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1.
JAMA Cardiol ; : 1-9, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642869

RESUMO

Importance: The prevalence of hypertension and the risk for hypertension-related cardiovascular disease (CVD) are high among black adults. The population-attributable risk (PAR) accounts for both prevalence and excess risk of disease associated with a risk factor. Objective: To examine the PAR for CVD associated with hypertension among black adults. Design, Setting, and Participants: This prospective cohort study used data on 12 497 black participants older than 21 years without CVD at baseline who were enrolled in the Jackson Heart Study (JHS) from September 26, 2000, through March 31, 2004, and cardiovascular events were adjudicated through December 31, 2015. The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study participants were enrolled from July 1, 2003, through September 12, 2007, and cardiovascular events were adjudicated through March 31, 2016. Data analysis was performed from March 26, 2018, through July 10, 2019. Exposures: Normal blood pressure and hypertension were defined using the 2017 American College of Cardiology/American Heart Association blood pressure guideline thresholds. Main Outcomes and Measures: The PAR for CVD associated with hypertension, calculated using multivariable-adjusted hazard ratios (HRs) for CVD, coronary heart disease, heart failure, and stroke associated with hypertension vs normal blood pressure. Prevalence of hypertension among non-Hispanic black US adults 21 years and older without CVD was calculated using data from the National Health and Nutrition Examination Survey, 2011-2014. Results: Of 12 497 participants, 1935 had normal blood pressure (638 [33.0%] male; mean [SD] age, 53.5 [12.4] years), 929 had elevated blood pressure (382 [41.1%] male; mean [SD] age, 58.6 [11.8] years), and 9633 had hypertension (3492 [36.3%] male; mean [SD] age, 62.0 [10.3] years). For a maximum 14.3 years of follow-up, 1235 JHS and REGARDS study participants (9.9%) experienced a CVD event. The multivariable-adjusted HR associated with hypertension was 1.91 (95% CI, 1.48-2.46) for CVD, 2.41 (95% CI,1.59-3.66) for coronary heart disease, 1.52 (95% CI, 1.01-2.30) for heart failure, and 2.20 (95% CI, 1.44-3.36) for stroke. The prevalence of hypertension was 53.2% among non-Hispanic black individuals. The PAR associated with hypertension was 32.5% (95% CI, 20.5%-43.6%) for CVD, 42.7% (95% CI, 24.0%-58.4%) for coronary heart disease, 21.6% (95% CI, 0.6%-40.8%) for heart failure, and 38.9% (95% CI, 19.4%-55.6%) for stroke. The PAR was higher among those younger than 60 years (54.6% [95% CI, 37.2%-68.7%]) compared with those 60 years or older (32.0% [95% CI, 11.9%-48.1%]). No differences were present in subgroup analyses. Conclusions and Relevance: These findings suggest that a substantial proportion of CVD cases among black individuals are associated with hypertension. Interventions to maintain normal blood pressure throughout the life course may reduce the incidence of CVD in this population.

2.
Sci Rep ; 9(1): 15192, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645637

RESUMO

Previous research has shown that genes play a substantial role in determining a person's susceptibility to age-related hearing impairment. The existing studies on this subject have different results, which may be caused by difficulties in determining the phenotype or the limited number of participants involved. Here, we have gathered the largest sample to date (discovery n = 9,675; replication n = 10,963; validation n = 356,141), and examined phenotypes that represented low/mid and high frequency hearing loss on the pure tone audiogram. We identified 7 loci that were either replicated and/or validated, of which 5 loci are novel in hearing. Especially the ILDR1 gene is a high profile candidate, as it contains our top SNP, is a known hearing loss gene, has been linked to age-related hearing impairment before, and in addition is preferentially expressed within hair cells of the inner ear. By verifying all previously published SNPs, we can present a paper that combines all new and existing findings to date, giving a complete overview of the genetic architecture of age-related hearing impairment. This is of importance as age-related hearing impairment is highly prevalent in our ageing society and represents a large socio-economic burden.

