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1.
Sleep ; 42(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31139831

RESUMO

STUDY OBJECTIVES: Daytime sleepiness is a consequence of inadequate sleep, sleep-wake control disorder, or other medical conditions. Population variability in prevalence of daytime sleepiness is likely due to genetic and biological factors as well as social and environmental influences. DNA methylation (DNAm) potentially influences multiple health outcomes. Here, we explored the association between DNAm and daytime sleepiness quantified by the Epworth Sleepiness Scale (ESS). METHODS: We performed multi-ethnic and ethnic-specific epigenome-wide association studies for DNAm and ESS in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 619) and the Cardiovascular Health Study (n = 483), with cross-study replication and meta-analysis. Genetic variants near ESS-associated DNAm were analyzed for methylation quantitative trait loci and followed with replication of genotype-sleepiness associations in the UK Biobank. RESULTS: In MESA only, we detected four DNAm-ESS associations: one across all race/ethnic groups; three in African-Americans (AA) only. Two of the MESA AA associations, in genes KCTD5 and RXRA, nominally replicated in CHS (p-value < 0.05). In the AA meta-analysis, we detected 14 DNAm-ESS associations (FDR q-value < 0.05, top association p-value = 4.26 × 10-8). Three DNAm sites mapped to genes (CPLX3, GFAP, and C7orf50) with biological relevance. We also found evidence for associations with DNAm sites in RAI1, a gene associated with sleep and circadian phenotypes. UK Biobank follow-up analyses detected SNPs in RAI1, RXRA, and CPLX3 with nominal sleepiness associations. CONCLUSIONS: We identified methylation sites in multiple genes possibly implicated in daytime sleepiness. Most significant DNAm-ESS associations were specific to AA. Future work is needed to identify mechanisms driving ancestry-specific methylation effects.

2.
PLoS Genet ; 15(4): e1007739, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30990817

RESUMO

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.


Assuntos
Hexoquinase/genética , Subunidade alfa de Receptor de Interleucina-18/genética , Oxiemoglobinas/metabolismo , Sono/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Moléculas de Adesão Celular Neuronais/genética , Biologia Computacional , Proteínas da Matriz Extracelular/genética , Feminino , Redes Reguladoras de Genes , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Hipóxia/sangue , Hipóxia/genética , Masculino , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas do Tecido Nervoso/genética , Oxigênio/sangue , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Serina Endopeptidases/genética , Síndromes da Apneia do Sono/sangue , Síndromes da Apneia do Sono/genética , Adulto Jovem
4.
PLoS Genet ; 14(8): e1007586, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30096133

RESUMO

For many complex traits, gene regulation is likely to play a crucial mechanistic role. How the genetic architectures of complex traits vary between populations and subsequent effects on genetic prediction are not well understood, in part due to the historical paucity of GWAS in populations of non-European ancestry. We used data from the MESA (Multi-Ethnic Study of Atherosclerosis) cohort to characterize the genetic architecture of gene expression within and between diverse populations. Genotype and monocyte gene expression were available in individuals with African American (AFA, n = 233), Hispanic (HIS, n = 352), and European (CAU, n = 578) ancestry. We performed expression quantitative trait loci (eQTL) mapping in each population and show genetic correlation of gene expression depends on shared ancestry proportions. Using elastic net modeling with cross validation to optimize genotypic predictors of gene expression in each population, we show the genetic architecture of gene expression for most predictable genes is sparse. We found the best predicted gene in each population, TACSTD2 in AFA and CHURC1 in CAU and HIS, had similar prediction performance across populations with R2 > 0.8 in each population. However, we identified a subset of genes that are well-predicted in one population, but poorly predicted in another. We show these differences in predictive performance are due to allele frequency differences between populations. Using genotype weights trained in MESA to predict gene expression in independent populations showed that a training set with ancestry similar to the test set is better at predicting gene expression in test populations, demonstrating an urgent need for diverse population sampling in genomics. Our predictive models and performance statistics in diverse cohorts are made publicly available for use in transcriptome mapping methods at https://github.com/WheelerLab/DivPop.

