios (HR) from weighted Cox models were 1.06 (95% confidence interval [CI]: 0.77, 1.46) an...
TL;DR: Targeted sequencing around TMEM18 identified 2 novel BMI variants with possible regulatory function that are located in transcription factor binding regions and conditional on previous genome-wide association study single-nucleotide polymorphisms associated with BMI in the region.
Abstract: Background— Genome-wide association studies for body mass index (BMI) previously identified a locus near TMEM18. We conducted targeted sequencing of this region to investigate the role of common, low-frequency, and rare variants influencing BMI.
Methods and Results— We sequenced TMEM18 and regions downstream of TMEM18 on chromosome 2 in 3976 individuals of European ancestry from 3 community-based cohorts (Atherosclerosis Risk in Communities, Cardiovascular Health Study, and Framingham Heart Study), including 200 adults selected for high BMI. We examined the association between BMI and variants identified in the region from nucleotide position 586 432 to 677 539 (hg18). Rare variants (minor allele frequency, <1%) were analyzed using a burden test and the sequence kernel association test. Results from the 3 cohort studies were meta-analyzed. We estimate that mean BMI is 0.43 kg/m2 higher for each copy of the G allele of single-nucleotide polymorphism rs7596758 (minor allele frequency, 29%; P =3.46×10−4) using a Bonferroni threshold of P <4.6×10−4. Analyses conditional on previous genome-wide association study single-nucleotide polymorphisms associated with BMI in the region led to attenuation of this signal and uncovered another independent ( r 2<0.2), statistically significant association, rs186019316 ( P =2.11×10−4). Both rs186019316 and rs7596758 or proxies are located in transcription factor binding regions. No significant association with rare variants was found in either the exons of TMEM18 or the 3′ genome-wide association study region.
Conclusions— Targeted sequencing around TMEM18 identified 2 novel BMI variants with possible regulatory function.
TL;DR: TpTe has excellent repeatability supporting its use as a supplement to QT in observational and clinical studies, and for a hypothetical clinical trial designed to detect drug-induced prolongation of TpTe and QT.
TL;DR: These data do not provide evidence for an association between egg consumption and prevalent CAC in adult men and women.
TL;DR: Great participation in sports and leisure physical activity and greater physical performance are associated with lower central arterial stiffness in a large population-based sample of community-dwelling older adults.
Abstract: Introduction: Arterial stiffness increases with advancing age and is associated positively with coronary artery disease, stroke, dementia, and death. Regular physical activity appears to attenuate or even reverse age-related arterial stiffening. Yet, it is not clear if the reduced stiffening associated with habitual physical activity is also observed in community-dwelling older adults. Methods: We analyzed pulse wave velocity (PWV) data from 4,294 participants (mean age: 75 years, 42% male, 19% African-American) in the 5th clinic examination of the ARIC cohort conducted in 2011-13. Out of 6538 participants who completed the examination, we included all who had proper consent, PWV data, BMI Results: Both sports and leisure physical activity scores were significantly and inversely associated with cfPWV (Pearson r = -0.126 and -0.091; both P Conclusions: Greater participation in sports and leisure physical activity and greater physical performance are associated with lower central arterial stiffness in a large population-based sample of community-dwelling older adults.
TL;DR: It is estimated that the magnitude of the cross-sectional effect of diabetes on arterial stiffness is equivalent to 4 years of arterial aging in older adults.
Abstract: Introduction: Arterial stiffness measured by pulse wave velocity (PWV) predicts cardiovascular disease and mortality. Diabetes and impaired fasting glucose (IFG) have been related to arterial stiffness in smaller studies. We assessed whether diabetes and impaired fasting glucose are associated with greater arterial stiffness measured by PWV in older adults, and to evaluate gender as a modifier. Methods: PWV data on 5,147 men and women with mean age of 75.5 years (range 66-90) examined in 2011-2013 by the Atherosclerosis Risk in Communities (ARIC) study were analyzed. Diabetes was defined as fasting glucose >126 mg/dl or on hypoglycemic agents and IFG as non-diabetics with fasting glucose 100-125 mg/dl. Technicians measured carotid-femoral (cfPWV) and brachial-ankle (baPWV) velocities at least twice using the Omron VP-1000 plus system (Colin Co., Ltd., Komaki, Japan). The mean of the last two available measurements was used. The path length for cfPWV was calculated by: path length (cm) = carotid to femoral distance (cm) - (suprasternal notch - carotid distance (cm)). Path length for baPWV was automatically calculated using height-based formulas. Multivariable linear regression was used to model the cross-sectional association between diabetes status and PWV. The multivariable association of age categories with PWV was evaluated for comparison to the effect size of diabetes. Results: Participants were 57% female, 20% African-American, and 73% hypertensive. Among them 1,354 had diabetes (26%) and 2,295 (45%) had impaired fasting glucose. After adjustment for age, race-center, gender, heart rate, hypertension, BMI, and smoking status (current, former and never), cfPWV was 87 cm/s higher on average for those with diabetes, and 21 cm/s higher for those with IFG, as compared to those free of diabetes or IFG. In comparison, a 4 year increase in age (after multivariable adjustment) was associated with 64 cm/s higher cfPWV among non-smokers without diabetes. Estimates for baPWV were smaller than those for cfPWV but showed a similar pattern. There was no significant interaction by gender (P >0.1). Conclusion: Diabetes and impaired fasting glucose are both associated with arterial stiffness in older adults. We estimate that the magnitude of the cross-sectional effect of diabetes on arterial stiffness is equivalent to 4 years of arterial aging.
