High Serum Branched-Chain Amino Acids Level Independently Predicts Incident Heart Failure—The Hong Kong Diabetes Register
Authors: LIM LEE-LING , LAU ERIC S.H. , LUK ANDREA , CHOW ELAINE , LEE HEUNG MAN , MA RONALD C. , CHAN JULIANA C. , KONG ALICE P. 
Published: June 2018

Background: Obesity predicts cardiovascular(CV)-renal disease. Contrary to claims that branched-chain amino acids (BCAA)-rich diet/supplements may improve weight and insulin resistance, recent data suggest impaired oxidation of BCAA (leucine, isoleucine and valine) may contribute to CV-renal disease. We examined the associations of serum BCAA, obesity and CV-renal events in a prospective Chinese T2D cohort (1994-2007).
Method: We measured serum total BCAA in 579 and 566 patients (top and lowest BMI quintiles respectively) using the colorimetric ELISA kit. Patients were monitored for clinical outcomes with data censored on May 2015. We analysed the effect of serum BCAA on incident CV-renal events using multivariate Cox regression.
Results: At baseline, obese group had shorter T2D duration, worse clinical profile and higher serum BCAA than lean group. After 11 years of follow-up, obese group had higher incidence of heart failure (HF), chronic kidney and any CV disease than the lean group. In all patients, every unit increase in Ln (BCAA) elevated the risk of incident HF by 64% (hazard ratio [HR] 1.64, 95% CI 1.01-2.66).
Conclusions: Serum BCAA independently predicted incident HF in T2D population even after adjustment for obesity. The associations of this biomarker with dietary patterns and clinical outcomes will provide new insights regarding the health impacts of nutrition.
Model 1Model 2EventHR (95% CI)P-valueEventHR (95% CI)P-valueAny CV disease181 (21.5%)1.37 (1.01-1.85)0.044167 (21.0%)1.26 (0.88-1.79)0.206Heart failure91 (9.4%)1.59 (1.06-2.39)0.02585 (9.3%)1.64 (1.01-2.66)0.045Coronary heart disease103 (11.4%)1.19 (0.78-1.81)0.42897 (11.4%)1.05 (0.65-1.71)0.836Stroke100 (10.2%)1.42 (0.96-2.10)0.08390 (9.8%)1.35 (0.86-2.10)0.191Chronic kidney disease401 (52.0%)1.15 (0.89-1.49)0.271379 (51.6%)0.89 (0.65-1.22)0.463Model 1: adjusted for age, sex, T2D duration Model 2: Model 1 + A1c, systolic BP, LDL-cholesterol, log(triglyceride), BMI top and lowest quintiles (0,1), log(ACR), baseline eGFR, use of insulin, RAS inhibitors, oral blood glucose/lipid lowering agents, smoking status

Disclosure
L. Lim: Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Sanofi-Aventis. E.S.H. Lau: None. A. Luk: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Sanofi. E. Chow: Research Support; Self; Sanofi. H. Lee: None. R.C. Ma: Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp., Pfizer Inc.. Advisory Panel; Self; Boehringer Ingelheim GmbH, Nippon Boehringer Ingelheim Co. Ltd. J.C. Chan: Consultant; Self; Bayer AG. Other Relationship; Self; Bayer AG. Consultant; Self; Sanofi. Other Relationship; Self; Sanofi, Eli Lilly and Company, Amgen Inc.. Consultant; Self; AstraZeneca, Merck & Co., Inc., Pfizer Inc.. Other Relationship; Self; Pfizer Inc.. Board Member; Self; Asia Diabetes Foundation. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; Merck Sharp & Dohme Corp.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Eli Lilly and Company. A.P. Kong: Research Support; Self; AstraZeneca.