5.
Nat Commun ; 9(1): 3391, 2018 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-30140000

RESUMO

Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia.

7.
Nat Commun ; 9(1): 2606, 2018 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-29973585

RESUMO

Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans.

8.
Am J Respir Cell Mol Biol ; 58(3): 391-401, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29077507

RESUMO

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10-8) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.


Assuntos
Estudo de Associação Genômica Ampla , Locos de Características Quantitativas/genética , Apneia Obstrutiva do Sono/genética , Sono REM/fisiologia , Fatores de Transcrição/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidiletanolamina N-Metiltransferase/genética , Caracteres Sexuais , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteínas ras/genética
9.
Am J Kidney Dis ; 68(5): 743-751, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27555103

RESUMO

BACKGROUND: Kidney failure disproportionately affects older blacks versus whites. The reasons are unknown and may be related to lower measured glomerular filtration rate (GFR) and higher levels of albuminuria in community-based population samples. STUDY DESIGN: Cross-sectional analysis of a substudy of a prospective cohort. SETTING & PARTICIPANTS: Ancillary study following Multi-Ethnic Study of Atherosclerosis (MESA) visit 5. PREDICTOR: Age, sex, and race. OUTCOMES & MEASUREMENTS: Measured GFR using plasma clearance of iohexol and urine albumin-creatinine ratio (ACR). RESULTS: GFR was measured in 294 participants. Mean age was 71±9 (SD) years, 47% were black, 48% were women, mean GFR was 73±19mL/min/1.73m2, and median ACR was 10.0 (IQR, 5.8-20.9) mg/g. Measured GFR was on average 1.02 (95% CI, 0.79-1.24) mL/min/1.73m2 lower per year older. Mean GFR indexed for body surface area was not different between blacks versus whites (mean difference, 2.94 [95% CI, -1.37 to 7.26] mL/min/1.73m2), but was lower in women than men (mean difference, -9.34 [95% CI, -13.53 to -5.15] mL/min/1.73m2); this difference persisted and remained significant after adjustment for demographics, clinical characteristics, and measures of body size. The difference between men and women, but not between blacks and whites, was substantially greater when GFR was not indexed for body surface area. ACR was higher in older versus younger participants (mean difference, 3.2% [95% CI, 1.5%-4.8%] per year), but geometric mean ratio of ACR did not differ between blacks versus whites (mean difference, 19.7%; 95% CI, -39.1% to 6.1%) or between men versus women (mean difference, -4.4%; 95% CI, -27.7% to 26.3%). LIMITATIONS: This is a study of survivors. People who agreed to participate were younger than those who refused. CONCLUSIONS: In this first community-based study that included blacks and whites, no differences in measured GFR between races were found, suggesting that other factors must account for the disproportionately higher burden of kidney failure in older blacks versus whites.


Assuntos
Grupo com Ancestrais do Continente Africano , Grupo com Ancestrais do Continente Europeu , Taxa de Filtração Glomerular , Idoso , Aterosclerose/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores Sexuais
10.
Am J Respir Crit Care Med ; 194(7): 886-897, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26977737

