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Metabolite Profiles of Healthy Aging Index Are Associated With Cardiovascular Disease in African Americans: The Health, Aging, and Body Composition Study.

ABSTRACT: Background:Metabolic dysfunction is a hallmark of differential aging, specifically in African Americans. Investigation of systemic metabolic state, multiorgan aging, and long-term cardiovascular outcome in African Americans has not been reported. Methods:We studied 291 African American males in the Health, Aging, and Body Composition (Health ABC) study to identify circulating metabolites related to the Newman healthy aging index (HAI; a multiparametric score comprised of blood pressure, blood glucose, neurocognitive function, creatinine, and forced vital capacity). We examined the relationship of selected metabolites differential abundant at the extremes of HAI with long-term survival from cardiovascular mortality. Results:The median age was 73 years. We identified 19 metabolites differentially expressed in blood in 86 study participants at the extremes of HAI (HAI 0-3: N = 30 vs 8-10: N = 56). At a median follow-up of 10 years, 78 participants (27 per cent) died from cardiovascular causes. After adjustment for age, body mass index, presence of prevalent cardiovascular disease, creatinine, and HAI, six of these 19 metabolites were associated with long-term cardiovascular mortality. Although several metabolites had been previously reported in Caucasians (eg, isocitrate), we identified several metabolites with unreported association with cardiac disease. Metabolites associated with HAI and cardiac death in African Americans specified pathways relevant to nitric oxide, oxidative stress, mitochondrial function, urea cycle, and gut microbial metabolism. Conclusions:Metabolite profiling in African Americans identified known and novel metabolic pathways linked to HAI and cardiovascular death. Further investigation in larger patient cohorts is required to uncover race-based signatures of cardiovascular disease with aging.

SUBMITTER: Yeri A

PROVIDER: S-EPMC6298181 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Metabolite Profiles of Healthy Aging Index Are Associated With Cardiovascular Disease in African Americans: The Health, Aging, and Body Composition Study.

Yeri Ashish A Murphy Rachel A RA Marron Megan M MM Clish Clary C Harris Tamara B TB Lewis Gregory D GD Newman Anne B AB Murthy Venkatesh L VL Shah Ravi V RV

The journals of gerontology. Series A, Biological sciences and medical sciences 20190101 1

<h4>Background</h4>Metabolic dysfunction is a hallmark of differential aging, specifically in African Americans. Investigation of systemic metabolic state, multiorgan aging, and long-term cardiovascular outcome in African Americans has not been reported.<h4>Methods</h4>We studied 291 African American males in the Health, Aging, and Body Composition (Health ABC) study to identify circulating metabolites related to the Newman healthy aging index (HAI; a multiparametric score comprised of blood pre ...[more]

PMID: 29253112

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Project description:BackgroundHigh diet quality is associated with a lower risk of chronic diseases. Metabolomics can be used to identify objective biomarkers of diet quality.ObjectivesWe used metabolomics to identify serum metabolites associated with 4 diet indices and the components within these indices in 2 samples from African Americans and European Americans.MethodsWe studied cross-sectional associations between known metabolites and Healthy Eating Index (HEI)-2015, Alternative Healthy Eating Index (AHEI)-2010, the Dietary Approaches to Stop Hypertension Trial (DASH) diet, alternate Mediterranean diet (aMED), and their components using untargeted metabolomics in 2 samples (n1 = 1,806, n2 = 2,056) of the Atherosclerosis Risk in Communities study (aged 45-64 y at baseline). Dietary intakes were assessed using an FFQ. We used multivariable linear regression models to examine associations between diet indices and serum metabolites in each sample, adjusting for participant characteristics. Metabolites significantly associated with diet indices were meta-analyzed across 2 samples. C-statistics were calculated to examine if these candidate biomarkers improved prediction of individuals in the highest compared with lowest quintile of diet scores beyond participant characteristics.ResultsSeventeen unique metabolites (HEI: n = 6; AHEI: n = 5; DASH: n = 14; aMED: n = 2) were significantly associated with higher diet scores after Bonferroni correction in sample 1 and sample 2. Six of 17 significant metabolites [glycerate, N-methylproline, stachydrine, threonate, pyridoxate, 3-(4-hydroxyphenyl)lactate)] were associated with ≥1 dietary pattern. Candidate biomarkers of HEI, AHEI, and DASH distinguished individuals with highest compared with lowest quintile of diet scores beyond participant characteristics in samples 1 and 2 (P value for difference in C-statistics <0.02 for all 3 diet indices). Candidate biomarkers of aMED did not improve C-statistics beyond participant characteristics (P value = 0.930).ConclusionsA considerable overlap of metabolites associated with HEI, AHEI, DASH, and aMED reflects the similar food components and similar metabolic pathways involved in the metabolism of healthy diets in African Americans and European Americans.