3.
Am J Hum Genet ; 105(4): 706-718, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31564435

RESUMO

Hemoglobin A1c (HbA1c) is widely used to diagnose diabetes and assess glycemic control in individuals with diabetes. However, nonglycemic determinants, including genetic variation, may influence how accurately HbA1c reflects underlying glycemia. Analyzing the NHLBI Trans-Omics for Precision Medicine (TOPMed) sequence data in 10,338 individuals from five studies and four ancestries (6,158 Europeans, 3,123 African-Americans, 650 Hispanics, and 407 East Asians), we confirmed five regions associated with HbA1c (GCK in Europeans and African-Americans, HK1 in Europeans and Hispanics, FN3K and/or FN3KRP in Europeans, and G6PD in African-Americans and Hispanics) and we identified an African-ancestry-specific low-frequency variant (rs1039215 in HBG2 and HBE1, minor allele frequency (MAF) = 0.03). The most associated G6PD variant (rs1050828-T, p.Val98Met, MAF = 12% in African-Americans, MAF = 2% in Hispanics) lowered HbA1c (-0.88% in hemizygous males, -0.34% in heterozygous females) and explained 23% of HbA1c variance in African-Americans and 4% in Hispanics. Additionally, we identified a rare distinct G6PD coding variant (rs76723693, p.Leu353Pro, MAF = 0.5%; -0.98% in hemizygous males, -0.46% in heterozygous females) and detected significant association with HbA1c when aggregating rare missense variants in G6PD. We observed similar magnitude and direction of effects for rs1039215 (HBG2) and rs76723693 (G6PD) in the two largest TOPMed African American cohorts, and we replicated the rs76723693 association in the UK Biobank African-ancestry participants. These variants in G6PD and HBG2 were monomorphic in the European and Asian samples. African or Hispanic ancestry individuals carrying G6PD variants may be underdiagnosed for diabetes when screened with HbA1c. Thus, assessment of these variants should be considered for incorporation into precision medicine approaches for diabetes diagnosis.

4.
Birth Defects Res ; 111(18): 1420-1435, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31580536

RESUMO

BACKGROUND: Using the National Birth Defects Prevention Network (NBDPN) annual data report, U.S. national prevalence estimates for major birth defects are developed based on birth cohort 2010-2014. METHODS: Data from 39 U.S. population-based birth defects surveillance programs (16 active case-finding, 10 passive case-finding with case confirmation, and 13 passive without case confirmation) were used to calculate pooled prevalence estimates for major defects by case-finding approach. Fourteen active case-finding programs including at least live birth and stillbirth pregnancy outcomes monitoring approximately one million births annually were used to develop national prevalence estimates, adjusted for maternal race/ethnicity (for all conditions examined) and maternal age (trisomies and gastroschisis). These calculations used a similar methodology to the previous estimates to examine changes over time. RESULTS: The adjusted national birth prevalence estimates per 10,000 live births ranged from 0.62 for interrupted aortic arch to 16.87 for clubfoot, and 19.93 for the 12 critical congenital heart defects combined. While the birth prevalence of most birth defects studied remained relatively stable over 15 years, an increasing prevalence was observed for gastroschisis and Down syndrome. Additionally, the prevalence for atrioventricular septal defect, tetralogy of Fallot, omphalocele, and trisomy 18 increased in this period compared to the previous periods. Active case-finding programs generally had higher prevalence rates for most defects examined, most notably for anencephaly, anophthalmia/microphthalmia, trisomy 13, and trisomy 18. CONCLUSION: National estimates of birth defects prevalence provide data for monitoring trends and understanding the impact of these conditions. Increasing prevalence rates observed for selected conditions warrant further examination.

