Heinz Judith, Kropf Siegfried, Luley Claus, Dierkes Jutta
Institute of Clinical Chemistry and Pathobiochemistry, University Hospital Magdeburg, Magdeburg, Germany.
Am J Kidney Dis. 2009 Sep;54(3):478-89. doi: 10.1053/j.ajkd.2009.01.266. Epub 2009 Apr 8.
In the general population, increased homocysteine concentrations are a risk factor for cardiovascular disease and mortality. However, it is not known whether this also applies to patients with end-stage renal disease.
Meta-analysis of retrospective (11 studies including 1,506 individuals), prospective observational studies (12 studies including 1,975 individuals), and intervention trials (5 studies including 1,642 dialysis patients). Analyses were carried out separately, according to the study design.
SETTING & POPULATION: Studies of patients with end-stage renal disease treated by means of hemodialysis or peritoneal dialysis.
Studies investigating the association between total homocysteine level and cardiovascular disease or total mortality or the influence of vitamin supplementation on cardiovascular or mortality risk.
In intervention studies, vitamin preparations with folic acid alone or in combination with other vitamins, such as vitamin B(12) and B(6), were used.
In retrospective studies, cases are patients with cardiovascular diseases. Outcomes for prospective observational and intervention studies are cardiovascular events and total mortality.
In retrospective studies, there was no significant overall difference in homocysteine concentrations between cases and controls (weighted mean difference in homocysteine, 2.82 micromol/L; 95% confidence interval [CI], -2.22 to 7.86; P = 0.3). The pooled overall risk estimate for prospective observational studies suggests no association between homocysteine level (5-micromol/L increase) and total mortality (hazard ratio [HR], 1.02; 95% CI, 0.93 to 1.12; P = 0.7), but there was an association with cardiovascular events (HR, 1.09; 95% CI, 1.03 to 1.14; P = 0.001). In subgroup analysis of patients not receiving vitamins, an increase in homocysteine level was associated with increased mortality (HR, 1.07; 95% CI, 1.02 to 1.13; P = 0.01). For intervention trials with B vitamins, there was a significant risk reduction for cardiovascular disease (relative risk, 0.73; 95% CI, 0.56 to 0.94; P = 0.02), but no risk reduction for total mortality or the composite end point including total mortality (relative risk, 1.01; 95% CI, 0.88 to 1.15; P = 0.9).
Many studies are small, which may lead to the observed heterogeneity. Some intervention trials are neither placebo controlled nor randomized. Separate analyses for specific end points and patients treated by means of hemodialysis or peritoneal dialysis were not possible.
Total homocysteine level may be a risk factor for cardiovascular events and total mortality in patients with end-stage renal disease not receiving vitamin supplementation or folic acid food fortification. There may be a potential for reducing cardiovascular disease in this population by folic acid supplementation.
在普通人群中，同型半胱氨酸浓度升高是心血管疾病和死亡的危险因素。然而，这是否也适用于终末期肾病患者尚不清楚。
对回顾性研究（11项研究，共1506例个体）、前瞻性观察性研究（12项研究，共1975例个体）和干预试验（5项研究，共1642例透析患者）进行荟萃分析。根据研究设计分别进行分析。
对接受血液透析或腹膜透析治疗的终末期肾病患者的研究。
研究总同型半胱氨酸水平与心血管疾病或总死亡率之间的关联，或维生素补充对心血管或死亡风险的影响。
在干预研究中，使用单独含叶酸或与其他维生素（如维生素B12和B6）联合的维生素制剂。
在回顾性研究中，病例组和对照组的同型半胱氨酸浓度总体上无显著差异（同型半胱氨酸加权平均差异为2.82 μmol/L；95%置信区间[CI]为-2.22至7.86；P = 0.3）。前瞻性观察性研究的汇总总体风险估计表明，同型半胱氨酸水平升高（升高5 μmol/L）与总死亡率无关联（风险比[HR]为1.02；95% CI为0.93至1.12；P = 0.7），但与心血管事件有关联（HR为1.09；95% CI为1.03至1.14；P = 0.001）。在未接受维生素治疗的患者亚组分析中，同型半胱氨酸水平升高与死亡率增加有关（HR为1.07；95% CI为1.02至1.13；P = 0.01）。对于使用B族维生素的干预试验，心血管疾病风险显著降低（相对风险为0.73；95% CI为0.56至0.94；P = 0.02），但总死亡率或包括总死亡率在内的复合终点风险未降低（相对风险为1.01；95% CI为0.88至1.15；P = 0.9）。
许多研究规模较小，这可能导致观察到的异质性。一些干预试验既未设安慰剂对照也未随机分组。无法对特定终点以及接受血液透析或腹膜透析治疗的患者进行单独分析。
对于未接受维生素补充剂或叶酸强化食品的终末期肾病患者，总同型半胱氨酸水平可能是心血管事件和总死亡率的危险因素。补充叶酸可能有降低该人群心血管疾病的潜力。
