Hatlen Gudrun, Romundstad Solfrid, Salvesen Øyvind, Dalen Havard, Hallan Stein I
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Nephron. 2016;133(1):44-52. doi: 10.1159/000445856. Epub 2016 Apr 30.
The association between albuminuria and coronary heart disease (CHD) is well-known, but uncertainties related to day-to-day variability and effect modification of gender complicate the risk assessment process. This study evaluates the associations of CHD with albuminuria level in men and women based on the number of urine samples.
Nine thousand one hundred and fifty-eight adults provided 3 urine samples and were followed for 14 years in the population-based HUNT-2 cohort study. The association of myocardial infarction or coronary death with different albumin-creatinine ratio (ACR) cut-offs, based on gender and number of positive ACRs, were estimated by hazard ratios (HRs) and adjusted for by Framingham variables.
Associations between ACR and CHD were similar in men and women. For example, HRs for moderately increased (3.0≤ ACR ≤30.0 mg/mmol) vs. normal albuminuria (ACR <1.0 mg/mmol) were 1.40 (95% CI 1.27-2.03) and 1.61 (95% CI 1.15-1.71) respectively, (psex-equality = 0.3). However, median intra-individual day-to-day ACR coefficient of variation was 22.4% in women vs. 17.5% in men (p < 0.001). Two or 3 positive ACRs were required to establish a significant association with CHD at levels below 4.0 mg/mmol in women, while one positive ACR implied a significant association at all levels in men. Based on receiver-operating-characteristics curves, the Youden index suggested possible equal cut-offs for women (1.12 mg/mmol) and men (0.88 mg/mmol), p = 0.06.
There were no significant gender differences in the association between albuminuria and coronary events. However, women had increased intra-individual albuminuria variability compared to men, necessitating several positive urine samples if mildly increased albuminuria is used in coronary risk evaluation.
蛋白尿与冠心病（CHD）之间的关联已为人熟知，但日常变异性以及性别对效应的修饰所带来的不确定性使风险评估过程变得复杂。本研究基于尿样数量评估男性和女性中冠心病与蛋白尿水平的关联。
在基于人群的HUNT-2队列研究中，9158名成年人提供了3份尿样，并随访了14年。根据性别和阳性白蛋白肌酐比值（ACR）数量，通过风险比（HRs）估计心肌梗死或冠心病死亡与不同ACR临界值之间的关联，并对弗雷明汉变量进行校正。
男性和女性中ACR与冠心病之间的关联相似。例如，中度升高（3.0≤ACR≤30.0mg/mmol）与正常蛋白尿（ACR<1.0mg/mmol）相比的HRs分别为1.40（95%CI 1.27 - 2.03）和1.61（95%CI 1.15 - 1.71），（p性别平等 = 0.3）。然而，女性个体内每日ACR变异系数中位数为22.4%，而男性为17.5%（p<0.001）。在女性中，ACR低于4.0mg/mmol时，需要2次或3次阳性ACR才能与冠心病建立显著关联，而在男性中，1次阳性ACR在所有水平都意味着显著关联。根据受试者工作特征曲线，约登指数表明女性（1.12mg/mmol）和男性（0.88mg/mmol）可能有相同的临界值，p = 0.06。
蛋白尿与冠心病事件之间的关联不存在显著性别差异。然而，与男性相比，女性个体内蛋白尿变异性增加，如果在冠心病风险评估中使用轻度升高的蛋白尿，则需要多个阳性尿样。
