中青年脑梗死与高同型半胱氨酸血症的关系

背景高同型半胱氨酸血症是冠心病的一个新的独立危险因素,但与脑血管疾病的关系尚有争议,空腹血浆总同型半胱氨酸水平难以完全揭示高同型半胱氨酸血症对脑梗死的影响.目的探索高同型半胱氨酸血症及叶酸、维生素B12等营养因素和中青年脑梗死的关系,以及蛋氨酸负荷试验对于发现隐匿性高同型半胱氨酸血症的作用.设计病例-对照实验.Spearman相关分析.对象选择2000/2003解放军海军总医院神经内科发病2 d内收住入院的脑梗死患者85例.男63例,女22例;年龄29～55岁,平均(48.74±5.05)岁.腔隙性脑梗死48例,动脉血栓性脑梗死37例.同期选择本科医务工作者及本院体检健康志愿者44名作为正常对照组,男30名,女14名,年龄29～55岁,平均(47.75±6.71)岁.方法住院第1天空腹抽取静脉血6 mL,取2 mL测定空腹血浆总同型半胱氨酸水平利用高效液相色谱法,空腹采血后即刻口服蛋氨酸0.1 g/kg,4 h后再次取血检测血浆总同型半胱氨酸水平;取其余4 mL空腹抽取的静脉血检测血清叶酸、维生素B12采用化学发光法.主要观察指标①脑梗死组与对照组空腹及负荷后血浆总同型半胱氨酸水平.②脑梗死组与对照组高同型半胱氨酸血症发生率以高于正常对照组空腹或/和负荷后4 h血浆总同型半胱氨酸水平95%参考范围的上限作为诊断高同型半胱氨酸血症的标准,即空腹,男性＞17.26 μmol/L,女性＞14.17 μmol/L;负荷后,男性＞44.57 μmol/L,女性＞40.02 μmol/L].③脑梗死组与对照组血清叶酸、维生素B12水平.④血浆总同型半胱氨酸水平与相关危险因素的单因素分析.结果85例脑梗死患者,44例正常对照组均进入结果分析.①脑梗死组与对照组空腹及负荷后血浆总同型半胱氨酸水平脑梗死组空腹及负荷后显著高于对照组(22.49±9.80),(13.08±2.33)μmol/L;(48.07±11.20),(37.23±3.48)μmol/L,(t=8.409,8.187,P＜0.01)].②脑梗死组与对照组高同型半胱氨酸血症发生率脑梗死组显著高于对照组68%(58/85),(9%,4/44),X2=40.628,P＜0.01],其中空腹血浆总同型半胱氨酸水平高于正常35例(41%,35/85),负荷后血浆总同型半胱氨酸水平高于正常23例(27%,23/85).③脑梗死组与对照组血清叶酸、维生素B12水平脑梗死组显著低于对照组(5.73±2.52),(7.14±2.20)μg/L;(473.47±190.19),(576.70±212.05)ng/L,(t=3.151,2.809,P＜0.01)].④血浆总同型半胱氨酸水平与相关危险因素的单因素分析空腹及负荷后血浆总同型半胱氨酸水平与性别、叶酸及维生素B12均具有显著性相关(r=-0.306～0.488,P＜0.01),而与其他危险因素及神经功能缺损评分无相关性(r=0.021～0.173,P＞0.05),仅空腹血浆总同型半胱氨酸水平与空腹血糖水平呈显著正相关(r=0.186,P＜0.05).结论高同型半胱氨酸血症是中青年脑梗死的一个独立的危险因素,而蛋氨酸负荷试验是发现隐匿性高同型半胱氨酸血症必要手段,叶酸与维生素B12缺乏是引起高同型半胱氨酸血症间接导致脑梗死的重要营养因素.

