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1.
Stroke ; : STROKEAHA120031792, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34727735

RESUMO

BACKGROUND AND PURPOSE: Stroke is the leading cause of death and long-term disability worldwide. Previous genome-wide association studies identified 51 loci associated with stroke (mostly ischemic) and its subtypes among predominantly European populations. Using whole-genome sequencing in ancestrally diverse populations from the Trans-Omics for Precision Medicine (TOPMed) Program, we aimed to identify novel variants, especially low-frequency or ancestry-specific variants, associated with all stroke, ischemic stroke and its subtypes (large artery, cardioembolic, and small vessel), and hemorrhagic stroke and its subtypes (intracerebral and subarachnoid). METHODS: Whole-genome sequencing data were available for 6833 stroke cases and 27 116 controls, including 22 315 European, 7877 Black, 2616 Hispanic/Latino, 850 Asian, 54 Native American, and 237 other ancestry participants. In TOPMed, we performed single variant association analysis examining 40 million common variants and aggregated association analysis focusing on rare variants. We also combined TOPMed European populations with over 28 000 additional European participants from the UK BioBank genome-wide array data through meta-analysis. RESULTS: In the single variant association analysis in TOPMed, we identified one novel locus 13q33 for large artery at whole-genome-wide significance (P<5.00×10-9) and 4 novel loci at genome-wide significance (P<5.00×10-8), all of which need confirmation in independent studies. Lead variants in all 5 loci are low-frequency but are more common in non-European populations. An aggregation of synonymous rare variants within the gene C6orf26 demonstrated suggestive evidence of association for hemorrhagic stroke (P<3.11×10-6). By meta-analyzing European ancestry samples in TOPMed and UK BioBank, we replicated several previously reported stroke loci including PITX2, HDAC9, ZFHX3, and LRCH1. CONCLUSIONS: We represent the first association analysis for stroke and its subtypes using whole-genome sequencing data from ancestrally diverse populations. While our findings suggest the potential benefits of combining whole-genome sequencing data with populations of diverse genetic backgrounds to identify possible low-frequency or ancestry-specific variants, they also highlight the need to increase genome coverage and sample sizes.

2.
Clin J Am Soc Nephrol ; 16(11): 1620-1629, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34737201

RESUMO

BACKGROUND AND OBJECTIVES: Moderate coffee consumption has been associated with lower risk of CKD; however, the exact biologic mechanisms underlying this association are unknown. Metabolomic profiling may identify metabolic pathways that explain the association between coffee and CKD. The goal of this study was to identify serum metabolites associated with coffee consumption and examine the association between these coffee-associated metabolites and incident CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using multivariable linear regression, we identified coffee-associated metabolites among 372 serum metabolites available in two subsamples of the Atherosclerosis Risk in Communities study (ARIC; n=3811). Fixed effects meta-analysis was used to pool the results from the two ARIC study subsamples. Associations between coffee and metabolites were replicated in the Bogalusa Heart Study (n=1043). Metabolites with significant associations with coffee in both cohorts were then evaluated for their prospective associations with incident CKD in the ARIC study using Cox proportional hazards regression. RESULTS: In the ARIC study, mean (SD) age was 54 (6) years, 56% were daily coffee drinkers, and 32% drank >2 cups per day. In the Bogalusa Heart Study, mean (SD) age was 48 (5) years, 57% were daily coffee drinkers, and 38% drank >2 cups per day. In a meta-analysis of two subsamples of the ARIC study, 41 metabolites were associated with coffee consumption, of which 20 metabolites replicated in the Bogalusa Heart Study. Three of these 20 coffee-associated metabolites were associated with incident CKD in the ARIC study. CONCLUSIONS: We detected 20 unique serum metabolites associated with coffee consumption in both the ARIC study and the Bogalusa Heart Study, and three of these 20 candidate biomarkers of coffee consumption were associated with incident CKD. One metabolite (glycochenodeoxycholate), a lipid involved in primary bile acid metabolism, may contribute to the favorable kidney health outcomes associated with coffee consumption. Two metabolites (O-methylcatechol sulfate and 3-methyl catechol sulfate), both of which are xenobiotics involved in benzoate metabolism, may represent potential harmful aspects of coffee on kidney health.