RESUMO

RATIONALE: Obstructive sleep apnea is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. Although there is strong clinical and epidemiologic evidence supporting the importance of genetic factors in influencing obstructive sleep apnea, its genetic basis is still largely unknown. Prior genetic studies focused on traits defined using the apnea-hypopnea index, which contains limited information on potentially important genetically determined physiologic factors, such as propensity for hypoxemia and respiratory arousability. OBJECTIVES: To define novel obstructive sleep apnea genetic risk loci for obstructive sleep apnea, we conducted genome-wide association studies of quantitative traits in Hispanic/Latino Americans from three cohorts. METHODS: Genome-wide data from as many as 12,558 participants in the Hispanic Community Health Study/Study of Latinos, Multi-Ethnic Study of Atherosclerosis, and Starr County Health Studies population-based cohorts were metaanalyzed for association with the apnea-hypopnea index, average oxygen saturation during sleep, and average respiratory event duration. MEASUREMENTS AND MAIN RESULTS: Two novel loci were identified at genome-level significance (rs11691765, GPR83, P = 1.90 × 10-8 for the apnea-hypopnea index, and rs35424364; C6ORF183/CCDC162P, P = 4.88 × 10-8 for respiratory event duration) and seven additional loci were identified with suggestive significance (P < 5 × 10-7). Secondary sex-stratified analyses also identified one significant and several suggestive associations. Multiple loci overlapped genes with biologic plausibility. CONCLUSIONS: These are the first genome-level significant findings reported for obstructive sleep apnea-related physiologic traits in any population. These findings identify novel associations in inflammatory, hypoxia signaling, and sleep pathways.

11.
Hum Mol Genet ; 25(1): 167-79, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26464489

RESUMO

Sleep duration is implicated in the etiologies of chronic diseases and premature mortality. However, the genetic basis for sleep duration is poorly defined. We sought to identify novel genetic components influencing sleep duration in a multi-ethnic sample. Meta-analyses were conducted of genetic associations with self-reported, habitual sleep duration from seven Candidate Gene Association Resource (CARe) cohorts of over 25 000 individuals of African, Asian, European and Hispanic American ancestry. All individuals were genotyped for ∼50 000 SNPs from 2000 candidate heart, lung, blood and sleep genes. African-Americans had additional genome-wide genotypes. Four cohorts provided replication. A SNP (rs17601612) in the dopamine D2 receptor gene (DRD2) was significantly associated with sleep duration (P = 9.8 × 10(-7)). Conditional analysis identified a second DRD2 signal with opposite effects on sleep duration. In exploratory analysis, suggestive association was observed for rs17601612 with polysomnographically determined sleep latency (P = 0.002). The lead DRD2 signal was recently identified in a schizophrenia GWAS, and a genetic risk score of 11 additional schizophrenia GWAS loci genotyped on the IBC array was also associated with longer sleep duration (P = 0.03). These findings support a role for DRD2 in influencing sleep duration. Our work motivates future pharmocogenetics research on alerting agents such as caffeine and modafinil that interact with the dopaminergic pathway and further investigation of genetic overlap between sleep and neuro-psychiatric traits.


Assuntos
Receptores de Dopamina D2/genética , Sono/genética , Estudos de Coortes , Grupos Étnicos , Humanos , Polimorfismo de Nucleotídeo Único , Polissonografia , Fatores de Tempo
12.
Gerontol Geriatr Med ; 1: 2333721415605989, 2015 Jan-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28138467

RESUMO

Objective: To create personalized estimates of future health and ability status for older adults. Method: Data came from the Cardiovascular Health Study (CHS), a large longitudinal study. Outcomes included years of life, years of healthy life (based on self-rated health), years of able life (based on activities of daily living), and years of healthy and able life. We developed regression estimates using the demographic and health characteristics that best predicted the four outcomes. Internal and external validity were assessed. Results: A prediction equation based on 11 variables accounted for about 40% of the variability for each outcome. Internal validity was excellent, and external validity was satisfactory. The resulting CHS Healthy Life Calculator (CHSHLC) is available at http://healthylifecalculator.org. Conclusion: CHSHLC provides a well-documented estimate of future years of healthy and able life for older adults, who may use it in planning for the future.

