Abstract 048: Circulating Branched-Chain Amino Acids and Incident Cardiovascular Disease in a Prospective Cohort of US Women

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Deirdre K Tobias ◽  
Patrick R Lawler ◽  
Paulo H Harada ◽  
Olga V Demler ◽  
Paul M Ridker ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Amino Acids ◽  
Prospective Cohort ◽  
Branched Chain Amino Acids ◽  
Health Study ◽  
Blood Collection ◽  
Cvd Risk ◽  
Isoleucine Leucine ◽  
Branched Chain

Introduction: Recent metabolomics studies have identified circulating levels of branched-chain amino acids (BCAAs; isoleucine, leucine, valine) as strong predictors of type 2 diabetes (T2D). Whether BCAAs are implicated in cardiovascular disease (CVD) risk has not been established. Hypothesis: We hypothesized that higher baseline levels of plasma BCAAs are associated with an elevated risk of incident CVD events, and evaluated whether this relationship was dependent on an intermediate diagnosis of T2D. Methods: Participants enrolled in the Women’s Health Study prospective cohort were eligible if they did not report CVD or cancer prior to baseline blood collection (N=27,172, mean baseline age=54.7 years). Plasma BCAA metabolites were measured via proton NMR spectroscopy, ln-transformed, and standardized for analysis. We used multivariable Cox proportional regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) per standard deviation (SD) of total and individual BCAAs with incident CVD (myocardial infarction [MI], stroke, coronary revascularization). Results: 1,917 confirmed CVD events occurred over follow-up (mean 18.6 years). In models adjusted for age, body mass index, smoking status, diet quality, physical activity, and other established CVD risk factors, total BCAAs were positively associated with CVD (per SD, HR=1.13, CI=1.08 to 1.19), comparable in magnitude to the association of LDL cholesterol with CVD (per SD, HR=1.15, CI=1.09 to 1.21). In particular, BCAAs were associated with coronary events (MI: HR=1.21, CI=1.10 to 1.33; revascularization: HR=1.15, CI=1.07 to 1.23), but not with stroke (HR=1.07, CI=0.98 to 1.15). The BCAA-CVD relationship was notably greater (p-interaction=0.008) among participants who developed T2D prior to a CVD event (HR=1.25, CI=1.13 to 1.39), vs. women without T2D (HR=1.07, CI=1.01 to 1.13). Isoleucine, leucine, and valine were each associated with CVD (p<0.05). Further adjusting for biomarkers of potential intermediates, HbA1c, lipids, and a lipoprotein-based insulin resistance score entirely eliminated the associations of BCAAs with CVD. Conclusions: Circulating plasma BCAAs were positively associated with long-term incident CVD in a cohort of US women, in particular among women who developed T2D prior to a CVD event. Impaired BCAA metabolism may represent a shared pathway of insulin resistance that links the risks of T2D and CVD.

scholarly journals Plasma Branched-Chain Amino Acids and Incident Cardiovascular Disease in the PREDIMED Trial

2016 ◽  
Vol 62 (4) ◽  
pp. 582-592 ◽  
Author(s):  
Miguel Ruiz-Canela ◽  
Estefania Toledo ◽  
Clary B Clish ◽  
Adela Hruby ◽  
Liming Liang ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Amino Acids ◽  
Cardiovascular Death ◽  
Branched Chain Amino Acids ◽  
Control Group ◽  
Cvd Risk ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Branched Chain