3.
Am J Prev Cardiol ; 7: 100190, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34611635

RESUMO

Objective: A significant proportion of persons with metabolic syndrome (MetS), prediabetes, or type 2 diabetes (T2D) do not develop atherosclerotic cardiovascular disease (ASCVD).We sought to determine whether discordantly normal apolipoprotein B (ApoB) relative to elevated LDL-C may help to explain heterogeneity in ASCVD risk among persons with metabolic disorders. Methods: There were 278 Bogalusa Heart Study participants with MetS (n=95), prediabetes (n=233), or T2D (n=31) and LDL-C ≥100 mg/dL who were free of carotid plaque at baseline (2001-02) and underwent carotid ultrasound at follow-up (2013-16). Multivariable modified Poisson regression estimated the long-term absence of carotid plaque for lower ApoB, continuously and categorically. Results: Participants were on average 36.1 years old at baseline, 61.5% were women, and 31.7% were black. A total of 50.7% had discordantly normal ApoB (<90 mg/dL) and the mean ApoB and LDL-C concentrations were 91.6 mg/dL and 137.7 mg/dL, respectively. In addition to having higher HDL-C and lower triglyceride values, individuals with ApoB <90 were more likely to maintain persistent absence of plaque compared to those with ApoB ≥90 (73.1% versus 58.4%, p=0.01). Contrastingly, there was no significant difference in the proportion of individuals who remained free of plaque with increasing LDL-C (p=0.45). Independent of traditional risk factors including LDL-C, each 10 mg/dL lower ApoB (RR=1.11, 95% CI: 1.03-1.19) and ApoB <90 (RR=1.22, 95% CI: 1.00-1.43) were significantly associated with the persistent absence of carotid plaque. Conclusions: One-half of young persons with metabolic disorders and elevated LDL-C had discordantly normal ApoB and a low burden of carotid atherosclerosis over 13 years, suggesting that ApoB better represents the atherogenic lipid burden compared to LDL-C in this patient population. These results suggest a utility for assessing whether routine ApoB measurement can improve ASCVD risk stratification in young persons with metabolic disorders who have high triglycerides and low HDL-cholesterol.

4.
Am J Cardiol ; 159: 121-128, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34656312

RESUMO

Deceleration in the decline of cardiovascular disease mortality has been observed recently in the US. We aimed to examine the recent secular trends of cardiovascular health metrics in the US general population. A total of 32,832 adults aged ≥20 years from the National Health and Nutrition Examination Surveys 2007 to 2018 were included in this analysis. Cardiovascular health included 7 health metrics: smoking status, body mass index, physical activity, healthy diet score, total cholesterol, blood pressure, and fasting plasma glucose. Age-standardized mean of overall cardiovascular health score did not significantly change during 2007 to 2010, 2011 to 2014, and 2015 to 2018 in the US adult population (7.88, 8.03, and 7.91, respectively, P-trend = 0.85). The age-standardized proportions of ideal smoking status (P-trend = 0.003), ideal physical activity (P-trend = 0.03), and untreated total cholesterol <200 mg/dL (P-trend <0.001) were significantly increased but the proportions of body mass index <25.0 kg/m2 (P-trend <0.001), systolic/diastolic blood pressure <120/80 mmHg (P-trend = 0.02), and fasting plasma glucose <100 mg/dL (P-trend <0.001) were significantly decreased during the same period of time in the US adults. In conclusion, from 2007 to 2018, overall cardiovascular health did not change in the US general adult population. Of note, body mass index, blood pressure, and fasting plasma glucose significantly worsened during the same period.


Assuntos
Doenças Cardiovasculares/epidemiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto Jovem
5.
J Nutr ; 151(10): 2894-2907, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34195833

RESUMO

BACKGROUND: In individuals with chronic kidney disease (CKD), healthy dietary patterns are inversely associated with CKD progression. Metabolomics, an approach that measures many small molecules in biofluids, can identify biomarkers of healthy dietary patterns. OBJECTIVES: We aimed to identify known metabolites associated with greater adherence to 4 healthy dietary patterns in CKD patients. METHODS: We examined associations between 486 known plasma metabolites and Healthy Eating Index (HEI)-2015, Alternative Healthy Eating Index (AHEI)-2010, the Dietary Approaches to Stop Hypertension (DASH) diet, and alternate Mediterranean diet (aMED) in 1056 participants (aged 21-74 y at baseline) in the Chronic Renal Insufficiency Cohort (CRIC) Study. Usual dietary intake was assessed using a semiquantitative FFQ. We conducted multivariable linear regression models to study associations between healthy dietary patterns and individual plasma metabolites, adjusting for sociodemographic characteristics, health behaviors, and clinical factors. We used principal component analysis to identify groups of metabolites associated with individual food components within healthy dietary patterns. RESULTS: After Bonferroni correction, we identified 266 statistically significant diet-metabolite associations (HEI: n = 60; AHEI: n = 78; DASH: n = 77; aMED: n = 51); 78 metabolites were associated with >1 dietary pattern. Lipids with a longer acyl chain length and double bonds (unsaturated) were positively associated with all 4 dietary patterns. A metabolite pattern low in saturated diacylglycerols and triacylglycerols, and a pattern high in unsaturated triacylglycerols was positively associated with intake of healthy food components. Plasmalogens were negatively associated with the consumption of nuts and legumes and healthy fat, and positively associated with the intake of red and processed meat. CONCLUSIONS: We identified many metabolites associated with healthy dietary patterns, indicative of food consumption. If replicated, these metabolites may be considered biomarkers of healthy dietary patterns in patients with CKD.