13.
Am J Clin Nutr ; 101(1): 135-43, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25527757

RESUMO

BACKGROUND: Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. Also, common genetic variants in the human Circadian Locomotor Output Cycles Kaput (CLOCK) show associations with ghrelin and total energy intake. OBJECTIVES: We examined associations between habitual sleep duration, body mass index (BMI), and macronutrient intake and assessed whether CLOCK variants modify these associations. DESIGN: We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations of sleep duration and BMI and macronutrient intake as percentages of total energy as well as interactions with CLOCK variants from 9 cohort studies including up to 14,906 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. RESULTS: We observed a significant association between sleep duration and lower BMI (ß ± SE = 0.16 ± 0.04, P < 0.0001) in the overall sample; however, associations between sleep duration and relative macronutrient intake were evident in age- and sex-stratified analyses only. We observed a significant association between sleep duration and lower saturated fatty acid intake in younger (aged 20-64 y) adults (men: 0.11 ± 0.06%, P = 0.03; women: 0.10 ± 0.05%, P = 0.04) and with lower carbohydrate (-0.31 ± 0.12%, P < 0.01), higher total fat (0.18 ± 0.09%, P = 0.05), and higher PUFA (0.05 ± 0.02%, P = 0.02) intakes in older (aged 65-80 y) women. In addition, the following 2 nominally significant interactions were observed: between sleep duration and rs12649507 on PUFA intake and between sleep duration and rs6858749 on protein intake. CONCLUSIONS: Our results indicate that longer habitual sleep duration is associated with lower BMI and age- and sex-specific favorable dietary behaviors. Differences in the relative intake of specific macronutrients associated with short sleep duration could, at least in part, explain previously reported associations between short sleep duration and chronic metabolic abnormalities. In addition, the influence of obesity-associated CLOCK variants on the association between sleep duration and macronutrient intake suggests that longer habitual sleep duration could ameliorate the genetic predisposition to obesity via a favorable dietary profile.


Assuntos
Proteínas CLOCK/genética , Dieta , Ingestão de Energia , Obesidade/genética , Obesidade/prevenção & controle , Polimorfismo de Nucleotídeo Único , Sono , Adulto , Índice de Massa Corporal , Proteínas CLOCK/metabolismo , Estudos de Coortes , Estudos Transversais , Dieta/efeitos adversos , Proteínas na Dieta/administração & dosagem , Proteínas na Dieta/efeitos adversos , Grupo com Ancestrais do Continente Europeu , Ácidos Graxos Insaturados/administração & dosagem , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Adulto Jovem
14.
Diabetes ; 64(5): 1853-66, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25524916

RESUMO

Insulin sensitivity, insulin secretion, insulin clearance, and glucose effectiveness exhibit strong genetic components, although few studies have examined their genetic architecture or influence on type 2 diabetes (T2D) risk. We hypothesized that loci affecting variation in these quantitative traits influence T2D. We completed a multicohort genome-wide association study to search for loci influencing T2D-related quantitative traits in 4,176 Mexican Americans. Quantitative traits were measured by the frequently sampled intravenous glucose tolerance test (four cohorts) or euglycemic clamp (three cohorts), and random-effects models were used to test the association between loci and quantitative traits, adjusting for age, sex, and admixture proportions (Discovery). Analysis revealed a significant (P < 5.00 × 10(-8)) association at 11q14.3 (MTNR1B) with acute insulin response. Loci with P < 0.0001 among the quantitative traits were examined for translation to T2D risk in 6,463 T2D case and 9,232 control subjects of Mexican ancestry (Translation). Nonparametric meta-analysis of the Discovery and Translation cohorts identified significant associations at 6p24 (SLC35B3/TFAP2A) with glucose effectiveness/T2D, 11p15 (KCNQ1) with disposition index/T2D, and 6p22 (CDKAL1) and 11q14 (MTNR1B) with acute insulin response/T2D. These results suggest that T2D and insulin secretion and sensitivity have both shared and distinct genetic factors, potentially delineating genomic components of these quantitative traits that drive the risk for T2D.