5.
Am J Hypertens ; 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31545351

RESUMO

BACKGROUND: Only a handful of genetic discovery efforts in apparent treatment resistant hypertension (aTRH) have been described. METHODS: We conducted a case-control genome-wide association study (GWAS) of aTRH among persons treated for hypertension, using data from 10 cohorts of European ancestry (EA) and 5 cohorts of African ancestry (AA). Cases were treated with 3 different antihypertensive medication classes and had blood pressure (BP) above goal (systolic (SBP)≥140 mm Hg and/or diastolic (DBP)≥90 mm Hg) or 4 or more medication classes regardless of BP control (nEA =931, nAA= 228). Both a normotensive control group and a treatment-responsive control group were considered in separate analyses. Normotensive controls were untreated (nEA = 14210, nAA= 2480) and had SBP/DBP <140/90 mm Hg. Treatment-responsive controls (nEA = 5266, nAA= 1817) had BP at goal (<140/90 mm Hg) while treated with one antihypertensive medication class. Individual cohorts used logistic regression with adjustment for age, sex, study site and principal components for ancestry to examine the association of SNPs with case-control status. Inverse variance-weighted fixed-effects meta-analyses were carried out using METAL. RESULTS: The known hypertension locus, CASZ1, was a top finding among EAs (P=1.1*10-8) and in the race-combined analysis (P=1.5*10-9) using the normotensive control group (rs12046278 OR=0.71[95% CI 0.6-0.8]). SNPs in this locus were robustly replicated in the Million Veterans Program (MVP) study in consideration of a treatment-responsive control group. There were no statistically significant findings for the discovery analyses including treatment-responsive controls. CONCLUSION: This genomic discovery effort for aTRH identified CASZ1 as an aTRH risk locus.

6.
Diabetes Care ; 42(11): 2083-2089, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31511234

RESUMO

OBJECTIVE: African Americans (AA) suffer disproportionately from diabetic nephropathy (DN). C-reactive protein (CRP) has been associated with prevalent DN, but its association with incident DN in AA is unknown. We examined hs-CRP and incident DN in AA. RESEARCH DESIGN AND METHODS: We conducted a longitudinal analysis of data from exams 1, 2, and 3 in 4,043 eligible Jackson Heart Study (JHS) participants. Participants with DN or without hs-CRP at exam 1 were excluded. Incident DN was defined as urinary albumin-to-creatinine ratio (ACR) >30 mg/g or self-reported dialysis/transplantation and type 2 diabetes mellitus (DM) or HbA1c >6.5% by exam 2 or 3 among participants free of DN at exam 1. Kaplan-Meier curves examined DN event-free survival probability by hs-CRP. With Cox proportional hazards regression we estimated hazard ratios (HRs) and 95% CI for DN by hs-CRP tertiles, adjusting for demographics and clinical and laboratory data. RESULTS: During 7.8 years of median follow-up time, participants who developed DN had significantly higher baseline hs-CRP, age, fasting glucose, triglycerides, ACR, systolic blood pressure, waist circumference, and duration of DM (P < 0.05). The overall incident rate of DN was 7.9%. The mean time to incident DN was shorter for participants with hs-CRP in the high tertile (>4.24 mg/L) than in the low tertile (<1.46 mg/L); P < 0.001. Participants with high hs-CRP had higher incidence of DN (HR 2.34, 95% CI 1.04-5.24) versus the reference group. CONCLUSIONS: Inflammation, as measured by hs-CRP levels, may be associated with incident DN in AA. Further studies are warranted to replicate and elucidate the basis for this association.

8.
Obesity (Silver Spring) ; 27(9): 1527-1532, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31328900

RESUMO

OBJECTIVE: Abdominal obesity and wall thickness of the central arteries have been associated with higher risk of cardiovascular disease. Despite the higher burden of overweight and cardiovascular disease among African Americans, limited data are available on the association of abdominal obesity with aortic wall thickness in African Americans. We assessed the cross-sectional and the longitudinal associations of abdominal obesity with aortic intima-media thickness (aIMT) in a cohort of African Americans from the Jackson Heart Study. METHODS: Data on aIMT and repeated measures of waist circumference (WC) and waist to height ratio from 1,572 participants, as well as on abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and aIMT from 1,223 participants, were analyzed. aIMT was measured at proximal ascending aorta (PA-aIMT), proximal descending aorta (PD-aIMT), and distal aorta (bifurcation) using cardiac magnetic resonance. SAT and VAT were measured using computerized tomography. RESULTS: WC and WHtR were longitudinally associated with PA-aIMT and PD-aIMT; SAT and VAT were associated with PA-aIMT only. Only WC was associated with distal aIMT. CONCLUSIONS: Abdominal obesity measures are associated with increased proximal aIMT in adult African Americans. Only WC is associated with wall thickness in all three segments of the aorta.

