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. 2016 Apr;62(4):582-92.
doi: 10.1373/clinchem.2015.251710. Epub 2016 Feb 17.

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

Miguel Ruiz-Canela  1 , Estefania Toledo  1 , Clary B Clish  2 , Adela Hruby  3 , Liming Liang  4 , Jordi Salas-Salvadó  5 , Cristina Razquin  1 , Dolores Corella  6 , Ramón Estruch  7 , Emilio Ros  8 , Montserrat Fitó  9 , Enrique Gómez-Gracia  10 , Fernando Arós  11 , Miquel Fiol  12 , José Lapetra  13 , Lluis Serra-Majem  14 , Miguel A Martínez-González  1 , Frank B Hu  15
Affiliations

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

Miguel Ruiz-Canela et al. Clin Chem. 2016 Apr.

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.

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Figures

Figure 1
Figure 1. Multivariate-adjusted Hazard Ratios (95%CI) of Incident CVD and Quartiles of BCAA Score at Baseline, Stratified by Intervention group (MedDiet versus Control Group)
Panel A) Composite CVD. Panel B) Stroke. An inverse normal transformation was applied to raw values of leucine, isoleucine, and valine and a weighted sum of these 3 values was computed to calculate the BCAA score. The hazard ratios are adjusted for age (years), sex (male/female), intervention group, body mass index (kg/m2), smoking (never, current, former), leisure-time physical activity (metabolic equivalent tasks in minutes/day), and family history of premature coronary heart disease. P for interaction with 2 degrees of freedom between each MedDiet intervention group (EVOO and nuts) (binary, yes/no) and the BCAA score (continuous), with 2 cross-product terms (EVOO*BCAA and NUTS*BCAA). Abbreviations: BCAA, branched-chain amino acid; CI, confidence interval; HR, hazard ratio; MedDiet, Mediterranean diet intervention groups.
Figure 2
Figure 2. Changes in Leucine, Isoleucine, and Valine after 1 Year of Intervention, by Intervention Group
Changes are adjusted for age (years), sex (male, female), and body mass index (kg/m2). Abbreviations: BCAA, branched-chain amino acid; EVOO, extra virgin olive oil; MedDiet, Mediterranean diet intervention group. *Baseline means comparison between intervention groups
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