Assuntos
Glicemia/genética , Diabetes Mellitus Tipo 2/metabolismo , Variação Genética , Homeostase/fisiologia , Glicemia/metabolismo , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/etnologia , Regulação da Expressão Gênica/fisiologia , Genoma , Estudo de Associação Genômica Ampla , Genótipo , Hispano-Americanos , Homeostase/genética , Humanos
15.
Am J Clin Nutr ; 100(6): 1462-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25411281

RESUMO

BACKGROUND: Poor vitamin K status is linked to greater risk of several chronic diseases. Age, sex, and diet are determinants of circulating vitamin K; however, there is still large unexplained interindividual variability in vitamin K status. Although a strong genetic component has been hypothesized, this has yet to be examined by a genome-wide association (GWA) study. OBJECTIVE: The objective was to identify common genetic variants associated with concentrations of circulating phylloquinone, the primary circulating form of vitamin K. DESIGN: We conducted a 2-stage GWA meta-analysis of circulating phylloquinone in 2 populations of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium Nutrition Working Group. Circulating phylloquinone was measured by using reversed-phase high-performance liquid chromatography. Results from adjusted cohort-specific discovery GWA analyses were meta-analyzed with inverse variance weights (n = 2138). Associations with circulating phylloquinone at P < 1 × 10(-6) were then evaluated in a second-stage analysis consisting of one independent cohort (n = 265). RESULTS: No significant association was observed for circulating phylloquinone at the genome-wide significance level of 5 × 10(-8). However, from the discovery GWA, there were 11 single-nucleotide polymorphism (SNP) associations with circulating phylloquinone at P < 1 × 10(-6), including a functional variant previously associated with warfarin dose and altered phylloquinone metabolism. These SNPs are on 5 independent loci on 11q23.3, 8q24.3, 5q22.3, 2p12, and 19p13.12, and they fall within or near the candidate genes APOA1/C3/A4/A5 cluster (involved in lipoprotein metabolism), COL22A1, CDO1, CTNAA2, and CYP4F2 (a phylloquinone oxidase), respectively. Second-stage analysis in an independent cohort further suggests the association of the 5q22.3 locus with circulating phylloquinone (P < 0.05). CONCLUSIONS: Multiple candidate genes related to lipoprotein and vitamin K metabolism were identified as potential determinants of circulating phylloquinone. Further investigation with a larger sample is warranted to verify our initial findings and identify other loci contributing to circulating phylloquinone. Trials related to this study were registered at clinicaltrials.gov as NCT00005121 (Framingham Offspring Study) and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).


Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Vitamina K 1/sangue , Cromatografia Líquida , Ingestão de Energia , Grupo com Ancestrais do Continente Europeu/genética , Loci Gênicos , Técnicas de Genotipagem , Humanos , Lipoproteínas/metabolismo , Família Multigênica , Estudos Observacionais como Assunto , Vitamina K 1/metabolismo
16.
Circulation ; 126(14): 1681-8, 2012 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-22932258

RESUMO

BACKGROUND: Changes in right ventricular (RV) morphology are associated with morbidity and mortality in heart and lung disease. We examined the association of abnormal RV structure and function with the risk of heart failure or cardiovascular death in a population-based multiethnic sample free of clinical cardiovascular disease at baseline. METHODS AND RESULTS: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on 5098 participants between 2000 and 2002 with follow-up for incident heart failure and cardiovascular death ("death") until January 2008. RV volumes and mass were available for 4204 participants. The study sample (n=4144) was 61.4±10.1 years old and 47.6% male. The presence of RV hypertrophy (increased RV mass) was associated with more than twice the risk of heart failure or death after adjustment for demographics, body mass index, education, C-reactive protein level, hypertension, and smoking status (hazard ratio, 2.52; 95% confidence interval, 1.55-4.10; P<0.001) and a doubling (or more) of risk with left ventricular mass at the mean value or lower (P for interaction=0.05). CONCLUSIONS: RV hypertrophy was associated with the risk of heart failure or death in a multiethnic population free of clinical cardiovascular disease at baseline.