6.
J Am Heart Assoc ; 10(12): e020774, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34096330

RESUMO

Background Early identification of healthy arterial aging versus premature atherosclerosis is important for optimal atherosclerotic cardiovascular disease risk stratification and prevention. We sought to identify predictors for the long-term absence of carotid plaque among young adults. Methods and Results We included 508 participants from the Bogalusa Heart Study without clinical atherosclerotic cardiovascular disease who were free of carotid plaque at baseline (2001-2002) and underwent ultrasound imaging at follow-up (2013-2016). Modified Poisson regression estimated the persistent absence of plaque over 12.8 years. Participants were on average age 36.2 years at baseline, 64% were women, and 29% were Black. Although nearly all participants (97%) had a 10-year atherosclerotic cardiovascular disease risk <7.5%, there were 162 people (32%) who developed premature atherosclerosis. Aside from younger age (risk ratio [RR], 1.21; 95% CI, 1.07-1.36, per 10 years) and a total cholesterol/high-density lipoprotein cholesterol ratio <3.5 (RR, 1.15; 95% CI, 1.01-1.30), normal values of traditional risk factors did not predict long-term absence of plaque. Independent from traditional markers including glomerular filtration rate, serum calcium-phosphate product (RR, 1.07; 95% CI, 1.01-1.14, per 1-SD lower), phosphate (RR, 1.15; 95% CI, 1.03-1.29, per 1 mg/dL lower), and dietary sodium <2300 mg/day (RR, 1.20; 95% CI, 1.02-1.41) were significantly associated with the non-development of plaque. Conclusions Nearly one third of young adults with a low burden of traditional risk factors developed premature atherosclerosis. Beyond younger age and an ideal lipoprotein profile, lower calcium-phosphate homeostasis and low sodium intake were associated with long-term absence of carotid plaque. These results suggest that dietary and intrinsic minerals are early contributors to the development of arterial aging phenotypes.


Assuntos
Doenças das Artérias Carótidas/epidemiologia , Envelhecimento Saudável , Adulto , Idade de Início , Biomarcadores/sangue , Cálcio/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Feminino , Humanos , Estilo de Vida , Lipídeos/sangue , Estudos Longitudinais , Louisiana/epidemiologia , Masculino , Fosfatos/sangue , Placa Aterosclerótica , Prognóstico , Medição de Risco , Fatores de Risco , Sódio na Dieta/efeitos adversos , Fatores de Tempo
7.
Hypertension ; 78(1): 4-15, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33993724

RESUMO

More than half of US adults have hypertension by 40 years of age and a subsequent increase in atherosclerotic cardiovascular disease risk. Dietary sodium and potassium are intricately linked to the pathophysiology of hypertension. However, blood pressure responses to dietary sodium and potassium, phenomena known as salt and potassium sensitivity of blood pressure, respectively, are heterogenous and normally distributed in the general population. Like blood pressure, salt and potassium sensitivity are complex phenotypes, and previous research has shown that up to 75% of individuals experience a blood pressure change in response to such dietary minerals. Previous research has also implicated both high salt sensitivity and low salt sensitivity (or salt resistance) of blood pressure to an increased risk of hypertension and potentially atherosclerotic cardiovascular disease risk. Given the clinical challenges required to accurately measure the sodium and potassium response phenotypes, genomic characterization of these traits has become of interest for hypertension prevention initiatives on both the individual and population levels. Here, we review advances in human genomics research of blood pressure responses to dietary sodium and potassium by focusing on 3 main areas, including the phenotypic characterization of salt sensitivity and resistance, clinical challenges in diagnosing such phenotypes, and the genomic mechanisms that may help to explain salt and potassium sensitivity and resistance. Through this process, we hope to further underline the value of leveraging genomics and broader multiomics for characterizing the blood pressure response to sodium and potassium to improve precision in lifestyle approaches for primordial and primary atherosclerotic cardiovascular disease prevention.