9.
Circulation ; 140(1): 42-54, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31216868

RESUMO

BACKGROUND: Truncating variants in the Titin gene (TTNtvs) are common in individuals with idiopathic dilated cardiomyopathy (DCM). However, a comprehensive genomics-first evaluation of the impact of TTNtvs in different clinical contexts, and the evaluation of modifiers such as genetic ancestry, has not been performed. METHODS: We reviewed whole exome sequence data for >71 000 individuals (61 040 from the Geisinger MyCode Community Health Initiative (2007 to present) and 10 273 from the PennMedicine BioBank (2013 to present) to identify anyone with TTNtvs. We further selected individuals with TTNtvs in exons highly expressed in the heart (proportion spliced in [PSI] >0.9). Using linked electronic health records, we evaluated associations of TTNtvs with diagnoses and quantitative echocardiographic measures, including subanalyses for individuals with and without DCM diagnoses. We also reviewed data from the Jackson Heart Study to validate specific analyses for individuals of African ancestry. RESULTS: Identified with a TTNtv in a highly expressed exon (hiPSI) were 1.2% individuals in PennMedicine BioBank and 0.6% at Geisinger. The presence of a hiPSI TTNtv was associated with increased odds of DCM in individuals of European ancestry (odds ratio [95% CI]: 18.7 [9.1-39.4] {PennMedicine BioBank} and 10.8 [7.0-16.0] {Geisinger}). hiPSI TTNtvs were not associated with DCM in individuals of African ancestry, despite a high DCM prevalence (odds ratio, 1.8 [0.2-13.7]; P=0.57). Among 244 individuals of European ancestry with DCM in PennMedicine BioBank, hiPSI TTNtv carriers had lower left ventricular ejection fraction (ß=-12%, P=3×10-7), and increased left ventricular diameter (ß=0.65 cm, P=9×10-3). In the Geisinger cohort, hiPSI TTNtv carriers without a cardiomyopathy diagnosis had more atrial fibrillation (odds ratio, 2.4 [1.6-3.6]) and heart failure (odds ratio, 3.8 [2.4-6.0]), and lower left ventricular ejection fraction (ß=-3.4%, P=1×10-7). CONCLUSIONS: Individuals of European ancestry with hiPSI TTNtv have an abnormal cardiac phenotype characterized by lower left ventricular ejection fraction, irrespective of the clinical manifestation of cardiomyopathy. Associations with arrhythmias, including atrial fibrillation, were observed even when controlling for cardiomyopathy diagnosis. In contrast, no association between hiPSI TTNtvs and DCM was discerned among individuals of African ancestry. Given these findings, clinical identification of hiPSI TTNtv carriers may alter clinical management strategies.

11.
Nature ; 570(7759): 71-76, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31118516

RESUMO

Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10-3) and candidate genes from knockout mice (P = 5.2 × 10-3). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000-185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.


Assuntos
Diabetes Mellitus Tipo 2/genética , Exoma/genética , Sequenciamento Completo do Exoma , Animais , Estudos de Casos e Controles , Técnicas de Apoio para a Decisão , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Masculino , Camundongos , Camundongos Knockout
12.
J Am Coll Cardiol ; 73(19): 2388-2397, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31097157

RESUMO

BACKGROUND: Primary prevention strategies to mitigate the burden of heart failure (HF) are urgently needed. However, no validated risk prediction tools are currently in use. OBJECTIVES: This study sought to derive 10-year risk equations of developing incident HF. METHODS: Race- and sex-specific 10-year risk equations for HF were derived and validated from individual-level data from 7 community-based cohorts with at least 12 years of follow-up. Participants who were recruited between 1985 and 2000, between 30 to 79 years, and were free of cardiovascular disease at baseline were included to create a pooled cohort (PC) and were randomly split for derivation and internal validation. Model performance was also assessed in 2 additional cohorts. RESULTS: In the derivation sample of the PC (n = 11,771), 58% were women, 22% were black with a mean age of 52 ± 12 years, and HF occurred in 1,339 participants. Predictors of HF included in the race-sex-specific models were age, blood pressure (treated or untreated), fasting glucose (treated or untreated), body mass index, cholesterol, smoking status, and QRS duration. The PC equations to Prevent HF model had good discrimination and strong calibration in internal and external validation cohorts. A web-based tool was developed to facilitate clinical application of this tool. CONCLUSIONS: The authors present a contemporary analysis from 33,010 men and women demonstrating the utility of the sex- and race-specific 10-year PC equations to Prevent HF risk score, which integrates clinical parameters readily available in primary care settings. This tool can be useful in risk-based decision making to determine who may merit intensive screening and/or targeted prevention strategies.

