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.

中文翻译：

---

血浆支链氨基酸与女性炎症和脂质代谢生物标志物的关联

背景：支链氨基酸（BCAAs；异亮氨酸、亮氨酸和缬氨酸）与胰岛素抵抗和血糖控制不佳相关，这可能部分解释了 2 型糖尿病与心血管疾病之间的关联。然而，BCAAs 与其他心脏代谢途径（包括炎症和血脂异常）的关系尚不清楚。我们假设血浆 BCAA 与心脏代谢功能障碍的多种途径相关。方法：我们对女性健康研究中没有 2 型病史的 19 472 名参与者（平均年龄 = 54.9 岁，SD = 7.2 岁）进行了横断面分析糖尿病、心血管疾病或癌症。我们量化了各个 BCAA 四分位数的炎症和脂质生物标志物的浓度，并根据年龄、吸烟、体重指数、身体活动、纤维蛋白原的P趋势 = 0.0002；对于其他人， P <0.0001）。同样对于脂质，具有较高 BCAA 的女性具有较低的 HDL-C（高密度脂蛋白胆固醇；49.0 对 55.0 mg/dL）和较高的甘油三酯（143 对 114 mg/dL）、LDL-C（低密度脂蛋白胆固醇； 133 vs 124 mg/dL）和脂蛋白胰岛素抵抗评分（52.6 vs 37.3；所有：P<0.0001)。分别在异亮氨酸、亮氨酸和缬氨酸中观察到与这些生物标志物的类似关联。结论：较高的循环 BCAA 浓度与炎症和血脂异常的生物标志物的不良特征相关，与已确定的心血管疾病风险因素无关，因此可能反映较差的心脏代谢健康通过多种途径。注册：网址：https://www.clinicaltrials.gov；唯一标识符：NCT00000479。