Assuntos
Doença da Artéria Coronariana/etnologia , Doença da Artéria Coronariana/patologia , Morte , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/patologia , Ventrículos do Coração/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Doença da Artéria Coronariana/mortalidade , Grupos Étnicos/etnologia , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Circ Cardiovasc Imaging ; 5(3): 357-66, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22499849

RESUMO

BACKGROUND: A high degree of noncompacted (trabeculated) myocardium in relationship to compact myocardium (trabeculated to compact myocardium [T/M] ratio >2.3) has been associated with a diagnosis of left ventricular noncompaction (LVNC). The purpose of this study was to determine the normal range of the T/M ratio in a large population-based study and to examine the relationship to demographic and clinical parameters. METHODS AND RESULTS: The thickness of trabeculation and the compact myocardium were measured in 8 left ventricular regions on long axis cardiac MR steady-state free precession cine images in 1000 participants (551 women; 68.1±8.9 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Of 323 participants without cardiac disease or hypertension and with all regions evaluable, 140 (43%) had a T/M ratio >2.3 in at least 1 region; in 20 of 323 (6%), T/M >2.3 was present in >2 regions. A multivariable linear regression model revealed no association of age, sex, ethnicity, height, and weight with maximum T/M ratio in participants without cardiac disease or hypertension (P>0.05). In the entire cohort (n=1000), left ventricular ejection fraction (ß=-0.02/%; P=0.015), left ventricular end-diastolic volume (ß=0.01/mL; P<0.0001), and left ventricular end-systolic volume (ß=0.01/mL; P<0.001) were associated with maximum T/M ratio in adjusted models, whereas there was no association with hypertension or myocardial infarction (P>0.05). At the apical level, T/M ratios were significantly lower when obtained on short- compared with long-axis images (P=0.017). CONCLUSIONS: A ratio of T/M of >2.3 is common in a large population-based cohort. These results suggest re-evaluation of the current cardiac MR criteria for left ventricular noncompaction may be necessary.


Assuntos
Aterosclerose/diagnóstico , Aterosclerose/etnologia , Grupos Étnicos/estatística & dados numéricos , Miocárdio Ventricular não Compactado Isolado/diagnóstico , Miocárdio/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Aumento da Imagem/métodos , Imagem Cinética por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Vigilância da População , Sensibilidade e Especificidade , Função Ventricular Esquerda
18.
Atherosclerosis ; 218(2): 344-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21726862

RESUMO

BACKGROUND: Common carotid artery inter-adventitial diameter (IAD) and intima-media thickness (IMT) are measurable by ultrasound. IAD may be associated with left ventricular mass (LV mass) while IMT is a marker of subclinical atherosclerosis. It is not clear if IAD is associated with LV mass after accounting for IMT and traditional cardiovascular risk factors. METHODS: IAD and IMT were measured on participants of the Multi-Ethnic Study of Atherosclerosis (MESA) IMT progression study. A total of 5641 of the originally enrolled 6814 MESA participants were studied. LV mass was measured by magnetic resonance imaging. Multivariable linear regression was used with IAD as the outcome and adjustment for risk factors, as well as IMT and LV mass. RESULTS: Traditional cardiovascular risk factors, height, weight and ethnicity were significantly associated with IAD. After adjustment for risk factors, a 1mm difference in IMT was associated with a 1.802mm (95% CI: 1.553, 2.051) higher mean IAD. A 1g difference in LV mass was associated with a 0.006mm (95% CI: 0.005, 0.007) higher mean IAD. After adjusting for cardiovascular risk factors and IMT, a 1g difference in LV mass was associated with a 0.006mm (95% CI: 0.005, 0.008) higher mean IAD for women and 0.004mm (95% CI: 0.003, 0.005) higher IAD for men. CONCLUSIONS: Inter-adventitial diameters are associated with left ventricular mass after adjusting for cardiovascular risk factors and IMT. IAD might serve as a surrogate for left ventricular mass and have predictive value for cardiovascular outcomes.