13.
Blood Press Monit ; 24(3): 130-136, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30998553

RESUMO

BACKGROUND: In longitudinal research studies with follow-up examinations, the devices used to measure phenotypes may change over time. When a device change occurs, the two devices should be calibrated to each other to ensure that measurements are comparable. This paper details the Jackson Heart Study (JHS) blood pressure (BP) comparability study. PARTICIPANTS AND METHODS: During its second clinic exam (2005-2008), the JHS switched from a random-zero sphygmomanometer (RZS) BP measurement device to an oscillometric device (OD). During this exam, BP measurements from both an RZS and an OD were taken simultaneously in 2117 participants for the purpose of calibration. Five methods for calibrating systolic BP (SBP) and diastolic BP (DBP) were considered: ignoring the change, ordinary least squares regression, adding the average difference, Deming regression, and robust regression. RESULTS: Using the RZS and OD, the mean (SD) SBP was 125.5 (19.2) and 126.5 (19.9), respectively, and the mean (SD) DBP was 76.4 (10.6) and 74.0 (11.0), respectively. The correlation between RZS and the OD was 0.90 for SBP and 0.80 for DBP. The prevalence of high BP and hypertension and associations with albuminuria were similar when applying each of the five calibration methods. Robust regression was chosen for calibration, giving the following equations:(Equation is included in full-text article.)These equations had a higher R statistic than using calibration equations from the Coronary Artery Risk Development in Young Adults Study and the Heinz Nixdorf Recall Study. CONCLUSIONS: The JHS BP data have been calibrated using the above equations for use in future analyses.

15.
Am Heart J ; 212: 72-79, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30954832

RESUMO

BACKGROUND: Emerging data suggest that neck circumference (NC) is associated with cardiometabolic risk factors. Limited research is available regarding the association between NC and cardiovascular outcomes in African Americans. METHODS: Using data from the Jackson Heart Study, we included participants with recorded NC measurements at baseline (2000-2004). Baseline characteristics for the included population were summarized by tertiles of NC. We then calculated age- and sex-adjusted cumulative incidence of clinical cardiovascular outcomes and performed Cox proportional-hazards with stepwise models. RESULTS: Overall, 5,290 participants were categorized into tertiles of baseline NC defined as ≤37 cm (n = 2179), 38-40 cm (n = 1552), and >40 cm (n = 1559). After adjusting for age and sex, increasing NC was associated with increased risk of heart failure (HF) hospitalization (cumulative incidence = 13.4% [99% CI, 10.7-16.7] in the largest NC tertile vs 6.5% [99% CI, 4.7-8.8] in the smallest NC tertile), but not mortality, stroke, myocardial infarction, or coronary heart disease (all P ≥ .1). Following full risk adjustment, there was a nominal increase in the risk of HF hospitalization with increasing NC, but this was not statistically significant (hazard ratio per 1-cm increase, 1.04 [99% CI, 0.99-1.10], P = .06). CONCLUSIONS: In this large cohort of African American individuals, a larger NC was associated with increased risk for HF hospitalization following adjustment for age and sex, but this risk was not statistically significant after adjusting for other clinical variables. Although NC is not independently associated with increased risk for cardiovascular events, it may offer prognostic information particularly related to HF hospitalization.

