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Novel Findings From a Metabolomics Study of Left Ventricular Diastolic Function: The Bogalusa Heart Study.

ABSTRACT: Background Diastolic dysfunction is one important causal factor for heart failure with preserved ejection fraction, yet the metabolic signature associated with this subclinical phenotype remains unknown. Methods and Results Ultra-high-performance liquid chromatography-tandem mass spectroscopy was used to conduct untargeted metabolomic analysis of fasting serum samples in 1050 white and black participants of the BHS (Bogalusa Heart Study). After quality control, 1202 metabolites were individually tested for association with 5 echocardiographic measures of left ventricular diastolic function using multivariable-adjusted linear regression. Measures of left ventricular diastolic function included the ratio of peak early filling velocity to peak late filling velocity, ratio of peak early filling velocity to mitral annular velocity, deceleration time, isovolumic relaxation time, and left atrial maximum volume index (LAVI). Analyses adjusted for multiple cardiovascular disease risk factors and used Bonferroni-corrected alpha thresholds. Eight metabolites robustly associated with left ventricular diastolic function in the overall population and demonstrated consistent associations in white and black study participants. N-formylmethionine (B=0.05; P=1.50×10-7); 1-methylhistidine (B=0.05; P=1.60×10-7); formiminoglutamate (B=0.07; P=5.60×10-7); N2, N5-diacetylornithine (B=0.05; P=1.30×10-7); N-trimethyl 5-aminovalerate (B=0.04; P=5.10×10-6); 5-methylthioadenosine (B=0.04; P=1.40×10-5); and methionine sulfoxide (B=0.04; P=3.80×10-6) were significantly associated with the natural log of the ratio of peak early filling velocity to mitral annular velocity. Butyrylcarnitine (B=3.18; P=2.10×10-6) was significantly associated with isovolumic relaxation time. Conclusions The current study identified novel findings of metabolite associations with left ventricular diastolic function, suggesting that the serum metabolome, and its underlying biological pathways, may be implicated in heart failure with preserved ejection fraction pathogenesis.

SUBMITTER: Razavi AC

PROVIDER: S-EPMC7033875 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Novel Findings From a Metabolomics Study of Left Ventricular Diastolic Function: The Bogalusa Heart Study.

Razavi Alexander C AC Bazzano Lydia A LA He Jiang J Fernandez Camilo C Whelton Seamus P SP Krousel-Wood Marie M Li Shengxu S Nierenberg Jovia L JL Shi Mengyao M Li Changwei C Mi Xuenan X Kinchen Jason J Kelly Tanika N TN

Journal of the American Heart Association 20200129 3

Background Diastolic dysfunction is one important causal factor for heart failure with preserved ejection fraction, yet the metabolic signature associated with this subclinical phenotype remains unknown. Methods and Results Ultra-high-performance liquid chromatography-tandem mass spectroscopy was used to conduct untargeted metabolomic analysis of fasting serum samples in 1050 white and black participants of the BHS (Bogalusa Heart Study). After quality control, 1202 metabolites were individually ...[more]

PMID: 31992159

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Project description:BackgroundElevated 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.MethodsNine 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.ResultsThere 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.ConclusionsCardiac 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.

Project description:ObjectiveTo identify novel and confirm previously reported metabolites associated with SBP, DBP, and hypertension in a biracial sample of Bogalusa Heart Study (BHS) participants.MethodsWe employed untargeted, ultra-high performance liquid chromatography tandem mass spectroscopy metabolomics profiling among 1249 BHS participants (427 African-Americans and 822 whites) with BP and covariable data collected during the 2013 to 2016 visit cycle. A total of 1202 metabolites were tested for associations with continuous and binary BP phenotypes using multiple linear and logistic regression models, respectively, in overall and race-stratified analyses.ResultsA total of 24 novel metabolites robustly associated with BP, achieving Bonferroni-corrected P less than 4.16 × 10 in the overall analysis and consistent effect sizes across race groups. The identified metabolites included three amino acid and nucleotide metabolites from histidine, pyrimidine, or tryptophan metabolism sub-pathways, seven cofactor and vitamin or xenobiotic metabolites from the ascorbate and aldarate metabolism, bacterial/fungal, chemical, and food component sub-pathways, 10 lipid metabolites from the eicosanoid, phosphatidylcholine, phosphatidylethanolamine, and sphingolipid metabolism sub-pathways, and four still unnamed metabolites. Six previously described metabolites were robustly confirmed by our study (Bonferroni-corrected P < 4.95 × 10 and consistent effect directions across studies). Furthermore, previously reported metabolites for SBP, DBP, and hypertension demonstrated 5.92-fold, 4.77-fold, and 4.54-fold enrichment for nominally significant signals in the BHS (P = 3.08 × 10, 5.93 × 10, and 2.30 × 10, respectively).ConclusionIn aggregate, our study provides new information about potential molecular mechanisms underlying BP regulation. We also demonstrate reproducibility of findings across studies despite differences in study populations and metabolite profiling methods.

Project description:BackgroundLeft ventricular diastolic dysfunction has a significant impact on perioperative morbidity and mortality, and its incidence is high in elderly individuals. Anesthetic agents may impair diastolic function, which may increase the incidence of perioperative complications. The aim of this prospective, clinical, phase 4 study was to investigate the effects of remifentanil on left ventricle (LV) diastolic function in patients with diastolic dysfunction. The study was performed on 30 spontaneously breathing subjects (aged 60-80 years) with diastolic dysfunction.MethodsThirty patients (aged 60-80 years) with diastolic dysfunction scheduled for surgery were recruited between November 2019 and March 2023. Left ventricle function was evaluated once the intravenous remifentanil infusion reached a target-controlled concentration of 2 ng/ml with transthoracic echocardiography. Analysis of systolic function focused on left ventricular ejection fraction and mean mitral annular S velocity (Sm), whereas diastolic function focused on changes in transmitral peak flow (E), E/A, mitral septal and lateral e' waves, E/e' ratios and left atrial volume index following remifentanil infusion.ResultsDiastolic function measures of LV (mitral E/e', septal and lateral e' waves) statistically significantly improved (E/e' from 10.6 ± 2.9 cm.sn- 1 to 9.5 ± 2.2 cm.sn- 1; p = 0.006) following remifentanil infusion. Left atrial volume index decreased following remifentanil infusion without statistical significance (from 55 ± 14.4 ml.cm- 2 to 51.6 ± 13.3 ml.cm- 2; p = 0.1). Systolic function (ejection fraction and Sm) did not change following remifentanil infusion.ConclusionsRemifentanil improves left ventricular diastolic parameters in patients with preexisting diastolic dysfunction. Our study suggests that remifentanil at a plasma concentration of 2 ng.ml- 1 might be used safely in patients with left ventricular diastolic dysfunction.

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Novel Findings From a Metabolomics Study of Left Ventricular Diastolic Function: The Bogalusa Heart Study.

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Novel Findings From a Metabolomics Study of Left Ventricular Diastolic Function: The Bogalusa Heart Study.

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