Assuntos
Pesquisa Biomédica/métodos , Pressão Sanguínea/fisiologia , Genômica/métodos , Hipertensão/fisiopatologia , Potássio na Dieta/administração & dosagem , Sódio na Dieta/administração & dosagem , Pesquisa Biomédica/tendências , Pressão Sanguínea/genética , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Genômica/tendências , Humanos , Hipertensão/genética , Hipertensão/prevenção & controle , Estilo de Vida , Fatores de Risco
8.
Atherosclerosis ; 326: 56-62, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824003

RESUMO

BACKGROUND AND AIMS: A large proportion of statin eligible candidates have a baseline absence of coronary artery calcium (CAC) and low 10-year atherosclerotic cardiovascular disease (ASCVD) risk. We sought to determine the proportion of statin eligible individuals who had long-term healthy arterial aging (persistent CAC = 0) and their examined 15-year ASCVD outcomes. METHODS: We included 561 statin eligible candidates from the Multi-Ethnic Study of Atherosclerosis who were not on statin therapy with CAC = 0 at Visit 1 (2000-02) and underwent a subsequent CAC scan at Visit 5 (2010-11). Adjusted Cox proportional hazards regression assessed the association between persistent CAC = 0 and ASCVD events over 15.9 years. RESULTS: Participants were on average 61.7 years old, 50% were women, and 43% maintained long-term CAC = 0. Individuals with an LDL-C ≥190 mg/dL (54%) and those with an ASCVD risk ≥20% (33%) had the highest and lowest proportion of persistent CAC = 0, respectively. There were 57 ASCVD events, and 15-year ASCVD event rates were low for individuals with and without healthy arterial aging (4.3 versus 8.6 per 1,000 persons-years), but the 10-year number needed to treat to prevent one ASCVD event differed by more than two fold (117 versus 54). In multivariable modeling, persistent CAC = 0 conferred a 51% lower risk of ASCVD compared to those with incident CAC (HR = 0.49, 95% CI: 0.27-0.90, p=0.02). CONCLUSIONS: More than 40% of statin eligible individuals with baseline CAC = 0 had long-term healthy arterial aging. Statin eligible candidates with persistent CAC = 0 had a very low 15-year ASCVD risk, suggesting that statin therapy may be of limited benefit among this group of individuals.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Calcificação Vascular , Envelhecimento , Feminino , Humanos , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco
10.
Am J Epidemiol ; 190(10): 1977-1992, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33861317

RESUMO

Genotype-phenotype association studies often combine phenotype data from multiple studies to increase statistical power. Harmonization of the data usually requires substantial effort due to heterogeneity in phenotype definitions, study design, data collection procedures, and data-set organization. Here we describe a centralized system for phenotype harmonization that includes input from phenotype domain and study experts, quality control, documentation, reproducible results, and data-sharing mechanisms. This system was developed for the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine (TOPMed) program, which is generating genomic and other -omics data for more than 80 studies with extensive phenotype data. To date, 63 phenotypes have been harmonized across thousands of participants (recruited in 1948-2012) from up to 17 studies per phenotype. Here we discuss challenges in this undertaking and how they were addressed. The harmonized phenotype data and associated documentation have been submitted to National Institutes of Health data repositories for controlled access by the scientific community. We also provide materials to facilitate future harmonization efforts by the community, which include 1) the software code used to generate the 63 harmonized phenotypes, enabling others to reproduce, modify, or extend these harmonizations to additional studies, and 2) the results of labeling thousands of phenotype variables with controlled vocabulary terms.


Assuntos
Estudos de Associação Genética/métodos , Fenômica/métodos , Medicina de Precisão/métodos , Agregação de Dados , Humanos , Disseminação de Informação , National Heart, Lung, and Blood Institute (U.S.) , Fenótipo , Avaliação de Programas e Projetos de Saúde , Estados Unidos
11.
Genetics ; 218(1)2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-33720349

RESUMO

Traditional Hardy-Weinberg equilibrium (HWE) tests (the χ2 test and the exact test) have long been used as a metric for evaluating genotype quality, as technical artifacts leading to incorrect genotype calls often can be identified as deviations from HWE. However, in data sets composed of individuals from diverse ancestries, HWE can be violated even without genotyping error, complicating the use of HWE testing to assess genotype data quality. In this manuscript, we present the Robust Unified Test for HWE (RUTH) to test for HWE while accounting for population structure and genotype uncertainty, and to evaluate the impact of population heterogeneity and genotype uncertainty on the standard HWE tests and alternative methods using simulated and real sequence data sets. Our results demonstrate that ignoring population structure or genotype uncertainty in HWE tests can inflate false-positive rates by many orders of magnitude. Our evaluations demonstrate different tradeoffs between false positives and statistical power across the methods, with RUTH consistently among the best across all evaluations. RUTH is implemented as a practical and scalable software tool to rapidly perform HWE tests across millions of markers and hundreds of thousands of individuals while supporting standard VCF/BCF formats. RUTH is publicly available at https://www.github.com/statgen/ruth.