Abstract BACKGROUND The role of branched-chain amino acids (BCAAs) in cardiovascular disease (CVD) remains poorly understood. We hypothesized that baseline BCAA concentrations predict future risk of CVD and that a Mediterranean diet (MedDiet) intervention may counteract this effect. METHODS We developed a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED), with 226 incident CVD cases and 744 noncases. We used LC-MS/MS to measure plasma BCAAs (leucine, isoleucine, and valine), both at baseline and after 1 year of follow-up. The primary outcome was a composite of incident stroke, myocardial infarction, or cardiovascular death. RESULTS After adjustment for potential confounders, baseline leucine and isoleucine concentrations were associated with higher CVD risk: the hazard ratios (HRs) for the highest vs lowest quartile were 1.70 (95% CI, 1.05–2.76) and 2.09 (1.27–3.44), respectively. Stronger associations were found for stroke. For both CVD and stroke, we found higher HRs across successive quartiles of BCAAs in the control group than in the MedDiet groups. With stroke as the outcome, a significant interaction (P = 0.009) between baseline BCAA score and intervention with MedDiet was observed. No significant effect of the intervention on 1-year changes in BCAAs or any association between 1-year changes in BCAAs and CVD were observed. CONCLUSIONS Higher concentrations of baseline BCAAs were associated with increased risk of CVD, especially stroke, in a high cardiovascular risk population. A Mediterranean-style diet had a negligible effect on 1-year changes in BCAAs, but it may counteract the harmful effects of BCAAs on stroke.

scholarly journals Association of Dietary Branched-Chain Amino Acids With Obesity: The Filipino Women's Diet and Health Study (FiLWHEL)

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1072-1072
Author(s):  
Akinkunmi Okekunle ◽  
Heejin Lee ◽  
Sherlyn Mae Provido ◽  
Grace Chung ◽  
Sangmo Hong ◽  
...  
Keyword(s):  
Amino Acids ◽  
Statistical Significance ◽  
Branched Chain Amino Acids ◽  
Health Study ◽  
Dietary Intakes ◽  
Obesity Risk ◽  
Isoleucine Leucine ◽  
Dietary Recall ◽  
Filipino Migrants ◽  
Branched Chain

Abstract Objectives Migration plays a significant role in dietary choices and health of populations. Studies on dietary intakes of branched-chain amino acids (BCAA) and health status of migrant populations are scarce. This study examined the association between dietary BCAA intake and risk of obesity among migrant Filipino women in Korea. Methods This study included 428 women (20–57years) enrolled in the FiLWHEL study. Demographic information and anthropometric measurements (weight and height) were obtained using a standard protocol. Dietary BCAA (isoleucine, leucine, and valine) intakes were derived from a one-day 24-hour dietary recall. Body mass index (BMI) was calculated from weight and height. Obesity was defined as BMI ≥ 25 kg/m2. Energy-adjusted BCAA intakes were categorized in quartile distribution with the lowest quartile as a reference and multivariable-adjusted odds ratio (OR) with 95% confidence interval (CI) of obesity risk were estimated using logistic regression at a statistical significance of P &lt; 0.05. Results Mean age and BMI were 35.0 ± 8.1 years and 23.6 ± 3.9 kg/m2 respectively. 30.8% had BMI ≥ 25 kg/m2. Also, median and interquartile range of BCAA intakes (mg/day) were isoleucine: 1920.9 (1231.9–2719.1), leucine: 3318.9 (2134.2–4774.1), valine: 2257.3 (1442.6–3283.1) and total BCAA: 7519.0 (4762.0–10,726.9). Multivariable-adjusted OR and 95% CI for obesity risk given dietary BCAA intakes for each subsequent quartile compared to the bottom quartile were; isoleucine: 0.48 (0.27–0.89), 0.67 (0.37–1.02), and 0.49 (0.27–0.89) P for trend = 0.09; leucine: 0.69 (0.37–1.28), 0.80 (0.44–1.46), and 0.62 (0.34–1.13) P for trend = 0.23; valine: 0.51 (0.27–0.95), 0.77 (0.43–1.37), and 0.52 (0.28–0.95) P for trend = 0.15 and total BCAA: 0.58 (0.31–1.09), 0.82 (0.45–1.48), and 0.56 (0.31–1.03) P for trend = 0.23. Conclusions Dietary BCAA intake appears inversely related to the odds of obesity in this sample of Filipino migrants in Korea. Cohort studies among migrant population might significantly benefit the validation of these observations. Funding Sources This work was supported by the Hanmi Pharmaceutical Co., Ltd, (No. 201300000001270), Chong Kun Dang Pharm. Seoul, Korea (No. 201600000000225) and the Brain Pool Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (No. 2020H1D3A1A04081265).

