Blood test for branched-chain amino acids may predict long-term cardiometabolic risk

Because impaired branched-chain amino acid (BCAA) metabolism appears to be a shared pathway of metabolic dysfunction that links type 2 diabetes and cardiovascular disease (CVD) in women, a blood test measuring BCAA may identify long-term cardiometabolic risk.

This finding comes from a prospective targeted analysis of participants in the Women’s Health Study (WHS). Researchers from Brigham & Women’s Hospital, Boston, MA, claim it is the largest prospective analysis of BCAA metabolites and incident CVD to date, and published their results in Circulation: Genomic and Precision Medicine.

BCAAs are thought to play a causal role in the development of insulin resistance and type 2 diabetes. In addition, cross-sectional studies have previously shown an association between BCAAs (isoleucine, leucine, and valine) and several cardiometabolic risk factors, including excess weight and adiposity, impaired fasting glucose, insulin resistance, hypertension, dyslipidemia, and coronary artery disease.

"We examined more than 27,000 women in the Women's Health Study and found that a one-time measurement of branched chain amino acids in the blood stream—a test that now can be easily done—predicted future risk of cardiovascular events to the same extent and independent of LDL cholesterol and other risk factors,” said co-author Samia Mora, MD, of the Center for Lipid Metabolomics at Brigham and Women’s. “This was particularly so for women who developed type 2 diabetes prior to their cardiovascular disease.”

To assess whether high baseline levels of BCAAs would be associated with an elevated risk of incident CVD events, Dr. Mora and colleagues measured plasma BCAA metabolites using nuclear magnetic resonance spectroscopy in 27,041 healthy WHS participants.

Over the follow-up, 2,207 women experienced a CVD event. In age- and treatment-adjusted models, total BCAAs were associated with a 23% greater risk (P < 0.0001) over the follow-up period. The risk was attenuated to a 16% greater risk (P < 0.0001) when the model was adjusted for traditional CVD risk factors, and was attenuated slightly more when further adjusted for body mass index, to a 13% greater risk (P < 0.0001).

The effect of BCAAs on CVD risk was modified significantly according to type 2 diabetes status (P interaction: 0.036). The relationship between total BCAAs with CVD risk was significantly greater when type 2 diabetes preceded the CVD event. In the multivariable model, the association between BCAAs and CVD was weaker among women without type 2 diabetes, but still significant (HR: 1.08; 95% CI: 1.03-1.14).

Baseline CVD risk factors, including body mass index, postmenopausal status, postmenopausal hormone use, or metabolic syndrome, did not significantly modify the association between total BCAAs and CVD risk.

The predictive value of baseline BCAA levels held for short-term ( < 10 years) CVD risk (HR: 1.18; 95% CI: 1.10-1.26) and long-term ( ≥ 10 years) CVD risk (HR: 1.11; 95% CI: 1.04-1.18).

For now, their discovery may help elucidate the connection between cardiovascular disease and diabetes, and help identify women at risk for both diseases. But more research is needed on BCAA.

"There is little known at this time as to what leads to elevated levels of BCAAs or what can be done clinically to reduce them, and if this leads to a reduction in risk, but further research will target these important questions," concluded Dr. Tobias.

The Women’s Health Study is supported by National Institutes of Health (NIH).