12.
J Hypertens ; 39(5): 961-969, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33560053

RESUMO

OBJECTIVES: Heart disease is the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Emerging data have shown that NAFLD may affect subclinical myocardial remodeling, mainly left ventricular hypertrophy; however, evidence from the prospective studies is still lacking. METHODS: Prospective analyses were performed to investigate the association of fatty liver index (FLI) with left ventricular mass (LVM) among 1962 participants from the Bogalusa Heart Study (BHS, 1995-2010) and 1547 participants from the Cardiovascular Risk in Young Finns Study (YFS, 2001-2011) free of cardiovascular diseases (CVD) at baseline. LVM was assessed by two-dimensional guided M-mode echocardiography and indexed (LVMI) to body height (m2.7). Multivariable regression models were applied after adjustment for traditional CVD risk factors. RESULTS: In both cohorts, we observed significant and positive associations between FLI and LVM (BHS: ß=0.59, P < 0.001; YFS: ß=0.41, P < 0.001) and LVMI (BHS: ß=0.14, P < 0.001; YFS: ß=0.09, P < 0.001). In addition, we found that the relationship between FLI and LVMI was stronger in women than men (BHS: P-interaction = 0.01; YFS: P-interaction < 0.01); and the relationship between FLI and LVM/LVMI was stronger in black than white individuals (LVM: P-interaction = 0.02; LVMI: P-interaction = 0.04). Moreover, we found that the associations of FLI with LVM and LVMI were attenuated by high physical activity, especially in BHS (P-interaction = 0.02). CONCLUSION: Our findings from two independent prospective cohorts indicate that FLI is positively associated with LVM/LVMI, independent of traditional cardiovascular risk factors. Such relationships are more pronounced among women and black individuals and are attenuated by high physical activity.


Assuntos
Doenças Cardiovasculares , Fígado Gorduroso , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco
13.
EBioMedicine ; 63: 103157, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33418499

RESUMO

BACKGROUND: Genetic factors that influence kidney traits have been understudied for low frequency and ancestry-specific variants. METHODS: We combined whole genome sequencing (WGS) data from 23,732 participants from 10 NHLBI Trans-Omics for Precision Medicine (TOPMed) Program multi-ethnic studies to identify novel loci for estimated glomerular filtration rate (eGFR). Participants included European, African, East Asian, and Hispanic ancestries. We applied linear mixed models using a genetic relationship matrix estimated from the WGS data and adjusted for age, sex, study, and ethnicity. FINDINGS: When testing single variants, we identified three novel loci driven by low frequency variants more commonly observed in non-European ancestry (PRKAA2, rs180996919, minor allele frequency [MAF] 0.04%, P = 6.1 × 10-11; METTL8, rs116951054, MAF 0.09%, P = 4.5 × 10-9; and MATK, rs539182790, MAF 0.05%, P = 3.4 × 10-9). We also replicated two known loci for common variants (rs2461702, MAF=0.49, P = 1.2 × 10-9, nearest gene GATM, and rs71147340, MAF=0.34, P = 3.3 × 10-9, CDK12). Testing aggregated variants within a gene identified the MAF gene. A statistical approach based on local ancestry helped to identify replication samples for ancestry-specific variants. INTERPRETATION: This study highlights challenges in studying variants influencing kidney traits that are low frequency in populations and more common in non-European ancestry.


Assuntos
Genômica , Taxa de Filtração Glomerular , Medicina de Precisão , Sequenciamento Completo do Genoma , Alelos , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genômica/métodos , Humanos , Masculino , National Heart, Lung, and Blood Institute (U.S.) , Polimorfismo de Nucleotídeo Único , Medicina de Precisão/métodos , Vigilância em Saúde Pública , Característica Quantitativa Herdável , Estados Unidos/epidemiologia
14.
JACC Cardiovasc Imaging ; 14(1): 219-229, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33129732