Abstract 13479: Association of Plasma Branched Chain Amino Acid With Biomarkers of Inflammation and Lipid Metabolism in Women

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Rikuta Hamaya ◽  
Samia Mora ◽  
Patrick R Lawler ◽  
Nancy R Cook ◽  
Paul M Ridker ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Health Study ◽  
Cardiometabolic Health ◽  
Blood Collection ◽  
Impaired Glucose Metabolism ◽  
Cvd Risk ◽  
Branched Chain ◽  
Shared Risk

Introduction: We previously observed that circulating branched-chain amino acids (BCAAs) were associated with a higher risk of cardiovascular disease (CVD). However, the relationships of BCAAs with other cardiometabolic pathways other than type 2 diabetes (T2D) are unclear, including inflammation, dyslipidemia, and impaired glucose metabolism. Hypothesis: We hypothesized plasma BCAAs are correlated with cardiometabolic dysfunction in women, independent of shared risk factors. Methods: We conducted a cross-sectional analysis of 19,472 participants (mean age=54.9 years, SD=7.2) in the Women’s Health Study without a history of T2D, CVD, or cancer at baseline blood collection. We used multivariable linear regression models comparing quartiles of BCAAs (sum of fasting isoleucine, leucine and valine concentrations via NMR spectroscopy) with biomarkers of inflammation, lipids, and glucose metabolism, adjusting for age, body mass index, smoking, diet, and other CVD risk factors. Results: Women in the highest vs. lowest quartiles of plasma BCAAs had higher inflammatory markers including high-sensitivity C-reactive protein (hsCRP; adjusted mean: 2.7 vs. 2.0 mg/L), fibrinogen (390 vs. 384 mg/dL), GlycA (420 vs. 384 μmol/L), and soluble intercellular cell adhesion molecule-1 (sICAM-1; 350 vs. 341 ng/mL) (p<0.001 for linear trends across quartiles). Similarly for lipids, women with higher BCAAs had lower HDL-c (48.8 vs. 54.7 mg/dL), and higher LDL-c (142 vs. 135 mg/dL) and triglycerides (142 vs. 114 mg/dL) (p<0.001). BCAAs were positively associated with insulin resistance (lipoprotein insulin resistance [LPIR] score [54.8 vs. 40.0]) and HbA1c (5.2 vs. 5.1%). BCAAs remained associated with GlycA and hsCRP, but not fibrinogen or sICAM-1, when we further adjusted for LPIR and HbA1c, and remained associated with lipids after additional adjustment for HbA1c. Conclusions: Circulating BCAAs are concurrently associated with biomarkers of inflammation, dyslipidemia and impaired glucose metabolism indicative of an overall poorer cardiometabolic health profile. BCAAs remained positively associated with some of these pathways when adjusted for impaired glucose metabolism, suggesting elevated BCAAs may be an independent CVD risk factor in women.

scholarly journals Association of Plasma Branched Chain Amino Acid with Biomarkers of Inflammation and Lipid Metabolism in Women

2021 ◽  
Author(s):  
Rikuta Hamaya ◽  
Samia Mora ◽  
Patrick R. Lawler ◽  
Nancy R. Cook ◽  
Paul M. Ridker ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Health Study ◽  
Cardiometabolic Health ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Blood Draw ◽  
Isoleucine Leucine ◽  
Cross Sectional ◽  
Branched Chain