TL;DR: Estimated frequency of ADHF hospitalizations by ARIC validation criteria is about two times higher than ICD 428 in primary position; with an overall increasing vs. declining trend over the last decade.
Abstract: Background: Trends for acute decompensated heart failure (ADHF) hospitalizations based on the primary discharge ICD codes have declined in the U.S. However, HF ICD codes are increasingly found in non-primary positions. Validation data are needed to estimate the frequency of ADHF hospitalizations. Methods: The ARIC Study conducts surveillance for hospitalized ADHF in four U.S. communities for age ≥ 55 years since 2005. Hospital records are sampled, abstracted, and classified as ADHF or not by an expert physician panel. Analyses were stratified on code groups (a) 428.xx in primary-position, (b) 428.xx in non-primary position, and (c) other sampled HF ICD code (398, 402, 404, 415, 416, 425, 518, 786) in any position. We calculated ADHF probability in each group overall (positive predictive value, PPV), and by using regression models. We estimated the nationwide trends of ADHF hospitalizations from the National Inpatient Sample (NIS), a 20% probability sample of U.S. community hospitals, by applying the calibration factors derived in the ARIC study. Results: In ARIC surveillance 42% of eligible hospitalizations (n=12,450 charts) validated as ADHF. NIS data included 9 million eligible hospitalizations during 1999-2010. The estimated numbers of US ADHF hospitalization in 2010 among Americans ≥ 55 years old was 1.8 (SE 0.02) million as compared to 0.8 (SE 0.002) million with 428.xx in the primary position ( Figure ). The estimated ADHF hospitalizations in the U.S. increased from 1.6 million in 1999 to 1.9 million in 2006, and then decreased to 1.8 million in 2010 (average annual increase of 1%, p-trend Conclusions: Estimated frequency of ADHF hospitalizations by ARIC validation criteria is about two times higher than ICD 428 in primary position; with an overall increasing vs. declining trend over the last decade.
01 Jan 2014
TL;DR: Findings demonstrate a no vel pleiotropic association between the breast cancer LSP1 risk region marked by variant rs3817198 and lung cancer risk.
Abstract: Methods W e included 18 023 patients with lung cancer and 60 543 control subjects from two consor tia, Population Architecture using Genomics and Epidemiology (PAGE) and Transdisciplinary Research in Cancer of the Lung (TRICL). We examined 165 single-nucleotide polymorphisms (SNPs) that were previously associated with at least one of 16 non–lung cancer sites. Study-specific logistic regression results underwent meta-analysis, and associations were also examined by race/ethnicity, histological cell type, sex, and smoking status. A Bonferroni-corrected P value of 2.5 × 1 0–5 was used to assign statistical significance. Results The breast cancer SNP LSP1 rs3817198 was associated with an increased risk of lung cancer (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.05 to 1.14; P = 2.8 × 10–6). This association was strongest for women with adenocarcinoma (P = 1.2 × 10–4) and not statistically significant in men (P = .14) with this cell type (Phet by sex = .10). Two glioma risk variants, TERT rs2853676 and CDKN2BAS1 rs4977756, which are located in regions previously associated with lung cancer, were associated with increased risk of adenocarcinoma (OR = 1.16; 95% CI = 1.10 to 1.22; P = 1.1 × 10–8) and squamous cell carcinoma (OR = 1.13; CI = 1.07 to 1.19; P = 2.5 × 10–5), respectively. Conclusions Our findings demonstrate a no vel pleiotropic association between the breast cancer LSP1 risk region marked by variant rs3817198 and lung cancer risk.