RESUMO

OBJECTIVES: The purpose of this study was to identify predictors of healthy arterial aging (long-term coronary artery calcification [CAC] of 0) among individuals with metabolic syndrome (MetS) or type 2 diabetes (T2D), which may improve primary prevention strategies. BACKGROUND: Individuals with MetS or T2D have a heterogeneously increased risk of atherosclerotic cardiovascular disease and not all have a high-intermediate risk. METHODS: We included 574 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with MetS or T2D who had CAC=0 at baseline and a repeat CAC scan 10 years later. Multivariable logistic regression assessed the association of traditional and novel atherosclerotic cardiovascular disease risk factors and the MetS severity score (based on the 5 MetS criteria) with healthy arterial aging. RESULTS: The mean age of participants was 58.9 years, 67% were women, 422 participants had MetS, and 152 had T2D. The proportion with long-term CAC=0 was similar for MetS (42%) and T2D (44%). A younger age was the only individual low/normal traditional risk factor associated with an increased likelihood of long-term CAC=0 (odds ratio [OR]: 1.50; 95% confidence interval [CI]: 1.22 to 1.85 per 10-years younger). The strongest associations of nontraditional risk factors were observed for an absence of thoracic calcification (OR: 2.42; 95% CI: 1.24 to 4.72), absence of carotid plaque (OR: 1.81; 95% CI: 1.25 to 2.61), and among persons with a high sensitivity troponin <3 ng/ml (OR: 1.55; 95% CI: 1.01 to 2.38). In addition, persons with the lowest quartile MetS severity score had a substantially higher odds of healthy long-term CAC=0 (OR: 2.71; 95% CI: 1.27 to 5.76). CONCLUSIONS: More than 40% of adults with MetS or T2D and baseline CAC=0 had long-term absence of CAC, which was most strongly associated with an absence of extracoronary atherosclerosis and a low MetS score. An optimal overall cardiovascular profile appears to be more important than an ideal value of any individual risk factor to maintain healthy arterial aging.


Assuntos
Doença da Artéria Coronariana , Síndrome Metabólica , Cálcio , Vasos Coronários , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Calcificação Vascular
15.
ESC Heart Fail ; 7(5): 2700-2710, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33350106

RESUMO

AIMS: Left ventricular diastolic dysfunction (LVDD) is an early heart failure with preserved ejection fraction (HFpEF) phenotype that is reversible. Identifying dietary predictors associated with LVDD in diverse populations may help broadly improve HFpEF primary prevention. METHODS AND RESULTS: This longitudinal analysis included 456 individuals of the Bogalusa Heart Study (27% Black, 63% women, baseline age = 36.1 ± 4.4 years). Diet was measured at baseline through food frequency questionnaires. LVDD was defined at follow-up (median = 12.9 years) through echocardiographic measurement of the E/A ratio, E/e' ratio, isovolumic relaxation time, and deceleration time. Multivariable-adjusted logistic regression estimated the risk of LVDD according to dietary predictor, adjusting for traditional cardiovascular disease risk factors. Compared with the lowest tertile, participants in the middle tertile of total protein (OR = 3.30, 95% CI: 1.46, 7.45) and animal protein (OR = 2.91, 95% CI: 1.34, 6.34) consumption experienced the highest risk of LVDD. There was a 77% and 56% lower risk of LVDD for persons in the middle vs. lowest tertile of vegetable (OR = 0.23, 95% CI: 0.11, 0.49) and legume consumption (OR = 0.44, 95% CI: 0.22, 0.85), respectively. Total protein, animal protein, processed meat, and egg consumption indicated a quadratic trend towards increased risk of LVDD, while legume and vegetable intake conferred a quadratic trend towards decreased risk of LVDD (all quadratic P < 0.05). CONCLUSIONS: Diets higher in animal foods and lower in plant foods are associated with an increased risk for LVDD. These findings suggest threshold effects of diet on LVDD, past which more traditional cardiometabolic determinants occupy a larger role in HFpEF risk.


Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Adulto , Animais , Ecocardiografia , Feminino , Humanos , Estudos Longitudinais , Masculino , Volume Sistólico , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Esquerda/etiologia
16.
Circ Cardiovasc Imaging ; 13(8): e010335, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32772573

RESUMO

BACKGROUND: Elevated cardiovascular disease risk factor burden is a recognized contributor to poorer cognitive function; however, the physiological mechanisms underlying this association are not well understood. We sought to assess the potential mediation effect of left ventricular (LV) remodeling on the association between lifetime systolic blood pressure and cognitive function in a community-based cohort of middle-aged adults. METHODS: Nine hundred sixty participants of the Bogalusa Heart Study (59.2% women, 33.8% black, aged 48.4±5.1 years) received 2-dimensional echocardiography to quantify relative wall thickness, LV mass, and diastolic and systolic LV function; and a standardized neurocognitive battery to assess memory, executive functioning, and language processing. Multivariable linear regression assessed the association of cardiac structure and function with a global composite cognitive function score, adjusting for traditional cardiovascular disease risk factors. Mediation analysis assessed the effect of LV mass index on the association between lifetime systolic blood pressure burden and cognitive function. RESULTS: There were 233 (24.3%) and 136 (14.2%) individuals with concentric LV remodeling and concentric LV hypertrophy, respectively. Each g/m2.7 increment in LV mass index was associated with a 0.03 standardized unit decrement in global cognitive function (P=0.03). Individuals with concentric LV remodeling and isolated diastolic dysfunction had the poorest cognitive function, and a greater ratio between early mitral inflow velocity and early diastolic mitral annular velocity (E/e') was associated with poorer cognitive function, even after adjustment for LV mass index (B=-0.12; P=0.03). A total of 18.8% of the association between lifetime systolic blood pressure burden and midlife cognitive function was accounted for by LV mass index. CONCLUSIONS: Cardiac remodeling partially mediates the association between lifespan systolic blood pressure burden and adult cognition in individuals without dementia or clinical cardiovascular disease. Slowing or reversing the progression of cardiac remodeling in middle-age may be a novel therapeutic approach to prevent cognitive decline.