Relationship between hyperhomocysteinemia and cerebral stroke in young and middle-aged people

BACKGROUND: Hyperhomocysteinemia is a new independent risk factor for coronary heart disease (CHD), but its association with cerebrovascular diseases is still controversial. The level of fasting plasma total homocysteine (plasma tHcy) alone is not enough to reveal the effect of hyperhomocysteinemia on cerebral infarction (CI).OBJECTIVE: To explore the association of hyperhomocysteinemia with folacin and vitamin B12 and with CI in young and middle-aged people, as well as the role of methionine loading test in the diagnosis of latent hyperhomocysteinemia.DESIGN: A case-control study, Spearman correlation analysis.PARTICIPANTS: A total of 85 patients were hospitalized within 2 days after the onset of CI at the Department of Neurology, the General Navy Hospital of Chinese PLA, from 2000 to 2003. There were 63 males and 22females aged 29-55 years old with the mean age of (48.74±5.05) years.There were 48 cases of lacunar CI and 37 cases of arterial thrombotic CI.Meanwhile, 44 normal controls, 30 males and 14 females aged 29-55 years old with the mean age of (47.75±6.71), were recruited from the department staff and those who came to the hospital for routine health examination.METHODS: Fasting vein blood of 6 mL was collected from the patients on the 1st day of hospitalization, and 2 mL of the blood was used for detecting the level of fasting plasma tHcy using high efficiency liquid chromatography. Methionine of 0.1 g/kg was taken orally by patients immediately after blood sampling; 4 hours later, the level of loading plasma tHcy was also determined. The remaining 4 mL was used for detecting the level of serum folacin and vitamine B12 with bioradiation assay.MAIN OUTCOME MEASURES: ① The level of fasting and loading plasma tHcy in CI group and control group. ② Incidence of hyperhomocysteinemia in CI group and control group Hyperhomocysteinemia was confirmed if hyperhomocysteine was higher than 95% of the upper limit of fasting plasma tHcy or 4-hour loading plasma tHey of normal control group, that is, fasting plasma tHcy ＞17.26 μnol/L in males and ＞14.17 μnol/L in females; and loading plasma tHcy should be ＞ 44.57 μmol/L in males and ＞ 40.02 μmol/L in females. ③ The level of serum folacin and vitamine B12 in CI group and control group. ④ Single factor analysis of fasting plasma tHcy and related risk factors.RESULTS: Totally 85 CI patients and 44 normal controls were recruited in this study and all data were statistically analyzed. ① The level of fasting and loading plasma tHcy in CI group and control group: Both fasting and loading plasma tHcy was significantly higher in CI group than in control group (22.49±9.80), (13.08±2.33) μmol/L; (48.07±11.20), (37.23±3.48)μmol/L, (t=8.409, 8.187, P ＜ 0.01)]. ② Incidence of hyperhomocysteinemia: The incidence was obviously higher in CI group than in control group 68% (58/85), (9%, 4/44), X2=40.628, P ＜ 0.01]. Totally 35 patients (41%, 35/85) had higher fasting plasma tHcy than that of normal controls, and 23 (27%, 23/85) had higher loading plasma tHcy than that of normal controls. ③ The level of serum folacin and vitamine B12 in CI group and control group: They were (5.73±2.52), (7.14±2.20) μg/L] in CI group,significantly lower than control group (473.47±190.19), (576.70±212.05) rng/L,(t =3.151, 2.809, P ＜ 0.01)]. ④ Single factor analysis of plasma tHcy with related risk factors: Fasting and loading plasma tHcy was found obviously associated with sex, and folacin and vitamine B12 level (r = -0.306 to 0.488, P ＜ 0.01), but not with other risk factors and neurological deficit scores (r = 0.021-0.173, P ＞ 0.05). Moreover, only plasma tHcy level was proved to have significant positive correlation with fasting blood glucose (r=0.186, P ＜ 0.05).CONCLUSION: Hyperhomooysteinemia is an independent risk factor for CI in young and middle-aged people. Methionine loading test is an essential means for detecting latent hyperhomocysteinemia. Insufficiency of folacin and vitamine B12, two important nutrition factors, may lead to hyperhomocysteinemia and indirectly result in CI.