Ventura P, Panini R, Verlato C, Scarpetta G, Salvioli G
Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy.
Metabolism. 2001 Dec;50(12):1466-71. doi: 10.1053/meta.2001.28079.
Hyperhomocysteinemia (HHcy) is a metabolic disorder frequently occurring in the elderly population. Recently several reports have suggested abnormalities in homocysteine (tHcy) metabolism implicating HHcy as a metabolic link in the multifactorial processes characterizing many geriatric illnesses-with special emphasis on atherosclerotic vascular diseases and cognitive impairment. The present study was undertaken in a large sample of elderly hospitalized subjects to determine (1) the prevalence of HHcy, (2) the association of HHcy with vascular and cognitive disorders, and (3) the factors independently predicting Hhcy. Six hundred elderly subjects (264 men and 336 women; mean age, 79 +/- 9 years) were randomly chosen from those admitted as inpatients over a period of 3 years. In all patients, body mass index (BMI), mid-upper arm muscle area (MUAMA), plasma cholesterol, triglycerides, total proteins, albumin, lymphocyte count, creatinine, homocysteine (fasting and 4 hours after methionine oral load), serum vitamin B(6), vitamin B(12), and folate concentrations were measured. The presence of disease or use of medications known to affect homocysteine plasma levels were also recorded. The mean fasting tHcy level was 16.8 +/- 12 micromol/L in the whole sample, 18.18 +/- 13.25 micromol/L in men, and 15.86 +/- 12.14 micromol/L in women (P =.005 men v women). The mean Hcy level 4 hours after methionine load was 37.95 +/- 20.9 in the whole sample. Prevalence of hyperhomocysteinemia (fasting Hcy > or = 15 micromol/L or 4 hours after methionine load > or = 35 micromol/L) was 61% (365/600) (67% in men and 56% in women, P <.05). HHcy was rarely (8%) an isolated disorder; in addition to diabetes (20%), renal failure (48.2%), and malnutrition (20.2%), it was often associated with heart failure (30%), malignancies (20.5%), and the use of diuretics (56%) and anticonvulsant drugs (13%). Plasma homocysteine progressively increases across subjects from those with no diabetes, malnutrition, renal failure, obesity, inflammatory bowel disease, heart failure to those with 1, 2, or more concurrent diseases. Multiple stepwise regression analysis showed that 72% of plasma total fasting tHcy variability was explained by age, serum folate, plasma albumin, use of diuretics, and renal function (measured as plasma creatinine clearance). In conclusion, the present study documents that hyperhomocysteinemia, in elderly hospitalized patients is (1) a common finding, (2) frequently associated with vascular and cognitive disorders, and (3) probably a secondary phenomenon in most cases. The major predictor of high plasma homocysteine levels were age, serum folate, plasma albumin, plasma creatinine clearance, and use of diuretic drugs. These variables explain a large proportion of plasma Hcy variability.
高同型半胱氨酸血症（HHcy）是一种在老年人群中频繁出现的代谢紊乱疾病。最近有几份报告指出同型半胱氨酸（tHcy）代谢异常，这表明HHcy是许多老年疾病多因素进程中的一个代谢环节，尤其与动脉粥样硬化性血管疾病和认知障碍有关。本研究针对大量老年住院患者样本进行，以确定：（1）HHcy的患病率；（2）HHcy与血管及认知障碍的关联；（3）独立预测HHcy的因素。从3年期间住院的患者中随机选取了600名老年受试者（264名男性和336名女性；平均年龄79±9岁）。对所有患者测量了体重指数（BMI）、上臂中部肌肉面积（MUAMA）、血浆胆固醇、甘油三酯、总蛋白、白蛋白、淋巴细胞计数、肌酐、同型半胱氨酸（空腹及口服蛋氨酸负荷后4小时）、血清维生素B6、维生素B12和叶酸浓度。还记录了已知会影响血浆同型半胱氨酸水平的疾病或药物使用情况。整个样本的平均空腹tHcy水平为16.8±12微摩尔/升，男性为18.18±13.25微摩尔/升，女性为15.86±12.14微摩尔/升（男性与女性相比，P = 0.005）。蛋氨酸负荷后4小时的平均Hcy水平在整个样本中为37.95±20.9。高同型半胱氨酸血症的患病率（空腹Hcy≥15微摩尔/升或蛋氨酸负荷后4小时≥35微摩尔/升）为61%（365/600）（男性为67%，女性为56%，P < 0.05）。HHcy很少（8%）是一种孤立的病症；除了糖尿病（20%）、肾衰竭（48.2%）和营养不良（20.2%）外，它还常与心力衰竭（30%）、恶性肿瘤（20.5%）以及使用利尿剂（56%）和抗惊厥药物（13%）有关。血浆同型半胱氨酸水平在无糖尿病、营养不良、肾衰竭、肥胖、炎症性肠病、心力衰竭的受试者中逐渐升高，到患有1种、2种或更多种并发疾病的受试者中更高。多元逐步回归分析表明，血浆总空腹tHcy变异性的72%可由年龄、血清叶酸、血浆白蛋白、利尿剂使用情况和肾功能（以血浆肌酐清除率衡量）来解释。总之，本研究证明，在老年住院患者中，高同型半胱氨酸血症：（1）是一个常见发现；（2）常与血管及认知障碍相关；（3）在大多数情况下可能是一种继发现象。血浆高同型半胱氨酸水平的主要预测因素是年龄、血清叶酸、血浆白蛋白、血浆肌酐清除率和利尿剂药物的使用。这些变量解释了血浆Hcy变异性的很大一部分。
