FOLIC ACID FOR VASCULAR OUTCOME REDUCTION IN TRANSPLANTATION (FAVORIT)

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。慢性肾脏疾病患者是随后发生动脉硬化性心血管疾病（CVD）事件的高危人群。慢性肾脏疾病中心血管疾病的高风险部分是由于动脉硬化危险因素的较高患病率，包括年龄较大、高血压、糖尿病、血脂异常和缺乏运动。然而，独特的肾功能不全/尿毒症相关的危险因素也可能导致这种额外的心血管疾病风险。在慢性肾脏疾病人群中，这些独特的危险因素中突出的是假定的动脉粥样硬化血栓硫氨基酸同型半胱氨酸水平升高。纯合子遗传疾病（即“同型半胱氨酸尿症”）导致明显的高同型半胱氨酸血症（总同型半胱氨酸水平为100至500 μ mol/L）与早发性动脉粥样硬化血栓事件明显相关，降低总同型半胱氨酸（tHcy）的治疗似乎可以减少这些患者发生此类结果的发生率。此外，来自前瞻性观察性研究的汇总数据表明，在普通人群中，轻度至中度高同型半胱氨酸血症（tHcy水平为12至99 umol/L）也可能是动脉硬化性心血管疾病的一个重要危险因素。然而，目前尚无证实这些关联的随机对照临床试验数据。此外，在普通人群中，谷物面粉中添加叶酸对血浆tHcy水平的影响可能会混淆在美国进行的任何此类试验的结果。慢性肾脏疾病患者，包括肾移植受者，具有轻度至中度高同型半胱氨酸血症的超高患病率，在最近的前瞻性观察性研究中，这与他们CVD的发展结果独立相关。这些研究人员假设，降低慢性肾脏疾病患者的tHcy水平将降低其动脉硬化性心血管疾病的发生率。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Patients with chronic renal disease occupy the highest risk stratum for subsequent arteriosclerotic cardiovascular disease (CVD) events. The excess risk of CVD in chronic renal disease is due in part to a higher prevalence of established arteriosclerotic risk factors, including older age, hypertension, diabetes, dyslipidemia, and physicial inactivity. However, unique renal insufficiency/"uremia"-related risk factors likely also contribute to this excess CVD risk. Prominent among these unique risk factors in the chronic renal disease population are elevated levels of the putatively atherothrombotic sulfur amino acid homocysteine. Homozygous genetic disorders (i.e., the "homocystinurias") resulting in marked hyperhomocysteinemia (total homocysteine levels of 100 to 500 umol/L) are clearly associated with precocious atherothrombotic events, and total homocysteine (tHcy)-lowering treatment appears to reduce the incidence of such outcomes among these patients. In addition, pooled data from prospective observational studies suggest that mild to moderate hyperhomocysteinemia (tHcy levels of 12 to 99 umol/L) may also be a significant risk factor for arteriosclerotic CVD among general populations of men and women. However, randomized, controlled clinical trial data confirming these reported associations are unavailable. Moreover, the impact of cereal grain flour fortification with folic acid on plasma tHcy levels within the general population may obfuscate the results from any such trials conducted in the United States. Chronic renal disease patients, including renal transplant recipients, have an excess prevalence of mild to moderate hyperhomocysteinemia, which has been independently linked to their development of CVD outcomes in recent prospective observational studies. These investigators hypothesize that lowering tHcy levels in patients with chronic renal disease will reduce their excess incidence of arteriosclerotic CVD outcomes.