LOSARTAN INTERVENTION FOR ENDPOINT REDUCTION (LIFE)

LIFE试验的假设是（积极招募阶段已完成，仅患者随访仍在继续），与阿替洛尔相比，氯沙坦将使原发性高血压和左心室肥厚（LVH）患者的心血管（CV）发病率和死亡率降低15%。主要终点是心血管疾病发病率和死亡率的综合发生率。主要目的是评估氯沙坦与阿替洛尔对LVH高血压患者心血管发病率和死亡率的长期影响（+/>4年）（CV死亡率定义为致死性心肌梗死[MI]、致死性卒中、猝死、进行性心力衰竭死亡和其他CV死亡；CV发病率定义为非致死性MI[不包括无症状MI]和非致死性卒中）。LIFE研究包括以下亚研究：生活质量（亚研究ID号133-03）——该亚研究的目的是评估氯沙坦与阿替洛尔治疗1、2、6和12个月时高血压和LVH患者生活质量的差异。本子研究考察了治疗相关的影响，通过患者对健康相关领域（心理健康）活力评分（心理健康的子领域）和与疲劳/疲劳相关的症状清单项目的反应来定义。这些回答记录在自我管理的生活质量（QoL）问卷上，该问卷是专门为高血压临床研究设计的。该问卷是一组使用现有的、经过验证的生活质量工具的量表。非裔美国人生命试验回声亚研究（子研究ID号133-05）——生命试验在每个国家12%的研究人群中进行超声心动图亚研究。大约360名非裔美国人将在美国接受随访（美国患者总数的目标是3000人）。心电图是否存在LVH （Cornell标准）是主要LIFE试验的主要纳入标准，心电图LVH回归的比较被列为研究目的。然而，一些研究已经证明，黑人心电图对LVH的评估明显低于其他种族人群。超声心动图对LVH的诊断在黑人和白人人群中相似。LIFE试验使用了一种被认为更准确的康奈尔标准（QRS电压持续时间产品）来评估LVH；然而，这种方法还没有在大量黑人高血压患者中得到充分的评估。这显然会在将LIFE试验结果外推到主要高血压人群时产生问题。在黑人和白人人群中，心电图识别LVH的准确性存在差异的原因尚不清楚，由于准确评估LVH风险对试验至关重要，因此对于LIFE试验来说，利用最佳方法确定所有人群中LVH的存在是至关重要的。因此，LIFE纳入了一项超声心动图亚研究，通过LIFE试验心电图标准和其他方法确定LVH与超声心动图诊断的LVH的相关性。如果美国研究人口中10-15%（~360）的非裔美国人达到预期的组成，并且这一人口统计概况被延续到“LIFE试验超声心动图亚研究”样本中，那么只有35-50名黑人受试者将被研究。在完整的研究中，黑人的数量不足以验证黑人的心电图结果。因此，“非裔美国人生命试验的回声亚研究”在生命试验和超声心动图亚研究中过量抽样黑人；该队列将使用LIFE试验心电图标准和超声心动图进行随访，以确认LIFE试验结果在黑人高血压中的有效性。具体而言，将评估LIFE试验心电图标准在超声心动图确认的黑人受试者LVH检测中的特异性。

The hypothesis of the LIFE trial is (active enrollment phase is completed--only patient followup is continuing) that, compared to atenolol, losartan will reduce the incidence of cardiovascular (CV) morbidity and mortality in patients with essential hypertension and left ventricular hypertrophy (LVH) by 15%. The primary endpoint is the combined incidence of CV morbidity and mortality. The primary objective is to evaluate the long-term effects (+/>4 years) of losartan compared to atenolol in hypertensive patients with documented LVH on the combination of CV morbidity and mortality (CV mortality defined as death due to fatal myocardial infarction [MI], fatal stroke, sudden death, death resulting from progressive heart failure and other CV deaths; CV morbidity defined as nonfatal MI [excluding silent MI]and nonfatal stroke). The LIFE Study includes the following substudies: QUALITY OF LIFE (Substudy ID No. 133-03)--The purpose of this substudy is to assess differences in quality of life among patients with hypertension and LVH who are treated with losartan versus atenolol at 1, 2, 6 and 12 months of therapy. This substudy examines the treatment-related influences, as defined by patient responses on the health-related domain (psychological well-being) score for vitality ( a subdomain under psychological well-being) and the symptom inventory item relating to tiredness/fatigue. These responses are recorded on a self-administered quality of like (QoL) questionnaire which has been specifically designed for hypertensive clinical studies. This questionnaire is a battery of scales utilizing groups of existing, validated QoL instruments. AFRICAN AMERICAN ECHO-SUBSTUDY FOR LIFE TRIAL (Substudy ID No. 133-05)--The LIFE trial is to conduct an echocardiographic substudy in 12% of the study population in each country. Approximately 360 African Americans will be followed in the U.S. (goal for total U.S. patients is 3,000). The presence of LVH by ECG (Cornell criteria) is a major inclusion criteria for the main LIFE trial, and the comparison of LVH regression by ECG is listed as a study objective. However, several studies have documented that the assessment of LVH by ECG in Blacks is significantly less accurate than in other ethnic populations. The diagnosis of LVH by echocardiogram was similar in Black and White populations. The LIFE trial uses a supposedly more accurate modification of the Cornell criteria (QRS voltage duration product) for LVH assessment; however, this method has not been adequately evaluated in significant numbers of Black hypertensives. This will clearly create problems in extrapolating the results of the LIFE trial to a major population of hypertensives. The reasons for the difference in accuracy of the ECG in identifying LVH in Black vs White populations are unknown and, since the accurate assessment of LVH risk is essential for the Trial, it is essential for the LIFE trial that it is utilizing the best method for determining the presence of LVH in all populations. Thus, LIFE included an echocardiographic substudy to determine the correlation of LVH by the LIFE Trial ECG criteria and other methods with echocardiographically diagnosed LVH. If the desired composition of the U.S. study population of 10-15% (~360) African Americans is achieved and this demographic profile is carried over into the "LIFE Trial Echocardiographic Substudy" sample, only 35-50 Black subjects will be studied. This is an insufficient number of Blacks to validate the ECG findings in Blacks in the full study. Thus, the "AFRICAN AMERICAN Echo-Substudy for the LIFE Trial" oversampled Blacks in the LIFE Trial and Echocardiographic Substudy; this cohort will be followed using both the LIFE Trial ECG criteria and echocardiography to confirm the validity of the LIFE Trial results in Black hypertensives. Specifically, the specificity of the LIFE Trial ECG criteria in the detection of echocardiographically confirmed LVH in the Trial's Black participants will be assessed.