Backgrounds - Branched-chain amino acids (BCAAs; isoleucine, leucine and valine) correlate with insulin resistance and poor glucose control, which may in part explain associations between type 2 diabetes (T2D) and cardiovascular disease (CVD). However, the relationships of BCAAs with other cardiometabolic pathways, including inflammation and dyslipidemia, are unclear. We hypothesized that plasma BCAAs would correlate with multiple pathways of cardiometabolic dysfunction. Methods - We conducted a cross-sectional analysis among 19,472 participants (mean age=54.9 years, SD=7.2 years) in the Women's Health Study without a history of T2D, CVD, or cancer. We quantified the concentrations of individual biomarkers of inflammation and lipids, across quartiles of BCAAs, adjusting for age, smoking, BMI, physical activity, and other established CVD risk factors at blood draw. Results - Women in the highest vs. lowest quartiles of plasma BCAAs had higher inflammatory markers including high-sensitivity C-reactive protein (multivariable-adjusted means: 1.96 vs. 1.43 mg/L), fibrinogen (367 vs. 362 mg/dL), soluble intercellular cell adhesion molecule-1 (361 vs. 353 ng/mL), and glycoprotein acetylation (407 vs. 371 µmol/L) (p-trend=0.0002 for fibrinogen; p<0.0001 for others). Similarly for lipids, women with higher BCAAs had lower HDL-c (49.0 vs. 55.0 mg/dL), and higher triglycerides (143 vs. 114 mg/dL), LDL-c (133 vs. 124 mg/dL), and lipoprotein insulin resistance score (52.6 vs. 37.3) (all: p<0.0001). Similar associations with these biomarkers were observed in isoleucine, leucine and valine, respectively. Conclusions - Higher circulating BCAA concentrations are associated with adverse profiles of biomarkers of inflammation and dyslipidemia independent of established CVD risk factors, and thus may reflect poorer cardiometabolic health through multiple pathways.

Food consumption of branched chain amino acids and insulin resistance: A systematic review of observational studies in humans

2020 ◽  
Vol 40 ◽  
pp. 277-281
Author(s):  
Eduardo Emanuel Sátiro Vieira ◽  
Irislene Costa Pereira ◽  
Amanda Ferraz Braz ◽  
Marcus Vinicius Nascimento-Ferreira ◽  
Lucillia Rabelo de Oliveira Torres ◽  
...  
Keyword(s):  
Systematic Review ◽  
Insulin Resistance ◽  
Amino Acids ◽  
Food Consumption ◽  
Observational Studies ◽  
Branched Chain Amino Acids ◽  
Branched Chain

Insulin resistance and the metabolism of branched-chain amino acids

2013 ◽  
Vol 7 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Jingyi Lu ◽  
Guoxiang Xie ◽  
Weiping Jia ◽  
Wei Jia
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Branched Chain Amino Acids ◽  
Branched Chain

Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes

2004 ◽  
Vol 82 (7) ◽  
pp. 506-514 ◽  
Author(s):  
Enoka P Wijekoon ◽  
Craig Skinner ◽  
Margaret E Brosnan ◽  
John T Brosnan
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Plasma Concentrations ◽  
Branched Chain Amino Acids ◽  
Insulin Resistant ◽  
Branched Chain

We investigated amino acid metabolism in the Zucker diabetic fatty (ZDF Gmi fa/fa) rat during the prediabetic insulin-resistant stage and the frank type 2 diabetic stage. Amino acids were measured in plasma, liver, and skeletal muscle, and the ratios of plasma/liver and plasma/skeletal muscle were calculated. At the insulin-resistant stage, the plasma concentrations of the gluconeogenic amino acids aspartate, serine, glutamine, glycine, and histidine were decreased in the ZDF Gmi fa/fa rats, whereas taurine, α-aminoadipic acid, methionine, phenylalanine, tryptophan, and the 3 branched-chain amino acids were significantly increased. At the diabetic stage, a larger number of gluconeogenic amino acids had decreased plasma concentrations. The 3 branched-chain amino acids had elevated plasma concentrations. In the liver and the skeletal muscles, concentrations of many of the gluconeogenic amino acids were lower at both stages, whereas the levels of 1 or all of the branched-chain amino acids were elevated. These changes in amino acid concentrations are similar to changes seen in type 1 diabetes. It is evident that insulin resistance alone is capable of bringing about many of the changes in amino acid metabolism observed in type 2 diabetes.Key words: plasma amino acids, liver amino acids, muscle amino acids, gluconeogenesis.

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