Assuntos
Aterosclerose/patologia , Doenças Cardiovasculares/diagnóstico , Artéria Carótida Primitiva/patologia , Espessura Intima-Media Carotídea , Tecido Conjuntivo/patologia , Idoso , Aterosclerose/etnologia , Doenças Cardiovasculares/metabolismo , Estudos de Coortes , Grupos Étnicos , Feminino , Ventrículos do Coração/patologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Fatores de Risco
19.
Circulation ; 123(22): 2542-51, 2011 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-21646505

RESUMO

BACKGROUND: Right ventricular (RV) morphology is an important predictor of outcomes in heart and lung disease; however, determinants of RV anatomy have not been well studied. We examined the demographic factors associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease. METHODS AND RESULTS: In the Multi-Ethnic Study of Atherosclerosis (MESA), cardiac magnetic resonance imaging was performed on 5098 participants. Right ventricular volumes and mass were available for 4204 participants. Normative equations for RV parameters were derived with an allometric approach. The study sample (n=4123) was 61.5±10.1 years of age and 47.5% men. Older age was associated with lower RV mass (≈5% lower mass per decade), with larger age-related decrements in men than in women (P<0.05 for interaction). Older age was also associated with higher RV ejection fraction, an association that differed between races/ethnicities (P≤0.01 for interaction). Overall, men had greater RV mass (≈8%) and larger RV volumes than women, but had lower RV ejection fraction (4% in absolute terms; P<0.001). Blacks had lower RV mass than whites (P≤0.002), whereas Hispanics had higher RV mass (P≤0.02). When the derived normative equations were used, 7.3% (95% confidence interval, 6.5 to 8.1) met the criteria for RV hypertrophy, and 5.9% (95% confidence interval, 5.2 to 6.6) had RV dysfunction. CONCLUSION: Age, sex, and race are associated with significant differences in RV mass, RV volumes, and RV ejection fraction, potentially explaining distinct responses of the RV to cardiopulmonary disease.


Assuntos
Aterosclerose/etnologia , Grupos de Populações Continentais/etnologia , Grupos Étnicos/etnologia , Ventrículos do Coração/anatomia & histologia , Caracteres Sexuais , Função Ventricular Direita/fisiologia , Grupo com Ancestrais do Continente Africano/etnologia , Idoso , Idoso de 80 Anos ou mais , Americanos Asiáticos/etnologia , Aterosclerose/patologia , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/etnologia , Feminino , Hispano-Americanos/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
20.
Am J Respir Crit Care Med ; 183(3): 396-404, 2011 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-20813888

RESUMO

RATIONALE: Intense exercise in elite athletes is associated with increased left ventricular (LV) and right ventricular (RV) mass and volumes. However, the effect of physical activity on the RV in an older community-based population is unknown. OBJECTIVES: We studied the association between levels of physical activity in adults and RV mass and volumes. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on community-based participants without clinical cardiovascular disease. RV volumes were determined from manually contoured endocardial margins. RV mass was determined from the difference between epicardial and endocardial volumes multiplied by the specific gravity of myocardium. Metabolic equivalent-minutes/day were calculated from the self-reported frequency, duration, and intensity of physical activity. MEASUREMENTS AND MAIN RESULTS: The study sample (n = 1,867) was aged 61.8 ± 10 years, 48% male, 44% white, 27% African American, 20% Hispanic, and 9% Chinese. Higher levels of moderate and vigorous physical activity were linearly associated with higher RV mass (P = 0.02) after adjusting for demographics, anthropometrics, smoking, cholesterol, diabetes mellitus, hypertension, and LV mass. Higher levels of intentional exercise (physical activity done for the sole purpose of conditioning or fitness) were nonlinearly associated with RV mass independent of LV mass (P = 0.03). There were similar associations between higher levels of physical activity and larger RV volumes. CONCLUSIONS: Higher levels of physical activity in adults were associated with greater RV mass independent of the associations with LV mass; similar results were found for RV volumes. Exercise-associated RV remodeling may have important clinical implications.


Assuntos
Ventrículos do Coração/anatomia & histologia , Atividade Motora/fisiologia , Função Ventricular Direita/fisiologia , Exercício/fisiologia , Feminino , Humanos , Modelos Lineares , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/fisiologia
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