An association between atherosclerosis in the carotid ultrasonography and a novel risk factor of cardio-vascular diseases

在日本普通人群中研究了血浆同型半胱氨酸（Hcy）、肝细胞生长因子（HGF）或不对称二甲基精氨酸（ADMA）浓度与高血压和颈动脉粥样硬化之间的关系。1999年，我们在日本田岛丸的一个农业社区对1,920名40岁或40岁以上的受试者进行了健康检查。我们测量了传统的危险因素，如体重指数（BMI）、血压（BP）、吸烟状况、总胆固醇、HDL-胆固醇和糖化血红蛋白A_<1c>。受试者接受B型颈动脉超声检查，以确定颈动脉内膜中层厚度（IMT）。在这些受试者中，分别在1，111例（452名男性和659名女性），1，474例（597名男性和877名女性）和712例（305名男性和407名女性）病例中测量了Hcy，HGF和ADMA水平。校正年龄、性别和肌酐水平后的多元线性回归分析显示，BMI（p&lt;0.01）、收缩压和舒张压（p&lt;0.001）、HDL-胆固醇（p&lt;0.001）、糖化血红蛋白A_<1c>（p&lt;0.001）和Hcy水平（p&lt;0.05）与IMT显著相关。HGF水平与高血压的严重程度有关，但与IMT无关。相反，ADMA水平升高是颈动脉IMT的一个强有力的独立决定因素。除了传统的危险因素如高血压和糖代谢受损外，Hcy是颈动脉粥样硬化的一个新的危险因素。并且，我们在一项为期6年的颈动脉超声前瞻性研究中提出，血浆ADMA是颈动脉IMT进展的最强预测因子。

The relationships between plasma concentrations of homocysteine (Hcy), hepatocyte growth factor (HGF) or asymmetric dimethylarginine (ADMA) and hypertension as well as carotid atherosclerosis were examined in a Japanese general population. In 1999, we conducted a health examination in 1,920 subjects, aged 40 years or older in a farming community, Tanushimaru, Japan. We measured conventional risk factors such as body mass index(BMI), blood pressure (BP), smoking status, total cholesterol, HDL-cholesterol, and glycosylated hemoglobin A_<1c>. Subjects underwent B-mode carotid ultrasonography to determine the carotid intimal-medial thickness (IMT). Of these subjects, Hcy, HGF, and ADMA levels were measured in 1,111 (452 men and 659 women), 1,474 (597 men and 877 women) and 712 (305 men and 407 women) cases, respectively. With multiple linear regression analysis after adjustments for age, sex, and creatinine levels, BMI (p<0.01), systolic and diastolic blood pressure (p<0.001), HDL-cholesterol(p<0.001, inversely), glycosylated hemoglobin A_<1c> (p<0.001), and Hcy levels (p<0.05) were significantly related to IMT. Although HGF was related to the severity of hypertension, the levels were not related to IMT. On the contrary, elevated levels of ADMA were a strong and independent determinant of IMT of the carotid artery. In addition to conventional risk factors such as hypertension and impaired glucose metabolism, Hcy is a novel risk factor for carotid atherosclerosis. And, we suggested that plasma ADMA was the strongest predictor for the progression of carotid IMT in a prospective study for 6 years with carotid ultrasonography.