16.
Circ Cardiovasc Imaging ; 12(3): e008641, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30879330

RESUMO

Background We investigated the associations of glycemic markers (HbA1C [hemoglobin A1C], fasting plasma glucose, and insulin resistance-homeostasis model assessment of insulin resistance) with subclinical cardiovascular disease (CVD) among blacks. Methods We included 4303 community-dwelling blacks (64% women; mean age, 54.5 years) without prevalent CVD. Subclinical CVD was defined as ≥1 of the following: any coronary artery calcification (CAC), elevated carotid intima-media thickness (cIMT), left ventricular (LV) hypertrophy, LV ejection fraction <50%, and peripheral artery disease (ankle-brachial index, <0.90). Estimates of cross-sectional associations of glycemic markers (fasting plasma glucose, HbA1C, and homeostasis model assessment of insulin resistance) with subclinical CVD measures were adjusted for traditional CVD risk factors. Results Each 1% increment in HbA1C was associated with higher odds of CAC, abnormal cIMT, and subclinical CVD (all P <0.001). Adjusted mean values of LV mass (LVM), LVM index, relative wall thickness, CAC, and cIMT were increasingly abnormal with worsening HbA1C categories (all P<0.05). Each 10-mg/dL increase in fasting plasma glucose was associated with higher odds of LV hypertrophy, CAC, abnormal cIMT, and subclinical CVD (all P <0.005). Adjusted mean values of LVM, LVM index, relative wall thickness, CAC, ankle-brachial index, and cIMT were more abnormal across categories of worsening fasting plasma glucose (all P <0.05). Each unit increment in log-transformed homeostasis model assessment of insulin resistance conferred a higher odd of having LV hypertrophy ( P<0.01). Across quartiles of homeostasis model assessment of insulin resistance, we observed progressively abnormal adjusted mean values of LVM, LVM index, relative wall thickness, and ankle-brachial index (all P <0.01). Conclusions Among blacks, glycemic markers were differentially associated with various measures of subclinical CVD.

17.
Ethn Dis ; 29(1): 39-46, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30713415

RESUMO

Objective: We examined whether life course socioeconomic position (SEP) was associated with incidence of type 2 diabetes (t2DM) among African Americans. Design: Secondary analysis of data from the Jackson Heart Study, 2000-04 to 2012, using Cox proportional hazard regression to estimate hazard ratios (HR) with 95% CI for t2DM incidence by measures of life course SEP. Participants: Sample of 4,012 nondiabetic adults aged 25-84 years at baseline. Outcome Measure: Incident t2DM identified by self-report, hemoglobin A1c ≥6.5%, fasting plasma glucose ≥126 mg/dL, or use of diabetes medication. Results: During 7.9 years of follow-up, 486 participants developed t2DM (incidence rate 15.2/1000 person-years, 95% CI: 13.9-16.6). Among women, but not men, childhood SEP was inversely associated with t2DM incidence (HR=.97, 95% CI: .94-.99) but was no longer associated with adjustment for adult SEP or t2DM risk factors. Upward SEP mobility increased the hazard for t2DM incidence (adjusted HR=1.52, 95% CI: 1.05-2.21) among women only. Life course allostatic load (AL) did not explain the SEP-t2DM association in either sex. Conclusions: Childhood SEP and upward social mobility may influence t2DM incidence in African American women but not in men.

18.
J Am Heart Assoc ; 8(3): e010674, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30672360

RESUMO

Background Prevalence of peripheral artery disease ( PAD ) is significantly higher among blacks as compared with non-Hispanic whites, but the role of cigarette smoking in PAD is understudied in blacks. We aimed to evaluate the relationship between cigarette smoking and PAD in blacks in the (JHS) Jackson Heart Study. Methods and Results JHS participants (n=5306) were classified by self-reported baseline smoking status into current, past (smoked at least 400 cigarettes/life), or never smokers. We examined multivariable logistic and robust linear regression models to estimate the associations between baseline smoking status, smoking intensity, and measures of subclinical PAD (ankle-brachial index [visit 1] and aortic calcium by computed tomography [visit 2]) to yield odds ratios and ß-coefficients (estimated adjusted difference) to compare each smoking status with never smokers (reference group). There were 3579 (68%) never smokers, 986 (19%) past smokers, and 693 (13%) current smokers self-identified at baseline. After adjustment for covariates, current smokers had increased risk of ankle-brachial index <1 (odds ratio, 2.2, 95% CI, 1.5-3.3) and increased risk of abdominal aortic (odds ratio, 8.4, 95% CI, 5.8-12.0) and aortoiliac calcium (odds ratio, 9.6, 95% CI, 6.7-13.7). When stratifying by smoking intensity, those smoking more than 20 cigarettes daily (1 pack) had higher likelihood of subclinical PAD by all of these measures compared with lower-intensity use, suggesting a dose-dependent relationship. Conclusions In a large black cohort, cigarette smoking was associated with measures of subclinical PAD in a dose-dependent manner. These findings highlight the association between smoking and PAD in blacks and support further research exploring the impact of interventions on smoking cessation to reduce PAD in this population.