Assuntos
Cognição , Disfunção Cognitiva/psicologia , Ecocardiografia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Fatores Etários , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Função Executiva , Feminino , Humanos , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Louisiana/epidemiologia , Masculino , Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos , Medição de Risco , Fatores de Risco , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Esquerda/fisiopatologia
17.
J Hypertens ; 38(12): 2435-2442, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32649643

RESUMO

OBJECTIVE: Dietary factors mediate racial disparities in hypertension. However, the physiological mechanisms underlying this relationship are incompletely understood. We sought to assess the association between 1-methylhistidine (1-MH), a metabolite marker of animal protein consumption, and blood pressure (BP) in a community-based cohort of black and white middle-aged adults. METHODS: This analysis consisted of 655 participants of the Bogalusa Heart Study (25% black, 61% women, aged 34-58 years) who were not taking antihypertensive medication. Fasting serum 1-MH was measured using liquid chromatography-tandem mass spectroscopy. Animal food intakes were quantified by food-frequency questionnaires. Multivariable linear regression assessed the association between 1-MH and BP in combined and race-stratified analyses, adjusting for demographic, dietary, and cardiometabolic factors. RESULTS: A significant dose--response relationship was observed for the association of red meat (P-trend <0.01) and poultry (P-trend = 0.03) intake with serum 1-MH among all individuals. Serum 1-MH, per standard deviation increase, had a significant positive association with SBP (ß=3.4 ±â€Š1.6 mmHg, P = 0.04) and DBP (ß=2.0 ±â€Š1.1 mmHg, P = 0.05) in black participants, whereas no appreciable association was observed in white participants. Among a subgroup of black participants with repeat outcome measures (median follow-up = 3.0 years), one standard deviation increase in 1-MH conferred a 3.1 and 2.2 mmHg higher annual increase in SBP (P = 0.03) and DBP (P = 0.03), respectively. CONCLUSION: Serum 1-MH associates with higher SBP and DBP in blacks, but not whites. These results suggest a utility for further assessing the role of dietary 1-MH among individuals with hypertension to help minimize racial disparities in cardiovascular health.


Assuntos
Afro-Americanos/estatística & dados numéricos , Proteínas Animais da Dieta/metabolismo , Pressão Sanguínea/fisiologia , Metilistidinas/sangue , /estatística & dados numéricos , Adulto , Biomarcadores/sangue , Feminino , Humanos , Hipertensão/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
18.
Aging (Albany NY) ; 12(12): 11914-11941, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32482911

RESUMO

Age-related declines in physical performance predict cognitive impairment, disability, chronic disease exacerbation, and mortality. We conducted a metabolome-wide association study of physical performance among Bogalusa Heart Study participants. Bonferroni corrected multivariate-adjusted linear regression was employed to examine cross-sectional associations between single metabolites and baseline gait speed (N=1,227) and grip strength (N=1,164). In a sub-sample of participants with repeated assessments of gait speed (N=282) and grip strength (N=201), significant metabolites from the cross-sectional analyses were tested for association with change in physical performance over 2.9 years of follow-up. Thirty-five and seven metabolites associated with baseline gait speed and grip strength respectively, including six metabolites that associated with both phenotypes. Three metabolites associated with preservation or improvement in gait speed over follow-up, including: sphingomyelin (40:2) (P=2.6×10-4) and behenoyl sphingomyelin (d18:1/22:0) and ergothioneine (both P<0.05). Seven metabolites associated with declines in gait speed, including: 1-carboxyethylphenylalanine (P=8.8×10-5), and N-acetylaspartate, N-formylmethionine, S-adenosylhomocysteine, N-acetylneuraminate, N2,N2-dimethylguanosine, and gamma-glutamylphenylalanine (all P<0.05). Two metabolite modules reflecting sphingolipid and bile acid metabolism associated with physical performance (minimum P=7.6×10-4). These results add to the accumulating evidence suggesting an important role of the human metabolome in physical performance and specifically implicate lipid, nucleotide, and amino acid metabolism in early physical performance decline.


