Department of Nutrition (R.H., D.K.T.), Harvard T.H
bDivision of Preventive Medicine, Department of Medicine (R.H., S.M., N.R.C., P.M.R., J.E.B., I.L., J.E.M., D.K.T.), Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
cRikuta Hamaya https://orcid.org/0000-0003-1635-1983 Division of Preventive Medicine, Department of Medicine (R.H., S.M., N.R.C., P.M.R., J.E.B., I.L., J.E.M., D.K.T.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Department of Nutrition (R.H., D.K.T.), Harvard T.H
dCenter for Lipid Metabolomics, Division of Cardiovascular Medicine (S.M.), Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
eSamia Mora https://orcid.org/0000-0001-6283-0980 Division of Preventive Medicine, Department of Medicine (R.H., S.M., N.R.C., P.M.R., J.E.B., I.L., J.E.M., D.K.T.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Center for Lipid Metabolomics, Division of Cardiovascular Medicine (S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA
fChan School of Public Health, Boston, MA. Peter Munk Cardiac Centre, University Health Network, and Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, University of Toronto, ON, Canada (P.R.L.)
gPatrick R. Lawler https://orcid.org/0000-0001-5155-5071 Chan School of Public Health, Boston, MA. Peter Munk Cardiac Centre, University Health Network, and Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, University of Toronto, ON, Canada (P.R.L.)
hDepartment of Epidemiology (N.R.C., J.E.B., I.L., J.E.M.), Harvard T.H
iNancy R. Cook https://orcid.org/0000-0002-9705-0842 Division of Preventive Medicine, Department of Medicine (R.H., S.M., N.R.C., P.M.R., J.E.B., I.L., J.E.M., D.K.T.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Department of Epidemiology (N.R.C., J.E.B., I.L., J.E.M.), Harvard T.H
jPaul M. Ridker https://orcid.org/0000-0003-1249-4522 Division of Preventive Medicine, Department of Medicine (R.H., S.M., N.R.C., P.M.R., J.E.B., I.L., J.E.M., D.K.T.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA
kMary Horrigan Connors Center for Women’s Health and Gender Biology (J.E.M.), Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
lJulie E. Buring https://orcid.org/0000-0003-2648-8692 Division of Preventive Medicine, Department of Medicine (R.H., S.M., N.R.C., P.M.R., J.E.B., I.L., J.E.M., D.K.T.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Mary Horrigan Connors Center for Women's Health and Gender Biology (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Department of Epidemiology (N.R.C., J.E.B., I.L., J.E.M.), Harvard T.H
mI-Min Lee https://orcid.org/0000-0002-1083-6907 Department of Epidemiology (N.R.C., J.E.B., I.L., J.E.M.), Harvard T.H
nJoAnn E. Manson Department of Epidemiology (N.R.C., J.E.B., I.L., J.E.M.), Harvard T.H
Papers open inside SciRah from the original publisher or repository; SciRah never hosts them.
Abstract
Background: 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 and cardiovascular disease. 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 type 2 diabetes, cardiovascular disease, or cancer. We quantified the concentrations of individual biomarkers of inflammation and lipids, across quartiles of BCAAs, adjusting for age, smoking, body mass index, physical activity, and other established cardiovascular disease risk factors at blood draw. Results: Women in the highest versus lowest quartiles of plasma BCAAs had higher inflammatory markers including high-sensitivity C-reactive protein (multivariable-adjusted means: 1.96 versus 1.43 mg/L), fibrinogen (367 versus 362 mg/dL), soluble intercellular cell adhesion molecule-1 (361 versus 353 ng/mL), and glycoprotein acetylation (407 versus 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 (high-density lipoprotein cholesterol; 49.0 versus 55.0 mg/dL), and higher triglycerides (143 versus 114 mg/dL), LDL-C (low-density lipoprotein cholesterol; 133 versus 124 mg/dL), and lipoprotein insulin resistance score (52.6 versus 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 cardiovascular disease risk factors, and thus, may reflect poorer cardiometabolic health through multiple pathways. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00000479.
TL;DRHigher 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. (Semantic Scholar)