Project description:Genome-wide association studies of obesity have typically assumed fixed genetic effects across ethnicities, rarely attempting to thoroughly compare and contrast findings across various ethnic groups. Therefore, our study aimed to identify novel genetic associations with body mass index (BMI), a common measure of obesity, and explore their cross-ethnic generalizability in a multiethnic population. To that end, we conducted ?ethnic-specific genome-wide association analyses among 1235 Hispanic, 706 Asian, 1549 African American, and 2395 European American subjects from the Multi-ethnic Study of Atherosclerosis (MESA). We compared findings ?across ethnicities and investigated single-nucleotide polymorphisms (SNPs) with suggestive BMI-association p-values among 3379 Hispanic and 6871 African American subjects from the Women's Health Initiative (WHI).We identified a genome-wide significant association in MESA Hispanics-rs12253976 in KLF6 (beta?=?5.792 kg/m(2) per-allele, 95 % confidence interval (CI): 3.885, 7.698; p?=?3.43?×?10(-9))-and suggestive SNPs with p?<?5?×?10(-6) in MESA Hispanics, European Americans and African Americans that display ethnic-specific effects on BMI. Of these suggestive SNPs, Hispanic SNP rs12255372 and African American SNP rs6435678 had the most evidence of replication in WHI. rs12255372 (in TCF7L2) was associated with lower BMI in both MESA (beta?=?-1.111 kg/m(2), 95 % CI: -1.578, -0.645; p?=?3.33?×?10(-6)) and WHI Hispanics (beta?=?-0.304 kg/m(2), 95 % CI: -0.613, 0.006; p?=?0.054). This TCF7L2 intronic region contains several SNPs (rs7901695, rs4506565, rs4132670, and rs12243326) with low p-values (p < 10(-3)) in MESA and betas of similar magnitude and direction in MESA and WHI, but only rs12243326 is in strong linkage disequilibrium with rs12255372 in our Hispanic populations, suggesting independent signals in this region. rs6435678 (in ERBB4) was associated with greater BMI in both MESA (beta?=?1.104 kg/m(2), 95 % CI: 0.643, 1.564; p?=?2.85?×?10(-6)) and WHI African Americans (beta?=?0.219 kg/m(2), 95 % CI: -0.021, 0.460; p?=?0.074).Two BMI-association signals are present in the TCF7L2 intronic region of Hispanics, one of which is tagged by rs12255372. ERBB4 rs6435678 is a novel BMI-association signal in African Americans. Overall, our data suggest that ethnic-specific associations are involved in the genetic determination of BMI. Ethnic-specificity has potential implications for the development of gene-based therapies for obesity.

Project description:IntroductionGovernments across Europe want to promote healthy and active aging, as a matter of both public health and economic sustainability. Designing policies focused on the most vulnerable groups requires information at the individual level. However, a measure of healthy and active aging at the individual level does not yet exist.ObjectivesThis paper develops the Selfie Aging Index (SAI), an individual-level index of healthy and active aging. The SAI is developed thinking about a tool that would allow each person to take a selfie of her aging status. Therefore, it is based entirely on self-assessed indicators. This paper also illustrates how the SAI may look like in practice.MethodsThe SAI is based on the Biopsychosocial Assessment Model (MAB), a tool for the multidimensional assessment of older adults along three domains: biological, psychological, and social. Indicators are selected and their weights determined based on an ordered probit model that relates the MAB indicators to self-assessed health, which proxies healthy and active aging. The ordered probit model predicts the SAI based on the estimated parameters. Finally, predictions are rescaled to the 0-1 interval. Data for the SAI development come from the Study of the Aging Profiles of the Portuguese Population and the Survey of Health, Aging, and Retirement in Europe.ResultsThe selected indicators are BMI, having difficulties moving around indoors and performing the activities of daily living, feeling depressed, feeling nervous, lacking energy, time awareness score, marital status, having someone to confide in, education, type of job, exercise, and smoking status. The model also determines their weights.ConclusionResults shed light on various factors that contribute significantly to healthy and active aging. Two examples are mental health and exercise, which deserve more attention from individuals themselves, health-care professionals, and public health policy. The SAI has the potential to put the individual at the center of the healthy and active aging discussion, contribute to patient empowerment, and promote patient-centered care. It can become a useful instrument to monitor healthy and active aging for different actors, including individuals themselves, health-care professionals, and policy makers.

Dataset Information

Metabolite Profiles of Healthy Aging Index Are Associated With Cardiovascular Disease in African Americans: The Health, Aging, and Body Composition Study.

Publications

Metabolite Profiles of Healthy Aging Index Are Associated With Cardiovascular Disease in African Americans: The Health, Aging, and Body Composition Study.

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