Assuntos
Envelhecimento/sangue , Metaboloma/fisiologia , Desempenho Físico Funcional , Adulto , Envelhecimento/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos Transversais , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Metabolômica , Pessoa de Meia-Idade
19.
J Am Heart Assoc ; 9(13): e016997, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32418463

RESUMO

Medicine and public health have traditionally separated the prevention and treatment of communicable and noncommunicable diseases. The coronavirus disease 2019 (COVID-19) pandemic has challenged this paradigm, particularly in the setting of cardiovascular disease (CVD). Overall, individuals with underlying CVD who acquire severe acute respiratory syndrome coronavirus 2 experience up to a 10-fold higher case-fatality rate compared with the general population. Although the impact of the pandemic on cardiovascular health continues to evolve, few have defined this association from a frontline, public health perspective of populations disproportionately affected by CVD and COVID-19. Louisiana is ranked within the bottom 5 states for cardiovascular health, and it is home to several parishes that have experienced among the highest COVID-19 case-fatality rates nationally. Herein, we review CVD prevention and implications of COVID-19 in New Orleans, LA, a city holding a sobering yet resilient history with previous public health disasters. In particular, we discuss potential pandemic-driven changes in access to health care, preventive pharmacotherapy, and lifestyle behaviors, all of which may adversely affect CVD prevention and management, while amplifying racial disparities. Through this process, we highlight proposed recommendations for how CVD prevention efforts can be improved in the midst of the current COVID-19 pandemic and future public health crises.


Assuntos
Betacoronavirus , Doenças Cardiovasculares/prevenção & controle , Infecções por Coronavirus/complicações , Atenção à Saúde/métodos , Estilo de Vida , Pandemias , Pneumonia Viral/complicações , Saúde Pública , COVID-19 , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Infecções por Coronavirus/epidemiologia , Humanos , Incidência , Nova Orleans/epidemiologia , Pneumonia Viral/epidemiologia , SARS-CoV-2
20.
Am J Kidney Dis ; 76(4): 511-520, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32387023

RESUMO

RATIONALE & OBJECTIVE: Biomarkers that provide reliable evidence of future diabetic kidney disease (DKD) are needed to improve disease management. In a cross-sectional study, we previously identified 13 urine metabolites that had levels reduced in DKD compared with healthy controls. We evaluated associations of these 13 metabolites with future DKD progression. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 1,001 Chronic Renal Insufficiency Cohort (CRIC) participants with diabetes with estimated glomerular filtration rates (eGFRs) between 20 and 70mL/min/1.73m2 were followed up prospectively for a median of 8 (range, 2-10) years. PREDICTORS: 13 urine metabolites, age, race, sex, smoked more than 100 cigarettes in lifetime, body mass index, hemoglobin A1c level, blood pressure, urinary albumin, and eGFR. OUTCOMES: Annual eGFR slope and time to incident kidney failure with replacement therapy (KFRT; ie, initiation of dialysis or receipt of transplant). ANALYTICAL APPROACH: Several clinical metabolite models were developed for eGFR slope as the outcome using stepwise selection and penalized regression, and further tested on the time-to-KFRT outcome. A best cross-validated (final) prognostic model was selected based on high prediction accuracy for eGFR slope and high concordance statistic for incident KFRT. RESULTS: During follow-up, mean eGFR slope was-1.83±1.92 (SD) mL/min/1.73m2 per year; 359 (36%) participants experienced KFRT. Median time to KFRT was 7.45 years from the time of entry to the CRIC Study. In our final model, after adjusting for clinical variables, levels of metabolites 3-hydroxyisobutyrate (3-HIBA) and 3-methylcrotonyglycine had a significant negative association with eGFR slope, whereas citric and aconitic acid were positively associated. Further, 3-HIBA and aconitic acid levels were associated with higher and lower risk for KFRT, respectively (HRs of 2.34 [95% CI, 1.51-3.62] and 0.70 [95% CI, 0.51-0.95]). LIMITATIONS: Subgroups for whom metabolite signatures may not be optimal, nontargeted metabolomics by flow-injection analysis, and 2-stage modeling approaches. CONCLUSIONS: Urine metabolites may offer insights into DKD progression. If replicated in future studies, aconitic acid and 3-HIBA could identify individuals with diabetes at high risk for GFR decline, potentially leading to improved clinical care and targeted therapies.


Assuntos
Nefropatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/urina , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/urina , Idoso , Biomarcadores/urina , Estudos de Coortes , Nefropatias Diabéticas/metabolismo , Progressão da Doença , Feminino , Humanos , Masculino , Metabolômica , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/metabolismo
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