19.
Am J Hum Genet ; 104(2): 260-274, 2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30639324

RESUMO

With advances in whole-genome sequencing (WGS) technology, more advanced statistical methods for testing genetic association with rare variants are being developed. Methods in which variants are grouped for analysis are also known as variant-set, gene-based, and aggregate unit tests. The burden test and sequence kernel association test (SKAT) are two widely used variant-set tests, which were originally developed for samples of unrelated individuals and later have been extended to family data with known pedigree structures. However, computationally efficient and powerful variant-set tests are needed to make analyses tractable in large-scale WGS studies with complex study samples. In this paper, we propose the variant-set mixed model association tests (SMMAT) for continuous and binary traits using the generalized linear mixed model framework. These tests can be applied to large-scale WGS studies involving samples with population structure and relatedness, such as in the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine (TOPMed) program. SMMATs share the same null model for different variant sets, and a virtue of this null model, which includes covariates only, is that it needs to be fit only once for all tests in each genome-wide analysis. Simulation studies show that all the proposed SMMATs correctly control type I error rates for both continuous and binary traits in the presence of population structure and relatedness. We also illustrate our tests in a real data example of analysis of plasma fibrinogen levels in the TOPMed program (n = 23,763), using the Analysis Commons, a cloud-based computing platform.

20.
Diabetes Care ; 42(3): 457-465, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30617142

RESUMO

OBJECTIVE: To estimate the long-term absolute risk for cardiovascular disease (CVD) according to fasting glucose (FG) levels below the threshold of diabetes. RESEARCH DESIGN AND METHODS: We pooled data from seven observational cohorts of U.S. black and white men and women followed from 1960 to 2015. We categorized FG as follows: <5.0, 5.0-5.5, 5.6-6.2, 6.3-6.9 mmol/L, and diabetes (FG ≥7.0 mmol/L or use of diabetes medications). CVD was defined as fatal/nonfatal coronary heart disease and fatal/nonfatal stroke. We estimated the risk of CVD by FG category at index age 55 years using a modified Kaplan-Meier survival analysis, adjusted for the competing risk of non-CVD death. We also assessed risk for incident CVD according to change in FG before 50 years of age, specifically among the categories <5.6 mmol/L, 5.6-6.9 mmol/L, and diabetes. RESULTS: Our sample included 19,630 individuals (6,197 blacks and 11,015 women) without a prior CVD event. Risk for CVD through 85 years of age ranged from 15.3% (<5.0 mmol/L) to 38.6% (diabetes levels) among women and from 21.5% (5.0-5.5 mmol/L) to 47.7% (diabetes levels) among men. An FG of 6.3-6.9 mmol/L was associated with higher long-term CVD risk compared with the lowest FG among men but not women. Increases in glucose during midlife with conversion to diabetes were associated with higher cardiovascular risk (1.3- to 3.6-fold) than increases in glucose below the diabetes threshold. CONCLUSIONS: Middle-age individuals with diabetes have high long-term absolute risk for CVD. These data strongly support the importance of blood glucose monitoring in midlife for CVD prevention.


Assuntos
Glicemia/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/sangue , Angiopatias Diabéticas/sangue , Adulto , Idoso , Glicemia/análise , Automonitorização da Glicemia , Doenças Cardiovasculares/classificação , Doenças Cardiovasculares/epidemiologia , Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Diabetes Mellitus/epidemiologia , Angiopatias Diabéticas/classificação , Angiopatias Diabéticas/epidemiologia , Jejum , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologia
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